Mental stress: A novel cardiovascular risk factor

Table 2 Some recent studies on the cardiovascular effects of chronic stress

Ref.	Setting	Main results
Li et al[163], 2015	Systematic review of 5 papers derived from 4 prospective studies conducted in Sweden and Canada	Significant effect of work stress (based on the Demand Control model or the Effort-Reward Imbalance model) on the risk of recurrent CHD events (HR = 1.65, 95%CI: 1.23-2.22)
Endrighi et al[138], 2016	HF patients longitudinally evaluated for psychological stress and CV hospitalizations/death	Patients reporting high average perceived stress a higher likelihood of adverse events compared to those with lower stress (OR = 1.10, 95%CI: 1.04-1.17). Perceived stress was elevated after a CV hospitalization (P = 0.004). An association between stress and adverse events was present when accounting for prior hospitalizations (P = 0.05)
Hirokawa et al[159], 2016	Between 2001 and 2009 in Osaka, Japan, authors examined 928 healthy Japanese employees from two occupational statuses: Managers/professionals and general workers. Changes in stress reactivity were calculated as the difference between the measured variables during the tasks and the rest period	Men showed inverse associations between quantitative job overload and DBP, HR, and LF/HF HRV, between physical demands and SBP, DBP, and between a poor physical environment and HF. Men also had positive associations between qualitative job overload and HR, and between physical demands and peripheral blood flow (all P < 0.05). Significant associations between job stress and changes in stress reactivity were observed in male managers/professionals and female general workers (P < 0.05)
Theorell et al[164], 2016	Systematic review of associations between occupational exposures and CHD. Ninety-six articles of high or medium high scientific quality were finally included	Moderately strong evidence for a relationship between job strain and small decision latitude on one hand and CHD incidence on the other hand. Limited evidence was found for pressing work, effort-reward imbalance, low support, lack of justice, lack of skill discretion, insecure employment, night work, long working week, and noise in relation to CHD
Jacob and Kostev[162], 2017	The study population consisted of 7374 patients who experienced a workplace conflict and 7374 controls for analysis identified by 699 general practitioners (Frankfurt, Germany)	After a maximum of five years of follow-up, 2.9% of subjects who experienced workplace conflict were affected by CVD, while 14% in the control group (P < 0.001). Workplace conflict was associated with a 163-fold increase in the risk of developing CVD. Finally, the impact of workplace conflict was higher for AMI than for angina pectoris and stroke (respectively OR = 2.03, 1.79, and 1.56)
Stewart et al[82], 2017	A total of 950 participants in the LIPID trial completed General Health Questionnaires-30. Cox proportional hazards models evaluated the risk of CV and total mortality by increasing levels of psychological distress over a median of 12.1 years	Patients with persistent moderate or greater psychological stress had a higher risk of both CV death (aHR = 3.94, 95%CI: 2.05-7.56, P < 0.001) and all-cause mortality (aHR = 2.85, 95%CI: 1.74-4.66, P < 0.001) compared with patients with no distress. In contrast, patients who reported persistent mild distress did not have an increased risk of CV or all-cause mortality during follow-up
Hagström et al[121], 2018	Psychosocial stress was assessed by a questionnaire in 14577 patients with stable CHD on optimal secondary preventive therapy in the prospective randomized STABILITY clinical trial	After 3.7 years of follow-up, financial stress was associated with increased risk (HR, 95%CI) of CV death (1.19, 1.08-1.30) and the primary composite endpoint of CV death, nonfatal AMI or nonfatal stroke (1.17, 1.10-1.24)
Lecca et al[154], 2018	Overall, 568 healthy workers of a flight logistic company were evaluated using the Health and Safety Executive questionnaire, the Framingham Heart Study General CVD Risk Prediction Score, and the WHO general well-being index (WHO-5)	Low job support significantly increases the CVD risk score and decreases the WHO well-being index with reference to subjects reporting high support on the job. In addition, job control, job support, low strain, and high demand coupled with high control (active job) showed a beneficial effect on psychological well-being
Stewart et al[122], 2018	Systematic review of literature (37 studies examining stress in mid-life and either CVD endpoints or subclinical CVD outcomes)	Significant risk of CVD due to stress. Most studies showed that mid-life women experiencing greater levels of stress had more subclinical CVD, as indicated by CIMT, flow-mediated dilation and arterial stiffness
Virtanen and Kivimäki[166], 2018	Large-scale meta-analyses with published and individual participant observational data on more than 740000 men and women free of CVD	Link between long working hours (≥ 55 hours a week) and the onset of CVD. Overall, 1.12-fold (95%CI: 1.03-1.21) increased risk of CHD and 1.21-fold (95%CI: 1.01-1.45) increased risk of stroke
Cabeza de Baca et al[116], 2019	The cross-sectional association between financial strain and ICH were examined in the Women’s Health Study follow-up cohort (n = 22048; mean age= 72 ± 6.0 years)	Number of financial stressors was associated with lower ideal cardiovascular health after adjustment for potential confounders (1 financial stressor: β = -0.10, 95%CI: -0.13 to -0.07; 2 financial stressor: β = -0.20, 95%CI: -0.26 to -0.15; 3+ financial stressor: β = -0.44, 95%CI: -0.50 to -0.38)
Burroughs Peña et al[183], 2019	In 25062 women participating in the Women’s Health Study, authors examined the relationship between CPS and ICH, as defined by the American Heart Association Strategic 2020 goals. A CPS score summarized acute (e.g., negative life events) and chronic stressors (e.g., work, work-family spillover, financial, discrimination, relationship, and neighbourhood) and traumatic life event stress reported on a stress questionnaire	White women had the lowest mean CPS scores (White: 161.7 ± 50.4; Hispanic: 171.2 ± 51.7; Black: 172.5 ± 54.9; Asian: 170.8 ± 50.6; P overall < 0.01). Mean ICH scores varied by race/ethnicity (P < 0.01) and were significantly lower in Black women and higher in Asian women when compared to White women (β coefficient and 95%CI: Hispanics -0.02: -0.13 to -0.09; Blacks -0.34: -0.43 to -0.25; Asians 0.34: 0.24-0.45). Interactions between CPS and race/ethnicity in ICH models were not significant
Endrighi et al[83], 2019	In a prospective cohort study (BETRHEART), 144 HF patients were evaluated for stress (PSS) and anger at baseline and every 2 weeks for 3 months. Functional status (6MWT) and health status (KCCQ) were also measured	Average PSS and greater than usual increases in PSS were associated with worsened KCCQ scores. Greater than usual increases in PSS were associated with worsened 6MWT. Average anger levels were associated with worsened KCCQ, and increases in anger were associated with worsened 6MWT
Moran et al[126], 2019	The Jackson Heart Study is a longitudinal cohort study of cardiovascular disease risks in 2256 African Americans in the Jackson, Mississippi metropolitan statistical area. Financial stress was assessed from the Jackson Heart Study Weekly Stress Inventory	Participants with moderate to high (vs no) financial stress were more likely to have incident CHD events after controlling for demographics, SES, access to care, and traditional clinical risk factors (HR = 2.42, 95%CI: 1.13-5.17). The association between financial stress and CHD was no longer statistically significant adjusting for three specific risk factors: Depression, smoking status, and diabetes (HR = 199, 95%CI: 0.91-4.39)
Song et al[124], 2019	Population based, sibling-controlled cohort study on 136637 patients in the Swedish National Patient Register with stress related disorders, including PTSD, acute stress reaction, adjustment disorder, and other stress reactions, with a follow-up of 27 years	The crude incidence rate of any CVD was 10.5, 8.4, and 6.9 per 1000 person years among exposed patients, their unaffected full siblings, and the matched unexposed individuals, respectively. In sibling-based comparisons, the HR for any CVD was 1.64 (95%CI: 1.45-1.84), with the highest subtype specific HR observed for heart failure (6.95, 1.88-25.68). Stress related disorders were more strongly associated with early onset CVD (HR = 1.4, 1.32-1.49) for attained age < 50 than later onset ones (1.24, 1.18-1.30) for attained age ≥ 50 (P = 0.002)
Wu et al[151], 2019	The Taiwan bus driver cohort study recruited 1650 professional drivers	Occupational drivers with high overcommitment scores had an elevated risk for CVD (HR = 1.71; 95%CI: 1.04-2.82). Regarding target disease, overcommitment had an increased risk for CVD (HR = 1.27; 95%CI: 1.05-1.54) and CHD (HR = 1.32; 95%CI: 1.05-1.65)
Smaardijk et al[185], 2020	Metanalysis identified studies (44 articles including 227647 women and 321894 men) assessing the risk of psychological factors (anger/hostility, anxiety, depression, psychological distress, social support, type A behaviour pattern, type D personality, and PTSD) for MACE in samples with CHD	The association between psychological factors (all combined) and MACE was stronger in men (HR = 1.37, 95%CI: 1.27-1.48) than in women (HR = 1.21, 95%CI: 1.12-1.30; P = 0.017). A subset of the studies focusing on women showed significant associations between anger/hostility, depression, and distress with MACE. For men, statistically significant associations were found for anxiety, depression, and distress with MACE
Crom and Trappe[132], 2021	40 patients with an acute STEMI confirmed by ECG. The control group consisted of 80 patients without CAD	Patients with STEMI did not show significantly higher HCC compared to controls, nor was there correlation with the extent of AMI. Correlations were found between HCC and T2DM (P = 0.046, OR = 6.346), low high-density lipoprotein cholesterol concentration (P = 0.107), glycated haemoglobin concentration (P = 0.083), and chronic HF (P = 0.110)
Li et al[167], 2021	Prospective cohort study identified hypertensive workers from the population-based MONICA/KORA study in Southern Germany, who were free of any CVD and diabetes, interviewed at baseline for work stress (high demand plus low control) and impaired sleep (difficulties falling asleep and/or maintaining sleep)	In comparison to participants with low work stress and non-impaired sleep, participants with work stress (HR = 1.56, 95%CI: 0.81-2.98), or impaired sleep (HR = 1.76, 95%CI: 0.96-3.22) had an increased risk of CVD, while participants with both work stress and impaired sleep had the highest risk of CVD mortality (HR = 2.94, 95%CI: 1.18-7.33). Similar risk patterns were found for CHD mortality
Cain-Shields et al[146], 2022	The relationship between GSS and incident hypertension, diabetes, and obesity among 4485 participants in the Jackson Heart Study	Among men, those with high (vs low) GSS were 41% less likely to become obese over a mean period of eight years: 0.59 (0.36, 0.95), P = 0.03
Gaffey et al[120], 2022	Systematic review (28 studies on 58331 participants without a past psychiatric diagnosis, screened at baseline for depression, anxiety, PTSD, stress, and followed for > 6 months)	Subjects reporting high psychological distress showed a 28% greater risk of incident CVD compared to those with low or no distress
Kautzky et al[184], 2022	Healthy women were assessed for glucose metabolism, fatty liver index and anthropometric parameters. Psychological stress assessment included the “Brief Symptom Inventory”, and PSS. Biological stress response was evaluated with HRV and cortisol levels	Burnout and PSS scores were associated with insulin secretion, sputum cortisol, thyroid-stimulating hormone, anthropometric measures, and gender role. Brief Symptom Inventory ratings for psychiatric symptom dimensions were associated with insulin resistance, sex hormones, anthropometric measures, and gender role
Kubera et al[104], 2022	From the Whitehall II cohort data of 4969 men and 2138 women were analysed. Psychological stress (General Health Questionnaire) and body shape were measured	Increase in the expected hazard to develop CHD with high psychological stress (P = 0.017) in both genders. Subjects with consistently high psychological stress had a 24-fold (men) or 2.3-fold (women) higher risk for later CHD events compared to never-stressed subjects. Subjects with a high sum score of childhood experiences had a 10% increased hazard to develop fatal or non-fatal CHD events in adulthood
Gao et al[89], 2022	In stable CHD patients the Chinese version of the PSS was used. Patients were divided into HPS (Chinese version of the PSS ≥ 31) and NHPS groups	The log-rank analysis showed that risk of cardiovascular events with HPS was higher than NHPS (P = 0.012). After adjusting for demographic, lifestyle, and clinical information, the HPS group had significantly increased risk of events within 24 months (HR = 1.369, 95%CI: 1.037-1.807, P = 0.027), but less impact after 24 months
Birdit et al[115], 2023	A total of 238 individuals from the Stress and Well-being in Everyday Life Study reported life event stress. Of those individuals, 169 completed an ecological momentary assessment study in which they reported stress exposure every 3 hours, and 164 wore a heart rate monitor for up to 5 days	The study revealed 2 longitudinal trajectories of life event stress: Moderate-increasing and low-decreasing. Individuals in the moderate-increasing stress trajectory reported greater daily stress exposure. Black individuals in the low-decreasing trajectory and White individuals in the moderate-increasing trajectory showed positive associations between daily stress and heart rate
Söderberg et al[160], 2023	Cross-sectional study was conducted in a sub-cohort of the SCAPIS. Psychosocial exposure was evaluated with the job demand-control model and analysed according to the standard categorization: High strain (high demands-low control), active, passive (low demands-low control) and low strain	High strain was linked to increased adjusted PR for low HDL cholesterol in women (PR = 1.76; 95%CI: 1.25-2.48). High strain was also related to moderately increased PR for metabolic syndrome in men (PR = 1.25; 95%CI: 1.02-1.52). In addition, passive work was associated with diastolic hypertension in women (adjusted PR = 1.29; 95%CI: 1.05-1.59)
Lavigne-Robichaud et al[152], 2023	Prospective cohort in Quebec, Canada. In six thousand four hundred sixty-five white-collar workers without cardiovascular disease followed for 18 years job strain and ERI were measured with validated questionnaires	Exposure to either job strain or ERI was associated with an adjusted 49% CHD risk increase (HR = 1.49, 95%CI: 1.07-2.09). Combined exposure to job strain and ERI was associated with an adjusted 103% CHD risk increase (HR = 2.03, 95%CI: 1.38-2.97)
Pogosova et al[127], 2023	Patients with arterial hypertension and CHD managed in primary health care institutions in multi-year prospective COMETA study, using a VAS for assessment of stress level	The composite endpoint that included all-cause death and/or severe adverse cardiovascular outcomes was significantly associated with a high (VAS score ≥ 8) stress level (OR = 1.53; 95%CI: 1.00-2.33, P = 0.04)
Wendel et al[98], 2023	In 213 adults participating in the Pittsburgh Cold Study 3, early environment stress was assessed by four self-report measures consistent with the biological sensitivity to context theory. Average HR and mean BP reactivity to the TSTT were assessed on two occasions	Results generally did not support the stress reactivity hypothesis; little evidence that high-stress early environments were reliably associated with exaggerated CV reactivity or slower CV recovery. There was some support for the biological sensitivity to context theory; both high-stress and low-stress early environments were associated with exaggerated CV reactivity
Won et al[112], 2024	Retrospective observational study using data from the National Hospital Ambulatory Care Survey, Federal Reserve Economic Database, National Bureau of Economic Research, and CVD groupings from National Vital Statistics and Center for Medicare and Medicaid Services from 1999 to 2020 to analyse ED visits in relation to macroeconomic indicators	A significantly higher proportion of CVD ED visits related to HF and other acute CHD was observed during recessionary time periods both directly and with a 6-month lead and lag (P < 0.05). The proportion of aortic aneurysm and dissection and atherosclerotic CVD ED visits was significantly higher (P = 0.024) in the recession period with a 6-month lead and lag
Swarup et al[140], 2024	Meta-analysis (7 studies) on the association between financial stress and the incidence of major cardiac outcome	A significant association was found between financial stress and major cardiac outcomes (combined HR = 1.191, 95%CI: 1.00-1.47, P < 0.001)
Osibogun et al[117], 2024	Cross-sectional analysis of 6453 adults from the Multi-Ethnic Study of Atherosclerosis. Financial strain was assessed by questionnaire and responses were categorized as yes or no. ICH was measured from 7 metrics (smoking, BMI, physical activity, diet, total cholesterol, blood glucose and blood pressure)	Participants who reported financial strain had lower odds of average (OR = 0.82, 95%CI: 0.71-0.94) and optimal (0.73, 0.62-0.87) ICH scores. However, in the fully adjusted model, the association was only significant for optimal ICH scores (0.81, 0.68-0.97)
Ajibewa et al[203], 2024	Data from 3401 adults from the Coronary Artery Risk Development in Young Adults study, with no prior CVD event were analysed. Chronic stress lasting ≥ 6 months across five life domains (work, financial, relationships, health of self, and health of close other) was self-reported	Chronic stress was associated with lowered survival (time ratio = 0.92; 95%CI: 0.854-0.989), when adjusted for sociodemographic and lifestyle variables but no longer significant when adjusting for clinical factors. Social support was not a significant modifier (P > 0.05)
Méndez-Chacón[129], 2026	In the Costa Rica Longevity and Healthy Aging Study, multiple logistic regression models were used to analyse the relationship between stress and chronic diseases	Stress related to the health of close relatives is associated with an increased risk of developing cardiovascular events. Financial stress was associated with twice the risk of developing hypertension
Gopep et al[118], 2025	Cross-sectional analysis using publicly available data from 18, adults in the National Health and Nutrition Examination Survey	After adjustment, stress was significantly linked to higher odds of hypertension (β = 0.3, P < 0.03)
Ayaz Khan et al[123], 2025	Overall, 385 young adults from Islamabad, Pakistan completed the PSS in conjunction with the Hill-Bone Compliance to High Blood Pressure Therapy Scale	Perceived stress was moderately positively correlated with blood pressure control (P < 0.001). The greater the stress, the less effective blood pressure is controlled (P < 0.001)
Kutal et al[128], 2025	In young patients with a first-ever CIS and sex/age-matched stroke-free controls from 19 European centres self-perceived stress was assessed using a modified version of the PSS. Scores were categorized into low (0-13), moderate (14-26), and high (27-40) perceived stress	Patients were more often at least moderately stressed compared with controls (46.2% vs 33.3%, P < 0.001). Higher self-perceived stress as a discrete measure was independently associated with CIS (aOR = 1.04 per point increase; 95%CI: 1.01-1.07). Categorical PSS score analysis showed an independent association between moderate stress and CIS (OR = 1.47; 95%CI: 1.00-2.14), but not with high stress (2.62; 0.81-8.45)
Eleazu et al[190], 2025	In participants from the Dallas Heart Study phase 2 without prevalent CVD, individual chronic stress subcomponents (generalized stress, psychosocial, financial, and neighbourhood stress) were standardized and integrated to create a novel CSS	CSS was higher among participants who were younger, women, and Black or Hispanic individuals, with lower income and educational attainment (P < 0.0001 for each). In multivariable regression models, higher CSS associated with hypertension, smoking, higher BMI, haemoglobin A1C, high sensitivity C-reactive protein, and sedentary time (P < 0.01 for each). Over a median follow-up of 12.4 years, higher CSS associated with atherosclerotic CVD (aHR = 1.22 per SD, 95%CI: 1.01-1.47) and global CVD (aHR = 1.2, 95%CI: 1.03-1.40)
Hallab et al[139], 2025	Data from the multiethnic ≥ 50-year-old study population (2173 participants), a subset of the Health and Aging Brain Study: Health Disparities study	Having chronic stress is associated with 53% higher odds of disclosing concomitant CVD (aOR = 1.53, 1.1-2.53), 31% of type 2 diabetes (aOR = 1.31, 1.06-1.62), 23% of hypertension (aOR = 1.23, 1.02-1.49), and 30% obesity (aOR = 1.3, 1.09-1.55)
Nakhutina and McFarlane[125], 2025	From the National Health Interview Survey (2004-2013) (284497 individuals) psychological distress was measured using the Six-Item Kessler Psychological Distress Scale (a score of ≥ 13 indicated distress)	Unadjusted OR for stroke among psychologically distressed individuals was 3.1 (95%CI: 2.8-3.3; P < 0.01). After adjusting, the odds of stroke in those with psychological distress was nearly threefold (OR = 2.7; 95%CI: 2.3-3.2; P < 0.01). Classical risk factors attenuated this association, but the relationship remained highly significant (OR = 2.17, 95%CI: 1.81.3-2.60; P < 0.01)
Liu et al[141], 2025	A total of 7493 participants from Wave 3 (2015) of the China Health and Retirement Longitudinal Study were included. Stressful life events were assessed using five simple questions. CMM was defined as having two or more cardiometabolic diseases, including diabetes, heart disease and stroke	The prevalence of CMM increased with the number of stressful life events, ranging from 5.73% for one stressful life event to 6.61% for two or more. In the fully adjusted model, the OR (95%CI) for CMM were 149 (1.01-2.20) for participants experiencing marital problems. Compared with no stressful life events, an increasing number of stressful life events was associated with a higher risk of CMM (P < 0.001)
Lavigne-Robichaud et al[153], 2025	Prospective cohort study including 6295 employees without CVD at baseline from Quebec, Canada	During 15-year follow-up, the attributable fraction for job strain was 18.2% (95%CI 1.8-34.7), and for ERI 3.3% (95%CI: 1.6-8.2). Combined exposure to both stressors resulted in an attributable fraction of 19.5% (95%CI: 0.7-38.4)

CHD: Coronary heart disease; HR: Hazard ratio; CI: Confidence interval; HF: Heart failure; CV: Cardiovascular; OR: Odds ratio; DBP: Diastolic blood pressure; LF: Low frequency; HRV: Heart rate variability; SBP: Systolic blood pressure; CVD: Cardiovascular disease; LIPID: Long-Term Intervention with Pravastatin in Ischaemic Disease; aHR: Adjusted hazard ratio; AMI: Acute myocardial infarction; WHO: World Health Organization; CIMT: Carotid intima media thickness; ICH: Ideal cardiovascular health; BMI: Body mass index; CPS: Cumulative psychosocial stress; PSS: Perceived stress score; 6MWT: Six minutes walking test; KCCQ: Kansas City Cardiomyopathy Questionnaire; PTSD: Post-traumatic stress disorder; MACE: Major adverse cardiovascular events; STEMI: ST elevation myocardial infarction; ECG: Electrocardiogram; CAD: Coronary artery disease; HCC: Hair cholesterol concentration; T2DM: Type 2 diabetes mellitus; GSS: Goal striving stress; CHD: Coronary heart disease; HPS: High perceived stress; NHPS: Non-high perceived stress; SCAPIS: Swedish CArdioPulmonary bioImage Study; PR: Prevalence ratio; HDL: High-density lipoprotein; ERI: Effort reward imbalance; VAS: Visual analogue scale; BP: Blood pressure; TSTT: Trier Social Stress Test; ED: Emergency department; CIS: Cryptogenic ischemic stroke; CSS: Composite stress score; aOR: Adjusted odds ratio; CMM: Cardiometabolic multimorbidity.