Cardiovascular disease (CVD), a global epidemic, is responsible for about 30% of all deaths worldwide. While mortality rates from CVD have been mostly declining in the advanced industrialized nations, CVD risk factors, including hypertension, obesity, and diabetes, have been on the increase everywhere. Researchers investigating the social causes of CVD have produced a robust body of evidence documenting the relationships between the work environment and CVD, including through the mechanisms of psychosocial work stressors. We review the empirical evidence linking work, psychosocial stressors, and CVD. These work stressors can produce chronic biologic arousal and promote unhealthy behaviors and thus, increased CVD risk. We offer a theoretical model that illustrates how economic globalization influences the labor market and work organization in high-income countries, which, in turn, exacerbates job characteristics, such as demands, low job control, effort-reward imbalance, job insecurity, and long work hours. There is also a growing interest in “upstream” factors among work stress researchers, including precarious employment, downsizing/restructuring, privatization, and lean production. We conclude with suggestions for future epidemiologic research on the role of work in the development of CVD, as well as policy recommendations for prevention of work-related CVD.

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