Author	A.I. Lazzarino
Author	A. Steptoe
Abstract	Background Mental stress is a recognized risk factor and trigger for heart disease. Socioeconomic status (SES) is associated with morbidity and mortality, with low SES people having poorer health compared to their counterparts. I hypothesised that those two factors may interact with each other, so that when they are present simultaneously the total harmful effect is more than the sum of the two risk factors alone. Research aim My aim was to test whether lower SES interacts with mental stress and amplifies its effect on heart disease, so that the effect of mental stress on heart disease would be more pronounced in people from low SES backgrounds. Studies I carried out three studies. For my first study, I analysed data from a cross-sectional study involving about 500 disease-free middle/old-aged men and women drawn from the Whitehall II epidemiological cohort. I evaluated their salivary cortisol responses to standardized mental stress tests (exposure variable) and their cardiac troponin T plasma concentration (a marker of heart damage) using a high-sensitivity assay (HS-CTnT, outcome variable). I also used measures of coronary calcification levels using electron-beam dual-source computed tomography and Agatston scores. After adjustment for demographic and clinical variables associated with heart disease as well as for inflammatory factors, I found a robust association between cortisol response to mental stress and detectable troponin T (odds ratio [OR] =3.8, 95% confidence interval [CI] =1.5-9.4, P =0.005). The association remained when I restricted the analysis to participants without coronary calcification (n =222, OR =4.8; 95% CI =1.2-18.3; P =0.023) or when I further adjusted for coronary calcification in participants with positive Agatston scores (n =286, OR =6.2, 95% CI =1.9-20.6; P =0.003). In analyses stratified by SES, there was a trend showing that the lower the SES was, the higher the OR, although this trend was not significant (P >0.05). In my second study, I selected about 67,000 male and female participants from the Health Survey for England who were 35 years or older, free of cancer and cardiovascular disease at baseline, and living in private households in England from 1994 to 2004. Selection used stratified random sampling (hence representative of the nation), and participants were linked prospectively to mortality records from the Office of National Statistics (mean follow-up, 8.2 years). Mental stress was measured using the 12-item General Health Questionnaire, and SES was indexed by occupational class. The crude incidence rates for heart disease and all-cause mortality of the cohort were 1.9 (95%CI =1.7-2.0) and 14.5 (95%CI =14.2-14.8) per 1,000 person-years. After adjustment for age and sex, mental stress was associated with increased mortality rates. In a stratified analysis, the association of mental stress with the outcomes differed with SES, with the strongest associations being observed in the lowest SES categories (the adjusted P values for interaction were 0.012 for all-cause mortality and 0.047 for heart disease mortality). My third study involved about 80,000 post-menopausal women selected from the United Kingdom Collaborative Trial of Ovarian Cancer Screening study, who were followed up for about three years on average. Mental stress was measured using the hopelessness/helplessness index and incident heart disease was assessed using hospital electronic records. The overall incidence rate of hospitalisation for acute heart disease event was 2.7 per 1,000 person years (95% CI=2.5-3.0). The augmented incidence for people who experienced mental stress was higher in people of low SES, medium in people of medium SES, and lower in people of high SES (adjusted P value for interaction =0.013). Conclusion These studies suggest that the interaction between socioeconomic status and mental stress is associated with ischemic heart disease, in such a way that people in low socioeconomic circumstances are more vulnerable to the negative effects of mental stress. In other words, the harmful effect of mental stress for human cardiac health may be modified by socioeconomic position and rendered more deleterious for people from disadvantaged backgrounds. Further research is needed to disentangle the dynamics of this effect amplification.