Cortisol Responses to Mental Stress and the Progression of Coronary Artery Calcification in Healthy Men and Women

Background: Psychosocial stress is a risk factor for coronary heart disease (CHD). The mechanisms are incompletely understood, although dysfunction of the hypothalamic pituitary adrenal (HPA) axis might be involved. We examined the association between cortisol responses to laboratory-induced mental stress and the progression of coronary artery calcification (CAC). Methods and Results: Participants were 466 healthy men and women (mean age = 62.7±5.6 yrs), without history or objective signs of CHD, drawn from the Whitehall II epidemiological cohort. At the baseline assessment salivary cortisol was measured in response to mental stressors, consisting of a 5-min Stroop task and a 5-min mirror tracing task. CAC was measured at baseline and at 3 years follow up using electron beam computed tomography. CAC progression was defined as an increase >10 Agatston units between baseline and follow up. 38.2% of the sample demonstrated CAC progression over the 3 years follow up. There was considerable variation in the cortisol stress response, with approximately 40% of the sample responding to the stress tasks with an increase in cortisol of at least 1 mmol/l. There was an association between cortisol stress reactivity (per SD) and CAC progression (odds ratio = 1.27, 95% CI, 1.02–1.60) after adjustments for age, sex, pre-stress cortisol, employment grade, smoking, resting systolic BP, fibrinogen, body mass index, and use of statins. There was no association between systolic blood pressure reactivity and CAC progression (odds ratio per SD increase = 1.03, 95% CI, 0.85–1.24). Other independent predictors of CAC progression included age, male sex, smoking, resting systolic blood pressure, and fibrinogen. Conclusion: Results demonstrate an association between heightened cortisol reactivity to stress and CAC progression. These data support the notion that cortisol reactivity, an index of HPA function, is one of the possible mechanisms through which psychosocial stress may influence the risk of CHD

Effect of Revascularization on Exercise-Induced Changes in Cardiac and Prothrombotic Biomarkers in Patients with Coronary Artery Disease

We examined whether resting levels and exercise-induced changes during exercise ECG stress test (EST) of cardiac Troponin T (cTnT), NT-proBNP and prothrombotic markers were affected by revascularization in patients with coronary artery disease (CAD). EST1 was performed before coronary angiography and revascularization, and patients (n  =  20) with confirmed CAD, performed another EST (EST2) 9 weeks later. Blood samples were drawn at rest and within five min after termination of ESTs. cTnT and NT-proBNP increased during exercise at both ESTs (p &lt; 0.001, all). Resting cTnT levels at EST2 versus EST1 were significantly higher (p  =  0.02) whereas NT-proBNP did not differ. At both visits, increased D-dimer (p  =  0.008 and &lt;0.001), pro-thrombin fragment 1  +  2 (p  =  0.009 and 0.001) and tissue factor pathway inhibitor (TFPI) (p &lt; 0.001 and 0.001) during exercise were demonstrated. Resting levels of endogenous thrombin potential (ETP) and TFPI were reduced at EST2 versus EST1 (p &lt; 0.01). Revascularization did not affect exercise-induced release of cardiac and prothrombotic biomarkers and did not reduce resting levels of cTnT or NT-proBNP, suggesting revascularization per se not to prevent secretion of biomarkers. The lower resting levels of ETP and TFPI after revascularization may however, be indicative of reduced thrombin generation and endothelial activation. Clinicaltrials.gov, CADENCE, NCT01495091 https://clinicaltrials.gov/ct2/show/NCT01495091?term = 01495091&amp;draw = 2&amp;rank = 1 . </jats:p

Effect of revascularization on exercise-induced changes in cardiac and pro-thrombotic biomarkers in patients with coronary artery disease

Abstract Introduction Exercise-induced increase in cardiac and pro-thrombotic biomarkers have previously been shown in patients with coronary artery disease (CAD) before revascularization, which may be due to myocardial ischemia. Purpose We aimed to examine whether resting levels and exercise-induced changes of high sensitive cardiac Troponin T (cTnT), NT-proBNP, pro-thrombin fragment (F) 1+2, D-dimer, tissue factor pathway inhibitor (TFPI) and endogenous thrombin potential (ETP) were affected by revascularization in patients with CAD. We hypothesized that resting and exercise-induced levels of the biomarkers would be reduced after revascularization. Methods Patients presenting with symptoms of CAD were included. A maximal exercise ECG stress test (EST) (EST1) was performed, and venous blood samples were drawn at rest and within five min after termination. All patients underwent coronary angiography. Patients (n=20) with confirmed CAD, fully revascularized with percutaneous coronary intervention (PCI) and without symptoms of angina, were invited to perform a second EST (EST2), at the same workload (median 145W), at a median of 66 days after revascularization. Mean exercise duration at both time points were 11:30 min:sec. Of the total population 15 patients were treated with PCI on stenosis located on LAD and 5 patients with stenosis on RCA. Results Significant increase in cTnT and NT-proBNP from resting to post exercise levels at EST1 was found as expected (p&amp;lt;0.001, both). Also at EST2, increased levels were observed (p&amp;lt;0.01, both), however, not significantly different from the changes at EST1. Resting levels of cTnT at EST2 compared to EST1 were significantly higher (median 8.1 vs 7.1 ng/L, p=0.02). At both visits significant increase in D-dimer (p=0.008 and &amp;lt;0.001), F1+2 (p=0.009 and 0.001) and TFPI (p&amp;lt;0.001 and 0.001) during exercise were demonstrated, with no difference in these changes. There were no significant changes in ETP during exercise at any visit, but resting levels were reduced at EST2 vs EST1 (p&amp;lt;0.01). Also resting levels of TFPI were reduced at EST2 (p&amp;lt;0.01). Conclusion After revascularization there was still significant increase in exercise-induced release of cardiac and pro-thrombotic biomarkers, thus revascularization does not affect the ability to release these biomarkers. Also, the higher resting levels of cTnT after revascularization indicate that revascularization per se does not affect secretion of cardiac biomarkers, probably due to the disease state. The lower resting levels of ETP and TFPI after revascularization may, however, be indicative of reduced thrombin generation potential and endothelial activation. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Stein Erik Hagens Foundation for Clinical Heart Research, Oslo, Norway </jats:sec