Low Vitamin D Levels Associated With Peripheral Artery Disease 

New data presented this week have shown that low serum vitamin-D levels are associated with a higher prevalence of peripheral artery disease (PAD) [1]. The association was observed in a large, nationally representative sample and was present even after adjustment for multiple cardiovascular risk factors, report investigators.

"Further studies are going to be needed, but right now, I think there is a fair size of the population that is not getting enough vitamin D," said lead investigator Dr Michal Melamed (Albert Einstein College of Medicine, Bronx, New York). "I think there are proven health benefits to taking it, such as in children to prevent rickets or to prevent osteoporosis in older patients. For somebody who thinks they might be at risk for osteoporosis, it might not be a bad idea for your doctor to check your vitamin-D levels."

The researchers presented their findings at the Arteriosclerosis, Thrombosis and Vascular Biology Annual Conference 2008, in Atlanta, GA. Melamed stated that, in mice, vitamin D is a regulator of the renin-angiotensin system and cardiac myocyte hypertrophy. Additional research has shown that rats that break down active vitamin D and are fed a high-fat/high-cholesterol diet develop atherosclerosis, she said.

There is also some evidence suggesting that low levels of vitamin D, also known as 25-hydroxyvitamin D, may adversely affect the cardiovascular system, although the evidence remains conflicting. Vitamin-D receptors have a broad tissue distribution that includes vascular smooth muscle, endothelium, and cardiomyocytes. In addition, higher rates of coronary heart disease and hypertension in populations farther away from the equator with less exposure to the sun have been observed, a phenomenon that has been attributed to the higher prevalence of vitamin-D deficiency in regions with less exposure to sunlight.

In this study, the investigators obtained data on vitamin-D levels in 4839 participants in the National Health and Nutrition Examination Survey (NHANES) and evaluated the association between vitamin levels and PAD. The researchers found that higher levels of vitamin D were associated with a lower prevalence of PAD. Among individuals with the highest vitamin-D levels, those in the fourth quartile, only 3.7% had PAD. Among those with the lowest vitamin-D levels, 8.1% had PAD.
Prevalence of peripheral artery disease by quartiles of serum vitamin D

Melamed noted that another study showed extremely high levels of vitamin D to be associated with an increased risk of cardiovascular disease, although the vitamin-D levels in that study were greater than 90 ng/mL. In this study, there was no observed U-shaped association with increasing vitamin levels and PAD risk, although no patient had vitamin-D levels exceeding 60 ng/mL, she said.

Vitamin-D deficiency is highly prevalent in the US and worldwide, affecting as many as one-third to one-half of otherwise healthy middle-aged to elderly adults, according to some estimates. The principal causes of low vitamin-D levels are inadequate sun exposure, pigmented skin, and inadequate dietary intake. Foods such as fish and fortified dairy products contain vitamin D, and adequate levels are necessary for bone health.

Melamed said that larger prospective and mechanistic studies are needed to confirm the association between low vitamin-D levels and higher prevalence of PAD, cautioning that vitamin-D levels might only serve as a marker for eating a healthy diet. She also noted that while their study included a large, nationally representative sample, it is possible that vitamin-D levels were underestimated. The NHANES survey assesses vitamin-D levels in northern states in the summer and southern states in the winter, which could affect the amount of serum vitamin D.

Practice Pearls

• Vitamin D can inhibit the renin-angiotensin system and myocardial cellular hypertrophy in animal models. Supplementation with vitamin D may also reduce the serum concentration of inflammatory markers such as C-reactive protein, but the effects of vitamin D levels on incident coronary heart disease remains unclear.
• In the current study, lower levels of 25-hydroxyvitamin D predicted an increased prevalence of PAD, but levels of calcium, phosphate, and intact parathyroid hormone did not affect the prevalence of PAD.

Melamed ML, Muntner P, Michos ED, et al. Serum 25-hydroxyvitamin D levels and the prevalence of peripheral arterial disease. Arterioscler Thromb Vasc Biol. 2008;28.

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FACT: Aspirin Less Effective in Diabetic Patients in Preventing Mortality: In a recent meta-analysis it was suggested that antiplatelet agents confer less benefit to diabetic patients with stable vascular disease, compared with non-diabetic subjects. Based on this observation, a retrospective analysis of the Evaluation of Methods and Management of Acute Coronary Events (EMMACE)-2 Study was performed, examining outcomes in 2,499 unselected patients with acute coronary syndrome. Despite similar dosing regimens, the results suggested that aspirin offers less effective mortality reduction to patients with diabetes, which supports the idea that there is a need for more effective antiplatelet strategies to improve outcomes in patients with diabetes and unstable coronary disease  This might be explained by aspirin resistance in diabetes mellitus?

Cubbon RM, Gale CP, Rajwani A, Abbas A, Morrell C, Das R, et al. Aspirin and mortality in patients with diabetes sustaining acute coronary syndrome. Diabetes Care. 2008;31:363-5.