There is insufficient evidence to conclude whether vitamin D supplementation is beneficial in patients with CAD, according to a new review.
“Longitudinal studies have demonstrated increased morbidity and mortality associated with vitamin D deficiency,” Vijay Kunadian, MBBS, MD, FRCP, of Newcastle University in the United Kingdom, and colleagues wrote. “However, so far, few randomized controlled trials have investigated the potential benefits of vitamin D supplementation in preventing cardiovascular events, and most available trials have tested low doses of supplementation in relatively low-risk populations.”
Kunadian and colleagues reviewed three types of studies: those that assessed the effects of vitamin D on surrogate markers or predictors of CAD; those that assessed the association between vitamin D deficiency and adverse CV outcomes, acute MI, CAD burden, coronary artery calcium and restenosis; and randomized studies of vitamin D supplementation with CV-specific endpoints.
Several studies confirmed that vitamin D deficiency is associated with impaired endothelial function, vascular stiffness, inflammation that could lead to accelerated atherosclerosis, decreased renal plasma flow, insulin resistance and type 2 diabetes.
Deficiency could predict CAD
A number of longitudinal studies have demonstrated a link between low vitamin D levels and increased CV adverse events, the researchers wrote. In one retrospective analysis of 10,899 patients, vitamin D deficiency was associated with hypertension and CAD (both P<.05) and was an independent predictor of all-cause mortality (OR=2.64, 95% CI, 1.9-3.66). Vitamin D supplementation in that study reduced the OR for death in those with vitamin D deficiencies (OR=1.46; 95% CI, 0.76-2.799) compared with those deficient but not taking supplementation (OR=3.7; 95% CI, 2.6-5.4).
Two longitudinal studies reported similar results, but several other studies did not report an association between low vitamin D levels and increased CV morbidity and mortality, according to the researchers.
Kunadian and colleagues also found population studies showing that vitamin D deficiency is associated with increased risk for acute MI, major adverse cardiac events after MI, CAD burden and higher coronary artery calcium levels.
Other studies and meta-analysis demonstrated a dose-response association between vitamin D levels and CVD risk or mortality.
Lack of randomized controlled trials
The review yielded only six randomized controlled trials that investigated the effect of vitamin D supplementation on CV events or surrogate markers of CAD. Only one was positive: a 2013 study of 283 black participants that found 3 months of oral vitamin D3 supplementation decreased systolic BP (–1.4 mm Hg for each 1,000 additional IU/day of vitamin D; P=.04).
The trials “are limited by the generally low-risk cohorts, small sample sizes and lack of hard clinical endpoints,” Kunadian and colleagues wrote. “Furthermore, there are no [randomized controlled trials] that have evaluated the benefit of vitamin D supplementation among older patients presenting with ACS and undergoing PCI.”
However, they wrote, large-scale randomized controlled trials of vitamin D for primary prevention of CVD are underway in the United States, Europe, Australia, Finland and New Zealand. The US trial, VITAL, has enrolled 25,000 men aged at least 50 years and women aged at least 55 years without history of CVD or cancer.
“Whether vitamin D supplementation among patients with CAD, in particular high-risk older patients presenting with ACS, will be of benefit is unknown and warrants further investigation,” Kunadian and colleagues wrote.
Disclosure: The researchers report no relevant financial disclosures.