Global Analysis Finds High Stress Levels Raise Risk of Cardiovascular Disease

Annika Rosengren, MD, PhD

A new study with more than 110,000 participants from 21 countries on 5 continents is providing what could be the most comprehensive overview yet of the effects of stress on development of cardiovascular disease events and mortality.

Results of the population-based cohort study, which assessed psychosis stress as a composite score of self-perceived stress, life events, and financial stress, suggest patients considered to have high stress levels had a 22% greater risk of cardiovascular disease, a 24% greater risk of congestive heart disease, and a 30% greater risk of stroke compared to their counterparts with no stress.

“It’s not known exactly what causes the elevated risk of cardiovascular disease among the severely stressed people. But many different processes in the body, such as atherosclerosis and blood clotting, may be affected by stress,” said Annika Rosengren, MD, PhD, Professor of Medicine at the Institute of Medicine at Sahlgrenska Academy at University of Gothenburg, in a statement. “If we want to reduce the risk of cardiovascular disease globally, we need to consider stress as another modifiable risk factor.”

To provide a more thorough consensus on stress as a potential risk factor for cardiovascular disease, Rosengren and a team of investigators designed the current study as an analysis of data from the Prospective Urban Rural Epidemiological (PURE) population study. With data collected from January 2003-March 2021, PURE followed 225,000 participants in detail from more than 1000 urban and rural communities in 27 high, middle, and low-income countries

For the purpose of analysis, countries were classified based on gross national income per capita. Canada, Saudi Arabia, Sweden, and the United Arab Emirates were considered high-income, Argentina, Brazil, Chile, China, Colombia, Iran, Malaysia, Occupied Palestinian Territory, Philippines, Poland, South Africa, and Turkey were considered middle-income, and Bangladesh, India, Pakistan, Tanzania, and Zimbabwe were considered low-income.

Stress was assessed using a composite score calculated by summing the score of psychological stress, major life event, and financial stress. Each individual component of the composite stress score was assessed and, based on responses, participants were either given a score of 0 or 1, with 1 indicating presence of stress. Scores ranged from 0-3, with 0 considered no stress, 1 considered low stress, 2 considered moderate stress, and 3 considered high stress.

After exclusion of those with prior cardiovascular disease and those without complete baseline and follow-up data, investigators identified a cohort of 118,705 participants from 21 countries for inclusion. The cohort consisted of 15,588 participants from high-income countries, 86,937 from middle-income countries, and 16,181 from low-income countries.

The study cohort had a mean age of 50.4 (SD, 9.6) years and 58.8% were women. Of the 118,705 participants included in the study, 8699 participants (7.3%) were categorized as having high stress, 21,797 participants (18.4%) were categorized as having moderate stress, 34,958 (29.4%) were categorized as having low stress, and 53,252 participants (44.8%) were categorized as having no stress.

Compared to those with no stress, those with high stress were more likely to be younger (mean age: 48.9 [SD, 8.9] years vs 51.1 [SD, 9.8] years), have abdominal obesity (34.3% vs 19.9%), be current (26.7% vs 19.7%) and former smokers (18.1% vs 7.5%), report alcohol use (48.5% vs 24.8%), and have family history of cardiovascular disease (62.5% vs 38.0%).

The primary outcomes of interest were major cardiovascular disease, major congestive heart disease, stroke, and all-cause mortality. Major cardiovascular disease was defined as a composite of cardiovascular death, stroke, myocardial infarction, and heart failure. Major congestive heart disease was defined as acute myocardial infarction and coronary death.

During the follow-up period, which lasted a median of 10.2 (IQR, 8.6-11.9) years, 7248 deaths occurred among the study cohort. A total of 5934 major cardiovascular disease events, 4107 major congestive heart disease events, and 2880 stroke events. In analyses adjusted age, sex, education, marital status, location, abdominal obesity, hypertension, smoking, diabetes, and family history, increased stress levels were associated with increased risk of mortality (low stress: HR, 1.09 [95% CI, 1.03-1.16]; high stress: 1.17 [95% CI, 1.06-1.29]) and congestive heart disease (low stress: HR, 1.09 [95% CI, 1.01-1.18]; high stress: HR, 1.24 [95% CI, 1.08-1.42]). However, in these same models, only high stress was associated with major cardiovascular disease and stroke (HR, 1.30 [95% CI, 1.09-1.56]).

Investigators noted the need for further studies examining the association of increased stress with cardiovascular risk and means of intervention to alleviate this potential burden.

“Substantial evidence has accumulated with respect to the associations of stress and other psychosocial factors with CVD, mainly CHD and stroke, which is supported by our findings. How these factors should be assessed and quantified in a more reliable and reproducible manner across different settings remains to be determined,” wrote investigators.

This study, “Psychosocial Risk Factors and Cardiovascular Disease and Death in a Population-Based Cohort From 21 Low-, Middle-, and High-Income Countries,” was published in JAMA Network Open.