ATVB: Too Little Vitamin D May Increase Risk of Peripheral Arterial Disease

By Todd Neale
ATLANTA, 17 April 2008 -- Low levels of vitamin D were associated with an increased risk for peripheral arterial disease (PAD) in a large, cross-sectional study.
Participants in the lowest quartile of 25-hydroxyvitamin D levels were 80% more likely to have peripheral arterial disease than those in the highest quartile (prevalence ratio 1.80, 95% CI 1.19 to 2.74), Michal Melamed, M.D., M.H.S., of Albert Einstein College of Medicine in Bronx, N.Y., and colleagues, reported at the American Heart Association's Arteriosclerosis, Thrombosis, and Vascular Biology meeting here.
The results were published simultaneously online in Arteriosclerosis, Thrombosis, and Vascular Biology: Journal of the American Heart Association.
For every 10 ng/mL that vitamin D levels decreased, the risk was increased by 35% (PR 1.35, 95% CI 1.15 to 1.59).
However, because a causal relationship could not be determined, "we would not recommend people start taking vitamin D supplements without talking to their doctors," Dr. Melamed said in a statement.
Because there are conflicting results in the literature about the association between levels of vitamin D and cardiovascular disease, the researchers evaluated the relationship between the nutrient and peripheral arterial disease in a large, population-based sample, the National Health and Nutrition Examination Survey 2001-2004.
They looked at data from 4,839 participants ages 40 and older with values calculated for ankle-brachial index.
Peripheral arterial disease was defined as a score of less than 0.9 on the index.
The participants were divided into quartiles of vitamin D levels -- less than 17.8 ng/mL, 17.8 to 23.4 ng/mL, 23.5 to 29.1 ng/mL, and 29.2 ng/mL or more.
Prevalence of peripheral arterial disease decreased with each successive quartile from lowest to highest: 8.1%, 5.4%, 4.9%, and 3.7%, respectively (P<0.001 for the trend).
Those who had peripheral arterial disease were older, less physically active, and more likely to be a former smoker, to have diabetes, hypertension, chronic kidney disease, or a history of myocardial infarction, and to use statins (P<0.001 for all).
Also, mean 25-hydroxyvitamin D level was lower in those with peripheral arterial disease compared with those without PAD (21.5 versus 24.6 ng/mL, P<0.001).
In a secondary analysis, higher levels of serum calcium, phosphate, and intact parathyroid hormone were not associated with peripheral arterial disease, despite findings from previous studies that suggested high levels of these markers were related to increased risk of cardiovascular disease, the researchers said.
The cross-sectional nature of this study could not prove a causal effect of vitamin D levels on risk of peripheral arterial disease, Dr. Melamed said, and a large, randomized clinical trial will be needed to confirm the association.
An alternative explanation for the results, she said, was that patients with peripheral arterial disease do not go outside as much and, therefore, have less exposure to the sun.
However, Dr. Melamed said, that is unlikely to explain the findings because all of the participants were ambulatory and able to get to the mobile examination centers used in the study.
The authors noted some potential limitations of the study, including the cross-sectional design, the lack of data on sun exposure, geographic location, and season during which examinations were conducted, and the fact that angiography was not used to detect peripheral arterial disease.
As strengths of the study, the researchers mentioned that the use of the ankle-brachial index detected subclinical disease, the study included a broad range of and quality control for data collection, and the sample was large and nationally representative.
Dr. Melamed's work was funded by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases and by an American Heart Association Heritage Affiliate Clinically Applied Research Award. One of her co-authors was supported by the PJ Schafer Memorial Cardiovascular Research award at Johns Hopkins and has served as a consultant to Abbott.
Additional source: Arteriosclerosis, Thrombosis, and Vascular BiologySource reference: Melamed M, et al "Serum 25-hydroxyvitamin D levels and the prevalence of peripheral arterial disease: results from NHANES 2001 to 2004" Arterioscler Thromb Vasc Biol 2008; DOI: 10.1161/ATVBAHA.108.165886.