The effects of vitamin D supplementation on major cardiac events

Heart disease and stroke are the leading (and growing) causes of death, especially in older individuals. Vitamin D acts on cells throughout the vascular system, reducing inflammation, regulating the renin-angiotensin-aldosterone system, and inhibiting vascular smooth muscle proliferation. Observational studies have shown an inverse relationship between vitamin D levels and the risk of cardiovascular disease. Prospective controlled studies, on the other hand, have produced conflicting results. Some studies indicate an inverse association with cardiovascular disease risk at certain vitamin D levels, while others have found no significant association. As a result, there is ongoing interest in whether vitamin D can reduce disease risk.

A meta-analysis of randomized controlled trials concluded that vitamin D supplementation does not prevent cardiovascular events. However, that analysis relied heavily on the Women’s Health Initiative Trial, which had limitations in terms of participant characteristics, vitamin D dosage, and compliance. The Vitamin D Assessment (ViDA) study and the Vitamin D and Omega 3 study (VITAL) also found no effect on cardiovascular disease outcomes, but both noted limitations.
The D-Health Trial was a large study involving 21,315 older Australians. Previous analyzes of the study showed no reduction in all-cause mortality or cardiovascular mortality with vitamin D supplementation. However, the impact on major cardiovascular events had not been specifically analyzed. In this current study, we examined data from the D-Health Trial to determine whether monthly vitamin D supplementation (60,000 IU) affected the incidence of major cardiovascular events in Australians aged 60 and older.

The D-Health process

The D-Health Trial was a randomized controlled trial with two groups: Vitamin D recipients (60,000 IU of vitamin D₃ (cholecalciferol)), or placebo, taken once a month. The study included adults aged 60-79 from across Australia. Each year, participants were sent 12 tablets and reminded to take them monthly via text, email, or landline call. Participants were randomly selected from voter registration, which is mandatory in Australia. In addition, people aged between 60 and 84 were also recruited through media coverage and contacts of existing participants. Individuals with specific conditions (hypercalcemia, hyperparathyroidism, kidney stones, osteomalacia, sarcoidosis) or those already consuming more than 500 IU of vitamin D per day were excluded from the trial. Study participants provided information about their demographics, lifestyle, health conditions, and vitamin D intake through a baseline questionnaire.

Participants were asked each year to report how many study tablets they consumed and whether they took any other vitamin D supplements outside of the study. Adherence was assessed by comparing the number of tablets taken with the total number they would have needed to take if they were fully adherent (60, except for those who died during the study). Participants were encouraged to limit their use of vitamin D supplements not provided by the study, but were allowed to continue in the study as long as their intake did not exceed 2000 IU per day. (This would keep your intake below 4000 IU per day.)

Cardiovascular events were one of the planned outcomes in the D-Health Trial, along with 44 other outcomes. The primary outcome measure was the occurrence of the first major cardiovascular event (myocardial infarction, stroke, or coronary revascularization). Secondary outcomes included first myocardial infarction, stroke (total, ischemic, and hemorrhagic), and coronary revascularization. Events were determined from linked hospital data, Medicare benefit data and mortality records, which were very comprehensive due to Australia’s universal health insurance system. Australia’s Pharmaceutical Benefits Scheme contains data on the use of prescription medicines and has been used to determine the use of statins and other cardiovascular medicines.

The sample size was determined to have 80% power to detect a 9% difference in fatality rate, with a type 1 error rate of 0.05. Based on the sample size available for this analysis (n=21,302), the authors estimated that they would have 80% power to detect a 16% difference in the incidence of the first major cardiovascular event. Participants were followed from the time of randomization until the first occurrence of a major cardiovascular event, the last known date of life, five years and one month after randomization, or December 31, 2019 (the date hospital data were available). for all states).

Over 21,000 participants were recruited and participated. At the end of the five-year trial, the majority of participants (79%) were still taking the study tablets. The percentage was similar between the vitamin D group (80%) and the placebo group (78%). Before the completion of the intervention period, 866 people died. The median duration of treatment was five years, and over 80% of participants reported taking at least 80% of the study tablets. This compliance rate was consistent in both the vitamin D group (84%) and the placebo group (82%).

During the study, the mean serum 25(OH)D concentration was 77 nmol/L (with a standard deviation of 25) In the placebo group, while it was 115 nmol/L (with a standard deviation of 30) In the vitamin D group. The incidence of adverse events was comparable between the two groups.

Overall, a total of 1336 major cardiovascular events occurred. Of these, 637 occurred in the vitamin D group (6.0%) and 699 in the placebo group (6.6%). The rate of major cardiovascular events was slightly lower in the vitamin D group than in the placebo group, with a hazard ratio of 0.91 (confidence interval, 0.81 to 1.01). Since the confidence interval crossed one, this means that there was no statistically significant effect. On average, 172 participants would need to be treated (NNT) with vitamin D supplementation to prevent a major cardiovascular event. The confidence interval for this estimate (not provided by the authors) is 82 to infinity. Self 1,000 people aged 60 to 84 in this group of participants took a placebo, 66 will have a cardiovascular event. If the same group took vitamin D, it could drop to 60. Or there might be no difference at all.

Figure 2: Cumulative cause specific incidence of major cardiovascular events by randomization group and time since randomization.