Abstract

Objective: Cardiovascular disease (CVD) remains the major contributor to premature death globally, with black populations presenting with a disproportionate burden of CVD and early target organ damage. Renin angiotensin system dysregulation is a key factor involved in hypertension development and organ damage in black populations. Angiotensin converting enzyme 2 (ACE2) counteracts the deleterious effects of angiotensin II, and increased circulating ACE2 predicts cardiovascular events and mortality in the general population, and in patients with CVD. However, the role of ACE2 activity as a cardiovascular risk marker in young healthy individuals remains largely unclear. We explored ethnic and sex differences in ACE2 activity and associations between blood pressure (BP), left ventricular mass index (LVMi) and ACE2 activity in young healthy black and white adults. Design and method: We included 1134 black (men, N = 280; women, N = 285) and white (men, N = 277; women, N = 292) participants aged 20–30 years. The participants were normotensive at screening (BP≦140/90 mmHg) with no known CVD. Ambulatory systolic and diastolic BP were recorded and LVMi (m2.7) was obtained from echocardiography and plasma ACE2 activity measured using a validated assay. Results: Overall, mean plasma ACE2 activity was higher in black [1.33 pmol/min/ml (0.02; 19.6)] than in white [0.73 pmol/min/ml (0.02; 12.5)] participants, and higher in men [3.63 pmol/min/ml (0.02; 20.5)] than in women [0.28 pmol/min/ml (0.02; 9.87)] (both P < 0.001). When comparing ethnic groups according to sex, ACE2 activity was higher in black men and women than in white men and women (both P ≦ 0.012). After adjustments for covariates (ethnicity, sex, age, body mass index, socioeconomic status, physical activity, glucose, low density lipoprotein cholesterol, C-reactive protein, alcohol intake and smoking), 24-hour systolic BP was positively associated with ACE2 activity in the total group (R2 = 0.43; β=0.07; P = 0.019) and black men (R2 = 0.19; β=0.18; P = 0.007). There were no independent associations of diastolic BP and LVMi with ACE2 activity in any of the groups. Conclusions: 24-hour systolic BP was independently and positively associated with ACE2 activity in the total group. When stratifying the group according to ethnicity and sex, a similar association was evident in black men, a group previously identified to be at high cardiovascular risk. The observed ethnic and sex differences in ACE2 activity and associations with BP suggest that ACE2 may be a useful biomarker in cardiovascular risk profiling in young populations.

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