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Aims: Psychosocial stress is a risk factor for coronary heart disease (CHD), although the mechanisms are incompletely understood. We examined the cross-sectional association between the cortisol response to laboratory-induced mental stress and a marker of sub-clinical coronary atherosclerosis., Methods and Results: Participants were 514 healthy men and women (mean age = 62.9 +/- 5.7 years), without history or objective signs of CHD, drawn from the Whitehall II epidemiological cohort. Salivary cortisol was measured in response to mental stressors, consisting of a 5 min Stroop task and a 5 min mirror tracing task. Coronary artery calcification (CAC) was measured using electron beam computed tomography. Approximately 40% of the sample responded to the stress tasks with a notable (>or=1 nmol/L) increase in cortisol. Significant CAC (Agatston score >or= 100) was recorded in 23.9% of the sample. The cortisol response group demonstrated a higher risk of significant CAC (odds ratio = 2.20, 95% CI, 1.39-3.47) after adjustments for age, gender, baseline cortisol, employment grade, and conventional risk factors, although cortisol was unrelated to the presence of detectable CAC. Among participants with detectable CAC, the cortisol response group also demonstrated higher log Agatston scores compared with non-responders (age and sex adjusted scores; 4.51 +/- 0.15 vs. 3.94 +/- 0.13, P = 0.004)., Conclusion: In healthy, older participants without history or objective signs of CHD, heightened cortisol reactivity is associated with a greater extent of CAC. These data support the notion that heightened hypothalamic pituitary adrenal activity is a risk factor for CHD.

Positive affective states are associated with favorable health outcomes, but the underlying mechanisms are poorly understood. The authors assessed associations between positive affect, cortisol sampled over the day, and inflammatory markers (C-reactive protein and interleukin-6) among 2,873 healthy members of the Whitehall II study. Data for this study were collected in 2002-2004 in London, United Kingdom. Saliva free cortisol was assessed on waking, 30 minutes later, and four times over the day and evening. Positive affect was indexed by aggregating ecological momentary assessments of positive mood over the day. Salivary cortisol averaged over the day was inversely associated with positive affect after controlling for age, gender, income, ethnicity, body mass index, waist/hip ratio, smoking, paid employment, time of waking in the morning, and depression (p = 0.003). There was no association with cortisol responses to waking. The adjusted odds of C-reactive protein >/=3.00 mg/liter was 1.89 (95% confidence interval: 1.08, 3.31) in low- compared with high-positive-affect women, and plasma interleukin-6 was also inversely related to positive affect in women (p = 0.016). Neither inflammatory marker was related to positive affect in men. These results confirm findings from smaller studies relating cortisol with positive affect while suggesting that in women, positive affect is associated with reduced levels of inflammatory markers.