Prevalence of Micronutrient Deficiencies and Relationship with Clinical and Patient-Related Outcomes in Pulmonary Hypertension Types I and IV.
Vinke Paulien,Koudstaal Thomas,Muskens Femke,van den Bosch Annemien,Balvers Michiel,Poland Mieke,Witkamp Renger F,van Norren Klaske,Boomars Karin A
Nutrients
BACKGROUND:Pulmonary hypertension (PH) is a rare progressive and lethal disease affecting pulmonary arteries and heart function. The disease may compromise the nutritional status of the patient, which impairs their physical performance. This study aimed to determine the prevalence of micronutrient deficiencies in pulmonary arterial hypertension (PAH) and chronic thrombo-embolic pulmonary hypertension (CTEPH) patients. METHODS:Eighty-one blood samples from a prospective observational cohort study were analyzed for concentrations of micronutrients and inflammation-related factors. The samples consisted of newly diagnosed (treatment-naive) PAH and CTEPH patients and patients treated for 1.5 years according to ERS/ESC guidelines. RESULTS:In the newly diagnosed group, 42% of PAH patients and 21% of CTEPH patients were iron deficient compared to 29% of PAH patients and 20% of CTEPH patients in the treatment group. Vitamin D deficiency occurred in 42% of the newly diagnosed PAH patients, 71% of the newly diagnosed CTEPH patients, 68% of the treated PAH patients, and 70% of the treated CTEPH patients. Iron levels correlated with the 6 min walking distance (6MWD). CONCLUSIONS:Iron and vitamin D deficiencies are highly prevalent in PAH and CTEPH patients, underlining the need for monitoring their status. Studies evaluating the effects of supplementation strategies for iron and vitamin D are necessary.
10.3390/nu13113923
Supplementation with Iron in Pulmonary Arterial Hypertension. Two Randomized Crossover Trials.
Annals of the American Thoracic Society
Iron deficiency, in the absence of anemia, is common in patients with idiopathic and heritable pulmonary arterial hypertension (PAH) and is associated with a worse clinical outcome. Oral iron absorption may be impeded by elevated circulating hepcidin concentrations. The safety and benefit of parenteral iron replacement in this patient population is unclear. To evaluate the safety and efficacy of parenteral iron replacement in PAH. In two randomized, double-blind, placebo-controlled 12-week crossover studies, 39 patients in Europe received a single infusion of ferric carboxymaltose (Ferinject) (1,000 mg or 15 mg/kg if weight <66.7 kg) or saline as placebo, and 17 patients in China received iron dextran (Cosmofer) (20 mg iron/kg body weight) or saline placebo. All patients had idiopathic or heritable PAH and iron deficiency at entry as defined by a serum ferritin <37 μg/L or iron <10.3 μmol/L or transferrin saturations <16.4%. Both iron treatments were well tolerated and improved iron status. Analyzed separately and combined, there was no effect on any measure of exercise capacity (using cardiopulmonary exercise testing or 6-minute walk test) or cardiopulmonary hemodynamics, as assessed by right heart catheterization, cardiac magnetic resonance, or plasma NT-proBNP (N-terminal-pro hormone brain natriuretic peptide) at 12 weeks. Iron repletion by administration of a slow-release iron preparation as a single infusion to patients with PAH with iron deficiency without overt anemia was well tolerated but provided no significant clinical benefit at 12 weeks. Clinical trial registered with ClinicalTrials.gov (NCT01447628).
10.1513/AnnalsATS.202009-1131OC
Short-Term Impact of Iron Deficiency in Different Subsets of Patients with Precapillary Pulmonary Hypertension from an Eastern European Pulmonary Hypertension Referral Center.
International journal of general medicine
BACKGROUND:Over the last few decades, interest in the role of iron status in pulmonary hypertension (PH) has grown considerably due to its potential impact on symptoms, exercise capacity (as assessed by the 6-minute walk distance [6MWD]), prognosis, and mortality. The aim of the present study was to identify iron deficiency (ID) prevalence in specific precapillary PH subgroups of Romanian patients and its short-term impact on 6MWD. PATIENTS AND METHODS:Complete datasets from 25 precapillary PH adults were examined and included in the analysis. Data were collected at baseline and after continuous follow-up of an average of 13.5 months. Enrolled patients were assigned to group 1 (pulmonary arterial hypertension) or subgroup 4.1 (chronic thromboembolic pulmonary hypertension), and individualized targeted therapy was prescribed. General characteristics, World Health Organization functional class, 6MWD, pulse oximetry, laboratory parameters, and echocardiographic and hemodynamic parameters were recorded. Ferritin values and transferrin saturation were used to assess ID. RESULTS:At baseline, 16 out of 25 patients were iron deficient. The univariate linear regression analysis did not show a statistically significant impact of ID on 6MWD (p=0.428). In multivariate regression analysis, possible predictors of 6MWD, including ID, were not statistically significant at baseline or after an average of 13.5 months follow-up (p=0.438, 0.361, respectively) and ID indicates a negative impact on 6MWD independent of applied corrections. CONCLUSION:The results of this study demonstrate that 1.4.1 subgroup PAH patients have an increased prevalence of ID compared with other etiologies. ID has a negative impact on the functional status (assessed by 6MWD), in specific groups and subgroups of patients with precapillary PH, albeit not independently nor significant to other known predictors such as age, gender, oxygen saturation, and hemoglobin value. These data can be integrated with global research and are consistent with phenotypes of patients diagnosed with PH of different etiologies.
10.2147/IJGM.S318343
Ferric carboxymaltose improves exercise capacity and quality of life in patients with pulmonary arterial hypertension and iron deficiency: a pilot study.
Viethen Thomas,Gerhardt Felix,Dumitrescu Daniel,Knoop-Busch Susanne,ten Freyhaus Henrik,Rudolph Tanja K,Baldus Stephan,Rosenkranz Stephan
International journal of cardiology
BACKGROUND:Pulmonary arterial hypertension (PAH) is a progressive condition harboring a poor prognosis. Iron deficiency in PAH correlates with disease severity and mortality. While replacement therapy may be beneficial, dietary iron absorption is impaired in PAH patients by hepcidin, a key regulatory protein of iron homoeostasis. We therefore assessed the therapeutic potential and safety of intravenous iron supplementation in patients with PAH and iron deficiency. METHODS:20 patients with PAH and iron deficiency, who were on stable targeted PAH therapy, received a single infusion of ≤1000 mg ferric carboxymaltose. All patients were assessed at baseline and two months after iron treatment. Exercise capacity was evaluated based on the 6-minute-walking distance (6MWD), and quality of life (QoL) was assessed by the SF-36 questionnaire (100 point scale). The effects were compared to 20 matched patients with stable PAH without iron deficiency who did not receive ferric carboxymaltose. RESULTS:In iron deficient patients, iron supplementation led to a marked improvement of iron status (serum iron 5.7±0.4 to 11.1±1.1 μmol/L, ferritin 29.3±6.3 to 145.2±25.4 μg/L, transferrin saturation 7.5±0.7 to 19.3±2.3%, all p≤0.001). Iron-deficient patients receiving ferric carboxymaltose showed a significant increase of the 6MWD from 346.5±28.3 to 374.0±25.5 m (p=0.007), whereas no significant changes were found in the control group not receiving iron supplementation (6MWD 389.9±25.3 to 379.6±26.2 m; n.s.), resulting in a net increase in the 6MWD of 37.8m (p=0.003). This was associated with an improvement in QoL (SF-36 score from 44.3±3.7 to 50.6±3.6; p=0.01). Only minimal side-effects were reported. CONCLUSIONS:These data indicate that parenteral iron supplementation with ferric carboxymaltose significantly improves exercise capacity and QoL and is well tolerated in patients with PAH and iron deficiency, and when administered in addition to targeted PAH therapies. Our results provide proof of concept for further studies evaluating the potential of iron as an adjunct in PAH treatment on a larger scale.
10.1016/j.ijcard.2014.04.233
Iron deficiency in pulmonary arterial hypertension associated with congenital heart disease.
Yu Xue,Zhang Yi,Luo Qin,Liu Zhihong,Zhao Zhihui,Zhao Qing,Gao Liu,Jin Qi,Yan Lu
Scandinavian cardiovascular journal : SCJ
OBJECTIVES:We aimed to investigate the prevalence of iron deficiency (ID) in congenital heart disease associated with pulmonary arterial hypertension (CHD-PAH) and to explore the influence of ID on CHD-PAH patients. What was associated with ID in these patients was also looked into. DESIGN:One hundred and fifty-three patients who were newly diagnosed with CHD-PAH were enrolled. Patients were divided into iron-deficient and iron-replete groups according to the following criteria. ID was defined as transferrin saturation <20% in male and transferrin saturation <25% in female. Clinical data of all participants were collected and compared. Logistic regression was performed to explore factors associated with ID in CHD-PAH. RESULTS:Thirty-nine percent of 153 CHD-PAH patients were founded with ID. Iron-deficient group had greater proportion of female patients, shorter six minutes walking distance (6-MWD), higher N-terminal pro-brain natriuretic peptide levels, lower creatinine levels, greater ratio of diastolic right ventricle diameter to left ventricle diameter. Female (OR = 15.44, 95%CI 4.91-48.54, p < .01), 6-MWD (OR = 0.99, 95%CI 0.98-1.00, p = .02) and mean right atrial pressure (OR = 1.13, 95%CI 1.02-1.26, p = .02) were independently associated with ID in the overall CHD-PAH patients. Menstruation was independently associated with ID in the female subgroup (OR = 3.88, 95%CI 1.09-13.84, p = .04). CONCLUSIONS:ID was highly prevalent in CHD-PAH patients. Worse exercise tolerance and right heart function were observed in iron-deficient patients with CHD-PAH. Female, 6-MWD, mean right atrial pressure and menstruation are important variables indicating the presence of ID in CHD-PAH.
10.1080/14017431.2019.1567934
Ferric carboxymaltose in patients with pulmonary arterial hypertension and iron deficiency: a long-term study.
Kramer Tilmann,Wissmüller Max,Natsina Kristiana,Gerhardt Felix,Ten Freyhaus Henrik,Dumitrescu Daniel,Viethen Thomas,Hellmich Martin,Baldus Stephan,Rosenkranz Stephan
Journal of cachexia, sarcopenia and muscle
BACKGROUND:Pulmonary arterial hypertension (PAH) is a progressive disease with limited survival. Iron deficiency (ID) correlates with disease severity and mortality. While oral iron supplementation was shown to be insufficient in such patients, the potential impact of parenteral iron on clinical measures warrants further investigation. METHODS:We retrospectively analysed the long-term effects of intravenous ferric carboxymaltose (FCM) on iron status and clinical measures in patients with PAH and ID [ferritin < 100 μg/L or ferritin 100-300 μg/L and transferrin saturation (TSAT) < 20%] who were on stable targeted PAH therapy, compared with matched controls without ID. Patients with ID received a single infusion of FCM (500 to 1000 mg). Clinical measures monitored included exercise capacity, World Health Organization (WHO) functional class, ESC/ERS risk status, and hospitalizations. The observation period was up to 18 months. RESULTS:One hundred and seventeen patients (mean age 60.9 ± 16.1 years; 64.1% females) with confirmed PAH and on stable targeted therapy for ≥3 months were included (58 with and 59 patients without ID who did not receive FCM). In patients with ID, iron supplementation with FCM resulted in an immediate and sustained improvement of iron status for up to 18 months (serum iron, ferritin, TSAT, all P < 0.01). Fourteen patients in the FCM group received a second FCM infusion after 9.6 ± 4.8 months due to recurrent ID. At 6 and 18 months after FCM infusion, 6 min walk distance improved from 377.5 ± 15.9 at baseline to 412.5 ± 15.1 and 400.8 ± 14.5 m, respectively (both P < 0.05). WHO functional class (P < 0.05) and ESC/ERS risk status also improved, and there was a reduction of hospitalizations for worsening PAH in the 12 months post vs. prior to iron repletion (P = 0.029). No significant changes were observed in the control group. FCM was well tolerated in all patients, with no severe adverse events. CONCLUSIONS:In addition to targeted therapy, correction of ID by parenteral iron supplementation with FCM appears feasible and safe, has sustained effects on iron status, and may improve the clinical status and hospitalization rates in patients with PAH. Larger controlled studies are required to confirm this finding.
10.1002/jcsm.12764
Unexplained iron deficiency in idiopathic and heritable pulmonary arterial hypertension.
Thorax
BACKGROUND:Anaemia is common in left heart failure and is associated with a poorer outcome. Many patients with pulmonary arterial hypertension (PAH) are anaemic or iron-deficient. This study was performed to investigate the prevalence of iron deficiency in PAH and to identify possible causes. METHODS:All patients with idiopathic or heritable PAH diagnosed in 1995-2008 were identified. Controls were selected from patients with chronic thromboembolic pulmonary hypertension (CTEPH). Full blood counts were examined and any abnormality was investigated. Patients were excluded if they had a cause for iron deficiency. The prevalence study was based on 85 patients with idiopathic PAH and 120 with CTEPH. A separate group of 20 patients with idiopathic PAH and 24 with CTEPH with matching haemodynamics were prospectively investigated for serum factors affecting iron metabolism. RESULTS:The prevalence study identified a point prevalence of unexplained iron deficiency of 50% in premenopausal women with idiopathic PAH compared with 8% in premenopausal women with CTEPH (p=0.002); 14% in postmenopausal women with idiopathic PAH compared with 6% in postmenopausal women with CTEPH (p=0.16); 28% in men with idiopathic PAH men compared with 2% in men with CTEPH (p=0.002); and 60% in patients with heritable PAH. The serum study showed that patients with idiopathic PAH had lower serum iron and transferrin saturations than those with CTEPH. Interleukin-6 levels correlated with iron levels (r=-0.6, p=0.006) and transferrin saturations (r=-0.68, p=0.001) in idiopathic PAH but not in CTEPH. CONCLUSIONS:The prevalence of unexplained iron deficiency is significantly higher in idiopathic PAH than in CTEPH. This may be linked to interleukin-6.
10.1136/thx.2010.147272
Iron deficiency in pulmonary arterial hypertension: prevalence and potential usefulness of oral supplementation.
Ghio Stefano,Fortuni Federico,Capettini Anna Clizia,Scelsi Laura,Greco Alessandra,Vullo Eleonora,Raineri Claudia,Guida Stefania,Turco Annalisa,Gargiulo Chiara,Oltrona Visconti Luigi
Acta cardiologica
BACKGROUND:The aim of this study was to evaluate the prevalence of iron depletion in a prevalent population of patients with pulmonary arterial hypertension (PAH) and to gain preliminary insights on the possibility of its treatment with oral drugs. METHODS:Iron status was determined in 31 consecutive prevalent idiopathic patients with PAH. Iron depletion was defined as serum iron <10 mmol/L and decreased transferrin saturation irrespective of the coexistence of anaemia. Patients underwent laboratory examinations, 6-min walking test and echocardiography in the same day. A subgroup of iron depleted patients received one oral capsule/day containing 30 mg of pyrophosphate sucrosomial iron for 16 weeks. After this period all patients were re-evaluated. RESULTS:Iron depletion was observed in 22 patients (71%), of whom 6 were also anaemic and 16 were not anaemic. Iron depletion was associated with higher systolic pulmonary artery pressure (60 [50-90] vs. 45 [40-50] mmHg, = .007), greater prevalence of moderate to severe tricuspid regurgitation (36% vs. 0%, = .039), lower tricuspid annular plane systolic excursion (23 [21-24] vs. 19 [18-20] mm; = .025]) and higher left ventricular eccentricity index (1.35 vs. 1, = .042). After 16 weeks of treatment, 6-min walking distance significantly improved (500 [390-500] vs. 530 [410-550] metres; = .043). CONCLUSIONS:Iron deficiency is highly prevalent in patients with PAH and is associated with worse clinical conditions. Treatment with oral sucrosomial iron is a therapeutic option which should be further investigated in future trials.
10.1080/00015385.2019.1694760
Influence of Iron Deficiency on Clinical and Haemodynamic Parameters in Pulmonary Arterial Hypertension Cohorts.
Heart, lung & circulation
BACKGROUND:Iron deficiency (Fe) has been shown to be common in patients with group 1 or pulmonary arterial hypertension (PAH). Several studies have shown a negative impact of Fe on clinical and haemodynamic parameters of the disease, but data from individual studies have not been strong enough to lead to incorporation of the finding of Fe into prognostic or therapeutic algorithms. The goal of this meta-analysis was to combine data from available studies to better define any associations between Fe and established variables of prognostic importance in PAH. METHODS:A literature search identified nine studies with extractable data relevant to the study questions. The impact of Fe upon the following parameters was evaluated: 6-minute walk distance (6MWD), WHO-functional class, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, echocardiography, and findings from right heart catheterisation (RHC). Pooled results were reported as mean difference or risk difference with 95% confidence intervals utilising a random effects modeling approach. RESULTS:Fe in the PAH population was common (47% of cases) and was associated with cardiovascular dysfunction (lower tricuspid annular plane systolic excursion [TAPSE], elevated NT-proBNP, and lower mixed venous oxygen saturation) and with reduction in functional capacity (lower 6MWD and higher functional class). CONCLUSION:This meta-analysis strengthens the relationships between Fe and several markers of poor outcome in PAH. Fe in patients with PAH warrants further scrutiny and merits consideration as a cause of clinical deterioration. Even though causation and longitudinal relationships between Fe and PAH could not be identified, effect of Fe on factors that affect disease prognosis is noteworthy and worthy of more focussed studies.
10.1016/j.hlc.2022.09.001