BACKGROUND : Sympatho-adrenal responses are activated as an innate defense coping (DefS) mechanism during emotional stress. Whether these sympatho-adrenal responses drive cardiac troponin T (cTnT) increases are unknown. Therefore, associations between cTnT and sympatho-adrenal responses were assessed. METHODS : A prospective bi-ethnic cohort, excluding atrial fibrillation, myocardial infarction and stroke cases, was followed for 3 years (N = 342; 45.6 ± 9.0 years). We obtained serum high-sensitive cTnT and exposure measures [Coping-Strategy-Indicator, depression/Patient-Health-Questionnarie-9, 24 h BP, 24 h heart-rate-variability (HRV) and 24 h urinary catecholamines]. RESULTS : Blacks showed moderate depression (45% vs. 16%) and 24 h hypertension (67% vs. 42%) prevalence compared to Whites. A receiver-operating-characteristics cTnT cut-point 4.2 ng/L predicting hypertension in Blacks was used as binary outcome measure in relation to exposure measures [AUC 0.68 (95% CI 0.60-0.76); sensitivity/specificity 63/70%; P ≤ 0.001]. Bi-ethnic cTnT-incidence was similar (25-27%) with cTnT-recovery better in Blacks (9%) compared to Whites (5%), P = 0.001. In cross-sectional analyses, elevated cTnT was related to DefS [OR 1.08 (95% CI 0.99–1.16); P = 0.06]; 24 h BP [OR 1.03–1.04 (95% CI 1.01–1.08); P ≤ 0.02] and depressed HRV [OR 2.19 (95% CI 1.09–4.41); P = 0.03] in Blacks, but not in Whites. At 3 year follow-up, elevated cTnT was related to attenuated urine norepinephrine:creatinine ratio in Blacks [OR 1.46 (95% CI 1.01–2.10); P = 0.04]. In Whites, a cut point of 5.6 ng/L cTnT predicting hypertension was not associated with exposure measures. CONCLUSION : Central neural control systems exemplified a brain-heart stress pathway. Desensitization of sympatho-adrenal responses occurred with initial neural- (HRV) followed by neuroendocrine dysfunction (norepinephrine:creatinine) in relation to elevated cTnT. Chronic defensiveness may thus drive the desensitization or physiological depression, reflecting ischemic heart disease risk at a novel 4.2 ng/L cTnT cut-point in Blacks.