This nested case-control study found that a vitamin D deficiency has been associated with twice the risk of a myocardial infarction over a decade for men with undiagnosed coronary disease.

by Judith Groch, Contributing Writer, MedPage Today

BOSTON, June 9 — A vitamin D deficiency has been associated with twice the risk of a myocardial infarction over a decade for men with undiagnosed coronary disease at baseline, a nested case-control study found.

Action Points 
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Explain to interested patients that although this study found low levels of vitamin D in men were linked to an increased risk of heart attack over 10 years, it is not clear whether the relationship is causal.

Men with intermediate levels of the vitamin had a 60% increased MI risk, epidemiologist Edward Giovannucci, M.D., Sc.D., of the Harvard School of Public Health, and colleagues reported in the June 9 issue of the Archives of Internal Medicine.

Studies have shown that deaths from cardiovascular disease rise at higher latitudes, increase during the winter months, and are lower at high altitudes, the investigators wrote.

This pattern is consistent with an adverse effect of low vitamin D which is more prevalent at higher latitudes, during the winter, and at lower altitudes, said Dr. Giovannucci and colleagues.

To determine whether plasma 25-hydroxyvitamin D concentrations are associated with risk of coronary heart disease, the researchers undertook the nested case-control study of 18,225 men in the Health Professionals Follow-up Study.

Only 23% of the men in this study had vitamin D levels considered normal (at least 30 ng/mL). This percentage is typical of many populations, and deficiency is even higher in dark-skinned individuals and elderly persons.

The men (ages 40 to 75) were free of diagnosed cardiovascular disease at blood collection. The blood samples were returned from April 1, 1993 to Nov. 30, 1999 with 99% received by Nov. 30, 1995.

During 10 years of follow-up, 454 men developed nonfatal myocardial infarction or fatal coronary heart disease.

These men were matched (2:1 ratio) with records and blood samples from 900 living men with no history of cardiovascular disease. Age, smoking status, diet, and lifestyle factors were recorded from self-administered questionnaires.

After adjustment for matched variables, men deficient in vitamin D (15 ng/mL or less) had 2.42 times the risk for MI compared with those with ≥30 ng/mL (relative risk 2.42, 95% confidence 1.53 to 3.84, P< 0.001 for trend).

This relationship remained significant (RR, 2.09, 95% CI 1.24 to 3.54, P=0.02 for trend), even after additional adjustment for family MI history, BMI, alcohol consumption, physical activity, history of diabetes and hypertension, ethnicity, region, marine omega-3 intake, low and high-density lipoprotein cholesterol levels, and triglyceride levels.

Even men with intermediate vitamin D levels of 22.6 to 29.9 ng/mL) had a greater risk compared with those with sufficient levels: RR 1.60, 95% CI 1.10 to 2.32.

The association was suggestively stronger for fatal coronary heart disease, but the number of cases was too small for definitive conclusions, the researchers said.

Individuals in sun-rich environments, where clothing or cultural practices do not appreciably limit vitamin D production, often reach vitamin D levels of 54 to 90 ng/mL.

Because vitamin D levels are largely affected by sun exposure, it is possible that some other consequences of sun exposure other than vitamin D production are responsible for the observed association with MI, the researchers said.

Although alternative explanations are possible, a variety of plausible biological mechanisms support a role for vitamin D.

The vitamin affects vascular smooth-muscle cell proliferation,

inflammation, a cytokine profile that favors inflammation, vascular calcification, and blood pressure through the renin-angiotensin system, all of which affect the risk for cardiovascular disease and MI, the researchers wrote.

Other possible mechanisms include vitamin D deficiency possibly combined with low calcium intake, which has been associated with impaired fasting glucose and possibly a risk of diabetes, all risks associated with cardiovascular disease.

Vitamin D deficiency has been related to an increasing number of conditions and to total mortality. These results further support an important role for vitamin D in MI risk, the investigators said.

If the association between vitamin D deficiency and MI risk is causal, which remains to be established, the amount of vitamin D required for optimal benefit may be much higher than would be provided by current recommendations (200-600 IU/d), especially for those with minimal sun exposure, they said.

To increase circulating levels of vitamin D from 12 to 35.5 ng/mL would require approximately 3,000 IU of vitamin D daily. A glass of milk has approximately 100 IU, so that those who achieve 35 ng/mL do so largely through sun exposure.

Thus, the present findings “add further support to the belief that the current dietary requirements of vitamin D need to be increased to have an effect on circulating vitamin D levels substantially large enough for potential health benefits,” the investigators said.

Dr. Giovannucci reported no financial conflicts. This study was supported by grants from the National Cancer Institute and the National Heart, Lung, and Blood Institute.


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Primary source: Archives of Internal Medicine

Source reference: Giovannucci E, et al “25-hydroxyvitamin D and risk of myocardial infarction in men: A prospective study” Arch Intern Med 2008; 168: 1174-1180.

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

Published: June 09, 2008

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