Left ventricular diastolic function and its relationship with the renin-angiotensin-aldosterone system and amino-terminal prohormone B-type natriuretic peptide: the African-PREDICT study

Abstract

Motivation: The association of left ventricular (LV) diastolic function markers with the renin-angiotensin-aldosterone system (RAAS) and amino-terminal prohormone B-type natriuretic peptide (Nt-proBNP) in older and diseased populations are known. Our study was motivated by the lack of evidence in young, healthy adults regarding the associations of LV diastolic function markers with the RAAS and Nt-proBNP to establish early manifestations of cardiovascular compromise. Aim: To compare the cardiovascular characteristics along with the RAAS and Nt-proBNP levels, as well as to explore the associations of LV diastolic function with the RAAS and Nt-proBNP in young apparently healthy black and white South Africans. Methodology: Cross-sectional data of the first 400 participants (age between 20—30 years) from the African prospective study on the early detection and identification of cardiovascular disease and hypertension (African-PREDICT) was used in this sub-study. Participants with missing data (n=55), as well as individuals with identified left or right bundle branch block (n=9) were excluded. This study obtained approval from the Health Research Ethics Committee of the North-West University (NWU-00032-17-A1) and complied with the Declaration of Helsinki (2008). Ambulatory blood pressure was measured along with a 12-lead electrocardiogram. A standard transthoracic echocardiography procedure was followed, to acquire variables of LV diastolic function including: E/A (peak early filling E-wave/late diastolic filling A-wave) ratio, E/é (mitral peak velocity of early filling/early diastolic mitral annular velocity) ratio, left atrium to aortic root ratio (LA/Ao) and LV end-diastolic volume. Anthropometric measurements included body height and weight, while body mass index and body surface area were additionally calculated. Among other biomarkers, renin, prorenin, aldosterone and Nt-proBNP were analyzed. Results: Age and body composition were lower in the black group (all p<0.005) compared to the white group. Blood pressures were comparable between the groups. The LV end diastolic volume was lower in the black (p<0.0001) compared to the white group. The E/A and E/e' ratios were higher in the black (both p<0.05) compared to the white group, whereas heart rate and the LA/Ao ratio were similar in both groups. Total renin was higher in the black group (p=0.010), whereas aldosterone and Nt-proBNP were lower in the black group (all p<0.005) compared to the white group. In multiple regression analysis with covariates age, sex, body surface area (except for LV end-diastolic volume), systolic blood pressure, heart rate, gamma-glutamyl-transferase, C-reactive protein, cotinine, total cholesterol-to-high density lipoprotein cholesterol ratio, estimated glomerular filtration rate and activity energy expenditure the following associations were found. The E/A ratio associated positively with prorenin in the black group (adj. R2=0.201; β=0.15; p=0.049) and total renin in the white group (adj. R2=0.131; β=0.16; p=0.042), whereas the LA/Ao ratio associated positively with prorenin (adj. R2=0.050; β=0.18; p=0.032) in the white group only. No associations were evident between markers of LV diastolic function and Nt-proBNP in either group. General conclusion: In conclusion, our study indicated that diastolic function markers associated adversely with components of the RAAS, in both groups. Our findings may indicate that higher E/A and LA/Ao ratios may be attributed to potential changes in the RAAS. This may suggest that both groups are prone to premature RAAS modifications, probably due to lifestyle risk factors, which may lead to future diastolic dysfunction.