Vitamin D Supplementation May Reduce Incidence of Cardiovascular Events

Supplementing older adults with monthly doses of vitamin D might reduce the prevalence of major cardiovascular events, although the absolute risk difference was small and the confidence interval (CI) was indicative of a null finding, according to a study published in the British Medical Journal.

The randomized, double-blind, placebo-controlled trial enrolled older adults between the ages of 60 and 84 years and lasted for 5 years. Participants were given 12 vitamin D study tablets each year and were told to take 1 tablet at the beginning of each month, the study authors explained.

The main outcome for the study was the first major cardiovascular event, defined as any of myocardial infarction, stroke, or coronary revascularization. A total of 21,302 participants were included in the final analysis population, with 10,658 receiving vitamin D supplements and 10,644 receiving a placebo, the study authors wrote.

Overall, 16,822 (79%) participants (vitamin D, n = 8552 [80%]; placebo, n = 8270 [78%]) were still taking tablets at the end of 5 years, whereas 866 participants died prior to completing the intervention period, the results of the study show.

More than 80% of participants reported taking at least 80% of the study tablets that were provided (vitamin D, n = 9006 [84%]; placebo, n = 8783 [82%]). The main serum 25(OH)D concentration was 77 nmol/L (standard deviation = 25) in the placebo group and 115 nmol/L (standard deviation = 30) in the vitamin D group, the study authors found.

During the follow-up period, there were 1336 major cardiovascular events (vitamin D, n = 637 [6.0%]; placebo, n = 699 [6.6%]). The rate of major cardiovascular events was lower in the vitamin D group compared with the placebo group (hazard ratio: 0.91; 95% CI, 0.81-1.01), although the upper bound of the CI was consistent with there being no effect, according to the results of the study. When looking specifically at baseline characteristics such as age, sex, or body mass index, there was no effect modification found.

Further analysis of specific cardiovascular events revealed that the cumulative incidence and hazard of myocardial infarction were lower in the vitamin D group (hazard ratio: 0.81; 95% CI, 0.67-0.98). Similar results were found for coronary revascularization, though the CI for the hazard ratio included the null (hazard ratio: 0.89; 95% CI, 0.78-1.01), according to the results of the study.

Investigators discussed an indication of a stronger effect of vitamin D on major cardiovascular events in participants who were using statins or other cardiovascular drugs at baseline, though the interaction was not deemed statistically significant.

This trial had many strengths, including the large population size that was recruited from the general population with strong retention and adherence to the study protocols, and determination of cardiovascular events and mortality outcomes was achieved through comprehensive data linkage, the investigators discussed.

The study authors sought to determine whether their research could be generally applied to the population at large—in this case, the study was conducted in Australia, so they considered whether the results could be generalizable to the broader Australian population.

They determined that a direct comparison was not possible due to differences in reporting regarding myocardial infarction in Australia. However, due to participants in the trial being less likely to use statins compared to the general population (33% versus 44%), the researchers predicted that a greater effect may be expected in the Australian population.

“In the meantime, these findings suggest that conclusions that vitamin D supplementation does not alter risk of cardiovascular disease are premature,” the study investigators concluded.

Reference

Thompson B, Waterhouse M, English D R, McLeod D S, et al. Vitamin D supplementation and major cardiovascular events: D-Health randomized controlled trial. BMJ. 2023;381: e075230. doi:10.1136/bmj-2023-075230