The Impact of Psychological Stress on Cardiovascular Disease Risk

A substantial body of research highlights the association between psychological stress and mental health disorders such as depression and anxiety. Additionally, extensive research points to a significant link between stress and physical illness, with the bulk of these studies focused on cardiovascular risk.¹

The term “stress” generally represents “experiences in which the environmental demands of a situation outweigh the individual’s perceived psychological and physiological ability to cope with it effectively,” according to Crosswell et al.¹ In research exploring the relationship between stress and heart health, the concept of stress may refer to acute or chronic stress or exposure to daily stressors, stressful life events, or traumatic experiences.¹

Recent Evidence Linking Stress and CVD

A 2021 cohort study published in JAMA Network Open examined associations between a composite measure of psychological distress (based on assessments of self-perceived stress, life events, and financial stress) and the risk for cardiovascular disease (CVD), stroke, and death in 118,706 individuals (58.8% women) from 21 countries. Participants had a mean age of 50.4 years and no history of CVD at baseline.²

The results showed that high stress was linked to an increased risk for CVD (hazard ratio [HR], 1.22; 95% CI, 1.08-1.37) and stroke (HR, 1.30; 95% CI, 1.09-1.56) after adjustment for demographic variables and traditional CVD risk factors. Increasing stress levels were associated with an increasing risk for coronary heart disease (low stress: HR, 1.09; 95% CI, 1.01-1.18; high stress: HR, 1.24; 95% CI, 1.08-1.42) and death (low stress: HR, 1.09; 95% CI, 1.03-1.16; high stress: 1.17; 95% CI, 1.06-1.29).

In a 2021 study described in JAMA, researchers conducted a pooled analysis of data from 2 cohort studies to determine the association between mental stress-induced myocardial ischemia and cardiovascular events in 918 patients (mean age, 60 years; 34% women) with stable coronary heart disease. Investigators used myocardial perfusion single-photon emission computed tomography to compare the effects of myocardial ischemia provoked by mental stress (via a public speaking task) and conventional stress (via exercise stress testing or a pharmacological stress test with regadenoson).³

The findings revealed a higher risk for cardiovascular death or nonfatal myocardial infarction in patients with vs without mental stress-induced ischemia, after adjustment for a range of confounding variables (HR, 2.5; 95% CI, 1.8-3.5), with an event rate of 4.8 vs 2.3 per 100 patient-years, respectively), while those with conventional stress ischemia alone showed no significant increase in CVD risk.

Patients with both mental and conventional stress ischemia also demonstrated a substantially higher CVD risk than those with no ischemia (event rate, 8.1 per 100 patient-years; HR, 3.8; 95% CI, 2.6-5.6) and those with conventional stress ischemia only (HR, 2.7; 95% CI, 1.7-4.3).

Hospitalizations for heart failure were also higher among patients with vs without mental stress-induced ischemia (event rate, 12.6 vs 5.6 per 100 patient-years; HR, 2.0; 95% CI, 1.5-2.5).

This study and others showing associations between acute stress and myocardial ischemia seem to align with frequent patient reports of angina precipitated by stressful events, according to a 2022 review by Glenn N. Levine, MD, FACC, FAHA, master clinician and professor of medicine at Baylor College of Medicine and chief of cardiology at the Michael E. DeBakey VA Medical Center in Houston, Texas. In his paper published in the American Journal of Medicine, Dr Levine also examined evidence regarding the relationship between acute and chronic psychological stress and other types of cardiovascular dysfunction such as myocardial infarction.⁴

Proposed Mechanisms and Expert Insights

Regarding potential mechanisms driving the effects of psychological stress on CVD risk, Osborne et al wrote that chronic stress increases activity in the hypothalamic-pituitary-adrenocortical axis and the sympathetic nervous system, which increases inflammation and CVD risk factors including hypertension and insulin resistance. These processes lead to “increased arterial inflammation and noncalcified coronary plaque burden, resulting in higher CVD risk independent of traditional risk factors,” they explained.⁵

In addition, Dr Levine wrote that acute stress “leads to acute increases in sympathetic activity and increased circulating and local levels of catecholamines, prothrombotic effects, epicardial coronary arterial vasoconstriction in areas of pre-existing atherosclerotic disease, and impaired microvascular function, all in the setting of increased myocardial oxygen demand.”⁴

We interviewed Dr Levine as well as the following experts to learn more about the stress-CVD link: Viola Vaccarino, MD, PhD, the Wilton Looney Distinguished Professor of Cardiovascular Research in the Rollins School of Public Health at Emory University in Atlanta and professor in the division of cardiology at the Emory University School of Medicine; and Allison E. Gaffey, PhD, clinical psychologist and instructor in the section of cardiovascular medicine at Yale University School of Medicine in New Haven, Connecticut, and clinical investigator at the VA Connecticut Healthcare System.

Dr Vaccarino is the lead author of the 2021 study on stress-induced myocardial ischemia described above, and Dr Gaffey is the lead author of a 2022 meta-analysis of 15 studies indicating that psychological stress assessed by brief screening measures (such as the Patient Health Questionnaire and the Perceived Stress Scale) was associated with an increased risk for first-onset CVD.^3,6

What does the strongest evidence suggest about the impact of psychological stress on CVD risk? 

Dr Levine: The strongest evidence that psychological stress can affect the heart comes from 2 areas. One, psychological stress is the major cause of what is called Takotsubo cardiomyopathy, or “stress cardiomyopathy,” in which it seems like the patient is having a heart attack and major dysfunction of the left ventricle can be observed.⁴ 

Second, there are many well-done reports that catastrophic events, such as earthquakes, are associated with a short-term rise in heart attack, arrhythmias, and cardiac death. There is also a growing body of data that seems to suggest that psychological stress is associated with an increased long-term risk of developing heart disease.⁴

Dr Vaccarino: There are many studies that have described an association between various forms of stress exposure and CVD risk, despite different study designs, different populations, and differences in the definition of “stress.” Although this evidence applies to many different types of populations, the harmful effects appear stronger in high-risk groups, such as people who already have CVD. This evidence, however, is mostly based on perceived or self-reported stress, which could be imprecise or biased.

Our study used an objective way to provoke stress, with a laboratory stressor, and examined the prognostic significance of developing ischemia with mental stress. Those who developed ischemia with mental stress had a more than 2-fold increased risk of adverse events during a 5-year follow-up period, an association that was not explained by other factors. We believe these results provide possibly the strongest evidence linking psychological stress to CVD risk.³

Dr Gaffey: Over 40 years of evidence indicates that experiencing psychological stress, especially chronically, and related psychological distress, is associated with a greater risk for CVD. The strongest evidence in this area pertains to symptoms of depression and anxiety. In our recent study collapsing across different types of distress, there was a 28% greater risk of CVD onset for adults who reported high distress compared to those who reported no or low distress.⁶

What are the current implications for clinicians? For example, are there any specific recommendations about screening, prevention, or discussing this issue with certain patients?

Dr Levine: While the field has not advanced enough to strongly recommend psychological stress screening and treatment as an intervention that definitively decreases future risk, it is reasonable and prudent to at least be alert to increased psychological stress in patients at risk for or with heart disease, and in those who do seem to suffer from this, consider referral to a mental health expert.

Dr Vaccarino: The implications are that emotional factors are very important for the clinical course and outcome of patients with heart disease. There is a compelling need to include stress and mental health indicators in the risk assessment of patients with CVD. The current practice is mainly focused on addressing conventional risk factors and atherosclerotic disease. This is important because stress and mental health factors can be intervened upon—for example, using stress management training and, in some cases, medications.

Dr Gaffey: Using brief screeners to regularly assess psychological distress—as part of primary and secondary cardiovascular prevention—is advantageous for CVD risk stratification, and any distress screening is really more ethical than not screening. High distress captured via screening should be followed by connection with mental health, social work, or other supportive resources, depending on the needs of the patient.

What should be the focus of future research in this area? 

Dr Levine: Future research should include more prospective studies on the impact of psychological health on cardiac risk and further well-designed randomized trials of psychological stress reduction interventions and their impact on cardiovascular risk.

Dr Vaccarino: Further studies are needed to prove the utility of recognizing and treating myocardial ischemia provoked by psychological stress in the clinical setting. Also, we need to investigate alternative ways to identify the people who are most vulnerable to the harmful effects of stress on the cardiovascular system. This is because cardiac imaging, as we have done in this study, is expensive and carries radiation, and the protocol is time-consuming. If we can identify ways that are more practical in the clinical setting, such as vascular reactivity testing for stress, or even a blood panel of “stress biomarkers,” that would be extremely useful.

Dr Gaffey: There are socially- and biologically-based differences in the types of stressors experienced and impact of those stressors on men and women, respectively. Understanding associations between psychological distress and CVD risk by sex may help clarify the benefits of psychological distress screening and psychological care needed for each group.