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1.  Cortisol Responses to Mental Stress and the Progression of Coronary Artery Calcification in Healthy Men and Women 
PLoS ONE  2012;7(2):e31356.
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.
doi:10.1371/journal.pone.0031356
PMCID: PMC3273460  PMID: 22328931
2.  Socioeconomic Status and Subclinical Coronary Disease in the Whitehall II Epidemiological Study 
PLoS ONE  2010;5(1):e8874.
Background
There are pronounced socioeconomic disparities in coronary heart disease, but the extent to which these primarily reflect gradients in underlying coronary artery disease severity or in the clinical manifestation of advanced disease is uncertain. We measured the relationship between socioeconomic status (SES) as indexed by grade of employment and coronary artery calcification (CAC) in the Whitehall II epidemiological cohort, and tested the contribution of lifestyle, biological and psychosocial factors in accounting for this association.
Methods and Findings
CAC was assessed in 528 asymptomatic men and women aged 53–76 years, stratified into higher, intermediate and lower by grade of employment groups. Lifestyle (smoking, body mass index, alcohol consumption, physical activity), biological (blood pressure, lipids, fasting glucose, inflammatory markers) and psychosocial factors (work stress, financial strain, social support, depression, hostility, optimism) were also measured. Detectable CAC was present in 293 participants (55.5%). The presence of calcification was related to lifestyle and biological risk factors, but not to grade of employment. But among individuals with detectable calcification, the severity of CAC was inversely associated with grade of employment (p = 0.010), and this relationship remained after controlling for demographic, lifestyle, biological and psychosocial factors. Compared with the higher grade group, there was a mean increase in log Agatston scores of 0.783 (95% C.I. 0.265–1.302, p = 0.003) in the intermediate and 0.941 (C.I. 0.226–1.657, p = 0.010) in the lower grade of employment groups, after adjustment for demographic, lifestyle, biological and psychosocial factors.
Conclusions
Low grade of employment did not predict the presence of calcification in this cohort, but was related to the severity of CAC. These findings suggest that lower SES may be particularly relevant at advanced stages of subclinical coronary artery disease, when calcification has developed.
doi:10.1371/journal.pone.0008874
PMCID: PMC2810334  PMID: 20111604

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