The majority of the investigations described either overall cardiovascular disease or coronary Y-27632 cost heart disease, either based on mortality

registers or (for morbidity) collected by questionnaires, clinical diagnosis based on ECG or enzyme measurement. Some analyses regarded solely stroke (Tsutsumi et al. 2009; André-Petersson et al. 2007; Kuper et al. 2006; Hibbard and Pope 1993), angina pectoris (Chandola et al. 2005) or hypertension (Fauvel et al. 2003; Markovitz et al. 2004). Since most of the studies investigated cardiovascular disease or heart disease as a whole, it was not possible to evaluate whether work stress acts differently in relation to myocardial infarction, angina pectoris, hypertension or stroke within the same study population. Results were significant for six out of 14 publications investigating CHD,

and for five out of seven articles on CVD. One of the two publications on hypertension, GSK3235025 research buy one of the two publications on stroke and one publication on angina pectoris revealed statistically significant positive associations. The two publications with the highest level of evidence (SIGN classification 2++, indicating a study with high-quality and a very low risk of confounding and bias) for the relationship between stress and cardiovascular disease were based on the Whitehall cohort. One publication (Kuper et al. 2003) used the job strain model and the other one (Kuper et al. 2002) the effort–reward imbalance model to describe stress at the workplace (Tables 1, 2). Both found

statistically significant results. Thirteen publications showed a low risk of bias and a moderate probability that the relationship investigated was causal (SIGN classification 2+), eight of these 13 studies described significant results. The remaining eleven publications had a high risk of confounding and bias (SIGN classification 2−). Statistical analysis and adjustment for potentially confounding factors were insufficient in some of these studies. Demand–control PtdIns(3,4)P2 model Seventeen publications used the job strain model to describe stress at the workplace (Table 1). In seven of the 13 cohorts, workers with high strain had a significantly higher risk to develop cardiovascular diseases than workers in the low-strain group. Risk estimates varied between 1.33 and 2.62. Markovitz et al. (2004) reported a significant association between changes in job strain (of increasing demands relative to decreasing decision latitude) and risk of hypertension. A cumulative index was used in one study (Chandola et al. 2008), and the results indicate a dose–response relationship between the frequency of stress and cardiovascular outcomes. In three publications, also ‘isostrain’, a combination of high job strain and lack of social support at work, was investigated (André-Petersson et al. 2007; De Bacquer et al. 2005; Chandola et al.