Anna Grodzinsky’s research while affiliated with University of Missouri–Kansas City and other places

Background Women with chronic coronary disease have more frequent angina and worse health status than men, despite having less coronary artery disease (CAD). We examined whether perceived stress and depressive symptoms mediate sex differences in angina, and whether this relationship differs in the setting of obstructive CAD or ischemia with no obstructive coronary artery disease (INOCA). Methods We analyzed the association between sex, stress (Perceived Stress Scale‐4) and depressive symptoms (Patient Health Questionnaire‐8) on angina‐related health status (Seattle Angina Questionnaire [SAQ]) at enrollment in the ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial and CIAO‐ISCHEMIA (Changes in Ischemia and Angina Over 1 Year Among ISCHEMIA Trial Screen Failures With No Obstructive CAD on Coronary CT [Computed Tomography] Angiography) ancillary study. Results Scores for the SAQ, Perceived Stress Scale‐4, and Patient Health Questionnaire‐8 were available in 1626 participants (N=1439 CAD and N=187 INOCA). Women had lower (worse) SAQ‐7 summary scores than men in both CAD and INOCA cohorts (CAD: median 76 [25th, 75th percentiles 60, 90] versus 83 [70, 96], P <0.001; INOCA: 80 [64,89] versus 85 [75, 93], P =0.012). Higher stress and depressive symptoms were associated with worse angina in both cohorts. Female sex, Perceived Stress Scale‐4 score, and Patient Health Questionnaire‐8 score were each independently associated with lower SAQ summary score, but CAD versus INOCA cohort was not. There was no interaction between sex and stress (−0.39 [95% CI, –1.01 to 0.23]) or sex and depression (−0.00 [95% CI, –0.53 to 0.53]) on SAQ summary score. Conclusions High stress and depressive symptoms were independently associated with worse angina and poorer health status, without interaction with sex with or without obstructive CAD. Factors other than stress or depression contribute to worse health status in women with obstructive CAD or INOCA. Registration URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT02347215, NCT01471522.

Despite marked advancements in the recognition and diagnosis of spontaneous coronary artery dissection (SCAD) over the past decade, knowledge of the basic pathophysiologic mechanisms of disease, contributing factors, and treatment continue to be poorly understood. We describe significant research gaps in our knowledge of SCAD and introduce strategies including the role of patient advocacy, independent registries, and creation of diverse centers of excellence to bridge the gap in clinical care, research, and outcomes. Lastly, we introduce an innovative patient-centered clinical care and research framework established through the SCAD Alliance and International Spontaneous Coronary Artery Dissection registry as a model for advancing knowledge of SCAD.

Background: Despite a lesser extent and severity of coronary artery disease (CAD), women had a higher burden of angina than men in the ISCHEMIA trial, suggesting that other factors may explain symptom severity in women. We aim to describe demographic and clinical characteristics, as well as differences in care patterns, associated with health status differences in women, as compared with men, in the conservative and invasive treatment groups of the ISCHEMIA trial. Methods: The ISCHEMIA trial randomized participants with moderate or severe ischemia to a routine invasive strategy of cardiac catheterization with complete revascularization plus guideline-directed medical therapy (GDMT), or an initial conservative strategy of GDMT alone with catheterization reserved for GDMT failure. Health status was a key secondary outcome. Using linear regression models we compared raw and adjusted Seattle Angina Questionnaire (SAQ) scores in women and men at baseline and at 1 year, stratified by randomized treatment strategy. Within the invasive strategy, sex differences were adjusted for completeness of revascularization among those with ≥1 coronary stenosis ≥70%. Results: Of 4,617 ISCHEMIA participants with valid SAQ data, women had lower (worse) baseline SAQ summary scores (SS) throughout follow up (Figure) after adjustment for demographics and clinical characteristics, including severity of CAD (difference 5.4 points, 95% CI 4.0-6.7). Women had lower SAQ SS after adjustment for post-randomization treatment (i.e., medical therapy, achievement of risk factor goals and, in the invasive strategy, complete revascularization), 2.4 points lower (95% CI 0.7-4.1) in the conservative group (Figure), and 1.9 points lower than in men (95% CI 0.1-3.7) in the invasive group. Findings were similar for all SAQ subscales. Conclusions: Women with chronic coronary disease in ISCHEMIA had worse health status than men at baseline and 1 year later, which was not explained by demographic or clinical characteristics, intensity of medical therapy, or completeness of revascularization.

Background: Sex differences in angina frequency and health status have been previously described in patients with chronic coronary disease (CCD), with women more severely affected despite lesser coronary artery disease (CAD) severity. Psychosocial factors, such as perceived stress and depression, are associated with increased angina and are more common in women and in those with ischemia and no obstructive coronary artery disease (INOCA). We examined whether perceived stress and depressive symptoms mediate sex differences in angina severity among patients with CCD, and whether this relationship differs between those with CAD vs. INOCA. Methods: The association between sex, stress (Perceived Stress Scale-4) and depressive symptoms (Patient Health Questionnaire-8) and angina-specific health status (Seattle Angina Questionnaire, SAQ) at enrollment and changes over 1 year in North American ISCHEMIA participants and in the CIAO-ISCHEMIA study (INOCA) were compared using linear regression. Results: Among 1,626 participants (N=1,439 CAD and N=187 INOCA) with available SAQ, PSS-4 and PHQ-8 data, women had worse SAQ-7 summary scores than men in both CAD and INOCA cohorts (Table). Higher stress and depressive symptoms were associated with worse angina in both CAD and INOCA cohorts. Given consistency of results, cohorts were pooled for multivariable analysis. Female sex, PSS-4 score and PHQ-8 score were each independently associated with lower SAQ scores, (female vs. male difference -5.12 points, 95% CI -7.21, -3.02, p=0.001; PSS-4 -0.78 per point, 95% CI -1.06, -0.50, p=0.001; PHQ-8 -1.38 per point, 95% CI -1.58, -1.18, p=0.001) but CAD vs. INOCA was not and the effects were similar by sex. Conclusions: Women, with both CAD and INOCA, had worse angina and angina-related health status than men. High stress and depressive symptoms were each independently associated without a significant interaction by sex, and regardless of presence of obstructive CAD. Therefore, stress and depression levels are not a central explanation for worse health status in women than men with CAD or INOCA.

Introduction: Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic cause of myocardial infarction. Migraine headache has been reported to be common among patients with SCAD, but the degree of migraine-related disability has not been quantified. Methods: Clinical data and headache variables were obtained from the baseline assessment of the prospective, multicenter iSCAD Registry. Migraine-related disability was quantified using the self-reported Migraine Disability Assessment (MIDAS). Demographic, clinical, psychosocial, and medical characteristics from data entry forms were compared between patients with and without migraine. Results: Of the 773 patients with available data, 46% reported previous or current migraines. Those with migraines were more likely to be women (96.9% vs 90.3%, p = 0.0003). The presence of underlying carotid fibromuscular dysplasia was associated with migraine (35% vs 27%, p = 0.0175). There was not a significant association with carotid artery dissection and migraine. Current migraine frequency was less than monthly (58%), monthly (24%), weekly (16%), and daily (3%). Triptan use was reported in 32.5% of patients, and 17.5% used daily migraine prophylactic medications. Using the MIDAS to quantify disability related to migraine, 60.2% reported little or no disability, 14.4% mild, 12.7% moderate, and 12.7% severe. The mean MIDAS score was 9.9 (mild to moderate disability). Patients with SCAD had higher rates of depression and anxiety (28.2% vs 17.7% [p = 0.0004] and 35.3% vs 26.7% [p = 0.0099], respectively). Conclusions: Migraines are common, frequent, and a source of disability in patients with SCAD. The association between female sex, anxiety, and depression may provide some insight for potential treatment modalities.

Background Myocardial infarction secondary to spontaneous coronary artery dissection (SCAD) can be traumatic and potentially trigger posttraumatic stress disorder (PTSD). In a large, multicenter, registry‐based cohort, we documented prevalence of lifetime and past‐month SCAD‐induced PTSD, as well as related treatment seeking, and examined a range of health‐relevant correlates of SCAD‐induced PTSD. Methods and Results Patients with SCAD were enrolled in the iSCAD (International SCAD) Registry. At baseline, site investigators completed medical report forms, and patients reported demographics, medical/SCAD history, psychosocial factors (including SCAD‐induced PTSD symptoms), health behaviors, and health status via online questionnaires. Of 1156 registry patients, 859 patients (93.9% women; mean age, 52.3 years) completed questionnaires querying SCAD‐induced PTSD. Nearly 35% (n=298) of patients met diagnostic criteria for probable SCAD‐induced PTSD in their lifetime, and 6.4% (n=55) met criteria for probable past‐month PTSD. Of 811 patients ever reporting any SCAD‐induced PTSD symptoms, 34.8% indicated seeking treatment for this distress. However, 46.0% of the 298 patients with lifetime probable SCAD‐induced PTSD diagnoses reported never receiving trauma‐related treatment. Younger age at first SCAD, fewer years since SCAD, being single, unemployed status, more lifetime trauma, and history of anxiety were associated with greater past‐month PTSD symptom severity in multivariable regression models. Greater past‐month SCAD‐induced PTSD symptoms were associated with greater past‐week sleep disturbance and worse past‐month disease‐specific health status when adjusting for various risk factors. Conclusions Given the high prevalence of SCAD‐induced PTSD symptoms, efforts to support screening for these symptoms and connecting patients experiencing distress with empirically supported treatments are critical next steps. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04496687.

Spontaneous coronary artery dissection (SCAD) is a condition primarily seen in young women and is characterized by non-atherosclerotic arterial damage. It can occur with or without conventional risk factors for coronary heart disease and is often associated with chronic inflammatory conditions. Here, we present a unique instance of a 67-year-old woman without known risk factors who developed sudden onset chest pain in the setting of an asymptomatic coronavirus 2019 (COVID-19) infection three weeks earlier. Subsequent evaluation revealed SCAD in the distal left anterior descending (LAD) artery.