Vitamin D3 repletion versus placebo as adjunctive treatment of heart failure patient quality of life and hormonal indices: a randomized, double-blind, placebo-controlled trial

Abstract

BackgroundVitamin D status may influence heart failure (HF) patient outcomes by affecting b-type natriuretic peptide (BNP), parathyroid hormone (PTH), and enhancing cardiac contractility. Vitamin D deficiency is associated with morbidity and mortality in HF patients. The objective of this study was to determine if vitamin D3 at a comparatively high dose would replete 25-hydroxyvitamin D (25(OH)D) stores, improve BNP, PTH, cardiopulmonary function, reduce inflammatory markers, and improve quality of life (QOL) in HF patients.MethodsThis was a 6 month, parallel group, double-blind, placebo-controlled, single clinic center, randomized trial of supplemental vitamin D3 using a dose of 10,000 IU daily or placebo in 40 vitamin D deficient or insufficient (25(OH)D level ≤ 32 ng/ml) patients with stable New York Heart Association Class II-III HF in a specialty cardiology clinic. All variables were measured at baseline and 6 months. Values between the two treatment groups were assessed using Student’s t-test or Mann-Whitney Test. Univariate analysis of covariance was conducted to adjust for variance in baseline 25(OH)D.ResultsAll results were adjusted for baseline 25(OH)D. The change in BNP from baseline was ∆ +30 ± 950 pg/ml for treatment vs. placebo ∆ +400 ± 1900 pg/ml, p = 0.003. 25(OH)D serum levels rose by 49 ± 32 ng/ml in the treatment group vs 4 ± 10 ng/ml in the placebo group, p < 0.001. PTH and exercise chronotropic response index improved in the treatment group vs placebo group, respectively, but both were attenuated by adjustment ((∆-20 ± 20 pg/ml vs ∆ + 7 ± 53 pg/ml respectively (p = 0.01, adjusted p = 0.07)) and (∆ + 0.13 ± 0.26 vs. ∆-0.03 ± 02.9 respectively, p < 0.01, adjusted p = 0.17)). Other measured cardiopulmonary parameters remained unchanged. High sensitivity C-reactive protein (hsCRP) remained unchanged for women, but improved for men (∆-2 ± 4 treatment versus ∆2 ± 5 mg/L placebo, p = 0.05). QOL scores, including composite overall and clinical summary scores significantly improved in treatment compared to placebo (∆ + 10 ± 15 versus −6 ± 15, p < 0.01 and ∆ + 8 ± 14 versus −8 ± 18, p = 0.01, respectively).ConclusionsRepletion of 25(OH)D may improve QOL in HF patients and may help to normalize BNP, PTH, and hsCRP.Trial registrationClinicaltrials.gov, Trial Registration Number: NCT01636570, First registered 3 July 2012.Electronic supplementary materialThe online version of this article (10.1186/s12872-017-0707-y) contains supplementary material, which is available to authorized users.

Impact of serum 25-hydroxyvitamin D on cardiac prognosis in Chinese patients with heart failure

“…Interestingly, a previous study suggested that vitamin D supplementation has great benefits as an anti-inflammatory agent in infants with chronic HF by helping acceleration of the clinical improvement and cytokine profile balance (43) . Previous studies found that vitamin D supplementation was significantly associated with better survival, specifically in patients with documented deficiency (14) , and vitamin D may be an important adjunct to standard HF therapy (44) and improve quality of life (QOL) (45) . In contrast, a study found that treatment with Vitamin D supplementation did not show clear evidence of benefit for preventing HF or influencing its clinical course (46) , while another study found that vitamin D supplementation has no beneficial effects on improvement of LV function and exercise tolerance in chronic HF patients (47) .…”

Inclusion and exclusion criteria and the problem of describing homogeneity of study populations in clinical trials

“…The problem is that the same criteria can be named inclusion (patients with a particular disease are included) or exclusion criteria (patients without this particular disease are excluded) 6 7. Criteria should be specified as inclusion or exclusion 8 9…”

Vitamin D deficiency is an independent predictor of mortality in patients with chronic heart failure

“…Early trials of vitamin D supplementation in CHF were inconclusive possibly due to inclusion criteria, calciumbased placebo, dosing regimen, use of vitamin D 2 (rather than D 3 ) and heterogeneous CHF population [56][57][58], limiting their ability to provide clarity of benefit [25], whilst no trials have shown any adverse safety signals including up to 10,000 IU daily [59]. Recent meta-analyses have suggested that vitamin D might reduce inflammation (assessed by tumour necrosis factor-alpha levels (TNF-α) [60]), but that it is neutral for heart function [61].…”