New research indicates that vitamin D supplementation might reduce the incidence of major cardiovascular events, particularly myocardial infarction and coronary revascularization, among people aged over 60. This protective effect could be more marked in those taking statins or other cardiovascular drugs at baseline. The findings could prompt further evaluation of the role of vitamin D supplementation, particularly in people taking drugs for prevention or treatment of cardiovascular disease.
Coronary heart disease and stroke are the leading causes of death globally. The risk of these events increases with age, and they are more prevalent in men than women.
The number of cardiovascular disease events will probably continue to increase in developed countries as populations age, and in low to middle income countries as non-communicable diseases become dominant.
Observational studies have consistently shown a link between vitamin D levels and cardiovascular disease risk, but randomized controlled trials have found no evidence that vitamin D supplements prevent cardiovascular events, possibly due to differences in trial design that can affect results.
To address this uncertainty, Professor Rachel Neale from the QIMR Berghofer Medical Research Institute and colleagues set out to investigate whether supplementing older adults with monthly doses of vitamin D alters the rate of major cardiovascular events.
Their D-Health Trial was carried out from 2014 to 2020 and involved 21,315 Australians aged 60-84 who randomly received one capsule of either 60,000 IU vitamin D (10,662 participants) or placebo (10,653 participants) taken orally at the beginning of each month for up to 5 years.
The participants with a history of high calcium levels (hypercalcemia), overactive thyroid (hyperparathyroidism), kidney stones, soft bones (osteomalacia), sarcoidosis, an inflammatory disease, or those already taking more than 500 IU/day vitamin D were excluded.
Data on hospital admissions and deaths were then used to identify major cardiovascular events, including heart attacks, strokes, and coronary revascularization (treatment to restore normal blood flow to the heart).
The average treatment duration was 5 years and more than 80% of participants reported taking at least 80% of the study tablets.
During the trial, 1,336 participants experienced a major cardiovascular event (6.6% in the placebo group and 6% in the vitamin D group).
The rate of major cardiovascular events was 9% lower in the vitamin D compared with the placebo group (equivalent to 5.8 fewer events per 1,000 participants).
The rate of heart attack was 19% lower and the rate of coronary revascularization was 11% lower in the vitamin D group, but there was no difference in the rate of stroke between the two groups.
There was some indication of a stronger effect in those who were using statins or other cardiovascular drugs at the start of the trial, but the researchers say these results were not statistically significant.
Overall, the researchers calculate that 172 people would need to take monthly vitamin D supplements to prevent one major cardiovascular event.
They acknowledge that there may be a small underestimate of events and say the findings may not apply to other populations, particularly those where a higher proportion of people are vitamin D deficient. However, this was a large trial with extremely high retention and adherence, and almost complete data on cardiovascular events and mortality outcomes.
“Our findings suggest that vitamin D supplementation may reduce the risk of major cardiovascular events,” the scientists said.
“This protective effect could be more marked in those taking statins or other cardiovascular drugs at baseline. Further evaluation is needed to help to clarify this issue.”
“In the meantime, these findings suggest that conclusions that vitamin D supplementation does not alter risk of cardiovascular disease are premature.”
The results appear in the journal BMJ.
Bridie Thompson et al. 2023. Vitamin D supplementation and major cardiovascular events: D-Health randomised controlled trial. BMJ 381: e075230; doi: 10.1136/bmj-2023-075230