Impact of epicardial fat on coronary vascular function, cardiac morphology, and cardiac function in women with suspected INOCA.

INTRODUCTION: Epicardial fat is a metabolically active adipose tissue depot situated between the myocardium and visceral pericardium that covers ∼80% of the heart surface. While epicardial fat has been associated with the development of atherosclerotic coronary artery disease (CAD), less is known about the relationship between epicardial fat and coronary vascular function. Moreover, the relations between excess epicardial fat and cardiac morphology and function remains incompletely understood. METHODS AND RESULTS: To address these knowledge gaps, we retrospectively analyzed data from 294 individuals from our database of women with suspected ischemia with no obstructive coronary disease (INOCA) who underwent both invasive coronary function testing and cardiac magnetic resonance imaging (cMRI). Epicardial fat area, biventricular morphology, and function, as well as left atrial function, were assessed from cine images, per established protocols. The major novel findings were twofold: First, epicardial fat area was not associated with coronary vascular dysfunction. Second, epicardial fat was associated with increased left ventricular concentricity (ß= 0.15, p= 0.01), increased septal thickness (ß= 0.17, p= 0.002), and reduced left atrial conduit fraction (ß= -0.15, p= 0.02), even after accounting for age, BMI, and history of hypertension. CONCLUSIONS: Taken together, these data do not support a measurable relationship between epicardial fat and coronary vascular dysfunction but does suggest that epicardial fat may be related to concentric remodeling and diastolic dysfunction in women with suspected INOCA. Prospective studies are needed to elucidate the long-term impact of epicardial fat in this patient population.

Large-Scale Proteomics in Early Pregnancy and Hypertensive Disorders of Pregnancy.

Importance: There is no consensus regarding the best method for prediction of hypertensive disorders of pregnancy (HDP), including gestational hypertension and preeclampsia. Objective: To determine predictive ability in early pregnancy of large-scale proteomics for prediction of HDP. Design, Setting, and Participants: This was a nested case-control study, conducted in 2022 to 2023, using clinical data and plasma samples collected between 2010 and 2013 during the first trimester, with follow-up until pregnancy outcome. This multicenter observational study took place at 8 academic medical centers in the US. Nulliparous individuals during first-trimester clinical visits were included. Participants with HDP were selected as cases; controls were selected from those who delivered at or after 37 weeks without any HDP, preterm birth, or small-for-gestational-age infant. Age, self-reported race and ethnicity, body mass index, diabetes, health insurance, and fetal sex were available covariates. Exposures: Proteomics using an aptamer-based assay that included 6481 unique human proteins was performed on stored plasma. Covariates were used in predictive models. Main Outcomes and Measures: Prediction models were developed using the elastic net, and analyses were performed on a randomly partitioned training dataset comprising 80% of study participants, with the remaining 20% used as an independent testing dataset. Primary measure of predictive performance was area under the receiver operating characteristic curve (AUC). Results: This study included 753 HDP cases and 1097 controls with a mean (SD) age of 26.9 (5.5) years. Maternal race and ethnicity were 51 Asian (2.8%), 275 non-Hispanic Black (14.9%), 275 Hispanic (14.9%), 1161 non-Hispanic White (62.8% ), and 88 recorded as other (4.8%), which included those who did not identify according to these designations. The elastic net model, allowing for forced inclusion of prespecified covariates, was used to adjust protein-based models for clinical and demographic variables. Under this approach, no proteins were selected to augment the clinical and demographic covariates. The predictive performance of the resulting model was modest, with a training set AUC of 0.64 (95% CI, 0.61-0.67) and a test set AUC of 0.62 (95% CI, 0.56-0.68). Further adjustment for study site yielded only minimal changes in AUCs. Conclusions and Relevance: In this case-control study with detailed clinical data and stored plasma samples available in the first trimester, an aptamer-based proteomics panel did not meaningfully add to predictive utility over and above clinical and demographic factors that are routinely available.

Skin sympathetic nerve activity and ST-segment depression in women.

Background: ST-segment depression (ST depression) on exercise electrocardiogram (ECG) and ambulatory ECG monitoring may occur without myocardial ischemia. The mechanisms of nonischemic ST depression remain poorly understood. Objective: The study sought to test the hypothesis that the magnitudes of skin sympathetic nerve activity (SKNA) correlate negatively with the ST-segment height (ST height) in ambulatory participants. Methods: We used neuECG (simultaneous recording of SKNA and ECG) to measure ambulatory ST height and average SKNA (aSKNA) in 19 healthy women, 6 women with a history of Takotsubo syndrome (TTS), and 4 women with ischemia and no obstructive coronary arteries (INOCA). Results: Baseline aSKNA was similar between healthy women, women with TTS, and women with INOCA (1.098 ± 0.291 µV, 0.980 ± 0.061 µV, and 0.919 ± 0.0397 µV, respectively; P = .22). The healthy women had only asymptomatic upsloping ST depression. All participants had a significant (P < .05) negative correlation between ST height and aSKNA. Ischemic episodes (n = 15) were identified in 2 TTS and 4 INOCA participants. The ischemic ST depression was associated with increased heart rate and elevated aSKNA compared with baseline. An analysis of SKNA burst patterns at similar heart rates revealed that SKNA total burst area was significantly higher during ischemic episodes than nonischemic episodes (0.301 ± 0.380 µV·s and 0.165 ± 0.205 µV·s; P = .023) in both the TTS and INOCA participants. Conclusion: Asymptomatic ST depression in ambulatory women is associated with elevated SKNA. Heightened aSKNA is also noted during ischemic ST depression in women with TTS and INOCA. These findings suggest that ST segment depression is a physiological response to heightened sympathetic tone but may be aggravated by myocardial ischemia.

Endogenous androgens, coronary atheroma and remodeling in women with suspected ischemic heart disease: A report from the Women's Ischemia Syndrome Evaluation (WISE) study.

Background: Women have smaller coronary size than men independent of body surface area. Female to male heart transplantation demonstrates coronary lumen enlargement. Purpose: To investigate relationships between endogenous androgens and coronary luminal size in women with suspected ischemic heart disease (IHD). Methods: We analyzed 69 women with available androgen levels. Results: Group mean age was 54 ± 10 years with 64 % post-menopausal. Lumen cross-sectional area (CSA) and external elastic membrane (EEM) CSA positively correlated with free testosterone (FT) (r = 0.29, p = 0.049; r = 0.29, p = 0.01), respectively, and negatively correlated with SHBG (r = -0.26, p = 0.03; r = -0.29, p = 0.02), respectively. Atheroma CSA positively correlated with FT (r = 0.24. p = 0.05). These correlations became non-significant after adjusting for waist circumference. Conclusions: In women with suspected ischemic heart disease, endogenous androgens, coronary atheroma and luminal size are related, and may be moderated by waist circumference.

Alterations in genes associated with cytosolic RNA sensing in whole blood are associated with coronary microvascular disease in SLE.

Systemic lupus erythematosus (SLE) patients are 90% women and over three times more likely to die of cardiovascular disease than women in the general population. Chest pain with no obstructive cardiac disease is associated with coronary microvascular disease (CMD), where narrowing of the small blood vessels can lead to ischemia, and frequently reported by SLE patients. Using whole blood RNA samples, we asked whether gene signatures discriminate SLE patients with coronary microvascular dysfunction (CMD) on cardiac MRI (n=4) from those without (n=7) and whether any signaling pathway is linked to the underlying pathobiology of SLE CMD. RNA-seq analysis revealed 143 differentially expressed (DE) genes between the SLE and healthy control (HC) groups, with virus defense and interferon (IFN) signaling being the key pathways identified as enriched in SLE as expected. We next conducted a comparative analysis of genes differentially expressed in SLE-CMD and SLE-non-CMD relative to HC samples. Our analysis highlighted differences in IFN signaling, RNA sensing and ADP-ribosylation pathways between SLE-CMD and SLE-non-CMD. This is the first study to investigate possible gene signatures associating with CMD in SLE, and our data strongly suggests that distinct molecular mechanisms underly vascular changes in CMD and non-CMD involvement in SLE.

Socioeconomic disadvantage in pregnancy and postpartum risk of cardiovascular disease.

BACKGROUND: Pregnancy is an educable and actionable life stage to address social determinants of health (SDOH) and lifelong cardiovascular disease (CVD) prevention. However, the link between a risk score that combines multiple neighborhood-level social determinants in pregnancy and the risk of long-term CVD remains to be evaluated. OBJECTIVE: To examine whether neighborhood-level socioeconomic disadvantage measured by the Area Deprivation Index (ADI) in early pregnancy is associated with a higher 30-year predicted risk of CVD postpartum, as measured by the Framingham Risk Score. STUDY DESIGN: An analysis of data from the prospective Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be Heart Health Study longitudinal cohort. Participant home addresses during early pregnancy were geocoded at the Census-block level. The exposure was neighborhood-level socioeconomic disadvantage using the 2015 ADI by tertile (least deprived [T1], reference; most deprived [T3]) measured in the first trimester. Outcomes were the predicted 30-year risks of atherosclerotic cardiovascular disease (ASCVD, composite of fatal and nonfatal coronary heart disease and stroke) and total CVD (composite of ASCVD plus coronary insufficiency, angina pectoris, transient ischemic attack, intermittent claudication, and heart failure) using the Framingham Risk Score measured 2 to 7 years after delivery. These outcomes were assessed as continuous measures of absolute estimated risk in increments of 1%, and, secondarily, as categorical measures with high-risk defined as an estimated probability of CVD ≥10%. Multivariable linear regression and modified Poisson regression models adjusted for baseline age and individual-level social determinants, including health insurance, educational attainment, and household poverty. RESULTS: Among 4309 nulliparous individuals at baseline, the median age was 27 years (interquartile range [IQR]: 23-31) and the median ADI was 43 (IQR: 22-74). At 2 to 7 years postpartum (median: 3.1 years, IQR: 2.5, 3.7), the median 30-year risk of ASCVD was 2.3% (IQR: 1.5, 3.5) and of total CVD was 5.5% (IQR: 3.7, 7.9); 2.2% and 14.3% of individuals had predicted 30-year risk ≥10%, respectively. Individuals living in the highest ADI tertile had a higher predicted risk of 30-year ASCVD % (adjusted ß: 0.41; 95% confidence interval [CI]: 0.19, 0.63) compared with those in the lowest tertile; and those living in the top 2 ADI tertiles had higher absolute risks of 30-year total CVD % (T2: adj. ß: 0.37; 95% CI: 0.03, 0.72; T3: adj. ß: 0.74; 95% CI: 0.36, 1.13). Similarly, individuals living in neighborhoods in the highest ADI tertile were more likely to have a high 30-year predicted risk of ASCVD (adjusted risk ratio [aRR]: 2.21; 95% CI: 1.21, 4.02) and total CVD ≥10% (aRR: 1.35; 95% CI: 1.08, 1.69). CONCLUSION: Neighborhood-level socioeconomic disadvantage in early pregnancy was associated with a higher estimated long-term risk of CVD postpartum. Incorporating aggregated SDOH into existing clinical workflows and future research in pregnancy could reduce disparities in maternal cardiovascular health across the lifespan, and requires further study.

Pericardial fat volume is related to endothelial-mediated coronary blood flow in women with suspected coronary microvascular dysfunction. A report from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) study.

Background: Coronary microvascular dysfunction is prevalent in women with signs and symptoms of ischemia but no obstructive coronary artery disease (CAD) and is associated with an adverse prognosis. Elevated pericardial fat volume predicts adverse cardiac events, but mechanistic pathways of the association are not well understood. Methods: 118 women enrolled in the NHLBI-sponsored Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction study with suspected coronary microvascular dysfunction but no obstructive CAD underwent adenosine stress 1.5 T cardiovascular magnetic resonance imaging (CMR) imaging and invasive coronary reactivity testing. Semi-quantitative myocardial perfusion reserve index (MPR) index was derived from perfusion images. Pericardial fat volume was measured by manually contouring the cardiac margins and adjacent adipose tissue on a single trans-axial HASTE slice at the level of the left main coronary artery origin and indexed to body surface-area. Simple standard deviation analysis obtained for continuous variables and frequency (percent) for categorical variables. The relationships between pericardial fat volume and coronary reactivity testing parameters were examined by correlation and multivariable regression analyses. Results: Women with suspected coronary microvascular dysfunction had a mean age of 55 ± 10 years, body mass index (BMI) of 28 ± 7 kg/m2, 44 % had a history of smoking, 63 % hypertension, 8 % diabetes, and 20 % dyslipidemia. CMR imaging-derived pericardial fat volume and coronary blood flow response to intracoronary acetylcholine (Δ CBF) were negatively correlated (r = -0.32, p = 0.0013). After adjustment for age, number of risk factors, high-density lipoprotein (HDL), and cold pressor diameter response, pericardial fat volume remained a significant predictor of Δ coronary blood flow (p = 0.04). There was no association with other coronary reactivity testing measures or CMRI derived MPR index. Conclusions: Among women with suspected coronary microvascular dysfunction but no obstructive CAD, pericardial fat volume appears to be related in a hypothesized adverse direction to coronary microvascular endothelial function. These results support further work confirming and extending these results to investigate pericardial fat volume as mechanistic pathway and potential treatment target for coronary microvascular dysfunction-related adverse events.Trial registration: clinicaltrials.govNCT00832702.

Arterial stiffness assessment in coronary microvascular dysfunction and heart failure with preserved ejection fraction: An initial report from the WISE-CVD continuation study.

Background: Heart failure with preserved ejection fraction (HFpEF) is the most common cardiac complication in patients with coronary microvascular dysfunction (CMD), yet its underlying pathways remain unclear. Aortic pulse-wave velocity (aPWV) is an indicator of large artery stiffness and a predictor for cardiovascular disease. However, aPWV in CMD and HFpEF is not well characterized and may provide understanding of disease progression. Methods: Among participants without obstructive coronary artery disease, we evaluated 51 women with suspected CMD and 20 women and men with evidence of HFpEF. All participants underwent aPWV measurement (SphygmoCor, Atcor Medical) with higher aPWV indicating greater vascular stiffness. Cardiac magnetic resonance imaging (CMRI) assessed left ventricular (LV) ejection fraction, CMD via myocardial perfusion reserve index (MPRI), and ventricular remodeling via LV mass-volume ratio. . Statistical analysis was performed using Wilcoxon rank sum tests, Pearson correlations and linear regression analysis. Results: Compared to the suspected CMD group, the HFpEF participants were older (65 ± 12 vs 56 ± 11 yrs., p = 0.002) had higher BMI (31.0 ± 4.3 vs 27.8 ± 6.7 kg/m2, p = 0.013), higher aPWV (10.5 ± 2.0 vs 8.0 ± 1.6 m/s, p = 0.05) and lower MPRI (1.5 ± 0.3 vs1.8 ± 0.3, p = 0.02), but not remodeling. In a model adjusted for cardiovascular risk factors, the HFpEF group had a lower LVEF (estimate -4.78, p = 0.0437) than the suspected CMD group. Conclusions: HFpEF participants exhibit greater arterial stiffness and lower myocardial perfusion reserve, with lower LVEF albeit not remodeling, compared to suspected CMD participants. These findings suggest arterial stiffness may contribute to progression from CMD to HFpEF. Prospective work is needed and ongoing.

Adverse Pregnancy Outcomes and Predicted 30-Year Risk of Maternal Cardiovascular Disease 2-7 Years After Delivery.

OBJECTIVE: To determine whether adverse pregnancy outcomes are associated with a higher predicted 30-year risk of atherosclerotic cardiovascular disease (CVD; ie, coronary artery disease or stroke). METHODS: This was a secondary analysis of the prospective Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be Heart Health Study longitudinal cohort. The exposures were adverse pregnancy outcomes during the first pregnancy (ie, gestational diabetes mellitus [GDM], hypertensive disorder of pregnancy, preterm birth, and small- and large-for-gestational-age [SGA, LGA] birth weight) modeled individually and secondarily as the cumulative number of adverse pregnancy outcomes (ie, none, one, two or more). The outcome was the 30-year risk of atherosclerotic CVD predicted with the Framingham Risk Score assessed at 2-7 years after delivery. Risk was measured both continuously in increments of 1% and categorically, with high predicted risk defined as a predicted risk of atherosclerotic CVD of 10% or more. Linear regression and modified Poisson models were adjusted for baseline covariates. RESULTS: Among 4,273 individuals who were assessed at a median of 3.1 years after delivery (interquartile range 2.5-3.7), the median predicted 30-year atherosclerotic CVD risk was 2.2% (interquartile range 1.4-3.4), and 1.8% had high predicted risk. Individuals with GDM (least mean square 5.93 vs 4.19, adjusted ß=1.45, 95% CI, 1.14-1.75), hypertensive disorder of pregnancy (4.95 vs 4.22, adjusted ß=0.49, 95% CI, 0.31-0.68), and preterm birth (4.81 vs 4.27, adjusted ß=0.47, 95% CI, 0.24-0.70) were more likely to have a higher absolute risk of atherosclerotic CVD. Similarly, individuals with GDM (8.7% vs 1.4%, adjusted risk ratio [RR] 2.02, 95% CI, 1.14-3.59), hypertensive disorder of pregnancy (4.4% vs 1.4%, adjusted RR 1.91, 95% CI, 1.17-3.13), and preterm birth (5.0% vs 1.5%, adjusted RR 2.26, 95% CI, 1.30-3.93) were more likely to have a high predicted risk of atherosclerotic CVD. A greater number of adverse pregnancy outcomes within the first birth was associated with progressively greater risks, including per 1% atherosclerotic CVD risk (one adverse pregnancy outcome: 4.86 vs 4.09, adjusted ß=0.59, 95% CI, 0.43-0.75; two or more adverse pregnancy outcomes: 5.51 vs 4.09, adjusted ß=1.16, 95% CI, 0.82-1.50), and a high predicted risk of atherosclerotic CVD (one adverse pregnancy outcome: 3.8% vs 1.0%, adjusted RR 2.33, 95% CI, 1.40-3.88; two or more adverse pregnancy outcomes: 8.7 vs 1.0%, RR 3.43, 95% CI, 1.74-6.74). Small and large for gestational age were not consistently associated with a higher atherosclerotic CVD risk. CONCLUSION: Individuals who experienced adverse pregnancy outcomes in their first birth were more likely to have a higher predicted 30-year risk of CVD measured at 2-7 years after delivery. The magnitude of risk was higher with a greater number of adverse pregnancy outcomes experienced.

Prediction of metabolic syndrome following a first pregnancy.

BACKGROUND: The prevalence of metabolic syndrome is rapidly increasing in the United States. We hypothesized that prediction models using data obtained during pregnancy can accurately predict the future development of metabolic syndrome. OBJECTIVE: This study aimed to develop machine learning models to predict the development of metabolic syndrome using factors ascertained in nulliparous pregnant individuals. STUDY DESIGN: This was a secondary analysis of a prospective cohort study (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be Heart Health Study [nuMoM2b-HHS]). Data were collected from October 2010 to October 2020, and analyzed from July 2023 to October 2023. Participants had in-person visits 2 to 7 years after their first delivery. The primary outcome was metabolic syndrome, defined by the National Cholesterol Education Program Adult Treatment Panel III criteria, which was measured within 2 to 7 years after delivery. A total of 127 variables that were obtained during pregnancy were evaluated. The data set was randomly split into a training set (70%) and a test set (30%). We developed a random forest model and a lasso regression model using variables obtained during pregnancy. We compared the area under the receiver operating characteristic curve for both models. Using the model with the better area under the receiver operating characteristic curve, we developed models that included fewer variables based on SHAP (SHapley Additive exPlanations) values and compared them with the original model. The final model chosen would have fewer variables and noninferior areas under the receiver operating characteristic curve. RESULTS: A total of 4225 individuals met the inclusion criteria; the mean (standard deviation) age was 27.0 (5.6) years. Of these, 754 (17.8%) developed metabolic syndrome. The area under the receiver operating characteristic curve of the random forest model was 0.878 (95% confidence interval, 0.846-0.909), which was higher than the 0.850 of the lasso model (95% confidence interval, 0.811-0.888; P<.001). Therefore, random forest models using fewer variables were developed. The random forest model with the top 3 variables (high-density lipoprotein, insulin, and high-sensitivity C-reactive protein) was chosen as the final model because it had the area under the receiver operating characteristic curve of 0.867 (95% confidence interval, 0.839-0.895), which was not inferior to the original model (P=.08). The area under the receiver operating characteristic curve of the final model in the test set was 0.847 (95% confidence interval, 0.821-0.873). An online application of the final model was developed (https://kawakita.shinyapps.io/metabolic/). CONCLUSION: We developed a model that can accurately predict the development of metabolic syndrome in 2 to 7 years after delivery.

A practical guide for assessing and managing cardiovascular risk during androgen-deprivation therapy in patients with prostate cancer.

Prostate cancer is the most common malignancy among men worldwide, and androgen-deprivation therapy (ADT) is a mainstay of treatment. There are observational data demonstrating an increased risk of cardiovascular events in patients who receive ADT, particularly those who have an elevated baseline cardiovascular risk. Because, for most patients with prostate cancer, death is predominantly from noncancer-related causes, cardiovascular disease and its risk factors should be optimized during cancer treatment. This review provides an overview of the landscape of ADT treatment and serves as a guide for appropriate cardiovascular screening and risk-mitigation strategies. The authors emphasize the importance of shared communication between the multidisciplinary cancer team and primary care to improve baseline cardiovascular screening and treatment of modifiable risk factors within this higher risk population.

Elevated high-density lipoprotein cholesterol and adverse outcomes in women with symptoms of ischemic heart disease.

Background: Emerging data in the general population and those with coronary artery disease demonstrate higher risk of adverse outcomes with high (>70 mg/dL) HDL-C levels. There are limited data on the risk of adverse outcomes in women with suspected ischemic heart disease. Objective: To investigate relationships between high (>70 mg/dL), average (50-70 mg/dL), and low (<50 mg/dL) HDL-C levels with major adverse cardiac events (MACE) (death, myocardial infarction, stroke, and heart failure hospitalization), and all-cause mortality in women referred for coronary angiography for suspected myocardial ischemia. Methods: A total of 607 women enrolled in the Women's Ischemia Syndrome Evaluation (WISE) original cohort (NCT00000554) with available HDL-C values were included in this analysis. Associations between HDL-C level and outcomes were evaluated using both multivariate Cox proportional hazard regression and spline regression analysis. Results: The mean age was 59 ± 12 years, 62 % had 3 or more cardiac risk factors, and 66 (10.9 %) had a high HDL-C. High and low HDL-C were both associated with higher MACE risk compared to average HDL-C after adjusting for demographic and clinical characteristics (HR 1.80, CI 1.03-3.14, p = 0.038; HR 1.63, CI 1.09-2.42, p = 0.016, respectively). Similarly, high, and low HDL-C were associated with higher risk of all-cause mortality (HR 3.64, CI 1.84-7.20, p < 0.001; HR 2.81, CI 1.67-4.71, p < 0.001, respectively). Conclusions: High and low HDL-C levels are both independently associated with higher MACE and all-cause mortality in women with suspected ischemia undergoing coronary angiography.

Patient-physician sex concordance and outcomes in cardiovascular disease: a systematic review.

The sex disparity in outcomes of patients with cardiovascular disease is well-described and has persisted across recent decades. While there have been several proposed mechanisms to explain this disparity, there are limited data on female patient-physician sex concordance and its association with outcomes. The authors review the existing literature on the relationship between patient-physician sex concordance and clinical outcomes in patients with cardiovascular disease, the evidence of a benefit in clinical outcomes with female patient-physician sex concordance, and the possible drivers of such a benefit and highlight directions for future study.

Comparison of risk profiles of participants in the Women's IschemiA TRial to Reduce events In non-ObstRuctive CAD (WARRIOR) trial, using Coronary Computed Tomography Angiography vs Invasive Coronary Angiography.

OBJECTIVE: To compare baseline characteristics of participants in the Women's IschemiA TRial to Reduce Events In Non-ObstRuctive CAD (WARRIOR) trial by qualification by Coronary Computed Tomography Angiography (CCTA) or Invasive Coronary Angiography (ICA). METHODS: The WARRIOR trial (NCT03417388) is an ongoing multicenter, prospective, randomized, blinded outcome evaluation of intensive medical therapy vs. usual care in women with suspected Ischemia and No Obstructive Coronary Artery Disease (INOCA) identified by either CCTA or ICA on the outcome of major adverse cardiovascular events (MACE). No obstructive coronary artery disease is defined as <50% luminal stenosis and normal coronary arteries is defined as no evidence of atherosclerosis including calcified and non-calcified plaque. Data presented was extracted on May 27, 2020. No clinical outcomes were assessed. RESULTS: An initial sample cohort of 797 women was included. The majority were younger than 65 years, White participants (73.3%), 159 had diabetes (19.9%), and 676 had angina (84.8%) with the remainder having symptoms of suspected ischemic heart disease. Over 50% of randomized participants had normal coronaries without luminal irregularities by ICA or CCTA. Participants randomized to ICA were more likely to have worse baseline clinical risk profiles with older age, higher burden of cardiac risk factors and poor quality of life with disabling angina. CONCLUSIONS: Among this initial sample of women with suspected INOCA randomized in the WARRIOR trial, there is a differential baseline cardiac risk of participants enrolled after CCTA or ICA. However, the majority had no evidence of atherosclerotic plaque or obstructive stenosis, after evaluation by ICA or CCTA. These results suggest that non-invasive evaluation with CCTA is likely to be associated with lower risk of MACE.

Single Nucleotide Polymorphisms in Coronary Microvascular Dysfunction.

Coronary microvascular dysfunction is an underdiagnosed pathologic process that is associated with adverse clinical outcomes. There are data to suggest that coronary microvascular dysfunction, in some cases, may be genetically determined. We present an updated review of single nucleotide polymorphisms in coronary microvascular dysfunction.

Intraoperative Anemia Mediates Sex Disparity in Operative Mortality After Coronary Artery Bypass Grafting.

BACKGROUND: Women undergoing coronary artery bypass grafting (CABG) have higher operative mortality than men. OBJECTIVES: The purpose of this study was to evaluate the relationship between intraoperative anemia (nadir intraoperative hematocrit), CABG operative mortality, and sex. METHODS: This was a cohort study of 1,434,225 isolated primary CABG patients (344,357 women) from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (2011-2022). The primary outcome was operative mortality. The attributable risk (AR) (the risk-adjusted strength of the association of female sex with CABG outcomes) for the primary outcome was calculated. Causal mediation analysis derived the total effect of female sex on operative mortality risk and the proportion of that effect mediated by intraoperative anemia. RESULTS: Women had lower median nadir intraoperative hematocrit (22.0% [Q1-Q3: 20.0%-25.0%] vs 27.0% [Q1-Q3: 24.0%-30.0%], standardized mean difference 97.0%) than men. Women had higher operative mortality than men (2.8% vs 1.7%; P < 0.001; adjusted OR: 1.36; 95% CI: 1.30-1.41). The AR of female sex for operative mortality was 1.21 (95% CI: 1.17-1.24). After adjusting for nadir intraoperative hematocrit, AR was reduced by 43% (1.12; 95% CI: 1.09-1.16). Intraoperative anemia mediated 38.5% of the increased mortality risk associated with female sex (95% CI: 32.3%-44.7%). Spline regression showed a stronger association between operative mortality and nadir intraoperative hematocrit at hematocrit values <22.0% (P < 0.001). CONCLUSIONS: The association of female sex with increased CABG operative mortality is mediated to a large extent by intraoperative anemia. Avoiding nadir intraoperative hematocrit values below 22.0% may reduce sex differences in CABG operative mortality.

Sex Differences in Revascularization, Treatment Goals, and Outcomes of Patients With Chronic Coronary Disease: Insights From the ISCHEMIA Trial.

BACKGROUND: Women with chronic coronary disease are generally older than men and have more comorbidities but less atherosclerosis. We explored sex differences in revascularization, guideline-directed medical therapy, and outcomes among patients with chronic coronary disease with ischemia on stress testing, with and without invasive management. METHODS AND RESULTS: The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial randomized patients with moderate or severe ischemia to invasive management with angiography, revascularization, and guideline-directed medical therapy, or initial conservative management with guideline-directed medical therapy alone. We evaluated the primary outcome (cardiovascular death, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) and other end points, by sex, in 1168 (22.6%) women and 4011 (77.4%) men. Invasive group catheterization rates were similar, with less revascularization among women (73.4% of invasive-assigned women revascularized versus 81.2% of invasive-assigned men; P<0.001). Women had less coronary artery disease: multivessel in 60.0% of invasive-assigned women and 74.8% of invasive-assigned men, and no ≥50% stenosis in 12.3% versus 4.5% (P<0.001). In the conservative group, 4-year catheterization rates were 26.3% of women versus 25.6% of men (P=0.72). Guideline-directed medical therapy use was lower among women with fewer risk factor goals attained. There were no sex differences in the primary outcome (adjusted hazard ratio [HR] for women versus men, 0.93 [95% CI, 0.77-1.13]; P=0.47) or the major secondary outcome of cardiovascular death/myocardial infarction (adjusted HR, 0.93 [95% CI, 0.76-1.14]; P=0.49), with no significant sex-by-treatment-group interactions. CONCLUSIONS: Women had less extensive coronary artery disease and, therefore, lower revascularization rates in the invasive group. Despite lower risk factor goal attainment, women with chronic coronary disease experienced similar risk-adjusted outcomes to men in the ISCHEMIA trial. REGISTRATION: URL: http://wwwclinicaltrials.gov. Unique identifier: NCT01471522.