Stroke and coronary heart disease are the two most common causes of global death, with aging increasing the risk of both these events. Previous studies have indicated that vitamin D influences cardiovascular disease.
A recent BMJ study discusses the results of a randomized control trial (RCT) to evaluate the dose-dependent effect of vitamin D supplementation on the incidence of major cardiovascular events in older adults.
Study: Vitamin D supplementation and major cardiovascular events: D-Health randomised controlled trial. Image Credit: R_Szatkowski / Shutterstock.com
Within the vascular system, most of the cells that express the vitamin D receptor also express 1α-hydroxylase and can convert 25-hydroxyvitamin D (25(OH)D) to calcitriol, the active form of vitamin D. Calcitriol has several important biological functions including inflammation reduction, inhibition of proliferation of vascular smooth muscle, and regulation of the renin-angiotensin-aldosterone system.
One meta-analysis of RCTs indicated that vitamin D supplementation was ineffective in preventing cardiovascular events. However, this outcome was contradicted by the Women’s Health Initiative Trial, which included women participants and a low dose of Vitamin D.
The D-Health Trial was launched to evaluate whether monthly vitamin D supplementation improves the health outcomes of older adults. Although a previous analysis using the D-Health cohort reported that vitamin D supplementation did not reduce mortality due to cardiovascular disease or all-cause mortality, their effect on the incidence of major cardiovascular events was not determined.
About the study
The current study used data from the D-Health Trial to investigate whether vitamin D supplementation in Australian adults over the age of 60 years influenced the incidence of major cardiovascular events.
The D-Health Trial is a double-blind, placebo-controlled RCT with two parallel arms. The D-Health Trial cohort included adults from all Australian states and territories, except the Northern Territory, who were between 60 and 84 years of age.
Participants with a history of hyperparathyroidism, hypercalcemia, kidney stones, sarcoidosis, osteomalacia, or were under supplemental vitamin D of above 500 IU, were excluded.
Computer-generated permuted block randomization was used to assign participants in a 1:1 ratio in two groups randomly. One group received 60,000 IU of vitamin D3 (cholecalciferol), while the others received placebo tablets. Both vitamin D3 and placebo tablets were identical in appearance.
Every year, the study participants were given 12 tablets and asked to take one at the beginning of each month. Each participant received this intervention for five years, beginning February 2015 to February 2020.
At baseline, participants completed a questionnaire providing information about pre-existing health conditions, sociodemographic and lifestyle factors, and dietary patterns. Cardiovascular events, including myocardial infarction, stroke, or coronary revascularisation, of the participants were also reported.
A total of 21,315 participants were eligible for the D-Health Trial. Some participants left the trial for personal reasons, whereas others were removed for incomplete data.
Finally, 21,302 participants were considered,10,658 in the Vitamin D group and 10,644 in the placebo group. A total of 866 candidates died before the completion of the study.
Around 80% of participants reported taking at least 80% of the study tablets. The mean serum 25(OH)D concentration of the placebo and vitamin D group was 77 nmol/L and 115 nmol/L, respectively. Similar adverse events were reported in both groups.
During the follow-up period,1,336 major cardiovascular events were noted, including 6% and 6.6% of the vitamin D and placebo groups, respectively. This finding indicates a lower incidence of cardiovascular events, particularly myocardial infarction, and coronary revascularization, in the vitamin D group compared to the placebo group.
Although individuals treated with statins or other cardiovascular drugs at baseline or those with higher vitamin D status had better outcomes, these effects were not clinically significant. The effect of vitamin D on cardiovascular events was found to be independent of sex, age, or body mass index.
The extensive study cohort of over 21,000 participants is the key strength of this trial. High retention and adherence to the intervention are other advantages of this study.
The current study identified cardiovascular events and mortality outcomes using comprehensive data linked to population-based administrative data sources. However, a marginal underestimation of cardiovascular events is possible due to the lack of private hospital data, particularly from Tasmania and South Australia.
Despite this limitation, the study findings indicate that vitamin D supplementation in older adults might reduce the incidence of major cardiovascular events, particularly coronary revascularisation and myocardial infarction.
- Thompson, B., Waterhouse, M., English, D. R., et al. (2023) Vitamin D supplementation and major cardiovascular events: D-Health randomised controlled trial. BMJ, 381. doi:10.1136/bmj-2023-075230