A study published in JAMA revealed that mental stress-induced myocardial ischemia was associated with a 2.5-fold greater risk of cardiovascular death or nonfatal myocardial infarction in 918 patients with stable coronary heart disease. Participants underwent both a standardized mental stress test involving public speaking and conventional exercise or pharmacological stress testing, with myocardial ischemia assessed using single-photon emission computed tomography. Conventional stress-induced ischemia alone was not significantly associated with the primary outcome, while patients who developed ischemia during both tests had the greatest risk.
Although the study cannot establish causation or be generalized to people without established coronary disease, it demonstrates that mental stress can trigger a measurable cardiovascular response with prognostic significance. This response involves the brain–heart axis, through which emotional processing influences cardiovascular function via the autonomic nervous system and hypothalamic–pituitary–adrenal (HPA) axis. A review in Atherosclerosis describes how acute psychological stress can increase sympathetic activity, heart rate, blood pressure, and vascular tone, while altering myocardial blood flow.
Notably, mental stress can produce myocardial ischemia at lower levels of cardiac workload than physical stress. Coronary vasoconstriction and microvascular dysfunction may contribute, suggesting that the cardiovascular effects of psychological stress involve not only increased cardiac demand but also altered coronary vascular function.
Over time, repeated activation of these pathways may affect vascular health. A review in the Journal of Clinical Medicine identifies mental stress as an emerging risk and prognostic factor for coronary artery disease and stroke. Chronic sympathetic and HPA-axis activation may contribute to endothelial dysfunction, impaired nitric oxide (NO) signaling, vascular constriction, and inflammation—all processes implicated in atherosclerosis.
The endothelium is particularly relevant, as it regulates vascular tone and helps maintain arterial integrity. A companion review describes how mental stress can impair endothelial function through sympathetic activation, cortisol-related inhibition of nitric oxide signaling, and increased pro-inflammatory activity. Sympathetic activation may also influence bone marrow activity and immune-cell trafficking through a neural–hematopoietic–arterial pathway, promoting inflammatory processes within the arterial wall.
Yet the stress response itself is adaptive. Sympathetic and HPA-axis activation rapidly increase cardiovascular output and mobilize energy in response to challenge. The concern is not activation, but prolonged activation without adequate recovery. Persistent sympathetic activity, impaired parasympathetic regulation, endothelial dysfunction, and inflammatory signaling may sustain this physiological burden over time.
This brings stress resilience into focus. Heart-rate variability (HRV) provides one window into autonomic regulation, and lower HRV has generally been associated with impaired autonomic regulation and greater cardiovascular risk. HRV is influenced by numerous physiological and behavioral factors, however, and is best viewed as one indicator of autonomic adaptability rather than a standalone measure of stress or cardiovascular health.
The relationship between stress, the heart, and the brain may also be bidirectional. A 2025 review associated chronic emotional stress with persistent sympathetic and HPA-axis activation, neuroinflammation, oxidative stress, and changes in brain regions involved in emotional and cognitive regulation. More recent research describes the heart–brain axis as an integrated system of neural, hormonal, vascular, and immune signaling in which dysfunction in either organ can influence the other.
Repeated exposure to psychological stress may therefore increase cumulative physiological demand and contribute to cardiovascular vulnerability. Acute stress is adaptive, but prolonged activation without adequate recovery may be more consequential. Supporting that recovery may involve practices that promote autonomic regulation, such as paced breathing and HRV biofeedback, and may help strengthen the physiological response to stress. Time spent in nature may also help reduce physiological stress load, while nutrient density supports the systems required for adaptation and recovery. Cardiovascular resilience ultimately depends on the coordinated support of the systems that allow the body to adapt, respond and recover.