Silent myocardial ischemia, cardiac troponins and target organ damage in a bi-ethnic sex cohort: the SABPA study
Abstract
MOTIVATION - Cardiovascular disease (CVD) prevalence is escalating and influences general health and well-being. Blacks were more at risk of developing CVD and coronary artery disease (CAD). In addition, silent myocardial ischemia (SMI), which underscores the ischemic burden of CAD and CVD, is an underestimated health risk and unravelling the presence of SMI and reduced perfusion to coronary circulation and the myocardium may therefore be important in Blacks from South Africa. This ethnic group is also more likely to be diagnosed with symptomatic occlusive vascular disease. The determination of the CVD risk factors, insulin resistance (IR) and elevated high-sensitivity cardiac Troponin T (hs-cTnT) for prediction of SMI events in separate ethnic groups, can underpin the prognostic relevance of SMI, and contribute to prognostic screening in healthcare practice. In addition, considering subclinical atherosclerosis and conduction disturbances in relation to these risk markers, may further inform the medical community on the CAD and CVD burden in this cohort. AIMS - The main aim of this SABPA (Sympathetic activity and Ambulatory Blood Pressure) sub-study was to indicate the prevalence of SMI in an urban South African bi-ethnic sex cohort and its association with hs-cTnT. In addition, to predict the resulting compensatory hypertension, the effect of hs-cTnT was researched. Furthermore, assessing the risk markers IR and hs-cTnT to determine the possible emerging mechanism of SMI was also explored, since possible racial disparity may be evident. When taking conduction disturbances into account, the association between CVD risk markers hs-cTnT, and IR in relation to subclinical atherosclerosis improved our understanding of myocardial ischemia and CVD burden. METHODOLOGY - The SABPA is a target population study which encompassed 409 urban black and white South African teachers from the Dr Kenneth Kaunda Education district situated in the North West province, South Africa (13). The cohort ensured homogeneity with regards to socio-economic status and working environment, although diverse cultural backgrounds could not be accounted for. Eligible participants aged between 20 and 65 years partook in this study. The following individuals were excluded for the current sub-study: pregnant or lactating women, individuals who had donated blood or had vaccinations less than 3 months prior to the onset of data collection, dependance on or abuse of psychotropic substances and individuals with a history of any cardiac events or myocardial infarction (heart attack) (n=5). The final cohort used for this sub-study included 198 Blacks and 206 Whites (N=404). For Manuscript 2, clinically diagnosed individuals with diabetes (n=17) were excluded. Human immunodeficiency virus- (HIV) infected individuals (n=18) were excluded for Manuscript 3. Groups were stratified according to ethnicity and sex after interaction terms were fitted for CVD risk. Cardiometabolic variables included in this study were: body surface area (BSA), cholesterol, glycated haemoglobin A1C (HbA1C), glucose, homeostasis model of assessment (HOMA IR), high sensitivity C-reactive Protein (hs-CRP), plasma γ-glutamyl transferase (γ-GT), plasma cotinine levels, hs-cTnT and blood pressure (BP). Left carotid intima-media thickness (L-CIMT) of the far wall, left cross sectional wall-area (L-CSWA) and the lumen diameter of the left carotid indicated subclinical atherosclerosis. SMI was automatically detected by 24-hour (24-h) ambulatory electrocardiogram (ECG) measurement, where 1st degree atrioventricular-block (AV block) was determined with 6 cardiac cycles of 12-lead ECG. Means and proportion were calculated with student T-tests, analysis of covariance (ANCOVA) as well as Chi squares (X2). Multivariate linear regression analysis determined associations between major variables where receiver-operating characteristic (ROC) curves established cut-points for exacerbated CVD risk. RESULTS AND CONCLUSIONS: - The results and conclusions of the three manuscripts are as follows:
1.Troponin T release is associated with silent myocardial ischaemia in black men: theSABPA Study Significant differences were evident in hs-cTnT and its relation with SMI and hypertension in Blacks and Whites from this cohort. These findings indicate that hs-cTnT can possibly be a potential proficient marker of SMI and increases in compensatory systolic blood pressure (SBP). A lower hs-cTnT cut-point ≥ 4.2 pg/ml for 24-h systolic hypertension was predicted in Blacks compared to ≥ 5.6 pg/ml in Whites with a respective sensitivity/specificity of 64/68% and 61/71%. The SBP rises to alleviate myocardial ischemia in the Blacks and risk-factor clustering. The results also underscored the need for ethnic-specific reference values of hs-cTnT, which in turn should be interpreted in consideration of existing risk factors. In-depth assessment of hs-cTnT can thus be a useful improvement in risk prediction research. 2.Silent ischemia, insulin resistance and cardiovascular risk in a bi-ethnic sex cohort:the SABPA study Insulin resistance (IR) as determined by elevated homeostasis model of assessment (HOMA IR) levels, was positively related to longer SMI events over 24 hours in White sex groups. Furthermore, White men also showed significant relations between IR and more frequent SMI events. Our findings suggested that IR increases are related to metabolic susceptibility leading to the development of SMI in the Whites but not necessarily in the Blacks. However, the Black men presented positive associations between hs-cTnT and more frequent and longer SMI events. Findings in Blacks implied a cardiovascular susceptibility to develop ischemic heart disease and underscoring ethnic-related mechanism which could diagnose emergent SMI. 3.Troponin T release is associated with subclinical atherosclerosis in Blacks with firstdegree AV-block: the SABPA study In Blacks presenting 1st degree AV-block, elevations in hs-cTnT were positively associated with subclinical atherosclerosis. Similar associations were not evident in Whites. First (1st) degree AV-block in Blacks reflected increases in hs-cTnT and enhanced susceptibility for a compensatory high blood pressure system resulted in carotid hypertrophic remodelling. Thus, by identifying conduction disturbances and perfusion deficits in early screening programs a contribution can be made to CVD prevention programs. GENERAL CONCLUSION - In Blacks from this cohort, a higher cardiometabolic susceptibility to develop CVD was revealed. This was accentuated with lower hs-cTnT cut-points to predict compensatory SBP hypertension. In addition, when considering electricical conduction disturbances, the use of hs-cTnT cut-points may contribute to the preventive cardiology. In Whites, IR underscored the development of ischemic heart disease more so than hs-cTnT, and can be translated to heath care practice. The adverse CVD risk in a South African Black cohort is concerning and the contribution of risk factors due to urbanization (poor nutrition, lower activity levels, obesity, alcohol abuse and smoking) further exacerbated a CVD burden.
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