Left ventricular structure and urinary metabolomics in young adults: the African- PREDICT study
Motivation - African populations are more prone to the development of left ventricular structure abnormalities and dysfunction, however limited information exists on potential metabolic pathways contributing to early left ventricular structural changes. Consequently, the importance of identifying possible metabolomic markers in association with left ventricular mass in the youth is vital for future prediction and prevention of hypertension-related organ damage. To the best of our knowledge, no studies have been done to determine the relationship of left ventricular mass with urinary metabolomics in 20-30 year-old black and white populations from South Africa. Aim - We aimed to investigate the metabolomic profiles and identify possible metabolites associated with left ventricular mass index in young black and white South African adults. Methodology - This cross-sectional study formed part of the larger African prospective study on early detection and identification of cardiovascular disease and hypertension (African-PREDICT). We included 20-30 year-old normotensive black (N=80) and white (N=80) participants from the African-PREDICT study, with complete data on urinary metabolomics and echocardiography. This substudy was approved by the Health Research Ethics Committee of the North-West University (NWU-00029-18-S1) and adhered to all applicable requirements according to the revised Declaration of Helsinki for investigation on human participants. Questionnaires included a General Health and Demographic Questionnaire and a 24-hour dietary recall questionnaire. Anthropometric measurements included body height and weight to calculate body mass index, as well as waist circumference. Body surface area was additionally calculated. Twenty-four-hour ambulatory blood pressure (ABPM) was determined with a 24-hour ABPM and electrocardiogram (ECG) apparatus (CardXplore, Meditech, Budapest, Hungary). An appropriately sized cuff was used on the non-dominant arm to measure blood pressure in 30-minute intervals during the day, and hourly during night-time. A standard transthoracic echocardiogram was performed by a clinical technologist using the General Electric Vivid E9 device (GE Vingmed Ultrasound A/S, Horten, Norway) to determine left ventricular dimensions for calculating left ventricular mass. Basic biochemical analyses included serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, high sensitivity C-reactive protein, total serum protein, creatinine and sodium fluoride plasma glucose. Cotinine, total glutathione and creatine kinase-MB (muscle/brain) analyses were also included. Urinary metabolites were measured using nuclear magnetic resonance spectroscopy, liquid chromatography tandem mass spectrometry and gas chromatography time-of-flight mass spectrometry. We performed univariate statistical analysis, which included independent t-tests (adjusted for multiple comparisons), effect size (d≥0.3) and single regression analysis to identify the most prominent urinary metabolites. Multivariate adjusted analyses were performed to test for independent associations of left ventricular mass index with identified metabolites. Results - When comparing the black and white groups, the black group had lower body weight (p<0.001) and protein intake (p=0.014). Left ventricular mass index was similar between black and white participants (p=0.97). Our statistical analyses identified five from a total of 192 metabolites which differed between the groups and associated with left ventricular mass index. In the black group the five metabolites were identified to be more abundant (p<0.05) and these metabolites associated inversely with left ventricular mass index (only in the black group) in multi variable adjusted regression analyses: hydroxyproline (β=–0.24; p=0.012), methionine (β=–0.21; p=0.024), glycine (β=–0.22; p=0.031), serine (β=–0.19; p=0.047) and trimethylamine (β=–0.26; p=0.007). Conclusion - We found inverse associations between left ventricular mass index and glycine, hydroxyproline, serine, methionine and trimethylamine, only in young black adults. We propose that the biosynthesis of glycine, hydroxyproline, serine and methionine are possibly up-regulated under restricted dietary conditions in the black group. The biosynthesis of these amino acids may be upregulated to maintain homeostatic collagen synthesis and stability, glutathione synthesis and energy storage to aid in preventing a premature increase in left ventricular mass index.
- Health Sciences