Psychosocial stress in relation to blood pressure and cardivascular disease - epidemiological and genetic aspects

University dissertation from Department of Clinical Sciences, Lund University

Abstract: Psychosocial stress has been linked to both hypertension and cardiovascular disease (CVD), and hypertension has been proposed to be one mediator of the increased CVD risk in subjects reporting stress. Genetic susceptibility for blood pressure elevation in relation to stress has been proposed, but so far there is little evidence. We aimed to study the prospective CVD risk of chronic stress (Paper I), and the prospective effect on blood pressure levels of work-related stress (Paper II). In Papers III-IV the aim was to explore a hypothesised work stress?gene interaction in relation to blood pressure. In Paper I, 13,306 participants (2741 women) from the population-based screening and intervention programme Malmö Preventive Project were followed for a median of 21 years. Men and women with self-reported chronic stress at baseline suffered an increased risk of cardiovascular events compared to those without baseline stress (RR 1.27; 95%CI 1.15-1.27). The statistical significances were stronger in men than in women. In Papers II-IV different sub-cohorts from the population-based Malmö Diet and Cancer Study (MDCS) were included. Work stress was assessed according to the Karasek demand-control model. In Paper II, men with baseline job strain (?stress?) had a significantly greater systolic blood pressure (SBP) and diastolic blood pressure (DBP) elevation at follow-up compared to men with relaxed working conditions (significance for difference; SBP p= 0.025, DBP p=0.003, adjustments for age and follow-up time). In women, baseline job strain was associated with higher blood pressures at baseline, but no significant differences in blood pressure changes between groups with different work characteristics were seen at follow-up. In Paper III, an I/D polymorphism in the adrenergic ?2B-receptor was studied in women and men (n=2964). Men with the DD-variant of the receptor and job strain had higher SBP and DBP than all other gene?work characteristic combinations. The interaction between the DD polymorphism and job strain was significant; p=0.008 for SBP, and p=0.03 for DBP, adjusted for age, body mass index, occupational status and country of birth. The decision latitude dimension was more influential than the demand dimension. In Paper IV, an interaction between work characteristics and the Arg389Gly polymorphism in the ?1-adrenergic receptor in relation to blood pressure levels was studied, with significant findings in men. Our findings confirm previous results of the detrimental effects of chronic stress on the prospective CVD risk. The findings in Paper II indicate that elevation of blood pressure in men might mediate the increased CVD risk. For the first time, significant interactions between genetic factors and job stress, associating with elevated blood pressures, have been described. If these findings hold true in further research, they provide a new understanding of the mechanisms of stress, with potential implications for pharmacogenomics.

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