| dc.description.abstract | Motivation - Pathological cardiac remodelling is a manifestation of end-organ damage and can be characterised by myocyte death and myocyte hypertrophy. An increased hemodynamic burden may follow the cardiac remodelling process leading to an increase in cardiac stress. It has been reported that the cardiac stress risk markers, cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), may explain the increased susceptibility to subclinical vascular disease in African populations. Hence the interlinked associations of these cardiac stress risk markers with various other cardiovascular risk markers were investigated in a South African cohort. Indeed, a worsening of cardiovascular prognosis was found in South Africans individuals with the risk profile differing between Blacks and Whites. Compared to Whites of the Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) study, Blacks were proven to reveal an increased cardio-metabolic vulnerability that related to subclinical wall remodelling, as well as an increased risk for silent myocardial ischemia, coupled with compensatory inflammatory and blood pressure (BP) increases. The possible increased hemodynamic burden may further interfere with normal neurotrophin (brain-derived neurotrophic factor, BDNF) and glucose homeostasis. Maintenance of BDNF and glucose is not only needed for cardiovascular health, but also for optimal brain health and executive cognitive functioning. Aims - The main aim of this thesis was to determine whether cardiac stress changed in a bi-ethnic gender cohort over a period of three years and to determine whether cardiac stress risk markers associate with other cardiovascular risk markers, including inflammation (Manuscript 1), BP, left ventricular hypertrophy (LVH), BDNF (Manuscript 2), executive cognitive function and glucose dysregulation (Manuscript 3) over a follow-up period. Methods - This prospective study is embedded within the SABPA cohort study that was conducted in 2008/2009 (baseline) and again in 2011/2012 (follow-up). Urban Black and White teachers (N=409, aged between 20 and 63 years), that resided in the Dr Kenneth Kaunda Education District of the North West Province of South Africa were enrolled at baseline. At follow-up, 359 Black and White participants were included, with reasons for non-participation being pregnancy, lactation, deceased, having moved too far away from the data collection site or having chosen not to participate. For purposes of this thesis we included individuals who participated in both phases of the study and additionally excluded participants with an HIV positive status to avoid bias pertaining to cardio-metabolic risk. Therefore we included 152 Black and 186 White participants in this study. A well-controlled protocol was followed to obtain the various measurements in accordance with standardised procedures. Data were obtained concerning lifestyle factors (alcohol use, smoking status and physical activity), cardiovascular assessments (24-hour ambulatory blood pressure and electrocardiogram (ECG)-LVH and biochemical analyses of cTnT, NT-proBNP, C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), BDNF, glycated haemoglobin (HbA1c) and the homeostatic model assessment-insulin resistance (HOMA-IR). The STROOP-color-word conflict test (STROOP-CWT) was applied to assess response inhibition capacity of executive cognitive function. Hypotheses were tested by computing general linear models with interactions of main effects (ethnicity x gender) for cardiac stress and all cardiovascular risk markers. Statistical analyses comprised independent t-tests and Chi-square tests, which were used to compare baseline characteristics of the ethnic groups and prevalence as well as proportions at baseline. Differences over time (Δ) in each ethnic cohort were calculated via dependent t-tests and one-way covariance analyses. Multivariate linear regression analyses and logistic regression analyses were performed to determine associations between main variables. Results - Interactions between main effects (ethnicity × gender) were revealed for ΔBDNF [F(1,309), 9.86, p=0.002], ΔTNF-α [F(1,323), 4.91, p=0.03], STROOP-CWT [F(1,324), 97.20, p<0.001], [F(1,324), 21.73, p<0.001] and ΔHOMA-IR [F(1,320), 14.28, p<0.001], [F(1,320), 3.99, p=0.046]. Furthermore interactions between main effects (ethnicity) were shown for ΔNT-proBNP [F(1,306), 5.74, p=0.02] that motivated further stratification into ethnic-gender groups. At baseline, no differences were observed between Blacks and Whites concerning the cardiac stress risk markers, cTnT and NT-proBNP. NT-proBNP significantly increased in Blacks and Whites over the three-year period with cTnT remaining constantly high (≥4.2ng/L) over the three-year follow-up period. Pertaining to the cardiovascular risk markers, more Blacks were hypertensive with higher inflammation, HbA1c and insulin levels than were Whites at baseline. Over the three-year follow-up period BDNF and systolic blood pressure (SBP) increased while TNF-α and HOMA-IR decreased in Blacks. In contrast, Whites revealed higher cTnT and BDNF levels with a higher STROOP-CWT score than Blacks at baseline. Over the three-year follow-up period, TNF-α increased while cTnT, diastolic blood pressure (DBP) and HOMA-IR decreased in Whites. In Black men, NT-proBNP and BDNF showed increases, TNF-α decreased, with other markers remaining constant over the three-year period. No significant associations emerged in Black women. Chronic increased cTnT levels were positively associated with increased ΔNT-proBNP and with decreases in ΔTNF-α (Manuscript 1) in Black men only. In these men, ΔNT-proBNP increased the likelihood of 24-hour hypertension (Manuscript 1). Furthermore, ΔBDNF increased the likelihood of cTnT levels being lower than 4.2ng/L (Manuscript 2). Again in Black men, Hyperglycaemia (HbA1c≥5.7%) was positively associated with moderate IR (HOMA-IR>3) and with increases in ΔNT-proBNP (Manuscript 3). Lastly, baseline STROOP-CWT score was inversely associated with chronic higher cTnT (Manuscript 2) and moderate IR levels (Manuscript 3). Conclusion - Myocyte injury, hyperglycaemia and insulin resistance were accompanied by progressive myocardial stretch in Black men that may be reflective of cardiac metabolic over-demand increasing the likelihood of hypertension and ischemic heart disease risk. However, central neural control mechanisms potentially may have upregulated BDNF and down-regulated TNF-α in these men as a way of protecting against these demands and of improving processes related to interference control. | en_US |
