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INTRODUCTION: Epicardial fat is a metabolically active adipose tissue depot situated between the myocardium and visceral pericardium that covers â¼80% 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.
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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.
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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.
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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.
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Resultado del Embarazo , Humanos , Femenino , Embarazo , Adulto , Resultado del Embarazo/epidemiología , Estudios Prospectivos , Nacimiento Prematuro/epidemiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Estudios Longitudinales , Hipertensión Inducida en el Embarazo/epidemiología , Diabetes Gestacional/epidemiología , Factores de Riesgo , Recién Nacido , Medición de RiesgoRESUMEN
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.
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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.
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Antagonistas de Andrógenos , Enfermedades Cardiovasculares , Neoplasias de la Próstata , Humanos , Masculino , Antagonistas de Andrógenos/efectos adversos , Antagonistas de Andrógenos/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/etiología , Medición de Riesgo , Factores de Riesgo de Enfermedad Cardiaca , Factores de RiesgoRESUMEN
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.
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Enfermedades Cardiovasculares , Relaciones Médico-Paciente , Humanos , Femenino , Masculino , Factores Sexuales , Resultado del TratamientoRESUMEN
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.
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Anemia , Procedimientos Quirúrgicos Cardíacos , Adulto , Humanos , Femenino , Masculino , Estudios de Cohortes , Puente de Arteria Coronaria/efectos adversos , Anemia/epidemiología , Hematócrito , Factores de Riesgo , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
BACKGROUND: Proprotein convertase subtisilin/kexin 9 (PCSK9) raises low-density lipoprotein cholesterol (LDL-C) levels and is associated with inflammation, which is elevated in HIV and hepatitis C virus (HCV) infection. We compared PCSK9 levels in people with co-occurring HIV and HCV (HIV/HCV) vs. HIV alone, and evaluated the impact of HCV direct-acting antiviral (DAA) therapy on PCSK9. DESIGN: A prospective, observational cohort study. METHODS: Thirty-five adults with HIV/HCV and 37 with HIV alone were evaluated, all with HIV virologic suppression and without documented cardiovascular disease. Circulating PCSK9 and inflammatory biomarkers were measured at baseline and following HCV treatment or at week 52 (for HIV alone) and compared using Wilcoxon tests and Spearman correlations. RESULTS: At baseline, PCSK9 trended higher in HIV/HCV vs. HIV alone (307 vs. 284âng/ml, P â=â0.06). Twenty-nine participants with HIV/HCV completed DAA therapy with sustained virologic response. PCSK9 declined from baseline to posttreatment 1 (median 7.3âweeks after end of therapy [EOT]) and posttreatment 2 (median 43.5âweeks after EOT), reaching levels similar to HIV alone; median within-person reduction was -60.5âng/ml ( P â=â0.003) and -55.6âng/ml ( P â=â0.02), respectively. Decline in PCSK9 correlated with decline in soluble (s)E-selectin and sCD163 ( r â=â0.64, P â=â0.002; r â=â0.58, P â=â0.008, respectively), but not with changes in LDL-C or other biomarkers. No significant change in PCSK9 occurred in the HIV alone group over 52âweeks. CONCLUSION: PCSK9 declined with DAA therapy in participants with HIV/HCV, correlating with declines in several inflammatory biomarkers but not LDL-C. Elevated PCSK9 with HCV may be linked to particular HCV-associated inflammatory pathways more so than cholesterol homeostasis.
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Infecciones por VIH , Hepatitis C Crónica , Hepatitis C , Adulto , Humanos , Proproteína Convertasa 9 , Antivirales/uso terapéutico , Hepacivirus , LDL-Colesterol , Estudios Prospectivos , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Proproteína Convertasas/metabolismo , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Inflamación/complicaciones , BiomarcadoresAsunto(s)
Angiografía por Tomografía Computarizada , Enfermedad de la Arteria Coronaria , Humanos , Valor Predictivo de las Pruebas , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Tomografía Computarizada por Rayos X , Angiografía , Angiografía Coronaria/métodos , Pronóstico , Factores de RiesgoRESUMEN
OBJECTIVE: We aimed to investigate the hypothesis that interferon (IFN)-stimulated gene (ISG) expression in systemic lupus erythematosus (SLE) monocytes is linked to changes in metabolic reprogramming and epigenetic regulation of ISG expression. METHODS: Monocytes from healthy volunteers and patients with SLE at baseline or following IFNα treatment were analyzed by extracellular flux analysis, proteomics, metabolomics, chromatin immunoprecipitation, and gene expression. The histone demethylases KDM6A/B were inhibited using glycogen synthase kinase J4 (GSK-J4). GSK-J4 was tested in pristane and resiquimod (R848) models of IFN-driven SLE. RESULTS: SLE monocytes had enhanced rates of glycolysis and oxidative phosphorylation compared to healthy control monocytes, as well as increased levels of isocitrate dehydrogenase and its product, α-ketoglutarate (α-KG). Because α-KG is a required cofactor for histone demethylases KDM6A and KDM6B, we hypothesized that IFNα may be driving "trained immune" responses through altering histone methylation. IFNα priming (day 1) resulted in a sustained increase in the expression of ISGs in primed cells (day 5) and enhanced expression on restimulation with IFNα. Importantly, decreased H3K27 trimethylation was observed at the promoters of ISGs following IFNα priming. Finally, GSK-J4 (KDM6A/B inhibitor) resulted in decreased ISG expression in SLE patient monocytes, as well as reduced autoantibody production, ISG expression, and kidney pathology in R848-treated BALB/c mice. CONCLUSION: Our study suggests long-term IFNα exposure alters the epigenetic regulation of ISG expression in SLE monocytes via changes in immunometabolism, a mechanism reflecting trained immunity to type I IFN. Importantly, it opens the possibility that targeting histone-modifying enzymes, such as KDM6A/B, may reduce IFN responses in SLE.
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Interferón Tipo I , Lupus Eritematoso Sistémico , Ratones , Animales , Humanos , Ácidos Cetoglutáricos , Histonas , Epigénesis Genética , Interferón Tipo I/genética , Histona Demetilasas/genética , Expresión Génica , Histona Demetilasas con Dominio de Jumonji/genética , Histona Demetilasas con Dominio de Jumonji/metabolismoRESUMEN
BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with long-term maternal risks for cardiovascular disease for reasons that remain incompletely understood. METHODS: The HCHS/SOL (Hispanic Community Health Study/Study of Latinos), a multi-center community-based cohort of Hispanic/Latino adults recruited 2008 to 2011, was used to evaluate the associations of history of de novo HDP (gestational hypertension, preeclampsia, eclampsia) with echocardiographic measures of cardiac structure and function in Hispanic/Latina women with ≥1 prior pregnancy and the proportion of association mediated by current hypertension (>140/90 mm Hg or antihypertensive therapy). RESULTS.: The study cohort included 5168 Hispanic/Latina women with an average age (SD) of 58.7 (9.7) years at time of echocardiogram. Prior de novo HDP was reported by 724 (14%) of the women studied and was associated with lower left ventricle (LV) ejection fraction -0.66 (95% confidence interval [CI], -1.21 to -0.11), higher LV relative wall thickness 0.09 (95% CI, 0-0.18), and 1.39 (95% CI, 1.02-1.89) higher risk of abnormal LV geometry after adjusting for blood pressure and other confounders. The proportion of the association mediated by current hypertension between HDP and LV ejection fraction was 0.09 (95% CI, 0.03-0.45), LV relative wall thickness was 0.28 (95% CI, 0.16-0.51), abnormal LV geometry was 0.14 (95% CI, 0.12-0.48), concentric left ventricular hypertrophy was 0.31 (95% CI, 0.19-0.86), and abnormal LV diastolic dysfunction was 0.58 (95% CI, 0.26-0.79). CONCLUSIONS.: In a large cohort of Hispanic/Latina women those with history of de novo HDP had detectable and measurable subclinical alterations in cardiac structure and both systolic and diastolic dysfunction that were only partially mediated by current hypertension.
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Hipertensión Inducida en el Embarazo , Preeclampsia , Disfunción Ventricular Izquierda , Femenino , Humanos , Persona de Mediana Edad , Embarazo , Presión Sanguínea , Hispánicos o Latinos , Hipertensión Inducida en el Embarazo/epidemiología , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/epidemiología , AncianoRESUMEN
Myocardial infarction with no obstructive coronary artery disease (MINOCA) diagnostic work-up, risk stratification and tailored therapies are emerging as the recognition of this type of MI is increasingly recognized. Diagnostic workup using advanced imaging can include coronary angiography/intravascular ultrasound (IVUS)/optical coherent tomography (OCT), echo and cardiac magnetic resonance imaging (MRI). Risk stratification portends an intermediate risk compared to multivessel obstructive coronary artery disease (CAD). While event rates are high enough to warrant concern, they are relatively low enough to require trials with large sample sizes and hard outcomes. Tailored therapies include common sense therapeutic lifestyle change (TLC) and optimal medical therapy (OMT) due to the high prevalence of non-obstructive CAD, however therapeutic clinical trials are needed. Currently one large outcome trial in ischemia with no obstructive coronary artery disease (INOCA) is ongoing.