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    Impact of aldosterone-producing adenoma on cardiac structures in echocardiography. Hidaka Takayuki,Shiwa Tsuguka,Fujii Yuichi,Nishioka Kenji,Utsunomiya Hiroto,Ishibashi Ken,Mitsuba Naoya,Dohi Yoshihiro,Oda Noboru,Noma Kensuke,Kurisu Satoru,Nakano Yukiko,Yamamoto Hideya,Iishida Takafumi,Higashi Yukihito,Kihara Yasuki Journal of echocardiography BACKGROUND:Primary aldosteronism (PA) is a most common cause of secondary hypertension. In PA, left ventricular hypertrophy (LVH) is more progressive than in any other cause of hypertension. Aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) are major subtypes of PA. However there is little information concerned with differences of cardiac structures between these two subtypes. METHODS:We reviewed echocardiographic findings in 46 patients with PA. All patients had a positive screen test and subtypes of PA were confirmed by adrenal vein sampling. Subjects consisted of 20 patients with APA (APA group, 52.4 ± 10.8 years) and 26 patients with IHA (IHA group, 56.2 ± 9.5 years). We investigated differences of cardiac structures and functions in the left atrium and ventricle between the APA group and IHA group. RESULTS:In terms of clinical characteristics, the height and duration of hypertension were greater and serum potassium concentration and BMI were lower in the APA group than in the IHA group. Plasma aldosterone concentration (PAC) and PAC to plasma renin activity ratio were higher in the APA group than in the IHA group. In echocardiographic assessment, the left atrial volume, left ventricular end-diastolic and end-systolic diameters, left ventricular mass (LVM), and prevalence of LVH were greater in the APA group than in the IHA group. Multiple linear regression analysis revealed that the diagnosis of APA independently correlated with left atrial volume, left ventricular end-diastolic diameter, and LVM. CONCLUSIONS:We demonstrated that differences of cardiac structures between the APA group and IHA group existed. In APA, left atrial enlargement and LVH were more prominent than in IHA. 10.1007/s12574-013-0168-y
    Myocardial ultrasonic backscatter in hypertension: relation to aldosterone and endothelin. Kozàkovà Michaela,Buralli Simona,Palombo Carlo,Bernini Giampaolo,Moretti Angelica,Favilla Stefania,Taddei Stefano,Salvetti Antonio Hypertension (Dallas, Tex. : 1979) A disproportionate accumulation of fibrillar collagen is a characteristic feature of hypertensive heart disease, but the extent of myocardial fibrosis may differ in different models of hypertension. In experimental studies, aldosterone and endothelins emerge as important determinants of myocardial fibrosis. Changes in myocardial extracellular matrix and collagen deposition can be estimated noninvasively by analysis of the ultrasonic backscatter signal, which arises from tissue heterogeneity within the myocardium and describes myocardial texture. This study was designed to investigate the relations between myocardial integrated backscatter and circulating aldosterone and immunoreactive endothelin in human hypertension. The study population consisted of 56 subjects: 14 healthy normotensive volunteers and 42 hypertensive patients (14 with primary aldosteronism, 7 with renovascular hypertension, and 21 with essential hypertension). The patients with essential and secondary hypertension were matched for age, gender, body mass index, and blood pressure. Myocardial integrated backscatter at diastole was 19.8+/-2.0 and 20.8+/-2.9 decibels in normotensive control subjects and patients with essential hypertension and significantly higher in patients with primary aldosteronism (27.4+/-3.8 decibels, P<0.01) and renovascular hypertension (26.8+/-4.8 decibels, P<0.01). In the population as a whole, as well as in the hypertensive subpopulation, myocardial integrated backscatter was directly related to plasma aldosterone (r=0.73 and 0.71, P<0.01 for both) and immunoreactive endothelin (r=0.60 and 0.56, P<0.01 for both). The data of this study suggest that in human hypertension, circulating aldosterone and immunoreactive endothelin may induce alterations in left ventricular myocardial texture, possibly related to increased myocardial collagen content. 10.1161/01.hyp.0000052542.68896.2b
    A Comparison of Adrenalectomy and Eplerenone on Vascular Function in Patients with Aldosterone-producing Adenoma. Kishimoto Shinji,Oki Kenji,Maruhashi Tatsuya,Kajikawa Masato,Hashimoto Haruki,Takaeko Yuji,Harada Takahiro,Yamaji Takayuki,Han Yiming,Kihara Yasuki,Chayama Kazuaki,Goto Chikara,Yusoff Farina Mohamad,Nakashima Ayumu,Higashi Yukihito The Journal of clinical endocrinology and metabolism CONTEXT:It remains unclear whether adrenalectomy has more beneficial effects than treatment with a mineralocorticoid receptor antagonist on vascular function in patients with aldosterone-producing adenoma (APA). OBJECTIVE:The aim of this study was to compare the effects of adrenalectomy and treatment with eplerenone on vascular function in patients with APA. DESIGN, SETTING, AND PATIENTS:Flow-mediated vasodilation (FMD), as an index of endothelium-dependent vasodilation, and nitroglycerine-induced vasodilation (NID), as an index of endothelium-independent vasodilation, were measured to assess vascular function before and after a 3-month treatment with eplerenone and at 3 months after adrenalectomy in 23 patients with APA. RESULTS:Flow-mediated vasodilation and NID after adrenalectomy were significantly higher than those before treatment with eplerenone (5.4 ± 2.6% vs 2.7 ± 1.9% and 14.8 ± 4.7% vs 9.6 ± 4.6%, P < 0.01, respectively) and those after treatment with eplerenone (5.4 ± 2.6% vs 3.1 ± 2.3% and 14.8 ± 4.7% vs 11.0 ± 5.3%, P < 0.01 and P = 0.03, respectively), while treatment with eplerenone did not alter FMD and NID compared with those before treatment with eplerenone. After adrenalectomy, the increase in FMD and NID were significantly correlated with a decrease in plasma aldosterone concentration and a decrease in the aldosterone-renin ratio. There were no significant relationships between FMD and changes in other parameters or between NID and changes in other parameters. CONCLUSIONS:Adrenalectomy, but not treatment with eplerenone, improved vascular function in patients with APA. Adrenalectomy may be more effective than treatment with eplerenone for reducing the incidence of future cardiovascular events in patients with APA. Clinical Trial Information: URL for the clinical trial: http://UMIN; Registration Number for the clinical trial: UMIN000003409. 10.1210/clinem/dgaa561
    Plasma aldosterone levels are elevated in patients with pulmonary arterial hypertension in the absence of left ventricular heart failure: a pilot study. Maron Bradley A,Opotowsky Alexander R,Landzberg Michael J,Loscalzo Joseph,Waxman Aaron B,Leopold Jane A European journal of heart failure AIMS:Elevated levels of the mineralocorticoid hormone aldosterone are recognized as a modifiable contributor to the pathophysiology of select cardiovascular diseases due to left heart failure. In pulmonary arterial hypertension (PAH), pulmonary vascular remodelling induces right ventricular dysfunction and heart failure in the absence of left ventricular (LV) dysfunction. Hyperaldosteronism has emerged as a promoter of pulmonary vascular disease in experimental animal models of PAH; however, the extent to which hyperaldosteronism is associated with PAH in patients is unknown. Thus, the central aim of the current study is to determine if hyperaldosteronism is an unrecognized component of the PAH clinical syndrome. METHODS AND RESULTS:Plasma aldosterone levels and invasive cardiopulmonary haemodynamic measurements were obtained for 25 patients referred for evaluation of unexplained dyspnoea or pulmonary hypertension. Compared with controls (n = 5), patients with PAH (n = 18) demonstrated significantly increased plasma aldosterone levels (1200.4 ± 423.9 vs. 5959.1 ± 2817.9 pg/mL, P < 0.02), mean pulmonary artery pressure (21.4 ± 5.0 vs. 45.5 ± 10.4 mmHg, P < 0.002), and pulmonary vascular resistance (PVR) (1.41 ± 0.6 vs. 7.3 ± 3.8 Wood units, P < 0.003) without differences in LV ejection fraction or pulmonary capillary wedge pressure between groups. Among patients not prescribed PAH-specific pharmacotherapy prior to cardiac catheterization, a subgroup of the cohort with severe pulmonary hypertension, aldosterone levels correlated positively with PVR (r = 0.72, P < 0.02) and transpulmonary gradient (r = 0.69, P < 0.02), but correlated inversely with cardiac output (r = -0.79, P < 0.005). CONCLUSIONS:These data demonstrate a novel cardiopulmonary haemodynamic profile associated with hyperaldosteronism in patients: diminished cardiac output due to pulmonary vascular disease in the absence of LV heart failure. 10.1093/eurjhf/hfs173
    Incidental Congestive Heart Failure in Patients With Aldosterone-Producing Adenomas. Huang Wei-Chieh,Chen Ying-Ying,Lin Yen-Hung,Chen Likwang,Lin Po-Chih,Lin Yu-Feng,Liu Yu-Chun,Wu Che-Hsiung,Chueh Jeff S,Chu Tzong-Shinn,Wu Kwan Dun,Huang Chun-Yao,Wu Vin-Cent, , Journal of the American Heart Association Background Previous studies show that patients with primary aldosteronism are associated with higher risk of congestive heart failure (CHF). However, the effect of target treatment to the incidental CHF has not been elucidated. We aimed to investigate the risk of new-onset CHF in patients with aldosterone-producing adenomas (APAs) and explore the effect of adrenalectomy on new onset of CHF. Methods and Results From 1997 to 2009, 688 APA were identified and matched with essential hypertension controls. The risks of developing incidental CHF (hazard ratio, 0.49; 95% CI, 0.31-0.75; =0.001) and mortality (hazard ratio, 0.29; 95% CI, 0.20-0.44; <0.001) were significantly lower in the APA group after targeted treatment. A total of 605 patients with APAs who underwent adrenalectomy lowered the risks of CHF (subdistribution hazard ratio, 0.55; 95% CI, 0.34-0.90; =0.017) and mortality (adjusted hazard ratio, 0.27; 95% CI, 0.16-0.44; <0.001) compared with essential hypertension controls. Conclusions In conclusion, for patients with APAs, adrenalectomy can be associated with lower risk of incidental CHF and all-cause mortality in a long-term follow-up. 10.1161/JAHA.119.012410
    Left ventricular structural and functional characteristics in patients with renovascular hypertension, primary aldosteronism and essential hypertension. Yoshihara F,Nishikimi T,Yoshitomi Y,Nakasone I,Abe H,Matsuoka H,Omae T American journal of hypertension To investigate the effect of different etiologies of hypertension on left ventricular structure and function, we compared echocardiographic findings in 10 patients with renovascular hypertension (35 +/- 9 years), 10 patients with primary aldosteronism (42 +/- 9 years), and 14 patients with essential hypertension (41 +/- 6 years). There were no significant differences among the three groups in age, sex, body surface area, blood pressure, interventricular septal thickness, posterior wall thickness, left ventricular end-diastolic dimension or end-systolic dimension, relative wall thickness, left ventricular mass index, or spectrum of left ventricular adaptation (concentric remodeling, concentric hypertrophy, or eccentric hypertrophy). There were no differences in systolic function or diastolic function, which was assessed in terms of the peak rate of increase in dimension normalized for left ventricular end-diastolic dimension (dD/dt/D), the relaxation time, and the relaxation time to peak velocity of lengthening among groups. Multiple regression analysis showed that the systolic blood pressure was the most important determinant of left ventricular mass index (r = 0.56, P < .01), and that left ventricular mass index was the most important determinant of relaxation time and the relaxation time to peak velocity of lengthening (r = 0.48, P < .01 and r = 0.59, P < .01, respectively). The dD/dt/D was correlated only with left ventricular end-systolic dimension (r = 0.59, P < .01). Our results suggest that blood pressure may be a strong determinant of left ventricular hypertrophy, irrespective of the etiology of hypertension, and that the degree of hypertrophy may be related to left ventricular diastolic dysfunction in hypertensive patients with normal systolic function. 10.1016/0895-7061(96)00031-3
    Increased myocardial sodium signal intensity in Conn's syndrome detected by 23Na magnetic resonance imaging. Christa Martin,Weng Andreas M,Geier Bettina,Wörmann Caroline,Scheffler Anne,Lehmann Leane,Oberberger Johannes,Kraus Bettina J,Hahner Stefanie,Störk Stefan,Klink Thorsten,Bauer Wolfgang R,Hammer Fabian,Köstler Herbert European heart journal cardiovascular Imaging AIMS:Sodium intake has been linked to left ventricular hypertrophy independently of blood pressure, but the underlying mechanisms remain unclear. Primary hyperaldosteronism (PHA), a condition characterized by tissue sodium overload due to aldosterone excess, causes accelerated left ventricular hypertrophy compared to blood pressure matched patients with essential hypertension. We therefore hypothesized that the myocardium constitutes a novel site capable of sodium storage explaining the missing link between sodium and left ventricular hypertrophy. METHODS AND RESULTS:Using 23Na magnetic resonance imaging, we investigated relative sodium signal intensities (rSSI) in the heart, calf muscle, and skin in 8 PHA patients (6 male, median age 55 years) and 12 normotensive healthy controls (HC) (8 male, median age 61 years). PHA patients had a higher mean systolic 24 h ambulatory blood pressure [152 (140; 163) vs. 125 (122; 130) mmHg, P < 0.001] and higher left ventricular mass index [71.0 (63.5; 106.8) vs. 55.0 (50.3; 66.8) g/m2, P = 0.037] than HC. Compared to HC, PHA patients exhibited significantly higher rSSI in the myocardium [0.31 (0.26; 0.34) vs. 0.24 (0.20; 0.27); P = 0.007], calf muscle [0.19 (0.16; 0.22) vs. 0.14 (0.13; 0.15); P = 0.001] and skin [0.28 (0.25; 0.33) vs. 0.19 (0.17; 0.26); P = 0.014], reflecting a difference of +27%, +38%, and +39%, respectively. Treatment of PHA resulted in significant reductions of the rSSI in the myocardium, calf muscle and skin by -13%, -27%, and -29%, respectively. CONCLUSION:Myocardial tissue rSSI is increased in PHA patients and treatment of aldosterone excess effectively reduces rSSI, thus establishing the myocardium as a novel site of sodium storage in addition to skeletal muscle and skin. 10.1093/ehjci/jey134
    Left ventricle remodeling in men with moderate to severe volume-dependent hypertension. Indra Tomás,Holaj Robert,Zelinka Tomás,Petrák Ondrej,Strauch Branislav,Rosa Ján,Somlóová Zuzana,Malík Jan,Janota Tomás,Hradec Jaromír,Widimsky Jirí Journal of the renin-angiotensin-aldosterone system : JRAAS We evaluated the influence of increased intravascular volume on the heart anatomy in salt-sensitive types of hypertension, represented by primary aldosteronism (PA) and low-renin essential hypertension (LREH). Echocardiography was performed in 128 males with moderate to severe or resistant hypertension: 44 patients had PA, 40 patients had LREH and 44 patients had normal-renin essential hypertension (NREH). Groups were comparable in demographic characteristics, blood pressure, duration of hypertension and previous antihypertensive treatment. Patients with PA and LREH, in comparison with NREH patients, showed both greater end-systolic (37.6±5.4 and 35.6±4.5 vs 32.6±4.4 mm, p<0.001 and p<0.05) and end-diastolic (56.1±4.5 and 54.0±4.8 vs 50.4±5.1 mm; p<0.001 and p<0.01) left ventricle (LV) diameter. There were no significant differences either in LV wall thicknesses or LV mass, although a higher percentage of patients with PA and LREH met the criteria of eccentric hypertrophy (p<0.001 and p<0.05 respectively). Aldosterone concentration was positively related to LV cavity dimensions, whether wall thicknesses were rather associated with blood pressure levels. In conclusion, plasma volume overload was identified as an important factor influencing LV remodeling in PA and LREH, whether due to excessive aldosterone levels in PA or other pathophysiological mechanisms. 10.1177/1470320312446240
    The relation among aldosterone, galectin-3, and myocardial fibrosis: a prospective clinical pilot follow-up study. Liao Che-Wei,Lin Yen-Tin,Wu Xue-Ming,Chang Yi-Yao,Hung Chi-Sheng,Wu Vin-Cent,Wu Kwan-Dun,Lin Yen-Hung, Journal of investigative medicine : the official publication of the American Federation for Clinical Research UNLABELLED:Primary aldosteronism has been associated with myocardial fibrosis, and is the most common cause of secondary hypertension. We previously showed that aldosterone can induce the secretion of galectin-3. The aim of this study was to investigate the association between myocardial fibrosis and plasma galectin-3 level in patients with primary aldosteronism. We prospectively analyzed 11 patients with aldosterone-producing adenoma (APA) who received adrenalectomy from December 2006 to October 2008, and 17 patients with essential hypertension as controls. Levels of plasma galectin-3 were determined in both groups, and both groups underwent echocardiography with cyclic variations of integrated backscatter (CVIBS) to characterize tissue initially and 1 year after surgery in the APA group. Diastolic blood pressure, concentration of plasma aldosterone and aldosterone-renin ratio were significantly higher, and serum potassium level and plasma renin activity significantly lower in the APA group compared to the controls. In addition, left ventricular mass index was significantly higher and CVIBS significantly lower in the APA group (7.3±2.0 vs 9.2±1.7 dB, p=0.015). Furthermore, the concentration of plasma galectin-3 was significantly higher in the APA group (2.1±0.9 vs 1.1±0.6 ng/mL, p=0.005) compared to the controls. CVIBS was correlated to plasma galectin-3 level. In the APA group, CVIBS increased significantly (7.3±2.0 to 9.2±2.4 dB, p=0.032) and plasma galectin-3 decreased (2.1±0.9 to 1.2±0.6, p=0.049) 1 year postadrenalectomy. The patients with APA had increased myocardial fibrosis, and this was associated with a higher plasma galectin-3 level. Both increased myocardial fibrosis and plasma galectin-3 level recovered at least partially after adrenalectomy. TRIAL REGISTRATION NUMBER:200611031R; Results. 10.1136/jim-2015-000014
    Impaired endothelium-dependent flow-mediated vasodilation in hypertensive subjects with hyperaldosteronism. Nishizaka Mari K,Zaman M Amin,Green Sharon A,Renfroe Kerry Y,Calhoun David A Circulation BACKGROUND:Recent studies suggest that aldosterone may impair endothelium-dependent vascular function through suppression of nitric oxide formation. Assessments of forearm blood flow or arterial compliance suggest a similar effect in humans. The present study was designed to determine whether chronic aldosterone excess in subjects with resistant hypertension impairs endothelium-dependent vascular reactivity as indexed by direct assessment of brachial artery flow-mediated dilation (FMD). METHODS AND RESULTS:Consecutive subjects (n=80) with resistant hypertension were prospectively evaluated with an early-morning ratio of plasma aldosterone to plasma renin activity and 24-hour urinary aldosterone and sodium. Changes in brachial artery diameter during reactive hyperemia were measured by high-resolution ultrasound. Hyperaldosteronism was diagnosed on the basis of a renin activity <1.0 ng x mL(-1) x h(-1), urinary aldosterone >12 microg/24 h, and urinary sodium >200 mEq/24 h. FMD was significantly lower in 36 subjects with hyperaldosteronism (1.8+/-1.3% versus 3.9+/-1.9% from baseline; P<0.0001) compared with the 44 subjects without hyperaldosteronism. FMD was negatively and significantly correlated with plasma aldosterone (r=-0.38, P=0.0006), 24-hour urinary aldosterone (r=-0.49, P<0.0001), and ratio of plasma aldosterone to plasma renin activity (r=-0.43, P<0.0001) but was independent of blood pressure, age, and body mass index. In 30 subjects, 3 months of treatment with spironolactone significantly increased FMD (2.5+/-1.7 versus 6.0+/-2.0%; P<0.0001) independently of blood pressure change. CONCLUSIONS:These data demonstrate a strong association between aldosterone excess and impaired endothelial function in human subjects as indexed by flow-mediated arterial vasodilation. These results suggest that chronic aldosteronism may have a blood pressure-independent effect on cardiovascular disease progression in subjects with resistant hypertension. 10.1161/01.CIR.0000129307.26791.8E
    Remodeling of the left ventricle in primary aldosteronism due to Conn's adenoma. Rossi G P,Sacchetto A,Pavan E,Palatini P,Graniero G R,Canali C,Pessina A C Circulation BACKGROUND:Since hyperaldosteronism has been experimentally related to myocardial interstitial fibrosis, we investigated the effects of hypertension and excess aldosterone due to aldosterone-producing adenomas (APAs) on the heart. METHODS AND RESULTS:In 52 hypertensive individuals, we performed Doppler echocardiography for estimation of left ventricular (LV) wall thickness and dimensions, transmitral LV filling flow velocity indexes, and 24-hour ambulatory blood pressure monitoring. Consecutive patients with APAs (n = 26) and essential hypertension (EH, n = 26) were individually matched for age, sex, race, body mass index, casual blood pressure, and known duration of hypertension. The matched groups were similar for demography, casual and 24-hour blood pressure values and variability, and duration of hypertension but differed for serum potassium, plasma renin activity, and aldosterone levels (all P < .001). A thicker interventricular septum (P = .015) and posterior wall (P = .009) and a higher LV mass index (118 +/- 5 versus 100 +/- 4 g/m2, P = .009) were observed in APA compared with EH patients. Both septum and posterior wall thicknesses had a significant direct relationship with age, plasma aldosterone, and mean blood pressure. The integral of the early diastolic filling wave (Ei) (P = .011) and the ratio Ei/Ai (A wave integral) (P = .038) were lower and the atrial contribution to LV filling was higher (52 +/- 2% versus 46 +/- 2%, P = .038) in APA than in EH patients. The ratio Ei/Ai was significantly (P = .008) inversely related only to age and plasma aldosterone. CONCLUSIONS:In APA patients, the excess aldosterone is associated with both increased LV wall thickness and mass and decreased early diastolic LV filling indexes compared with demographically similar EH with superimposable blood pressure values, profile, and variability. 10.1161/01.cir.95.6.1471
    Adrenalectomy improves increased carotid intima-media thickness and arterial stiffness in patients with aldosterone producing adenoma. Lin Yen-Hung,Lin Lian-Yu,Chen Aaron,Wu Xue-Ming,Lee Jen-Kuang,Su Ta-Chen,Wu Vin-Cent,Chueh Shih-Chieh,Lin Wei-Chou,Lo Men-Tzung,Wang Pa-Chun,Ho Yi-Lwun,Wu Kwan-Dun, Atherosclerosis CONTEXT:Primary aldosteronism (PA) is the most frequent cause of secondary hypertension, and is associated with more prominent vascular stiffness and atherosclerosis. However, the effect of adrenalectomy on reversibility of vascular damage is unclear. OBJECTIVE:Our objective was to investigate the vascular changes and possibility of reversibility after adrenalectomy in PA patients. METHODS:We prospectively analyzed 20 patients with aldosterone producing adenoma (APA) that received adrenalectomy from October 2006 to December 2008 and 21 patients with essential hypertension (EH) were enrolled as the control group. Carotid intima media thickness (CIMT) measurement by B-mode ultrasound of the right common carotid arteries and pulse wave velocity (PWV) measurement including brachial-ankle PWV (baPWV) and heart-ankle PWV (haPWV) were performed in both groups. The follow-up measurements were performed one-year after adrenalectomy in APA group. RESULTS:APA patients had significantly higher diastolic blood pressure, plasma aldosterone concentration (PAC) and aldosterone-renin ratio (ARR), but lower serum potassium level and plasma renin activity (PRA) than EH patients. APA patients had significantly higher CIMT (0.64±0.13 vs. 0.53±0.10 mm, p=0.006), higher baPWV (1589±296 vs. 1405±187 cm/s, p=0.024) and haPWV (1095±150 vs. 987±114 cm/s, p=0.013) comparing with EH patients. One-year after adrenalectomy, CIMT reduced significantly from 0.64±0.13 mm to 0.59±0.14 mm (p=0.014), and baPWV and haPWV also showed significant reduction (baPWV, 1589±296 to 1463±188 cm/s, p=0.035; haPWV, 1095±150 to 1017±109 cm/s, p=0.019). CONCLUSION:APA patients have higher degree of early atherosclerosis and vascular stiffness. Adrenalectomy not only corrects the high blood pressure and biochemical parameters but also reverse adverse vascular change in APA patients. 10.1016/j.atherosclerosis.2011.12.003
    Aldosterone-Related Myocardial Extracellular Matrix Expansion in Hypertension in Humans: A Proof-of-Concept Study by Cardiac Magnetic Resonance. Redheuil Alban,Blanchard Anne,Pereira Helena,Raissouni Zainab,Lorthioir Aurelien,Soulat Gilles,Vargas-Poussou Rosa,Amar Laurence,Paul Jean-Louis,Helley Dominique,Azizi Michel,Kachenoura Nadjia,Mousseaux Elie JACC. Cardiovascular imaging OBJECTIVES:This study sought to assess the respective effects of aldosterone and blood pressure (BP) levels on myocardial fibrosis in humans. BACKGROUND:Experimentally, aldosterone promotes left ventricular (LV) hypertrophy, and interstitial myocardial fibrosis in the presence of high salt intake. METHODS:The study included 20 patients with primary aldosteronism (PA) (high aldosterone and high BP), 20 patients with essential hypertension (HTN) (average aldosterone and high BP), 20 patients with secondary aldosteronism due to Bartter/Gitelman (BG) syndrome (high aldosterone and normal BP), and 20 healthy subjects (HS) (normal aldosterone and normal BP). Participants in each group were of similar age and sex distributions, and asymptomatic. Cardiac magnetic resonance including cine and T1 mapping was performed blind to the study group to quantify global LV mass index, as well as intracellular mass index and extracellular mass index considered as a measure of myocardial fibrosis in vivo. RESULTS:Median plasma aldosterone concentration was as follows: PA = 709 pmol/l (interquartile range [IQR]: 430 to 918 pmol/l); HTN = 197 pmol/l (IQR: 121 to 345 pmol/l); BG = 297 pmol/l (IQR: 180 to 428 pmol/l); and HS = 105 pmol/l (IQR: 85 to 227 pmol/l). Systolic BP was as follows: PA = 147 ± 15 mm Hg; HTN = 133 ± 19 mm Hg; BG = 116 ± 9 mm Hg; and HS = 117 ± 12 mm Hg. LV end-diastolic volume showed underloading in BG and overloading in patients with PA (63 ± 13 ml/m vs. 82 ± 15 ml/m; p < 0.0001). Intracellular mass index increased with BP across groups (BG: 36 [IQR: 29 to 41]; HS: 40 [IQR: 36 to 46]; HTN: 51 [IQR: 42 to 54]; PA: 50 [IQR: 46 to 67]; p < 0.0001). Extracellular mass index was similar in BG, HS, and HTN (16 [IQR: 12 to 20]; 15 [IQR: 11 to 18]; and 14 [IQR: 12 to 17], respectively) but 30% higher in PA (21 [IQR: 18 to 29]; p < 0.0001) remaining significant after adjustment for mean BP. CONCLUSIONS:Only primary pathological aldosterone excess combined with high BP increased both extracellular myocardial matrix and intracellular mass. Secondary aldosterone excess with normal BP did not affect extracellular myocardial matrix. (Study of Myocardial Interstitial Fibrosis in Hyperaldosteronism; NCT02938910). 10.1016/j.jcmg.2020.06.026
    Role of aldosterone in left ventricular hypertrophy in hypertension. Matsumura Kiyoshi,Fujii Koji,Oniki Hideyuki,Oka Masayo,Iida Mitsuo American journal of hypertension BACKGROUND:Aldosterone induces cardiac fibrosis in experimental animal models, but only limited information is available on the association between aldosterone and left ventricular (LV) hypertrophy in human beings. The aim of the present study was to determine the role of aldosterone in LV geometry and to investigate other types of target organ damage in hypertensive patients. METHODS:A total of 25 patients with primary aldosteronism caused by Conn's adenoma, 29 patients with renovascular hypertension, and 29 patients with essential hypertension (EHT) were included in the present study. Echocardiographic examinations and 24-h ambulatory blood pressure (BP) monitoring were conducted in all subjects. RESULTS:The mean 24-h systolic and diastolic BP in primary aldosteronism and renovascular hypertension were found to be comparable to those in EHT. However, LV mass index adjusted by age, sex, mean 24-h systolic BP, mean 24-h pulse rate, body mass index, and duration of hypertension was significantly increased in the patients with primary aldosteronism and renovascular hypertension compared with values in patients with EHT (150.2 +/- 7.7, 142.3 +/- 7.2, and 115.2 +/- 7.2 g/m(2), respectively). Hypertensive organ damages, such as proteinuria and hypertensive retinopathy, were more pronounced in the patients with renovascular hypertension; however, LV hypertrophy was especially exaggerated in patients with primary aldosteronism. CONCLUSIONS:These results indicate that aldosterone may induce LV hypertrophy in human beings as well as in experimental animals, and that angiotensin II and aldosterone may differentially participate in causing hypertensive target organ damage. 10.1016/j.amjhyper.2005.05.013
    Time course and factors predicting arterial stiffness reversal in patients with aldosterone-producing adenoma after adrenalectomy: prospective study of 102 patients. Liao Che-Wei,Lin Lian-Yu,Hung Chi-Sheng,Lin Yen-Tin,Chang Yi-Yao,Wang Shuo-Meng,Wu Vin-Cent,Wu Kwan-Dun,Ho Yi-Lwun,Satoh Fumitoshi,Lin Yen-Hung Scientific reports Primary aldosteronism not only results in hypertension but also stiffer arteries. The time course and factors predicting the reversal of arterial stiffness after treatment are unclear. We prospectively enrolled 102 patients with aldosterone-producing adenoma (APA) from March 2006 to January 2012. We measured the pulse wave velocity (PWV) between brachial-ankle (baPWV) and heart-ankle (haPWV) before, 6 and 12 months after their adrenalectomy. After treatment, the PWV decreased significantly during the first 6 months (both p < 0.001), but no further reduction in the following 6 months. The determinant factors for baseline baPWV were age, duration of hypertension, and baseline systolic blood pressure (SBP) in multivariate linear regression analysis, similar with baseline haPWV (determinants: age, duration of hypertension, baseline SBP and diastolic blood pressure (DBP)). In multivariate linear regression analysis, the decrease in DBP at 6 months (ΔDBP0-6mo) and baseline baPWV were significantly associated with the decrease in baPWV at 6 months (ΔbaPWV0-6mo). The associated factors of the change in haPWV at 6 months (ΔhaPWV0-6mo) were baseline haPWV, ΔDBP0-6mo and change in log-transformed plasma renin activity. Our result suggested that reversal of arterial stiffness in APA patients occurred early after adrenalectomy and determined by baseline vascular condition, hemodynamic factors, and humoral factors. 10.1038/srep20862
    Left ventricular structural characteristics in unilateral renovascular hypertension and primary aldosteronism. Suzuki T,Abe H,Nagata S,Saitoh F,Iwata S,Ashizawa A,Kuramochi M,Omae T The American journal of cardiology To assess the importance of the renin-angiotensin system and plasma volume as determinants of hypertensive left ventricular hypertrophy and its anatomy, patients with unilateral renovascular hypertension and primary aldosteronism were studied by echocardiography. Blood pressure, age and sex were matched as closely as possible. The 19 patients with unilateral renovascular hypertension and the 19 patients with primary aldosteronism were similar in age, sex and blood pressure (168 +/- 19/97 +/- 11 and 163 +/- 17/99 +/- 10 mm Hg, respectively), but plasma volume was increased in the patients with primary aldosteronism. Interventricular septal thickness, left ventricular posterior wall thickness, left ventricular mass index and relative wall thickness did not differ between the 2 groups of patients. There was a significant correlation between the level of systolic blood pressure and either left ventricular mass index (r = 0.34, p less than 0.05) or relative wall thickness (r = 0.58, p less than 0.001) in both groups of patients. Left ventricular end-diastolic dimension index was increased in the patients with primary aldosteronism compared with those with unilateral renovascular hypertension (3.2 +/- 0.4 vs 2.9 +/- 0.3 cm/m2, p less than 0.02). When confined to the patients with systolic pressure greater than or equal to 150 mm Hg, relative wall thickness was significantly increased in the patients with unilateral renovascular hypertension. Patients with primary aldosteronism and unilateral renovascular hypertension of similar blood pressure levels, age and sex have almost identical degrees of left ventricular hypertrophy and anatomy. In contrast, the patients with primary oldosteronism had increased left ventricular dimension index.(ABSTRACT TRUNCATED AT 250 WORDS) 10.1016/0002-9149(88)90264-0
    Comparison of cardiovascular complications in patients with and without KCNJ5 gene mutations harboring aldosterone-producing adenomas. Kitamoto Takumi,Suematsu Sachiko,Matsuzawa Yoko,Saito Jun,Omura Masao,Nishikawa Tetsuo Journal of atherosclerosis and thrombosis AIM:Our objective was to evaluate the incidence of cardiovascular complications before and after unilateral adrenalectomy in patients with and without KCNJ5 gene mutations harboring aldosterone-producing adenoma (APA). METHODS:A total of 108 APA patients were evaluated in the present study. We compared the clinical characteristics and laboratory findings according to the cardiovascular complications in the patients with or without KCNJ5 gene mutations harboring APA after excluding five APA patients with ATPase or CACNA1D gene mutations. RESULTS:There were 75 and 28 APA patients with somatic mutations of KCNJ5 (p.G151R, p.L168R, p.E145Q, p.T158A or 157del) and no mutations, respectively. There were no double mutations in any of the subjects. The KCNJ5-mutated and wild type groups demonstrated similar advances in left ventricular hypertrophy prior to surgery, although the mutated group was significantly younger, with higher plasma and urine aldosterone levels, than the wild type group (48.2 vs. 55.8 (years old); p<0.001, 436.0 vs. 247 (pg/mL); p<0.001, 22.2 vs. 12.6 (μg/day); p=0.008). Both groups displayed postoperative improvements in hyperaldosteronism and hypertension. Moreover, the LV mass index (LVMI) significantly improved after surgery in the mutated group (p<0.001), but not in the wild type group (p=0.256). A multiple linear regression analysis showed that an improvement in the LVMI was independently associated with KCNJ5 mutations and the plasma aldosterone level in that order (p=0.034, 0.050, respectively). CONCLUSION:The present findings clearly demonstrated that KCNJ5 mutations are common among Japanese APA patients (frequency: 69.4%). In this study, the KCNJ5-mutated group demonstrated significant postoperative improvements in LVMI, possibly due to strong autonomous aldosterone production. Hence, it is necessary to precisely diagnose younger APA patients possessing a strong capacity for aldosterone production due to KCNJ5 gene mutations, as such cases may be easily complicated by cardiovascular events. 10.5551/jat.24455
    Rapid reversal of left ventricular hypertrophy and intracardiac volume overload in patients with resistant hypertension and hyperaldosteronism: a prospective clinical study. Gaddam Krishna,Corros Cecilia,Pimenta Eduardo,Ahmed Mustafa,Denney Thomas,Aban Inmaculada,Inusah Seidu,Gupta Himanshu,Lloyd Steven G,Oparil Suzanne,Husain Ahsan,Dell'Italia Louis J,Calhoun David A Hypertension (Dallas, Tex. : 1979) We have shown previously that patients with resistant hypertension and hyperaldosteronism have increased brain natriuretic peptide suggestive of increased intravascular volume. In the present study, we tested the hypothesis that hyperaldosteronism contributes to cardiac volume overload. Thirty-seven resistant hypertensive patients with hyperaldosteronism (urinary aldosterone > or = 12 microg/24 hours and plasma renin activity < or = 1.0 ng/mL per hour) and 71 patients with normal aldosterone status were studied. Both groups had similar blood pressure and left ventricular mass, whereas left and right ventricular end-diastolic volumes measured by cardiac MRI were greater in high versus normal aldosterone subjects (P<0.05). Spironolactone treatment (19 patients in the high aldosterone group and 15 patients from the normal aldosterone group participated in the follow-up) resulted in a significant decrease in clinic systolic blood pressure, right and left ventricular end diastolic volumes, left atrial volume, left ventricular mass, and brain natriuretic peptide at 3 and 6 months of follow-up in patients with high aldosterone, whereas in those with normal aldosterone status, spironolactone decreased blood pressure and left ventricular mass without changes in ventricular or atrial volumes or plasma brain natriuretic peptide. Hyperaldosteronism causes intracardiac volume overload in patients with resistant hypertension in spite of conventional thiazide diuretic use. Mineralocorticoid receptor blockade induces rapid regression of left ventricular hypertrophy irrespective of aldosterone status. In subjects with high aldosterone, mineralocorticoid receptor blockade induces a prominent diuretic effect compared with a greater vasodilatory effect in subjects with normal aldosterone status. 10.1161/HYPERTENSIONAHA.109.141531
    Endothelial dysfunction is related to aldosterone excess and raised blood pressure. Tsuchiya Kyoichiro,Yoshimoto Takanobu,Hirata Yukio Endocrine journal Primary aldosteronism (PA) is a secondary hypertension characterized by autonomous aldosterone hypersecretion from adrenocortical adenoma and/or hyperplasia. Recently it has been suggested that aldosterone excess is directly involved in the development of cardiovascular injury in PA independent of its hypertensive effect. The present study was designed to examine the relationship between aldosterone excess and endothelial dysfunction in PA patients. 25 PA patients were studied for vascular endothelial function by ultrasound measurement of flow-mediated vasodilation (FMD), and 10 PA patients were re-evaluated 3 months after surgical or medical treatment; 10 age-, gender-, and blood pressurematched hypertensive patients served as control subjects. Percent (%) FMD in PA patients (4.6+/-2.0%) was significantly (p < 0.0001) lower than that in the control subjects (7.9+/-2.0%). %FMD showed significant (p < 0.05) negative correlations with systolic blood pressure (SBP) (r=-0.48), brachial-ankle pulse wave velocity (r=-0.52), plasma aldosterone concentration (PAC) (r=-0.42), and aldosterone-renin ratio (ARR) (r=-0.42), while SBP showed a positive correlation with PAC (r=0.47). Percent FMD, SBP, PAC, and ARR significantly (p < 0.05) improved after surgical and medical treatment, although the changes of %FMD did not correlate with those of SBP, PAC or ARR. In conclusion, the present study has demonstrated that PA patients have endothelial dysfunction, which is related to aldosterone excess and raised blood pressure, and reversible after treatment, suggesting that aldosterone excess contributes to the development of endothelial dysfunction due to its hypertensive effect and/or its direct effect on the cardiovascular system.
    [Left ventricular myocardial structure and function in patients with primary aldosteronism]. Arabidze G G,Chikhladze N M,Sergakova L M,Iarovaia E B Terapevticheskii arkhiv AIM:To study severity of left ventricular hypertrophy (LVH) and left ventricular function in patients with primary aldosteronism (PA) in comparison with hyperaldosteronemia and preoperative arterial hypertension, to follow the dynamics of these parameters early and late after surgical removal of aldosteroma. MATERIALS AND METHODS:Concentration of aldosterone (AC), plasma renin activity (PRA) were measured in 28 PA patients aged 26-58 years before removal of aldosteroma and 1 month, 1 year and 2-5 years after the surgical treatment. Myocardial status was assessed by echocardiography, Doppler echocardiography. 30 healthy subjects aged 25-55 years served control. RESULTS:All the PA patients showed initial or moderate LVH. Index of left ventricular myocardial mass was influenced at the first regression step by primarily diastolic pressure, at the second step--by basal PRA. The diastolic function was affected. One month after unilateral adrenalectomy PRA level and arterial pressure decreased but regression of LVH was noted only 1 year and later after the surgery. Diastolic function improved 1 year after the operation but without normalization within 2-5-year follow-up. CONCLUSION:The lack of a complete normalization of diastolic function of the left ventricle late after the surgery despite regression of LVH and preoperative correlation of the isometric relaxation time with PRA level may be caused by fibrous changes in the myocardium and by hyperaldosteronemia effects.
    Myocardial scintigraphic characteristics in patients with primary aldosteronism. Abe M,Hamada M,Matsuoka H,Shigematsu Y,Sumimoto T,Hiwada K Hypertension (Dallas, Tex. : 1979) To evaluate the difference in myocardial damage between primary aldosteronism and untreated essential hypertension, we performed thallium-201 myocardial single-photon emission computed tomography in 10 patients with primary aldosteronism and 10 patients with essential hypertension who were matched for age, sex, blood pressure, and the severity of left ventricular hypertrophy for primary aldosteronism. From the analysis of thallium-201 myocardial scintigraphy, extent score was calculated. Extent score was significantly higher in primary aldosteronism than in essential hypertension (45.8 +/- 23.5% versus 9.5 +/- 7.3%, P < .01). After operation, blood pressure significantly decreased, and the precordial voltages (SV1 + RV5) and left ventricular mass indexes were significantly reduced in patients with primary aldosteronism. Extent score was also significantly improved. These results suggest that despite the same severity of myocardial hypertrophy between primary aldosteronism and essential hypertension, the myocardial damage estimated by thallium-201 myocardial scintigraphy is more severe in primary aldosteronism than in essential hypertension. Extent score was useful for evaluation of the severity of myocardial damage in hypertensive patients. 10.1161/01.hyp.23.1_suppl.i164
    Circulating tissue inhibitor of matrix metalloproteinase-1 is associated with aldosterone-induced diastolic dysfunction. Hung Chi-Sheng,Chou Chia-Hung,Wu Xue-Ming,Chang Yi-Yao,Wu Vin-Cent,Chen Ying-Hsien,Chang Yuan-Shian,Tsai Yao-Chou,Su Ming-Jai,Ho Yi-Lwun,Chen Ming-Fong,Wu Kwan-Dun,Lin Yen-Hung, Journal of hypertension OBJECTIVE:To test if collagen markers are associated with aldosterone-induced diastolic dysfunction. BACKGROUND:Although primary aldosteronism is associated with more prominent cardiac remodeling and diastolic dysfunction, the reversibility of diastolic function is unclear. In addition, there is no known biomarker associated with aldosterone-induced diastolic dysfunction. METHODS:We enrolled 27 patients with aldosterone-producing adenoma (APA) preparing for adrenalectomy, and 27 patients with essential hypertension prospectively from October 2006 to March 2010 at a tertiary referral center. Plasma matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were measured, and echocardiography including tissue Doppler images was performed in both groups and 1 year after receiving adrenalectomy in the APA group. RESULTS:The baseline plasma TIMP-1 level (88.4 ± 38.7 vs. 63.6 ± 32.5 ng/ml; P = 0.014), left ventricular mass index (LVMI), and E/E' ratio (11.5 ± 2.9 vs. 9.0 ± 2.1; P < 0.001) were significantly higher in the APA group. The baseline plasma TIMP-1 level significantly correlated with the E/E' ratio, LVMI, interventricular septum, and left atrial diameter. The plasma MMP-2 level did not correlate with the left ventricular structure parameters, except for interventricular septum thickness. After adrenalectomy, LVMI and E/E' ratio improved significantly. The postadrenalectomy plasma TIMP-1 levels, but not MMP-2 levels, also decreased. The change of plasma TIMP-1 levels was negatively associated with the postadrenalectomy E/E' ratio after adjustment for age, sex, BMI, and mean blood pressure (β-coefficient = - 3.6, P = 0.004). CONCLUSION:Excess of aldosterone induces cardiac diastolic dysfunction, which is reversible by adrenalectomy. TIMP-1 is associated with the aldosterone-induced diastolic dysfunction. 10.1097/HJH.0000000000000619
    Reduced renal extraction of atrial natriuretic peptide in primary aldosteronism. Tunny T J,Gordon R D,Klemm S A,Stowasser M Hypertension (Dallas, Tex. : 1979) We investigated renal and peripheral forearm extraction of atrial natriuretic peptide in patients with primary aldosteronism to determine whether alterations in extraction may contribute to the elevated levels of circulating atrial natriuretic peptide observed in primary aldosteronism. We obtained simultaneous venous blood samples from the left renal vein and a peripheral vein and from the radial artery in 28 patients with primary aldosteronism and 10 patients with essential hypertension. Renal extraction of atrial natriuretic peptide was significantly (P < .001) reduced (40 +/- 2%) in primary aldosteronism compared with essential hypertensive patients (62 +/- 3%). Peripheral forearm extraction was also reduced (P < .01) in primary aldosteronism compared with essential hypertensive patients (24 +/- 3% versus 38 +/- 4%). These findings are consistent with widespread downregulation of atrial natriuretic peptide receptors in primary aldosteronism. Consistent with reports that marked reduction in glomerular filtration rate is required before the renal extraction of atrial natriuretic peptide is reduced, no significant relationship between renal extraction of atrial natriuretic peptide and plasma creatinine was seen in primary aldosteronism or essential hypertension. Although the major regulators of atrial natriuretic peptide secretion in primary aldosteronism are presumably alterations in arterial blood pressure and plasma volume, reduced renal and peripheral extraction of atrial natriuretic peptide in primary aldosteronism may also contribute significantly to the elevated circulating levels observed. 10.1161/01.hyp.26.4.624
    Changes in left ventricular anatomy and function in hypertension and primary aldosteronism. Rossi G P,Sacchetto A,Visentin P,Canali C,Graniero G R,Palatini P,Pessina A C Hypertension (Dallas, Tex. : 1979) We investigated the effects on the heart of hypertension due to the excess of aldosterone and suppression of the renin-angiotensin system caused by primary aldosteronism with M-mode echocardiography and transmitral Doppler flow velocity measurements. We studied 34 consecutive patients with primary aldosteronism and 34 with essential hypertension individually matched for age, gender, race, body mass index, blood pressure values, and duration of hypertension. The groups were similar in age, body mass index, blood pressure, and duration of hypertension. However, lower serum potassium levels (3.5 +/- 0.6 versus 4.1 +/- 0.2 mmol/L, P < .0001) and plasma renin activity (0.53 +/- 0.45 versus 1.82 +/- 1.59 ng Ang I x mL-1 x h-1, P < .0001) and higher plasma aldosterone levels (1107 +/- 774 versus 206 +/- 99 pmol/L, P < .0001), left ventricular wall thickness, and left ventricular mass index (112 +/- 4.7 versus 98 +/- 3.7 g/m2, P = .029) were found in patients with primary aldosteronism compared with those with essential hypertension. Similarly, the PQ interval was longer (173 +/- 20 versus 141 +/- 14 milliseconds, P < .001) in primary aldosteronism than in essential hypertension patients. Significantly more primary aldosteronism than essential hypertension patients had left ventricular hypertrophy or left ventricular concentric remodeling (50% versus 15%, chi 2 = 11.97, P = .007). Both the E wave flow velocity integral (1063 +/- 65 versus 1323 +/- 78, P = .013) and the E/A integral ratio (0.91 +/- 0.05 versus 1.25 +/- 0.08, P < .001) were lower, and atrial contribution to left ventricular filling was higher (53.3 +/- 1.5% versus 45.5 +/- 1.3% P < .001) in patients with primary aldosteronism compared with essential hypertension patients. After 1 year of follow-up, highly significant decreases of left ventricular wall thickness and mass were observed in patients treated with surgical excision of an aldosterone-producing tumor, but not in those with medical therapy. Thus, in patients with primary aldosteronism, the excess aldosterone with suppression of the renin-angiotensin system is associated with both increased left ventricular mass and significant changes of left ventricular diastolic filling. The former changes appear to be reversible on removal of the cause of excessive aldosterone production. 10.1161/01.hyp.27.5.1039
    Prevalence of extracranial carotid artery lesions at duplex in primary aldosteronism. Rossi G,Rossi A,Zanin L,Calabró A,Crepaldi G,Pessina A C American journal of hypertension Renovascular hypertension and high renin hypertension were found to be associated with an excess prevalence of carotid artery atherosclerotic lesions and to a higher risk of stroke, respectively, as compared to low-to-normal renin hypertension. Primary aldosteronism, being characterized by hypertension and a chronically suppressed plasma renin activity, should be accompanied by a low prevalence of carotid artery lesions. To verify this hypothesis we investigated prospectively, by a high resolution duplex ultrasound technique, the prevalence of extracranial carotid artery lesions in a case-controlled study of 34 (22 women and 12 men, aged 22 to 76 years) patients with no history or symptoms of cerebrovascular disease. Primary aldosteronism was diagnosed in 17 patients; 12 had a surgically confirmed unilateral aldosterone-secreting adenoma; and 5 had idiopathic hyperaldosteronism. Each primary aldosteronism patient was individually matched with a control with primary hypertension for sex, race, age, body mass index, casual blood pressure levels, duration of hypertension, smoking, diabetes mellitus, total serum cholesterol, and triglycerides. After the matching, the two groups were similar in terms of demographic features and overall cardiovascular risk profile (all P = NS). However, plasma renin activity and aldosterone levels were significantly lower and higher, respectively, in primary aldosteronism than in primary hypertensive patients. In primary aldosteronism the overall prevalence of carotid artery lesions at duplex was 59%, not significantly different from that (53%) found in primary hypertensives. Thus, at variance with renovascular hypertension, primary aldosteronism is not associated with an excess prevalence of carotid artery lesions. 10.1093/ajh/6.1.8
    Evidence for abnormal left ventricular structure and function in normotensive individuals with familial hyperaldosteronism type I. Stowasser Michael,Sharman James,Leano Rodel,Gordon Richard D,Ward Gregory,Cowley Diane,Marwick Thomas H The Journal of clinical endocrinology and metabolism OBJECTIVES:To explore whether aldosterone excess can induce adverse cardiovascular effects independently of effects on blood pressure (BP), we sought evidence of disturbed cardiovascular structure or function in normotensive individuals with primary aldosteronism. METHODS:Eight normotensive subjects with genetically proven familial hyperaldosteronism type I (FH-I) were compared with 24 age- and sex-matched normotensive controls in terms of BP, biochemical parameters, pulse wave velocity, and echocardiographic characteristics. RESULTS:Subjects with FH-I demonstrated higher serum aldosterone levels and aldosterone/renin ratios than controls, as expected. Despite having similar 24-h ambulatory BPs, subjects with FH-I demonstrated evidence of concentric remodeling with greater septal (mean +/- sd, 9.4 +/- 1.1 vs. 7.9 +/- 0.9 mm; P < 0.001), posterior wall (9.2 +/- 1.7 vs. 7.7 +/- 1.0 mm; P < 0.01), and relative wall (0.29 +/- 0.03 vs. 0.24 +/- 0.02; P < 0.001) thicknesses, and lower mitral early peak velocities (0.74 +/- 0.10 vs. 0.90 +/- 0.16 m/sec; P < 0.05), ratios of early to late peak diastolic transmitral flow velocity (1.56 +/- 0.24 vs. 2.06 +/- 0.41; P < 0.01), and myocardial early peak velocities (8.3 +/- 1.8 vs. 10.3 +/- 2.6 cm/sec; P < 0.05). There were no significant differences in pulse wave velocity or left ventricular ejection fraction, long axis strain rate, peak systolic strain, cyclic variation of integrated backscatter, or posterior wall calibrated integrated backscatter. CONCLUSIONS:Aldosterone excess is associated with increased left ventricular wall thicknesses and reduced diastolic function, even in the absence of hypertension. 10.1210/jc.2005-0681
    PENTRAXIN 3 AS A NEW CARDIOVASCULAR MARKER IN ADRENAL ADENOMAS. Kizilgul Muhammed,Beysel Selvihan,Ozcelik Ozgur,Kan Seyfullah,Apaydin Mahmut,Caliskan Mustafa,Ucan Bekir,Sencar Erkam,Ozdemir Seyda,Cakal Erman Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists OBJECTIVE:Pentraxin 3 (PTX3) is an acute-phase glycoprotein, which is increased in patients with cardiovascular disease (CVD) and considered as a predictor of CVD in the general population. Both functional and nonfunctional adrenal tumors are associated with a higher risk of cardiovascular events and mortality. We aimed to investigate plasma PTX3 levels in patients with functioning and nonfunctioning adrenal tumors and determine its relationship with cardiovascular risk factors. METHODS:Twenty-one patients with functional adrenal tumors (11 pheochromocytomas, 9 Cushing syndrome, and 1 primary hyperaldosteronism), 28 patients with nonfunctional adrenal incidentalomas, and 40 healthy controls were enrolled in the study. Serum PTX3 levels were measured using a human PTX3 enzyme-linked immunosorbent assay. RESULTS:PTX3 concentrations were significantly higher in the adrenal tumor group compared with the control group (3,001.64 ± 374.64 pg/mL vs. 1,173.59 ± 168.89 pg/mL; P<.001). PTX3 concentrations were positively correlated with carotid intima media thickness (CIMT) (r, 0.464; P<.001), high-sensitivity C-reactive protein (hsCRP) (r, 0.551; P<.001), diastolic blood pressure (r, 0.334; P = .003), systolic blood pressure (r, 0.312; P = .006), and urinary metanephrine concentrations (r, 0.320; P = .041). Serum PTX3 concentrations in patients with functional adrenal tumors and comorbidities including hypertension, diabetes mellitus, or CVD were higher than in those without comorbidities (3,654.54 ± 447 pg/mL vs. 1,026.96 ± 447.97 pg/mL; P = .008). CONCLUSION:We found that serum PTX3 concentrations increased in both functional and nonfunctional adrenal tumors. PTX3 levels were correlated with cardiovascular risk factors such as CIMT, hsCRP, and blood pressure. ABBREVIATIONS:BMI = body mass index; CIMT = carotid intima-media thickness; CRP = C-reactive protein; CT = computed tomography; CVD = cardiovascular disease; FGF2 = fibroblast growth factor 2; hsCRP = high-sensitivity C-reactive protein; PA = primary hyperaldosteronism; PTX3 = pentraxin 3. 10.4158/EP161713.OR
    Aldosterone Impairs Vascular Smooth Muscle Function: From Clinical to Bench Research. Chou Chia-Hung,Chen Ying-Hsien,Hung Chi-Sheng,Chang Yi-Yao,Tzeng Yu-Lin,Wu Xue-Ming,Wu Vin-Cent,Tsai Chia-Ti,Wu Cho-Kai,Ho Yi-Lwun,Wu Kwan-Dun,Lin Yen-Hung, The Journal of clinical endocrinology and metabolism CONTEXT:The effect of aldosterone on vascular smooth muscle cell function is still unclear. One method to measure vascular smooth muscle cell function is endothelial-independent vascular dilation, for which the key factor is sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA). OBJECTIVE:Our objective was to investigate the effect of aldosterone on vascular smooth muscle cell function and SERCA regulation. DESIGN:We prospectively analyzed 35 patients with primary aldosteronism (PA; 32 patients with aldosterone-producing adenoma and three patients with idiopathic hyperaldosteronism) and 30 patients with essential hypertension (EH) who were enrolled as the control group. Flow and nitrate-mediated dilation were performed in both groups and 1 year after adrenalectomy in the patients with aldosterone-producing adenoma. In addition, we investigated the effect of aldosterone on SERCA regulation in human aortic smooth muscle cells. SETTING:This study took place in an academic clinical research center. PARTICIPANTS:Participants included 35 patients with PA and 30 patients with EH. INTERVENTIONS:Adrenalectomy was undertaken in patients with aldosterone-producing adenoma. RESULTS:The PA patients had significantly lower flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) values than the patients with EH (FMD: 13 ± 6 vs 16 ± 4; NMD: 16 ± 6 vs 19 ± 5; both P < .05). FMD/NMD were significantly correlated with log 24 hour-urine aldosterone (FMD: r = -0.287, P = .048; NMD: r = -0.402, P = .005) but not blood pressure. The impaired FMD and NMD values were significantly restored 1 year after adrenalectomy (FMD: 11 ± 4 to 19 ± 7; NMD: 15 ± 6 to 21 ± 6; both P < .01). Under confocal microscopy, aldosterone was shown to suppress the expression of SERCA2a of human aortic smooth muscle cells. Aldosterone significantly suppressed the expression of SERCA2a from 10(-8) M in mRNA and protein levels. This suppression was through down-regulation of mineralocorticoid receptor dependent mitochondrial transcription factors A and B2. CONCLUSIONS:Aldosterone impairs vascular smooth muscle cell function and suppresses SERCA 2a expression. 10.1210/jc.2015-2752
    Factors determining cardiovascular and renal outcomes after adrenalectomy in patients with aldosterone-producing adrenal adenoma. Chiou Terry Ting-Yu,Chiang Po-Hui,Fuh Morgan,Liu Rue-Tsuan,Lee Wei-Ching,Lee Wen-Chin,Ng Hwee-Yeong,Tsai Yu-Che,Chuang Fong-Rong,Huang Chao-Cheng,Lee Chien-Te The Tohoku journal of experimental medicine Primary aldosteronism is an important cause of secondary hypertension, because it is potentially curable, especially in case of unilateral aldosterone-producing adrenal adenoma (APA). However, the information is limited concerning the cardiovascular and renal outcomes in this patient population. We studied 52 patients with APA in order to determine the pre-operative and post-operative factors predicting cardiovascular and renal outcomes. All 52 patients were hypertensive before the operation. Among 35 patients who underwent pre-operative electrocardiogram, 23 patients had left ventricular hypertrophy (LVH). Patients with LVH had lower estimated glomerular filtration rate (eGFR). Adrenalectomy successfully normalized or improved hypertension, hypokalemia, and aldosterone excess. One month after the adrenalectomy, 32 patients (62%) became normotensive, but 20 patients (38%) remained hypertensive. However, after an average follow-up period of 51 months, only 18 patients remained normotensive, while 34 patients were hypertensive. Thus, the rate of recurrent hypertension after adrenalectomy was high (14/32, 43%). Pre-operative systolic blood pressure (BP), diastolic BP, and post-operative plasma aldosterone concentrations were the only variables significantly different between the hypertensive and normotensive patients. Using pre-operative BP 165/110 mmHg as a cutoff has good positive predictive values (73-92%) for post-operative long-term hypertension. Patients whose renal function worsened after adrenalectomy had significantly higher pre-operative plasma active renin levels. Thus, in patients with APA, the presence of LVH is correlated with impaired renal function (lower eGFR). In conclusion, pre-operative BP and post-operative plasma aldosterone are important in predicting post-adrenalectomy hypertension, and a lower pre-operative plasma renin predicts the improvement in renal function after adrenalectomy.
    Effect of Increased Potassium Intake on Adrenal Cortical and Cardiovascular Responses to Angiotensin II: A Randomized Crossover Study. Dreier Rasmus,Andersen Ulrik B,Forman Julie L,Sheykhzade Majid,Egfjord Martin,Jeppesen Jørgen L Journal of the American Heart Association Background Increased potassium intake lowers blood pressure in patients with hypertension, but increased potassium intake also elevates plasma concentrations of the blood pressure-raising hormone aldosterone. Besides its well-described renal effects, aldosterone is also believed to have vascular effects, acting through mineralocorticoid receptors present in endothelial and vascular smooth muscle cells, although mineralocorticoid receptors-independent actions are also thought to be involved. Methods and Results To gain further insight into the effect of increased potassium intake and potassium-stimulated hyperaldosteronism on the human cardiovascular system, we conducted a randomized placebo-controlled double-blind crossover study in 25 healthy normotensive men, where 4 weeks treatment with a potassium supplement (90 mmol/day) was compared with 4 weeks on placebo. At the end of each treatment period, we measured potassium and aldosterone in plasma and performed an angiotensin II (AngII) infusion experiment, during which we assessed the aldosterone response in plasma. Hemodynamics were also monitored during the AngII infusion using ECG, impedance cardiography, finger plethysmography (blood pressure-monitoring), and Doppler ultrasound. The study showed that higher potassium intake increased plasma potassium (mean±SD, 4.3±0.2 versus 4.0±0.2 mmol/L; =0.0002) and aldosterone (median [interquartile range], 440 [336-521] versus 237 [173-386] pmol/L; <0.0001), and based on a linear mixed model for repeated measurements, increased potassium intake potentiated AngII-stimulated aldosterone secretion (=0.0020). In contrast, the hemodynamic responses (blood pressure, total peripheral resistance, cardiac output, and renal artery blood flow) to AngII were similar after potassium and placebo. Conclusions Increased potassium intake potentiates AngII-stimulated aldosterone secretion without affecting systemic cardiovascular hemodynamics in healthy normotensive men. Registration EudraCT Number: 2013-004460-66; URL: https://www.ClinicalTrials.gov; Unique identifier: NCT02380157. 10.1161/JAHA.120.018716
    Evidence of exercise-induced myocardial ischemia in patients with primary aldosteronism: the Cross-sectional Primary Aldosteronism and Heart Italian Multicenter Study. Napoli C,Di Gregorio F,Leccese M,Abete P,Ambrosio G,Giusti R,Casini A,Ferrara N,De Matteis C,Sibilio G,Donzelli R,Montemarano A,Mazzeo C,Rengo F,Mansi L,Liguori A Journal of investigative medicine : the official publication of the American Federation for Clinical Research BACKGROUND:Primary aldosteronism (PA) is a disease associated with hypersecretion of aldosterone caused by an aldosterone-producing adrenal adenoma, bilateral adrenal hyperplasia, and, although rarely, by adrenal carcinoma. Arterial hypertension induces several cardiovascular alterations that yield a high cardiovascular risk. It has been shown that reduced myocardial perfusion at rest, assessed by thallium-201 myocardial scintigraphy, was greater in PA than in essential hypertension (EH). However, it is still unknown whether reduced myocardial perfusion at rest and/or regional function abnormalities are present during exercise-induced myocardial stress. PURPOSE:We addressed the impact of PA on myocardial ischemia and sought to identify signs of exercise-induced myocardial ischemia (assessed by MIBI-SPECT and echocardiography) in patients with PA compared to patients with EH. Patients with consistent signs of myocardial ischemia on all of the tests were studied by coronary arteriography. PATIENTS:We studied 72 patients with PA and an age/sex-matched group of 72 patients with EH enrolled in the cross-sectional Primary Aldosteronism and Heart Italian Multicenter Study (PAHIMS). METHODS:Regional function was detected from echocardiographic measurement of wall motion done at baseline and immediately after exercise. Myocardial perfusion was evaluated by SPECT imaging after injecting 99mTc-MIBI with the same-day protocol using the rest-stress sequence. RESULTS:Although the conditions of arterial pressure, duration of hypertension, and target organ damage were equivalent, the patients with PA had greater incidence of both reversible perfusion defects and abnormalities of regional function. Moreover, multiple regression analysis showed that the high plasma aldosterone level was highly predictive for SPECT ischemic score and wall motion index, suggesting that PA contributes to cardiovascular risk over and above that associated with ventricular hypertrophy. Exercise-induced myocardial ischemia in PA was not segmental but widely distributed suggesting that this phenomenon was not related to abnormal coronary perfusion. Accordingly, of the 38 patients with PA who underwent coronarography, there was no presence of significant coronary atherosclerotic lesions in 30 (78.9%) of the patients. CONCLUSIONS:The PAHIMS observed more exercise-induced moderate myocardial ischemic defects (co-detected by SPECT and echocardiograms and not segmental but widely allocated) in patients with PA than in patients with EH. This phenomenon occurred in a greater percentage of patients with PA without significant coronary lesions (78.95%, n = 38), which supports the possible presence of small-vessel intramyocardial disease.
    Hyperaldosteronism induces left atrial systolic and diastolic dysfunction. Reil Jan-Christian,Tauchnitz Marcus,Tian Qinghai,Hohl Mathias,Linz Dominik,Oberhofer Martin,Kaestner Lars,Reil Gert-Hinrich,Thiele Holger,Steendijk Paul,Böhm Michael,Neuberger Hans-Ruprecht,Lipp Peter American journal of physiology. Heart and circulatory physiology Patients with hypertension and hyperaldosteronism show an increased risk of stroke compared with patients with essential hypertension. Aim of the study was to assess the effects of aldosterone on left atrial function in rats as a potential contributor to thromboembolism. Osmotic mini-pumps delivering 1.5 μg aldosterone/h were implanted in rats subcutaneously (Aldo, n = 39; controls, n = 38). After 8 wk, left ventricular pressure-volume analysis of isolated working hearts was performed, and left atrial systolic and diastolic function was also assessed by atrial pressure-diameter loops. Moreover, left atrial myocytes were isolated to investigate their global and local Ca handling and contractility. At similar heart rates, pressure-volume analysis of isolated hearts and in vivo hemodynamic measurements revealed neither systolic nor diastolic left ventricular dysfunction in Aldo. In particular, atrial filling pressures and atrial size were not increased in Aldo. Aldo rats showed a significant reduction of atrial late diastolic A wave, atrial active work index, and increased V waves. Consistently, in Aldo rats, sarcomere shortening and the amplitude of electrically evoked global Ca transients were substantially reduced. Sarcoplasmic reticulum-Ca content and fractional Ca release were decreased, substantiated by a reduced sarcoplasmic reticulum calcium ATPase activity, resulting from a reduced CAMKII-evoked phosphorylation of phospholamban. Hyperaldosteronism induced atrial systolic and diastolic dysfunction, while atrial size and left ventricular hemodynamics, including filling pressures, were unaffected in rats. The described model suggests a direct causal link between hyperaldosteronism and decreased atrial contractility and diastolic compliance. 10.1152/ajpheart.00261.2016
    Cardiovascular complications in patients with primary aldosteronism. Nishimura M,Uzu T,Fujii T,Kuroda S,Nakamura S,Inenaga T,Kimura G American journal of kidney diseases : the official journal of the National Kidney Foundation Primary aldosteronism (PA) is widely believed to be a relatively benign form of hypertension associated with a low incidence of vascular complications. However, several recent studies showed that cardiovascular complications were not rare in PA. PA is known as one of the most typical forms of sodium-sensitive hypertension. Recently, we found that the sodium sensitivity of blood pressure was a marker for greater risk for cardiovascular complications, especially stroke, in patients with essential hypertension. Therefore, we investigated cardiovascular complications in 58 patients with PA confirmed to be Conn's adenoma. Cardiovascular complications were found in 34% of 58 patients. Coronary artery disease was found in only one patient (1.7%), as angina pectoris. Stroke was found in nine patients (15.5%), four patients (6.9%) with cerebral infarctions and five patients (8.6%) with cerebral hemorrhages. Proteinuria and renal insufficiency were found in 14 (24.1%) and 4 (6.9%) patients, respectively. The incidence of cerebral infarction and renal insufficiency was greater in men than women. The prevalence of proteinuria was greater in patients with than without stroke (P = 0.03) among those aged older than 40 years. These results indicated that cardiovascular complications, especially stroke and proteinuria, were common in patients with PA, and proteinuria might be an indicator for stroke as target-organ damage.
    Impaired baroreflex function and arterial compliance in primary aldosteronism. Veglio F,Molino P,Cat Genova G,Melchio R,Rabbia F,Grosso T,Martini G,Chiandussi L Journal of human hypertension The purpose of this study was to evaluate if changes in vascular properties were related to baroreflex function in patients with primary aldosteronism. Twenty-three patients with primary aldosteronism, 22 essential hypertensive patients and 16 normal controls were studied. Continuous finger blood pressure (BP) was recorded by Portapres device during supine rest and active stand up. Compliance was estimated from the time constant of pressure decay during diastole. Baroreflex sensitivity was calculated by autoregressive cross-spectral analysis of systolic BP and interbeat interval. The result was that baroreflex gain and compliance were lower in primary aldosteronism patients in the supine position (P = 0.002 and P < 0.05 respectively). Aldosterone plasma levels (R2 = 0.31, P = 0.01), age, systolic and diastolic BP, high and low frequency components of diastolic BP variability were independently related to compliance in primary aldosteronism. In conclusion primary aldosteronism is associated with an impaired baroreflex function related in part to a reduced arterial compliance. Despite a reduction of BP values and aldosterone levels, surgical or pharmacological treatment did not significantly change compliance values. 10.1038/sj.jhh.1000737
    Microvascular endothelial function is impaired in patients with idiopathic hyperaldosteronism. Kishimoto Shinji,Matsumoto Takeshi,Oki Kenji,Maruhashi Tatsuya,Kajikawa Masato,Matsui Shogo,Hashimoto Haruki,Kihara Yasuki,Yusoff Farina Mohamad,Higashi Yukihito Hypertension research : official journal of the Japanese Society of Hypertension The aims were to evaluate the relationship between idiopathic hyperaldosteronism (IHA) and grade of vascular function in the macrovasculature and microvasculature. Vascular function, including reactive hyperemia index (RIH), flow-mediated vasodilation (FMD), and nitroglycerine-induced vasodilation (NID) were evaluated in 52 patients with IHA, 53 patients with aldosterone-producing adenoma (APA), and 52 age-, sex-, and blood pressure-matched patients with essential hypertension (EHT). Log RHI was lower in the IHA and APA groups than in the EHT group (0.54 ± 0.25 and 0.55 ± 0.23 versus 0.79 ± 0.28; P < 0.01, respectively). FMD was lower in the APA group than in the EHT group (3.4 ± 2.1% versus 4.8 ± 2.8%; P = 0.02), whereas there was no significant difference in FMD between the IHA and the APA and EHT groups. NID was lower in the APA group than in the EHT group (10.0 ± 4.5% versus 12.5 ± 5.7%; P = 0.03), whereas there was no significant difference in NID between the IHA, APA, and EHT groups. Multiple regression analysis revealed an association of log RHI with plasma aldosterone concentration (t = -2.24; P = 0.03) and an association of FMD with plasma aldosterone concentration (t = -3.07; P < 0.01). Microvascular endothelial function was impaired in patients with IHA compared with that in patients with EHT. 10.1038/s41440-018-0093-6
    Aldosterone Induces Vascular Damage. Hung Chi-Sheng,Sung Shih-Hsien,Liao Che-Wei,Pan Chien-Ting,Chang Chin-Chen,Chen Zheng-Wei,Wu Vin-Cent,Chen Chen-Huan,Cheng Hao-Min,Lin Yen-Hung, Hypertension (Dallas, Tex. : 1979) Primary aldosteronism (PA) is hemodynamically independently associated with arterial wall stiffness as assessed by pulse wave velocity (PWV) compared with essential hypertension. Arterial wave reflection parameters derived from pulse wave analysis, such as forward and backward wave amplitudes (Pf and Pb), are promising vascular markers to predict cardiovascular outcomes in addition to PWV. These vascular parameters have never been studied in patients with PA before. In study part A, we prospectively enrolled 67 patients with PA and 132 patients with essential hypertension. In study part B, another 54 patients with PA were enrolled. Heart-carotid PWV was measured, and carotid pressure waveforms were recorded to calculate Pf, Pb, and augmentation index at baseline (part A and B) and 6 months after treatment (part B). The results showed that the patients with PA had significantly higher Pf (P=0.001), Pb (P=0.01), and PWV (P=0.021) than the patients with essential hypertension. In univariate correlation analysis, both log Pf and Pb were significantly correlated with age, office blood pressure, serum potassium level, log PWV, and the presence of PA. However, only Pb was significantly correlated with log plasma renin activity and log aldosterone to renin ratio. In multivariate analysis, log Pf was significantly correlated with the presence of PA (P=0.001), male sex, age, and mean arterial blood pressure. Pb was significantly correlated with the presence of PA (P=0.031), age, and mean arterial pressure. Six months after treatment, Pf and Pb decreased significantly. In conclusion, the patients with PA had significantly increased wave reflections compared with the patients with essential hypertension. Our results provide clinical evidence of aldosterone-related extensive vascular dysfunction of the arterial system. 10.1161/HYPERTENSIONAHA.118.12342
    Excess aldosterone is associated with alterations of myocardial texture in primary aldosteronism. Rossi Gian Paolo,Di Bello Vitantonio,Ganzaroli Chiara,Sacchetto Alfredo,Cesari Maurizio,Bertini Alessio,Giorgi Davide,Scognamiglio Roldano,Mariani Mario,Pessina Achille C Hypertension (Dallas, Tex. : 1979) Hyperaldosteronism has been causally linked to myocardial interstitial fibrosis experimentally, but it remains unclear if this link also applies to humans. Thus, we investigated the effects of excess aldosterone due to primary aldosteronism (PA) on collagen deposition in the heart. We used echocardiography to estimate left ventricular (LV) wall thickness and dimensions and for videodensitometric analysis of myocardial texture in 17 consecutive patients with PA and 10 patients with primary (essential) hypertension who were matched for demographics, casual blood pressure, and known duration of hypertension. The groups differed in serum K+, ECG PQ interval duration, plasma renin activity, and aldosterone levels (all P< or =0.002) but not for casual blood pressure values, demographics, and duration of hypertension. Compared with hypertensive patients, PA patients showed a higher LV mass index (53.7+/-1.8 versus 45.5+/-2.0 g/m(2.7); P=0.008) and lower values of the cyclic variation index of the myocardial mean gray level of septum (CVI(s); -12.02+/-5.84% versus 6.06+/-3.08%; P=0.012) and posterior wall (-11.13+/-6.42% versus 8.63+/-9.62%; P=0.012). A regression analysis showed that CVI(s) was predicted by the PQ duration, supine plasma renin activity, plasma aldosterone, and age, which collectively accounted for approximately 36% of CVI(s) variance. PA is associated with alterations of myocardial textures that suggest increased collagen deposition and that can explain both the dependence of LV diastolic filling from presystole and the prolongation of the PQ interval. 10.1161/01.hyp.0000023182.68420.eb
    Long-term BP control and vascular health in patients with hyperaldosteronism treated with low-dose, amiloride-based therapy. Izzo Joseph L,Hong Michael,Hussain Tanveer,Osmond Peter J Journal of clinical hypertension (Greenwich, Conn.) Whether aldosterone itself contributes directly to macro- or microcirculatory disease in man or to adverse cardiovascular outcomes is not fully known. We report our long-term single-practice experience in 5 patients with chronic hyperaldosteronism (HA, including 3 with glucocorticoid remediable aldosteronism, GRA) treated with low-dose amiloride (a specific epithelial sodium channel [ENaC] blocker) 5-10 (mean 7) mg daily for 14-28 (mean 20) years. Except for 1 GRA diagnosed in infancy, all had severe resistant hypertension. In each case, BP was normal or near-normal within 1-4 weeks after starting amiloride and office BP's were well controlled for 20 years thereafter. Vascular studies and 24-hour ambulatory BP monitoring with pulse wave analysis (cardiac output, vascular resistance, augmentation index, and reflection magnitude) were assessed after a mean of 18 years as were regional pulse wave velocities, pulse stiffening ratio, ankle-brachial index, serum creatinine, estimated glomerular filtration rate, and spot urinary albumin:creatinine ratio. All indicators were completely normal in all patients after 18 years of amiloride, and none had a cardiovascular event during the 20-year mean follow-up. We conclude that long-term ENaC blockade can normalize BP and protect macro- and microvascular function in patients with HA. This suggests that (a) any vasculopathic effects of aldosterone are mediated via ENaC, not MR activation itself, and are fully preventable or reversible with ENaC blockade or (b) aldosterone may not play a major BP-independent role in human macro- and microcirculatory diseases. These and other widely divergent results in the literature underscore the need for additional studies regarding aldosterone, ENaC, and vascular disease. 10.1111/jch.13567
    Adipokines and cardiometabolic profile in primary hyperaldosteronism. Iacobellis Gianluca,Petramala Luigi,Cotesta Dario,Pergolini Mario,Zinnamosca Laura,Cianci Rosario,De Toma Giorgio,Sciomer Susanna,Letizia Claudio The Journal of clinical endocrinology and metabolism CONTEXT:Primary aldosteronism (PA) has been recently associated with an unfavorable cardiometabolic profile. However, whether pro- and antiinflammatory adipokines levels can vary in PA is unknown. OBJECTIVE:We evaluated the circulating levels of resistin, leptin, and adiponectin, echocardiographic left ventricle (LV) parameters, and the prevalence of metabolic syndrome (SM) in subjects with PA. PATIENTS:Seventy-five subjects with established diagnosis of PA and 232 consecutive individuals with known or suspected hypertension were enrolled. MAIN OUTCOME MEASURES:Plasma adipokine levels and echocardiographic parameters were calculated. Prevalence of SM was also estimated. RESULTS:Among the 75 PA subjects, 37 patients were affected by aldosterone-producing adenoma and 38 by idiopathic hyperaldosteronism; 40 subjects were affected by essential hypertension (EH) and SM (EH SM+); 152 subjects were affected by EH without SM (EH SM-); and 40 subjects were normotensive (NT). Subjects with PA had the highest plasma resistin levels among the four groups (P < 0.01). Plasma resistin concentration was significantly higher in PA subjects when compared with EH SM+ individuals (P < 0.01) and EH SM- subjects (P < 0.01). PA subjects showed the higher LV mass and left atrium than EH individuals, irrespectively of the presence of SM (P < 0.01 for both). Plasma resistin levels was significantly correlated with ejection fraction and LV end-diastolic volume. The prevalence of SM was higher in PA subjects than in those with EH (25.4 vs. 20.3%). CONCLUSIONS:Our data suggest that elevated aldosterone levels is associated with elevated circulating resistin levels and cardiac morphological changes independently of the presence of SM. 10.1210/jc.2009-2204
    Maintenance of long-term blood pressure control and vascular health by low-dose amiloride-based therapy in hyperaldosteronism. Izzo Joseph L,Hong Michael,Hussain Tanveer,Osmond Peter J Journal of clinical hypertension (Greenwich, Conn.) Whether aldosterone itself contributes directly to macro- or microcirculatory disease in man or to adverse cardiovascular outcomes is not fully known. We report our long-term single-practice experience in an unusual group of five patients with chronic hyperaldosteronism (HA, including three with glucocorticoid-remediable aldosteronism, GRA) treated with low-dose amiloride (a specific epithelial sodium channel [ENaC] blocker) 5-10 (mean 7) mg daily for 14-28 (mean 20) years. Except for one GRA diagnosed in infancy, all had severe resistant hypertension. In each case, BP was normalized within 1-4 weeks after starting amiloride and office BP's remained well controlled throughout the next two decades. 24-hour ambulatory BP monitoring with pulse wave analysis (cardiac output, vascular resistance, augmentation index, reflection magnitude), regional pulse wave velocities, pulse stiffening ratio, ankle-brachial index, serum creatinine, estimated glomerular filtration rate, and spot urinary albumin:creatinine ratio were measured after a mean of 18 years; all of these indicators were essentially normal. Over two additional years of observation (100 patient-years total), no cardiovascular or renal event occurred. We conclude that long-term ENaC blockade with amiloride can normalize BP and protect macro- and microvascular function in patients with HA. This suggests that either (a) putative vasculopathic effects of aldosterone are mediated via ENaC or (b) aldosterone may not play a direct role in age-dependent vasculopathic changes in humans independent of blood pressure. These findings, coupled with our literature review in both animal and human results, underscore the need for additional studies. 10.1111/jch.13597
    Refractory hyperaldosteronism in heart failure is associated with plasma renin activity and angiotensinogen polymorphism. Vergaro Giuseppe,Fatini Cinzia,Sticchi Elena,Vassalle Cristina,Gensini Gianfranco,Ripoli Andrea,Rossignol Patrick,Passino Claudio,Emdin Michele,Abbate Rosanna Journal of cardiovascular medicine (Hagerstown, Md.) AIMS:Refractory hyperaldosteronism is frequently observed in heart failure patients on up-to-date treatment, and holds prognostic value. Our aim was to identify which factors, either genetic or nongenetic, are associated with refractory hyperaldosteronism. METHODS:We enrolled 109 consecutive patients with left ventricular systolic dysfunction [left ventricular ejection fraction (LVEF) 32 ± 10%; 86% males; age 65 ± 13 years (mean ± standard deviation)] on optimized adrenergic and renin-angiotensin-aldosterone system (RAAS) antagonism, undergoing clinical and neuroendocrine characterization, and genotyping for six polymorphisms in key RAAS-regulating genes [angiotensinogen (AGT M235T), angiotensin-converting enzyme (ACE-240A>T and I/D), angiotensin II type I receptor (AGTR1 1166A>C), aldosterone synthase (CYP11B2-344C>T) and renin (REN rs7539596)]. RESULTS:Patients with refractory hyperaldosteronism (n = 41, 38%, with plasma concentration >180 ng/l, URL, median 283 ng/l, interquartile range 218-433), when compared with those without (106 ng/l, 74-144; P < 0.001), were not different either for treatment or LVEF, while presented with different AGT M235T genotype distribution (P = 0.047). After adjustment for several humoral, instrumental, functional and therapeutical variables, only plasma renin activity (PRA) (P < 0.001) and potassium (P = 0.027) were independently associated with refractory hyperaldosteronism. Among polymorphisms, only AGT M235T (P = 0.038) was associated with refractory hyperaldosteronism, after adjustment for nongenetic variables. CONCLUSIONS:In conclusion, refractory hyperaldosteronism in heart failure may be influenced by AGT M235T polymorphism, among RAAS candidate genes, and by PRA, which may represent, respectively, a constitutive (genotype dependent) and a nongenetic (phenotype-dependent) trigger for aldosterone elevation. 10.2459/JCM.0000000000000156
    Plasma osteopontin levels are higher in patients with primary aldosteronism than in patients with essential hypertension. Irita Jun,Okura Takafumi,Manabe Seiko,Kurata Mie,Miyoshi Ken-Ichi,Watanabe Sanae,Fukuoka Tomikazu,Higaki Jitsuo American journal of hypertension BACKGROUND:The incidence of cardiovascular events is higher in patients with primary aldosteronism (PA) than in patients with essential hypertension (EHT). Aldosterone has been shown to play an important role in the development of vascular inflammation and myocardial fibrosis in animal models. Elevated serum inflammatory cytokine is an independent cardiovascular risk factor in patients with EHT. In the present study, we compared levels of inflammatory cytokines between patients with PA and EHT. METHODS:The study subjects were 15 patients with PA and 15 age-matched patients with EHT. Serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), high sensitive C-reactive protein (hsCRP), and plasma osteopontin (OPN) levels were measured by enzyme-linked immunosorbent assays. RESULTS:Systolic and diastolic blood pressure (BP) did not differ between the PA and EHT patient groups. Levels of serum IL-6 (P = .563), TNF-alpha (P = .480), and hsCRP (P = .870) did not differ between the two groups. In contrast, plasma OPN levels in patients with PA were significantly higher than those in patients with EHT (P < .0001). There was no relationship between BP and plasma OPN levels in patients with PA. CONCLUSIONS:The present study showed that plasma OPN levels were higher in patients with PA than in patients with EHT. 10.1016/j.amjhyper.2005.08.019
    Increased arterial wall stiffness in primary aldosteronism in comparison with essential hypertension. Strauch Branislav,Petrák Ondrej,Wichterle Dan,Zelinka Tomás,Holaj Robert,Widimský Jirí American journal of hypertension BACKGROUND:Aldosterone has been shown to substantially contribute to the accumulation of collagen fibers and growth factors in the arterial wall, which can increase wall stiffness. This study aimed at comparing arterial stiffness between patients with primary aldosteronism (PA), essential hypertension (EH), and normotensive controls using carotid-femoral pulse wave velocity (PWV) and central augmentation index (AI). METHODS:Thirty-six patients with confirmed PA, 28 patients with EH, and 20 normotensive subjects were investigated by Sphygmocor applanation tonometer. RESULTS:The office blood pressure (BP) at the time of the measurement (PA 167+/-34/92+/-12 mm Hg; EH 166+/-19/91+/-10 mm Hg), age, body mass index (BMI), cholesterol, triglyceride, blood glucose levels were comparable between PA and EH groups. The patients with PA had significantly higher PWV than the EH patients and control subjects (9.8+/-2.6 m/sec v 7.5+/-1.0 m/sec v 5.9+/-0.7 m/sec, respectively; all mutual differences P<.001). The difference in PWV between PA and EH remained statistically significant also after the adjustment for all clinical variables including 24-h BP using multivariate analysis (P=.001). CONCLUSIONS:Arterial wall stiffness is independently increased in PA compared to EH. This could be caused by the deleterious effects of aldosterone excess (potentially modulated by hypernatremia) on the fibrosis and remodeling of the arterial wall. 10.1016/j.amjhyper.2006.02.002
    Hypertension caused by primary hyperaldosteronism: increased heart damage and cardiovascular risk. Abad-Cardiel María,Alvarez-Álvarez Beatriz,Luque-Fernandez Loreto,Fernández Cristina,Fernández-Cruz Arturo,Martell-Claros Nieves Revista espanola de cardiologia (English ed.) INTRODUCTION AND OBJECTIVES:Primary hyperaldosteronism is the most common cause of secondary hypertension. Elevated aldosterone levels cause heart damage and increase cardiovascular morbidity and mortality. Early diagnosis could change the course of this entity. The objective of this report was to study the clinical characteristics, cardiac damage and cardiovascular risk associated with primary hyperaldosteronism. METHODS:We studied 157 patients with this diagnosis. We analyzed the reason for etiological investigation, and the routinely performed tests, including echocardiography. We used a cohort of 720 essential hypertensive patients followed in our unit for comparison. RESULTS:Compared with essential hypertensive patients, those with hyperaldosteronism were younger (56.9 [11.7] years vs 60 [14.4] years; P<.001), had higher blood pressure prior to the etiological diagnosis (136 [20.6] mmHg vs 156 [23.2] mmHg), more frequently had a family history of early cardiovascular disease (25.5% vs 2.2%; P<.001), and had a higher prevalence of concentric left ventricular hypertrophy (69% vs 25.7%) and higher cardiovascular risk. Specific treatment resulted in optimal control of systolic and diastolic blood pressures (from 150.7 [23.0] mmHg and 86.15 [14.07] mmHg to 12.69 [15.3] mmHg and 76.34 [9.7] mmHg, respectively). We suspected the presence of hyperaldosteronism because of resistant hypertension (33.1%), hypokalemia (38.2%), and hypertensive crises (12.7%). Only 4.6% of these patients had been referred from primary care with a suspected diagnosis of hyperaldosteronism. CONCLUSIONS:Hyperaldosteronism should be suspected in cases of resistant hypertension, hypokalemia and hypertensive crises. The diagnosis of hyperaldosteronism allows better blood pressure control. The most prevalent target organ damage is left ventricular hypertrophy. 10.1016/j.recesp.2012.07.025
    Reversal of myocardial fibrosis in patients with unilateral hyperaldosteronism receiving adrenalectomy. Lin Yen-Hung,Lee Hsiu-Hao,Liu Kao-Lang,Lee Jen-Kuang,Shih Shyang-Rong,Chueh Shih-Chieh,Lin Wei-Chou,Lin Lung-Chun,Lin Lian-Yu,Chung Shiu-Dong,Wu Vin-Cent,Kuo Chin-Chi,Ho Yi-Lwun,Chen Ming-Fong,Wu Kwan-Dun, Surgery BACKGROUND:Primary aldosteronism is the most frequent cause of secondary hypertension and is associated with more prominent left ventricular hypertrophy and increased myocardial fibrosis. Unilateral hyperaldosteronism can be cured by adrenalectomy. However, the reversibility of cardiac fibrosis is still unclear. METHODS:We analyzed 11 patients prospectively with unilateral hyperaldosteronism (including 10 aldosterone-producing adenomas and 1 unilateral nodular hyperplasia) who received adrenalectomy from October 2006 to October 2007, and 17 patients with essential hypertension (EH) were enrolled as the control group. Echocardiography included ultrasonic tissue characterization by cyclic variation of integrated backscatter; it was performed in both groups and 1 year after operation in the unilateral hyperaldosteronism group. RESULTS:Patients with unilateral hyperaldosteronism had significantly higher diastolic blood pressure, higher plasma aldosterone concentration, lower serum potassium level, and lower plasma renin activity than patients with EH. In echocardiography, patients with unilateral hyperaldosteronism had thicker interventricular septal thickness, left ventricular posterior wall thickness, and higher left ventricular mass index than EH patients. Patients with unilateral hyperaldosteronism had significant lower cyclic variation of integrated backscatter than EH patients (7.1 ± 2.1 vs 8.7 ± 1.5 dB, P = .037). After analyzing the correlation of cyclic variation of integrated backscatter with clinical parameters for all participants, only log-transformed plasma renin activity was correlated significantly with cyclic variation of integrated backscatter. One year after adrenalectomy, interventricular septal thickness, left ventricular posterior wall thickness, and left ventricular mass index decreased significantly. In addition, cyclic variation of integrated backscatter increased significantly after adrenalectomy (7.1 ± 2.1 to 8.5 ± 1.5 dB, P = .02). CONCLUSION:Adrenalectomy not only reversed left ventricular geometry but also altered myocardial texture in patients with unilateral hyperaldosteronism. This finding implies that increases in collagen content in the myocardium of patients with unilateral hyperaldosteronism might be reversed by adrenalectomy. 10.1016/j.surg.2011.02.006
    Comparisons of microvascular and macrovascular changes in aldosteronism-related hypertension and essential hypertension. Varano Monica,Iacono Pierluigi,Tedeschi Massimiliano M,Letizia Claudio,Curione Mario,Savoriti Claudio,Baiocco Erika,Zinnamosca Laura,Marinelli Cristiano,Boccassini Barbara,Parravano Mariacristina Scientific reports Case-control observational study to evaluate the microvascular and macrovascular changes in patients with hypertension secondary to primary aldosteronism (PA), essential hypertension (EH) and healthy subjects. Measurements of arterial stiffness including augmentation index (AIx) and pulse wave velocity (PWV) were assessed using a TensioClinic arteriograph system. Retinal microcirculation was imaged by a Retinal Vessel Analyzer (RVA) and a non-midriatic camera (Topcon-TRC-NV2000). IMEDOS software analyzed the retinal artery diameter (RAD), retinal vein diameters (RVD) and arteriole-to-venule ratio (AVR) of the vessels coming off the optic disc. Thirty, 39 and 35 patients were included in the PA, EH and control group, respectively. The PA group showed higher PWV values compared only with the control group. The mean brachial and aortic AIx values did not show significant difference between groups. In the PA group, the mean RVD and AVR values were significantly lower than in the EH and control groups, whereas the parameters did not differ between the EH and control groups. In conclusion, AVR appears significantly modified in the PA group compared with the EH group and could represent an early and more reliable indicator of microvascular remodeling. 10.1038/s41598-017-02622-2
    Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. Milliez Paul,Girerd Xavier,Plouin Pierre-François,Blacher Jacques,Safar Michel E,Mourad Jean-Jacques Journal of the American College of Cardiology OBJECTIVES:The aim of this report was to show that the rate of cardiovascular events is increased in patients with either subtype of primary aldosteronism (PA). BACKGROUND:Primary aldosteronism involves hypertension (HTN), hypokalemia, and low plasma renin. The two major PA subtypes are unilateral aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia. METHODS:During a three-year period, the diagnosis of PA was made in 124 of 5,500 patients referred for comprehensive evaluation and management. Adenomas were diagnosed in 65 patients and idiopathic hyperaldosteronism in 59 patients. During the same period, clinical characteristics and cardiovascular events of this group were compared with those of 465 patients with essential hypertension (EHT) randomly matched for age, gender, and systolic and diastolic blood pressure. RESULTS:A history of stroke was found in 12.9% of patients with PA and 3.4% of patients with EHT (odds ratio [OR] = 4.2; 95% confidence interval [CI] 2.0 to 8.6]). Non-fatal myocardial infarction was diagnosed in 4.0% of patients with PA and in 0.6% of patients with EHT (OR = 6.5; 95% CI 1.5 to 27.4). A history of atrial fibrillation was diagnosed in 7.3% of patients with PA and 0.6% of patients with EHT (OR = 12.1; 95% CI 3.2 to 45.2). The occurrence of cardiovascular complications was comparable in both subtypes of PA. CONCLUSIONS:Patients presenting with PA experienced more cardiovascular events than did EHT patients independent of blood pressure. The presence of PA should be detected, not only to determine the cause of HTN, but also to prevent such complications. 10.1016/j.jacc.2005.01.015
    Adrenalectomy improves arterial stiffness in primary aldosteronism. Strauch Branislav,Petrák Ondrej,Zelinka Tomás,Wichterle Dan,Holaj Robert,Kasalický Mojmír,Safarík Libor,Rosa Ján,Widimský Jirí American journal of hypertension BackgroundAldosterone has been shown to substantially contribute to the accumulation of different types of collagen fibers and growth factors in the arterial wall, which increase wall stiffness. We previously showed that arterial wall stiffness is increased in primary aldosteronism (PA) independently of concomitant hypertension. This study was aimed at assessing the effects of specific treatment of PA on the arterial stiffness.MethodsTwenty-nine patients with confirmed PA (15 with aldosterone-producing adenoma treated by unilateral laparoscopic adrenalectomy, 14 treated with spironolactone (mainly idiopathic aldosteronism) were investigated by Sphygmocor applanation tonometer (using measurement of carotid-femoral pulse wave velocity (PWV) and augmentation index (AI)) at the time of the diagnosis and then approximately 1 year after the specific treatment.ResultsThe office blood pressure (BP) decreased from 167 +/- 18/96 +/- 9 to 136 +/- 12/80 +/- 7 mm Hg after adrenalectomy (P = 0.001), and from 165 +/- 21/91 +/- 13 to 151 +/- 22/88 +/- 8 mm Hg (not significant (n.s.)) on spironolactone. The mean 24-h BP decreased from 150 +/- 18/93 +/- 11 mm Hg to 126 +/- 17/80 +/- 10 mm Hg after adrenalectomy (P < 0.01), and from 155 +/- 16/94 +/- 12 to 139 +/- 18/88 +/- 8 mm Hg (n.s.) on spironolactone. The PWV significantly decreased after surgery from 9.5 +/- 2.7 m/s to 7.6 +/- 2 m/s (P = 0.001), and the AI (recalculated for heart rate 75/min) decreased significantly from 27 +/- 10 to 19 +/- 9% (P < 0.01). On the other hand, we did not find significant change of arterial stiffness indices in patients treated with spironolactone (PWV: 9.3 +/- 1.6 m/s vs. 8.8 +/- 1.3 m/s (n.s.); AI: 25 +/- 9% vs. 25 +/- 8% (n.s.)).ConclusionsSurgical but not conservative treatment of PA led to a significant decrease of BP and arterial stiffness parameters.American Journal of Hypertension (2008). doi:10.1038/ajh.2008.243American Journal of Hypertension (2008); 21, 10, 1086-1092. doi 10.1038/ajh.2008.243. 10.1038/ajh.2008.243
    Cardiac remodeling in patients with primary aldosteronism. Galetta F,Bernini G,Franzoni F,Bacca A,Fivizzani I,Tocchini L,Bernini M,Fallahi P,Antonelli A,Santoro G Journal of endocrinological investigation OBJECTIVE:To evaluate the morpho-functional changes of the myocardium in patients with primary aldosteronism (PA). DESIGN:An observational study in a university referral center for blood pressure diseases. PATIENTS:Twenty- three patients with PA, 24 patients with essential hypertension (EH), and 15 normotensive controls (C) underwent conventional echocardiography with integrated backscatter (IBS) and tissue Doppler imaging (TDI) analysis. The corrected IBS (C-IBS) values and the systo-diastolic variation of IBS (CV-IBS) were performed at both interventricular septum and the posterior wall levels. TDI myocardial systolic (Sm), early diastolic (Em), and late diastolic (Am) velocities of both left ventricular walls were also determined. RESULTS:In PA patients, septal and posterior wall CV-IBS were significantly lower than C (p<0.0001) and EH patients (p<0.001). In EH, CV-IBS was significantly lower than C (p<0.001). Patients with PA exhibited lower Sm, lower Em, and higher Am, and a subsequently reduced Em/Am ratio than C (p<0.001 for all) and EH (p<0.01 for all) at interventricular septum and lateral wall levels. In the latter, Sm, Em, and Em/Am ratio were lower and Am was higher than C (p<0.001 for all). In PA and EH patients, CV-IBS at both septum (r=-0.66, p<0.001) and posterior wall levels (r=-0.67, p<0.001) and Sm peak of both septum (r=-0.52, p<0.001) and lateral wall (r=-0.55, p<0.001) were inversely related to plasma aldosterone. CONCLUSIONS:Patients with PA showed myocardial wall remodeling characterized by increased myocardial fibrosis and early left ventricular systodiastolic function abnormalities. 10.3275/6380
    Myocardial and aortic stiffening in the early course of primary aldosteronism. Tsioufis Costas,Tsiachris Dimitrios,Dimitriadis Kyriakos,Stougiannos Pavlos,Missovoulos Platonas,Kakkavas Apostolis,Stefanadis Christodoulos,Kallikazaros Ioannis Clinical cardiology BACKGROUND:Primary aldosteronism (PA) has been experimentally and clinically linked to myocardial and vascular fibrosis, and it has been further associated with left ventricular (LV) structural adaptations. HYPOTHESIS:Functional cardiovascular adaptations in hypertensive patients with PA precede structural alterations in the early stages of the disease. METHODS:We studied 17 hypertensive subjects with a recent diagnosis of PA (10 male patients, aged approximately 55 y, with office blood pressure [BP] of 137/88 mm Hg), and 30 essential hypertensives matched for age, sex, office BP levels, treatment status, and LV mass index (LVMI). Apart from standard 2-Dimensional (2-D) and conventional Doppler parameters, tissue Doppler imaging (TDI) methodology was used to assess LV diastolic function; averaging early and late diastolic mitral annular peak velocities (Emav/, Amav, Emav/Amav ratio) from 4 separate sites of measurement (septal, lateral, anterior, and inferior walls). Aortic stiffness was evaluated by means of carotid-femoral pulse wave velocity (cf-PWV) measurements. RESULTS:Although transmitral E/A ratio was similar in both groups (0.95+/-0.26 versus 0.98+/-0.24, p=0.66), hypertensive subjects with PA compared with essential hypertensives are characterized by significantly higher relative wall thickness (0.50+/-0.07 versus 0.41+/-0.06, p<or=0.001), decreased values of Emav (7+/-1.7 versus 8.1+/-1.8 cm/s, p=0.048), and Emav/Amav ratio (0.63+/-0.16 versus 0.77+/-0.17, p=0.015). The higher PWV in the PA population failed to reach statistical significance (8.5+/-1.6 versus 7.9+/-0.9 msec, p=0.19). CONCLUSION:Our study demonstrates altered LV geometry and TDI-revealed diastolic dysfunction in hypertensives with PA compared with demographically- and LVMI-matched essential hypertensives. Furthermore, the increased aortic stiffening in PA patients failed to reach statistical significance. 10.1002/clc.20270
    Corrigendum: IRB Approval Number Correction. Cardiac Dysfunction in Association with Increased Inflammatory Markers in Primary Aldosteronism. Lim Jung Soo,Park Sungha,Park Sung Il,Oh Young Taik,Choi Eun Hee,Kim Jang Young,Rhee Yumie Endocrinology and metabolism (Seoul, Korea) 10.3803/EnM.2020.305
    [Prevalence of primary aldosteronism in hypertensive patients and its effect on the heart]. Morillas Pedro,Castillo Jesús,Quiles Juan,Núñez Daniel,Guillén Silvia,Bertomeu-González Vicente,Pomares Francisco,Bertomeu Vicente Revista espanola de cardiologia Primary hyperaldosteronism (PHA) is thought to have a harmful effect on the cardiovascular system and, in recent years, the number of cases of hypertension due to PHA has been increasing. The aims of this study were to determine the prevalence of PHA and to assess cardiac damage associated with the condition in 183 consecutive hypertensive patients. A full secondary hypertension work-up was performed, and included ECG and echocardiography. In total, 11 (6%) patients were diagnosed with PHA. Compared with other hypertensives, those with PHA had higher systolic blood pressure, more frequently had evidence of left ventricular hypertrophy on ECG (45.5% vs 11.6%; P< .01), and had a larger left ventricular mass on echocardiography (145.5 g/m(2) vs 97.52 g/m(2); P< .0001). In conclusion, PHA is a significant contributor to the increasing prevalence of hypertension and its effect on the heart is greater than that of other causes of hypertension.
    Cardiovascular and cerebrovascular comorbidities of hypokalemic and normokalemic primary aldosteronism: results of the German Conn's Registry. Born-Frontsberg E,Reincke M,Rump L C,Hahner S,Diederich S,Lorenz R,Allolio B,Seufert J,Schirpenbach C,Beuschlein F,Bidlingmaier M,Endres S,Quinkler M, The Journal of clinical endocrinology and metabolism CONTEXT:Primary aldosteronism (PA) is associated with vascular end-organ damage. OBJECTIVE:Our objective was to evaluate differences regarding comorbidities between the hypokalemic and normokalemic form of PA. DESIGN AND SETTING:This was a retrospective cross-sectional study collected from six German centers (German Conn's registry) between 1990 and 2007. PATIENTS:Of 640 registered patients with PA, 553 patients were analyzed. MAIN OUTCOME MEASURES:Comorbidities depending on hypokalemia or normokalemia were examined. RESULTS:Of the 553 patients (61 +/- 13 yr, range 13-96), 56.1% had hypokalemic PA. The systolic (164 +/- 29 vs. 155 +/- 27 mm Hg; P < 0.01) and diastolic (96 +/- 18 vs. 93 +/- 15 mm Hg; P < 0.05) blood pressures were significantly higher in hypokalemic patients than in those with the normokalemic variant. The prevalence of cardiovascular events (angina pectoris, myocardial infarction, chronic cardiac insufficiency, coronary angioplasty) was 16.3%. Atrial fibrillation occurred in 7.1% and other atrial or ventricular arrhythmia in 5.2% of the patients. Angina pectoris and chronic cardiac insufficiency were significantly more prevalent in hypokalemic PA (9.0 vs. 2.1%, P < 0.001; 5.5 vs. 2.1%, P < 0.01). Overall, cerebrovascular comorbidities were not different between hypokalemic and normokalemic patients, however, stroke tended to be more prevalent in normokalemic patients. CONCLUSIONS:Our data indicate a high prevalence of comorbidities in patients with PA. The hypokalemic variant is defined by a higher morbidity than the normokalemic variant regarding some cardiovascular but not cerebrovascular events. Thus, PA should be sought not only in hypokalemic but also in normokalemic hypertensives because high-excess morbidity occurs in both subgroups. 10.1210/jc.2008-2116
    Cardiac Remodeling in Patients With Primary and Secondary Aldosteronism: A Tissue Doppler Study. Cesari Maurizio,Letizia Claudio,Angeli Paolo,Sciomer Susanna,Rosi Silvia,Rossi Gian Paolo Circulation. Cardiovascular imaging BACKGROUND:Primary aldosteronism (PA) causes excess left ventricular (LV) hypertrophy and diastolic dysfunction; whether this occurs also in secondary aldosteronism (SA) without hypertension is unknown. We investigated the cardiac modifications in patients with preserved LV ejection fraction who had PA or SA. METHODS AND RESULTS:We measured several Doppler echocardiography-derived variables, including tissue Doppler imaging (TDI) parameters and strain rate analysis, in 262 patients with PA, 117 with SA because of liver cirrhosis, and in 61 control healthy subjects. SA and PA patients showed markedly elevated aldosterone levels (67 versus 39 ng/dL, respectively; normal values <15 ng/dL) but contrasting values of plasma renin activity (15.00 versus 0.56 ng/mL/h; P<0.001). Compared with PA, SA patients showed higher heart rate, and lower blood pressure and vascular resistance values. Both PA and SA showed increased LV diameters, LV volumes, stroke volume, stroke work, and septal peak systolic tissue velocity, and had more LV hypertrophy (61% and 39%, respectively) and diastolic dysfunction (35% and 36%, respectively) than healthy subjects. Peak systolic septal strain (20% versus 23%; P=<0.001) and midwall fractional shortening (15.9% versus 16.7%; P=0.001) were lower in PA than in SA patients. CONCLUSIONS:Primary and secondary hyperaldosteronism correlate with LV enlargement and high prevalence of LV hypertrophy and diastolic dysfunction; a subclinical systolic dysfunction is evident only in PA. In SA, the high rate of LV hypertrophy, in spite of low peripheral resistances and low-to-normal blood pressure, could be accounted for the high renin and aldosterone values, and the work overload associated with a hyperdynamic circulatory state. 10.1161/CIRCIMAGING.116.004815
    Cardiac Dysfunction in Association with Increased Inflammatory Markers in Primary Aldosteronism. Lim Jung Soo,Park Sungha,Park Sung Il,Oh Young Taik,Choi Eunhee,Kim Jang Young,Rhee Yumie Endocrinology and metabolism (Seoul, Korea) BACKGROUND:Oxidative stress in primary aldosteronism (PA) is thought to worsen aldosterone-induced damage by activating proinflammatory processes. Therefore, we investigated whether inflammatory markers associated with oxidative stress is increased with negative impacts on heart function as evaluated by echocardiography in patients with PA. METHODS:Thirty-two subjects (mean age, 50.3±11.0 years; 14 males, 18 females) whose aldosterone-renin ratio was more than 30 among patients who visited Severance Hospital since 2010 were enrolled. Interleukin-1β (IL-1β), IL-6, IL-8, monocyte chemoattractant protein 1, tumor necrosis factor α (TNF-α), and matrix metalloproteinase 2 (MMP-2), and MMP-9 were measured. All patients underwent adrenal venous sampling with complete access to both adrenal veins. RESULTS:Only MMP-2 level was significantly higher in the aldosterone-producing adenoma (APA) group than in the bilateral adrenal hyperplasia (BAH). Patients with APA had significantly higher left ventricular (LV) mass and A velocity, compared to those with BAH. IL-1β was positively correlated with left atrial volume index. Both TNF-α and MMP-2 also had positive linear correlation with A velocity. Furthermore, MMP-9 showed a positive correlation with LV mass, whereas it was negatively correlated with LV end-systolic diameter. CONCLUSION:These results suggest the possibility that some of inflammatory markers related to oxidative stress may be involved in developing diastolic dysfunction accompanied by LV hypertrophy in PA. Further investigations are needed to clarify the role of oxidative stress in the course of cardiac remodeling. 10.3803/EnM.2016.31.4.567
    Peripheral arterial stiffness in primary aldosteronism. Rosa J,Somlóová Z,Petrák O,Strauch B,Indra T,Senitko M,Zelinka T,Holaj R,Widimský J Physiological research Aldosterone overproduction increases arterial wall stiffness by accumulation of different types of collagen fibres and growth factors. Our previous studies showed that central (aortic) arterial stiffness is increased in primary aldosteronism (PA) independently of concomitant hypertension and that these changes might be reversible after successful adrenalectomy. There is limited data available on the potential impact of mineralocorticoid overproduction on the deterioration of peripheral arterial stiffness. The current study was thus aimed at investigating the effect of aldosterone overproduction on peripheral arterial stiffness assessed by peripheral (femoral-ankle) pulse wave velocity (PWV) in PA patients compared with essential hypertension (EH) patients. Forty-nine patients with confirmed PA and 49 patients with EH were matched for age, blood pressure, body mass index, lipid profile, and fasting glucose. PWV was obtained using the Sphygmocor applanation tonometer. Both peripheral and central PWV were significantly higher in PA patients compared to EH patients, while clinical blood pressures were similar. Plasma aldosterone level was the main predictor of peripheral PWV in PA. Our data indicate aldosterone overproduction in PA does not preferentially affect central arterial system. Fibroproliferative effect of higher aldosterone levels lead to alteration of central-elastic as well as peripheral-muscular arteries with subsequent increase in its stiffness. 10.33549/physiolres.932344
    Primary aldosteronism can alter peripheral levels of transforming growth factor beta and tumor necrosis factor alpha. Carvajal C A,Herrada A A,Castillo C R,Contreras F J,Stehr C B,Mosso L M,Kalergis A M,Fardella C E Journal of endocrinological investigation UNLABELLED:Primary aldosteronism (PA) is the most common secondary cause of hypertension that has recently been implicated in alterations of the immune system and progression of cardiovascular disease. OBJECTIVE:To study the cytokines transforming growth factor beta1 (TGF-beta1), tumor necrosis factor alpha (TNF-alpha), and interleukin 10 (IL-10) in patients with PA and essential hypertensives (EH) and evaluate its association with the renin-angiotensin-aldosterone system. PATIENTS AND METHODS:We studied 26 PA and 52 EH patients as controls, adjusted by their blood pressure, body mass index, age, and gender. In both groups, PA and EH, we measured serum aldosterone (SA), plasma renin activity (PRA), and cytokines TGF- beta1, TNF-alpha, and IL-10. In addition, 17 PA patients were treated for 6 months with spironolactone, a mineralocorticoid receptor (MR) antagonist. RESULTS:PA patients had lower levels of TGF-beta1 (17.6+/-4.1 vs 34.5+/-20.5 pg/ml, p<0.001) and TNF-alpha (17.0+/-4.4 vs 35.6+/-21.7 pg/ml, p<0.001) and similar IL-10 levels (99.7+/-18.7 vs 89.4+/-49.5 pg/ml, p: ns), as compared with EH controls. TGF-beta1 and TNF-alpha levels showed a remarkable correlation with SA/PRA ratio in the total group (PA+EH). The treatment of PA patients with spironolactone increased the TGF-beta1 levels (18.3+/-5.9 to 28.4+/-6.3 pg/ml, p<0.001), while TNF-alpha, and IL-10 remained unchanged. CONCLUSION:Our results showed that PA patients have lower TGF-beta1 and TNF-alpha cytokine serum levels than EH. TGF-beta1 levels were restored with spironolactone, showing a MR-dependent regulation. In this way, the chronic aldosterone excess modifies the TGF-beta1 levels, which could produce an imbalance in the immune system homeostasis that may promote an early proinflammatory cardiovascular phenotype. 10.3275/6429
    Eplerenone improves endothelial function and arterial stiffness and inhibits Rho-associated kinase activity in patients with idiopathic hyperaldosteronism: a pilot study. Kishimoto Shinji,Oki Kenji,Maruhashi Tatsuya,Kajikawa Masato,Matsui Shogo,Hashimoto Haruki,Takaeko Yuji,Kihara Yasuki,Chayama Kazuaki,Goto Chikara,Aibara Yoshiki,Yusoff Farina Mohamad,Nakashima Ayumu,Noma Kensuke,Liao James K,Higashi Yukihito Journal of hypertension OBJECTIVE:Primary aldosteronism is one of the most common cause of secondary hypertension. It is well known that the incidence of cardiovascular events is higher in patients with primary aldosteronism than in patients with essential hypertension. In a previous study, we showed that aldosterone-producing adenoma is associated with vascular function and structure. The aim of this study was to evaluate the effects of eplerenone on vascular function in the macrovasculature and microvasculature, arterial stiffness and Rho-associated kinase (ROCK) activity in patients with idiopathic hyperaldosteronism (IHA). METHODS:Vascular function, including reactive hyperemia index (RHI), flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID), arterial stiffness including brachial-ankle pulse wave velocity (baPWV) and brachial intima-media thickness (IMT) and ROCK activity in peripheral leukocytes were measured before and after 12 weeks of treatment with eplerenone in 50 patients with IHA. RESULTS:After 12 weeks, eplerenone decreased the aldosterone renin ratio but did not alter SBP and DBP. Eplerenone treatment increased log RHI from 0.56 ± 0.25 to 0.69 ± 0.25 (P < 0.01) and NID from 12.8 ± 5.8 to 14.9 ± 6.9% (P = 0.02) and it decreased baPWV from 1540 ± 263 to 1505 ± 281 (P = 0.04) and ROCK activity from 1.20 ± 0.54 to 0.89 ± 0.42 (P < 0.01), whereas there was no significant change in FMD (increase from 4.6 ± 3.4 to 4.6 ± 3.6%, P = 0.99) or brachial IMT (decrease from 0.28 ± 0.07 to 0.28 ± 0.04 mm, P = 0.14). CONCLUSION:Eplerenone improves microvascular endothelial function, vascular smooth muscle function, arterial stiffness and ROCK activity in patients with IHA. CLINICAL TRIAL REGISTRATION INFORMATION:URL for Clinical Trial: http://UMIN; Registration Number for Clinical Trial: UMIN000003409. 10.1097/HJH.0000000000001989
    Increased intima-media thickness of the common carotid artery in primary aldosteronism in comparison with essential hypertension. Holaj Robert,Zelinka Tomás,Wichterle Dan,Petrák Ondrej,Strauch Branislav,Widimský Jirí Journal of hypertension BACKGROUND:Aldosterone contributes to the accumulation of collagen fibers and extracellular matrix in arterial wall. The aim of this study was to compare intima-media thickness (IMT) of the common carotid artery and carotid bifurcation in patients with primary aldosteronism, essential hypertension and healthy controls. METHODS:Carotid ultrasound studies were carried out in 33 patients aged 42-72 years with primary aldosteronism, 52 patients with essential hypertension and in 33 normotensive controls. RESULTS:The patients with primary aldosteronism had significantly higher IMT of the common carotid artery than patients with essential hypertension and controls (0.987 +/- 0.152 mm; 0.892 +/- 0.154 mm versus 0.812 +/- 0.124 mm; P < 0.001; P < 0.05). There was also significantly higher IMT of the common carotid in patients with essential hypertension compared to control group (0.892 +/- 0.154 mm versus 0.812 +/- 0.124 mm; P < 0.01). The differences between both hypertensive groups remained statistically significant after adjustment for age and 24-h systolic blood pressure (P = 0.001). The differences of the IMT in the carotid bifurcation were statistically significant only between patients with primary aldosteronism and controls (1.157 +/- 0.243 mm versus 0.994 +/- 0.199 mm; P <0.05). CONCLUSION:Patients with primary aldosteronism have increased common carotid IMT compared to the patients with essential hypertension. This finding could be caused by the deleterious effects of aldosterone excess on the fibrosis and thickening of the arterial wall, mainly in the straight segments of vessels. 10.1097/HJH.0b013e3281268532
    Mean platelet volume in patients with primary aldosteronism and its relation to left ventricular hypertrophy. Kurisu Satoshi,Shimonaga Takashi,Iwasaki Toshitaka,Mitsuba Naoya,Ishibashi Ken,Dohi Yoshihiro,Kihara Yasuki International journal of cardiology 10.1016/j.ijcard.2013.04.156
    Factors influencing left ventricular mass regression in patients with primary aldosteronism post adrenalectomy. Lin Yen-Hung,Huang Kuo-How,Lee Jen-Kuang,Wang Shuo-Meng,Yen Ruoh-Fang,Wu Vin-Cent,Chung Shiu-Dong,Liu Kao-Lang,Chueh Shih-Chieh,Lin Lian-Yu,Ho Yi-Lwun,Chen Ming-Fong,Wu Kwan-Dun, Journal of the renin-angiotensin-aldosterone system : JRAAS BACKGROUND:Primary aldosteronism (PA) is a type of secondary hypertension with prominent left ventricular hypertrophy (LVH). Unilateral aldosterone-producing adenoma (APA) is the most common subtype that can be cured by adrenalectomy. OBJECTIVE:To investigate left ventricular structural change after surgery and the factors associated with the degree of LVH regression in patients with PA. METHODS:We performed a retrospective analysis in the Taiwan Primary Aldosteronism Investigation (TAIPAI) database, including demography, biochemical data, echocardiography and medication. RESULTS:From July 1994 to January 2007, 20 patients (8 men) with APA receiving adrenalectomy and having pre- and postoperative echocardiography were selected. After 21 ± 19 months post operation, the left ventricular wall thickness and left ventricular mass index (LVMI) decreased significantly. The decrease of LVMI is significant only in patients who had LVH before operation. In analysis of factors associated with net LVMI decrease (ΔLVMI; post-operative LVMI - pre-operative LVMI), only pre-operative LVMI (r = -.783, p < .001), and ΔSBP (r = .472, p = .036) significantly correlated with ΔLVMI. In conclusion, LVH in PA could be significantly reversed by adrenalectomy. Pre-operative LVMI and ΔSBP were associated with the degree of LVMI decrease. CONCLUSION:LVH in PA could be significantly reversed by adrenalectomy. Pre-operative LVMI and ΔSBP were associated with the degree of LVMI decrease. 10.1177/1470320310376424
    Aldosterone induces left ventricular subclinical systolic dysfunction: a strain imaging study. Chen Zheng-Wei,Huang Kuan-Chih,Lee Jen-Kuang,Lin Lung-Chun,Chen Ching-Way,Chang Yi-Yao,Liao Che-Wei,Wu Vin-Cent,Hung Chi-Shen,Lin Yen-Hung, Journal of hypertension BACKGROUND:Primary aldosteronism is associated with a higher incidence of left ventricular (LV) hypertrophy and diastolic dysfunction than essential hypertension. However, systolic function via endocardial measurements is similar between patients with primary aldosteronism and essential hypertension. Speckle-tracking echocardiography is a sensitive tool which can detect subclinical impairments in systolic function. The aim of this study was to investigate aldosterone-induced subclinical impairments in systolic function. METHODS:We prospectively enrolled patients with primary aldosteronism and essential hypertension and analyzed their clinical data, biochemical data, and echocardiographic parameters, including myocardial strain [global longitudinal strain (GLS)]. RESULTS:Thirty-six patients with primary aldosteronism and 31 patients with essential hypertension were enrolled for analysis. The patients with primary aldosteronism had significantly lower serum potassium levels, lower plasma renin activity, higher aldosterone-to-renin ratio (ARR), and higher 24-h urinary aldosterone levels than patients with essential hypertension. With regards to echocardiographic parameters, the patients with primary aldosteronism had a thicker ventricular wall and higher LV mass index than those with essential hypertension. Most importantly, we found significant degradation of GLS in the patients with primary aldosteronism compared with those with essential hypertension (-17.84 ± 2.36 vs. -20.13 ± 2.32, P < 0.001). In correlation analysis, GLS was significantly correlated with serum potassium level, LV mass index, log-transformed plasma renin activity, log-transformed ARR, and log-transformed 24-h urinary aldosterone levels (all P < 0.05). Multivariate linear regression analysis further identified log-transformed ARR (β = 0.771, 95% confidence interval: 0.011-1.530, P = 0.047), and log-transformed 24-h urinary aldosterone level (β = 1.765, 95% confidence interval: 0.01-3.529, P = 0.050) as independent factors correlated with GLS. CONCLUSION:Patients with primary aldosteronism have a lower magnitude of GLS than patients with essential hypertension, suggesting that aldosterone induces a subclinical decline in LV systolic function. 10.1097/HJH.0000000000001534
    Cardiac dimensions are largely determined by dietary salt in patients with primary aldosteronism: results of a case-control study. Pimenta Eduardo,Gordon Richard D,Ahmed Ashraf H,Cowley Diane,Leano Rodel,Marwick Thomas H,Stowasser Michael The Journal of clinical endocrinology and metabolism CONTEXT:Animal studies have demonstrated that dietary sodium intake is a major influence in the pathogenesis of aldosterone-induced effects in the heart such as left ventricular (LV) hypertrophy and fibrosis. LV hypertrophy is an important predictor for cardiovascular morbidity and mortality. OBJECTIVE:We aimed to investigate the relationships between aldosterone and dietary salt and LV dimensions in patients with primary aldosteronism (PA). DESIGN AND PARTICIPANTS:This case-control study included 21 patients with confirmed PA and 21 control patients with essential hypertension matched for age, gender, duration of hypertension, and 24-h systolic and diastolic blood pressure. MAIN OUTCOME MEASURES:Patients were evaluated by echocardiography and 24-h urinary sodium (UNa) excretion while consuming their usual diets. RESULTS:Patients with PA had significantly greater mean LV end-diastolic diameter, interventricular septum and posterior wall thicknesses, LV mass (LVM) and LV mass index, and end systolic and diastolic volumes than control patients. UNa significantly positively correlated with interventricular septum, posterior wall thicknesses, and LVM in the patients with PA but not in control patients. In a multivariate analysis, UNa was an independent predictor for LV wall thickness and LV mass among the patients with PA but not in patients with essential hypertension. CONCLUSIONS:These findings emphasize the importance of dietary sodium in determining the degree of cardiac damage in those patients with PA, and we suggest that aldosterone excess may play a permissive role. In patients with PA, because a high-salt diet is associated with greater LVM, dietary salt restriction might reduce cardiovascular risk. 10.1210/jc.2011-0354
    The association of serum potassium level with left ventricular mass in patients with primary aldosteronism. Lin Yen-Hung,Wang Shuo-Meng,Wu Vin-Cent,Lee Jen-Kuang,Kuo Chin-Chi,Yen Ruoh-Fang,Liu Kao-Lang,Huang Kuo-How,Chueh Shih-Chieh,Wang Wei-Jie,Lin Lian-Yu,Chien Kuo-Long,Ho Yi-Lwun,Chen Ming-Fong,Wu Kwan-Dun, European journal of clinical investigation BACKGROUND:Primary aldosteronism (PA) is associated a worse cardiovascular outcome than essential hypertension. Hypokalemia, which is one major characteristic of PA, can affect both cardiac structure and function. The goal of this study is to evaluate the influence of serum potassium level on left ventricular (LV) mass and function in PA patients. MATERIALS AND METHODS:We prospectively analysed 85 PA patients from October 2006 to September 2008 and 27 essential hypertension patients as the control group (group 1). Thirty-two patients with serum potassium < 3·5 mmol L(-1) were defined as hypokalemia (group 2), and 53 patients with serum potassium ≥ 3·5 mmol L(-1) were defined as normokalemia (group 3). Echocardiography including tissue Doppler image (TDI) recordings was performed in all patients. RESULTS:Group 2 patients had significant higher systolic and diastolic blood pressure (DBP), log-transformed plasma aldosterone concentration, log-transformed aldosterone-to-renin ratio and lower serum potassium level than groups 1 and 3. In echocardiographic measurement, group 2 patients had higher LV mass index (LVMI) than groups 1 and 3. In multivariate analysis for factors affecting LVMI in PA patients, only serum potassium level (P = 0·001), use of spironolactone (P = 0·004) and DBP (P = 0·005) were independent factors. In the TDI study, both groups 2 and 3 had lower e' and E/e' values than group 1. CONCLUSIONS:Serum potassium level is significantly associated with LVMI in PA patients. Compared with essential hypertensive patients, PA patients had a greater impairment of cardiac diastolic function. 10.1111/j.1365-2362.2010.02462.x
    Clinical impacts of endothelium-dependent flow-mediated vasodilation assessment on primary aldosteronism. Watanabe Daisuke,Morimoto Satoshi,Morishima Noriko,Ichihara Atsuhiro Endocrine connections Objective:Primary aldosteronism (PA) is divided into two major subtypes, aldosterone-producing adenoma (APA) and bilateral idiopathic hyperplasia (IHA) and is associated with a higher risk of cardiovascular events. However, the nature of vascular function in PA patients remains to be determined. The aim of this study was to determine the vascular function and investigate the implications of vascular function assessments in the patients. Methods:Flow-mediated dilation (FMD), as an index of endothelial function, and cardio-ankle vascular index (CAVI), as an index of arterial stiffness, were retrospectively compared between 42 patients with APA, 37 patients with IHA, and 42 patients with essential hypertension (EH). These values were also compared with background factors, KCNJ5 mutation and clinical outcome in terms of blood pressure reduction after adrenalectomy in the APA group. Results:FMD was significantly lower in the APA group (4.8 ± 2.1%) and IHA group (4.1 ± 1.9%) than in the EH group (5.7 ± 2.1%). CAVI did not differ significantly among groups. Although no significant correlations were seen between FMD and background factors in the IHA group, FMD correlated negatively with BMI and plasma aldosterone concentration in the APA group (rs = -0.313, rs = -0.342, respectively). KCNJ5 mutational status was not associated with FMD value. High FMD was associated with blood pressure normalization after adrenalectomy in the APA group. Conclusions:Patients with PA displayed impaired endothelial function. Complete clinical success after adrenalectomy was associated with preserved endothelial function. This study provides a better understanding of FMD assessment in patients with PA. 10.1530/EC-21-0057
    Myocardial ultrasound tissue characterization of patients with primary aldosteronism. Lee Hsiu-Hao,Hung Chi-Sheng,Wu Xue-Ming,Wu Vin-Cent,Liu Kao-Lang,Wang Shuo-Meng,Lin Lung-Chun,Chen Pau-Chung,Guo Yue-Leon,Chueh Shih-Chieh,Lin Yen-Hung,Ho Yi-Lwun,Wu Kwan-Dun, Ultrasound in medicine & biology Primary aldosteronism (PA), an underdiagnosed cause of hypertension, is associated with more significant cardiac remodeling and myocardial fibrosis than is essential hypertension (EH). The aim of this study was to validate myocardial fibrosis and to evaluate factors associated with the degree of myocardial fibrosis in patients with PA. We prospectively analyzed 62 patients with PA (including 46 patients with aldosterone-producing adenoma and 16 with bilateral hyperplasia) between October 2006 and October 2010, and we enrolled 17 patients with EH as the control group. Echocardiography, including ultrasonic tissue characterization using cyclic variation of integrated backscatter (CVIBS), was performed in individuals in both groups. Among patients with PA, the diastolic blood pressures and plasma aldosterone concentrations were significantly higher than those of patients with EH. Moreover, the serum potassium levels and the plasma renin activities were significantly lower in patients with EH. As observed by echocardiography, patients with PA had greater interventricular septal thickness, greater left ventricular posterior wall thickness, and higher left ventricular mass indexes than did patients with EH. Patients with PA had significantly lower CVIBS values than patients with EH (7.1 ± 2.2 vs. 8.7 ± 1.5 dB; p = .005). In a correlation study that corrected for various clinical parameters, only log-transformed plasma renin activity values correlated significantly with CVIBS values. Ultrasonic tissue characterization with CVIBS is a useful tool for determining the extent of myocardial fibrosis. Patients with PA exhibit a more severe degree of myocardial fibrosis, as detected by CVIBS, than do patients with EH. Moreover, the severity of fibrosis, as detected by CVIBS, correlates with log-transformed plasma renin activity values. 10.1016/j.ultrasmedbio.2012.08.023
    Demonstration of blood pressure-independent noninfarct myocardial fibrosis in primary aldosteronism: a cardiac magnetic resonance imaging study. Freel E Marie,Mark Patrick B,Weir Robin A P,McQuarrie Emily P,Allan Karen,Dargie Henry J,McClure John D,Jardine Alan G,Davies Eleanor,Connell John M C Circulation. Cardiovascular imaging BACKGROUND:Primary aldosteronism (PA) is common and associates with excess cardiovascular morbidity independent of blood pressure. Exposure to aldosterone and sodium leads to cardiac fibrosis and hypertrophy in humans and animals possibly mediated by inflammation and oxidative stress. We aimed to clarify the effects of aldosterone excess on myocardial structure and composition in human subjects with PA and essential hypertension using contrast-enhanced cardiac magnetic resonance imaging as well as explore the mechanistic basis for any observed differences. METHODS AND RESULTS:Twenty-seven subjects with recently diagnosed PA and 54 essential hypertension controls were recruited. Subjects underwent gadolinium-enhanced cardiac magnetic resonance; noninfarct related myocardial fibrosis was identified by a diffuse pattern of late gadolinium enhancement. Patients also underwent assessment of pulse wave velocity, measurement of circulating superoxide anion and C-reactive protein, as well as blood pressure and biochemical assessment. Subjects were well matched with no difference in severity or duration of hypertension. There was a significant increase in the frequency of noninfarct late gadolinium enhancement in PA (70%) when compared with essential hypertension subjects (13%; P<0.0001) with no difference in left ventricular mass. Pulse wave velocity, superoxide, and C-reactive protein were significantly higher in subjects with PA. CONCLUSIONS:These data illustrate that patients with PA exhibit frequent myocardial fibrosis as demonstrated by late gadolinium enhancement using cardiac magnetic resonance imaging; this finding is independent of blood pressure. This may be mediated partly through inflammation and oxidative stress. This study highlights the importance of specific targeting of aldosterone excess as well as blood pressure reduction to minimize cardiac morbidity in PA. 10.1161/CIRCIMAGING.112.974576
    Cardiac magnetic resonance imaging of myocardial mass and fibrosis in primary aldosteronism. Grytaas Marianne Aa,Sellevåg Kjersti,Thordarson Hrafnkell B,Husebye Eystein S,Løvås Kristian,Larsen Terje H Endocrine connections BACKGROUND:Primary aldosteronism (PA) is associated with increased cardiovascular morbidity, presumably due to left ventricular (LV) hypertrophy and fibrosis. However, the degree of fibrosis has not been extensively studied. Cardiac magnetic resonance imaging (CMR) contrast enhancement and novel sensitive T1 mapping to estimate increased extracellular volume (ECV) are available to measure the extent of fibrosis. OBJECTIVES:To assess LV mass and fibrosis before and after treatment of PA using CMR with contrast enhancement and T1 mapping. METHODS:Fifteen patients with newly diagnosed PA (PA1) and 24 age- and sex-matched healthy subjects (HS) were studied by CMR with contrast enhancement. Repeated imaging with a new scanner with T1 mapping was performed in 14 of the PA1 and 20 of the HS median 18 months after specific PA treatment and in additional 16 newly diagnosed PA patients (PA2). RESULTS:PA1 had higher baseline LV mass index than HS (69 (53-91) vs 51 (40-72) g/m;  < 0.001), which decreased significantly after treatment (58 (40-86) g/m;  < 0.001 vs baseline), more with adrenalectomy ( = 8; -9 g/m;  = 0.003) than with medical treatment ( = 6; -5 g/m;  = 0.075). No baseline difference was found in contrast enhancement between PA1 and HS. T1 mapping showed no increase in ECV as a myocardial fibrosis marker in PA. Moreover, ECV was lower in the untreated PA2 than HS 10 min post-contrast, and in both PA groups compared with HS 20 min post-contrast. CONCLUSION:Specific treatment rapidly reduced LV mass in PA. Increased myocardial fibrosis was not found and may not represent a common clinical problem. 10.1530/EC-18-0039
    Endothelial progenitor cells in primary aldosteronism: a biomarker of severity for aldosterone vasculopathy and prognosis. Wu Vin-Cent,Lo Shyh-Chyi,Chen Yuh-Lien,Huang Po-Hsun,Tsai Chia-Ti,Liang Chan-Jung,Kuo Chin-Chi,Kuo Yih-Shing,Lee Bai-Chin,Wu En-Ling,Lin Yen-Hung,Sun Yun-Yu,Lin Shuei-Liong,Chen Jaw-Wen,Lin Shing-Jong,Wu Kwan-Dun, The Journal of clinical endocrinology and metabolism CONTEXT:Primary aldosteronism (PA) is associated with a higher incidence of cardiovascular events, probably through mineralocorticoid receptor (MR)-dependent endothelial cell dysfunction, in comparison with essential hypertension (EH). OBJECTIVE:Our objective was to investigate the number and function of endothelial progenitor cells (EPC) in PA and the relationship with arterial stiffness and disease progression. DESIGN AND SETTING:We conducted a prospective study of the change of EPC number and outcome of PA patients after treatment at a tertiary medical center. PRIMARY OUTCOMES:Changes in arterial stiffness and EPC number after treatment and the curability of hypertension were assessed. PATIENTS:A total of 113 PA patients (87 patients diagnosed with aldosterone-producing adenoma, 26 with idiopathic hyperaldosteronism) and 55 patients with EH participated. RESULTS:PA patients had higher arterial stiffness than EH patients (P = 0.006), with a lower numbers of circulating EPC and endothelial colony-forming units (P < 0.05). The differences were ameliorated at 6 months after unilateral adrenalectomy or treatment with spironolactone. Expression of MR was identified in the EPC. The number of circulating EPC was inversely correlated with the plasma aldosterone concentration (P = 0.021), arterial stiffness (P = 0.029) and serum high-sensitivity C-reactive protein (P = 0.03). High-dose aldosterone (10(-5) and 10(-6) m) attenuated EPC proliferation and angiogenesis in vitro. Among the 45 patients who underwent unilateral adrenalectomy, 32 (71%) were cured of hypertension. The preoperative number of EPC [log(EPC number percent) >-3.6] predicted the curability of hypertension after adrenalectomy (P = 0.003). CONCLUSIONS:The relative deficiency of EPC in PA patients may contribute to aldosterone vasculopathy, which can be reversed by adrenalectomy and spironolactone. High aldosterone levels attenuated EPC proliferation and angiogenesis. Circulating EPC number may be a valuable biomarker to identify PA patients with a high incidence of arterial stiffness and to predict postoperative residual hypertension of aldosterone-producing adenoma. 10.1210/jc.2011-1135
    Endothelial dysfunction in patients with primary aldosteronism: a biomarker of target organ damage. Liu G,Yin G-S,Tang J-y,Ma D-J,Ru J,Huang X-H Journal of human hypertension Primary aldosteronism (PA) has been associated with increased target organ damage (TOD), most likely through mineralocorticoid receptor-dependent endothelial dysfunction, in comparison with essential hypertension (EH). The aim of this study was to evaluate the level of biomarkers of endothelial dysfunction in PA and the relationship with left ventricular hypertrophy (LVH) and microalbuminuria (MAU). A total of 50 PA patients and 51 patients with EH individually matched for age, sex, blood pressure and duration of hypertension participated in this study. Biomarkers of endothelial dysfunction, including von Willebrand factor (vWF), intercellular adhesion molecule 1 (ICAM-1) and oxidized low-density lipoprotein (ox-LDL), were measured. Plasma aldosterone concentration (PAC), MAU and echocardiography were also evaluated. In PA patients, vWF, ICAM-1, ox-LDL, LVH and MAU were all significantly higher than in EH patients (all P<0.05). Furthermore, LVH was positively correlated with PAC (P=0.002), vWF (P=0.013) and ox-LDL (P=0.020). MAU was positively correlated with PAC (P<0.001), vWF (P=0.013) and ICAM-1 (P=0.001). Multiple regression analysis indicated that vWF, ICAM-1 and PAC independently predicted MAU (all P<0.05). Likewise, PAC, vWF and ox-LDL were significant predictors of LVH (all P<0.05). Taken together, our results suggest that endothelial dysfunction may contribute to TOD in PA patients. 10.1038/jhh.2014.11
    Ventricular repolarization before and after treatment in patients with secondary hypertension due to renal-artery stenosis and primary aldosteronism. Maule Simona,Bertello Chiara,Rabbia Franco,Milan Alberto,Mulatero Paolo,Milazzo Valeria,Papotti Grazia,Veglio Franco Hypertension research : official journal of the Japanese Society of Hypertension A prolonged QT interval is a risk factor for ischemic heart disease in hypertensive subjects. Patients with renal-artery stenosis and primary aldosteronism (PA) are at increased risk of cardiovascular events. The objective of the present study was to evaluate the QT interval in patients with renovascular hypertension (RV) and PA before and after treatment. A total of 24 patients with RV and 38 with PA were studied; 89 patients with essential hypertension (EH) served as control group. Corrected QT intervals (QTcH) were measured from a 12-lead ECG. Basal QTcH was longer in RV (429±30 ms) and PA (423±23 ms) compared with EH controls (407±18 ms; P<0.001). The prevalence of QTcH >440 ms was higher in RV (29%) and PA patients (29%) compared with EH controls (4%; P<0.001). QTcH interval was evaluated after treatment in 19 RV and 15 PA patients. QTcH was reduced after renal-artery angioplasty in RV patients (419±14 ms; P=0.02), and after spironolactone or adrenalectomy in PA (403±12 ms; P=0.01). In conclusion, QT interval was prolonged in patients with RV and PA compared with controls with EH. After angioplasty of renal-artery stenosis in RV, and treatment with spironolactone or adrenalectomy in PA, the cardiovascular risk of such patients may be reduced by concomitant blood pressure lowering and QT duration shortening. 10.1038/hr.2011.77
    QT interval in patients with primary aldosteronism and low-renin essential hypertension. Maule Simona,Mulatero Paolo,Milan Alberto,Leotta Giannina,Caserta Mimma,Bertello Chiara,Rabbia Franco,Veglio Franco Journal of hypertension INTRODUCTION:QT interval prolongation increases the risk of sudden death in several medical conditions. Patients with primary aldosteronism and salt-sensitive hypertension experience more cardiovascular events than those with normal-renin essential hypertension. QT interval prolongation might represent one of the risk factors for cardiovascular events in these patients. The aim of the present study was to evaluate the QT interval in patients with primary aldosteronism and low-renin essential hypertension (LREH). METHODS:Twenty-seven patients with primary aldosteronism, 17 patients with LREH, 117 patients with essential hypertension and 25 healthy individuals were studied. Plasma aldosterone, plasma renin activity, and aldosterone to plasma renin activity ratio (ARR) were determined. Corrected QT intervals (QTcs) were measured from a 12-lead electrocardiogram. RESULTS:The QTc was longer in primary aldosteronism (434 +/- 23 ms) and LREH (430 +/- 18 ms) compared with essential hypertension (419 +/- 22 ms) and healthy controls (412 +/- 19 ms) (P = 0.0004). The prevalence of QTc longer than 440 ms was higher in primary aldosteronism (48%) and LREH (23%) compared with essential hypertension (11%) and healthy controls (4%) (P < 0.0001). QTc correlated with plasma aldosterone (P = 0.01), ARR (P = 0.02), and diastolic blood pressure (P = 0.01). ARR (P = 0.01) and systolic blood pressure (P = 0.01) were identified as independent predictors of QTc. CONCLUSIONS:We postulate that the elevated aldosterone secretion contributes to the prolongation of the QT interval in patients with primary aldosteronism and LREH through both a depletion of intracellular potassium concentration and higher blood pressure values. QTc measurement might represent one simple, non-invasive and reproducible index to characterize the cardiovascular risk in patients with primary aldosteronism and LREH. 10.1097/01.hjh.0000251908.93298.a0
    Prospective appraisal of the prevalence of primary aldosteronism in hypertensive patients presenting with atrial flutter or fibrillation (PAPPHY Study): rationale and study design. Rossi G P,Seccia T M,Gallina V,Muiesan M L,Leoni L,Pengo M,Ragazzo F,Caielli P,Belfiore A,Bernini G,Cipollone F,Cottone S,Ferri C,Giacchetti G,Grassi G,Letizia C,Maccario M,Olivieri O,Palumbo G,Rizzoni D,Rossi E,Sechi L,Volpe M,Mantero F,Morganti A,Pessina A C Journal of human hypertension Primary aldosteronism (PA) is the most common endocrine form of hypertension and may carry an increased risk of atrial flutter or fibrillation (AFF). The primary goal of this multicentre cohort study is thus to prospectively establish the prevalence of PA in consecutive hypertensive patients referred for lone (non-valvular), paroxysmal or permanent AFF. Secondary objectives are to determine: (1) the predictors of AFF in patients with PA; (2) the rate of AFF recurrence at follow-up after specific treatment in the patients with PA; (3) the effect of AFF that can increase atrial natriuretic peptide via the atrial stretch and thereby blunt aldosterone secretion, on the aldosterone-to-renin ratio (ARR), and thus the case detection of PA; (4) the diagnostic accuracy of ARR based on plasma renin activity or on the measurement of active renin (DRA) for diagnosing PA in AFF patients. Case detection and subtyping of PA will be performed according to established criteria, including the 'four corners criteria' for diagnosing aldosterone-producing adenoma. Pharmacologic or direct current cardioversion will be undertaken whenever indicated following current guidelines. The hormonal values and ARR will be compared within patient between AFF and sinus rhythm. Organ damage, cardiovascular events and recurrence of AFF will also be assessed during follow-up in patients with PA. 10.1038/jhh.2012.21
    Atherosclerotic Burden and Arterial Stiffness are Not Increased in Patients with Milder Forms of Primary Aldosteronism Compared to Patients with Essential Hypertension. Lottspeich Christian,Köhler Anton,Czihal Michael,Heinrich Daniel A,Schneider Holger,Handgriff Laura,Reincke Martin,Adolf Christian Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme Patients with primary aldosteronism (PA) are at increased cardiovascular risk, compared to patients with essential hypertension (EH). Cardiovascular damage could depend on PA phenotype, potentially being lower in milder forms of PA. Our aim was to assess atherosclerotic burden and arterial stiffness in 88 prospectively recruited patients, including 44 patients with mild PA and EH respectively. All patients underwent a structured study program, including measurements of ankle-brachial index, oscillometric measurement of central pulse wave velocity (cPWV) and vascular ultrasound examination of the supraaortic arteries, the abdominal aorta, and the femoropopliteal arteries. A plaque score was calculated to estimate atherosclerotic burden for each patient. This is a prospective case-control study set at a tertiary care hospital. Patients with PA and EH matched well for age, gender, blood pressure, BMI, and cardiovascular risk factors such as diabetes mellitus and smoking status. Common carotid intima-media thickness (0.77 vs. 0.75 mm; p=0.997) and cPWV (7.2 vs. 7.1 m/s; p=0.372) were comparable between patients with PA and EH. The atherosclerotic burden, as expressed by the plaque score, did not differ between the two groups (p=0.159). However, after initiation of treatment cPWV was significantly decreased in patients with PA (p=0.017). This study shows that subclinical atherosclerotic burden and arterial stiffness in patients with milder forms of PA is comparable to patients with EH. Nevertheless, specific treatment for PA significantly improved cPWV, which argues for a more liberal use of mineralocorticoid receptor antagonists in patients with arterial hypertension. 10.1055/a-1326-2164
    Arterial stiffness, intima-media thickness and carotid artery fibrosis in patients with primary aldosteronism. Bernini Giampaolo,Galetta Fabio,Franzoni Ferdinando,Bardini Michele,Taurino Chiara,Bernardini Melania,Ghiadoni Lorenzo,Bernini Matteo,Santoro Gino,Salvetti Antonio Journal of hypertension OBJECTIVES:To evaluate vascular wall structure and conduit artery stiffness in patients with primary aldosteronism. METHODS:This observational study, conducted in a University Hypertension Center, evaluated the carotid wall by 2-D ultrasonography and ultrasonic tissue characterization, and analyzed arterial stiffness by applanation tonometer. Twenty-three consecutive patients with primary aldosteronism, 24 matched patients with essential hypertension and 15 controls were studied. Intima-media thickness and corrected integrated backscatter signal of the carotid arteries were evaluated. Radial and femoral pulse wave velocity and aortic augmentation index were also investigated. RESULTS:Intima-media thickness in patients with essential hypertension (0.69 +/- 0.03 mm) was higher (P < 0.04) than that in controls (0.59 +/- 0.02 mm). This finding was more evident in primary aldosteronism patients (0.84 +/- 0.03 mm), in whom intima-media thickness was greater than that in controls (P < 0.0001) or in patients with essential hypertension (P < 0.01). Similarly, corrected integrated backscatter signal in patients with essential hypertension (-23.6 +/- 0.35 dB) was higher (P < 0.0001) than that in controls (-26.2 +/- 0.44 dB), but it was even more elevated in patients with primary aldosteronism (-22.1 +/- 0.46 dB), who showed greater corrected integrated backscatter signal than was the case in patients with essential hypertension (P < 0.009) or in controls (P < 0.0001). Femoral pulse wave velocity was higher in primary aldosteronism patients (10.8 +/- 0.57 m/s) than in patients with essential hypertension (9.1 +/- 0.34 m/s, P < 0.03) or in controls (7.1 +/- 0.51 m/s, P < 0.0001). Femoral pulse wave velocity was lower in controls than in patients with essential hypertension (P < 0.0001). The same pattern was observed for radial pulse wave velocity. Aortic augmentation index was higher in primary aldosteronism patients (28.2 +/- 2.1%) than in patients with essential hypertension (26.0 +/- 1.8%) or in controls (16.8 +/- 2.0%, P < 0.001). Patients with essential hypertension likewise exhibited higher aortic augmentation index than controls (P < 0.001). CONCLUSION:Aldosterone excess is responsible per se for vascular morphological (wall thickening and carotid artery fibrosis) and functional (central stiffness) damage. 10.1097/HJH.0b013e32831286fd
    Adrenalectomy reverses myocardial fibrosis in patients with primary aldosteronism. Lin Yen-Hung,Wu Xue-Ming,Lee Hsiu-Hao,Lee Jen-Kuang,Liu Yu-Chun,Chang Hung-Wei,Lin Chien-Yu,Wu Vin-Cent,Chueh Shih-Chieh,Lin Lung-Chun,Lo Men-Tzung,Ho Yi-Lwun,Wu Kwan-Dun, Journal of hypertension OBJECTIVE:Primary aldosteronism is the most frequent cause of secondary hypertension and is associated with more prominent left ventricular hypertrophy and increased myocardial fibrosis. However, the reversibility of cardiac fibrosis is still unclear. Our objective was to investigate myocardial fibrosis in primary aldosteronism patients and its change after surgery. METHOD:We prospectively analyzed 20 patients with aldosterone-producing adenoma (APA) who received adrenalectomy from December 2006 to October 2008 and 20 patients with essential hypertension were enrolled as the control group. Plasma carboxy-terminal propeptide of procollagen type I (PICP) determination and echocardiography including ultrasonic tissue characterization by cyclic variation of integrated backscatter (CVIBS) were performed in both groups and 1 year after operation in the APA group. RESULTS:APA patients had significantly higher SBP and DBP, higher plasma aldosterone concentration (PAC), higher aldosterone-renin ratio (ARR), lower serum potassium levels, and lower plasma renin activity (PRA) than patients with essential hypertension. In echocardiography, APA patients had a higher left ventricular mass index than essential hypertension patients. APA patients had significantly lower CVIBS (6.2 ± 1.5 vs. 8.7 ± 2.0 dB, P < 0.001) and higher plasma PICP levels (107 ± 27 vs. 85 ± 24 μg/l, P = 0.009) than essential hypertension patients. In the correlation study, CVIBS is correlated with log-transformed PRA and log-transformed ARR and PICP is correlated with log-transformed PRA, log-transformed PAC, and log-transformed ARR. One year after adrenalectomy, CVIBS increased significantly (6.2 ± 1.5 to 7.3 ± 1.7 dB, P = 0.033) and plasma PICP levels decreased (107 ± 27 vs. 84 ± 28 μg/l, P = 0.026). CONCLUSION:Increases in collagen content in the myocardium of APA patients may be reversed by adrenalectomy. 10.1097/HJH.0b013e3283550f93
    Time-Dependent Risk of Atrial Fibrillation in Patients With Primary Aldosteronism After Medical or Surgical Treatment Initiation. Kim Kyoung Jin,Hong Namki,Yu Min Heui,Lee Hokyou,Lee Seunghyun,Lim Jung Soo,Rhee Yumie Hypertension (Dallas, Tex. : 1979) [Figure: see text]. Increased risk of atrial fibrillation was reported in patients with primary aldosteronism. However, data are limitedregarding the time-dependent risk of atrial fibrillation in surgically or medically treated primary aldosteronism. From theNational Health Insurance Claim database in Korea (2003–2017), a total of 1418 patients with primary aldosteronism(adrenalectomy [ADX], n=755, mineralocorticoid receptor antagonist n=663) were age- and sex-matched at a 1:5 ratiosto patients with essential hypertension (n=7090). Crude incidence of new onset atrial fibrillation was 2.96% in primaryaldosteronism and 1.97% in essential hypertension. Because of nonproportional hazard observed in new onset atrialfibrillation, analysis time was split at 3 years. Compared with essential hypertension, risk of new onset atrial fibrillation peaked at 1 year gradually declined but remained elevated up to 3 years in overall treated primary aldosteronism (adjusted hazard ratio [aHR] 3.02; P<0.001) as well as in both ADX (aHR, 3.54; P<0.001) and mineralocorticoid receptor antagonist groups (aHR 2.27; P=0.031), which became comparable to essential hypertension afterward in both groups (ADX aHR, 0.38; P=0.102; mineralocorticoid receptor antagonist aHR, 0.60; P=0.214). Nonetheless, mineralocorticoid receptor antagonist group was associated with increased risk of nonfatal stroke (aHR, 1.21; P=0.031) compared with essential hypertension, whereas ADX was not (aHR, 1.26; P=0.288). Our results suggest the risk of new-onset atrial fibrillation remained elevated up to 3 years in treated primary aldosteronism compared with essential hypertension, which declined to comparable risk in essential hypertension thereafter. Monitoring for atrial fibrillation up to 3 years after treatment, particularly ADX, might be warranted. 10.1161/HYPERTENSIONAHA.120.16909
    Effects of Altered Calcium Metabolism on Cardiac Parameters in Primary Aldosteronism. Lim Jung Soo,Hong Namki,Park Sungha,Park Sung Il,Oh Young Taik,Yu Min Heui,Lim Pil Yong,Rhee Yumie Endocrinology and metabolism (Seoul, Korea) BACKGROUND:Increasing evidence supports interplay between aldosterone and parathyroid hormone (PTH), which may aggravate cardiovascular complications in various heart diseases. Negative structural cardiovascular remodeling by primary aldosteronism (PA) is also suspected to be associated with changes in calcium levels. However, to date, few clinical studies have examined how changes in calcium and PTH levels influence cardiovascular outcomes in PA patients. Therefore, we investigated the impact of altered calcium homeostasis caused by excessive aldosterone on cardiovascular parameters in patients with PA. METHODS:Forty-two patients (mean age 48.8±10.9 years; 1:1, male:female) whose plasma aldosterone concentration/plasma renin activity ratio was more than 30 were selected among those who had visited Severance Hospital from 2010 to 2014. All patients underwent adrenal venous sampling with complete access to both adrenal veins. RESULTS:The prevalence of unilateral adrenal adenoma (54.8%) was similar to that of bilateral adrenal hyperplasia. Mean serum corrected calcium level was 8.9±0.3 mg/dL (range, 8.3 to 9.9). The corrected calcium level had a negative linear correlation with left ventricular end-diastolic diameter (LVEDD, ρ=-0.424, =0.031). Moreover, multivariable regression analysis showed that the corrected calcium level was marginally associated with the LVEDD and corrected QT (QTc) interval (β=-0.366, =0.068 and β=-0.252, =0.070, respectively). CONCLUSION:Aldosterone-mediated hypercalciuria and subsequent hypocalcemia may be partly involved in the development of cardiac remodeling as well as a prolonged QTc interval, in subjects with PA, thereby triggering deleterious effects on target organs additively. 10.3803/EnM.2018.33.4.485
    The Relation Between the Degree of Left Ventricular Mass Regression and Serum Potassium Level Change in Patients With Primary Aldosteronism After Adrenalectomy. Liao Che-Wei,Chen Aaron,Lin Yen-Tin,Chang Yi-Yao,Wang Shuo-Meng,Wu Vin-Cent,Hung Chi-Sheng,Wu Kwan-Dun,Chueh Shih-Chieh,Lin Yen-Hung, Journal of investigative medicine : the official publication of the American Federation for Clinical Research BACKGROUND:Primary aldosteronism (PA) is one of the major etiologies for secondary hypertension featuring more prominent left ventricular hypertrophy. The purpose of the study was to investigate the predictive factors of left ventricular mass index (LVMI) regression in patients with PA after adrenalectomy. METHODS:We prospectively analyzed 30 patients with aldosterone-producing adenoma (APA) who received adrenalectomy from October 2006 to September 2008. Echocardiography was performed preoperation and 1 year after operation. RESULTS:Thirty patients with aldosterone-producing adenoma undergoing adrenalectomy were enrolled. In a 1-year follow-up, LVMI decreased significantly by an average of 18.6%. Net LVMI decrease (ΔLVMI) was associated with preoperative LVMI, preoperative serum potassium level, baseline systolic blood pressure (SBP), baseline diastolic blood pressure, net SBP decrease (ΔSBP), net diastolic blood pressure decrease, preoperative/postoperative change of log-transformed plasma aldosterone concentration, preoperative/postoperative change of log-transformed plasma renin activity, and preoperative/postoperative change of serum potassium level (Δserum potassium level). In a multiple regression analysis, preoperative LVMI (β = -0.287, P = 0.049), ΔSBP (β = 0.518, P = 0.01), and Δserum potassium level (β = -20.471, P = 0.014) were significantly correlated with ΔLVMI. CONCLUSIONS:The LVMI in patients with PA regressed significantly after adrenalectomy. Preoperative LVMI, ΔSBP, and Δserum potassium levels are independent factors associated with the degree of LVMI regression. 10.1097/JIM.0000000000000215
    Cardiometabolic risk in patients with primary aldosteronism and autonomous cortisol secretion. Case-control study. Araujo-Castro Marta,Bengoa Rojano Nuria,Fernández Argüeso María,Pascual-Corrales Eider,Jiménez Mendiguchía Lucía,García Cano Ana M Medicina clinica OBJECTIVE:To analyse the differences in the cardio-metabolic profile of patients with primary aldosteronism (PA) and autonomous cortisol secretion (ACS) matched by age and sex. METHODS:Case-control study; cases of PA without associated ACS and as controls patients with ACS (dexamethasone suppression test ≥ 1.8 μg/dL in the absence of specific hypercortisolism clinical data), matched by age and sex. Comorbidities of hypertension, diabetes, obesity, dyslipidaemia, chronic kidney failure, and cardiovascular and cerebrovascular events were analysed, as well as their degree of control. RESULTS:57 patients with PA and 57 with ACS were included. On diagnosis, in addition to a higher prevalence of hypertension in the PA patients (100 vs. 52.7%, p < .0001) and higher systolic blood pressure levels (143.2 (2.5) vs. 135.3 (2.6) mmHg, p = .032) than in the ACS patients, no other differences were detected in the prevalence of other cardio-metabolic comorbidities. Nevertheless, the patients with ACS had higher HbA1c levels (p = .028) than the PA patients. After a median follow-up of 2.25 years, the patients with PA presented a greater deterioration in kidney function (Average decrease in glomerular filtration rate (MDRD-4) -17.4 (3.0) vs. -2.3 (4.4) mL/min/1.73 m p = .005) and lipid profile (Δtriglycerides of 34.5 (15.8) vs. -6.7 (11.3) mg/dL, p = .038) than the ACS patients. CONCLUSIONS:Despite the higher prevalence of hypertension in the patients with PA than in the patients with ACS matched by age and sex, no differences were detected in the prevalence of other cardio-metabolic comorbidities. However, the PA patients showed a greater deterioration in kidney function and lipid profile throughout the follow-up than the ACS patients. 10.1016/j.medcli.2020.07.025
    Regression of left ventricular hypertrophy in patients with primary aldosteronism/low-renin hypertension on low-dose spironolactone. Ori Yaacov,Chagnac Avry,Korzets Asher,Zingerman Boris,Herman-Edelstein Michal,Bergman Michael,Gafter Uzi,Salman Hertzel Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association BACKGROUND:The incidence of left ventricular hypertrophy (LVH) in primary aldosteronism (PA) is higher than in essential hypertension. LVH is an independent cardiovascular risk factor. Treatment of PA with mineralocorticoid receptor blockers (MRBs) improves LVH. Previous studies included relatively small groups, low incidence of LVH and used high MRB dose. We tested the hypothesis that long-term regression of LVH in PA/low-renin hypertension may be achieved with low-dose MRB. METHODS:Forty-eight patients (male/female 28/20, age 61.4 years, range 47-84) had PA (low renin, high aldosterone and high aldosterone/renin ratio, n=24) or low-renin hypertension (low renin, normal aldosterone and high aldosterone/renin ratio, n=24). All had either LVH or concentric remodelling. All had an echocardiogram both at baseline and at 1 year after the initiation of spironolactone. A subgroup of 29 patients had an echocardiogram at baseline, 1 year (range 0.5-1.5) and 3 years (range 1.8-7). RESULTS:At baseline, spironolactone was commenced in all patients. The dose was 33.3±13.7 and 29.0±11.7 mg/day at 1 year and 3 years, respectively. A total of 73% of the patients received ≤37.5 mg/day. Introduction of spironolactone enabled the reduction of other antihypertensive medications (from 2.6±1.2 to 1.5±1.0 at 1 year). At 1 year, systolic and diastolic blood pressure decreased (149.3±14.1 to 126.2±12.0 mmHg, P<0.001, and 88.2±9.8 to 78.3±7.1 mmHg, P<0.001, respectively). At baseline, LVH was present in 39 of the 48 (81%) patients, and concentric remodelling, i.e. increased relative wall thickness (RWT) with a normal left ventricular mass index (LVMI), in 36 (75%). At 1 year, LVMI decreased in 44 of the 48 (92%) patients (142.9±25.4 versus 117.7±20.4 g/m2, P<0.001). LVH normalized in 16 of the 39 (41%) patients. RWT normalized in 36% of the patients. The changes in blood pressure and LVMI did not correlate. At 3 years, LVH decreased further and normalized in 57% of the patients. CONCLUSIONS:In patients with PA/low-renin hypertension, long-term regression of LVH may be achieved with low-dose MRB. 10.1093/ndt/gfs587
    Association between urine aldosterone and diastolic function in patients with primary aldosteronism and essential hypertension. Chang Yi-Yao,Lee Hsiu-Hao,Hung Chi-Sheng,Wu Xue-Ming,Lee Jen-Kuang,Wang Shuo-Meng,Liao Min-Tsun,Chen Ying-Hsien,Wu Vin-Cent,Wu Kwan-Dun,Lin Yen-Hung, Clinical biochemistry OBJECTIVE:To investigate the association between aldosterone and cardiac diastolic dysfunction. DESIGN AND METHODS:We prospectively enrolled 20 patients with primary aldosteronism (PA) and 22 patients with essential hypertension (EH). Plasma aldosterone concentration, plasma renin activity, and 24-h urine aldosterone level were measured. Echocardiography, including tissue Doppler image recordings, was performed. RESULTS:PA patients had a significantly higher left ventricular (LV) mass index and worse LV diastolic function than those in EH patients. Among various measures of aldosterone, log-transformed 24-h urine aldosterone level had the most consistent correlation with diastolic function. CONCLUSIONS:Aldosterone is strongly associated with LV diastolic dysfunction. Twenty-four hour urine aldosterone is a good indicator to evaluate the impact of aldosterone on LV diastolic function. 10.1016/j.clinbiochem.2014.05.062
    Microvascular and macrovascular endothelial function in two different types of primary aldosteronism. Kato Toru,Node Koichi Hypertension research : official journal of the Japanese Society of Hypertension 10.1038/s41440-018-0153-y
    Eplerenone improves carotid intima-media thickness (IMT) in patients with primary aldosteronism. Matsuda Yayoi,Kawate Hisaya,Matsuzaki Chitose,Sakamoto Ryuichi,Shibue Kimitaka,Ohnaka Keizo,Anzai Keizo,Nomura Masatoshi,Takayanagi Ryoichi Endocrine journal Primary aldosteronism (PA) is associated with a higher rate of cardiovascular events than essential hypertension. Although adrenalectomy has been reported to reduce carotid intima-media thickness (IMT) in patients with PA, the effects of the selective aldosterone blocker, eplerenone, on vascular damage in these patients remains unclear. To evaluate the effects of eplerenone on vascular status in PA patients, we sequentially measured carotid IMT (using computer software to calculate an average IMT for accurate and reproducible evaluation) in 22 patients including 8 patients treated by unilateral adrenalectomy and 14 patients treated with eplerenone for 12 months. Patients who underwent adrenalectomy showed significant reductions in aldosterone concentration (from 345 ± 176 pg/mL to 67 ± 34 pg/mL; P<0.01) and IMT (from 0.67 ± 0.07 mm to 0.63 ± 0.09 mm; P<0.05) 6 months after surgery. Patients treated with eplerenone showed significant reductions in IMT from baseline (0.75 ± 0.10 mm) to 6 (0.71 ± 0.11 mm; P<0.05) and 12 (0.65 ± 0.09 mm; P<0.01) months, although plasma aldosterone level increased significantly, from 141 ± 105 pg/mL to 207 ± 98 pg/mL (P<0.05). Eplerenone treatment of patients with PA reduces blood pressure, increases serum potassium level, and improves vascular status. Carotid IMT may be a useful marker for evaluating the effectiveness of eplerenone in patients with PA. 10.1507/endocrj.EJ15-0362
    Alterations in vascular function in primary aldosteronism: a cardiovascular magnetic resonance imaging study. Mark P B,Boyle S,Zimmerli L U,McQuarrie E P,Delles C,Freel E M Journal of human hypertension Excess aldosterone is associated with increased cardiovascular risk. Aldosterone has a permissive effect on vascular fibrosis. Cardiovascular magnetic resonance imaging (CMR) allows study of vascular function by measuring aortic distensibility. We compared aortic distensibility in primary aldosteronism (PA), essential hypertension (EH) and normal controls and explored the relationship between aortic distensibility and pulse wave velocity (PWV). We studied PA (n=14) and EH (n=33) subjects and age-matched healthy controls (n=17) with CMR, including measurement of aortic distensibility, and measured PWV using applanation tonometry. At recruitment, PA and EH patients had similar blood pressure and left ventricular mass. Subjects with PA had significantly lower aortic distensibility and higher PWV compared with EH and healthy controls. These changes were independent of other factors associated with reduced aortic distensibility, including ageing. There was a significant relationship between increasing aortic stiffness and age in keeping with physical and vascular ageing. As expected, aortic distensibility and PWV were closely correlated. These results demonstrate that PA patients display increased arterial stiffness compared with EH, independent of vascular ageing. The implication is that aldosterone invokes functional impairment of arterial function. The long-term implications of arterial stiffening in aldosterone excess require further study. 10.1038/jhh.2013.70
    Comparison of left ventricular structure and function in primary aldosteronism and essential hypertension by echocardiography. Yang Yan,Zhu Li-Min,Xu Jian-Zhong,Tang Xiao-Feng,Gao Ping-Jin Hypertension research : official journal of the Japanese Society of Hypertension Primary aldosteronism (PA) is the most common secondary cause of hypertension. The present study investigated differences in left ventricular structure and function between hypertensive patients with PA and sucjects with essential hypertension (EH). One hundred patients with PA and 100 controls with EH were matched for age, gender, and 24-h ambulatory monitoring blood pressure (BP). Left ventricular mass index (LVMI), left atrial volume index (LAVI) and ejection fraction were calculated. LV diastolic function was estimated as the ratio of the early diastolic velocities (E) from transmitral inflow to the early diastolic velocities (e') of tissue Doppler at mitral annulus. PA and EH patients had similar LV dimensions, LV wall thicknesses, LVMI and LV systolic function. PA was associated with greater impairment in diastolic function, as reflected by the lower e' (P=0.004), higher E/e' ratio (P=0.005) and higher LAVI (P=0.02). The LV geometric dimensions and patterns of LV hypertrophy were similar between male patients from the PA and EH groups. However, in female patients, PA was correlated with higher LV internal dimensions (P=0.001), higher LVMI (P=0.04) and lower relative wall thickness (RWT, P=0.001). Multivariate analysis showed that LV diastolic function was independently correlated with age (β=0.416, P<0.001), 24-h systolic BP (β=0.238, P=0.016) and serum potassium (β=-0.201, P=0.036) in PA patients. In conclusion, PA appears to contribute to the impairment of LV diastolic function in both sexes as well as the higher prevalence of eccentric hypertrophy in women than in men compared with EH. Age, 24-h systolic BP and serum potassium levels are independent risk factors for LV diastolic function in PA patients. 10.1038/hr.2016.127
    Long-term control of arterial hypertension and regression of left ventricular hypertrophy with treatment of primary aldosteronism. Rossi Gian Paolo,Cesari Maurizio,Cuspidi Cesare,Maiolino Giuseppe,Cicala Maria Verena,Bisogni Valeria,Mantero Franco,Pessina Achille C Hypertension (Dallas, Tex. : 1979) Primary aldosteronism (PA), a common cause of high blood pressure (BP), induces left ventricular (LV) hypertrophy and an excess rate of cardiovascular events. Whether its treatment provides long-term cure of hypertension and regression of cardiovascular damage remains uncertain. To the aim of assessing the effect of treatment of PA on BP and LV changes, we prospectively recruited 323 patients in a long-term follow-up study entailing serial echocardiography evaluations. Of them, 180 had PA and were assigned to either adrenalectomy (n=110) or medical therapy (n=70) on the basis of the adrenal vein sampling. The remaining 143 were consecutive optimally treated primary hypertensive patients. At baseline, the PA patients had more inappropriate LV mass than PH patients (27.1% versus 16.2%; P=0.020), despite similar BP values. At a median follow-up of 36 months (range, 6-225), BP was lowered (P<0.0001 versus baseline) to similar values in adrenalectomized (135±15/83±9 mm Hg), medically treated PA (133±11/83±7 mm Hg), and PH (139±15/86±9 mm Hg) patients. To this end, the adrenalectomized patients required significantly less drugs than the other groups. In PA patients, the LV mass index and the rate of LV hypertrophy fell through LV inward remodeling to the level of optimally treated PH patients, indicating that the LV work markedly decreased. Findings were similar when long-term (≥5 and ≥10 years) data were examined. Thus, an early diagnosis and a specific treatment of PA warrant normalization of BP and reversal of detrimental LV changes at long term. 10.1161/HYPERTENSIONAHA.113.01316
    Epicardial Fat Thickness and Primary Aldosteronism. Iacobellis G,Petramala L,Marinelli C,Calvieri C,Zinnamosca L,Concistrè A,Iannucci G,De Toma G,Letizia C Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme Primary aldosteronism (PA) is associated with increased cardiovascular risk and left ventricle (LV) changes. Given its peculiar biomolecular and anatomic properties, excessive epicardial fat, the heart-specific visceral fat depot, can affect LV morphology. Whether epicardial fat can be associated with aldosterone and LV mass (LVM) in patients with PA is unknown. We performed ultrasound measurement of the epicardial fat thickness (EAT) in 79 consecutive newly diagnosed patients with PA, 59 affected by bilateral adrenal hyperplasia (IHA), 20 aldosterone-producing adenoma (APA), and 30 patients with essential hypertension (low renin hypertension) (EH). The 3 groups did not differ by age, sex distribution, body mass index (BMI), waist circumference (WC), or blood pressure values. EAT showed a trend of increase in both APA and IHA groups when compared to patients with EH (8.3±1.8 vs. 7.9±1.3 vs. 7.8±2 mm, respectively). EAT was significantly correlated with indexed LVM in the IHA group (r=0.35, p<005), better than BMI or WC were. Interestingly, EAT was highly associated with plasma aldosterone concentrations (PAC) and PAC/plasma renin activity (PRA) (PAC/PRA) in the APA group (p=0.58, p=0.37, p<0.01, for both), whereas BMI and WC were not. EAT was also correlated with PRA in the IHA group (p=-0.28, p<0.05). Our study indicates a novel and interesting interaction of EAT with PA, independent of obesity, abdominal fat and blood pressure control. EAT can locally affect LVM, at least in patients with IHA. Further studies in larger population will be required to confirm these findings. 10.1055/s-0035-1559769
    Cardiovascular complications associated with primary aldosteronism: a controlled cross-sectional study. Savard Sébastien,Amar Laurence,Plouin Pierre-François,Steichen Olivier Hypertension (Dallas, Tex. : 1979) A higher risk of cardiovascular events has been reported in patients with primary aldosteronism (PA) than in otherwise similar patients with essential hypertension (EH). However, the evidence is limited by small sample size and potential confounding factors. We, therefore, compared the prevalence of cardiovascular events in 459 patients with PA diagnosed in our hypertension unit from 2001 to 2006 and 1290 controls with EH. PA cases and EH controls were individually matched for sex, age (± 2 years), and office systolic blood pressure (± 10 mm Hg). Patients with PA and EH differed significantly in duration of hypertension, serum potassium, plasma aldosterone and plasma renin concentrations, aldosterone-to-renin ratio, and urinary aldosterone concentration (P<0.001 for all comparisons). The prevalence of electrocardiographic and echocardiographic left ventricular hypertrophy was about twice higher in patients with PA even after adjustment for hypertension duration. PA patients also had a significantly higher prevalence of coronary artery disease (adjusted odds ratio, 1.9), nonfatal myocardial infarction (adjusted odds ratio, 2.6), heart failure (adjusted odds ratio, 2.9), and atrial fibrillation (adjusted odds ratio, 5.0). The risks associated with PA were similar across levels of serum potassium and plasma aldosterone. To conclude, patients with PA are more likely to have had a cardiovascular complication at diagnosis than otherwise similar patients with EH. Target organ damage and complications disproportionate to blood pressure should be considered as an additional argument for suspecting PA in a given individual and possibly for broadening the scope of screening at the population level. 10.1161/HYPERTENSIONAHA.113.01060
    Cardiovascular outcomes in patients with primary aldosteronism after treatment. Catena Cristiana,Colussi GianLuca,Nadalini Elisa,Chiuch Alessandra,Baroselli Sara,Lapenna Roberta,Sechi Leonardo A Archives of internal medicine BACKGROUND:Experimental and human studies demonstrate that long-term exposure to elevated aldosterone levels results in cardiac and vascular damage. METHODS:We investigated long-term cardiovascular outcomes in patients with primary aldosteronism after surgical or medical treatment. Fifty-four patients with or without evidence of adrenal adenomas were prospectively followed up for a mean of 7.4 years after treatment with adrenalectomy or spironolactone. Patients with primary aldosteronism were compared with patients with essential hypertension and were treated to reach a blood pressure of less than 140/90 mm Hg. The main outcome measure was a combined cardiovascular end point comprising myocardial infarction, stroke, any type of revascularization procedure, and sustained arrhythmias. RESULTS:At baseline, the prevalence of cardiovascular events was greater in primary aldosteronism (35%) than in essential hypertension (11%) (odds ratio, 4.61; 95% confidence interval, 2.38-8.95; P< .001), with odds ratios of 4.93, 4.36, and 2.80 for sustained arrhythmias, cerebrovascular events, and coronary heart disease, respectively. Blood pressure during follow-up was comparable in the primary aldosteronism and essential hypertension groups. Ten patients in the primary aldosteronism group and 19 in the essential hypertension group reached the primary end point (P= .85). Cox analysis indicated that older age and longer duration of hypertension were factors independently associated with the cardiovascular end point. Cardiovascular outcome was comparable in patients with aldosteronism treated with adrenalectomy vs aldosterone antagonists (P= .71). CONCLUSION:Primary aldosteronism is associated with a cardiovascular complication rate out of proportion to blood pressure levels that benefits substantially from surgical and medical treatment in the long term. 10.1001/archinternmed.2007.33
    New-Onset Atrial Fibrillation in Patients With Primary Aldosteronism Receiving Different Treatment Strategies: Systematic Review and Pooled Analysis of Three Studies. Tsai Cheng-Hsuan,Chen Ya-Li,Pan Chien-Ting,Lin Yen-Tin,Lee Po-Chin,Chiu Yu-Wei,Liao Che-Wei,Chen Zheng-Wei,Chang Chin-Chen,Chang Yi-Yao,Hung Chi-Sheng,Lin Yen-Hung Frontiers in endocrinology Background:Primary aldosteronism (PA) is a common cause of secondary hypertension and associated with higher incidence of new-onset atrial fibrillation (NOAF). However, the effects of surgical or medical therapies on preventing NOAF in PA patents remain unclear. The aim of this meta-analysis study was to assess the risk of NOAF among PA patients receiving mineralocorticoid receptor antagonist (MRA) treatment, PA patients receiving adrenalectomy, and patients with essential hypertension. Methods:We performed the meta-analysis of the randomized or observational studies that investigated the incidence rate of NOAF in PA patients receiving MRA treatment versus PA patients receiving adrenalectomy from database inception until December 01, 2020 which were identified from PubMed, Embase, and Cochrane Library. Results:A total of 172 related studies were reviewed, of which three fulfilled the inclusion criteria, including a total of 2,705 PA patients. The results of meta-analysis demonstrated a higher incidence of NOAF among the PA patients receiving MRA treatment compared to the PA patients receiving adrenalectomy (pooled odds ratio [OR]: 2.83, 95% confidence interval [CI]: 1.76-4.57 in the random effects model, = 0%). The pooled OR for the PA patients receiving MRA treatment compared to the patients with essential hypertension was 1.91 (95% CI: 1.11-3.28). The pooled OR for the PA patients receiving adrenalectomy compared to the patients with essential hypertension was 0.70 (95% CI: 0.28-1.79). Conclusion:Compared to the essential hypertension patients and the PA patients receiving adrenalectomy, the patients with PA receiving MRA treatment had a higher risk of NOAF. Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42021222022. 10.3389/fendo.2021.646933
    Increased levels of oxidative stress, subclinical inflammation, and myocardial fibrosis markers in primary aldosteronism patients. Stehr Carlos B,Mellado Rosemarie,Ocaranza Maria P,Carvajal Cristian A,Mosso Lorena,Becerra Elia,Solis Margarita,García Lorena,Lavandero Sergio,Jalil Jorge,Fardella Carlos E Journal of hypertension BACKGROUND:Patients with primary aldosteronism experience greater left ventricular hypertrophy and a higher frequency of cardiovascular events than do essential hypertensive patients with comparable blood pressure levels. Aldosterone has been correlated with increased oxidative stress, endothelial inflammation, and fibrosis, particularly in patients with heart disease. AIM:To evaluate oxidative stress, subclinical endothelial inflammation, and myocardial fibrosis markers in patients with primary aldosteronism and essential hypertension. DESIGN AND INDIVIDUALS: We studied 30 primary aldosteronism patients and 70 control essential hypertensive patients, matched by age, sex and median blood pressure. For all patients, we measured the serum levels of aldosterone, plasma renin activity, malondialdehyde (MDA), xanthine oxidase, metalloproteinase-9, ultrasensitive C-reactive protein and amino terminal propeptides of type I (PINP), and type III procollagen. We also evaluated the effect of PA treatment in 19 PA individuals. RESULTS:PA patients showed elevated levels of MDA (1.70 ± 0.53 versus 0.94 ± 0.65 μmol/l, P <0.001) and PINP (81.7 ± 50.6 versus 49.7 ± 27 mg/l, P = 0.002) compared with essential hypertensive controls. We found a positive correlation between MDA, PINP, and the serum aldosterone/plasma renin activity ratio in primary aldosteronism patients. Clinically, treating primary aldosteronism patients decreased MDA and PINP levels. CONCLUSION:We detected higher levels of MDA and PINP in primary aldosteronism patients, suggesting increased oxidative stress and myocardial fibrosis in these individuals. Treating primary aldosteronism patients reduced MDA and PINP levels, which may reflect the direct effect of aldosterone greater than endothelial oxidative stress and myocardial fibrosis, possibly mediated by a mineralocorticoid receptor. 10.1097/HJH.0b013e32833d0177
    Effect of aldosterone-producing adenoma on endothelial function and Rho-associated kinase activity in patients with primary aldosteronism. Matsumoto Takeshi,Oki Kenji,Kajikawa Masato,Nakashima Ayumu,Maruhashi Tatsuya,Iwamoto Yumiko,Iwamoto Akimichi,Oda Nozomu,Hidaka Takayuki,Kihara Yasuki,Kohno Nobuoki,Chayama Kazuaki,Goto Chikara,Aibara Yoshiki,Noma Kensuke,Liao James K,Higashi Yukihito Hypertension (Dallas, Tex. : 1979) The purpose of this study was to evaluate vascular function and activity of Rho-associated kinases (ROCKs) in patients with primary aldosteronism. Vascular function, including flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation, and ROCK activity in peripheral leukocytes were evaluated in 21 patients with aldosterone-producing adenoma (APA), 23 patients with idiopathic hyperaldosteronism (IHA), and 40 age-, sex-, and blood pressure-matched patients with essential hypertension (EHT). FMD was significantly lower in the APA group than in the IHA and EHT groups (3.2±2.0% versus 4.6±2.3% and 4.4±2.2%; P<0.05, respectively), whereas there was no significant difference in FMD between the IHA and EHT groups. There was no significant difference in nitroglycerine-induced vasodilation in the 3 groups. ROCK activity was higher in the APA group than in the IHA and EHT groups (1.29±0.57 versus 1.00±0.46 and 0.81±0.36l; P<0.05, respectively), whereas there was no significant difference in ROCK activity between the IHA and EHT groups. FMD correlated with age (r=-0.31; P<0.01), plasma aldosterone concentration (r=-0.35; P<0.01), and aldosterone:renin ratio (r=-0.34; P<0.01). ROCK activity correlated with age (r=-0.24; P=0.04), plasma aldosterone concentration (r=0.33; P<0.01), and aldosterone:renin ratio (r=0.46; P<0.01). After adrenalectomy, FMD and ROCK activity were restored in patients with APA. APA was associated with both endothelial dysfunction and increased ROCK activity compared with those in IHA and EHT. APA may have a higher risk of future cardiovascular events. 10.1161/HYPERTENSIONAHA.114.05001
    Hypokalemia correlated with arterial stiffness but not microvascular endothelial function in patients with primary aldosteronism. Chang Yi-Yao,Chen Aaron,Chen Ying-Hsien,Hung Chi-Sheng,Wu Vin-Cent,Wu Xue-Ming,Lin Yen-Hung,Ho Yi-Lwun,Wu Kwan-Dun, Journal of the renin-angiotensin-aldosterone system : JRAAS INTRODUCTION:Hypokalemia in primary aldosteronism (PA) patients correlates with higher levels of cardiovascular events and altered left ventricular geometry. However, the influence of aldosterone on microvascular endothelial function and the effect of hypokalemia on the vascular structure still remain unclear. OBJECTIVES:We investigated the peripheral arterial functions, including the endothelial function of microvasculature and arterial stiffness in PA and essential hypertension (EH) patients, and the correlation between hypokalemia and peripheral arterial function among PA patients. METHODS:Twenty patients diagnosed as EH and 37 patients with PA were enrolled in this study. Reactive hyperemia index (RHI) and the augmentation index (AI) were obtained by non-invasive peripheral arterial tonometry. RESULTS:Twenty EH patients and a total of 37 PA patients, including 21 patients with normokalemia and 16 patients with hypokalemia, were enrolled and divided into groups 1, 2 and 3 respectively. PA patients had significantly higher AI (p=0.024) but not RHI than EH patients. RHI showed no difference between groups 1, 2 and 3. Group 3 had higher AI than either group 1 or group 2. In the whole study population, serum potassium level, after multivariate regression analysis testing, was the only factor associated with AI (ß= -0.102; p=0.002). In PA patients, serum potassium level was the only significant factor correlated with AI. (r= -0.458; p=0.004) CONCLUSIONS: PA patients had higher arterial stiffness but comparable microvascular endothelial function to EH patients. Hypokalemia correlated with arterial stiffness but not microvascular endothelial function in PA patients. 10.1177/1470320314524996
    Comparison of biomarkers of endothelial dysfunction and microvascular endothelial function in patients with primary aldosteronism and essential hypertension. Sang Miaomiao,Fu Yu,Wei Chenmin,Yang Jing,Qiu Xueting,Ma Jingqing,Qin Chao,Wu Feiyan,Zhou Xueling,Yang Tao,Sun Min Journal of the renin-angiotensin-aldosterone system : JRAAS INTRODUCTION:Studies have shown that primary aldosteronism (PA) has a higher risk of cardiovascular events than essential hypertension (EH). Endothelial dysfunction is an independent predictor of cardiovascular events. Whether PA and EH differ in the endothelial dysfunction is uncertain. Our study was designed to investigate the levels of biomarkers of endothelial dysfunction (Asymmetric dimethylarginine, ADMA; E-selectin, and Plasminogen activator inhibitor-1, PAI-1) and assess the microvascular endothelial function in patients with PA and EH, respectively. METHODS:The biomarkers of endothelial dysfunction were measured by enzyme-linked immunosorbent assay (ELISA). Microvascular endothelial function was evaluated by Pulse amplitude tonometry (PAT). RESULTS:Thirty-one subjects with EH and 36 subjects with PA including 22 with aldosterone-producing adenoma (APA) and 14 with idiopathic hyperaldosteronism (IHA) were enrolled in our study. The ADMA levels among the three groups were different (APA 47.83 (27.50, 87.74) ng/ml vs EH 25.08 (22.44, 39.79) ng/ml vs IHA 26.00 (22.23, 33.75) ng/ml;  = 0.04), however, when the APA group was compared with EH and IHA group, there was no statistical significance (47.83 (27.50, 87.74) ng/ml vs 25.08 (22.44, 39.79) ng/ml for EH,  = 0.11; 47.83 (27.50, 87.74) ng/ml vs IHA 26.00 (33.75) ng/ml,  = 0.07). The results of ADMA levels are presented as Median (p25, p75). Whereas, levels of PAI-1 and E-selectin, microvascular endothelial function were not significantly different between PA and EH subjects. CONCLUSIONS:Our study shows no significant differences between PA and EH in terms of biomarkers of endothelial dysfunction and microvascular endothelial function. The microvascular endothelial function of PA and EH patients is comparable. 10.1177/1470320321999491
    Primary aldosteronism and cardiovascular risk, before and after treatment. Funder John W The lancet. Diabetes & endocrinology 10.1016/S2213-8587(17)30368-6
    Biochemical and clinical characteristics of patients with primary aldosteronism: Single centre experience. Vujačić Nataša,Paunović Ivan,Diklić Aleksandar,Živaljević Vladan,Slijepčević Nikola,Kalezić Nevena,Stojković Mirjana,Stojanović Miloš,Beleslin Biljana,Žarković Miloš,Ćirić Jasmina Journal of medical biochemistry Background:Primary aldosteronism (PA) is associated with increased prevalence of metabolic disorders (impaired glucose and lipid metabolism and insulin resistance), but also with more frequent cardiovascular, renal and central nervous system complications. Methods:Biochemical and clinical parameters were retrospectively analysed for 40 patients with PA caused by aldosterone-producing adenoma (APA) and compared to the control groups of 40 patients with nonfunctioning adrenal adenoma (NFA) and essential hypertension (HT), and 20 patients with adrenal Cushing syndrome (CS) or subclinical CS (SCS). Results:Systolic, diastolic and mean arterial blood pressures were significantly higher in the PA group (p=0.004; p=0.002; p=0.001, respectively) than in NFA+HT group. PA patients had longer hypertension history (p=0.001) than patients with hypercorticism and all had hypokalaemia. This group showed the smallest mean tumour diameter (p<0.001). The metabolic syndrome was significantly less common in the PA group (37.5% vs. 70% in CS+SCS and 65% in NFA+HT group; p=0.015), although there was no significant difference in any of the analysed metabolic parameters between groups. PA group was found to have the most patients with glucose intolerance (81.8%), although the difference was not significant. The mean BMI for all three groups was in the overweight range. Patients with PA had higher microalbuminuria and a higher tendency for cardiovascular, renal and cerebrovascular events, but the difference was not significant. Conclusions:Our results support the importance of the early recognition of primary aldosteronism on the bases of clinical presentation, as well as an increased screening intensity. 10.2478/jomb-2019-0035
    Reversible heart rhythm complexity impairment in patients with primary aldosteronism. Lin Yen-Hung,Wu Vin-Cent,Lo Men-Tzung,Wu Xue-Ming,Hung Chi-Sheng,Wu Kwan-Dun,Lin Chen,Ho Yi-Lwun,Stowasser Michael,Peng Chung-Kang Scientific reports Excess aldosterone secretion in patients with primary aldosteronism (PA) impairs their cardiovascular system. Heart rhythm complexity analysis, derived from heart rate variability (HRV), is a powerful tool to quantify the complex regulatory dynamics of human physiology. We prospectively analyzed 20 patients with aldosterone producing adenoma (APA) that underwent adrenalectomy and 25 patients with essential hypertension (EH). The heart rate data were analyzed by conventional HRV and heart rhythm complexity analysis including detrended fluctuation analysis (DFA) and multiscale entropy (MSE). We found APA patients had significantly decreased DFAα2 on DFA analysis and decreased area 1-5, area 6-15, and area 6-20 on MSE analysis (all p < 0.05). Area 1-5, area 6-15, area 6-20 in the MSE study correlated significantly with log-transformed renin activity and log-transformed aldosterone-renin ratio (all p < = 0.01). The conventional HRV parameters were comparable between PA and EH patients. After adrenalectomy, all the altered DFA and MSE parameters improved significantly (all p < 0.05). The conventional HRV parameters did not change. Our result suggested that heart rhythm complexity is impaired in APA patients and this is at least partially reversed by adrenalectomy. 10.1038/srep11249
    Downregulated Serum 14, 15-Epoxyeicosatrienoic Acid Is Associated With Abdominal Aortic Calcification in Patients With Primary Aldosteronism. Liu Pinming,Zhang Shaoling,Gao Jingwei,Lin Ying,Shi Guangzi,He Wanbing,Touyz Rhian M,Yan Li,Huang Hui Hypertension (Dallas, Tex. : 1979) Patients with primary aldosteronism (PA) have increased risk of target-organ damage, among which vascular calcification is an important indicator of cardiovascular mortality. 14, 15-Epoxyeicosatrienoic acid (14, 15-EET) has been shown to have beneficial effects in vascular remodeling. However, whether 14, 15-EET associates with vascular calcification in PA is unknown. Thus, we aimed to investigate the association between 14, 15-EET and abdominal aortic calcification (AAC) in patients with PA. Sixty-nine patients with PA and 69 controls with essential hypertension, matched for age, sex, and blood pressure, were studied. 14, 15-Dihydroxyeicosatrienoic acid (14, 15-DHET), the inactive metabolite from 14, 15-EET, was estimated to reflect serum 14, 15-EET levels. AAC was assessed by computed tomographic scanning. Compared with matched controls, the AAC prevalence was almost 1-fold higher in patients with PA (27 [39.1%] versus 14 [20.3%]; =0.023), accompanied by significantly higher serum 14, 15-DHET levels (7.18±4.98 versus 3.50±2.07 ng/mL; <0.001). Plasma aldosterone concentration was positively associated with 14, 15-DHET (β=0.444; <0.001). Multivariable logistic analysis revealed that lower 14, 15-DHET was an independent risk factor for AAC in PA (odds ratio, 1.371; 95% confidence interval, 1.145-1.640; <0.001), especially in young patients with mild hypertension and normal body mass index. In conclusion, PA patients exibited more severe AAC, accompanied by higher serum 14, 15-DHET levels. On the contrary, decreased 14, 15-EET was significantly associated with AAC prevalence in PA patients, especially in those at low cardiovascular risk. 10.1161/HYPERTENSIONAHA.117.10644
    Primary aldosteronism-associated cardiomyopathy: Clinical-pathologic impact of aldosterone normalization. Frustaci Andrea,Letizia Claudio,Verardo Romina,Grande Claudia,Francone Marco,Sansone Luigi,Russo Matteo Antonio,Chimenti Cristina International journal of cardiology BACKGROUND:Primary aldosteronism (PA) causes a cardiomyopathy (CM) which substrate and evolution after aldosterone normalization are unreported. METHODS:Four male patients with aldosterone-secreting adrenal adenoma and cardiomyopathy (PACM, group A) were evaluated with 2D-echo, Magnetic Resonance (CMR), coronary angiography and left ventricular endomyocardial biopsy. Biopsy samples were processed for histology, electron microscopy, immunohistochemistry, and Western Blot analysis of myocardial aldosterone receptors and aquaporin 1 and 4. Results were compared with endomyocardial samples from 5 patients with hypertensive cardiomyopathy of equivalent severity and normal plasma aldosterone (group B) and surgical samples from 5 controls (group C). One PACM patient was re-examined with CMR and endomyocardial biopsy 12 months after adrenalectomy with aldosterone and cardiac normalization. RESULTS:Coronary arteries were normal in all. Group A showed prominent myocardial hypertrophy and fibrosis, with water accumulation in the cytosol and organelles of cardiomyocytes and microvascular smooth muscle cells, associated to reduced myofibril concentration and 2.8-fold increase in myocardial aldosterone receptors and aquaporin 1. At CMR, LGE areas were diffusely present. After aldosterone normalization, cardiomyocyte diameter reduced with disappearance of intracellular vacuoles, recovery of electron-density of cytosol and cell organelles, and myofibrillar content, persisting fibrosis and down-regulation of aldosterone receptors and aquaporin 1 channels. At CMR, myocardial mass reduced with recovery of cardiac contractility. LGE signal remained unchanged. CONCLUSION:PACM is a reversible entity characterized by over-expression of aldosterone receptors and aquaporin 1. It induces a reversible intracellular water overloading causing impaired cardiomyocyte relaxation, contraction and ultrastructural integrity. 10.1016/j.ijcard.2019.06.055
    Characterization and Gene Expression Analysis of Serum-Derived Extracellular Vesicles in Primary Aldosteronism. Burrello Jacopo,Gai Chiara,Tetti Martina,Lopatina Tatiana,Deregibus Maria Chiara,Veglio Franco,Mulatero Paolo,Camussi Giovanni,Monticone Silvia Hypertension (Dallas, Tex. : 1979) Patients affected by primary aldosteronism (PA) display an increased risk of cardiovascular events compared with essential hypertension (EH). Endothelial dysfunction favors initiation and progression of atherosclerosis and circulating extracellular vesicles (EVs), reflecting endothelial cell activity, could represent one of the mediators of endothelial dysfunction in these patients. The aim of this study was to characterize circulating EVs from patients diagnosed with PA and to explore their functional significance. Serum EVs were isolated from 12 patients with PA and 12 with EH, matched by sex, age, and blood pressure, and compared with 8 normotensive controls. At nanoparticle tracking analysis, EVs concentration was 2.2× higher in patients with PA ( P=0.033) compared with EH and a significant correlation between EV number and serum aldosterone and potassium levels was identified. Fluorescence-activated cell sorting analysis demonstrated that patients with PA presented a higher absolute number of endothelial-derived EVs compared with both patients with EH and normotensive controls. Through EV mRNA profiling, 15 up-regulated and 4 down-regulated genes in patients with PA compared with EH were identified; moreover, EDN1 was expressed only in patients with PA. Microarray platform was validated by quantative real-time polymerase chain reaction on 4 genes ( CASP1, EDN1, F2R, and HMOX1) involved in apoptosis, inflammation, and endothelial dysfunction. After unilateral adrenalectomy, EVs number and expression of CASP1 and EDN1 significantly decreased in patients with PA ( P<0.05). Additionally, the incubation with PA-derived EVs reduced angiogenesis and induced apoptosis in vitro. Circulating EVs might not only represent a marker of endothelial dysfunction but also contribute themselves to vascular dysfunction in patients with PA. 10.1161/HYPERTENSIONAHA.119.12944
    Long-term cardio- and cerebrovascular events in patients with primary aldosteronism. Mulatero Paolo,Monticone Silvia,Bertello Chiara,Viola Andrea,Tizzani Davide,Iannaccone Andrea,Crudo Valentina,Burrello Jacopo,Milan Alberto,Rabbia Franco,Veglio Franco The Journal of clinical endocrinology and metabolism BACKGROUND:Aldosterone plays a detrimental role on the cardiovascular system and PA patients display a higher risk of events compared with EH. OBJECTIVES:The objectives of the study were to compare cardio- and cerebrovascular events in patients with primary aldosteronism (PA) and matched essential hypertension (EH). METHODS:We retrospectively compared the percentage of patients experiencing events at baseline and during a median follow-up of 12 years in 270 PA patients case-control matched 1:3 with EH patients and in PA subtypes [aldosterone-producing adenoma (n = 57); bilateral adrenal hyperplasia (n = 213)] vs matched EH. RESULTS:A significantly higher number of PA patients experienced cardiovascular events over the entire period of the study (22.6% vs 12.7%, P < .001). At the diagnosis of PA, a higher number of patients had experienced total events (14.1% vs 8.4% EH, P = .007); furthermore, during the follow-up period, PA patients had a higher rate of events (8.5% vs 4.3% EH, P = .008). In particular, stroke and arrhythmias were more frequent in PA patients. During the follow-up, a higher percentage of PA patients developed type 2 diabetes. Parameters that were independently associated with the occurrence of all events were age, duration of hypertension, systolic blood pressure, presence of diabetes mellitus, and PA diagnosis. After division into PA subtypes, patients with either aldosterone-producing adenoma or bilateral adrenal hyperplasia displayed a higher rate of events compared with the matched EH patients. CONCLUSIONS:This study demonstrates in a large population of patients the pathogenetic role of aldosterone excess in the cardiovascular system and thus the importance of early diagnosis and targeted PA treatment. 10.1210/jc.2013-2805
    Saline Infusion Test highly associated with the incidence of cardio- and cerebrovascular events in primary aldosteronism. Hayashi Reiko,Tamada Daisuke,Murata Masahiko,Mukai Kosuke,Kitamura Tetsuhiro,Otsuki Michio,Shimomura Iichiro Endocrine journal Primary aldosteronism (PA) is caused by excess secretion of aldosterone and is an independent risk factor for cardio-cerebro-vascular (CCV) events. The goal of treatment of PA should include prevention of CCV events. A definitive diagnosis of PA is established by confirmatory tests [saline infusion test (SIT), furosemide upright test (FUT) and captopril challenge test (CCT)]. However, there is no information on whether the hormone levels measured by these confirmatory tests are associated with CCV events. The aim of this retrospective study was to elucidate the relationship between the results of the above confirmatory tests and prevalence of CCV disease in patients with PA. The study subjects were 292 PA patients who were assessed for past history of CCV events at the time of diagnosis of PA. CCV events were significantly higher in patients with positive than negative SIT (12.8% vs. 3.3%, p=0.04). There were no differences in the incidences of CCV events between patients with positive and negative CCT and FUT (CCT: 11.0% vs. 3.9%, p=0.13, FUT: 6.1% vs. 5.7%, p=0.93). Our results demonstrated a higher incidence of CCV disease in PA SIT-positive patients compared to those with negative test. SIT is a potentially useful test not only for the diagnosis of PA but also assessment of the risk of CCV events. 10.1507/endocrj.EJ16-0337
    Cortisol Excess in Patients With Primary Aldosteronism Impacts Left Ventricular Hypertrophy. Adolf Christian,Köhler Anton,Franke Anna,Lang Katharina,Riester Anna,Löw Anja,Heinrich Daniel A,Bidlingmaier Martin,Treitl Marcus,Ladurner Roland,Beuschlein Felix,Arlt Wiebke,Reincke Martin The Journal of clinical endocrinology and metabolism Context:Primary aldosteronism (PA) represents the most frequent form of endocrine hypertension. Hyperaldosteronism and hypercortisolism both induce excessive left ventricular hypertrophy (LVH) compared with matched essential hypertensives. In recent studies frequent cosecretion of cortisol and aldosterone has been reported in patients with PA. Objective:Our aim was to investigate the impact of cortisol cosecretion on LVH in patients with PA. We determined 24-hour excretion of mineralocorticoids and glucocorticoids by gas chromatography-mass spectrometry and assessed cardiac remodeling using echocardiography initially and 1 year after initiation of treatment of PA. Patients:We included 73 patients from the Munich center of the German Conn's registry: 45 with unilateral aldosterone-producing adenoma and 28 with bilateral adrenal hyperplasia. Results:At the time of diagnosis, 85% of patients with PA showed LVH according to left ventricular mass index [(LVMI); median 62.4 g/m2.7]. LVMI correlated positively with total glucocorticoid excretion (r2 = 0.076, P = 0.018) as well as with tetrahydroaldosterone excretion (r2 = 0.070, P = 0.024). Adrenalectomy led to significantly reduced LVMI in aldosterone-producing adenoma (P < 0.001) whereas mineralocorticoid receptor antagonist therapy in bilateral adrenal patients with hyperplasia reduced LVMI to a lesser degree (P = 0.024). In multivariate analysis, the decrease in LVMI was positively correlated with total glucocorticoid excretion and systolic 24-hour blood pressure, but not with tetrahydroaldosterone excretion. Conclusion:Cortisol excess appears to have an additional impact on cardiac remodeling in patients with PA. Treatment of PA by either adrenalectomy or mineralocorticoid receptor antagonist improves LVMI. This effect was most pronounced in patients with high total glucocorticoid excretion. 10.1210/jc.2018-00617
    Impact of electrocardiographic findings for diagnosis of left ventricular hypertrophy in patients with primary aldosteronism. Kurisu Satoshi,Iwasaki Toshitaka,Mitsuba Naoya,Ishibashi Ken,Dohi Yoshihiro,Kihara Yasuki Journal of the renin-angiotensin-aldosterone system : JRAAS BACKGROUND:Compared to patients with similar levels of hypertension, patients with primary aldosteronism have a greater left ventricular hypertrophy (LVH). The presence of LVH should be detected as early as possible to prevent cardiovascular complications associated with the condition. We evaluated comparative diagnostic value of electrocardiographic (ECG) indexes for LVH in patients with primary aldosteronism. METHODS:ECG and echocardiographic data were obtained in 88 patients with primary aldosteronism. We analyzed the four most commonly used ECG indexes, including Sokolow-Lyon index, Cornell voltage index, Cornell product index, and Gubner index. RESULTS:Echocardiographic LVH was found in 35 patients (40%). Sensitivity ranged from 0% for Gubner index to 49% for Cornell product index. Specificity ranged from 81% for Sokolow-Lyon index to 100% for Gubner index. Sokolow-Lyon index (r=0.43, p<0.001), Cornell voltage index (r=0.55, p<0.001) and Cornell product index (r=0.52, p<0.001) correlated significantly with left ventricular mass (LVM) index. No significant correlation was found between Gubner index and LVM index. CONCLUSIONS:ECG indexes had a reasonably high specificity, but a low sensitivity for LVH in patients with primary aldosteronism. Cornell voltage index and Cornell product index had a better diagnostic value of LVH, and had a better correlation with LVM index in these patients. 10.1177/1470320313482604
    Arterial stiffness evaluated by pulse wave velocity is not predictive of the improvement in hypertension after adrenal surgery for primary aldosteronism: A multicentre study from the French European Society of Hypertension Excellence Centres. Bouhanick Béatrice,Amar Jacques,Amar Laurence,Gosse Philippe,Girerd Xavier,Reznik Yves,Mounier-Vehier Claire,Baguet Jean Philippe,Boutouyrie Pierre,Lepage Benoit,Lantelme Pierre,Chamontin Bernard, Archives of cardiovascular diseases BACKGROUND:Predictive factors associated with normal blood pressure (BP) after unilateral adrenalectomy for primary aldosteronism (PA) are not clearly identified. AIMS:To evaluate the predictive value of arterial stiffness before surgery on BP after surgery. METHODS:During 2009-2013, 96 patients with PA due to unilateral adrenal adenoma who underwent surgery were enrolled in a multicentre open-label, prospective study. Aortic pulse wave velocity (PWV) was assessed before surgery. Patients underwent ambulatory blood pressure monitoring (ABPM) before surgery and 6 and 12months after surgery. Twenty-four h SBP/DBP values were compared in subjects with PWV<vs. ≥10m/s. The primary outcome was 24-hour ABPM<130/80mmHg 6 months after adrenalectomy. RESULTS:BP and PWV were available for 82 patients (mean age 49±12years). Mean 24-hour systolic/diastolic BP (SBP/DBP) values decreased from 144±15/91±9 before surgery to 131±15/84±11mmHg 6months after surgery. At 6months, mean 24-hour SBP did not differ significantly between high versus low PWV groups (SBP-0.8mmHg, 95% confidence interval-6.9 to 5.2, P=0.79). A total of 42.3% of women versus 20.0% of men had 24-hour SBP/DBP<130/80mmHg at 6months (P=0.07) and 57.9% vs. 23.8% at 12months (P=0.03). Higher SBP/DBP was recorded for men versus women after 6months (P=0.01/0.001) and 1year (P=0.04/0.05). CONCLUSION:Preoperative arterial stiffness does not predict a beneficial effect of adrenalectomy on BP values. 10.1016/j.acvd.2018.01.004
    Cardiovascular changes in patients with primary aldosteronism after surgical or medical treatment. Bernini G,Bacca A,Carli V,Carrara D,Materazzi G,Berti P,Miccoli P,Pisano R,Tantardini V,Bernini M,Taddei S Journal of endocrinological investigation BACKGROUND:Data on the cardiovascular middle-term follow-up of patients with primary aldosteronism (PA) are scanty. AIM:To detect the cardiovascular effects of surgery in patients with aldosterone (ALD)-producing adenoma (APA) and of pharmacotherapy in those with bilateral adrenal hyperplasia (BAH), a prospective study involving 60 consecutive patients with PA was performed. MATERIAL/ METHODS: Clinical, biochemical, and cardiovascular assessment was obtained before and after (31.5±4.4 months) surgery or proper medical treatment (32.1±5.0 months) in 19 and 41 patients, respectively. RESULTS:As expected, plasma ALD normalized in all operated patients, while in the other group it did not change. Systolic and diastolic blood pressure decreased (p<0.001) after both treatments. However, absolute and percentage reduction was significantly more pronounced (p<0.01) in operated than in non-operated patients. Left ventricular (LV) mass showed significant reduction after surgery (LV mass g/m(2), p<0.0007; LV mass g/m(2.7), p<0.01), but no change after medical treatment, so that the differences between absolute and percentage values at follow- up were statistically significant (p<0.01) between groups. Basal LV mass/m(2.7) was positively associated with age (p<0.009), body mass index (p<0.0008), drug number (p<0.03), and ALD/plasma renin activity ratio (p<0.01). Allocating the patients according to plasma ALD and cardiac parameters, patients who presented ALD reduction during the study also had a decrement in cardiac mass (p<0.04). CONCLUSIONS:Our data indicate that in patients with PA the removal of ALD excess by surgery in APA is effective in reducing blood pressure and in improving cardiac parameters, while anti-hypertensive therapy in BAH shows less positive impact on cardiovascular system. 10.3275/7611
    Influence of Different Treatment Strategies on New-Onset Atrial Fibrillation Among Patients With Primary Aldosteronism: A Nationwide Longitudinal Cohort-Based Study. Pan Chien-Ting,Liao Che-Wei,Tsai Cheng-Hsuan,Chen Zheng-Wei,Chen Likwang,Hung Chi-Sheng,Liu Yu-Chen,Lin Po-Chih,Chang Chin-Chen,Chang Yi-Yao,Wu Vin-Cent,Lin Yen-Hung, Journal of the American Heart Association Background Primary aldosteronism (PA) is associated with higher atrial fibrillation prevalence and other cardiovascular complications. However, the effect of target treatment to prevent new-onset atrial fibrillation (NOAF) remains unclear. This study investigated incidence of NOAF under different treatment strategies in patients with PA. Methods and Results We analyzed longitudinal data for patients with PA without atrial fibrillation history from 1997 to 2009 within the National Health Insurance Research Database in Taiwan. Patients with essential hypertension matched by propensity score were enrolled as controls. The primary outcome measurement was NOAF, and secondary outcome measurements were mortality, major cardiac and cardiac/cerebrovascular events, and a combined end point of NOAF and mortality. We identified 2202 patients with PA (534 adrenalectomy, 1668 mineralocorticoid receptor antagonist [MRA] therapy) and 8808 essential hypertension controls with mean follow-up of 4.4 years. In primary outcome measurement, patients with PA who underwent adrenalectomy had a lower incidence of NOAF (adjusted hazard ratio; 0.28, =0.011) than controls. In contrast, the patients with PA who received MRA therapy had comparable risk of NOAF (adjusted hazard ratio, 1.20; =0.224). In secondary outcome measurement, patients with PA who underwent adrenalectomy had a lower rate of mortality and combined end point of NOAF and mortality than controls. Patients with PA who received MRA therapy had a higher risk of mortality, major cardiac and cardiac/cerebrovascular events, and combined NOAF with mortality than the essential hypertension controls. Conclusions Compared with patients with essential hypertension, patients with PA who underwent adrenalectomy had a lower incidence of NOAF. However, this finding was not observed in patients with PA who received MRA therapy with a lower dose. Differences between the 2 strategies may reduce with a higher dose of MRA therapy. 10.1161/JAHA.119.013699
    Comparison of ambulatory blood pressure between patients with primary aldosteronism and other forms of hypertension. Libianto Renata,Menezes Serena,Kaur Amrina,Gwini Stella May,Shen Jimmy,Narayan Om,Fuller Peter J,Yang Jun,Young Morag J Clinical endocrinology OBJECTIVE:Primary aldosteronism (PA) is a potentially curable cause of hypertension associated with worse cardiovascular prognosis than blood pressure-matched essential hypertension (EH). Effective targeted treatment for PA is available with the greatest benefit seen if treatment is started early, prior to the development of end-organ damage. However, PA is currently substantially under-diagnosed. The standard screening test for PA, the aldosterone-to-renin ratio (ARR), is performed infrequently in both primary and tertiary care. In contrast, ambulatory blood pressure monitoring (ABPM) is frequently utilized in the assessment of hypertension. The aim of this study was to compare ABPM parameters in hypertensive patients with and without PA, in order to identify features of ABPM associated with PA that can prompt screening. STUDY DESIGN:Patients with PA (n = 55) were identified from a tertiary clinic specializing in the management of endocrine causes of hypertension whilst the controls (n = 389) were consecutive patients with hypertension but without a known diagnosis of PA who were referred for ABPM. RESULTS:In this study, PA patients were younger and had higher 24-h, day, and night-time blood pressure compared with controls despite similar number of antihypertensive medications. However, there was no significant difference in nocturnal dipping or day-night blood pressure variability between the two groups. CONCLUSIONS:An elevated ambulatory blood pressure in patients on multiple antihypertensives could suggest underlying PA but in the absence of other distinguishing features, ABPM could not reliably differentiate PA from other forms of hypertension. Routine biochemical screening for PA remained the most reliable way of detecting this treatable secondary cause of hypertension. 10.1111/cen.14373
    Prevalence of Cardiovascular Disease and Its Risk Factors in Primary Aldosteronism: A Multicenter Study in Japan. Ohno Youichi,Sone Masakatsu,Inagaki Nobuya,Yamasaki Toshinari,Ogawa Osamu,Takeda Yoshiyu,Kurihara Isao,Itoh Hiroshi,Umakoshi Hironobu,Tsuiki Mika,Ichijo Takamasa,Katabami Takuyuki,Tanaka Yasushi,Wada Norio,Shibayama Yui,Yoshimoto Takanobu,Ogawa Yoshihiro,Kawashima Junji,Takahashi Katsutoshi,Fujita Megumi,Watanabe Minemori,Matsuda Yuichi,Kobayashi Hiroki,Shibata Hirotaka,Kamemura Kohei,Otsuki Michio,Fujii Yuichi,Yamamoto Koichi,Ogo Atsushi,Okamura Shintaro,Miyauchi Shozo,Fukuoka Tomikazu,Izawa Shoichiro,Yoneda Takashi,Hashimoto Shigeatsu,Yanase Toshihiko,Suzuki Tomoko,Kawamura Takashi,Tabara Yasuharu,Matsuda Fumihiko,Naruse Mitsuhide, , Hypertension (Dallas, Tex. : 1979) There have been several clinical studies examining the factors associated with cardiovascular disease (CVD) in patients with primary aldosteronism (PA); however, their results have left it unclear whether CVD is affected by the plasma aldosterone concentration or hypokalemia. We assessed the PA database established by the multicenter JPAS (Japan Primary Aldosteronism Study) and compared the prevalence of CVD among patients with PA with that among age-, sex-, and blood pressure-matched essential hypertension patients and participants with hypertension in a general population cohort. We also performed binary logistic regression analysis to determine which parameters significantly increased the odds ratio for CVD. Of the 2582 patients with PA studied, the prevalence of CVD, including stroke (cerebral infarction, cerebral hemorrhage, or subarachnoid hemorrhage), ischemic heart disease (myocardial infarction or angina pectoris), and heart failure, was 9.4% (stroke, 7.4%; ischemic heart disease, 2.1%; and heart failure, 0.6%). The prevalence of CVD, especially stroke, was higher among the patients with PA than those with essential hypertension/hypertension. Hypokalemia (K ≤3.5 mEq/L) and the unilateral subtype significantly increased adjusted odds ratios for CVD. Although aldosterone levels were not linearly related to the adjusted odds ratio for CVD, patients with plasma aldosterone concentrations ≥125 pg/mL had significantly higher adjusted odds ratios for CVD than those with plasma aldosterone concentrations <125 pg/mL. Thus, patients with PA seem to be at a higher risk of developing CVD than patients with essential hypertension. Moreover, patients with PA presenting with hypokalemia, the unilateral subtype, or plasma aldosterone concentration ≥125 pg/mL are at a greater risk of CVD and have a greater need for PA-specific treatments than others. 10.1161/HYPERTENSIONAHA.117.10263
    Aldosterone to Renin Ratio as a Screening Instrument for Primary Aldosteronism in a Middle-Aged Population with Atrial Fibrillation. Mourtzinis Georgios,Ebrahimi Ahmad,Gustafsson Helena,Johannsson Gudmundur,Manhem Karin Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme Atrial fibrillation seems to be overrepresented among patients with primary aldosteronism. The aim of this study was to determine the usefulness of aldosterone to renin ratio as a screening instrument for primary aldosteronism in an atrial fibrillation population with relatively low cardiovascular risk profile. A total of 149 patients <65 years and with history of AF were screened for primary aldosteronism using aldosterone to renin ratio. Pathologically increased aldosterone to renin ratio (>65 pmol/mIU) was found in 15 participants (10.1%). Further investigation of the positive screened participants and confirmatory saline infusion test resulted in a diagnosis of primary aldosteronism in four individuals out of 149 (2.6%). Three out of the four individuals with primary aldosteronism had previously been diagnosed with hypertension, but only one out of the four had uncontrolled blood pressure, that is, >140/90 mmHg. All participants had normal potassium levels. Individuals with increased aldosterone to renin ratio had significantly higher mean systolic and diastolic blood pressure in comparison to participants with normal aldosterone to renin ratio (136 vs. 126 mmHg, p=0.02 and 84 vs. 78 mmHg, p=0.02). These findings suggest that assessment of aldosterone to renin ratio can be useful for identification of underlying primary aldosteronism in patients with diagnosed atrial fibrillation and hypertension in spite of well controlled blood pressure and normokalemia. 10.1055/s-0043-119220
    Arterial Wall Inflammation and Increased Hematopoietic Activity in Patients With Primary Aldosteronism. van der Heijden Charlotte D C C,Smeets Esther M M,Aarntzen Erik H J G,Noz Marlies P,Monajemi Houshang,Kersten Simone,Kaffa Charlotte,Hoischen Alexander,Deinum Jaap,Joosten Leo A B,Netea Mihai G,Riksen Niels P The Journal of clinical endocrinology and metabolism CONTEXT:Primary aldosteronism (PA) confers an increased risk of cardiovascular disease (CVD), independent of blood pressure. Animal models have shown that aldosterone accelerates atherosclerosis through proinflammatory changes in innate immune cells; human data are scarce. OBJECTIVE:The objective of this article is to explore whether patients with PA have increased arterial wall inflammation, systemic inflammation, and reprogramming of monocytes. DESIGN:A cross-sectional cohort study compared vascular inflammation on 2'-deoxy-2'-(18F)fluoro-D-glucose; (18F-FDG) positron emission tomography-computed tomography, systemic inflammation, and monocyte phenotypes and transcriptome between PA patients and controls. SETTING:This study took place at Radboudumc and Rijnstate Hospital, the Netherlands. PATIENTS:Fifteen patients with PA and 15 age-, sex-, and blood pressure-matched controls with essential hypertension (EHT) participated. MAIN OUTCOME MEASURES AND RESULTS:PA patients displayed a higher arterial 18F-FDG uptake in the descending and abdominal aorta (P < .01, P < .05) and carotid and iliac arteries (both P < .01). In addition, bone marrow uptake was higher in PA patients (P < .05). Although PA patients had a higher monocyte-to-lymphocyte ratio (P < .05), systemic inflammatory markers, cytokine production capacity, and transcriptome of circulating monocytes did not differ. Monocyte-derived macrophages from PA patients expressed more TNFA; monocyte-derived macrophages of healthy donors cultured in PA serum displayed increased interleukin-6 and tumor necrosis factor-α production. CONCLUSIONS:Because increased arterial wall inflammation is associated with accelerated atherogenesis and unstable plaques, this might importantly contribute to the increased CVD risk in PA patients. We did not observe inflammatory reprogramming of circulating monocytes. However, subtle inflammatory changes are present in the peripheral blood cell composition and monocyte transcriptome of PA patients, and in their monocyte-derived macrophages. Most likely, arterial inflammation in PA requires interaction between various cell types. 10.1210/clinem/dgz306
    Circadian hemodynamic characteristics in hypertensive patients with primary aldosteronism. Kusunoki Hiroshi,Iwashima Yoshio,Kawano Yuhei,Hayashi Shin-Ichiro,Kishida Masatsugu,Horio Takeshi,Shinmura Ken,Yoshihara Fumiki Journal of hypertension OBJECTIVE:The present study aimed to compare circadian hemodynamic characteristics in hypertensive patients with and without primary aldosteronism. METHODS:Circadian hemodynamics, including 24-h brachial and central blood pressure (BP), SBP variability indices, central pulse wave velocity (PWV), augmentation index (AIx@75), cardiac index, and total vascular resistance (TVR), were evaluated using an oscillometric device, Mobil-O-Graph, in 60 patients with primary aldosteronism (63.4±13.3 years, 47% women) and 120 age-matched and sex-matched patients with essential hypertension. RESULTS:Office SBP, PWV, AIx@75, and BP variability indices were similar between groups; however, 24-h brachial (124 ± 14 vs 130 ± 11 mmHg) as well as central (112 ± 12 vs 120 ± 10 mmHg) SBP was higher (both P < 0.01), and the difference between 24-h brachial and central SBP (11 ± 5 vs 9 ± 3 mmHg, P < 0.05), an index of pressure amplification, was smaller in primary aldosteronism than in essential hypertension. In both groups, cardiac index decreased from daytime to night-time (both P < 0.01), but this decrease was smaller in primary aldosteronism (P < 0.05). During daytime, TVR in primary aldosteronism was higher than that in essential hypertension (P < 0.05), and the significant increase of TVR from daytime to night-time was lost in primary aldosteronism. In a multivariate stepwise regression model, primary aldosteronism emerged as an independent predictor of 24-h central SBP as well as the difference between 24-h brachial and central SBP. CONCLUSION:Our results demonstrated that circadian hemodynamics in primary aldosteronism patients are characterized by increased central SBP, smaller disparity between brachial and central SBP, and disturbed circadian hemodynamic variation. 10.1097/HJH.0000000000001800
    Risk of new-onset diabetes mellitus in primary aldosteronism: a population study over 5 years. Wu Vin-Cent,Chueh Shih-Chieh J,Chen Likwang,Chang Chia-Hui,Hu Ya-Hui,Lin Yen-Hung,Wu Kwan-Dun,Yang Wei-Shiung, Journal of hypertension OBJECTIVE:Abnormal glucose metabolism due to insulin resistance has been linked to aldosterone overproduction. However, the long-term incidence of new-onset diabetes mellitus (NODM) among patients with primary aldosteronism after targeted treatment has not been well documented. METHODS:The diagnosis of primary aldosteronism and essential hypertension were identified, and then the occurrence of NODM, all-cause mortality among these patients, was ascertained by a validated algorithm from a 23-million population insurance registry. RESULTS:From 1999 to 2007, 2367 primary aldosteronism patients without previously diabetes mellitus were identified and propensity score-matched with 9468 patients with essential hypertension. Among those primary aldosteronism patients, 754 aldosterone-producing adenomas patients were identified and matched with 3016 essential hypertension controls. After a mean 5.2 years of follow-up, primary aldosteronism patients who underwent adrenalectomy had an attenuated NODM incidence (hazard ratio = 0.60, P < 0.01, versus essential hypertension); whereas those treated with mineralocorticoid receptor antagonist had augmented risk of NODM (hazard ratio = 1.16, P < 0.001, versus essential hypertension). Among the aldosterone-producing adenoma patients, adrenalectomy is also protective from developing NODM (hazard ratio = 0.61, P < 0.001, versus essential hypertension), however, mineralocorticoid receptor antagonist treatment did not alter the risk of NODM (P = 0.10, versus essential hypertension). Adjusted hazard ratios for long-term risk of mortality from this analysis revealed that adrenalectomy is protective, but NODM and major cardiovascular disease are deleterious. CONCLUSION:The primary aldosteronism patients who underwent adrenalectomy had reduced risk for incident NODM and all-cause of mortality, compared with matched hypertensive controls. This observation adds more evidence on the association of primary aldosteronism with a higher risk of metabolic syndrome and long-term mortality. 10.1097/HJH.0000000000001361
    Primary aldosteronism and its various clinical scenarios. Martell-Claros Nieves,Abad-Cardiel María,Alvarez-Alvarez Beatriz,García-Donaire José A,Pérez Cristina Fernández Journal of hypertension BACKGROUND:Primary aldosteronism is the most frequent endocrine cause of secondary hypertension. Aldosterone excess damages the cardiovascular system. OBJECTIVES:We compared biochemical; morphological, and cardiovascular risk differences among hypokalemic and normokalemic primary aldosteronism. We evaluated either both presentations correspond to two different entities or a unique disease in different evolutive stage. MATERIAL AND METHODS:This is a retrospective study including 157 patients with primary aldosteronism divided into two groups: typical presentation (serum potassium < 3.5 mmol/l, n = 87) and atypical presentation (serum potassium > 3.5 mmol/l, n = 70). RESULTS:The typical presentation group showed higher family background of ischemic heart disease (P = 0.028), plasmatic aldosterone levels (P = 0.001), and cardiovascular added risk (P = 0.013). Although kalemia was corrected in the hypokalemic group after specific treatment, typical presentation maintained lower levels. Predictors of typical presentation were the highest tertile of aldosterone level, baseline DBP, and a longer evolution of hypertension. Aldosterone serum levels increased along time in primary aldosteronism and it can be considered as the most discriminative factor for the type of presentation. CONCLUSION:Primary aldosteronism presentation along with normokalemia or hypokalemia could be the same disease at different evolution stages. Adequate detection of normokalemic primary aldosteronism deserves an early and intentional diagnostic attitude. 10.1097/HJH.0000000000000546
    Plasma aldosterone level within the normal range is less associated with cardiovascular and cerebrovascular risk in primary aldosteronism. Murata Masahiko,Kitamura Tetsuhiro,Tamada Daisuke,Mukai Kosuke,Kurebayashi Shogo,Yamamoto Tsunehiko,Hashimoto Kunihiko,Hayashi Reiko D,Kouhara Haruhiko,Takeiri Sachi,Kajimoto Yoshitaka,Nakao Makoto,Hamasaki Toshimitsu,Otsuki Michio,Shimomura Iichiro Journal of hypertension BACKGROUND:Previous studies showed higher risk of cardiovascular and cerebrovascular (CCV) events in primary aldosteronism compared with essential hypertension, but the patients of these studies were limited to primary aldosteronism patients with high plasma aldosterone concentration (PAC). The introduction of the aldosterone-renin ratio as the screening test for primary aldosteronism led to the recognition of primary aldosteronism patients with normal PAC (nPA). However, there is no information on the risk of primary aldosteronism including nPA. METHOD:In this retrospectively and cross-sectional study, the clinical features and CCV event risk of primary aldosteronism at diagnosis including nPA were investigated and compared with essential hypertension. The study included 292 consecutive primary aldosteronism patients and 498 essential hypertension outpatients. All primary aldosteronism patients were diagnosed by autonomous aldosterone secretion using confirmatory tests, and then divided into nPA (n = 130) and primary aldosteronism patients with high PAC (hPA: n = 162) using a PAC cutoff level of less than 443 pmol/l (16 ng/dl), representing the normal upper limit of PAC. RESULTS:nPA patients were significantly older at diagnosis of primary aldosteronism and at onset of hypertension compared with hPA patients. They had milder hypokalemia and easier-to-control blood pressure. The results suggested that nPA could be considered a mild type of primary aldosteronism but not an early-stage hPA. Moreover, the risk of all CCV events in nPA was significantly lower than that in hPA (odds ratio 0.42, 95% confidence interval 0.18-0.90, P < 0.05) and not significantly higher than that in essential hypertension (odds ratio 0.95, 95% confidence interval 0.43-1.94, P = 0.899). CONCLUSION:This study suggests that aggressive diagnostic workout for nPA is less effective to prevent CCV events. 10.1097/HJH.0000000000001251
    Primary Aldosteronism in Patients in China With Recently Detected Hypertension. Xu Zhixin,Yang Jun,Hu Jinbo,Song Ying,He Wenwen,Luo Ting,Cheng Qingfeng,Ma Linqiang,Luo Rong,Fuller Peter J,Cai Jun,Li Qifu,Yang Shumin, Journal of the American College of Cardiology BACKGROUND:A total of 44.7% adults in China have hypertension, but the prevalence of primary aldosteronism (PA) in Chinese hypertensive patients is unknown. OBJECTIVES:This study prospectively investigated the prevalence, characteristics, and outcomes of PA in newly diagnosed hypertensive patients. METHODS:In a large community health center, consecutive hypertensive patients with an aldosterone-renin ratio >20 ng/mIU and plasma aldosterone concentration >10 ng/dl underwent captopril challenge test and/or saline infusion test for confirmation of PA. Adrenal computed tomography scan and adrenal vein sampling were used for subtyping. PA patients treated with surgery or medication were followed up for 1 year, and outcomes after treatment were evaluated. RESULTS:In total, 1,020 newly diagnosed hypertensive patients were screened over 16 months, of whom 40 were diagnosed with PA, 948 with non-PA, 32 with probable PA, resulting in a prevalence of more than 4.0%. Compared with non-PA, PA patients more frequently displayed microalbuminuria (p = 0.031), but the incidence of cardiovascular events was not different (p = 0.927). For surgically treated patients (n = 7), a complete biochemical success rate was 100% and a complete clinical success rate was 85.7%. For medically treated patients (n = 29), the proportion with optimal blood pressure control was 79%, and among them, 91% (21 of 23) only needed 1 antihypertensive drug: the mineralocorticoid receptor antagonist. CONCLUSIONS:The prevalence of PA in patients with newly diagnosed hypertension in China was at least 4%. PA screening in newly diagnosed hypertensive patients leads to good clinical outcomes. (Primary Aldosteronism In Hypertensive Patients in China [PA-China]; NCT03155139). 10.1016/j.jacc.2020.02.052
    Cardiometabolic outcomes and mortality in medically treated primary aldosteronism: a retrospective cohort study. Hundemer Gregory L,Curhan Gary C,Yozamp Nicholas,Wang Molin,Vaidya Anand The lancet. Diabetes & endocrinology BACKGROUND:Mineralocorticoid receptor (MR) antagonists are the recommended medical therapy for primary aldosteronism. Whether this recommendation effectively reduces cardiometabolic risk is not well understood. We aimed to investigate the risk of incident cardiovascular events in patients with primary aldosteronism treated with MR antagonists compared with patients with essential hypertension. METHODS:We did a cohort study using patients from a research registry from Brigham and Women's Hospital, Massachusetts General Hospital, and their affiliated partner hospitals. We identified patients with primary aldosteronism using International Classification of Disease, 9th and 10th Revision codes, who were assessed between the years 1991-2016 and were at least 18 years of age. We excluded patients who underwent surgical adrenalectomy, had a previous cardiovascular event, were not treated with MR antagonists, or had no follow-up visits after study entry. From the same registry, we identified a population with essential hypertension that was frequency matched by decade of age at study entry. We extracted patient cohort data and collated it into a de-identified database. The primary outcome was an incident cardiovascular event, defined as a composite of incident myocardial infarction or coronary revascularisation, hospital admission with congestive heart failure, or stroke, which was assessed using adjusted Cox regression models. Secondary outcomes were the individual components of the composite cardiovascular outcome, as well as incident atrial fibrillation, incident diabetes, and death. FINDINGS:We identified 602 eligible patients with primary aldosteronism treated with MR antagonists and 41 853 age-matched patients with essential hypertension from the registry. The two groups of patients had comparable cardiovascular risk profiles and blood pressure throughout the study. The incidence of cardiovascular events was higher in patients with primary aldosteronism on MR antagonists than in patients with essential hypertension (56·3 [95% CI 48·8-64·7] vs 26·6 [26·1-27·2] events per 1000 person-years, adjusted hazard ratio 1·91 [95% CI 1·63-2·25]; adjusted 10-year cumulative incidence difference 14·1 [95% CI 10·1-18·0] excess events per 100 people). Patients with primary aldosteronism also had higher adjusted risks for incident mortality (hazard ratio [HR] 1·34 [95% CI 1·06-1·71]), diabetes (1·26 [1·01-1·57]), and atrial fibrillation (1·93 [1·54-2·42]). Compared with essential hypertension, the excess risk for cardiovascular events and mortality was limited to patients with primary aldosteronism whose renin activity remained suppressed (<1 μg/L per h) on MR antagonists (adjusted HR [2·83 [95% CI 2·11-3·80], and 1·79 [1·14-2·80], respectively) whereas patients who were treated with higher MR antagonist doses and had unsuppressed renin (≥1 μg/L per h) had no significant excess risk. INTERPRETATION:The current practice of MR antagonist therapy in primary aldosteronism is associated with significantly higher risk for incident cardiometabolic events and death, independent of blood pressure control, than for patients with essential hypertension. Titration of MR antagonist therapy to raise renin might mitigate this excess risk. FUNDING:US National Institutes of Health. 10.1016/S2213-8587(17)30367-4
    A speckle tracking echocardiographic study on right ventricular function in primary aldosteronism. Chen Yi-Lin,Xu Ting-Yan,Xu Jian-Zhong,Zhu Li-Min,Li Yan,Wang Ji-Guang Journal of hypertension OBJECTIVE:We investigated right ventricular function using speckle tracking echocardiography (STE) in patients with primary aldosteronism. METHODS:Our study included 51 primary aldosteronism patients and 50 age and sex-matched primary hypertensive patients. We performed two-dimensional echocardiography to measure cardiac structure and function. We performed STE offline analysis on right ventricular four-chamber (RV4CLS) and free wall longitudinal strains (RVFWLS). RESULTS:Primary aldosteronism patients, compared with primary hypertensive patients, had a significantly (P ≤ 0.045) greater left ventricular mass index (112.0 ± 22.6 vs. 95.8 ± 18.5 g/m) and left atrial volume index (26.9 ± 6.0 vs. 24.7 ± 5.6 ml/m) and higher prevalence of left ventricular concentric hypertrophy (35.3 vs. 12.0%), although they had similarly normal left ventricular ejection fraction (55-77%). Primary aldosteronism patients also had a significantly (P ≤ 0.047) larger right atrium and ventricle, lower tricuspid annular plane systolic excursion, and higher E/E't (the peak early filling velocity of trans-tricuspid flow to the peak early filling velocity of lateral tricuspid annulus ratio), estimated pulmonary arterial systolic pressure and right ventricular index of myocardial performance. On the right ventricular strain analysis, primary aldosteronism patients had a significantly (P < 0.001) lower RV4CLS (-18.1 ± 2.5 vs. -23.3 ± 3.4%) and RVFWLS (-21.7 ± 3.7 vs. -27.9 ± 4.5%) than primary hypertensive patients. Overall, RV4CLS and RVFWLS were significantly (r = -0.58 to -0.41, P < 0.001) correlated with plasma aldosterone concentration and 24-h urinary aldosterone excretion. After adjustment for confounding factors, the associations for RV4CLS and RVFWLS with 24-h urinary aldosterone excretion remained significant (P < 0.001), with a standardized coefficient of -0.48 and -0.55, respectively. CONCLUSION:In addition to left ventricular abnormalities, primary aldosteronism patients also show impaired right ventricular function, probably because of hyperaldosteronism. 10.1097/HJH.0000000000002527
    Larger ascending aorta in primary aldosteronism: a 3-year prospective evaluation of adrenalectomy vs. medical treatment. Zavatta Guido,Di Dalmazi Guido,Pizzi Carmine,Bracchetti Giovanni,Mosconi Cristina,Balacchi Caterina,Pagotto Uberto,Vicennati Valentina Endocrine OBJECTIVE:Primary aldosteronism is associated with higher cardiovascular morbidity as compared with essential hypertension. Vascular complications encompass myocardial infarction and cerebrovascular events. Aortic damage in primary aldosteronism has never been explored, although a few cases of ascending aorta aneurisms have been reported. DESIGN AND METHODS:We consecutively enrolled patients affected by primary aldosteronism (n = 45) and compared them with patients affected by essential hypertension (n = 47), on an outpatient setting. Echocardiographic data of patients with primary aldosteronism were collected during a mean follow-up of 3 years, in subjects who underwent adrenal surgery (n = 12) and those on mineralocorticoid receptor antagonists (n = 33). RESULTS AND CONCLUSION:We found that patients with primary aldosteronism had larger ascending aorta diameters than those with essential hypertension before starting any specific treatment. Patients with primary aldosteronism did not show significant changes in the size of ascending aorta during a mean of 3 years of follow-up, irrespective of the type of treatment (medical vs. surgical treatment). A longer follow-up will better clarify if worsening of the aortic damage may be better prevented by surgery rather than by mineralocorticoid receptor antagonists. 10.1007/s12020-018-1801-3
    Adrenalectomy Lowers Incident Atrial Fibrillation in Primary Aldosteronism Patients at Long Term. Rossi Gian Paolo,Maiolino Giuseppe,Flego Alberto,Belfiore Anna,Bernini Giampaolo,Fabris Bruno,Ferri Claudio,Giacchetti Gilberta,Letizia Claudio,Maccario Mauro,Mallamaci Francesca,Muiesan Maria Lorenza,Mannelli Massimo,Negro Aurelio,Palumbo Gaetana,Parenti Gabriele,Rossi Ermanno,Mantero Franco, Hypertension (Dallas, Tex. : 1979) Primary aldosteronism (PA) causes cardiovascular damage in excess to the blood pressure elevation, but there are no prospective studies proving a worse long-term prognosis in adrenalectomized and medically treated patients. We have, therefore, assessed the outcome of PA patients according to treatment mode in the PAPY study (Primary Aldosteronism Prevalence in Hypertension) patients, 88.8% of whom were optimally treated patients with primary (essential) hypertension (PH), and the rest had PA and were assigned to medical therapy (6.4%) or adrenalectomy (4.8%). Total mortality was the primary end point; secondary end points were cardiovascular death, major adverse cardiovascular events, including atrial fibrillation, and total cardiovascular events. Kaplan-Meier and Cox analysis were used to compare survival between PA and its subtypes and PH patients. After a median of 11.8 years, complete follow-up data were obtained in 89% of the 1125 patients in the original cohort. Only a trend (=0.07) toward a worse death-free survival in PA than in PH patients was observed. However, at both univariate (90.0% versus 97.8%; =0.002) and multivariate analyses (hazard ratio, 1.82; 95% confidence interval, 1.08-3.08; =0.025), medically treated PA patients showed a lower atrial fibrillation-free survival than PH patients. By showing that during a long-term follow-up adrenalectomized aldosterone-producing adenoma patients have a similar long-term outcome of optimally treated PH patients, whereas, at variance, medically treated PA patients remain at a higher risk of atrial fibrillation, this large prospective study emphasizes the importance of an early identification of PA patients who need adrenalectomy as a key measure to prevent incident atrial fibrillation. 10.1161/HYPERTENSIONAHA.117.10596
    U-shaped relationship between left ventricular mass index and estimated glomerular filtration rate in patients with primary aldosteronism. Liao Min-Tsun,Liao Che-Wei,Tsai Cheng-Hsuan,Chang Yi-Yao,Chen Zheng-Wei,Pan Chien-Ting,Lin Lung-Chun,Wu Vin-Cent,Kuo Shu-Fen,Wu Xue-Ming,Hung Chi-Sheng,Lin Yen-Hung, Journal of investigative medicine : the official publication of the American Federation for Clinical Research Estimated glomerular filtration rate (eGFR) is an important topic in patients with primary aldosteronism (PA). However, the relationship between left ventricular structure and eGFR is unclear. We conducted a prospective, observational, and cross-sectional study to analyze 168 patients with PA and 168 propensity score-matched patients with essential hypertension (EH) as the control group, matched by age, gender, and systolic blood pressure. In the patients with PA, the eGFR was not correlated with left ventricular mass index (LVMI; r=-0.065, p=0.404), while in the patients with EH, the eGFR was negatively correlated with LVMI (r=-0.309, p<0.001). To test whether eGFR had a non-linear relationship with LVMI among the patients with PA, we stratified the patients with PA according to the tertile of eGFR (low, medium, and high tertile). The medium tertile of patients had a significantly lower LVMI than those in the other two tertiles (LVMI: 143.5±41.6, 120.5±40.5, and 133.1±34.3 g/m, from the lowest to highest tertile of eGFR; analysis of covariance p=0.032). The medium tertile of eGFR is associated with lowest LVMI. Patients with PA with high and low eGFR were associated with higher LVMI. The findings implied that the reasons for an increased LVMI in patients with PA may be different to those in patients with EH. 10.1136/jim-2019-001057
    Primary aldosteronism is associated with decreased low-density and high-density lipoprotein particle concentrations and increased GlycA, a pro-inflammatory glycoprotein biomarker. Berends Annika M A,Buitenwerf Edward,Gruppen Eke G,Sluiter Wim J,Bakker Stephan J L,Connelly Margery A,Kerstens Michiel N,Dullaart Robin P F Clinical endocrinology BACKGROUND:Primary aldosteronism (PA) may confer increased cardiovascular risk beyond effects on systemic blood pressure, but contributing mechanisms remain incompletely understood. We compared plasma (apo)lipoproteins and lipoprotein particle characteristics, GlycA, a pro-inflammatory glycoprotein biomarker of enhanced chronic inflammation, and plasma total branched-chain amino acids (BCAA), measured using nuclear magnetic resonance (NMR) spectroscopy, between patients with PA, control subjects without hypertension, subjects with untreated hypertension and subjects with treated hypertension. METHODS:Twenty PA patients were individually matched with 2819 control subjects without hypertension, 501 subjects with untreated hypertension and 878 subjects with treated hypertension participating in the PREVEND (Prevention of Renal and Vascular End-Stage Disease) cohort study with respect to age, sex, body mass index, smoking and statin use. The Vantera® Clinical Analyzer was used to determine NMR-based laboratory parameters. RESULTS:Total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein (apo) B, apolipoprotein A-I (apoA-I), LDL particle and HDL particle concentrations were all decreased in PA subjects vs control subjects and subjects with untreated hypertension (P < 0.016). Triglycerides (TG) and triglyceride-rich lipoprotein (TRL) concentrations were lower in PA subjects vs subjects with (untreated) hypertension. GlycA was increased in PA vs the three comparator groups (P < 0.016). Total BCAA concentrations were unaltered in PA. CONCLUSIONS:Primary aldosteronism is associated with lower concentrations of LDL and HDL particles and to some extent also with lower TG and TRL particle concentrations. PA is also characterized by increased GlycA levels, indicating enhanced low-grade chronic inflammation. Low HDL particle concentrations and increased GlycA could contribute to accelerated cardiovascular disease development in PA. 10.1111/cen.13891
    Primary aldosteronism: Higher volume load, cardiac output and arterial stiffness than in essential hypertension. Choudhary M K,Värri E,Matikainen N,Koskela J,Tikkakoski A J,Kähönen M,Niemelä O,Mustonen J,Nevalainen P I,Pörsti I Journal of internal medicine BACKGROUND:The diagnostics of primary aldosteronism (PA) are usually carried out in patients taking antihypertensive medications. We compared haemodynamics between medicated PA, medicated essential hypertension (EH), never-medicated EH and normotensive controls (n = 130 in all groups). METHODS:The hypertensive groups were matched for age (53 years), sex (84 male/46 female) and body mass index (BMI) (30 kg m ); normotensive controls had similar sex distribution (age 48 years, BMI 27 kg m ). Haemodynamics were recorded using whole-body impedance cardiography and radial pulse wave analysis, and the results were adjusted as appropriate. Radial blood pressure recordings were calibrated by brachial blood pressure measurements from the contralateral arm. RESULTS:Radial and aortic systolic and diastolic blood pressure was similar in PA and never-medicated EH, and higher than in medicated EH and normotensive controls (P ≤ 0.001 for all comparisons). Extracellular water balance was ~ 4% higher in PA than in all other groups (P < 0.05 for all), whilst cardiac output was ~ 8% higher in PA than in medicated EH (P = 0.012). Systemic vascular resistance and augmentation index were similarly increased in PA and both EH groups when compared with controls. Pulse wave velocity was higher in PA and never-medicated EH than in medicated EH and normotensive controls (P ≤ 0.033 for all comparisons). CONCLUSIONS:Medicated PA patients presented with corresponding systemic vascular resistance and wave reflection, but higher extracellular water volume, cardiac output and arterial stiffness than medicated EH patients. Whether the systematic evaluation of these features would benefit the clinical diagnostics of PA remains to be studied in future. 10.1111/joim.13115
    Myocardial mechano-energetic efficiency in primary aldosteronism. Salvetti Massimo,Paini Anna,Bertacchini Fabio,Aggiusti Carlo,Stassaldi Deborah,Capellini Sara,Arnoldi Chiara,Rizzoni Damiano,Agabiti Rosei Claudia,De Ciuceis Carolina,Muiesan Maria Lorenza Journal of hypertension BACKGROUND:Available data indicate that patients with primary aldosteronism have an increased risk of cardiovascular events and cardiovascular risk seems to be, at least in part, independent of blood pressure (BP) values. Patients with primary aldosteronism have a greater prevalence of left ventricular (LV) hypertrophy and subtle alterations of ventricular function, which might contribute to the increase in cardiovascular risk. Recently, a noninvasive approach for the estimation of LV mechanical efficiency, obtained by echocardiography has been proposed. AIM OF THE STUDY:To evaluate the determinants of myocardial mechanoenergetic efficiency index (MEEi), in a large group of patients with primary aldosteronism (n = 99) and in a control group of essential hypertensive patients (n = 99) matched for age, sex and BP values. RESULTS:No differences between groups for age, sex, BMI, BP values, glucose, lipid profile and renal function were observed. LV mass index was greater in primary aldosteronism vs. essential hypertensive patients (46.0 ± 16.7 vs. 36.9 ± 8.6 g/m2, P < 0.001); also relative wall thickness was greater in primary aldosteronism (0.36 ± 0.1 vs. 0.32 ± 0.4, P < 0.001). Left atrial dimensions were significantly greater in primary aldosteronism. Ejection fraction was not different between groups, while endocardial and midwall fractional shortening were lower in primary aldosteronism vs. essential hypertensive patients (40 ± 7 vs. 43 ± 6, and 18 ± 3 vs. 21 ± 2, both P < 0.01). MEEi was lower in primary aldosteronism vs. essential hypertensive patients (0.44 ± 0.14 vs. 0.52 ± 0.10 ml/s per g, P < 0.01). A negative correlation was observed between MEEi and aldosterone levels (r = -0.203, P < 0.05) and aldosterone : renin ratio (P = -0.172, P < 0.05); the correlation remained significant after adjustment for possible confounders. CONCLUSION:In patients with primary aldosteronism myocardial MEEi is lower as compared with essential hypertensive patients. A reduced MEEi may reflect an impairment of production and utilization of energy in the myocardium, which could lead to the occurrence of cardiovascular complications and therefore these findings may contribute to explain the increased risk of cardiovascular events in patients with primary aldosteronism. 10.1097/HJH.0000000000002637
    Diurnal blood pressure pattern and cardiac damage in hypertensive patients with primary aldosteronism. Wu Qihong,Hong Mona,Xu Jianzhong,Tang Xiaofeng,Zhu Limin,Gao Pingjin,Wang Jiguang Endocrine PURPOSE:The aim of our study was to evaluate the relationship between the 24-h blood pressure (BP) profile, plasma NT-proBNP levels and left ventricular hypertrophy (LVH) in subjects with primary aldosteronism (PA) compared to patients with essential hypertension (EH). METHODS:A total of 385 consecutive patients with PA [187 with aldosterone producing adenoma (APA) and 198 with idiopathic hyperaldosteronism (IHA)] and 385 patients with EH were matched based on age, sex, body mass index (BMI), BP values and duration of hypertension. Twenty-four-hour ambulatory BP monitoring (ABPM), plasma levels of NT-proBNP, left ventricular mass index (LVMI), and other clinical medical data were assessed in all patients. RESULTS:No differences in age, sex, BMI, clinical BP, 24-h mean BP, daytime BP, or duration of hypertension were found between groups. Nighttime systolic BP (130 ± 16 vs. 127 ± 17 mmHg, p < 0.05) and diastolic BP (82 ± 10 vs. 79 ± 11 mmHg, p < 0.01) were higher in PA patients than in EH patients. In addition, nocturnal BP decline was reduced, while median NT-proBNP (53.7 vs. 33.2 pg/ml, P < 0.001) and LVMI (113 ± 25 vs. 102 ± 26 g/m, P < 0.001) were higher in PA patients than in EH patients. Moreover, the median NT-proBNP level was higher in APA patients than in IHA patients (68.0 vs. 42.4 pg/ml, P < 0.001). In stepwise multivariate regression analysis, LVMI was correlated with NT-proBNP, nighttime systolic BP and sex in PA patients. CONCLUSIONS:Patients with PA show higher nighttime BP and NT-proBNP levels and lower nocturnal BP decline than those with EH. In addition, higher nocturnal systolic BP has been shown to be strongly associated with cardiac damage in PA patients. 10.1007/s12020-021-02606-3
    Diabetes Mellitus Itself Increases Cardio-Cerebrovascular Risk and Renal Complications in Primary Aldosteronism. Saiki Aya,Otsuki Michio,Tamada Daisuke,Kitamura Tetsuhiro,Shimomura Iichiro,Kurihara Isao,Ichijo Takamasa,Takeda Yoshiyu,Katabami Takuyuki,Tsuiki Mika,Wada Norio,Yanase Toshihiko,Ogawa Yoshihiro,Kawashima Junji,Sone Masakatsu,Inagaki Nobuya,Yoshimoto Takanobu,Okamoto Ryuji,Takahashi Katsutoshi,Kobayashi Hiroki,Tamura Kouichi,Kamemura Kohei,Yamamoto Koichi,Izawa Shoichiro,Kakutani Miki,Yamada Masanobu,Tanabe Akiyo,Naruse Mitsuhide The Journal of clinical endocrinology and metabolism CONTEXT:The prevalence of diabetes mellitus (DM) in patients with primary aldosteronism (PA) is higher than in those with essential hypertension and the general population. Although DM is a common major risk factor for cardio-cerebrovascular (CCV) diseases and renal complications, details of its effects in PA have not been demonstrated. OBJECTIVE:The aim of this study was to determine the effects of coexistent DM on the risk of CCV events and progression of renal complications in PA patients. DESIGN:A multi-institutional, cross-sectional study was conducted. PATIENTS AND METHODS:PA patients experienced between January 2006 and October 2016 and with available data of CCV events and DM were enrolled from the Japan PA registry of the Japan Primary Aldosteronism Study/Japan Rare Intractable Adrenal Diseases Study (n = 2524). CCV events and renal complications were compared between a DM group and a non-DM group by logistic and liner-regression analysis. RESULTS:DM significantly increased the odds ratio (OR) of CCV events (OR 1.59, 95% CI: 1.05-2.41) and that of proteinuria (OR 2.25, 95% CI: 1.59-3.16). DM correlated significantly with declines in estimated glomerular filtration rate (β = .05, P = .02). CONCLUSIONS:This the first report to demonstrate the presence of DM as an independent risk factor for CCV events and renal complications, even in PA patients. Management of DM should be considered in addition to the specific treatment of PA. 10.1210/clinem/dgaa177
    Nadir Aldosterone Levels After Confirmatory Tests Are Correlated With Left Ventricular Hypertrophy in Primary Aldosteronism. Ohno Youichi,Sone Masakatsu,Inagaki Nobuya,Kawashima Akiyuki,Takeda Yoshiyu,Yoneda Takashi,Kurihara Isao,Itoh Hiroshi,Tsuiki Mika,Ichijo Takamasa,Katabami Takuyuki,Wada Norio,Sakamoto Ryuichi,Ogawa Yoshihiro,Yoshimoto Takanobu,Yamada Tetsuya,Kawashima Junji,Matsuda Yuichi,Kobayashi Hiroki,Kamemura Kohei,Yamamoto Koichi,Otsuki Michio,Okamura Shintaro,Izawa Shoichiro,Okamoto Ryuji,Tamura Kouichi,Tanabe Akiyo,Naruse Mitsuhide, Hypertension (Dallas, Tex. : 1979) Left ventricular hypertrophy (LVH) is often seen in patients with primary aldosteronism (PA), and the prevalence of LVH is reportedly higher among patients with PA than patients with essential hypertension. However, the correlation between aldosterone levels and LVH is undefined, and how aldosterone affects LVH in patients with PA remains unclear. We, therefore, retrospectively assessed a large PA database established by the multicenter JPAS (Japan Primary Aldosteronism Study) to reveal the factors associated with LVH in patients with PA without suspected autonomous cortisol secretion. In the 1186 patients with PA studied, the basal plasma aldosterone concentration, plasma renin activity, and the aldosterone-to-renin ratio did not significantly correlate with left ventricular LV mass index (LVMI) in single or multiple regression analyses. However, the plasma aldosterone concentration after the captopril challenge test or saline-infusion test, which are associated with autonomous aldosterone secretion, correlated significantly with LVMI, even after adjusting for patients' backgrounds, including age and blood pressure. In addition, hypokalemia and the unilateral subtype also correlated with LVMI. Longitudinal subanalysis of medically or surgically treated patients with PA showed significant reductions in LVMI in both the surgery (63.0±18.1 to 55.3±19.5 g/m, <0.001) and drug treatment (56.8±14.1 to 52.1±13.5 g/m, <0.001) groups. Our results suggest the autonomous aldosterone secretion level, not the basal aldosterone level itself, is relevant to LVH in patients with PA. In addition, the elevated LVMI seen in patients with PA is at least partially reversible with surgical or medical treatment. 10.1161/HYPERTENSIONAHA.119.14601
    Left atrial myocardial dysfunction in patients with primary aldosteronism as assessed by speckle-tracking echocardiography. Wang Dian,Xu Jian-Zhong,Chen Xin,Xu Ting-Yan,Zhang Wei,Li Yan,Wang Ji-Guang Journal of hypertension BACKGROUND:We investigated the left atrial myocardial deformation in patients with primary aldosteronism using the speckle-tracking echocardiographic (STE) strain imaging technique. METHODS:Our study included 107 primary aldosteronism patients [52 aldosterone-producing adenoma (APA) and 55 idiopathic hyperaldosteronism (IHA)] and 50 primary hypertensive patients. We performed conventional echocardiography to measure left atrial volume and ejection fraction, and STE to estimate left atrial myocardial deformation including peak velocity, strain and strain rate and calculate the ratio of E/e' to left atrial strain during left ventricular systole as the left atrial stiffness index. RESULTS:Patients with APA, compared with those with IHA and primary hypertension had a significantly (P < 0.001) lower serum potassium concentration and higher 24-h urinary aldosterone excretion and plasma aldosterone-to-renin ratio. Patients with APA had a significantly (P < 0.01) larger maximal, precontraction, and minimal left atrial volumes and lower total, active and passive left atrial emptying fractions than those with IHA and primary hypertension. Among the three groups, patients with APA showed lowest left atrial velocity, strain, and strain rate during ventricular systole, early diastole and late diastole (P < 0.05) and highest left atrial stiffness index (P < 0.001). In unadjusted analysis, the left atrial strain, strain rate and stiffness index were significantly (P < 0.05) associated with plasma aldosterone concentration and urinary aldosterone excretion. After adjustment for various confounding factors, these associations remained statistically significant for urinary aldosterone excretion (P < 0.05) but not plasma aldosterone concentration (P ≥ 0.05). CONCLUSION:Patients with primary aldosteronism, especially APA, had impaired left atrial deformation mechanics and increased left atrial stiffness, providing a promising insight into early detection of subclinical left atrial dysfunction by strain echocardiography. 10.1097/HJH.0000000000002146
    Left Ventricular Dysfunction in Patients With Primary Aldosteronism: A Propensity Score-Matching Follow-Up Study With Tissue Doppler Imaging. Chang Yi-Yao,Liao Che-Wei,Tsai Cheng-Hsuan,Chen Ching-Way,Pan Chien-Ting,Chen Zheng-Wei,Chen Ya-Li,Lin Lung-Chun,Chang Yi-Ru,Wu Vin-Cent,Wu Kwan-Dun,Hung Chi-Sheng,Lin Yen-Hung, , Journal of the American Heart Association Background Primary aldosteronism is the most common cause of secondary hypertension and is associated with left ventricular hypertrophy. However, whether aldosterone excess is responsible for left ventricular (LV) diastolic dysfunction is unknown. Methods and Results We prospectively enrolled 129 patients with aldosterone-producing adenoma and 120 patients with essential hypertension, and analyzed their clinical, biochemical, and echocardiographic data, including tissue Doppler images. The patients with aldosterone-producing adenoma were reevaluated 1 year after adrenalectomy. After propensity score matching, there were 105 patients in each group. The patients with aldosterone-producing adenoma had worse diastolic function than the patients with essential hypertension, as reflected by lower e' (<0.001) and higher E/e' (=0.003). Multivariate analysis showed that LV diastolic function was significantly correlated with age (<0.001), sex (<0.001), body mass index (=0.002), systolic blood pressure (=0.004), creatinine (=0.008), and log-transformed aldosterone-renin ratio (=0.003). After adrenalectomy, the patients with aldosterone-producing adenoma had significant improvements in LV diastolic function as reflected by an increase in e' (=0.003) and decrease in E/e' (=0.002). The change in E/e' was independently correlated with baseline E/e' (<0.001) and change in LV mass index (=0.006). Conclusions The patients with primary aldosteronism had worse LV diastolic function than the patients with essential hypertension after propensity score matching, and this could be reversed after adrenalectomy, suggesting that aldosterone excess may induce LV diastolic dysfunction. 10.1161/JAHA.119.013263
    [Alteration of left ventricular longitudinal systolic function in 2D-strain in primary aldosteronism: A new target organ damage marker]. Boulestreau R,Cremer A,Delarche N,Gosse P Annales de cardiologie et d'angeiologie OBJECTIVE:Primary hyperaldosteronism is the leading cause of secondary hypertension, and leads to frequent cardiovascular complications. Many studies have studied left ventricular geometry and function in this population, but longitudinal systolic function is still poorly described. METHODS:We studied 35 hypertensive patients with primary aldosteronism, and 35 with essential hypertension matched for age, sex, body mass index, and 24h blood pressure. Patients benefited from an echocardiography to measure the mass and the geometry of the left ventricle, left ventricle ejection fraction, systolic longitudinal, circumferential, and radial strain, and diastolic function. RESULTS:Compared to essential hypertensive patients, patients with primary aldosteronism presented a significantly higher left ventricular mass index and relative wall thickness (60.3±16.1g/m vs 47.3±18.6, P=0.003, and 0.44±0.08 vs 0.36±0.06, P=0.00005, respectively), as well as a significantly reduced longitudinal systolic strain (-17.8±3,4 vs -20.3±3,6%, P=0.004). There were no significant differences in the other parameters. CONCLUSIONS:Primary aldosteronism is associated with a deterioration of longitudinal systolic function of the left ventricle compared with essential hypertensive patients. This marker of cardiac damage, reproducible and easily available in routine could help for the screening of these patients. 10.1016/j.ancard.2018.08.007
    Arterial Stiffness Is Associated with Clinical Outcome and Cardiorenal Injury in Lateralized Primary Aldosteronism. Chan Chieh-Kai,Yang Wei-Shiung,Lin Yen-Hung,Huang Kuo-How,Lu Ching-Chu,Hu Ya-Hui,Wu Vin-Cent,Chueh Jeff S,Chu Tzong-Shinn,Chen Yung-Ming The Journal of clinical endocrinology and metabolism CONTEXT:The association between arterial stiffness and clinical outcome in lateralized primary aldosteronism (PA) patients after adrenalectomy has not been clearly identified. OBJECTIVE:We hypothesized that arterial stiffness estimated by brachial-ankle pulse wave velocity (baPWV) before adrenalectomy was associated with the clinical outcomes and cardiorenal injury in lateralized PA patients after adrenalectomy. DESIGN AND PATIENTS:We designed a retrospective observational cohort study. We collected lateralized PA patients who had undergone adrenalectomy between 2013 and 2016 from the Taiwan Primary Aldosteronism Investigation database. The primary outcome was achieving complete clinical success at 1 year after adrenalectomy. The secondary outcome was estimated glomerular filtration rate declining over 20% and improved left ventricular mass index. RESULTS:We enrolled 221 patients with lateralized PA (50.7% men; mean age, 51.9 years), of whom 101 patients (45.7%) achieved complete clinical success at the 1-year follow-up assessment after adrenalectomy. Lower baPWV before adrenalectomy (odds ratio = 0.998; 95% confidence interval, 0.996-0.999; P = 0.003) correlated with higher likelihood of complete clinical success by multivariate logistic regression analysis. Multifactorial adjusted generalized additive model demonstrated that preoperative baPWV<1600 cm/sec was significantly associated with complete cure of hypertension. In addition, higher preoperative baPWV was associated with renal function decline and less left ventricular mass regression after adrenalectomy in lateralized PA patients during the follow-up period. CONCLUSIONS:Our study demonstrated that the preoperative severe arterial stiffness was associated with absent complete clinical success in lateralized PA patients after adrenalectomy, and this effect may contribute to cardiorenal injury, which at least partially explains kidney function deterioration and lessened regression of heart mass. 10.1210/clinem/dgaa566
    The cardiovascular markers copeptin and high-sensitive C-reactive protein decrease following specific therapy for primary aldosteronism. Remde Hanna,Dietz Anna,Emeny Rebecca,Riester Anna,Peters Annette,de Las Heras Gala Tonia,Then Cornelia,Seissler Jochen,Beuschlein Felix,Reincke Martin,Quinkler Marcus Journal of hypertension CONTEXT:Copeptin and high-sensitive C-reactive protein (hsCRP) are biomarkers associated with increased mortality in patients with cardiovascular and cerebrovascular disease as well as in the general population. No data exist regarding these markers in patients with primary aldosteronism. OBJECTIVE:To evaluate copeptin and hsCRP levels as cardiovascular risk markers in primary aldosteronism patients. METHODS:A total of 113 primary aldosteronism patients (64% male) from two centers of the prospective German Conn's Registry were identified, for whom a full data set and blood samples at baseline and follow-up (14 ± 3.4 months) after initiation of specific primary aldosteronism treatment were available. These cases were matched 1 : 3 (n = 339) for sex, renal function, BMI, age and SBP with participants from the Cooperative Health Research in the Region of Augsburg F4 survey. Copeptin and hsCRP were determined by sandwich fluoroimmunoassay. RESULTS:HsCRP was significantly higher in primary aldosteronism patients at baseline compared with matched controls. Following specific therapy, hsCRP and copeptin decreased significantly in primary aldosteronism patients [median (25th and 75th percentile): 1.6 (0.8, 3.4) to 1.2 (0.6, 2.1) mg/l, P < 0.001; 7.8 (4.6, 13.5) to 5.0 (3.1, 8.9) pmol/l, P < 0.001, respectively]. Men had higher hsCRP and copeptin levels at baseline and follow-up compared with women. The combination of sex, hypokalemia, lateralization index and blood pressure were the best predictors of outcome. However, copeptin and hsCRP had no predictive value despite the association of lower copeptin levels with better outcome regarding cure of primary aldosteronism. CONCLUSION:Copeptin and hsCRP levels decrease following specific primary aldosteronism therapy reflecting successful cardiovascular risk reduction. However, they are no independent predictors regarding cure of primary aldosteronism. 10.1097/HJH.0000000000001041
    Prevalence of primary aldosteronism and association with cardiovascular complications in patients with resistant and refractory hypertension. Parasiliti-Caprino Mirko,Lopez Chiara,Prencipe Nunzia,Lucatello Barbara,Settanni Fabio,Giraudo Giuseppe,Rossato Denis,Mengozzi Giulio,Ghigo Ezio,Benso Andrea,Maccario Mauro Journal of hypertension OBJECTIVES:To assess the prevalence of primary aldosteronism and its association with cardiometabolic complications in patients with resistant and refractory hypertension. METHODS:One hundred and ten consecutive patients with true resistant hypertension [insufficient blood pressure control despite appropriate lifestyle measures and treatment with at least three classes of antihypertensive medication, including a diuretic] and without previous cardiovascular events were screened for secondary hypertension. Refractory hypertension was diagnosed in case of uncontrolled blood pressure despite the use of at least five antihypertensive drugs. RESULTS:Primary aldosteronism was diagnosed in 32 cases (29.1%). The multivariate analysis showed that primary aldosteronism is a strong factor positively associated with left ventricular hypertrophy [odds ratio (OR) = 12.98, 95% confidence interval (CI) 3.82-60.88; P < 0.001], microalbuminuria (OR = 3.67, 95% CI 1.44-9.78; P = 0.007), carotid intima-media thickness at least 0.9 mm (OR = 2.69, 95% CI 1.02-7.82; P = 0.037), aortic ectasia (OR = 4.08, 95% CI 1,18-15.04; P = 0.027) and atrial fibrillation (OR 8.80, 95% CI 1.53-73.98; P = 0.022). Moreover, primary aldosteronism was independently associated with the presence of at least one (OR = 8.60, 95% CI 1.73-69.88; P = 0.018) and at least two types of organ damage (OR = 3.08, 95% CI 1.19-8.24; P = 0.022). Thirteen patients (11.8%) were affected by refractory hypertension. This group was characterized by significantly higher values of carotid intima-media thickness, higher rate of aldosterone-producing adenoma and atrial fibrillation, compared with the other individuals with resistant hypertension. CONCLUSION:The current study indicates that primary aldosteronism is a frequent cause of secondary hypertension and cardiovascular complications among patients with resistant and refractory hypertension, suggesting a crucial role of aldosterone in the pathogenesis of severe hypertensive phenotypes and cardiovascular disease. 10.1097/HJH.0000000000002441
    Association of aldosterone and blood pressure with the risk for cardiovascular events after treatments in primary aldosteronism. Haze Tatsuya,Hirawa Nobuhito,Yano Yuichiro,Tamura Kouichi,Kurihara Isao,Kobayashi Hiroki,Tsuiki Mika,Ichijo Takamasa,Wada Norio,Katabami Takuyuki,Yamamoto Koichi,Oki Kenji,Inagaki Nobuya,Okamura Shintaro,Kai Tatsuya,Izawa Shoichiro,Yamada Masanobu,Chiba Yoshiro,Tanabe Akiyo,Naruse Mitsuhide Atherosclerosis BACKGROUND AND AIMS:We used a dataset from a Japanese nationwide registry of patients with primary aldosteronism, to determine which of the parameters of hyperaldosteronism and blood pressure before or after treatments for primary aldosteronism (i.e., surgical adrenalectomy or a medication treatment) are important in terms of cardiovascular prognosis. METHODS:We assessed whether plasma aldosterone-to-renin ratio and pulse pressure levels before treatment and 6 months after treatment were associated with composite cardiovascular disease events during the 5-year follow-up period. RESULTS:The cohort included 1987 patients (mean age was 53.2 years, 52.0% were female, 37.2% had undergone surgical treatment, and the remainder had been treated with mineralocorticoid receptor antagonists). In the Cox proportional hazard model, the covariate-adjusted hazard ratio (95% confidence interval) for the composite cardiovascular disease events risk for each one-standard-deviation increase in the aldosterone-to-renin ratio or pulse pressure before treatment, those after treatment, or the duration of hypertension were 1.24 (1.05, 1.48), 0.74 (0.54, 1.02), and 1.07 (0.79, 1.44), 1.43 (1.07, 1.92), and 1.52 (1.19, 1.95), respectively. Patients with a high pre-treatment aldosterone-to-renin ratio of more than 603 and a large post-treatment pulse pressure of more than 49 mmHg showed approximately three-fold higher hazard ratios for cardiovascular events risk compared to those with a lower aldosterone-to-renin ratio and smaller pulse pressure. CONCLUSIONS:Higher aldosterone-to-renin ratio before treatments, higher pulse pressure after treatments, and longer duration of hypertension were prognostic factors for cardiovascular diseases. Early intervention may be important for preventing cardiovascular disease among patients with primary aldosteronism. 10.1016/j.atherosclerosis.2021.03.033
    Atrial fibrillation as presenting sign of primary aldosteronism: results of the Prospective Appraisal on the Prevalence of Primary Aldosteronism in Hypertensive (PAPPHY) Study. Seccia Teresa M,Letizia Claudio,Muiesan Maria L,Lerco Silvia,Cesari Maurizio,Bisogni Valeria,Petramala Luigi,Maiolino Giuseppe,Volpin Roberta,Rossi Gian Paolo Journal of hypertension BACKGROUND:Despite hyperaldosteronism being suggested as predisposing to arrhythmias, the relationship between atrial fibrillation and primary aldosteronism remains uncertain. Therefore, we tested the hypothesis that atrial fibrillation is a presentation of primary aldosteronism in hypertensive patients with unexplained atrial fibrillation. DESIGN AND METHODS:The Prospective Appraisal on the Prevalence of Primary Aldosteronism in Hypertensive (PAPPHY) Study recruited consecutive patients with atrial fibrillation and an unambiguous diagnosis of arterial hypertension at three referral centers for hypertension. RESULTS:In a cohort entailing 411 atrial fibrillation patients, we identified 18% (age 61 ± 11 years; 32% women), who showed no known cause of the arrhythmia. A thorough diagnostic work-up allowed us to identify primary aldosteronism in 73 of these patients, i.e. 42% [95% confidence interval (CI) 31.8-53.9]. Subtyping of primary aldosteronism demonstrated that surgically curable forms of primary aldosteronism accounted for 48% of the cases (95% CI 31.9-65.2). The high prevalence of primary aldosteronism was confirmed at sensitivity analyses. CONCLUSION:These results provided compelling evidence that primary aldosteronism is highly prevalent in hypertensive patients with unexplained atrial fibrillation. Accordingly, they suggest that patients with no identifiable cause of the arrhythmia should be screened for primary aldosteronism to identify those who can be cured or markedly improved with target treatment. CLINICAL TRIAL REGISTRATION: :: https://clinicaltrials.gov, Identifier: NCT01267747. 10.1097/HJH.0000000000002250
    Hypertension with primary aldosteronism is associated with increased carotid intima-media thickness and endothelial dysfunction. Demirkiran Ahmet,Everaars Henk,Elitok Ali,van de Ven Peter M,Smulders Yvo M,Dreijerink Koen M,Tanakol Refik,Ozcan Mustafa Journal of clinical hypertension (Greenwich, Conn.) Patients with primary aldosteronism induced hypertension are more likely to experience cardiovascular events compared to patients with essential hypertension. Primary aldosteronism may therefore have distinct adverse effects on cardiovascular structure and function, independent of hypertension. However, current data on such effects of primary aldosteronism are conflicting. The aim of the present study was to investigate the influence of primary aldosteronism on vascular structure and endothelial function, using intima-media thickness as a vascular remodeling index and flow-mediated dilation as a functional parameter. In total, 70 participants were recruited from patients with resistant hypertension. Twenty-nine patients diagnosed with primary aldosteronism and 41 patients with essential hypertension were prospectively enrolled. Primary aldosteronism was due to aldosterone-producing adenoma in 10 cases and due to idiopathic adrenal hyperplasia in 19 cases. All patients underwent ultrasound of the common carotid intima-media thickness and flow-mediated dilation of the brachial artery. Primary aldosteronism patients had significantly lower flow-mediated dilation (3.3 [2.4-7.4] % vs 14.7 [10.3-19.9] %, P < 0.01) and significantly higher carotid intima-media thickness (0.9 [0.7-1.0] mm vs 0.8 [0.6-0.9] mm, P = 0.02) compared to patients with essential hypertension. These differences remained significant after adjusting for age, sex, diabetes mellitus, 24-hours systolic blood pressure, and smoking (P < 0.01). No differences in either outcome were observed between the adenoma and adrenal hyperplasia groups (both P > 0.05). Hypertensive patients with hyperaldosteronism appear to exhibit deteriorative effects on both vascular structure and function, independent of hypertension. 10.1111/jch.13585