Cardiovascular risk and kidney function profiling using conventional and novel biomarkers in young adults: the African-PREDICT study.

BACKGROUND: Low- and middle-income countries experience an increasing burden of chronic kidney disease. Cardiovascular risk factors, including advancing age, may contribute to this phenomenon. We (i) profiled cardiovascular risk factors and different biomarkers of subclinical kidney function and (ii) investigated the relationship between these variables. METHODS: We cross-sectionally analysed 956 apparently healthy adults between 20 and 30 years of age. Cardiovascular risk factors such as high adiposity, blood pressure, glucose levels, adverse lipid profiles and lifestyle factors were measured. Various biomarkers were used to assess subclinical kidney function, including estimated glomerular filtration rate (eGFR), urinary albumin, uromodulin and the CKD273 urinary proteomics classifier. These biomarkers were used to divide the total population into quartiles to compare extremes (25th percentiles) on the normal kidney function continuum. The lower 25th percentiles of eGFR and uromodulin and the upper 25th percentiles of urinary albumin and the CKD273 classifier represented the more unfavourable kidney function groups. RESULTS: In the lower 25th percentiles of eGFR and uromodulin and the upper 25th percentile of the CKD273 classifier, more adverse cardiovascular profiles were observed. In multi-variable adjusted regression analyses performed in the total group, eGFR associated negatively with HDL-C (ß= -0.44; p < 0.001) and GGT (ß= -0.24; p < 0.001), while the CKD273 classifier associated positively with age and these same risk factors (age: ß = 0.10; p = 0.021, HDL-C: ß = 0.23; p < 0.001, GGT: ß = 0.14; p = 0.002). CONCLUSION: Age, lifestyle and health measures impact kidney health even in the third decade.

Arterial structure and function in Africans with HIV for > 5 years: longitudinal relationship with endothelial activation and cardiovascular risk markers.

OBJECTIVES: We aimed to determine whether people with human immunodeficiency virus (PWHIV) have increased measures of arterial injury [carotid intima-media thickness (cIMT)] and large artery stiffness [carotid-femoral pulse wave velocity (cfPWV)] when compared with their counterparts without HIV, and whether baseline markers of endothelial activation and cardiovascular risk are associated with cIMT and cfPWV after 5 years. METHODS: We matched 126 PWHIV from North West Province, South Africa, to 126 without HIV according to age, sex and locality. Cardiovascular risk and endothelial function markers [soluble intracellular adhesion molecule (ICAM-1) and soluble vascular cell adhesion molecule (VCAM-1)] were measured at baseline and cIMT and cfPWV at follow-up. RESULTS: This study included 21.4% men. The use of antiretroviral therapy (ART) increased from 44.1% at baseline to 81.4% at follow-up. At follow-up, cIMT (P = 0.90) and cfPWV (P = 0.35) were similar in the groups. Despite elevated ICAM-1 and VCAM-1 in the PWHIV (all P < 0.001) at baseline, these markers did not associate with cIMT and cfPWV after 5 years. In multivariable-adjusted regression analysis, cIMT associated positively with age (ß = 0.31, P = 0.002) and triglyceride: high-density lipoprotein-cholesterol (ß = 0.23, P = 0.016) in PWHIV. Mean arterial pressure (MAP) (ß = 0.28, P = 0.010) associated positively with cfPWV in the PWHIV. In the people without HIV, sex (ß = 0.31, P = 0.004) and glycated haemoglobin (HbA1c) (ß = 0.24, P = 0.026) associated with cIMT while age (ß = 0.17, P = 0.049), sex (ß = 0.29, P = 0.003), MAP (ß = 0.31, P = 0.001) and HbA1c (ß = 0.21, P = 0.041) associated positively with cfPWV. CONCLUSIONS: Measures of arterial structure and function were similar in Africans with HIV and their age, sex and locality matched controls. Traditional cardiovascular risk markers rather than elevated endothelial activation at baseline were independently associated with cIMT and cfPWV over 5 years.

Quantification of systemic renin-angiotensin system peptides of hypertensive black and white African men established from the RAS-Fingerprint®.

OBJECTIVE: The objective of this study was to make use of a quantitative and qualitative approach comparing the systemic renin-angiotensin system (RAS) of hypertensive black and white African men by using RAS equilibrium analysis. MATERIALS AND METHODS: This sub-study involved 23 black (n = 15) and white (n = 8) hypertensive men aged 39.5-41 years, living in the North West Province of South Africa. The RAS-Fingerprinting was determined with LC-MS/MS quantification of angiotensin peptides. Blood pressure and other variables were determined with known methods. RESULTS: The main finding of this study was the significant lower Ang I (<5.0 and 45.1 pg/ml; p = 0.005) and Ang II (15.6 and 123.9 pg/ml; p ⩽ 0.001) encountered in the hypertensive black African men compared to their white counterparts. Levels of Ang 1-5 (downstream metabolite of Ang 1-7) (1.8 and 3.0 pg/ml), were detected in black and white hypertensive men, respectively. CONCLUSIONS: The observed differences between circulating RAS components, which are reflected via equilibrium angiotensin levels, point to a distinctive molecular regulation of the RAAS in the two study cohorts. The increased peripheral resistance observed in hypertensive black individuals might take over a dominant role in control of blood pressure in this study population. A novel highly sensitive LC-MS/MS method resolved the issue of peptide recovery variations during sample preparation by using internal standards for each individual angiotensin metabolite.