Chronic stress and cardiovascular disease: autonomic, inflammatory, and mitochondrial mechanisms in the development and progression of cardiovascular dysfunction

Abstract

Chronic stress has been recognized as an important psychosocial determinant of cardiovascular health, exerting a significant influence on the incidence, progression, and prognosis of cardiovascular diseases. Unlike acute stress, prolonged exposure to stressors promotes persistent activation of neuroendocrine and autonomic pathways, with systemic repercussions that affect cardiovascular, metabolic, and inflammatory homeostasis. In this context, the present study aimed to synthesize recent evidence on the effects of chronic stress on the cardiovascular system, with emphasis on the autonomic, neuroendocrine, inflammatory, oxidative, and mitochondrial mechanisms involved. This is a systematic literature review conducted in the PubMed database, encompassing studies published in the last five years, using the descriptors “Chronic Stress” AND “Cardiovascular Disease” NOT “Animals,” with filters for original articles, full-text availability, and texts written in English or Portuguese. Initially, 89 studies were identified, of which 11 met the eligibility criteria after screening by titles, abstracts, and full-text reading. The results showed that chronic stress is consistently associated with hyperactivation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, reduced parasympathetic modulation, increased low-grade systemic inflammation, oxidative stress, and mitochondrial dysfunction, mechanisms that contribute to endothelial dysfunction, arterial stiffness, cardiovascular remodeling, and a higher risk of cardiovascular events. In addition, behavioral and psychosocial factors, such as physical inactivity, sleep disturbances, and mood changes, amplify the deleterious effects of stress on the cardiovascular system. It is concluded that chronic stress constitutes a relevant and modifiable cardiovascular risk factor and should be systematically incorporated into the assessment and clinical management of cardiovascular diseases, although the methodological heterogeneity of the studies highlights the need for future investigations with greater standardization and longitudinal designs.