Largest Epidemiologic Study to Date Links Low Vitamin D to CVD Risk

September 26, 2012

September 26, 2012 (Copenhagen, Denmark) — There is a firm association between low levels of vitamin D and higher rates of ischemic heart disease, MI, and early death, according to the largest epidemiological study to date to examine this issue [1]. And the researchers, led by Dr Peter Brøndum-Jacobsen (Copenhagen University Hospital, Denmark), further confirmed this finding by performing a meta-analysis of all such studies to date, published in their paper in Arteriosclerosis, Thrombosis Vascular, Biology.

"People with low levels of vitamin D have an increased risk of heart attack, of dying early on from cardiovascular disease, and this is an important message," senior author Dr Børge G Nordestgaard (Copenhagen University Hospital) told heartwire .

People with low levels of vitamin D have an increased risk of heart attack, of dying early on from cardiovascular disease, and this is an important message.

Nordestgaard stresses, however, that the findings don't prove cause and effect--while low vitamin-D levels may lead directly to heart disease and death, it's also possible that vitamin-D deficiency is a marker for poor health generally, he says. Nevertheless, he believes that advice regarding sun exposure needs to be modified.

"The cheapest and easiest way to get enough vitamin D is to let the sun shine on your skin at regular intervals. There's been a lot of focus on trying to avoid people getting too much sun, but maybe this has not been balanced. Cardiovascular disease kills many more people than skin cancer does," he notes. This is particularly important in countries where food is not fortified with vitamin D, he adds. He cautions, however, that "it is, of course, still important to avoid getting sunburned."

Increased Risk of CVD With Lowest Levels of Vitamin D Compared With Optimum

Brøndum-Jacobsen and colleagues measured baseline plasma 25-hydroxyvitamin D levels in 10 170 men and women from the Copenhagen City Heart Study from 1981–1983. Participants were then followed in nationwide Danish registries to the present. During approximately 29 years of follow-up, 3100 people developed ischemic heart disease, 1625 had an MI, and 6747 had died.

The scientists compared the 5% lowest levels of vitamin D (<5 nmol/L) with the 50% highest levels (>50 nmol/L). In Denmark--where foods are not fortified with vitamin D--it is currently recommended to have a vitamin-D status of at least 50 nmol/L, they note.

Following multivariate adjustment, they found a stepwise increase in risk: those with the lowest levels of vitamin D had a 40% increased risk of ischemic heart disease, a 64% higher chance of an MI, a 57% increased risk of early death, and an 81% higher likelihood of fatal ischemic heart disease/MI.

The meta-analysis gives exactly the same result as our study, so the results are quite robust when you look at the totality of the evidence.

To see whether this was a true finding, the researchers also performed a meta-analysis of all prior published population-based prospective studies on the association between plasma 25-hydroxyvitamin-D levels and risk of ischemic heart disease and early death until January 2012.

They identified 17 studies and performed the analysis with these, then also added in their own study. For both analyses, the risk of ischemic heart disease and early death were increased by 39% and 46% for lowest vs highest quartiles of vitamin D level.

In the meta-analysis, the increase in risk of heart disease and death with decreasing levels of vitamin D was seen independently of the fortification of food with vitamin D, the researchers note.

"The meta-analysis gives exactly the same result as our study, so the results are quite robust when you look at the totality of the evidence," Nordestgaard commented to heartwire .

Trial Results Needed Before Vitamin-D Supplements Can Be Recommended

Interest is high in vitamin D as a possible way to reduce the risk of cardiovascular disease, following the failure of many other vitamins to have an impact on CVD morbidity or mortality. But there is concern that many patients are taking vitamin-D supplements and/or doctors are prescribing them without any real evidence of benefit, effectively carrying out a massive uncontrolled experiment.

Nordestgaard says he does not advise taking vitamin-D supplements. "We need evidence that this is beneficial first," he observes.

There are two large, ongoing trials examining this issue--the 20 000-patient US Vitamin D and Omega-3 Trial (VITAL) study, results of which won't be available until 2016 or 2017, and the UK Vitamin D and Longevity (VIDAL) trial.

The authors report no conflicts of interest.

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