Gender Disparities in Cardiac Surgery Trials: Leadership, Authorship, and Patient Enrollment.

BACKGROUND: Studies have highlighted the paucity of women-led randomized controlled trials (RCTs) in cardiovascular medicine. Whether this finding also applies to cardiac surgery has not been evaluated. In this study, we evaluate women authorship, leadership, and women enrollment in cardiac surgery RCTs. METHODS: A systematic literature search was conducted to identify RCTs comparing 2 or more adult cardiac surgical procedures published from 2000 to 2022. Women-led RCTs were defined as those with a woman as either a first or last author. Linear regression and correlation analyses were used. RESULTS: Of 58 RCTs, 8 (13.8%) were women-led; 17 (29.3%) RCTs had no women authors. Overall, 17.9% of all authors were women, but only 1.2% of all authors were women cardiac surgeons and only 19% of the RCTs had a women cardiac surgeon among the authors. The median proportion of women authors was 14.3% by RCT, which was significantly higher in women-led compared with men-led RCTs (28.6% vs 11.8%; P = .01). No significant change in the proportion of women authors was observed during the study period. North American RCTs had a higher proportion of women authors compared with other geographic regions (28.6% vs 12.5%; P = .01). No correlation was found between the proportion of women authors and the proportion of women participants enrolled in individual RCTs. CONCLUSIONS: During the last 2 decades, only a minority of cardiac surgery RCTs were women-led, and no significant increase in women authorship occurred. There are important geographic differences in women authorship.

Disparities in Geographic Access to Cardiac Rehabilitation in Los Angeles County.

Background Exercise-based cardiac rehabilitation (CR) is known to reduce morbidity and mortality for patients with cardiac conditions. Sociodemographic disparities in accessing CR persist and could be related to the distance between where patients live and where CR facilities are located. Our objective is to determine the association between sociodemographic characteristics and geographic proximity to CR facilities. Methods and Results We identified actively operating CR facilities across Los Angeles County and used multivariable Poisson regression to examine the association between sociodemographic characteristics of residential proximity to the nearest CR facility. We also calculated the proportion of residents per area lacking geographic proximity to CR facilities across sociodemographic characteristics, from which we calculated prevalence ratios. We found that racial and ethnic minorities, compared with non-Hispanic White individuals, more frequently live ≥5 miles from a CR facility. The greatest geographic disparity was seen for non-Hispanic Black individuals, with a 2.73 (95% CI, 2.66-2.79) prevalence ratio of living at least 5 miles from a CR facility. Notably, the municipal region with the largest proportion of census tracts comprising mostly non-White residents (those identifying as Hispanic or a race other than White), with median annual household income <$60 000, contained no CR facilities despite ranking among the county's highest in population density. Conclusions Racial, ethnic, and socioeconomic characteristics are significantly associated with lack of geographic proximity to a CR facility. Interventions targeting geographic as well as nongeographic factors may be needed to reduce disparities in access to exercise-based CR programs. Such interventions could increase the potential of CR to benefit patients at high risk for developing adverse cardiovascular outcomes.

The Lancet women and cardiovascular disease Commission: reducing the global burden by 2030.

Cardiovascular disease is the leading cause of death in women. Decades of grassroots campaigns have helped to raise awareness about the impact of cardiovascular disease in women, and positive changes affecting women and their health have gained momentum. Despite these efforts, there has been stagnation in the overall reduction of cardiovascular disease burden for women in the past decade. Cardiovascular disease in women remains understudied, under-recognised, underdiagnosed, and undertreated. This Commission summarises existing evidence and identifies knowledge gaps in research, prevention, treatment, and access to care for women. Recommendations from an international team of experts and leaders in the field have been generated with a clear focus to reduce the global burden of cardiovascular disease in women by 2030. This Commission represents the first effort of its kind to connect stakeholders, to ignite global awareness of sex-related and gender-related disparities in cardiovascular disease, and to provide a springboard for future research.

Assessment of Vascular Dysfunction in Patients Without Obstructive Coronary Artery Disease: Why, How, and When.

Ischemic heart disease secondary to coronary vascular dysfunction causes angina and impairs quality of life and prognosis. About one-half of patients with symptoms and signs of ischemia turn out not to have obstructive coronary artery disease, and coronary vascular dysfunction may be relevant. Adjunctive tests of coronary vasomotion include guidewire-based techniques with adenosine and reactivity testing, typically by intracoronary infusion of acetylcholine. The CorMicA (Coronary Microvascular Angina) trial provided evidence that routine management guided by an interventional diagnostic procedure and stratified therapy improves angina and quality of life in patients with angina but no obstructive coronary artery disease. In this paper, the COVADIS study group provide a comprehensive review of why, how, and when coronary vascular dysfunction should be assessed invasively. They discuss the rationale through a shared understanding of vascular pathophysiology and clinical evidence. They propose a consensus approach to how an interventional diagnostic procedure is performed with focus on practical aspects. Finally, the authors discuss the clinical scenarios in patients with stable and acute coronary syndromes in which measurement of coronary vascular function may be helpful for patient care.

Predicted Versus Observed Major Adverse Cardiac Event Risk in Women With Evidence of Ischemia and No Obstructive Coronary Artery Disease: A Report From WISE (Women's Ischemia Syndrome Evaluation).

Background Primary prevention risk scores are commonly used to predict cardiovascular (CVD) outcomes. The applicability of these scores in patients with evidence of myocardial ischemia but no obstructive coronary artery disease is unclear. Methods and Results Among 935 women with signs and symptoms of ischemia enrolled in WISE (Women's Ischemia Syndrome Evaluation), 567 had no obstructive coronary artery disease on angiography. Of these, 433 had had available risk data for 6 commonly used scores: Framingham Risk Score, Reynolds Risk Score, Adult Treatment Panel III, Atherosclerotic Cardiovascular Disease, Systematic Coronary Risk Evaluation, Cardiovascular Risk Score 2. Score-specific CVD rates were assessed. For each score, we evaluated predicted versus observed event rates at 10-year follow-up using c statistic. Recalibration was done for 3 of the 6 scores. The 433 women had a mean age of 56.9±9.4 years, 82.5% were white, 52.7% had hypertension, 43.6% had dyslipidemia, and 16.9% had diabetes mellitus. The observed 10-year score-specific CVD rates varied between 5.54% (Systematic Coronary Risk Evaluation) to 28.87% (Framingham Risk Score), whereas predicted event rates varied from 1.86% (Systematic Coronary Risk Evaluation) to 6.99% (Cardiovascular Risk Score 2). The majority of scores showed moderate discrimination (c statistic 0.53 for Atherosclerotic Cardiovascular Disease and Systematic Coronary Risk Evaluation; 0.78 for Framingham Risk Score) and underestimated risk (statistical discordance -58% for Adult Treatment Panel III; -84% for Atherosclerotic Cardiovascular Disease). Recalibrated Reynolds Risk Score, Atherosclerotic Cardiovascular Disease, and Framingham Risk Score had improved performance, but significant underestimation remained. Conclusions Commonly used CVD risk scores fail to accurately predict CVD rates in women with ischemia and no obstructive coronary artery disease. These results emphasize the need for new risk assessment scores to reliably assess this population.

Prognostic Significance of Nonobstructive Left Main Coronary Artery Disease in Women Versus Men: Long-Term Outcomes From the CONFIRM (Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter) Registry.

BACKGROUND: Patients with obstructive (≥50% stenosis) left main (LM) coronary artery disease (CAD) are at high risk for adverse events; prior studies have also documented worse outcomes among women than men with severe multivessel/LM CAD. However, the prognostic significance of nonobstructive (1%-49% stenosis) LM CAD, including sex-specific differences, has not been previously examined. METHODS AND RESULTS: In the long-term CONFIRM (Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter) registry, patients underwent elective coronary computed tomographic angiography for suspected CAD and were followed for 5 years. After excluding those with obstructive LM CAD, 5166 patients were categorized as having normal LM or nonobstructive LM (18% of cohort). Cumulative 5-year incidence of death, myocardial infarction, or revascularization was higher among patients with nonobstructive LM than normal LM in both women and men: women (34.3% versus 15.4%; P<0.0001); men (24.6% versus 18.2%; P<0.0001). A significant interaction existed between sex and LM status for the composite outcome (P=0.001). In multivariable Cox regression, the presence of nonobstructive LM plaque increased the risk for the composite outcome in women (adjusted hazard ratio, 1.48; P=0.005) but not in men (adjusted hazard ratio, 0.98, P=0.806). In subgroup analysis, women with nonobstructive LM CAD had a nearly 80% higher risk for events than men with nonobstructive LM CAD (adjusted hazard ratio, 1.78; P=0.017); sex-specific interactions were not observed across other patterns (eg, location or extent) of nonobstructive plaque. CONCLUSION: Nonobstructive LM CAD was frequently detected on coronary computed tomographic angiography and strongly associated with adverse events among women. Recognizing the sex-specific prognostic significance of nonobstructive LM plaque may augment risk stratification efforts.

Quality and Equitable Health Care Gaps for Women: Attributions to Sex Differences in Cardiovascular Medicine.

The present review synthesizes evidence and discusses issues related to health care quality and equity for women, including minority population subgroups. The principle of "sameness" or women and men receiving equitable, high-quality care is a near-term target, but optimal population health cannot be achieved without consideration of the unique, gendered structural determinants of health and the development of unique care pathways optimized for women. The aim of this review is to promote enhanced awareness, develop critical thinking in sex and gender science, and identify strategic pathways to improve the cardiovascular health of women. Delineation of the components of high-quality health care, including a women-specific research agenda, remains a vital part of strategic planning to improve the lives of women at risk for or living with cardiovascular disease.

Advancing Women's Health and Women's Leadership With Endowed Chairs in Women's Health.

Gender-based bias and conflation of gender and status are root causes of disparities in women's health care and the slow advancement of women to leadership in academic medicine. More than a quarter of women physicians train in internal medicine and its subspecialties, and women physicians almost exclusively constitute the women's health focus within internal medicine. Thus, internal medicine has considerable opportunity to develop women leaders in academic medicine and promote women's health equity.To probe whether holding an endowed chair-which confers status-in women's health may be an effective way to advance women leaders in academic medicine and women's health, the authors explored the current status of endowed chairs in women's health in internal medicine. They found that the number of these endowed chairs in North America increased from 7 in 2013 to 19 in 2015, and all were held by women. The perceptions of incumbents and other women's health leaders supported the premise that an endowed chair in women's health would increase women's leadership, the institutional stature of women's health, and activities in women's health research, education, and clinical care.Going forward, it will be important to explore why not all recipients perceived that the endowed chair enhanced their own academic leadership, whether providing women's health leaders with fundraising expertise fosters future success in increasing the number of women's health endowed chairs, and how the conflation of gender and status play out (e.g., salary differences between endowed chairs) as the number of endowed chairs in women's health increases.

Use of bio-informatics assessment schema (BIAS) to improve diagnosis and prognosis of myocardial perfusion data: results from the NHLBI-sponsored women's ischemia syndrome evaluation (WISE).

BACKGROUND: We introduce an algorithmic approach to optimize diagnostic and prognostic value of gated cardiac single photon emission computed tomography (SPECT) and magnetic resonance (MR) myocardial perfusion imaging (MPI) modalities in women with suspected myocardial ischemia. The novel approach: bio-informatics assessment schema (BIAS) forms a mathematical model utilizing MPI data and cardiac metrics generated by one modality to predict the MPI status of another modality. The model identifies cardiac features that either enhance or mask the image-based evidence of ischemia. For each patient, the BIAS model value is used to set an appropriate threshold for the detection of ischemia. METHODS: Women (n=130), with symptoms and signs of suspected myocardial ischemia, underwent MPI assessment for regional perfusion defects using two different modalities: gated SPECT and MR. To determine perfusion status, MR data were evaluated qualitatively (MRIQL) and semi-quantitatively (MRISQ) while SPECT data were evaluated using conventional clinical criteria. Evaluators were masked to results of the alternate modality. These MPI status readings were designated "original". Two regression models designated "BIAS" models were generated to model MPI status obtained with one modality (e.g., MRI) compared with a second modality (e.g., SPECT), but importantly, the BIAS models did not include the primary Original MPI reading of the predicting modality. Instead, the BIAS models included auxiliary measurements like left ventricular chamber volumes and myocardial wall thickness. For each modality, the BIAS model was used to set a progressive threshold for interpretation of MPI status. Women were then followed for 38±14 months for the development of a first major adverse cardiovascular event [MACE: CV death, nonfatal myocardial infarction (MI) or hospitalization for heart failure]. Original and BIAS-augmented perfusion status were compared in their ability to detect coronary artery disease (CAD) and for prediction of MACE. RESULTS: Adverse events occurred in 14 (11%) women and CAD was present in 13 (10%). There was a positive correlation of maximum coronary artery stenosis and BIAS score for MRI and SPECT (P<0.001). Receiver operator characteristic (ROC) analysis was conducted and showed an increase in the area under the curve of the BIAS-augmented MPI interpretation of MACE vs. the original for MRISQ (0.78 vs. 0.54), MRIQL (0.78 vs. 0.64), SPECT (0.82 vs. 0.63) and the average of the three readings (0.80±0.02 vs. 0.60±0.05, P<0.05). CONCLUSIONS: Increasing values of the BIAS score generated by both MRI and SPECT corresponded to the increasing prevalence of CAD and MACE. The BIAS-augmented detection of ischemia better predicted MACE compared with the Original reading for the MPI data for both MRI and SPECT.

Noninvasive Imaging to Evaluate Women With Stable Ischemic Heart Disease.

Declines in cardiovascular deaths have been dramatic for men but occur significantly less in women. Among patients with symptomatic ischemic heart disease (IHD), women experience relatively worse outcomes compared with their male counterparts. Evidence to date has failed to adequately explore unique female imaging targets and their correlative signs and symptoms of IHD as major determinants of IHD risk. We highlight sex-specific anatomic and functional differences in contemporary imaging and introduce imaging approaches that leverage refined targets that may improve IHD risk prediction and identify potential therapeutic strategies for symptomatic women.

Focused Cardiovascular Care for Women: The Need and Role in Clinical Practice.

Over the past decade, an emerging clinical research focus on cardiovascular (CV) disease (CVD) risk in women has highlighted sex-specific factors that are uniquely important in the prevention and early detection of coronary atherosclerosis in women. Concurrently, a 30% decrease in the number of female deaths from CVD has been observed. Despite this, CVD continues to be the leading cause of death in women, outnumbering deaths from all other causes combined. Clinical practice approaches that focus on the unique aspects of CV care for women are needed to provide necessary resources for the prevention, diagnosis, and treatment of CVD in women. In addition to increasing opportunities for women to participate in CV research, Women's Heart Clinics offer unique settings in which to deliver comprehensive CV care and education, ensuring appropriate diagnostic testing, while monitoring effectiveness of treatment. This article reviews the emerging need and role of focused CV care to address sex-specific aspects of diagnosis and treatment of CVD in women.

Cardiac magnetic resonance imaging myocardial perfusion reserve index assessment in women with microvascular coronary dysfunction and reference controls.

OBJECTIVE: We sought to comparatively assess cardiac magnetic resonance imaging (CMRI) myocardial perfusion reserve index (MPRI) in women with confirmed microvascular coronary dysfunction (MCD) cases and reference control women. BACKGROUND: Women with signs or symptoms of myocardial ischemia in the absence of obstructive coronary artery disease (CAD) frequently have MCD which carries an adverse prognosis. Diagnosis involves invasive coronary reactivity testing (CRT). Adenosine CMRI is a non-invasive test that may be useful for the detection of MCD. METHODS: Fifty-three women with MCD confirmed by CRT and 12 age- and estrogen-use matched reference controls underwent adenosine CMRI. CMRI was assessed for MPRI, calculated using the ratio of myocardial blood flow at hyperemia/rest for the whole myocardium and separately for the 16 segments as defined by the American Heart Association. Statistical analysis was performed using repeated measures ANOVA models. RESULTS: Compared to reference controls, MCD cases had lower MPRI values globally and in subendocardial and subepicardial regions (1.63±0.39 vs. 1.98±0.38, P=0.007, 1.51±0.35 vs. 1.84±0.34, P=0.0045, 1.68±0.38 vs. 2.04±0.41, P=0.005, respectively). A perfusion gradient across the myocardium with lower MPRI in the subendocardium compared to the subepicardium was observed for both groups. CONCLUSIONS: Women with MCD have lower MPRI measured by perfusion CMRI compared to reference controls. CMRI may be a useful diagnostic modality for MCD. Prospective validation of a diagnostic threshold for MPRI in patients with MCD is needed.

Anxiety associations with cardiac symptoms, angiographic disease severity, and healthcare utilization: the NHLBI-sponsored Women's Ischemia Syndrome Evaluation.

BACKGROUND: Anxiety is common among patients presenting with suspected coronary artery disease (CAD). In a sample of women with signs and symptoms of ischemia, we examined three anxiety markers as predictors of CAD endpoints including: 1) cardiac symptom indicators; 2) angiographic CAD severity; and 3) healthcare utilization (cardiac hospitalizations and 5-year cardiovascular [CVD] healthcare costs). METHODS: Participants completed a baseline protocol including coronary angiogram, cardiac symptoms, psychosocial measures and a median 5.9-year follow-up to track hospitalizations. We calculated CVD costs based on cardiac hospitalizations, treatment visits, and CVD medications. Anxiety measures included anxiolytic medication use, Spielberger Trait Anxiety Inventory (STAI) scores, and anxiety disorder treatment history. RESULTS: The sample numbered 514 women with anxiety measure data and covariates (mean age=57.5 [11.1]). One in five (20.4%) women reported using anxiolytic agents. Anxiety correlated with cardiac symptom indicators (anxiolytic use with nighttime angina and nitroglycerine use; STAI scores and anxiety disorder treatment history with nighttime angina, shortness of breath, and angina frequency). Anxiety disorder treatment history (but not STAI scores or anxiolytics) predicted less severe CAD. Anxiolytic use (but not STAI scores or anxiety disorder treatment history) predicted hospitalizations for chest pain and coronary catheterization (HRs=2.0, 95% CIs=1.1-4.7). Anxiety measures predicted higher 5-year CVD costs (+9.0-42.7%) irrespective of CAD severity. CONCLUSIONS: Among women with signs and symptoms of myocardial ischemia, anxiety measures predict cardiac endpoints ranging from cardiac symptom severity to healthcare utilization. Based on these findings, anxiety may warrant greater consideration among women with suspected CAD.

Is cardiovascular disease in women inevitable?: preparing for menopause and beyond.

Cardiovascular disease (CVD) is the leading cause of death for American women. Women share many of the same risk factors (RFs) for CVD as men, and in both, women and men, these RFs are associated with age. Additionally, the prevalence of multiple RFs increases with age. Though menopause has been thought to increase CVD risk in women, the association between menopause and age obfuscates a causal relationship. While men's CVD mortality has decreased since the 1980s, women's CVD mortality has climbed until 2000. This has resulted in a sex-related CVD mortality gap, with women having higher mortality than men since 1984. Contributing to this female-majority CVD mortality gap is a lack of awareness of CVD risk among women and their physicians. Awareness campaigns, such as the Heart Truth and the Red Dress symbol, appear to have improved recognition of CVD risk in women. Further, female-specific guidelines have been developed to prevent and reduce CVD in women. Though the current understanding of the role of menopause in CVD is controversial, studies suggest that menopause does not exacerbate CVD independent of aging, and hormone replacement therapy is not effective for secondary prevention of CVD.

Self-rated versus objective health indicators as predictors of major cardiovascular events: the NHLBI-sponsored Women's Ischemia Syndrome Evaluation.

OBJECTIVE: To determine the association between self-rated health and major cardiovascular events in a sample of women with suspected myocardial ischemia. Previous studies showed that self-rated health is a predictor of objective health outcomes, such as mortality. METHOD: At baseline, 900 women rated their health on a 5-point scale ranging from poor to excellent as part of a protocol that included quantitative coronary angiography, cardiovascular disease (CVD) risk factor assessment, cardiac symptoms, psychotropic medication use, and functional impairment. Participants were followed for a maximum of 9 years (median, 5.9 years) to determine the prevalence of major CVD events (myocardial infarction, heart failure, stroke, and CVD-related death). RESULTS: A total of 354 (39.3% of sample) participants reported their health as either poor or fair. After adjusting for demographic factors, CVD risk factors, and coronary artery disease severity, women who rated their health as poor (hazard ratio, 2.1 [1.1-4.2]) or fair (hazard ratio, 2.0 [1.2-3.6]) experienced significantly shorter times to major CVD events compared with women who rated their health as excellent or very good. Further adjustment for functional impairment, however, attenuated the self-rated health relationships with major CVD events. CONCLUSIONS: Among women with suspected myocardial ischemia, self-rated health predicted major CVD events independent of demographic factors, CVD risk factors, and angiogram-defined disease severity. However, functional impairment seemed to explain much of the self-rated health association. These results support the clinical utility of self-rated health scores in women and encourage a multidimensional approach to conceptualizing these measures.

Depression and cardiovascular health care costs among women with suspected myocardial ischemia: prospective results from the WISE (Women's Ischemia Syndrome Evaluation) Study.

OBJECTIVES: This study evaluated 3 novel questions in a prospective clinical cohort of women undergoing evaluation for suspected myocardial ischemia: 1) What is the relationship between depression and cardiovascular costs? 2) Does the relationship vary by definition of depression? 3) Do depression-cost relationship patterns differ among women with versus without coronary artery disease (CAD)? BACKGROUND: Comorbid depression has been linked to higher medical costs in previous studies of cardiovascular patients. METHODS: A total of 868 women presenting with suspected myocardial ischemia completed an extensive baseline examination including cardiovascular risk factor assessment and coronary angiogram. Depression was defined by: 1) current use of antidepressants; 2) a reported history of depression treatment; and 3) Beck Depression Inventory scores. Direct (hospitalizations, office visits, procedures, and medications) and indirect (out-of-pocket, lost productivity, and travel) costs were collected through 5 years of follow-up to estimate cardiovascular costs. RESULTS: Using the study criteria, 17% to 45% of the women studied met study depression criteria. Depressed women showed adjusted annual cardiovascular costs $1,550 to $3,300 higher than nondepressed groups (r = 0.08 to 0.12, p < 0.05). Depression-cost relationships also varied by CAD status, with stronger associations present among women without evidence of significant CAD. CONCLUSIONS: Depression was associated with 15% to 53% increases in 5-year cardiovascular costs, and cost differences were present using 3 definitions of depression. The results reinforce the importance of assessing depression in clinical populations and support the hypothesis that improved management of depression in women with suspected myocardial ischemia could reduce medical costs.