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Low vitamin-D levels linked to atherosclerosis: 'the study is cross-sectional, we cannot establish yet a causal relationship'
August 1, 2011 | Allison Gandey
Adapted from Medscape Medical News-a professional news service of WebMD
New York, NY - Investigators have identified new evidence from the Northern Manhattan Study connecting low vitamin-D levels to atherosclerosis [1]. They found that low 25-hydroxy vitamin-D levels were associated with increased intima-media and maximal carotid thickness in those with plaque.
"Our report demonstrates an independent effect of low vitamin D on subclinical indices of carotid atherosclerosis," senior investigator Dr Shonni Silverberg (Columbia University College of Physicians and Surgeons, New York) said in an interview. "It is, however, important to note that our observations do not provide insight into the nature of the interaction of low vitamin D with the atherosclerotic process."
The work is published in the August 2011 issue of Stroke.
The investigators studied 203 adults from the Northern Manhattan Study who had serum measurements and carotid ultrasound. They looked at 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, calcium, phosphorus, and parathyroid hormone. After adjusting for cardiovascular risk factors, the researchers found that plaque number was associated with phosphorus levels (=0.39 per 1-mg/dL increase, p=0.02) and calcium-phosphorus product (=0.36 per 10-U increase, p=0.03). The majority of those studied-57%-had plaque, and investigators found the association of plaque number with phosphorus and calcium-phosphorus product persisted.
Vitamin D and carotid thickness
They found that 25-hydroxy vitamin D was inversely associated with both intima-media thickness (=-0.01 per 10-ng/mL increase, p=0.05) and maximal carotid plaque thickness (=-0.10 per 10-ng/mL increase, p=0.03). In a model containing traditional cardiac risk factors and indices of mineral metabolism, 25-hydroxy vitamin D accounted for 13% of the variance in both intima-media thickness and maximal carotid plaque thickness. Calcium, parathyroid hormone, and 1,25-dihydroxy vitamin-D levels were not associated with carotid measures.
"We confirmed prior data showing a relationship of carotid measures with calcium-phosphorus product," Silverberg said. "More important, we found a robust association of vitamin-D levels with subclinical markers of carotid atherosclerosis."
Silverberg pointed out that some of the prior literature in this area did not adequately control for cardiovascular risk factors and renal function, and most of the available data did not account for the interaction of vitamin D with other indices of mineral metabolism.
Asked to comment, Dr Michal Melamed (Albert Einstein College of Medicine, New York) said she was glad the authors looked at multiple bone minerals and not just vitamin D. "The sample size was small, but it is encouraging they still found an association."
Melamed complimented the study but acknowledged more work is needed. "This is a nice study, but it is still cross sectional. We cannot establish a causal relationship, and many questions remain regarding optimum vitamin-D levels."
Melamed says she hopes some of these questions will be answered by the Vitamin D and Omega-3 Trial (VITAL) study. The study is designed to include 20 000 men and women across the US.
Investigators from Brigham and Women's Hospital and Harvard Medical School in Boston, MA are studying whether daily dietary supplements of vitamin D3 or omega-3 fatty acids reduce the risk for developing heart disease, stroke, and cancer in people who do not have a history of these illnesses. Recruitment began in January 2010 and is continuing through 2011.
The Northern Manhattan Study was funded by the National Institute of Neurological Disorders and Stroke. Coauthor Dr Tatjana Rundek (University of Miami Miller School of Medicine, FL) reports receiving speaking fees from Bristol-Myers Squibb. The other authors have disclosed no relevant financial relationships.
Carrelli AL, Walker MD, Lowe H, et al. Vitamin D deficiency is associated with subclinical carotid atherosclerosis: the northern Manhattan study. Stroke 2011; 42:2240-2245.
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