Effect of vitamin D on endothelial and ventricular function in chronic heart failure patients: A prospective, randomized, placebo-controlled trial

Abstract

Background: Low 25-hydroxyvitamin D (25OHD) levels are common in patients with chronic heart failure (HF) and are associated with increased mortality risk. This study aimed to establish the safety and efficacy of oral vitamin D3 (cholecalciferol) supplementation and its effect on endothelial and ventricular function in patients with stable HF. Methods: This study was an investigator-initiated, multicenter, prospective, randomized, placebo-controlled trial. Seventy-three HF patients with 25OHD levels < 75 nmol/L (30 ng/mL) were randomized to receive 4000 IU vitamin D daily or a placebo for 6 months. The primary endpoint was a change in endothelial function between the baseline and after 6 months as assessed using EndoPAT. Secondary endpoints included changes in echocardiographic parameters and differences in quality of life (6-min walking test and New York Heart Association functional status) at 6 months. Results: There were no adverse events in either group during the study period. Vitamin D supplementation did not improve endothelial dysfunction (EndoPAT: baseline, 1.19 ± 0.4 vs 6 months later, 1.22 ± 0.3, P = .65). However, patients’ blood pressure, 6-min walking distance, and EQ-5D questionnaire scores improved after vitamin D treatment. In addition, a significant reduction in the left atrial diameter was observed. Conclusion: A daily vitamin D dose of 4000 IU for chronic HF appears to be safe. This dosage did not improve endothelial function but did improve the 6-min walk distance, symptoms, and left atrial diameter at 6 months.

Understanding the Role of Vitamin D in Heart Failure

“…Advanced heart failure patients, 18-80 yrs old men and women 4000 IU oral D3 daily for 3 years Increased LVEF in patients ≥50 years [42] No reduction in mortality; associated with greater need for MCS implants [45] No benefit on CVD risk factors [52] Did not improve lipid profile and does not influence the calcification inhibitors fetuin-A and non-phosphorylated undercarboxylated MGP; no reduction in anemia [55] Chronic heart failure patients, mean age 74 yrs men and women 4000 IU D3 daily for 6 months Increased/improved LVEF and lowered systolic blood pressure [43] Chronic heart failure patients, men and women 4000 IU D3 daily for 6 months No improvement in endothelial function. Improvements in 6-minute walk distance, blood pressure, EuroQol 5D health questionnaire and left atrial diameter at 6 months [44] Class II/III NYHA men and women 10,000 IU oral D3 daily for 6 months Improved QOL, normalized BNP, PTH and improved hsCRP in males [46] Heart failure patients, mean age 65, men and women 50,000 IU oral D3 weekly + calcium No improvement in VO2, 6-MWT or knee isokinetic muscle strength [47] Postmenopausal women age 40-60; no CVD or diabetes 2000 IU oral D3 for 12 weeks No effect on blood pressure or lipid profile [48] Heart failure patients 300,000 U oral D3 followed by 50,000 U monthly for 6 months Northern latitude, demonstrated that in order to maintain serum levels of 25-OH vitamin D of ≥12 ng/mL, it was estimated that more than a 2-fold higher intake of vitamin D was required in Somali women vs. Caucasian Finnish women. It was thus suggested that there are ethnic differences in the daily requirement of vitamin D and that it would be more appropriate to conduct dose-response studies based on ethnicity [59].…”

“…Overall, from the aforementioned clinical studies (summarized in the Table 1 (Ref. [42][43][44][45][46][47][48][49][50][51][52][55][56][57]) below), the efficacy and response to vitamin D supplementation is dependent on several factors and the extrapolation of some clinical endpoints and surrogate markers of heart disease to a beneficial effect of vitamin D is not conclusive. Therefore, some reservation may be exercised in the recommendation of vitamin D supplementation in heart failure under a vitamin D insufficient state and thus more large-scale studies are warranted.…”

“…Low plasma levels of 25-OH vitamin D are commonly observed in patients with advanced/chronic heart failure and have been linked to an increase in mortality risk [44,45]. However, the EVITA 3-year randomized clinical trial also revealed that there was no reduction in the mortality rate in patients with advanced heart failure following a daily vitamin D dose of 4000 IU for 3 years, despite a normalization of plasma levels of 25-OH vitamin D in the supplemental group.…”