Our study demonstrates that differences in CAC scores between AAs and Whites reported in the general population persist in patients with type 2 diabetes. The difference was more striking in men than women, in whom adjustment for metabolic factors, particularly TG, tended to attenuate the racial difference. Overall, in this type 2 diabetes sample, CAC scores were ~80% lower in AA compared to Whites. Thus, there was no evidence that the type 2 diabetes state attenuated racial differences in CAC scores.
Our findings in type 2 diabetes confirm work in population-based epidemiologic studies of ethnic differences in coronary calcification. The Multi-Ethnic Study of Atherosclerosis (MESA), the largest population-based study to date of CAC in different ethnic groups, reported higher CAC scores in Whites (N
= 2619) compared to African-Americans (N
= 1898) in both genders [9
]. Similar findings were reported by Lee et al. who described an almost two-fold increase in CAC in Whites of both genders in a relatively young sample aged 40–45 years [11
] and Hatwalkar et al. in an asymptomatic, physician-referred minority population which was age- and gender-matched with a control White population [21
In contrast, the Dallas Heart Study [13
] and Coronary Artery Risk Development in Young Adults (CARDIA) [15
] study reported no racial differences in CAC. The Dallas Heart Study was a population-based study in which AAs were oversampled (N
= 761) to achieve 50% representation. Type 2 diabetes was present in 13.7% of the sample (17.3% AA and 7.4% White). No differences in the prevalence or severity of CAC were found. CARDIA also failed to detect any significant racial differences in CAC, although this analysis was conducted in a relatively young population (mean age 35 years) with low prevalent CAC. Notably, in our analysis of patients with type 2 diabetes, significant racial differences were not apparent in subjects aged less than 45, it will be interesting to see if racial differences emerge in later CARDIA study visits.
There are very little published data on the relationship between race and CAC in patients with type 2 diabetes. The PREDICT study, one of the largest studies evaluating CAC in patients with type 2 diabetes recruited only White and Asian subjects and excluded Afro–Caribbean patients due to the low CHD event rate in this population in the United Kingdom [8
]. We demonstrate that differences between AAs and Whites in CAC persist, despite the strong independent and potential race-differential effect of type 2 diabetes on CAC and its progression [2
]. Notably, patients in our study had well controlled type 2 diabetes with median HbA1c
of 6.7–7.0%. This contrasts with other studies of CAC in patients with type 2 diabetes without clinical cardiovascular disease in which mean HbA1c
ranged between 8.1 and 8.2% [22
]. It is possible that the racial difference may be less marked in patients with worse glycemic control, if the effect of diabetes is indeed more significant in AAs than in Whites.
The association between lower CAC scores and AA race tended to be less robust in women than in men, although not statistically different. Furthermore, the association in women, but not men, was partially attenuated by adjustment for traditional and metabolic-adipose risk factors. Other studies have suggested no differences in CAC scores between AA and White women [12
] and even increased odds of CAC in AA women [10
]. The reasons for potential gender differences are not clear but could simply relate to sample size and power. However, our findings raise the possibility that metabolic factors might be more important contributors to CAC development in women than in men, at least in type 2 diabetes. However, larger population studies in the general population as well as in type 2 diabetes will be required to address this hypothesis.
The etiology of racial heterogeneity in CAC remains unclear. Traditional and novel risk factors do not appear, for the most part, to account for the differences [10
]. Race heterogeneity is true also for extracoronary vascular calcification [24
], suggesting a systemic difference in its regulation across race. Vascular calcification is a complex, highly-regulated process determined, in part, by interaction between bone and vasculature [25
]. Animal models have demonstrated a role for osteoprotegerin (OPG), a decoy receptor for receptor activator for nuclear factor κB ligand (RANKL), in inhibiting vascular calcification. In humans, serum OPG was associated with CAD in patients with and without diabetes [26
]. Other factors such as the calcium inhibitors matrix Gla proteins, osteopontin and fetuin-A and phosphorus have also been associated with CAC. However, racial differences have been demonstrated only for OPG, in a study of peripheral arterial disease [27
]. A relationship between bone and vascular calcification is further supported by the inverse relationship between 25-hydroxyvitamin D and incident CAC [28
]. In fact, racial differences in this hormone might contribute to racial heterogeneity in vascular calcification and bone diseases. Larger studies incorporating epidemiologic and genetic data are necessary to elucidate the factors influencing CAC and how they differ between AAs and Whites.
Remarkably, despite lower prevalence of CAC, AAs have higher rates of fatal CVD events. While disparities in treatment and access to care may account for some of the difference, there may also be underlying biological factors. Increased CAC in Whites might represent an increase in total burden of atherosclerosis, but could alternatively reflect greater calcification of similar or even lesser degrees of atherosclerosis relative to that found in AAs. While CAC serves as a surrogate for the extent of atherosclerotic plaque and predicts CVD events in AAs and Whites, it provides no information about the stability of the plaque. Non-calcified lipid plaque, which is more prone to rupture, might be more frequent in AA patients, thus, accounting for higher rates of CVD despite lower CAC scores. Alternatively, increased hypertension in AAs may lead to increased vascular stiffness and diastolic dysfunction with clinical CVD complications unrelated to atherosclerosis or coronary calcification. These hypotheses require further investigation.
Our study is the first conducted exclusively in a sample with type 2 diabetes with significant representation of both Whites and AAs. It does, however, have several limitations. It is a cross-sectional study and therefore, conclusions about causality cannot be made. CAC is also a surrogate measure of CVD, although its clinical predictive value and correlation with angiographic data have been well documented. We did not investigate the racial differences in CAC in a comparison group without diabetes. Although we did not measure novel biomarkers and genetic variation that might account for differences in rates of vascular calcification, our study did provide information on multiple lipoprotein, metabolic, adipose and inflammatory CVD risk markers and their influence on racial differences in CAC.
We report that racial differences in CAC observed in the general population are also strikingly present in patients with type 2 diabetes. The protective relationship in African-Americans tended to be more robust in men than in women. Further research is required to elucidate what factors account for this difference and why lower CAC scores do not translate into better CVD outcomes in AAs.