Exploring the links of cardiovascular structure and function with biomarkers related to vascular calcification : the African-PREDICT study

Abstract

Motivation Evidence linking the onset of vascular calcification via abnormal mineral metabolism as contributor to the development of cardiovascular disease (CVD) warrants exploring. Vascular calcification is linked to disease states including chronic kidney disease, hypertension and type 2 diabetes mellitus, especially in older populations, while less is known about the potential links of cardiac and arterial structure and function with markers related to vascular calcification in young black and white individuals with no apparent CVD. Aim To explore whether associations of left ventricular relative wall thickness and systolic function exists with biomarkers related to vascular calcification in young South Africans. Methodology This study formed part of the larger African prospective study on early detection and identification of cardiovascular disease and hypertension (African-PREDICT). Cross-sectional data of the first 400 participants which included black (n=160) and white (n=175) men and women after exclusion. Participants who presented with missing variables of interest were excluded from this study. This study obtained the appropriate ethical approval from the Health Research Ethics Committee of the North-West University (NWU-00048-17-S1). Anthropometric measures included body height, weight and waist circumference. Body mass index as well as body surface area were additionally calculated. Blood pressure was measured on the left arm in duplicate whilst participants remained in a rested seating position. The General Electric Vivid E9 device (GE Vingmed Ultrasound A/S; Hearten, Norway) and a 3-lead ECG was used to determine relative wall thickness. Stroke volume was determined and normalised for height in the power of 2.04 as the stroke volume index. By multiplying the stroke volume with heart rate, cardiac index was obtained. Additionally, fractional shortening as well as left ventricular ejection fraction was furthermore determined. We performed biochemical analyses which included a lipid profile (triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol and total cholesterol), gamma glutamyl-transferase, cotinine, high sensitivity C-reactive protein, creatinine, alkaline phosphatase, and calcium. The ratio of total cholesterol to high density lipoprotein cholesterol was additionally calculated. Glutathione peroxidase, a marker of oxidative stress was determined in whole blood and one of the measurable, reactive oxygen species (serum peroxides) was determined in serum. We performed independent T-tests and Chi-square tests to compare means and proportions. Single and multiple regression analyses were performed to investigate the associations of cardiac structure (relative wall thickness) and function (ejection fraction, fractional shortening, systolic index and cardiac index) with markers of vascular calcification (alkaline phosphatase and calcium). Results When comparing the black and white groups, we found that the black group presented with higher blood pressure measures, relative wall thickness as well as alkaline phosphatase (all p≤0.001). In single and multivariate regression analyses, after adjusting for age, sex and body mass index (stroke index additionally adjusted for waist circumference), positive associations of relative wall thickness and alkaline phosphatase existed in the black group only (adj. R²=0.030; β=0.176; p=0.037). Ejection fraction (adj. R²=0.083; β=–0.208; p=0.015) and fractional shortening (adj. R²=0.103; β=–0.195; p=0.021) associated inversely with alkaline phosphatase in the white group. Cardiac index associated inversely with calcium in both the black (adj. R²=0.096; β=–0.181; p=0.031) and white (adj. R²=0.403; β=–0.141; p=0.021) groups. Stroke index associated inversely with calcium in the black (adj. R²=0.165; β=–0.161; p=0.046) and white (adj. R²=0.353; β=–0.147; p=0.019) groups as well as alkaline phosphatase (adj. R²=0.354; β=–0.172; p=0.016) in the white group only. Conclusion Our results indicate that in young apparently healthy populations, cardiac structure (relative wall thickness) and function (systolic function markers) associated with markers of vascular calcification (alkaline phosphatase and calcium). Thus, an altered mineral metabolism may contribute to early vascular calcification manifestations and promote premature cardiac compromise. The different associations seen in the black versus the white group may suggest different mechanisms at play for the onset of vascular calcification in younger participants. These findings need to be confirmed in larger prospective studies.