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Low vitamin D effects on CHD risk vary by race

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Study adds important insights

The findings by Dr. Robinson-Cohen and her colleagues in their "well-designed investigation," which helps to "unravel the complex associations between race/ethnicity, 25(OH)D, and CHD," also raise important questions about those associations, Dr. Keith C. Norris and Dr. Sandra F. Williams wrote in an editorial.

These include questions about whether seasonal variability in concentrations might vary across racial and ethnic groups and influence previously reported findings (unlikely, based on the findings, they said); whether racial ethnic differences in those associations may be driven by differential regulation of parathyroid hormone (though not addressed in the study, this remains plausible based on previous findings, they noted); and whether racial and ethnic variations in vitamin D–mediated cellular activation/metabolism might contribute to the observed differences (JAMA 2013;310:153-4).

With regard to the third question, the data from the study raise the possibility that differences in up- or down-regulation of key pathways may underlie the racial and ethnic differences observed in the MESA cohort.

The study adds important insights about race/ethnicity, 25[OH]D concentrations, and CHD risk, they said, adding that "the heterogeneity of the findings underscores the importance of further exploring racial differences in clinical research and of not immediately generalizing results from ethnically homogeneous populations to other groups that may differ by race/ethnicity, sex, or age."

Dr. Norris is with the University of California, Los Angeles, and Dr. Williams is with Florida Atlantic University, Boca Raton, Fla. Dr. Norris reported receiving grant support from the National Institutes of Health, and payment for lectures and consulting from Abbott, Amgen, Davita, and Takeda. Dr. Williams reported having no relevant financial disclosures.


 

FROM JAMA

Associations between serum 25-hydoxyvitamin D concentration and coronary heart disease vary by race, according to findings from the Multi-Ethnic Study of Atherosclerosis (MESA).

Of 6,436 participants in the community-based, prospective cohort study, 361 experienced an incident CHD event during a median of 8.5 years of follow-up. A low baseline serum 25-hydroxyvitamin D (25[OH]D) level was associated with a greater risk of an event in 167 white participants (hazard ratio, 1.26 per 10-ng/mL decrement) and in 27 Chinese participants (HR, 1.67 per 10-ng/mL decrement), but not in 94 black participants or 73 Hispanic participants (HR, 0.93 and 1.01 per 10-ng/mL decrement), Cassianne Robinson-Cohen, Ph.D., of the University of Washington, Seattle, and her colleagues reported online July 9 in JAMA.

©Kaspri/Fotolia.com

Associations between serum 25-hydoxyvitamin D concentration and coronary heart disease vary by race, according to findings from the Multi-Ethnic Study of Atherosclerosis (MESA).

"Differences in associations across race/ethnicity groups were consistent for both a broad and restricted definition of CHD and persisted after adjustment for known CHD risk factors," the investigators said.

The findings require confirmation, but suggest that until such confirmation is available, the results of studies evaluating the effects of 25(OH)D in ethnically homogeneous populations should not be extrapolated to other racial or ethnic populations, the investigators said, noting that a low 25(OH)D level has consistently been linked with CHD in study populations composed largely or entirely of white subjects, but that the association has not been studied rigorously in other populations (JAMA 2013;310:179-88).

Study subjects were adults aged 45-84 years (mean, 62 years) who were free of known cardiovascular disease and who were recruited between July 2000 and September 2002. The subjects were followed via telephone every 9-12 months to assess for myocardial infarction, angina, cardiac arrest, or CHD death. Diagnoses were confirmed via death certificates and/or medical record review.

As for possible explanations for the racial and ethnic differences observed in this study, the data suggest that biologic differences account for much of the heterogeneity, the investigators said, explaining that although "results were robust ... we are unable to discern characteristics that could conceivably cause differential confounding by race, and chance findings are unlikely – at least for black vs. white comparison – due to reasonable numbers of events in each race."

Additionally, the lack of any trend toward association in blacks, the statistically significant global and black vs. white P values for interaction, and the fact that findings of studies looking at the associations of 25(OH)D with other health outcomes also support differing associations by race, support a biologic explanation, they said.

The findings in Hispanic and Chinese populations in this study, however, should be interpreted with caution, because the sample sizes for these groups were relatively small, and the number of events was low; additional studies of 25(OH)D and health outcomes are needed in these populations, they said.

Though limited by potential confounding (many unhealthy characteristics are linked with lower 25[OH]D concentrations) and by low power for detecting associations of small magnitude within individual racial and ethnic groups, the findings are bolstered by the large multiethnic population; the evaluation of adjudicated incident CHD events over a relatively long follow-up time; the use of an accurate assay for measuring 25(OH)D; and careful, high-quality approaches to measuring 25(OH)D.

In addition to studies to confirm these findings, well-powered clinical trials are also needed to evaluate the effects of vitamin D supplements on CHD risk, the investigators said, noting that at least five such trials are currently underway, including one (the Vitamin D and Omega-3 Trial, or VITAL) that is targeting enrollment of a large multiracial study population.

The current study was funded by grants from the National Heart, Lung, and Blood Institute. Dr. Robinson-Cohen reported having no relevant financial disclosures, but other study authors reported receiving grant funding, travel accommodations, and/or payment for lectures from the National Institutes of Health, Amgen, and/or Abbott Laboratories.

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