Electrical and cardiac stress reactivity associations with pre-clinical target organ damage : the SABPA study

MSc (Physiology), North-West University, Potchefstroom Campus, 2017Motivation: People’s physiological adaptive responses to chronic stressful environments have been persistently associated with an increased incidence of cardiovascular diseases (CVD) and co-morbidities. An inability to successfully respond to both mental and physical stressors is associated with an increased incidence of hypertension, coronary artery disease (CAD), stroke and cardiac structural remodelling. These adaptive responses not only depend on one’s personality and previous experiences, but also on factors such as age, gender and ethnicity. The link between cardiovascular risk and the development of CVD may be presented by reactivity of the autonomic nervous system (ANS), such as during acute mental stress application, and may accompany specific reactivity patterns. It has been demonstrated that during acute mental stress exposure, urban-dwelling Blacks (hereafter referred to as Africans) present elevated blood pressure (BP) values and exhibit α-adrenergic vascular responses, whilst their White (hereafter referred to as Caucasian) counterparts predominantly presented a central cardiac, β-adrenergic response accompanied by essentially normal BP values. Therefore, an increased cardiovascular risk may be linked to α-adrenergic vascular responses in those experiencing greater stress. However, whether these specific haemodynamic responses are linked to identifiable cardiac stress and electrical reactivity markers during acute mental stress has yet to be determined. Markers of cardiac stress include cardiac troponin T (cTnT) and N-terminal pro-Brain natriuretic peptide (NT-proBNP). These markers are traditionally used to indicate cardiac hypertrophy, ischemia and heart failure. However, recently increased levels of these markers have been associated with disrupted autonomic function and acute mental stress. Electrical markers pertaining to cardiac autonomic function, such as the corrected QT interval (QTc), may also indicate autonomic alterations during acute mental stress, seeing that the QTc has been shown to be a measure of cardiac sympathetic tone. Objectives: No ethnic-comparative data regarding BP, electrical or cardiac stress marker reactivity are available in sub-Saharan African individuals. Therefore, the objectives were firstly, to indicate and compare ethnic-specific differences in BP, QTc and cardiac stress reactivity during acute mental stress application. Secondly, to signify that α-adrenergic BP responses will associate with increased QTc prolongation and cardiac stress levels in Africans. Thirdly, to illustrate that an α-adrenergic BP response, QTc and cardiac stress markers’ reactivity will indicate pre-clinical alterations in the loading conditions and structure of the heart. Methodology: This cross-sectional, comparative target population study forms part of the Sympathetic Activity and Ambulatory Blood Pressure in Africans (SAPBA) study. The SABPA study was conducted between late summer until autumn in both 2008 (Africans) and 2009 (Caucasians) so as to avoid seasonal variations. The Health Research Ethics Committee (HREC) of the North-West University Potchefstroom Campus approved this study and all voluntary participants gave written informed consent prior to their inclusion in the study. All procedures pertained to the applicable institutional guidelines as stated by the Declaration of Helsinki. Exclusion criteria entailed the use of α-, β-blocker and psychotropic substance users, vaccination or blood donation within three months prior to the investigation, tympanum temperatures >37.5˚C and pregnant or lactating women. Participants were additionally excluded if they presented any sign of atrial fibrillation (N=16), history of myocardial infarction (N=4), electrocardiographic left ventricular hypertrophy (ECG-LVH) (N=1) and ventricular ectopic episodes (computationally excluded). The final sub-study sample comprised 388 teachers of whom 193 were urban dwelling Africans and 195 Caucasians. 24 hour Ambulatory BP measurements (24H ABPM) were recorded with the Cardiotens CE120®. Actical® accelerometers were equipped to attain physical activity recordings. Participants were requested to go to bed at 22h00, fasting overnight. The mentioned apparatus were removed the following day, followed by anthropometric measurements and blood sampling by a registered nurse. Fasting glucose, whole blood glycated haemoglobin, total cholesterol, high-density lipoproteins (HDL), as well as lifestyle markers such as gamma glutamyl transferase (alcohol consumption) and cotinine (smoking) were determined. The Finapres continuously assessed beat-to-beat BP changes throughout psychophysiological testing. Resting beat-to-beat BP and 10-lead ECG measurements were obtained for 5 min, followed by venous blood sampling. After a period of 5-10 min, the Stroop colour-word-conflict test was administered for 1 min, during which beat-to-beat BP and ECG responses were obtained. Another blood sample was obtained 10 min post-stress application. These blood samples (both prior and post-stress) were analysed for cardiac stress markers, cTnT and NT-proBNP, via electrochemiluminescence. The normality of all variables was verified and descriptive t-tests depicted ethnic characteristics. Chi-square statistics determined proportions and prevalence. Two-way ANCOVAs determined the least square mean difference in reactivity markers between ethnic groups, independent of a priori covariates. Regression analyses were performed in three models and F to enter was set at 2.5. For all the aforementioned analyses, significance was set at a p≤0.05. Additionally, receiver-operated characteristics (ROC) analyses determined ethnic-specific cTnT cut-point values predicting 24 hour diastolic hypertension (24H DBP HT). Odds ratios (OR) were also calculated for several models to establish CVD risk relation to RaVL amplitude increases in the detectable cTnT category in each ethnicity respectively. Results: A higher risk of cardiovascular vulnerability was observed in Africans as well as an increased RaVL amplitude, ECG-LVH prevalence and greater average number of ischemic events. Resting values for cardiovascular markers were quite similar between ethnicities. However, the degree to which these values changed during acute mental stress testing differed significantly. Acute mental stress responses of Africans were accompanied by a typical α-adrenergic response profile, whereas Caucasians predominantly presented a central cardiac β-adrenergic response pattern. A positive association existed between cTnT and NT-proBNP reactivity, in both ethnic groups, yet it was greater in the Caucasian group. ROC analyses revealed a higher cTnT cut-point during acute mental stress predicting 24H DBP HT in Africans (4.19pg.mL) compared to that of Caucasians (3.24pg/mL). An increased RaVL amplitude was associated with increased levels of cTnT during acute stress, in both ethnicities, giving rise to an OR of approximately 11. Conclusion: Cardiac stress (cTnT and NT-proBNP) and QTc reactivity were independently associated with an increased pre-clinical risk of structural and mechanistic alterations, specifically in the SABPA African cohort. In this African group, where cardio-metabolic vulnerability and α-adrenergic reactivity are predominant, the aforementioned modifications may be detrimental, evidenced by an increased DBP HT, CVD, ischemia and CAD. Increased cardiac stress and QTc reactivity, associated with α-adrenergic reactivity, may contribute to early sensitization and damage to the myocardium as well as signs of CVD, especially in an at-risk populationMaster