Stroke and coronary heart disease are the two most common causes of death worldwide, and aging increases the risk of both deaths. Previous studies have shown that vitamin D influences cardiovascular disease.
Recent BMJMore This study discusses the results of a randomized controlled trial (RCT) to assess the dose-dependent effects of vitamin D supplementation on the incidence of major cardiovascular events in older adults.
study: Vitamin D supplementation and major cardiovascular events: a D-Health randomized controlled trial. Image credit: R_Szatkowski / Shutterstock.com
Within the vasculature, most cells that express vitamin D receptors also express 1α-hydroxylase, which can convert 25-hydroxyvitamin D (25(OH)D) to calcitriol, the active form of vitamin D. . Calcitriol has several important biological functions. This includes reducing inflammation, inhibiting vascular smooth muscle proliferation, and modulating the renin-angiotensin-aldosterone system.
One meta-analysis of RCTs showed that vitamin D supplementation was ineffective in preventing cardiovascular events. However, this result was contradicted by a Women’s Health Initiative trial that included female participants and low doses of vitamin D.
The D-Health Trial was initiated to assess whether monthly vitamin D supplementation improves health in older adults. Previous analyzes using the D-Health cohort reported that vitamin D supplementation did not reduce mortality from cardiovascular disease or all-cause mortality; The effect was not confirmed.
The current study used data from the D-Health Trial to investigate whether vitamin D supplementation affects the incidence of major cardiovascular events in Australian adults aged 60 and over.
The D-Health Trial is a double-blind, placebo-controlled RCT with two parallel arms. The D-Health Trial cohort included adults from her 60 years to her 84 years from all Australian states and territories except the Northern Territory.
Participants with a history of hyperparathyroidism, hypercalcemia, kidney stones, sarcoidosis, osteomalacia, or taking vitamin D supplements >500 IU were excluded.
Participants were randomly assigned to two groups in a 1:1 ratio using computer-generated permuted block randomization. One group received 60,000 IU of vitamin D3 (cholecalciferol) and the other group received a placebo tablet. Both vitamin D3 and placebo tablets were identical in appearance.
Each year, study participants were given 12 tablets and asked to take one at the beginning of each month. Each participant received this intervention for his 5 years from February 2015 until he February 2020.
At baseline, participants completed a questionnaire providing information on pre-existing health conditions, sociodemographic and lifestyle factors, and dietary patterns. Cardiovascular events such as myocardial infarction, stroke, and coronary revascularization among participants were also reported.
A total of 21,315 participants qualified for the D-Health trial. Some participants left the trial for personal reasons, while others were removed due to incomplete data.
Ultimately, 21,302 participants were considered. Of these, 10,658 were in the vitamin D group and 10,644 were in the placebo group. A total of 866 candidates died before study completion.
Approximately 80% of participants reported taking at least 80% of the study tablets. Mean serum 25(OH)D concentrations in the placebo and vitamin D groups were 77 nmol/L and 115 nmol/L, respectively. Similar adverse events were reported in both groups.
During follow-up, 1,336 major cardiovascular events were recorded, including 6% in the vitamin D group and 6.6% in the placebo group. 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.
People treated with statins or other cardiovascular drugs at baseline or with higher vitamin D status had better outcomes, but these effects were not clinically significant. The effect of vitamin D on cardiovascular events was found to be independent of gender, age and BMI.
An extensive study cohort of over 21,000 participants is a key strength of this trial. High retention and adherence to the intervention are also advantages of this study.
The current study used comprehensive data linked to population-based administrative data sources to identify cardiovascular events and mortality outcomes. However, cardiovascular events may be slightly underestimated due to lack of data from private hospitals, especially in Tasmania and South Australia.
Despite this limitation, research results indicate that vitamin D supplementation in older adults may reduce the incidence of major cardiovascular events, particularly coronary revascularization and myocardial infarction.
- Thompson, B., Waterhouse, M., English, DR, other. (2023) Vitamin D supplementation and major cardiovascular events: a D-Health randomized controlled trial. BMJMore381. Doi: 10.1136/bmj-2023-075230