MONOCYTE SUBSETS HETEROGENEITY AND CORONARY ATHEROSCLEROSIS IN SOUTH ASIANS COMPARED TO WHITE CAUCASIANS

Abstract

BACKGROUND South Asians (SAs) have an increased prevalence of coronary artery disease (CAD) and myocardial infarction compared with age- and sex-adjusted White Caucasians (WCs). The mechanism for this increased risk is poorly understood. While classical CD14++CD16- monocytes act as independent predictors of cardiovascular disease, differences in the distribution of monocyte subsets between SA and WC have not been established. We aimed to determine if differences exist in monocyte subsets between SAs and WCs at risk for CAD. METHODS AND RESULTS 119 consecutive patients (59 SA, 60 WC) of at least intermediate CAD risk by the INTERHEART score were prospectively enrolled. Patients with history of malignancy, age > 70, GFR < 30 or on dialysis were excluded. A single blood sample was collected for monocyte analysis. Flow cytometry using dual colour fluorescence (CD14, CD16) within the monocyte gate was used to identify monocyte subsets (classical, intermediate, and non-classical) by staff blinded to the individuals’ characteristics. The SA group consisted of 64% males with a mean age of 54 (+/- 9), while the WC group consisted of 55% males with a mean age of 59 (+/- 7). Both groups had similar body mass index, rates of hypertension, dyslipidemia and family history of premature CAD. Compared to WCs, SAs had higher prevalence of diabetes (36% vs. 13%, p = 0.005) and hemoglobin A1C levels (6.0 +/- 1.1% vs. 5.6 +/- 0.6%, p < 0.001). SA patients had a higher proportion (85.3 +/- 10.7% vs. 81.4 +/- 11.0%, p = 0.009) and total level (449.0 +/- 180.4 vs. 388 +/- 127.4, p = 0.010) of classical CD14++CD16- monocytes compared to WCs. There was no difference between the two groups in the proportion of intermediate CD14++CD16+ and non-classical CD14+CD16++ monocytes (see Figure 1). There was no association between diabetes and the proportion of monocyte subsets. Ethnicity had a moderate association with the proportion of classical CD14++CD16- monocytes (Eta coefficient = 0.525) with a large effect size (Eta squared = 27.5%). The association of ethnicity with intermediate CD14++CD16+ and non-classical CD14+CD16++ monocytes was either weak or negligible with minimal to no effect size (see Table 1). CONCLUSION In patients with substantive risk for CAD, SAs had a significantly higher proportion and level of classical CD14++CD16- monocytes compared to WCs. Our findings provide a novel insight into the potential mechanism of increased CAD susceptibility amongst SAs compared to WCs. South Asians (SAs) have an increased prevalence of coronary artery disease (CAD) and myocardial infarction compared with age- and sex-adjusted White Caucasians (WCs). The mechanism for this increased risk is poorly understood. While classical CD14++CD16- monocytes act as independent predictors of cardiovascular disease, differences in the distribution of monocyte subsets between SA and WC have not been established. We aimed to determine if differences exist in monocyte subsets between SAs and WCs at risk for CAD. 119 consecutive patients (59 SA, 60 WC) of at least intermediate CAD risk by the INTERHEART score were prospectively enrolled. Patients with history of malignancy, age > 70, GFR < 30 or on dialysis were excluded. A single blood sample was collected for monocyte analysis. Flow cytometry using dual colour fluorescence (CD14, CD16) within the monocyte gate was used to identify monocyte subsets (classical, intermediate, and non-classical) by staff blinded to the individuals’ characteristics. The SA group consisted of 64% males with a mean age of 54 (+/- 9), while the WC group consisted of 55% males with a mean age of 59 (+/- 7). Both groups had similar body mass index, rates of hypertension, dyslipidemia and family history of premature CAD. Compared to WCs, SAs had higher prevalence of diabetes (36% vs. 13%, p = 0.005) and hemoglobin A1C levels (6.0 +/- 1.1% vs. 5.6 +/- 0.6%, p < 0.001). SA patients had a higher proportion (85.3 +/- 10.7% vs. 81.4 +/- 11.0%, p = 0.009) and total level (449.0 +/- 180.4 vs. 388 +/- 127.4, p = 0.010) of classical CD14++CD16- monocytes compared to WCs. There was no difference between the two groups in the proportion of intermediate CD14++CD16+ and non-classical CD14+CD16++ monocytes (see Figure 1). There was no association between diabetes and the proportion of monocyte subsets. Ethnicity had a moderate association with the proportion of classical CD14++CD16- monocytes (Eta coefficient = 0.525) with a large effect size (Eta squared = 27.5%). The association of ethnicity with intermediate CD14++CD16+ and non-classical CD14+CD16++ monocytes was either weak or negligible with minimal to no effect size (see Table 1). In patients with substantive risk for CAD, SAs had a significantly higher proportion and level of classical CD14++CD16- monocytes compared to WCs. Our findings provide a novel insight into the potential mechanism of increased CAD susceptibility amongst SAs compared to WCs.