Lucy Shallenberger

Background: Young and middle‐aged women with ischemic heart disease have a higher burden of psychosocial factors compared with male counterparts. They also have worse morbidity and mortality, despite less atherosclerotic burden. Data on daily life stress and autonomic physiology could help guide targeted interventions. Methods: We studied 302 individuals ≤61 years of age recently hospitalized for a myocardial infarction. All underwent a 7‐day home monitoring of mood and stress using ecological momentary assessments, with concomitant Holter monitoring for autonomic physiology. Deceleration capacity, a prognostic marker of parasympathetic activity, was the primary autonomic outcome; heart rate variability was also examined. Results: The sample was 43% women with mean age of 51 years (SD, 7 years). Across the week of monitoring, women reported higher levels of negative mood and stress than men. Women also exhibited significantly lower parasympathetic activity (daily average of deceleration capacity) than men; heart rate variability was also lower. Among women, daily negative mood was inversely associated with lower deceleration capacity: for each 1‐log unit higher daily negative mood score, deceleration capacity declined 4.5% in women, but among men, the difference was close to zero: 0.5% ( P =0.02 for interaction). Adjustment for other risk factors did not materially affect the associations. A similar pattern of results was observed for heart rate variability metrics. Conclusions: Young and middle‐aged women who recently survived a myocardial infarction have more parasympathetic withdrawal than men in daily life, especially during moments of negative mood. These results underscore the need for greater attention to psychosocial management in women after myocardial infarction.

Background: Women with premature myocardial infarction (MI) have worse outcomes than similarly aged men despite less severe disease, and stress-related factors have been implicated. We examined sex differences in the association of mental stress-induced myocardial ischemia (MSIMI) with cardiovascular outcomes after premature MI and explored vascular and inflammatory mechanisms. Methods: We studied 602 individuals (mean age 51 years; 46% women) within 8 months of MI who underwent 99mTc-sestamibi myocardial perfusion imaging at rest and after mental stress. MSIMI was defined as a summed difference score ≥3. We measured reactive hyperemia index (RHI) as peripheral microvascular reactivity to stress and interleukin-6 (IL-6) as inflammatory response to stress. The primary endpoint was cardiovascular death or nonfatal MI; the secondary endpoint added heart failure hospitalization. Cox proportional hazards models adjusted for sociodemographic factors, clinical, and psychiatric history. Results: MSIMI was more common in women than men (19.2% vs. 13.2%, p=0.04). Over a median follow-up of 34.2 months, 51 primary and 91 secondary endpoint events occurred. The hazard ratio (HR) of MSIMI for the primary endpoint was 3.2 (95% CI, 1.3, 7.6) in women and 1.9 (95% CI, 0.8, 4.5) in men (p for interaction=0.41), which remained similar after multivariable adjustment. The adjusted population attributable fraction was 27.6% (99% CI, 3.9%, 36.9%) in women and 11.1% (95% CI, −5.8%, 18.4%) in men. In exploratory analyses, all MSIMI-related primary endpoint events among women occurred in Black women (HR, 4.3; 95% CI, 1.7–11.1). Associations with the secondary endpoint were weaker and attenuated after adjustment. IL-6 and RHI responses did not attenuate associations. Conclusions: Among women, MSIMI was associated with about threefold increased risk and over one quarter attributable fraction for cardiovascular death or nonfatal MI. Black women were at especially high risk. While larger studies are warranted to confirm sex differences and explore mechanisms, these data underscore the impact of emotional factors on morbidity and mortality in post-MI women.

Background: Information is lacking about everyday psychological states of individuals with a recent myocardial infarction (MI) and whether they influence outcomes. We investigated real world psychological experiences and their association with subsequent cardiovascular events in survivors of an MI. Methods: We studied 287 individuals ≤ 60 years of age within 8 months from an MI. At the baseline visit, we assessed sociodemographic and clinical factors, and administered a battery of psychological scales of depression, anxiety, anger, perceived stress and social support. Participants underwent a 7-day home monitoring of mood and stress using ecological momentary assessments, and a momentary negative affect (MNA) score, integrating daily mean ratings of sadness, anxiety, anger, distress and loneliness, was calculated. Participants were followed for a median time of 28 months. The study endpoint was a composite index of major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal MI, stroke or hospitalizations for heart failure. Cox proportional hazards models adjusted for sociodemographic and clinical factors. Results: The mean age of the sample was 51 years, and 43% of participants were women. Each standard deviation increase in MNA was significantly associated with a 60% increased risk of MACE (95% confidence interval (CI), 20% to 100%), irrespective of adjustment for sociodemographic factors and clinical characteristics. The association was similar in women and men. Momentary positive mood and momentary perceived stress were not associated with MACE. The MNA score showed a larger independent contribution to MACE compared to the combined battery of baseline psychological assessments and the association was independent of baseline history of depression. Conclusion: Among individuals after MI, moment-to-moment negative affect during one week of monitoring in daily life is a powerful predictor of subsequent cardiovascular events. A prospective evaluation of negative mood during everyday living could represent a novel strategy to uncover residual risk after MI.

To enable timely intervention and reduce risk of returning to use in individuals with opioid use disorder (OUD), there is a need to monitor opioid withdrawal severity using physiological biomarkers. However, in the context of opioid withdrawal, prior studies have relied on data recorded in controlled lab settings over short periods of time and have only focused on a limited set of biomarkers. To address these limitations, using multimodal wearable signals, we extracted and characterized 32 cardiorespiratory features from 16 individuals with OUD experiencing varying levels of withdrawal severity over a 7-day period. Across all participants, we found statistically significant ( p < 0.05) differences in 6 features between high and low withdrawal. For machine learning-based classification of high vs. low withdrawal, we found that performance improved when leveraging respiratory-focused and sex-/BMI-stratified models (highest macro F1 of 0.812). Finally, in 14 out of 16 participants, at least 1 feature statistically significantly ( p < 0.1) tracked changes in withdrawal scores over the 7-day period. Therefore, our analyses of these features uncovered substantial phenotype sensitivity and physiological heterogeneity across the study cohort. These findings underscore the need for phenotype-aware and personalized modeling approaches for continuous, sensor-based monitoring of withdrawal severity in the future.

Background: Stark disparities in the outcome of myocardial infarction (MI) persist, with large unexplained variations affecting younger Black women. Mental stress–induced myocardial ischemia (MSIMI) is an emerging mechanistic pathway that may help explain excess risks in this group. We sought to determine whether MSIMI is more common in Black women with recent premature MI than other demographic groups. Methods: We cross‐sectionally studied 602 individuals 61 years and younger who were hospitalized for MI in the previous 8 months. Participants underwent 99mTc‐sestamibi myocardial perfusion imaging at rest and after mental stress (speech task). A summed difference score was used to quantify ischemia. Clinically significant MSIMI was defined as a summed difference score ≥3. Log‐binomial and robust Poisson regression were used to adjust for sociodemographic, lifestyle, clinical, and psychosocial factors. Results: The mean age of patients was 51 years (range, 25–61 years), 46% were women, and 59% self‐identified as Black. Black women had a more adverse psychosocial profile and higher rates of obesity and diabetes but a less severe index MI. The incidence of MSIMI was approximately doubled in Black women than the other groups ( P <0.001 for interaction). Clinical and psychosocial risk factors did not explain these differences. In a fully adjusted model, the risk ratio of MSIMI for Black women was 2.2 (95% CI, 2.0–2.5) compared with Black men, 2.3 (95% CI, 1.8–2.9) compared with non‐Black women, and 1.8 (95% CI, 1.4–2.2) compared with non‐Black men. Conclusions: Among midlife individuals with a recent MI, Black women have a disproportionately higher risk of MSIMI. Targeted interventions for this high‐risk group are needed.

Objective: Black Americans who survive a myocardial infarction (MI) face an elevated risk for adverse outcomes. Childhood trauma is associated with reduced cardiovascular reactivity, but its contribution to racial disparities in stress physiology is unclear. We investigated whether childhood trauma contributes to lower cardiovascular reactivity among Black compared with White MI survivors. Methods: Using a cross-sectional design, we assessed childhood trauma and heart rate and blood pressure responses (HRR, SBPR, DBPR) to public speaking in 183 White (30% female) and 311 Black (53% female) MI survivors [M_age (SD): 51 (7)]. Multiple linear regression tested the interaction between race and childhood trauma on cardiovascular reactivity, adjusting for resting values and relevant covariates. When no significant interaction was found, models were refitted to examine main effects. A 4-level race-trauma variable was used to assess group differences, with White participants with low trauma (n=115) as the reference group. Results: Black participants were more likely to report high childhood trauma (49% vs. 37%, p=.012) and showed significantly lower heart rate (HRR) and systolic (SBPR) and diastolic (DBPR) blood pressure reactivity to mental stress compared with White participants. High childhood trauma was independently associated with lower HRR and SBPR. No significant race × trauma interaction was observed, but additive effects were evident: Black participants with high trauma had the lowest HRR (β=−8.2; 95% CI: [−11.2, −5.2]), SBPR (β=−7.7; 95% CI: [−11.9, −3.5]), and DBPR (β=−2.9; 95% CI: [−5.4, −0.4]) relative to White participants with low trauma. Conclusions: Black MI survivors were more likely to report high childhood trauma and exhibit reduced cardiovascular responses to stress. Although no interaction was found, additive effects suggest trauma contributes to racial disparities. Addressing childhood trauma may help mitigate cardiovascular risk in Black Americans.

Background Stark disparities in the outcome of myocardial infarction (MI) persist, with large unexplained variations affecting younger Black women. Mental stress induced myocardial ischemia (MSIMI) is an emerging mechanistic pathway that may help explain excess risks in this group. Objectives To determine whether MSIMI is more common in Black women with recent premature MI than other demographic groups. Methods We studied 602 individuals ≤ 61 years of age who were hospitalized for MI in the previous 8 months. Participants underwent 99mTc-sestamibi myocardial perfusion imaging at rest and after mental stress (speech task). A summed difference score (SDS) was used to quantify ischemia. Clinically significant MSIMI was defined as an SDS ≥3. Log-binomial regression models adjusted for sociodemographic, lifestyle, clinical and psychosocial factors. Results The mean age was 51 years (range, 25-61), 46% were women and 59% self-identified as Black. Black women had a more adverse psychosocial profile and higher rates of obesity and diabetes, but a less severe index MI. The incidence of MSIMI was approximately doubled in Black women than the other groups (p<.001 for interaction). Clinical and psychosocial risk factors did not explain these differences. In a fully adjusted model, the risk ratio of MSIMI for Black women was 2.2 (95% CI, 2.0-2.5) compared to Black men, 2.3 (1.8-2.9) compared to non-Black women, and 1.8 (1.4-2.2) compared to non-Black men. Conclusions Among midlife individuals with a recent MI, Black women have a disproportionately higher risk of MSIMI. Targeted interventions for this high-risk group are needed. What is new?We show for the first time that Black women in midlife who have recently experienced a myocardial infarction face a disproportionately high risk of developing myocardial ischemia when under mental stress. This elevated risk cannot be attributed to more severe coronary artery disease, suggesting a stress-related cardiovascular vulnerability that may help explain why Black women experience both higher rates of premature heart attacks and worse outcomes following these events. What are the clinical implications?The high rate of ischemia with mental stress in Black women highlights the need for new targeted risk assessment protocols and prevention strategies that go beyond the control of conventional risk factors to address stress-related risk pathways. This paradigm shift in cardiac care should help reduce cardiovascular disparities and improve outcomes in this historically underserved population. Differences in Myocardial Ischemia with Mental Stress by Sex and Race Among 602 individuals ≤ 61 years of age who were hospitalized for a myocardial infarction in the previous 8 months, and who underwent myocardial perfusion imaging with mental stress, Black women had approximately a twofold higher risk of developing myocardial ischemia compared with other demographic groups, even after adjusting for clinical and psychosocial factors.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with maladaptive dysregulation of stress response systems, which could lead to an increased risk of heart failure. We investigated whether PTSD was independently associated with first and recurrent heart failure hospitalizations in the setting of coronary artery disease. METHODS: Individuals with stable coronary artery disease and without heart failure at baseline were enrolled in 2 parallel prospective cohort studies in metropolitan Atlanta, GA. Participants underwent a structured clinical interview to assess their lifetime history of PTSD. Current PTSD symptoms were assessed using the PTSD symptom checklist. Participants were followed up for a median time of 4.9 years. The primary end point was first or recurrent hospitalization for heart failure. Secondary end points included cardiovascular death and nonfatal myocardial infarction with and without hospitalization for heart failure. Survival analysis for repeated events was used to assess the association of PTSD with adverse events. RESULTS: We studied 736 individuals with a mean age of 60±10 years; 36% were Black, and 35% were women. In total, 69 (9.4%) patients met the criteria for PTSD. Having a PTSD diagnosis was associated with the primary end point of first or recurrent heart failure hospitalizations, with a hazard ratio of 4.4 (95% CI, 2.6–7.3). The results were minimally attenuated after adjusting for demographic and clinical factors (hazard ratio, 3.7 [95% CI, 2.1–6.3]). Similarly, a 10-point increase in the PTSD symptom checklist score was associated with a 30% (95% CI, 10%–50%) increase in heart failure hospitalizations. PTSD was not associated with an end point of cardiovascular death or nonfatal myocardial infarction, which excluded hospitalizations due to heart failure. CONCLUSIONS: Among patients with coronary artery disease, PTSD is associated with incident and recurrent heart failure hospitalizations. Future research is needed to investigate whether PTSD management can reduce the risk of heart failure.

Background: Mental stress–induced myocardial ischemia is a frequent phenomenon in patients with coronary artery disease and is associated with a greater risk of future cardiovascular events. The association between chronic symptoms of psychological distress and mental stress–induced ischemia is not clear. Methods and Results: We used a composite score of psychological distress derived from symptoms of depression, posttraumatic stress disorder, anxiety, anger, and perceived general stress. Participants underwent myocardial perfusion imaging with both mental (public speaking task) and conventional (exercise or pharmacological) stress testing. Overall, 142 (15.9%) patients experienced mental stress–induced myocardial ischemia. After adjusting for demographic factors, medical history, and medication use, patients in the highest tertile of psychological distress score had 35% higher odds of having mental stress–induced ischemia compared to those in the lowest tertile (odds ratio [OR], 1.35 [95% CI, 1.06–2.22]). Stratified analyses showed that the association between psychological distress score and mental stress–induced myocardial ischemia was significantly associated only within the subgroup of patients with a prior myocardial infraction, with patients with a prior myocardial infarction in the highest tertile having a 93% higher odds of developing myocardial ischemia with mental stress (95% CI, 1.07–3.60). There was no significant association between psychological distress and conventional stress–induced ischemia (OR, 1.19 [95% CI, 0.87–1.63]). Conclusions: Among patients with a history of myocardial infarction, a higher level of psychosocial distress is associated with mental stress–induced myocardial ischemia but not with ischemia induced by a conventional stress test.