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Effects of stress on the development and progression of cardiovascular disease

Key Points

  • Pooling of individual-level data and published data from multiple cohorts into mega-studies has allowed for a more precise assessment of the association between stress and cardiovascular disease

  • In the general population, adults with work stress or private-life stress have a 1.1-fold to 1.6-fold increased risk of incident coronary heart disease and stroke

  • The excess risk of cardiovascular disease associated with adulthood stress is less marked than the risks associated with smoking, high blood pressure, high serum cholesterol levels, obesity, or multiple severe stressful experiences in childhood

  • Stress in adulthood has an important role as a disease trigger in individuals with high atherosclerotic plaque burden and as a determinant of prognosis and outcomes in those with pre-existing cardiovascular or cerebrovascular disease

  • Potential pathophysiological effects of stress involve increased cardiac electrical instability, myocardial ischaemia, plaque disruption, and thrombus formation, contributing to clinical events such as arrhythmia, myocardial infarction, cardiomyopathy, and stroke

  • Only European guidelines for cardiovascular disease prevention acknowledge stress as a clinically meaningful risk factor in individuals with a high overall risk of cardiovascular disease or with established cardiovascular disease

Abstract

Cardiovascular disease remains the leading cause of disease burden globally, which underlies the continuing need to identify new complementary targets for prevention. Over the past 5–10 years, the pooling of multiple data sets into 'mega-studies' has accelerated progress in research on stress as a risk and prognostic factor for cardiovascular disease. Severe stressful experiences in childhood, such as physical abuse and household substance abuse, can damage health and increase the risk of multiple chronic conditions in adulthood. Compared with childhood stress and adulthood classic risk factors, such as smoking, high blood pressure, and high serum cholesterol levels, the harmful effects of stress in adulthood are generally less marked. However, adulthood stress has an important role as a disease trigger in individuals who already have a high atherosclerotic plaque burden, and as a determinant of prognosis and outcome in those with pre-existing cardiovascular or cerebrovascular disease. In real-life settings, mechanistic studies have corroborated earlier laboratory-based observations on stress-related pathophysiological changes that underlie triggering, such as lowered arrhythmic threshold and increased sympathetic activation with related increases in blood pressure, as well as pro-inflammatory and procoagulant responses. In some clinical guidelines, stress is already acknowledged as a target for prevention for people at high overall risk of cardiovascular disease or with established cardiovascular disease. However, few scalable, evidence-based interventions are currently available.

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Figure 1: Studies on stress as a risk and prognostic factor for cardiovascular disease.
Figure 2: Confounding as an explanation for stress effects.
Figure 3: Effects of stress.
Figure 4: Stress and factors linked to disease triggering.
Figure 5: Absolute risk difference between groups exposed and not exposed to stress.

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Acknowledgements

M.K.'s work was supported by the UK Medical Research Council (K013351), NordForsk (75021), the Academy of Finland (311492), and a Helsinki Institute of Life Science Fellowship.

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Kivimäki, M., Steptoe, A. Effects of stress on the development and progression of cardiovascular disease. Nat Rev Cardiol 15, 215–229 (2018). https://doi.org/10.1038/nrcardio.2017.189

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