Race/Ethnicity, Serum 25-Hydroxyvitamin D, and Heart Disease

A growing body of observational evidence had suggested that low 25-hydroxyvitamin D (25[OH]D) concentrationsmay be a key biological predictor of increased rates of coronary heart disease (CHD).1Because lowserum25(OH)Dconcentrationsare more common and more severe among racial/ethnic minority groups,which are also affected by higher rates of CHD and CHD risk factors, low vitamin D was being heralded as a potentialmodifiablecontributor to racial/ethnicdisparities incardiovascular health.2 However, the causal link between 25 (OH)D concentrations and CHD remains uncertain.3,4 Additionally, the potential clinical implications of low serum 25(OH)Dconcentrations, thepathologicalmechanismsthrough which vitamin Dmaymodulate CHD, and whether these factors differ across racial/ethnic groups are unclear. Todate, the literatureonvitaminDandCHDhasbeen limited due to larger studies being observational in nature. Randomized interventions are smaller, shorter in duration, and only addressCHDsurrogates. Previous studies have also been inconsistent in defining vitamin D status, in defining and determining cardiovascular outcomes, in the use of baseline 25 (OH)Dconcentrations, and in adjusting for seasonal variations in vitamin D concentrations.1 Further, in an attempt to address racial/ethnic influences on possible vitamin D–related health outcomes, the literature is limited by the lack of detailed patient-level information and adequate numbers of diverse populations. In this issue of JAMA, Robinson-Cohen and colleagues5 conducted a well-designed investigation to assess the associationof serum25(OH)Dconcentrationswith time to first adjudicatedCHDevent acrossmultiple racial groups and to provide information to help unravel the complex associations between race/ethnicity, 25(OH)D, and CHD. The authors analyzed data from 6436 diverse racial/ethnic study participants in a community-based prospective cohort, the Multi-Ethnic Study of Atherosclerosis (MESA). From 2000 to 2002, participants between 45 and 84 years of age without known cardiovascular disease at baseline were enrolled from 6 sites. Detaileddemographic, clinical, and laboratorydatawereobtained and for the present analysis participants had a mean follow-upof8.5 years. Theparticipants included38%white, 28% black, 22% Hispanic, and 12% Chinese individuals who completed detailed interviews including estimated vitamin D intake to complement themeasurement of 25(OH)D concentrations and in-person examinations assessing CHD risk factors. During the follow-up period, 361 study participants developed an incident CHD event (including myocardial infarction, angina, or CHD death). Robinson-Cohenetal estimated the relativehazardofCHD using 3 different Cox proportional hazards regression models. The first model included demographic data; the second model added likely potential confounding variables such as bodymass index, smokingstatus,educationalattainment, family income,physicalactivity,andvitaminDintake;andthethird model addedpossibly confounding ormediating variables including diabetes status, systolic blood pressure, chronic kidney disease, antihypertensive and lipid-lowering medications, cholesterol andtriglyceride levels, andC-reactiveprotein concentrations. In the fully adjusted third model, each 10ng/mL decrement in serum 25(OH)D concentrations was associatedwith a significant 15% greater overall risk of incident CHD. However, the investigators noted substantial differencesamongracial/ethnicgroups regarding theassociationbetween 25(OH)D concentrations and CHD, with a 26% greater risk of incident CHD among white participants and a 76% greater risk amongChinese participants. Unexpectedly, there was no significant association between 25(OH)D concentrations and CHD risk among black or Hispanic participants. In this study the lowestmeanbaselineserum25(OH)Dconcentrationswere found inblackparticipants (19.2ng/mL),moderately low 25(OH)D concentrations in Hispanic (24.6 ng/mL) andChineseparticipants (26.7ng/mL),andadequate levels (≥30 ng/mL) inwhiteparticipants (30.1ng/mL).Basedonthesebaseline findings, itmight be anticipated that if the serumconcentrationof 25(OH)Dwas a strongpredictor of CHD, the relationshipwouldbemostpronounced inblackparticipantswhohad the lowest 25(OH)Dconcentrationsatbaseline.However, these findings did not support the anticipated relationship between low 25(OH)D and increased CHD across all racial/ ethnic groups. Prior studies in nonwhite populations have shown variable findings.4 In a recent 3-month, double-blind, randomized trial of nearly 300 black patients, each 1-ng/mL increase inplasma25-hydroxyvitaminD led to a significant0.2-mmHg reduction in systolic bloodpressure (P = .02), but the studydid not assess CHD events.6 By contrast a double-blind, placebocontrolled study of 90 racial/ethnically diverse patients (ethnicity: 62% Hispanic; race: white 31%, black 18%, Asian 24%, other 27%) with CHD and vitamin D deficiency (<20 ng/mL) found no difference in surrogate markers of cardiovascular health (such as bloodpressure, endothelial function, circulating adhesion molecules, or serum proinflammatory cytokines) amongparticipants receiving 50 000 IUof oral ergocalRelated article page 179 Opinion