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

Background: Vitamin 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.

Methods: This 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.

Results: All 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).

Conclusions: Repletion of 25(OH)D may improve QOL in HF patients and may help to normalize BNP, PTH, and hsCRP.

Trial registration: Clinicaltrials.gov, Trial Registration Number: NCT01636570 , First registered 3 July 2012.

Keywords: 25-hydroxyvitamin D; B-type natriuretic peptide; C-reactive protein; Calcitriol; Heart failure; Inflammation; Parathyroid hormone; Quality of life; Vitamin D.

Fig. 1

Consort Diagram. Study Design and Enrollment

Fig. 2

Change in 25 hydroxyvitamin D (25(OH)D) level and calcium level at 3 and 6 months. 25(OH)D significantly increased from baseline in the treatment group by 3 months and 6 months compared to placebo group, *p = 0.001. Calcium levels remain unchanged

Fig. 3

Change in PTH from baseline at 12 weeks and 6 months. Change in PTH is depicted on the left, and change in PTH in cohort with hsCRP > 1 is shown in the left columns. * indicates p < 0.05 and ** indicates p < 0.01

Fig. 4

Change in Quality of Life Scores using the Kansas City Cardiomyopathy Questionnaire