No Benefit of Vitamin D for CVD Prevention

Damian McNamara

June 21, 2019

Countering results of multiple observational studies suggesting a protective effective of vitamin D supplementation against future cardiovascular events, a new meta-analysis shows no such advantage.

The likelihood of a major adverse cardiovascular event (MACE) was the same (a relative risk of 1.0) when investigators compared 41,669 people taking vitamin D supplements with 41,622 others taking a placebo in the meta-analysis of 21 randomized clinical trials.

"Vitamin D supplementation should not be taken for the purpose of prevention of cardiovascular disease [CVD], including myocardial infarction and stroke," lead author Mahmoud Barbarawi, MD, chief resident of internal medicine at Hurley Medical Center, Michigan State University in Flint, told Medscape Medical News. "Even in patients with a low vitamin D level, correcting their level does not mean that it will prevent the cardiovascular outcomes."

Barbarawi emphasized that the current findings do not rule out prescribing vitamin D for other indications, such as prevention of osteoporosis, osteomalacia, or chronic kidney disease.

The study was published online June 19 in JAMA Cardiology.

Seeking More Definitive Answers

Many observational studies point to an association between low vitamin D levels and increased risk for myocardial infarction, stroke, heart failure, and death from CVD. At the same time, the prescription of vitamin D supplementation in primary care has risen, the researchers note.

However, the US Preventive Services Task Force does not recommend vitamin D supplements to prevent adverse cardiovascular outcomes, citing insufficient evidence in a statement.

Historically, randomized trials looking at vitamin D supplementation and cardiovascular event risk were "limited and inconclusive," Barbarawi and colleagues note.

The recent addition of larger trials to the literature prompted them to conduct a meta-analysis. After exclusions, they included 21 randomized clinical trials with at least 1 year of vitamin D supplementation. The primary, composite MACE endpoint was defined in each trial. Incidence of myocardial infarction, stroke, and cardiovascular mortality were the secondary outcomes.

Mean age was 66 years and almost 75% of the 83,291 people studied were female. Mean follow-up varied from 1 to 12 years.

No Significant Differences Emerged

A total 6243 cases of MACE occurred, but the incidence did not vary significantly based on vitamin D supplementation vs placebo (relative risk, 1.0; 95% confidence interval [CI], 0.95 - 1.06; P = .85).

Similarly, no significant differences emerged among the secondary outcomes. For example, 2550 myocardial infarctions occurred across the studies, but the relative risk between groups was again 1.0 (95% CI, 0.93 - 1.08; P = .92).

In addition, the relative risk for stroke was 1.06 (95% CI, 0.98 - 1.15; P = .16); for cardiovascular mortality was 0.98 (95% CI, 0.90 - 1.07; P = .68); and for all-cause mortality was 0.97 (95% CI, 0.93 - 1.02; P = .23).

When asked if the relative equivalency of these outcomes was unexpected, Barbarawi said, "Yes, the results were surprising, as many observational studies did show an association between low vitamin D level and cardiovascular disease, so a marginal benefit was expected, but the result from this analysis is more real as it come from randomized controlled trials."

Interestingly, a possible signal emerged concerning advanced age, vitamin D supplementation, and reduced incidence of MACE in a meta-regression analysis (unadjusted P = .04).

Older people "are at higher risk of cardiovascular disease and the potential of having lower vitamin D level is higher, so giving vitamin D to this group of patients could help," Barbarawi said. "Indeed, large randomized trials that concentrate on this group of patients is needed as the data number regarding elderly patients in our study is low, so this should be carefully interpreted."

Many of the included studies did not prespecify cardiovascular outcomes, a potential limitation. In addition, few trials included heart failure as an endpoint.

Going forward, Barbarawi and colleagues plan to study the effects of vitamin D on people with diabetes.

A "Cautious" Conclusion

"The report by Barbarawi et al in this issue of JAMA Cardiology supports efforts aimed at curbing wasteful spending on vitamin D testing and treatment in populations not at risk for deficiency and/or for the purpose of preventing CVD morbidity and mortality," Arshed A. Quyyumi, MD, and Ibhar Al Mheid, MD, write in an accompanying invited commentary entitled "The Demise of Vitamin D for Cardiovascular Protection."

"At the same time, it also should be emphasized that vitamin D therapy in patients with chronic kidney disease and hyperparathyroidism is definitely indicated, and such therapy has established cardiovascular benefits, including blood pressure reduction, reduced electrolyte derangements and overall reduced cardiovascular mortality rates in patients on hemodialysis," note Quyyumi and Mheid, who are both affiliated with the Division of Cardiology, Emory Clinical Cardiovascular Research Institute at Emory University School of Medicine in Atlanta, Georgia.

"The authors cautiously conclude that vitamin D supplementation is not associated with reduced risk of major adverse cardiovascular events, myocardial infarctions, cerebrovascular accidents, cardiovascular mortality or all-cause mortality while pointing out limitations in their analysis," they note. "Only 4 of 21 included trials had prespecified primary CVD end points, and overall, they were mostly underpowered for CVD events."

Barbarawi, Quyyumi, and Mheid have disclosed no relevant financial relationships.

JAMA Cardiol. Published online June 19, 2019. Abstract, Commentary

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