Effects of stress on the development and progression of cardiovascular disease

In this Review, Kivimäki and Steptoe assess the current evidence on the association between stress and cardiovascular disease, covering the multiple roles of stress in the development and triggering of disease and as a determinant of prognosis and outcome. In addition, they discuss the clinical and public health importance of major stressors and the implications for prevention and treatment of cardiovascular disease. 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.