Racial differences in the burden of coronary artery calcium and carotid intima media thickness between Blacks and Whites

Our data from more than 1,200 participants in a study of racial disparities in CVD indicate that Black race is associated with higher CIMT but less CAC than White race. These associations were independent of traditional CVD risk factors. Of the novel CVD risk factors that were investigated, sdLDL was found to be significantly associated with CIMT but not with CAC. Interleukin-6 concentration was significantly associated with higher CAC in Blacks, and trended in the same direction in Whites.

Racial differences in the burden of subclinical atherosclerosis, which is a surrogate marker of CVD, have been previously reported [6, 10, 18‐21]. For instance, Kanaya et al. compared US Asians in the MASALA study with Whites, African Americans, Latin Americans and Chinese Americans in the MESA study. They found that South Asians and Whites have similar CAC scores, but that their CAC scores were higher than those in the other ethnic groups, including African Americans [31]. Our findings of higher CAC burden in Whites than Blacks are consistent with their report. Moreover, our study complements previous studies on the topic because we concomitantly investigated CIMT and CAC in a racially diverse study population and determined their associations with both conventional and novel CVD risk factors. Our study confirms significant inter-racial differences in CIMT and CAC, and reports their correlations with traditional and novel CVD risk factors. The present report builds on our previous work that demonstrated a difference in CAC burden between Blacks and Whites [7, 9] in that we studied CIMT, in addition to CAC, and were able to assess their associations with race and several novel inflammatory markers.

In our study, higher levels of IL-6 were associated with a greater burden of CAC in Blacks, and showed a trend in Whites. Also, higher levels of sdLDL concentrations were significantly associated with greater burden of CIMT in both Blacks and Whites. Of note, this association appeared stronger in Blacks than Whites (adjusted odds ratio = 1.7 versus 1.4), but the difference was not statistically significant. Compared with large buoyant LDL particles, sdLDL particles have increased penetration into the arterial wall and increased susceptibility to oxidation. Hence sdLDL is believed to be more pro-atherogenic than larger LDL particles [32]. Similarly, inflammation is known to play an important role in the progression of atherosclerotic plaque [33, 34]. For example, recent genetic studies have shown IL-6 to be a likely causal factor in CVD [35]. In our study, we found that sdLDL and IL-6 were associated with CIMT and CAC, respectively. Given the higher burden of CIMT and lower burden of CAC in Blacks, one would expect higher levels of sdLDL and lower levels of IL-6 in Blacks compared with Whites. However, our findings demonstrate the opposite; Blacks had significantly lower levels of sdLDL and higher levels of IL-6. This is likely because CAC and CIMT are multifactorial surrogates of CVD that are determined by the interaction of several variables, besides sdLDL and IL-6 concentrations. In addition, the concentrations sdLDL and IL-6 in blood may influence other characteristics of CAC and CIMT, such as ‘plaque vulnerability’ (see below). We also found that sICAM-1 and CD40L were not associated with either CIMT or CAC, in keeping with previous studies showing lack of association of these novel risk markers with CVD [25, 33].

Coronary artery calcium burden has been shown to be a predictor of CVD risk [11, 15, 16]. Therefore, it is surprising that Blacks, who have higher rates of stroke and CVD mortality than Whites, have lower burdens of CAC than Whites as reported in previous epidemiological studies [10, 19‐21]. Our study similarly found a substantially lower burden of CAC in Blacks compared with Whites. One proposed hypothesis for this paradoxical observation is that the level of CAC may not only be determined by traditional CVD risk factors, but also by certain aspects of calcium and vitamin D metabolism [36, 37]. For instance, Blacks as a group, have lower levels of vitamin D than Whites [38, 39]. Regardless of the mechanistic explanation for the lower calcium scores in Blacks, it is apparent that the use of the currently accepted cut-offs of CAC scores to predict CVD risk are more relevant to Whites than Blacks. On the other hand, the generally higher concentrations of inflammatory mediators (e.g., hsCRP, IL-6) observed in Black participants in our study, and the established role of inflammation in atherosclerotic plaque instability [40‐42], suggests that the increased risk of CVD in Blacks may be related to higher plaque vulnerability of less calcified coronary lesions. Therefore, our data support previous suggestions that Agatston score cut-offs for risk categories are most clinically relevant if defined separately by race [43, 44]. Additional data from large prospective studies that measure CAC, CVD risk factors, and incident CVD outcomes concomitantly in both Blacks and Whites would be required to establish such cut-points. The determination of such ethnicity-specific cut-points may improve CVD risk stratification and preventive measures.

As with CAC, CIMT is a widely accepted indicator of CVD risk and has been shown to predict future risk of stroke and coronary events [8, 12‐14]. In contrast to overall lower levels of CAC in Blacks compared with Whites, several studies, including ours, have demonstrated higher burden of CIMT in Blacks than Whites [6, 18]. These Black-White differences in CIMT have also been observed in children and adolescents, indicating that it is less likely to be explained by traditional CVD risk factors such as smoking [24]. A recent meta-analysis of eight observational studies showed that a 0.1 mm higher CIMT was associated with about a 15 % higher risk of CVD [8]. The mean racial difference in CIMT in our study was only 0.03, and the mean CIMT among Whites was greater than previously reported (0.81 vs. 0.75 mm) [17]. However, a substantial proportion of Blacks had CIMT >1 mm, compared with Whites, suggesting that the majority of the inter-racial disparity in CIMT may exist at the higher end of the spectrum. This finding supports the need for large prospective epidemiological studies of CVD outcomes to assess race-specific algorithms of CIMT as a predictor of CVD risk.

The strengths of the current study merit consideration. First, the study assessed CIMT and CAC in a general population composed of two races (Blacks and Whites), thereby allowing better characterisation of their relationships with race. Second, with >700 participants in each subset, the study was adequately powered to assess associations between race and subclinical atherosclerosis. Third, we had available data on a range of traditional and novel CVD risk factors thereby enabling detailed exploration of their role in the observed associations.

Our study also has a number of limitations. First, only a subset of our subjects had available data on both CIMT and CAC. Hence the separate analyses performed on CIMT and CAC were not directly comparable. However, sensitivity analyses of 327 participants with information on both CIMT and CAC yielded similar results. Second, the cross-sectional nature of our study limits the degree of inference that may be drawn. Third, due to lack of tabulation of ‘hard’ CVD outcomes, it is not possible to make specific recommendations of race-specific algorithms for characterising incident CVD risk using CIMT and CAC. Finally, we did not investigate certain aspects of inter-ethnic differences in cardiac variables, such as differences in cardiac morphology, which may influence CVD outcomes [45].

In conclusion, the current study provides evidence that Black race is associated with greater CIMT but less CAC than White race independent of conventional CVD risk factors. Small-dense LDL was associated with significant CIMT in both races, while IL-6 was associated with significant CAC burden in Blacks. The results suggest that additional studies are needed to develop race-specific algorithms for CVD risk stratification strategies that incorporate measures of subclinical atherosclerosis.