Chronic defensiveness and neuroendocrine dysfunction reflect a novel cardiac troponin T cut point: The SABPA study.

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 outcome measures [Coping-Strategy-Indicator, depression/Patient-Health-Questionnarie-9, 24h BP, 24h heart-rate-variability (HRV) and 24h urinary catecholamines]. Results: cTnT levels of the cohort remained similar over 3 years but recovery to cTnT-negative levels was higher in Blacks. Blacks showed moderate depression (45% vs. 16%) and 24h 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 exposure measure in relation to outcome measures [AUC 0.68 (95% CI 0.60-0.76); sensitivity/specificity 63/70%; 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]; 24h 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 outcome 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 4.2 ng/L cTnT cut-point in Blacks

Chronic depression symptoms and salivary NOx are associated with retinal vascular dysregulation: the SABPA study.

Background Depression has been associated with impaired nitric oxide (NO)-mediated vasodilation and vascular dysregulation (VD). Whether depression and NO levels will disturb retinal hemodynamics is not clear. Objectives and methods Associations between the retinal vasculature, diastolic ocular perfusion pressure (DOPP) as measure of hypoperfusion, NO metabolites (NOx) and depression symptoms were assessed. Chronic VD risk markers [depression symptoms (Patient Health Questionnaire/PHQ-9 ≥ 10) and 24h pulse pressure] were determined in a bi-ethnic cohort (n=313; 48.6 ± 9 years; 53.9% men). At 3 year follow-up, retinal vessel calibre and retinopathy signs were quantified from digital images. Salivary NOx, a novel approach, was obtained pre- and post-flicker light-induced provocation (FLIP). DOPP was defined as diastolic blood pressure minus intraocular pressure. Results Chronic VD risk was evident in Blacks opposed to acute risk in Whites (P<0.05). At follow-up, retinopathy (Blacks 60.4%/Whites 39.6%), lower pre-FLIP (µM) and higher post-FLIP NOx (%), arteriolar narrowing and wider venular calibre values were evident in Blacks compared to Whites, independent of confounders. A wider venular calibre, an index of stroke risk, was associated with chronic depression symptoms [cut point 248 MU: Area under the curve 0·61 (95% CI: 0·51, 0·72); 71% sensitivity; 55% specificity] as well as with hypoperfusion in the Blacks. In this group, arteriolar narrowing was associated with hypoperfusion; and attenuated arteriolar dilation with increased FLIP NOx responses (%). Conclusions Higher NOx increased arteriolar vasoconstriction, presumably impeded perfusion and facilitated VD. Chronic depression symptoms may trigger disturbed NOx and retinal hemodynamics in Blacks and thereby potentiate stroke ris

Schematic representation of the stress testing day.

<p>TSST = Trier Social Stress Test, B = biological samples (results from biological samples are reported elsewhere [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0169746#pone.0169746.ref025" target="_blank">25</a>]).</p

Associations between VO₂max and reactivity and area under the curve (AUC) for cardiovascular parameters.

<p>Associations between VO₂max and reactivity and area under the curve (AUC) for cardiovascular parameters.</p

Mean (±SEM) descriptive characteristics of Lower and Higher fit women.

<p>Mean (±SEM) descriptive characteristics of Lower and Higher fit women.</p

Mean (±SEM) pre-treatment, peak height/lowest trough, reactivity, area under the curve and recovery time for HR, LVET and Pulse interval in lower and higher fit women.

<p>Mean (±SEM) pre-treatment, peak height/lowest trough, reactivity, area under the curve and recovery time for HR, LVET and Pulse interval in lower and higher fit women.</p

Mean (± SEM) SBP, DBP and MAP in lower and higher fit women from 1430h-1700h.

<p>TSST: Trier Social Stress Test.</p