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    Impaired circadian rhythm of blood pressure in normotensive patients with rheumatic mitral valve stenosis. Cakici Musa,Dogan Adnan,Oylumlu Muhammed,Uckardes Fatih,Davutoglu Vedat Blood pressure monitoring BACKGROUND:The aim of the present cross-sectional study was to evaluate either non-dipper-type or dipper-type circadian rhythm of blood pressure (BP) in normotensive rheumatic mitral stenosis (MS) patients. METHODS AND RESULTS:Eighty-eight normotensive rheumatic mitral valve disease (RMVD) patients and 41 normal participants were enrolled in the study. All participants underwent ambulatory blood pressure monitoring. Nocturnal BP dipping was calculated as follows: (awake BP-asleep BP)×100/awake BP. Patients with a nocturnal reduction in average daytime systolic BP and diastolic BP of less than 10% were classified as nondippers. Patients with RMVD were divided into two groups with respect to the top and bottom 1.5 cm of the mitral valve area (MVA). There was a highly significant relationship between the two groups with control in the frequency of a nondipping status (χ=22.721; d.f.=2; P<0.001). Afterwards, the Mann-Whitney U-test was used to compare the two groups and the control group. There was no difference in the frequency of nondipping between patients with an MVA of greater than 1.5 cm and the control group (P>0.05). However, the nondipping level was higher in patients with an MVA of less than 1.5 cm than in the control group and in patients with RMVD with an MVA of greater than 1.5 cm (P<0.001 and <0.001, respectively). CONCLUSION:The circadian BP rhythm is impaired and the incidence of nondipping BP is higher in patients with MS than in normal patients. Moreover, we believe that autonomic nervous system dysfunction in patients with MS may be detected efficiently using ambulatory blood pressure monitoring. 10.1097/MBP.0000000000000025
    [Associations of circadian blood pressure rhythm with autonomic nervous system and myocardial energy expenditure level in patients with primary hypertension]. Shen Anna,Zheng Dezhong,Hu Zhaoting Nan fang yi ke da xue xue bao = Journal of Southern Medical University OBJECTIVE:To investigate the relationship among circadian blood pressure rhythm, autonomic nervous system and myocardial energy expenditure (MEE) level in patients with primary hypertension. METHODS:A total of 102 hypertensive and 45 normotensive subjects were recruited. According to blood pressure reduction rate at night, the hypertensive patients were divided into non-dipper group (NDH group, n=54) with a reduction rate of <10% and dipper group (DH group, n=48) with a reduction rate of ≥10%. The circadian blood pressure rhythm and heart rate variability were measured with ambulatory blood pressure monitoring and 24-hour electrocardiograph monitoring, respectively, and MEE was measured by Doppler echocardiography to analyze their correlations. RESULTS:SDNN, SDANN, SDNNindex, RMSSD, PNN50, and HF were significantly lower in the hypertensive patients than in the control group (P<0.05); these parameters, except for PNN50, were all significantly lower in NDH group than in DH group (P<0.05). The hypertensive patients had significantly higher MEE than the control group (P<0.05), and MEE was significantly higher in NDH group than in DH group (P<0.05). Bivariate correlation analysis showed significant correlations of MEE with SDANN in the hypertensive patients (P<0.01). CONCLUSION:Patients with primary hypertension, especially those in NDH group, have impaired autonomic nervous system function. The hypertensive patients in NDH group show a more prominent increase in MEE in relation to sympathetic activation, suggesting the importance of restoring circadian blood pressure rhythm in the treatment of hypertension.
    Melatonin secretion is impaired in women with preeclampsia and an abnormal circadian blood pressure rhythm. Bouchlariotou Sofia,Liakopoulos Vassilios,Giannopoulou Myrto,Arampatzis Spyridon,Eleftheriadis Theodoros,Mertens Peter R,Zintzaras Elias,Messinis Ioannis E,Stefanidis Ioannis Renal failure Non-dipping circadian blood pressure (BP) is a common finding in preeclampsia, accompanied by adverse outcomes. Melatonin plays pivotal role in biological circadian rhythms. This study investigated the relationship between melatonin secretion and circadian BP rhythm in preeclampsia. Cases were women with preeclampsia treated between January 2006 and June 2007 in the University Hospital of Larissa. Volunteers with normal pregnancy, matched for chronological and gestational age, served as controls. Twenty-four hour ambulatory BP monitoring was applied. Serum melatonin and urine 6-sulfatoxymelatonin levels were determined in day and night time samples by enzyme-linked immunoassays. Measurements were repeated 2 months after delivery. Thirty-one women with preeclampsia and 20 controls were included. Twenty-one of the 31 women with preeclampsia were non-dippers. Compared to normal pregnancy, in preeclampsia there were significantly lower night time melatonin (48.4 ± 24.7 vs. 85.4 ± 26.9 pg/mL, p<0.001) levels. Adjustment for circadian BP rhythm status ascribed this finding exclusively to non-dippers (p<0.01). Two months after delivery, in 11 of the 21 non-dippers both circadian BP and melatonin secretion rhythm reappeared. In contrast, in cases with retained non-dipping status (n=10) melatonin secretion rhythm remained impaired: daytime versus night time melatonin (33.5 ± 13.0 vs. 28.0 ± 13.8 pg/mL, p=0.386). Urinary 6-sulfatoxymelatonin levels were, overall, similar to serum melatonin. Circadian BP and melatonin secretion rhythm follow parallel course in preeclampsia, both during pregnancy and, at least 2 months after delivery. Our findings may be not sufficient to implicate a putative therapeutic effect of melatonin, however, they clearly emphasize that its involvement in the pathogenesis of a non-dipping BP in preeclampsia needs intensive further investigation. 10.3109/0886022X.2014.926216
    [Circadian rhythm of blood pressure in patients with chronic hypertension and pregnancy]. Rojo-Contreras Wendoline,Salazar-Páramo Mario,Parra-Carrillo José Z,Iñigo-Riesgo Carmen Armida,Bonilla-Rosales Irma,Villa-Manzano Alberto Iram,Canales-Muñoz José Luis Ginecologia y obstetricia de Mexico BACKGROUND:Ambulatory blood pressure monitoring during 24 hours shows a blood pressure variability. The prevalence of chronic hypertension in pregnant women is 1-5%, so it is important to know the changes in blood pressure and cardiovascular risk and prevent complications to the mother and fetus. OBJECTIVE:To know the circadian rhythm of the blood pressure in the chronic hypertensive pregnant patients, through the ambulatory blood pressure monitoring. MATERIAL AND METHODS:A cross-sectional and descriptive study included chronic hypertensive pregnant patients, with > 20 weeks of gestation. Assessment of factors related to gynaecologic characteristics, according to the inclusion criteria underwent a washout period of two weeks and they were monitored with a Spacelabs 90207 monitor blood pressure. Quantitative variables by Student t test, one-way ANOVA and Pearson correlation were analysed. RESULTS:16 chronic hypertensive pregnant patients were included, whose ambulatory blood pressure monitoring for the systolic blood pressure in 24 hours averaged 117.12 ± 5.85 mmHg; 24 hours diastolic blood pressure 71.31 ± 5.89 mmHg; daytime systolic blood pressure 120.18 ± 5.75 mmHg, nocturnal systolic blood pressure 110.31 ± 8.41 mmHg; daytime diastolic blood pressure 75.43 ± 7.32 mmHg, nocturnal diastolic blood pressure 64.25 ± 8.27 mmHg. Significant differences between daytime and night time were found. CONCLUSION:56% of chronic hypertensive pregnant patients had no nocturnal reduction in systolic blood pressure and 43.75% had no nocturnal changes on diastolic blood pressure. The fact that 50% of patients were non-dippers force us to use long-action antihypertensive therapy and obtain control of the blood pressure for 24 hours.
    Circadian blood pressure rhythm in normotensive offspring of hypertensive parents. Toker Rabia Tutuncu,Yildirim Ali,Demir Tevfik,Ucar Birsen,Kilic Zubeyir Cardiology journal BACKGROUND:The aim of this study was to explore the circadian blood pressure (BP) rhythm using ambulatory BP monitoring (ABPM) in normotensive children with a family history of essential hypertension. METHODS:Group 1 consisted of children with hypertensive mothers and/or fathers (n = 20), Group 2 consisted of children with hypertensive grandparents (n = 20), and Group 3 consisted of children with normotensive parents (n = 20). All participating children underwent a 24-h ABPM and echocardiography. RESULTS:Significantly higher systolic burden was found in children with hypertensive parents (p < 0.05) and grandparents (p < 0.05) compared to controls. Ambulatory BP measurements had a higher daytime systolic BP in Group 1 compared to controls (p < 0.05). While left ventricular (LV) posterior wall thickness was similar in Group 1 and Group 2, it was significantly higher in both of these groups compared to the controls. The LV mass index (LVMI) was significantly higher in Group 1 than in controls (p < 0.05). However, diastolic BP was significantly higher in dippers compared to non-dippers (p < 0.05). LV posterior wall thickness, interventricular septum thickness and LVMI were significantly higher among non-dippers compared to dippers (p < 0.05). In children with a family history of hypertension, a positive correlation between nocturnal systolic BP and LVMI was found, and increasing nocturnal BP values were associated with increasing LVMI (p < 0.01). CONCLUSIONS:In children with a family history of hypertension, target-organ damage may precede the clinical detection of hypertension, and in those with a nocturnal non-dipper status, a more marked effect on LVMI may occur. 10.5603/CJ.a2014.0053
    Smooth-muscle BMAL1 participates in blood pressure circadian rhythm regulation. Xie Zhongwen,Su Wen,Liu Shu,Zhao Guogang,Esser Karyn,Schroder Elizabeth A,Lefta Mellani,Stauss Harald M,Guo Zhenheng,Gong Ming Cui The Journal of clinical investigation As the central pacemaker, the suprachiasmatic nucleus (SCN) has long been considered the primary regulator of blood pressure circadian rhythm; however, this dogma has been challenged by the discovery that each of the clock genes present in the SCN is also expressed and functions in peripheral tissues. The involvement and contribution of these peripheral clock genes in the circadian rhythm of blood pressure remains uncertain. Here, we demonstrate that selective deletion of the circadian clock transcriptional activator aryl hydrocarbon receptor nuclear translocator-like (Bmal1) from smooth muscle, but not from cardiomyocytes, compromised blood pressure circadian rhythm and decreased blood pressure without affecting SCN-controlled locomotor activity in murine models. In mesenteric arteries, BMAL1 bound to the promoter of and activated the transcription of Rho-kinase 2 (Rock2), and Bmal1 deletion abolished the time-of-day variations in response to agonist-induced vasoconstriction, myosin phosphorylation, and ROCK2 activation. Together, these data indicate that peripheral inputs contribute to the daily control of vasoconstriction and blood pressure and suggest that clock gene expression outside of the SCN should be further evaluated to elucidate pathogenic mechanisms of diseases involving blood pressure circadian rhythm disruption. 10.1172/JCI76881
    Features of the Structure of the Circadian Rhythm of Blood Pressure and Heart Rate under Genetically Determined Hypertension in the Experiment. Blagonravov M L,Frolov V A,Goryachev V A,Azova M M Bulletin of experimental biology and medicine In SHR rats of different ages (22, 26, 30, 34, and 38 weeks), continuous 24-h telemetric monitoring of BP and HR was performed. The amplitude and power of oscillations of diastolic BP significantly decreased at the later stages of arterial hypertension (38 weeks), which was considered as a poor prognostic marker. We also observed a significant decrease in the mean daytime, nighttime, and maximum HR and mesor on weeks 30 and 34, but not on week 38, which can reflect triggering of the adaptive response followed by its exhaustion. 10.1007/s10517-015-2846-4
    Impact of anxiety level on circadian rhythm of blood pressure in hypertensive patients. Özpelit Mehmet Emre,Özpelit Ebru,Doğan Nazile Bilgin,Pekel Nihat,Ozyurtlu Ferhat,Yılmaz Akar,Saygı Serkan,Tengiz İstemihan,Ercan Ertugrul International journal of clinical and experimental medicine INTRODUCTION:Considering the high prevalence rates and growing incidences of hypertension (HT) and anxiety disorders in the modern world, a full understanding of anxiety's relationship to HT is crucial. In this study we aimed to investigate the effects of anxiety level on circadian rhythm of blood pressure (BP) in hypertensive patients. MATERIAL AND METHOD:This cross-sectional study included 160 previously diagnosed essential hypertensive patients (80 female, 80 male, mean age: 55.3±15.1 years). All participants underwent 24 h ambulatory blood pressure monitoring (ABPM) and filled State-Trait Anxiety Inventory (STAI) (trait) Questionnaire. The study population was divided into 2 groups according to their STAI scores; an anxiety group (n=97; STAI ≥45) and a control group (n=63; STAI<44). Clinical characteristics, laboratory findings and ABPM measurements were compared between the groups. RESULTS:There was no significant difference between the groups for ABPM parameters except morning blood pressure surge (MBPS). Anxiety group had a significantly higher MBPS compared to control group (14.4±17.0 vs 9.1±11.9 mmHg, P:0.03). Multivariate analysis showed that duration of HT and STAI score were the only independent predictors of MBPS. CONCLUSION:Patients' anxiety level is associated with MBPS which is an independent risk factor for cardiovascular complications. Assessment and control of anxiety seems to be worthy in effective treatment of hypertension.
    Albuminuria, renal dysfunction and circadian blood pressure rhythm in older men: a population-based longitudinal cohort study. Xu Hong,Huang Xiaoyan,Risérus Ulf,Cederholm Tommy,Sjögren Per,Lindholm Bengt,Ärnlöv Johan,Carrero Juan Jesús Clinical kidney journal BACKGROUND:Both albuminuria and kidney dysfunction may affect circadian blood pressure (BP) rhythm, while exacerbating each other's effects. We investigated associations and interactions of these two risk factors with circadian BP rhythm variation and non-dipper pattern progression in community-dwelling older men. METHODS:This was a cross-sectional and longitudinal analyses in the third and fourth cycles of the Uppsala Longitudinal Study of Adult Men, including 1051 men (age 71 years) with assessments on urinary albumin excretion rate (UAER), 24-h ambulatory BP monitoring (ABPM) and cystatin-C-estimated glomerular filtration rate (eGFR). Of these, 574 men attended re-examination after 6 years. Study outcomes were ABMP changes and non-dipping BP pattern (prevalence and progression). RESULTS:UAER associated with circadian BP rhythm both cross-sectionally and longitudinally. Longitudinally, significant interactions were observed between UAER and kidney dysfunction (eGFR < 60 mL/min/1.73 m(2)) in its association with the changes of both night-time systolic BP (SBP) and night-day SBP ratio. After stratification, UAER strongly predicted night-day SBP ratio change only in those with concurrent kidney dysfunction. At re-examination, 221 new cases of non-dipper were identified. In multivariable logistic models, high UAER associated with increased likelihood of non-dipper progression, but more strongly so among individuals with concurrent kidney dysfunction. These associations were evident also in the subpopulation of non-diabetics and in participants with normal range UAER. CONCLUSIONS:UAER associates with circadian BP rhythm variation and non-dipper progression in elderly men. Concurrent renal dysfunction modifies and exacerbates these associations. 10.1093/ckj/sfv068
    CIRCADIAN RHYTHM OF BLOOD PRESSURE RESTORATION AND NEPHROTIC PROTEINURIA ALLEVIATION IN A PATIENT WITH CHRONIC KIDNEY DISEASE AFTER RENAL SYMPATHETIC DENERVATION. Prkacin Ingrid,Corić-Martinović Valentina,Bulum Tomislav,Cavrić Gordana,Đermanović-Dobrota Vesna,Vidjak Vinko Acta clinica Croatica Renal sympathetic denervation (RSD) could be an effective antihypertensive treatment of resistant hypertension that triggers additional positive effects on glucose metabolism and insulin sensitivity in type 2 diabetes mellitus. We report the effects of RSD in a patient with chronic kidney disease, type 2 diabetes mellitus and resistant hypertension, manifesting as blood pressure reduction with dipping pattern restoration, followed by nephrotic proteinuria alleviation. The non-dipping blood pressure pattern and proteinuria increase the risk of cardiovascular complications and accelerate kidney disease progression. Thus, further research documenting the frequency and investigating the mechanisms of these effects reported after RSD in chronic kidney disease patients with type 2 diabetes mellitus and resistant hypertension is necessary for the benefit of this high-risk patient population.
    The Effects of Unilateral Nephrectomy on Blood Pressure and Its Circadian Rhythm. Ohashi Naro,Isobe Shinsuke,Ishigaki Sayaka,Suzuki Takahisa,Motoyama Daisuke,Sugiyama Takayuki,Nagata Masao,Kato Akihiko,Ozono Seiichiro,Yasuda Hideo Internal medicine (Tokyo, Japan) Objective Hypertension and diurnal blood pressure (BP) variation are widely accepted as risk factors for renal damage. However, the effects of unilateral nephrectomy on BP and its circadian rhythm have not yet been clarified in patients with a compromised renal function, including dialysis patients. Methods We investigated 22 unilateral nephrectomized patients (16 men and 6 women, age: 64.5±14.3 years). The function of the circulating renin-angiotensin system (RAS) (plasma renin activity and plasma angiotensin II) and 24-h ambulatory BP monitoring (ABPM) were evaluated before and after nephrectomy. Daytime and nighttime 24-h ABPM values were determined based on sleep and waking times. Results In non-dialysis patients, the estimated glomerular filtration rate after nephrectomy was significantly lower than that before (before, 62.4±23.2 mL/min/1.73 m vs. after, 43.7±16.8 mL/min/1.73 m; p<0.01). No significant differences were noted in the levels of BPs and circulating RAS before and after nephrectomy. However, the night-to-day (N/D) ratio of systolic BP (SBP) was significantly higher after nephrectomy than before (before, 93.3±6.5% vs. after, 98.4±6.9%; p<0.01), and the patterns of circadian BP rhythm also significantly differed before and after nephrectomy (p=0.022). Namely, the rates of dipper patterns decreased and nondipper and riser patterns increased after nephrectomy. In contrast, in dialysis patients, no significant differences were observed in the N/D ratio of SBP or the patterns of circadian BP rhythm before and after nephrectomy. Conclusion Unilateral nephrectomy affects the circadian rhythm of BP but not absolute values of BP. 10.2169/internalmedicine.55.7215
    Nocturnal and Circadian Rhythm of Blood Pressure Is Associated with Renal Structure Damage and Function in Patients with IgAN. Lin Lirong,Zhang Huhai,Yang Jurong,Zhang Jianguo,Li Kailong,Huo Bengang,Dai Huanzi,Zhang Weiwei,Yang Jie,Tan Wei,He Yani Archives of medical research BACKGROUND AND AIMS:Abnormal circadian rhythm of blood pressure (BP) is closely related to target organ damage in hypertension. However, the association between abnormal circadian rhythm of BP and renal injury is not clear. We investigated whether renal injury is associated with nocturnal BP and circadian rhythm of BP in Chinese IgAN patients. METHODS:Clinic and 24 h ambulatory BP monitoring data were obtained from 330 Chinese IgAN patients with mean 24 h BP < 130/80 and mean daytime BP < 135/85 mmHg. Renal histopathological injury was determined according to the Oxford classification of IgAN. RESULTS:Among the 330 IgAN subjects, 35.8% suffered from nocturnal hypertension, 61.5% had abnormal circadian BP, and 27% had nocturnal hypertension with a nondipping pattern. Compared with nocturnal normotensive patients, patients with nocturnal hypertension had significantly higher levels of blood cystatin C, blood uric acid, and lower estimated glomerular filtration rate (eGFR), and significantly a higher mean renal tissue injury score. The nondipping hypertensive group had significantly higher nocturnal diastolic and systolic BP, blood uric acid, and glomerulosclerosis rates, whereas eGFR was lower. In nondipping hypertensive patients, urinary sodium excretion and renal tissue injury scores were significantly higher than dipping patients. Nocturnal hypertension and abnormal circadian BP correlated with renal tissue injury, renal interstitial fibrosis, and aortic arch atherosclerosis. CONCLUSION:Abnormal circadian rhythm of BP and nocturnal hypertension are common clinical manifestations in Chinese IgAN patients with normal mean 24 h BP. Abnormal circadian BP and nocturnal hypertension may accelerate IgAN progression by inducing renal dysfunction and histopathological damage. 10.1016/j.arcmed.2016.01.001
    Eplerenone restores 24-h blood pressure circadian rhythm and reduces advanced glycation end-products in rhesus macaques with spontaneous hypertensive metabolic syndrome. Zhang Yan,Zheng Wen,Liu Yuli,Wang Jue,Peng Ying,Shang Haibao,Hou Ning,Hu Xiaomin,Ding Yi,Xiao Yao,Wang Can,Zeng Fanxin,Mao Jiaming,Zhang Jun,Ma Dongwei,Sun Xueting,Li Chuanyun,Xiao Rui-Ping,Zhang Xiuqin Scientific reports Hypertension is often associated with metabolic syndrome (MetS), and serves as a risk factor of MetS and its complications. Blood pressure circadian rhythm in hypertensive patients has been suggested to contribute to cardiovascular consequences and organ damage of hypertension. But circadian changes of BP and their response to drugs have not been clearly investigated in non-human primates (NHPs) of MetS with hypertension. Here, we identified 16 elderly, hypertensive MetS rhesus monkeys from our in-house cohort. With implanted telemetry, we investigate BP changes and its circadian rhythm, together with the effect of antihypertensive drugs on BP and its diurnal fluctuation. MetS hypertensive monkeys displayed higher BP, obesity, glucose intolerance, and dyslipidemia. We also confirmed impaired 24-h BP circadian rhythm in MetS hypertensive monkeys. Importantly, Eplerenone, a mineralocorticoid receptor blocker, exerts multiple beneficial effects in MetS hypertensive monkeys, including BP reduction, 24-h BP circadian rhythm restoration, and decreased plasma concentration of inflammation factors and advanced glycation end-products. In summary, we identified a naturally-developed hypertensive MetS NHP model, which is of great value in the studies on pathogenesis of MetS-associated hypertension and development of novel therapeutic strategies. We also provided multiple novel mechanistic insights of the beneficial effect of Eplerenone on MetS with hypertension. 10.1038/srep23957
    Epicardial adipose tissue volume a diagnostic study for independent predicting disorder of circadian rhythm of blood pressure in patients with essential hypertension. Zhou L,Deng Y,Gong J,Chen X,Zhang Q,Wang J Cellular and molecular biology (Noisy-le-Grand, France) The aim of the study was to determine whether epicardial adipose tissue volume (EATV), a new cardiometabolic risk factor, is associated with circadian changes of blood pressure (BP) in patients with newly diagnosed essential hypertension. Ninety patients with newly diagnosed essential hypertension underwent ambulatory blood pressure monitoring for 24 h. EATV was measured using cardiac computed tomography. These patients were categorized into three groups according to their BP patterns (group 1, n=46, dipper hypertension, also called normal pattern; group 2, n=24, non-dipper hypertension; group 3, n=20, anti-dipper hypertension; group 2 and 3 are also called abnormal pattern). Data were collected retrospectively and compared between hypertensive patients with normal pattern and abnormal pattern. The normal pattern hypertensive patient had significant lower mean EATV and BP ((EATV, 91.3±29.4 cm3) than those of abnormal pattern patients including group 2 (EATV, 116.2±31.06cm3, <0.01) and group 3 (EATV, 124.8±28.5cm3, P<0.01). Mean systolic BP over 24 h (BPs24) and mean diastolic BP over 24 h (BPd24) of group 1 (BPs24, 135.7 ± 12.6 mmHg; BPd24, 83.6 ± 10.6 mmHg) were significantly lower than those of group 2 (BPs24, 150.1± 17.6 mmHg, P<0.01; BPd24, 93.2 ± 16.5 mmHg, P<0.01) and group 3 (BPs24, 154.1 ± 16.6mmHg, P<0.01; BPd24, 93.8 ± 17.5 mmHg; P<0.01). Bivariate correlation analysis showed that correlation coefficient of EATV with abnormal blood pressure mode was 0.500 (p<0.001), partial correlation coefficient after adjustment for waist circumference and body mass index was 0.469 (p<0.001). When multivariate backward logistic regression analysis was performed to assess the correlation of BP pattern with EAT volume, it showed that the prevalence of abnormal BP pattern (non-dipper and anti-dipper BP pattern) increased by 1.54 times after adjusting for age and gender per additional 10 cm3 of EAT volume. Receiver operating characteristic curve for EAT alone indicated that the cutoff value of 95.17cm3 had the best performance in predicting abnormal BP pattern with a sensitivity of 75.0% and a specificity of 72.7%. EATV was elevated in newly diagnosed and untreated patients with non-dipper hypertension and anti-dipper hypertension. EATV measured by cardiac computed tomography can be used to indicate the increased risk of circadian rhythm of blood pressure.
    Circadian Blood Pressure Rhythm Is Changed by Improvement in Hypoalbuminemia and Massive Proteinuria in Patients with Minimal Change Nephrotic Syndrome. Ando Daisaku,Yasuda Gen Cardiorenal medicine BACKGROUND:Proteinuria and nighttime blood pressure (BP) elevation are notable risk markers of chronic kidney disease and correlate closely with each other. However, daily urinary protein excretion (UPE) always fluctuates. In patients with minimal change nephrotic syndrome (MCNS), serum albumin concentrations (SAC) decrease but fluctuate less than UPE. We evaluated whether SAC is a reliable marker for proteinuria, and compared the relations among circadian BP changes, SAC, and UPE. METHODS:In patients with MCNS (12 men and 11 women, 43 ± 18 years), blood and spot urine samples were collected on three consecutive days before treatment, and 24-hour BP was also measured on the three days. Then, an intervention study was conducted in the patients to examine circadian BP changes induced by treatment. Sleeping/waking BP ratio was analyzed as an indicator of circadian BP rhythm. RESULTS:In the three-day measurements before treatment, mean coefficient of variation, an index of dispersion of data, for SAC was 7.4 ± 7.4%, which was markedly lower (p < 0.01) than 35.7 ± 15.4% for UPE. SAC correlated inversely with sleeping/waking systolic and diastolic BP ratios on all three days, whereas UPE did not correlate significantly with sleeping/waking diastolic BP ratio on day 3. Sleeping/waking systolic and diastolic BP ratios were 96 ± 5 and 95 ± 6%, and were higher (p < 0.05) than in healthy subjects (89 ± 8 and 88 ± 10%). Treatment improved hyperproteinuria and hypoalbuminemia, and was accompanied by decreases (p < 0.05) in sleeping and waking systolic/diastolic BP ratio to 91 ± 8 and 89 ± 9%. CONCLUSION:These findings suggest that reduced SAC in patients with proteinuria is associated with disrupted circadian BP rhythm. 10.1159/000444095
    A sodium-glucose co-transporter 2 inhibitor empagliflozin prevents abnormality of circadian rhythm of blood pressure in salt-treated obese rats. Takeshige Yui,Fujisawa Yoshihide,Rahman Asadur,Kittikulsuth Wararat,Nakano Daisuke,Mori Hirohito,Masaki Tsutomu,Ohmori Koji,Kohno Masakazu,Ogata Hiroaki,Nishiyama Akira Hypertension research : official journal of the Japanese Society of Hypertension Studies were performed to examine the effects of the selective sodium-glucose co-transporter 2 (SGLT2) inhibitor empagliflozin on urinary sodium excretion and circadian blood pressure in salt-treated obese Otsuka Long Evans Tokushima Fatty (OLETF) rats. Fifteen-week-old obese OLETF rats were treated with 1% NaCl (in drinking water), and vehicle (0.5% carboxymethylcellulose, n=10) or empagliflozin (10 mg kg(-1)per day, p.o., n=11) for 5 weeks. Blood pressure was continuously measured by telemetry system. Glucose metabolism and urinary sodium excretion were evaluated by oral glucose tolerance test and high salt challenge test, respectively. Vehicle-treated OLETF rats developed non-dipper type blood pressure elevation with glucose intolerance and insulin resistance. Compared with vehicle-treated animals, empagliflozin-treated OLETF rats showed an approximately 1000-fold increase in urinary glucose excretion and improved glucose metabolism and insulin resistance. Furthermore, empagliflozin prevented the development of blood pressure elevation with normalization of its circadian rhythm to a dipper profile, which was associated with increased urinary sodium excretion. These data suggest that empagliflozin elicits beneficial effects on both glucose homeostasis and hypertension in salt-replete obese states. 10.1038/hr.2016.2
    Circadian blood pressure rhythm as a possible key target of SGLT2 inhibitors used for the treatment of Type 2 diabetes. Tamura Kouichi,Wakui Hiromichi,Azushima Kengo,Uneda Kazushi,Umemura Satoshi Hypertension research : official journal of the Japanese Society of Hypertension 10.1038/hr.2016.1
    The measurement of orthostatic blood pressure as a screening tool for masked hypertension with abnormal circadian blood pressure rhythm. Komori Takahiro,Eguchi Kazuo,Kario Kazuomi Hypertension research : official journal of the Japanese Society of Hypertension 10.1038/hr.2016.70
    A Novel Diabetic Mouse Model for Real-Time Monitoring of Clock Gene Oscillation and Blood Pressure Circadian Rhythm. Hou Tianfei,Su Wen,Guo Zhenheng,Gong Ming C Journal of biological rhythms Diabetic patients have an increased prevalence of blood pressure (BP) circadian rhythm disruption, which is associated with an increased risk of target organ damage and detrimental cardiovascular events. Limited information is available regarding the role of clock genes in the disruption of BP circadian rhythm in diabetes due to the lack of a diabetic animal model that allows real-time monitoring of clock gene oscillation. Here, we generated a novel diabetic db/db-mPer2 mouse model by crossing type 2 diabetic db/db mice with mPer2 knock-in mice. The daily rhythms of BP, heart rate, locomotor activity, and food and water intake were acquired by radiotelemetry or using metabolic chambers. The daily oscillation of mPer2 bioluminescence was recorded by LumiCycle in real-time in tissue explants and using the IVIS system in vivo. Our results show that db/db-mPer2 mice are obese, diabetic, and glucose intolerant. The db/db-mPer2 mice displayed a compromised BP daily rhythm, which was associated with disrupted daily rhythms in baroreflex sensitivity, locomotor activity, and metabolism, but not heart rate or food and water intake. The phase of the mPer2 daily oscillation was advanced to different extents in the explanted peripheral tissues from db/db-mPer2 mice relative to control mice. In contrast, no phase shift was detected in mPer2 daily oscillations in the explanted SCN. Moreover, advanced phase shift of the mPer2 daily oscillation was detected in the liver, kidney and submandibular gland in vivo of db/db-mPer2 mice. In conclusion, the diabetic db/db-mPer2 mouse is a novel animal model that allows real-time monitoring of mPer2 circadian rhythms ex vivo and in vivo. The results from db/db-mPer2 mice suggest that the desynchrony of mPer2 daily oscillation in peripheral tissues contributes to the loss of BP daily oscillation in diabetes. 10.1177/0748730418803719
    Relationships of Blood Pressure Circadian Rhythm and Brain Natriuretic Peptide with Left Ventricular Hypertrophy in the Patients with Primary Hypertension. Kou Hui-Juan,Wang Xin,Gao Deng-Feng,Dong Xin,Wei Jin,Ma Rui Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae Objective To investigate the relationships of blood pressure circadian rhythm and brain natriuretic peptide (BNP) with left ventricular hypertrophy (LVH) in patients with primary hypertension. Methods Totally 349 patients (74 with LVH and 275 without LVH) with primary hypertension were enrolled in this study.Echocardiography was performed to determine left ventricular mass index (LVMI) using the Devereux formula. The nocturnal blood pressure decline rate,24-hour blood pressure (24 h PP; especially 24 h mean systolic blood pressure,24 h SBP) and blood pressure index (PPI) were determined by 24 h-ambulatory blood pressure monitoring. These 349 hypertensive patients were divided into four groups including supper-dipper group (defined as≥;20%, n=7),dipper group (defined as 10%- 20%, n=77),non-dipper group (defined as 0- 10%, n=173),and anti-dipper group (defined as<0, n=92). The baseline demographic characteristics of patients were collected. Fasting blood sugar,blood lipids,blood urea nitrogen,serum cretinine,cystatin C,uric acid,and plasma BNP level were measured. Results The patients with LVH (n=74) had significantly higher percentage of grade 3 hypertension (85.1% vs. 46.9%;χ=34.428,P<0.001),24 h SBP (134 mmHg vs. 129 mmHg; t=3.175,P=0.002)(1 mmHg=0.133 kPa),daytime-mean SBP (134 mmHg vs. 130 mmHg; t=2.197,P=0.029),night-mean SBP(132 mmHg vs. 121 mmHg; t=4.763,P<0.001),and 24 h PP(57 mmHg vs. 52 mmHg; t=4.120,P<0.001) and PPI (0.43 vs. 0.41; t=3.335,P=0.001) and lower nocturnal blood pressure decline rate [(1.30±8.02)% vs. (5.68±7.25)%; t=-4.510,P<0.001] than the non-LVH patients (n=275). The LVH hypertensive group had significantly higher BNP level (87.8 pg/ml vs. 28.8 pg/ml; t=2.170,P=0.034) and LVMI (135.1 g/m vs. 88.7 g/m; t=15.285,P<0.001) than the control group. No significant difference was observed in the BNP level among supper-dipper,dipper,non-dipper and anti-dipper groups (P=0.137).However,the difference was statistically significant in the LVMI (P=0.001). Additionally,patients in the anti-dipper group had significantly higher LVMI than those in the dipper patients (100.3 g/m vs. 86.3 g/m; t=4.335,P<0.001) and non-dipper (100.3 g/m vs.93.7 g/m; t=1.987,P=0.048). Patients in the non-dipper group had significantly higher LVMI than those in the dipper group (93.7 g/m vs. 86.3 g/m; t=2.693,P=0.008). The multivariate linear correation analysis and logistic regressions analysis suggested a significant correlation of LVMI with BNP and the grade of hypertension. Conclusion With the increasing of plasma BNP level,the left ventricular hypertrophy is closely related to abnormal blood pressure circadian rhythm and the grade of hypertension in primary hypertensive patients. 10.3881/j.issn.1000-503X.2016.05.004
    Blood pressure circadian rhythm alterations in alpha-synucleinopathies. Vallelonga Fabrizio,Di Stefano Cristina,Merola Aristide,Romagnolo Alberto,Sobrero Gabriele,Milazzo Valeria,Burrello Alessio,Burrello Jacopo,Zibetti Maurizio,Veglio Franco,Maule Simona Journal of neurology INTRODUCTION:We sought to analyze the blood pressure (BP) circadian rhythm in Parkinson's disease (PD), multiple system atrophy (MSA), and pure autonomic failure (PAF) and to evaluate the effect of vasoactive and dopaminergic medications on BP fluctuations during activities of daily living. METHODS:We analyzed data from patients with PD (n = 72), MSA (n = 18), and PAF (n = 17) evaluated with 24-h ambulatory BP monitoring (ABPM) at our Center between 1996 and 2015. Comparisons between groups were performed according to (a) clinical diagnosis and (b) pharmacological treatment. ABPM parameters included 24-h BP variability, BP load, nocturnal dipping, and awakening hypotension. RESULTS:The average BP was 121 ± 14/72 ± 8 mmHg during daytime and 133 ± 20/76 ± 13 mmHg during nighttime (p < 0.01), with BP load of 24 ± 22/15 ± 16% (daytime) vs. 61 ± 36/52 ± 36% (nighttime) (p < 0.01). In-office BP measurements were consistent with OH in 95 patients (89%) and SH in 63 (59%). ABPM demonstrated increased BP variability in 67 patients (63%), awakening hypotension in 63 (59%), "reverse dipping" in 85 (79.4%), "reduced dipping" in 13 (12.1%), and "normal dipping" in 9 (8.4%). No differences were observed between PD, MSA, and PAF, but a sub-analysis of PD patients revealed two distinct patterns of BP alterations. No significant differences were observed in relation to the use of vasoactive or dopaminergic medications. CONCLUSION:Regardless of the neurological diagnosis and pharmacological treatment, patients with alpha-synucleinopathies showed a BP circadian rhythm characterized by increased BP variability, reverse dipping, increased BP load, and awakening hypotension. 10.1007/s00415-019-09244-w
    Clock time-based hourly blood pressure surge around 6 am: Blood pressure dynamics specific to awakening or endogenous circadian rhythm? Shin Jinho Journal of clinical hypertension (Greenwich, Conn.) 10.1111/jch.13497
    The Relation of Epicardial Fat Thickness, Neutrophil to Lymphocyte Ratio and Circadian Rhythm of Blood Pressure. Choi Jae Hyuk Journal of cardiovascular ultrasound 10.4250/jcu.2016.24.4.272
    Association of Circadian Rhythm of Blood Pressure and Cerebral Small Vessel Disease in Community-Based Elderly Population. Zhang Hua,Cui Yi,Zhao Yingxin,Dong Yuanli,Wang Juan,Duan Dandan,Ji Tiantian,Zhou Tingting,Hu Wenjing,Chen Yali,Sun Shangwen,Gong Gary,Chai Qiang,Liu Zhendong The journals of gerontology. Series A, Biological sciences and medical sciences BACKGROUND:Although it is accepted that the etiology of cerebral small vessel disease (CSVD) is associated with cardiovascular risk factors, the association between CSVD and the circadian rhythm of blood pressure (BP) is unclear. We aimed to determine if such an association existed in the elderly population. METHOD:White matter hyperintensities (WMHs), lacunes, microbleeds, nocturnal dipping pattern (NDP), and morning surge in systolic blood pressure (SBP) were assessed in 2,091 participants ≥60 years of age. RESULTS:During an average of 63 months of follow-up, WMH and the WMH-to-intracranial volume ratio were significantly increased in extreme dippers, nondippers, and reverse dippers than those in dippers (p < .001). For new-incident Fazekas scale ≥2, the hazard ratios were 1.77 (95% confidence interval [CI], 1.09-2.86) for extreme dippers, 2.20 (95% CI, 1.48-3.28) for nondippers, and 2.43 (95% CI, 1.59-3.70) for reverse dippers compared with dippers, and 1.04 (95% CI, 0.81-1.35) for higher morning surge compared with lower morning surge. Nondippers and reverse dippers were associated with higher risks of new-incident lacunes and microbleeds than dippers (p < .05). Higher morning surge was associated with a higher risk of new-incident microbleeds than lower morning surge (p < .05). CONCLUSION:NDPs in SBP played an important role in CSVD, and the morning surge in SBP was associated with cerebral microbleeds in community-based elderly population beyond the average SBP level. 10.1093/gerona/gly212
    Models of Variability and Circadian Rhythm in Heart Rate, Blood Pressure, and QT Interval for Healthy Subjects Who Received Placebo in Phase I Trials. Minocha Mukul,Li Hong,Chiu Yi-Lin,Carter David,Othman Ahmed A Clinical and translational science This work characterized the time-course, circadian rhythm, and inherent variability in key cardiovascular variables (heart rate, corrected QT interval, and systolic and diastolic blood pressure) that are routinely collected as part of safety monitoring in phase I trials. Longitudinal data from 1,035 healthy volunteers who received placebo in 65 single-dose and multiple-dose phase I trials conducted by AbbVie were compiled and analyzed using nonlinear mixed-effects modeling. An independent nonlinear mixed-effects model was developed for each variable, and combinations of cosine functions were used to capture circadian oscillations. Gender, race, age, and body weight were significant covariates for variability in baseline measures, and the contributions of these covariates were quantitatively characterized. Based on the extensive data set analyzed, the developed models represent valuable tools to help contextualize and differentiate inherent variability that can be expected in a typical phase I setting from true drug-related cardiovascular safety signals. In addition, these placebo models can be used to support exposure-response analyses that estimate treatment-related effects on the evaluated cardiovascular measures. 10.1111/cts.12640
    The impact of non-dipper circadian rhythm of blood pressure on left ventricular hypertrophy in patients with non-dialysis chronic kidney disease. Che Xiajing,Mou Shan,Zhang Weiming,Zhang Minfang,Gu Leyi,Yan Yucheng,Ying Hua,Hu Chunhua,Qian Jiaqi,Ni Zhaohui Acta cardiologica Objective The aim of this study was to investigate the correlation between non-dipper circadian rhythm of blood pressure (BP) and left ventricular hypertrophy (LVH) in patients with chronic kidney disease (CKD). Methods and results All 257 patients with stage 1 to 5 CKD were enrolled in the study and classified into a CKD1-3 group and a CKD4-5 group according to renal function. The parameters and circadian rhythm of BP were measured by a GE Marquette Tonoport V Eng dynamic sphygmomanometer, and cardiac structure was examined by echocardiography. The incidence of abnormal circadian BP rhythm (non-dipper rhythm) was quite high (75.4% in all enrolled patients and 71.3% in the patients with normal BP levels) in CKD patients and increased with the deterioration of renal function. Changes of cardiac structure such as LVH in patients with non-dipper BP were more distinct than in patients with dipper BP. The development of left ventricular mass index (LVMI) correlated positively with the incidence of non-dipper BP rhythm. Multiple regression analysis showed that 24-h systolic BP (β = 0.417, P < 0.01), triglycerides (TG) (β = -0.132, P = 0.007), Hb (β = -0.394, P = 0.016) and gender (β = 0.158, P = 0.039) were independent risk factors of LVMI. Conclusions The incidence of non-dipper circadian rhythm of blood pressure was quite high in CKD patients and increased with the deterioration of renal function. Non-dipper circadian rhythm of BP is closely related with LVMI. 10.1080/00015385.2017.1291133
    Correlations of Circadian Rhythm Disorder of Blood Pressure with Arrhythmia and Target Organ Damage in Hypertensive Patients. Zeng Lixiong,Zhang Zhihui,Wang Xiaoyan,Tu Shan,Ye Fei Medical science monitor : international medical journal of experimental and clinical research BACKGROUND The aim of this study was to investigate the correlations of circadian rhythm disorder of blood pressure with arrhythmia and target organ damage in hypertensive patients. MATERIAL AND METHODS A total of 198 patients admitted and treated in our hospital from May 2018 to April 2019 were selected to receive 24-h ambulatory blood pressure monitoring. The nighttime blood pressure decrease rate is 0-10% in people with normal circadian rhythm of blood pressure. In the present study, we divided patients into a normal circadian rhythm group (normal circadian rhythm of blood pressure, n=132) and a circadian rhythm disorder group (circadian rhythm disorder of blood pressure, n=66) according to the circadian rhythm of blood pressure. The systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean pulse pressure (PP) were observed, and dynamic electrocardiography was performed to observe the status of arrhythmia. Finally, the degree of damage to target organs such as heart, brain, and kidney was compared. RESULTS The circadian rhythm disorder group had remarkably higher daytime SBP (d-SBP), daytime DBP (d-DBP), and daytime PP (d-PP) but clearly lower nighttime SBP (n-SBP), nighttime DBP (n-DBP), and nighttime PP (n-PP) than in the normal circadian rhythm group (P<0.0001). The detection rate of arrhythmia and the degree of target organ damage were clearly higher in the circadian rhythm disorder group compared with the normal circadian rhythm group (P<0.0001). Moreover, the incidence rates of heart disease, cerebrovascular disease, and nephropathy were higher in the circadian rhythm disorder group than in the normal circadian rhythm group (P<0.0001). CONCLUSIONS The circadian rhythm disorder of blood pressure in hypertensive patients probably increases the risk of arrhythmia and worsens the target organ damage, so attention should be paid to the adjustment of disordered blood pressure rhythm in hypertensive patients in clinical practice. 10.12659/MSM.919328
    The effect of depression on sleep quality and the circadian rhythm of ambulatory blood pressure in older patients with hypertension. Ma Lina,Li Yun Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia OBJECTIVE:To explore the effect of depression on the sleep quality, and the circadian rhythm of ambulatory blood pressure in patients with essential hypertension. METHODS:A total of 73 older patients with hypertension were screened for depression and divided into two groups. The Pittsburgh Sleep Quality Index (PSQI) and the circadian rhythm of ambulatory blood pressure were compared between the non-depressed (control) and depressed (case) group. RESULTS:In the case group, 24h ambulatory SBP and DBP, and nocturnal SBP and DBP were higher than in the control group, and the circadian rhythm of non-dipper was higher (67.22% vs 40.13%,P<0.01). There was a positive correlation between PSQI and depression (r=0.432, P<0.01). CONCLUSION:There was a significant correlation between sleep quality and depression in older patients with hypertension. Depression increases the circadian rhythm of non-dipper in older patients with hypertension. 10.1016/j.jocn.2017.02.039
    Relation between circadian blood pressure rhythm and serum albumin level in non-diabetic patients with proteinuria. Ando Daisaku,Hirawa Nobuhito,Yasuda Gen Blood pressure It remains unclear whether the abnormal circadian blood pressure (BP) rhythm in non-diabetic chronic kidney disease (CKD) is related to hypoalbuminemia. We evaluated relationships between circadian BP rhythm and serum albumin concentration (SAC) and also examined autonomic nervous activities. Non-diabetic CKD patients with proteinuria (n = 197; 105 men, 92 women; aged 47.0 ± 13.3 years; estimated glomerular filtration rate ≥30 ml/min) were divided into nephrotic syndrome (NS: n = 46, SAC ≤ 30 g/l), hypoalbuminemia (n = 65, 30 < SAC < 40 g/l) and normoalbuminemia (n = 86, SAC ≥ 40 g/l) groups. Non-proteinuria subjects (n = 97, urinary protein/creatinine ratio < 30 mg/g creatinine) were enrolled as the non-proteinuria group. Ambulatory 24 h BP monitoring was conducted in all subjects. Simultaneously, power spectral analysis of heart rate was performed to evaluate the sympathovagal balance. Waking BP was lower in the hypoalbuminemia and NS groups than the other groups. Sleeping/waking mean BP ratio was not different between non-proteinuria (0.87 ± 0.07) and normoalbuminemia (0.89 ± 0.08) groups, but increased significantly (p < 0.05) in the hypoalbuminemia (0.92 ± 0.08) and NS groups (0.96 ± 0.08). Significant reverse correlations were observed between SAC and sleeping/waking mean BP ratio (r = -0.274, p < 0.001) in all patients. Multivariate regression analysis identified SAC and sympathovagal balance as predictors of increased sleeping/waking BP ratios as the dependent variable. In non-diabetic CKD patients with proteinuria, disturbed circadian BP rhythms were related to SAC and 24 h sympathovagal imbalance. 10.3109/08037051.2016.1095916
    Rotigotine Improves Abnormal Circadian Rhythm of Blood Pressure in Parkinson's Disease. Oka Hisayoshi,Nakahara Atuso,Umehara Tadashi European neurology INTRODUCTION:Cardiovascular autonomic failure is commonly associated with Parkinson's disease (PD), affecting the daily lives of patients. Rotigotine was recently reported not to influence cardiovascular autonomic responses in contrast to other dopaminergic drugs. The effect of rotigotine on daily blood pressure (BP) fluctuations might reflect autonomic failure in patients with PD. METHODS:Twenty-five PD patients who were receiving rotigotine and 12 patients not receiving rotigotine were recruited. Systolic BP during the daytime and nighttime was measured by 24-h BP monitoring at an interval of 2 years. The patients were divided into 3 groups according to the BP fluctuation type: dippers (nocturnal fall in BP ≥10%), non-dippers (0-10%), and risers (< 0%). The time course of BP was compared between the patients given rotigotine and those not given rotigotine. RESULTS:Among the 25 patients who received rotigotine, the BP type worsened in 2 patients, was unchanged in 16 patients, and improved in 7 patients. Among the 12 patients who were not receiving rotigotine, the BP type worsened in 5 patients, was unchanged in 4 patients, and improved only in 3 patients (p = 0.042). CONCLUSION:Rotigotine improves the abnormal circadian rhythm of BP in patients with PD. Rotigotine was suggested to have favorable effects on cardiovascular autonomic responses and circadian rhythm in patients with PD. 10.1159/000489574
    More Attention Should Be Paid to Abnormalities of Circadian Blood Pressure Rhythm in Heart Failure Patients. Kai Mamiko,Kai Hisashi Circulation journal : official journal of the Japanese Circulation Society 10.1253/circj.CJ-16-1269