Young women after MI have a 2-fold likelihood of developing MSIMI compared with men and a similar increase in conventional stress ischemia. Microvascular dysfunction and peripheral vasoconstriction with mental stress are implicated in MSIMI among women but not among men, perhaps reflecting women's proclivity toward ischemia because of microcirculatory abnormalities.

Importance Prior pandemics have disparately affected socially vulnerable communities. Whether regional variations in social vulnerability to disasters influence COVID-19 outcomes and incidence in the U.S. is unknown. Objective To examine the association of Social Vulnerability Index (SVI), a percentile-based measure of county-level social vulnerability to disasters, and its sub-components (socioeconomic status, household composition, minority status, and housing type/transportation accessibility) with the case fatality rate (CFR) and incidence of COVID-19. Design Ecological study of counties with at least 50 confirmed COVID-19 cases as of April 4th, 2020. Generalized linear mixed-effects models with state-level clustering were applied to estimate county-level associations of overall SVI and its sub-component scores with COVID-19 CFR (deaths/100 cases) and incidence (cases/1000 population), adjusting for population percentage aged >65 years, and for comorbidities using the average Hierarchical Condition Category (HCC) score. Counties with high SVI (≥median) and high CFR (≥median) were identified. Setting Population-based study of U.S. county-level data. Participants U.S. counties with at least 50 confirmed COVID-19 cases. Main outcomes and measures COVID-19 CFR and incidence. Results Data from 433 counties including 283,256 cases and 6,644 deaths were analyzed. Median SVI was 0.46 [Range: 0.01-1.00], and median CFR and incidence were 1.9% [Range: 0-13.3] and 1.2 per 1000 people [Range: 0.6-38.8], respectively. Higher SVI, indicative of greater social vulnerability, was associated with higher CFR (RR: 1.19 [1.05, 1.34], p=0.005, per-1 unit increase), an association that strengthened after adjustment for age>65 years and comorbidities (RR: 1.63 [1.38, 1.91], p<0.001), and was further confirmed in a sensitivity analysis limited to six states with the highest testing levels. Although the association between overall SVI and COVID-19 incidence was not significant, the SVI sub-components of socioeconomic status and minority status were both predictors of higher incidence and CFR. A combination of high SVI (≥0.46) and high adjusted CFR (≥2.3%) was observed in 28.9% of counties. Conclusions and Relevance Social vulnerability is associated with higher COVID-19 case fatality. High social vulnerability and CFR coexist in more than 1 in 4 U.S. counties. These counties should be targeted by public policy interventions to help alleviate the pandemic burden on the most vulnerable population.

Aims Mental stress-induced myocardial ischemia (MSIMI) in patients with coronary artery disease (CAD) is associated with adverse cardiovascular outcomes. We aim to assess hemodynamic, neuro-hormonal, endothelial, vasomotor and vascular predictors of MSIMI. Methods and Results We subjected 660 patients with stable CAD to 99mTc sestamibi myocardial perfusion imaging at rest, with mental (speech task) and with conventional (exercise/pharmacological) stress. Endothelium-dependent flow-mediated dilation (FMD), microvascular reactivity [reactive hyperemia index (RHI)] and arterial stiffness [pulse wave velocity (PWV)] were measured at rest and 30-min after mental stress. The digital microvascular vasomotor response during mental stress was assessed using peripheral arterial tonometry (PAT). A total of 106(16.1%) patients had MSIMI. Mental stress was accompanied by significant increases in rate-pressure-product (heart rate x systolic blood pressure; RPP), epinephrine levels and PWV, and significant decreases in FMD and PAT ratio denoting microvascular constriction. In comparison to those with no MSIMI, patients with MSIMI had higher hemodynamic and digital vasoconstrictive responses (p<0.05 for both), but did not differ in epinephrine, endothelial or macrovascular responses. Only presence of ischemia during conventional stress (OR of 7.1, 95%CI of 4.2, 11.9), high hemodynamic response (OR for RPP response ≥ vs < ROC cutoff of 1.8, 95%CI of 1.1, 2.8), and high digital vasoconstriction (OR for PAT ratio < vs ≥ ROC cutoff of 2.1, 95%CI of 1.3, 3.3) were independent predictors of MSIMI. Conclusion Ischemia during conventional stress testing and hemodynamic and vasoconstrictive responses to mental stress can help predict subjects with CAD at greater risk of developing MSIMI.

Women and men have distinct cardiovascular reactivity mechanisms for MSIMI. For women, stress-induced peripheral vasoconstriction with mental stress, and not increased hemodynamic workload, is associated with MSIMI, whereas for men, it is the opposite. Future studies should examine these pathways on long-term outcomes.

Background Higher symptom levels of a variety of measures of emotional distress have been associated with cardiovascular disease ( CVD ), especially among women. Here, our goal was to investigate the association between a composite measure of psychological distress and incident cardiovascular events. Methods and Results In a prospective cohort study, we assessed 662 individuals (28% women; 30% blacks) with stable coronary artery disease. We used a composite score of psychological distress derived through summation of Z‐transformed psychological distress symptom scales (depression, posttraumatic stress, anxiety, anger, hostility, and perceived stress) as a predictor of an adjudicated composite end point of adverse events (cardiovascular death, myocardial infarction, stroke, heart failure, or unstable angina). During a mean follow‐up of 2.8 years, 120 (18%) subjects developed CVD events. In the overall population, there was no association between the psychological distress measure and CVD events, but there was a sex‐based interaction ( P =0.004). In women, higher psychological distress was associated with a higher incidence of CVD events; each SD increase in the composite score of psychological distress was associated with 1.44 times adjusted hazard of CVD events (95% CI, 1.09–1.92). No such association was found in men. Conclusions Among patients with coronary artery disease, higher psychological distress is associated with future cardiovascular events in women only.