Prognostic Value of Cardiovascular Biomarkers in the Population.

Importance: Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies. Objective: To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors. Design, Setting, and Participants: Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age. The median follow-up was 11.8 years. Exposure: Measurement of high-sensitivity cardiac troponin I, high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, B-type natriuretic peptide, or high-sensitivity C-reactive protein. Main Outcomes and Measures: The primary outcome was incident atherosclerotic cardiovascular disease, which included all fatal and nonfatal events. The secondary outcomes were all-cause mortality, heart failure, ischemic stroke, and myocardial infarction. Subdistribution hazard ratios (HRs) for the association of biomarkers and outcomes were calculated after adjustment for established risk factors. The additional predictive value of the biomarkers was assessed using the C statistic and reclassification analyses. Results: The analyses included 164 054 individuals (median age, 53.1 years [IQR, 42.7-62.9 years] and 52.4% were women). There were 17 211 incident atherosclerotic cardiovascular disease events. All biomarkers were significantly associated with incident atherosclerotic cardiovascular disease (subdistribution HR per 1-SD change, 1.13 [95% CI, 1.11-1.16] for high-sensitivity cardiac troponin I; 1.18 [95% CI, 1.12-1.23] for high-sensitivity cardiac troponin T; 1.21 [95% CI, 1.18-1.24] for N-terminal pro-B-type natriuretic peptide; 1.14 [95% CI, 1.08-1.22] for B-type natriuretic peptide; and 1.14 [95% CI, 1.12-1.16] for high-sensitivity C-reactive protein) and all secondary outcomes. The addition of each single biomarker to a model that included established risk factors improved the C statistic. For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277). The combination of these biomarkers also improved reclassification compared with the conventional model. Improvements in risk prediction were most pronounced for the secondary outcomes of heart failure and all-cause mortality. The incremental value of biomarkers was greater in people aged 65 years or older vs younger people. Conclusions and Relevance: Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality.

Trimethylamine-N-Oxide and Related Metabolites: Assessing Cardiovascular Risk in the Dallas Heart Study.

OBJECTIVE: To evaluate the association between trimethylamine N-oxide (TMAO) and related metabolites with adverse cardiovascular events in a multiethnic urban primary prevention population. METHODS: We performed a case-control study of 361 participants of the Dallas Heart Study, including 88 participants with an incident atherosclerotic cardiovascular disease (ASCVD) event and 273 controls matched for age, sex, and body mass index without an ASCVD event during 12 years of follow-up (January 1, 2000, through December 31, 2015). Plasma levels of TMAO, choline, carnitine, betaine, and butyrobetaine were measured by mass spectrometry. The differential odds for incident ASCVD by metabolite levels between cases and controls were compared by a conditional logistic regression model adjusted for cardiovascular risk factors. RESULTS: Participants with incident ASCVD had higher levels of TMAO and related metabolites compared with those without ASCVD (P<.05 for all). Those with plasma TMAO concentrations in quartile 4 had a more than 2-fold higher odds of ASCVD compared with those in quartile 1 (odds ratio, 2.77 [95% CI, 1.05 to 7.7; P=.04] for hard ASCVD and 2.41 [95% CI, 1.049 to 5.709; P=.04]). Similar trends were seen with the related metabolites choline, betaine, carnitine, and butyrobetaine. CONCLUSION: Our results suggest that TMAO and related metabolites are independently associated with ASCVD events. Although further studies are needed, measurement of TMAO and related metabolites may have a role in ASCVD risk stratification for primary prevention.

Characteristics of High-Performing Hospitals in Cardiogenic Shock Following Acute Myocardial Infarction.

Cardiogenic shock after acute myocardial infarction (AMI-CS) carries significant mortality despite advances in revascularization and mechanical circulatory support. We sought to identify the process-based and structural characteristics of centers with lower mortality in AMI-CS. We analyzed 16,337 AMI-CS cases across 440 centers enrolled in the National Cardiovascular Data Registry's Chest Pain-MI Registry, a retrospective cohort database, between January 1, 2015, and December 31, 2018. Centers were stratified across tertiles of risk-adjusted in-hospital mortality rate (RAMR) for comparison. Risk-adjusted multivariable logistic regression was also performed to identify hospital-level characteristics associated with decreased mortality. The median participant age was 66 (interquartile range 57 to 75) years, and 33.0% (n = 5,390) were women. The median RAMR was 33.4% (interquartile range 26.0% to 40.0%) and ranged from 26.9% to 50.2% across tertiles. Even after risk adjustment, lower-RAMR centers saw patients with fewer co-morbidities. Lower-RAMR centers performed more revascularization (92.8% vs 90.6% vs 85.9%, p <0.001) and demonstrated better adherence to associated process measures. Left ventricular assist device capability (odds ratio [OR] 0.78 [0.67 to 0.92], p = 0.002), more frequent revascularization (OR 0.93 [0.88 to 0.98], p = 0.006), and higher AMI-CS volume (OR 0.95 [0.91 to 0.99], p = 0.009) were associated with lower in-hospital mortality. However, several such characteristics were not more frequently observed at low-RAMR centers, despite potentially reflecting greater institutional experience or resources. This may reflect the heterogeneity of AMI-CS even after risk adjustment. In conclusion, low-RAMR centers do not necessarily exhibit factors associated with decreased mortality in AMI-CS, which may reflect the challenges in performing outcomes research in this complex population.

Intensive Blood Pressure Lowering in Individuals With Low Diastolic Blood Pressure and Elevated Troponin Levels in SPRINT.

BACKGROUND: Among individuals with hypertension and low diastolic blood pressure (DBP), the optimal BP target remains controversial due to concerns that BP lowering may reduce coronary perfusion. We determined the impact of intensive BP control among individuals with elevated systolic BP who have low DBP and elevated hs-cTnT (high-sensitivity cardiac troponin T) levels. METHODS AND RESULTS: A total of 8828 participants in SPRINT (Systolic Blood Pressure Intervention Trial) were stratified by baseline DBP. Those with low DBP (<70 mm Hg) were further stratified by elevated hs-cTnT (≥14 ng/L) at baseline. The effects of intensive versus standard BP lowering on a cardiovascular disease composite end point, all-cause death, and 1-year change in hs-cTnT were determined. The combination of low DBP/high hs-cTnT was independently associated with a higher risk for cardiovascular disease and all-cause death, as well as greater 1-year increases in hs-cTnT, compared with DBP ≥70 mm Hg. However, randomization to intensive versus standard BP lowering led to similar reductions in cardiovascular disease risk among individuals with low DBP/high hs-cTnT (hazard ratio [HR], 0.82 [95% CI, 0.57-1.19]), low DBP/low hs-cTnT (HR, 0.48 [95% CI, 0.29-0.79]), and DBP ≥70 mm Hg (HR, 0.73 [95% CI, 0.60-0.89]; P for interaction=0.20). Intensive BP lowering also led to a reduction in all-cause death that was similar across groups (P for interaction=0.57). CONCLUSIONS: In this nonprespecified subgroup analysis of SPRINT, individuals with low DBP and elevated hs-cTnT, low DBP and nonelevated hs-cTnT, and DBP ≥70 mm Hg derived similar cardiovascular disease and mortality benefits from intensive BP lowering. These findings warrant confirmation in other studies.

Associations of ambulatory blood pressure measurements with high-sensitivity troponin and natriuretic peptide levels in SPRINT.

BACKGROUND: Nighttime blood pressure (BP) has greater prognostic importance for cardiovascular disease (CVD) than daytime BP, but less is known about nighttime and daytime BP associations with measures of subclinical CVD. METHODS: Among 897 Systolic Blood Pressure Intervention Trial Study (SPRINT) participants with 24-hour ambulatory BP monitoring obtained near the 27-month study visit, 849 (95%) had N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) measured at the 24-month study visit. Multivariable linear regression analyses were performed to evaluate the associations of nighttime and daytime BP with cardiac biomarker levels. RESULTS: Mean age was 69 ±12 years, 28% were African American, and mean nighttime and daytime SBP were 121 ±16 mm Hg and 132 ±14 mm Hg, respectively. In multivariable models, compared with the lowest tertile of nighttime systolic BP, the highest tertile was associated with 48% higher NT-proBNP levels (adjusted geometric mean ratio [GMR] = 1.48, 95% CI: 1.22, 1.79), and 19% higher hs-cTnT levels (adjusted GMR = 1.19, 95% CI: 1.07, 1.32). In contrast, the highest versus lowest tertile of daytime systolic BP was not associated with NT-proBNP (adjusted GMR = 1.09, 95% CI: 0.88, 1.34) but was associated with 16% higher hs-cTnT levels (adjusted GMR = 1.16, 95% CI: 1.04, 1.30). Similar results were observed using diastolic BP. CONCLUSION: In SPRINT, both higher nighttime and daytime BP were independently associated with higher hs-cTnT levels, but only higher nighttime BP was associated with higher NT-proBNP levels.

Type 2 Myocardial Infarction-Poorly Understood, Underevaluated, and Too Often Ignored.

This Viewpoint discusses diagnosis of type 2 myocardial infarction.

Circulating transthyretin and retinol binding protein 4 levels among middle-age V122I TTR carriers in the general population.

BACKGROUND: Hereditary transthyretin cardiac amyloidosis (ATTRv-CA) has a long latency phase before clinical onset, creating a need to identify subclinical disease. We hypothesized circulating transthyretin (TTR) and retinol binding protein 4 (RBP4) levels would be associated with TTR carrier status and correlated with possible evidence of subclinical ATTRv-CA. METHODS: TTR and RBP4 were measured in blood samples from V122I TTR carriers and age-, sex- and race-matched non-carrier controls (1:2 matching) among Dallas Heart Study participants (phases 1 (DHS-1) and 2 (DHS-2)). Multivariable linear regression models determined factors associated with TTR and RBP4. RESULTS: There were 40 V122I TTR carriers in DHS-1 and 54 V122I TTR carriers in DHS-2. In DHS-1 and DHS-2, TTR was lower in V122I TTR carriers (p < .001 for both), and RBP4 in DHS-2 was lower in V122I TTR carriers than non-carriers (p = .002). Among V122I TTR carriers, TTR was negatively correlated with markers of kidney function, and limb lead voltage (p < .05 for both) and TTR and RBP4 were correlated with atrial volume in DHS-2 (p < .05). CONCLUSIONS: V122I TTR carrier status is independently associated with lower TTR and RBP4 in comparison with non-carriers. These findings support the hypothesis that TTR and RBP4 may correlate with evidence of subclinical ATTRv-CA.

National Variation in Hospital MTEER Outcomes and Correlation With TAVR Outcomes: STS/ACC TVT Registry Analysis.

BACKGROUND: A single, multitiered valve center designation has been proposed to publicly identify centers with expertise for all valve therapies. The correlation between transcatheter aortic valve replacement (TAVR) and mitral transcatheter edge-to-edge repair (MTEER) procedures is unknown. OBJECTIVES: The authors sought to examine the relationship between site-level volumes and outcomes for TAVR and MTEER. We further explored variability between sites for MTEER outcomes. METHODS: Using the STS/ACC TVT (Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy) national registry, TAVR and MTEER procedures at sites offering both therapies from 2013 to 2022 were examined. Sites were ranked into deciles of adjusted in-hospital and 30-day outcomes separately for TAVR and MTEER and compared. Stepwise, hierarchical multivariable models were constructed for MTEER outcomes, and the median OR was calculated. RESULTS: Between 2013 and 2022, 384,394 TAVRs and 53,274 MTEERs (median annualized volumes: 93.6 and 18.8, respectively) were performed across 453 U.S. sites. Annualized TAVR and MTEER volumes were moderately correlated (r = 0.48; P < 0.001). After adjustment, 14.3% of sites had the same decile rank for TAVR and MTEER 30-day composite outcome, 50.6% were within 2 decile ranks; 35% had more discordant outcomes for the 2 procedures (P = 0.0005). For MTEER procedures, the median OR for the 30-day composite outcome was 1.57 (95% CI: 1.51-1.64), indicating a 57% variability in outcome by site. CONCLUSIONS: There is modest correlation between hospital-level volumes for TAVR and MTEER but low interprocedural correlation of outcomes. For similar patients, site-level variability for mortality/morbidity following MTEER was high. Factors influencing outcomes and "centers of excellence" as a whole may differ for TAVR and MTEER.

Novel plasma biomarkers of coronary artery calcium incidence or progression: Insights from the prospective multi-ethnic Dallas Heart Study cohort.

BACKGROUND AND AIMS: Identifying the association of novel plasma biomarkers with coronary artery calcium (CAC) incidence or progression may provide insights into the pathophysiology of atherogenesis and plaque formation. METHODS: Participants of the Dallas Heart Study (DHS), a multi-ethnic cohort of ambulatory individuals at low-intermediate risk for future atherosclerotic cardiovascular disease (ASCVD), who had their blood tested for 31 biomarkers reflecting multiple pathophysiological pathways, underwent 2 serial non-contrast computed tomography assessments for CAC a median ∼7 years apart. The collected biomarkers were explored for association with CAC incidence or progression using univariate and multivariate analysis. RESULTS: A total of 1424 participants were included; mean age 43 years, 39 % male, and nearly half African-American. Over a 7-year interval between the two CAC measurements, 340 participants (23.9 %) had CAC incidence or progression, 105 (7.4 %) with incident CAC, and 309 (21.7 %) with CAC progression. Although several plasma biomarkers were associated with CAC incidence or progression in a univariate model, only soluble intercellular adhesion molecule-1 (sICAM-1), related to atherosclerosis by the inflammatory pathway, remained independently associated in a multivariate model adjusted for traditional risk factors. CONCLUSIONS: Further studies are needed to characterize the role of sICAM-1 in CAC evolvement to establish whether it has a pivotal mechanistic contribution or is rather an innocent bystander. Alternate measures of coronary atherosclerosis may be needed to elucidate contributors to atherosclerosis incidence or progression.

High-Sensitivity Cardiac Troponins I and T and Cardiovascular Outcomes: Findings from the Systolic Blood Pressure Intervention Trial (SPRINT).

BACKGROUND: Cardiac troponins are associated with adverse cardiovascular disease (CVD) outcomes. The value of high-sensitivity cardiac troponin I (hs-cTnI) independently and in concert with troponin T (hs-cTnT) in the management of hypertension has not been well studied. METHODS: We assessed the utility of hs-cTnI independently and with hs-cTnT in identifying the highest risk individuals in the Systolic Blood Pressure Intervention Trial (SPRINT). Among 8796 eligible SPRINT participants, hs-cTnI was measured at baseline and 1 year. The association of baseline level and 1-year change in hs-cTnI with CVD events and all-cause death was evaluated using adjusted Cox regression models. We further assessed the complementary value of hs-cTnI and hs-cTnT by identifying concordant and discordant categories and assessing their association with outcomes. RESULTS: hs-cTnI was positively associated with composite CVD risk [myocardial infarction, other acute coronary syndrome, stroke, or cardiovascular death: hazard ratio 1.23, 95% confidence interval 1.08-1.39 per 1-unit increase in log(troponin I)] independent of traditional risk factors, N-terminal pro-B-type natriuretic peptide, and hs-cTnT. Intensive blood pressure lowering was associated with greater absolute risk reduction (4.5% vs 1.7%) and lower number needed to treat (23 vs 59) for CVD events among those with higher baseline hs-cTnI (≥6 ng/L in men, ≥4 ng/L in women). hs-cTnI increase at 1 year was also associated with increased CVD risk. hs-cTnI and hs-cTnT were complementary, and elevations in both identified individuals with the highest risk for CVD and death. CONCLUSIONS: Baseline levels and change in hs-cTnI over 1 year identified higher-risk individuals who may derive greater cardiovascular benefit with intensive blood pressure treatment. hs-TnI and hs-TnT have complementary value in CVD risk assessment. ClinicalTrials.gov Registration Number: NCT01206062.

Changes in Natriuretic Peptide Levels and Subsequent Kidney Function Decline in SPRINT.

RATIONALE & OBJECTIVE: Novel approaches to the assessment of kidney disease risk during hypertension treatment are needed because of the uncertainty of how intensive blood pressure (BP) lowering impacts kidney outcomes. We determined whether longitudinal N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements during hypertension treatment are associated with kidney function decline. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: 8,005 SPRINT (Systolic Blood Pressure Intervention Trial) participants with NT-proBNP measurements at baseline and 1 year. EXPOSURE: 1-year change in NT-proBNP categorized as a ≥25% decrease, ≥25% increase, or <25% change (stable). OUTCOME: Annualized change in estimated glomerular filtration rate (eGFR) and ≥30% decrease in eGFR. ANALYTICAL APPROACH: Linear mixed-effect and logistic regression models were used to evaluate the association of changes in NT-proBNP with subsequent annualized change in eGFR and ≥30% decrease in eGFR, respectively. Analyses were stratified by baseline chronic kidney disease (CKD) status. RESULTS: Compared with stable 1-year NT-proBNP levels, a ≥25% decrease in NT-proBNP was associated with a slower decrease in eGFR in participants with CKD (adjusted difference, 1.09%/y; 95% CI, 0.35-1.83) and without CKD (adjusted difference, 0.51%/y; 95% CI, 0.21-0.81; P = 0.4 for interaction). Meanwhile, a ≥25% increase in NT-proBNP in participants with CKD was associated with a faster decrease in eGFR (adjusted difference, -1.04%/y; 95% CI, -1.72 to -0.36) and risk of a ≥30% decrease in eGFR (adjusted odds ratio, 1.44; 95% CI, 1.06-1.96); associations were stronger in participants with CKD than in participants without CKD (P = 0.01 and P < 0.001 for interaction, respectively). Relationships were similar irrespective of the randomized BP arm in SPRINT (P > 0.2 for interactions). LIMITATIONS: Persons with diabetes and proteinuria >1 g/d were excluded. CONCLUSIONS: Changes in NT-proBNP during BP treatment are independently associated with subsequent kidney function decline, particularly in people with CKD. Future studies should assess whether routine NT-proBNP measurements may be useful in monitoring kidney risk during hypertension treatment. PLAIN-LANGUAGE SUMMARY: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a biomarker in the blood that reflects mechanical stress on the heart. Measuring NT-proBNP may be helpful in assessing the risk of long-term losses of kidney function. In this study, we investigated the association of changes in NT-proBNP with subsequent kidney function among individuals with and without chronic kidney disease. We found that increases in NT-proBNP are associated with a faster rate of decline of kidney function, independent of baseline kidney measures. The associations were more pronounced in individuals with chronic kidney disease. Our results advance the notion of considering NT-proBNP as a dynamic tool for assessing kidney disease risk.

Long term risk of death and readmission after hospital admission with covid-19 among older adults: retrospective cohort study.

OBJECTIVES: To characterize the long term risk of death and hospital readmission after an index admission with covid-19 among Medicare fee-for-service beneficiaries, and to compare these outcomes with historical control patients admitted to hospital with influenza. DESIGN: Retrospective cohort study. SETTING: United States. PARTICIPANTS: 883 394 Medicare fee-for-service beneficiaries age ≥65 years discharged alive after an index hospital admission with covid-19 between 1 March 2020 and 31 August 2022, compared with 56 409 historical controls discharged alive after a hospital admission with influenza between 1 March 2018 and 31 August 2019. Weighting methods were used to account for differences in observed characteristics. MAIN OUTCOME MEASURES: All cause death within 180 days of discharge. Secondary outcomes included first all cause readmission and a composite of death or readmission within 180 days. RESULTS: The covid-19 cohort compared with the influenza cohort was younger (77.9 v 78.9 years, standardized mean difference -0.12) and had a lower proportion of women (51.7% v 57.3%, -0.11). Both groups had a similar proportion of black beneficiaries (10.3% v 8.1%, 0.07) and beneficiaries with dual Medicaid-Medicare eligibility status (20.1% v 19.2%; 0.02). The covid-19 cohort had a lower comorbidity burden, including atrial fibrillation (24.3% v 29.5%, -0.12), heart failure (43.4% v 49.9%, -0.13), and chronic obstructive pulmonary disease (39.2% v 52.9%, -0.27). After weighting, the covid-19 cohort had a higher risk (ie, cumulative incidence) of all cause death at 30 days (10.9% v 3.9%; standardized risk difference 7.0%, 95% confidence interval 6.8% to 7.2%), 90 days (15.5% v 7.1%; 8.4%, 8.2% to 8.7%), and 180 days (19.1% v 10.5%; 8.6%, 8.3% to 8.9%) compared with the influenza cohort. The covid-19 cohort also experienced a higher risk of hospital readmission at 30 days (16.0% v 11.2%; 4.9%, 4.6% to 5.1%) and 90 days (24.1% v 21.3%; 2.8%, 2.5% to 3.2%) but a similar risk at 180 days (30.6% v 30.6%;-0.1%, -0.5% to 0.3%). Over the study period, the 30 day risk of death for patients discharged after a covid-19 admission decreased from 17.9% to 7.2%. CONCLUSIONS: Medicare beneficiaries who were discharged alive after a covid-19 hospital admission had a higher post-discharge risk of death compared with historical influenza controls; this difference, however, was concentrated in the early post-discharge period. The risk of death for patients discharged after a covid-19 related hospital admission substantially declined over the course of the pandemic.

Associations of Cumulative Perceived Stress with Cardiovascular Risk Factors and Outcomes: Findings from The Dallas Heart Study.

Background: Data remain sparse regarding the impact of chronic stress on cardiovascular disease (CVD) risk factors and outcomes. Prior work has been limited by incomplete assessments of perceived stress and focus on single stress domains. We evaluated the association between a composite measure of perceived stress and CVD risk factors and outcomes. Methods: Participants from the Dallas Heart Study phase 2 (2007-2009) without prevalent CVD who completed questionnaire assessments of perceived stress were included (n=2685). Individual perceived stress subcomponents (generalized stress, psychosocial, financial, and neighborhood stress) were standardized and integrated into a single cumulative stress score (CSS) with equal weighting for each component. Associations between CSS and demographics, psychosocial variables and cardiac risk factors were assessed in univariable and multivariable analyses. Cox proportional hazards models were used to determine associations of the CSS with atherosclerotic CVD (ASCVD) and Global CVD (ASCVD, heart failure, and atrial fibrillation) after adjustment for demographics and traditional risk factors. Results: Median age of the study population was 48 years, 55% were female, 49% Black and 15% Hispanic/Latinx. CSS was higher among participants who were younger, female, Black or Hispanic, and those with lower income and educational attainment (p<.0001 for each). Higher CSS was associated with self-report of racial/ethnic discrimination, lack of health insurance and last medical contact > one year previously (p<.0001 for each). In multivariable regression models adjusting for age, gender, race/ethnicity, income and education, higher CSS associated with hypertension, smoking, and higher body mass index, waist circumference Hemoglobin A1C, hs-CRP and sedentary time (p< 0.01 for each). Over a median follow-up of 12.4 years, higher CSS associated with ASCVD (adjusted HR 1.22 per SD, 95% CI 1.01-1.47) and Global CVD (HR 1.20, 95% CI 1.03-1.40). No interactions were seen between CSS, demographic factors, and outcomes. Conclusion: Composite multidimensional assessments of perceived stress may help to identify individuals at risk for CVD who may be targeted for stress mitigation or enhanced prevention strategies. These approaches may be best focused on vulnerable populations, given the higher burden of stress in women, Black and Hispanic individuals, and those with lower income and education. WHAT IS NEW?: A novel measure of cumulative stress was created that integrates generalized, psychosocial, financial, and neighborhood perceived stress.Cumulative stress was higher among women, Black and Hispanic participants, younger individuals and persons with lower income and educational attainment and was associated with adverse health behaviors and increased burden of cardiovascular disease (CVD) risk factors.In a diverse cohort, higher cumulative stress associated with incident CVD after adjustment for demographics and traditional risk factors. No interactions were seen based on demographic factors. CLINICAL IMPLICATIONS: Although associations of chronic stress with CVD were similar across demographic subgroups, the higher burden of stress among younger individuals, women, Black and Hispanic participants, and those with lower SES suggests that CVD risk associated with higher stress affects marginalized groups disproportionately.Cumulative Stress is associated with modifiable risk factors and health behaviors. Future studies should explore targeting behavioral modification and risk factor reduction programs, as well as stress reduction strategies, to individuals with high cumulative stress.Additional research is needed to uncover mechanisms that underly the association between chronic stress and cardiovascular disease.