Results:

A total of 25 studies were included from 24 cohorts in Europe, the United States, and Australia. The meta-analysis of CHD comprised data for 603,838 men and women who were free from CHD at baseline; the meta-analysis of stroke comprised data for 528,908 men and women who were free from stroke at baseline. Follow-up for CHD was 5.1 million person-years (mean 8.5 years), in which 4,768 events were recorded, and for stroke was 3.8 million person-years (mean 7.2 years), in which 1,722 events were recorded. In cumulative meta-analysis adjusted for age, sex, and socioeconomic status, compared with standard hours (35-40 hours per week), working long hours (≥55 hours per week) was associated with an increase in risk of incident CHD (relative risk [RR], 1.13; 95% confidence interval [CI], 1.02-1.26; p = 0.02) and incident stroke (1.33; 95% CI, 1.11-1.61; p = 0.002). The excess risk of stroke remained unchanged in analyses that addressed reverse causation, multivariable adjustments for other risk factors, and different methods of stroke ascertainment (range of RR estimates, 1.30-1.42). There was a dose–response association for stroke, with RR estimates of 1.10 (95% CI, 0.94-1.28; p = 0.24) for 41-48 working hours, 1.27 (95% CI, 1.03-1.56; p = 0.03) for 49-54 working hours, and 1.33 (95% CI, 1.11-1.61; p = 0.002) for 55 working hours or more per week compared with standard working hours (p_trend < 0.0001).