Ischemia Syndrome Evaluation Research Articles

Worse ischemic symptoms and cardiac function in women with suspected ischemia with no obstructive coronary artery disease and adverse pregnancy outcomes history

Abstract Background Adverse pregnancy outcomes (APO) are associated with increased maternal risk of cardiovascular disease (CVD) and mortality. Ischemia with no obstructive coronary artery disease (INOCA) is predominant in women, however the association of APO history with INOCA is poorly understood. Purpose To compare clinical characteristics, symptoms, cardiac structure and function and coronary microvascular dysfunction in women suspected to have INOCA with or without a history of APO. Methods Women’s Ischemia Syndrome Evaluation (WISE) CVD (NCT00832702) and WISE pre-HFpEF (NCT02582021) prospective cohorts of women with suspected INOCA were merged and utilized to determine among women with at least 1 prior pregnancy whether a history of APO was associated with ischemic symptoms, and to characterize CMRI measured left ventricle (LV) structure and function, myocardial deformation (systolic and diastolic strain) and coronary microvascular dysfunction on invasive coronary functional testing (CFT). Self-reported APO was defined as hypertensive disorder of pregnancy (HDP), gestational diabetes, preterm birth (<37-week gestation), low birth weight (<5lbs). Results In a cohort of 469 women with suspected INOCA, (mean average age 55 [SD 10.2] years) and at least 1 prior pregnancy, 138 (29%) had history of at least 1 APO. Among women with history of APO, 78 reported HDP, 50 gestational diabetes, 27 pre-term birth, 8 low birth weight. Women with a history of APO were younger, had higher rates of hypertension and diabetes, higher BMI and lower SAQ and DASI scores compared to those with no history of APO (Table). LV ejection fraction (EF) was lower and early diastolic strain rate/LVEDP was higher in women with APO history compared to those without APO history. Conclusion(s) In cohort of women with INOCA, history of APO was highly prevalent. Despite younger age, women with history of APO had higher rates of CVD risk factors, worse ischemic symptoms and functional capacity, lower EF, and higher filling pressures. Our findings suggest a potential for APO history to better identify women with worse prognosis that warrants further investigation and aggressive management.

Contributors to high left ventricular ejection fraction in women with ischemia and no obstructive coronary artery disease: Results from the Women's Ischemia Syndrome Evaluation—Coronary Vascular Dysfunction (WISE-CVD) Study

There are sex differences in left ventricular ejection fraction (LVEF) relevant to prognosis where women experience greater mortality at relatively higher LVEF compared to men, yet mechanistic understanding of this adverse prognosis is limited. Women with suspected ischemia with no obstructive coronary disease (INOCA) develop heart failure with preserved ejection fraction (HFpEF), yet contributors to LVEF remain largely unknown. In 370 women with suspected ischemia with no obstructive coronary disease (INOCA) who prospectively underwent cardiac magnetic resonance imaging (CMRI), we investigated the contributions of LV morphology, function, and myocardial perfusion reserve on LVEF using univariate and multiple linear regression. A majority 71% of participants had high LVEF (>65%), followed by 24% having normal LVEF (55%-65%), and only 5% having low EF (<55%). Baseline characteristics were comparable among the 3 groups, with the exception of age which was 6 years higher in the high LVEF group (P < .01). Women in the high LVEF group also had the lowest LV cavity volume, greatest LV mass-volume ratio, and highest LV end-systolic elastance (all P < .05, adjusted for age, BMI, diabetes, and blood pressure). Myocardial perfusion reserve index was low in all groups (mean MPRI < 2.1) but was not significantly different across the spectrum of LVEF (P = .458). Taken together, these data demonstrate that the majority of women with suspected INOCA have elevated LVEF related to smaller, thicker ventricles with greater contractility. Future work is needed to better understand the specific mechanisms driving morphologic and functional changes in women with INOCA, and relations to longer-term HFpEF and mortality. NCT02582021.

Depression Symptom Patterns as Predictors of Metabolic Syndrome and Cardiac Events in Symptomatic Women with Suspected Myocardial ischemia: The Women’s Ischemia Syndrome Evaluation (WISE and WISE-CVD) Projects

Depression Symptom Patterns as Predictors of Metabolic Syndrome and Cardiac Events in Symptomatic Women with Suspected Myocardial ischemia: The Women’s Ischemia Syndrome Evaluation (WISE and WISE-CVD) Projects

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

BackgroundWomen have smaller coronary size than men independent of body surface area. Female to male heart transplantation demonstrates coronary lumen enlargement. PurposeTo investigate relationships between endogenous androgens and coronary luminal size in women with suspected ischemic heart disease (IHD). MethodsWe analyzed 69 women with available androgen levels. ResultsGroup 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. ConclusionsIn women with suspected ischemic heart disease, endogenous androgens, coronary atheroma and luminal size are related, and may be moderated by waist circumference.

Dietary Composition, Angiographic Coronary Disease, and Cardiovascular Outcomes in the WISE Study (Women's Ischemia Syndrome Evaluation).

Studies relating diet to angiographic coronary artery disease (CAD) and subsequent major adverse cardiac events (MACE) in women are limited. Information on diet was collected in the Women's Ischemia Syndrome Evaluation (WISE), a prospective cohort study of symptomatic women referred for coronary angiography to evaluate suspected ischemic heart disease. A consecutive subgroup (n = 201 of 936) of enrolled women completed the modified Block food frequency questionnaire (FFQ). Data on outcomes were collected and adjudicated after 8-year follow-up. A set of logistic regression models were fitted for non-obstructive versus obstructive coronary stenosis (<50% versus ≥50%). Cox proportional hazard regression models were fitted for outcomes, with each dietary composition variable adjusted for the degree of coronary stenosis. At baseline, the subgroup cohort was 58 ± 12 years old with a body mass index (BMI) of 30 ± 7 kg/m2. An increased proportion of calories consumed from protein was associated with higher levels of baseline obstructive coronary stenosis. Those individuals who ate a higher amount of protein, carotene, and servings of vegetables and meat, however, were each associated with lower subsequent adverse outcomes, respectively. Among women undergoing coronary angiography for suspected CAD, a higher percentage of protein intake was associated with higher baseline stenosis severity; however, the amount of protein intake, vegetable, meat, and carotene intake, was conversely associated with subsequent lower adverse cardiovascular outcome risk.

Association of abnormal electrocardiography response on dobutamine stress echocardiogram with longer-term major adverse cardiovascular events in women with symptoms of ischemic heart disease.

Prior work demonstrates patients with positive (+) electrocardiogram (ECG) but negative (-) echocardiogram wall motion abnormalities (WMAs) on dobutamine stress echocardiography (DSE) testing have an elevated of major adverse cardiovascular events (MACEs). In this study, we aimed to evaluate the long-term prognosis of women with suspected ischemia with no obstructive coronary artery (INOCA) disease by utilizing core lab read DSE, specifically focusing on those with + ECG findings. Among women with signs and symptoms of myocardial ischemia undergoing clinically indicated coronary angiography enrolled in the Women's Ischemia Syndrome Evaluation (WISE) [1997-2001], a prospective cohort study, 99 underwent standardized DSE by site design. Women with positive DSE (n=17), defined as an increase in score based on wall motion scoring index were excluded except for akinetic to dyskinetic (n=10), providing 82 patients in this analysis. ECG was assessed by core laboratory and (+) ECG was defined as >1 mm ST change. Non-obstructive coronary artery disease (CAD) was assessed by core laboratory quantitative coronary angiography and defined as <50% epicardial stenosis. All-cause death follow-up was an average of 8 years, while adjudicated MACE [all-cause mortality, nonfatal myocardial infarction (MI), nonfatal stroke, heart failure hospitalization] was an average of 5.5 years. Comparisons among subject groups [i.e., (+) ECG and (-) ECG] were made using chi-square or Fisher's exact tests for categorical variables and t-test or Wilcoxon rank-sum test for continuous variables. Demographic profile included a mean age 59±10 years; 55% had hypertension (HTN), 29% diabetes mellitus (DM), and 72% non-obstructive CAD. Overall, 9/82 women (11%) had (+) ECG in the absence of WMAs. There were significant differences in family history of CAD (P=0.009) and vasodilator (P=0.042) use between the (+) ECG and (-) ECG groups, but otherwise had no significant demographic or clinical differences. At longer-term follow up, patients with (+) ECG had higher risk of MACE [unadjusted hazard ratio (HR): 4.91, 95% confidence interval (CI): 1.83, 13.19, P=0.002]. Abnormal stress ECG findings on dobutamine stress testing with a negative DSE should be viewed as an indicator of longer-term risk in women with signs and symptoms of ischemia.

High levels of high-density lipoprotein cholesterol (HDL-C) and major adverse cardiovascular events and 10-year all-cause mortality:results from Women's Ischemia Syndrome Evaluation (WISE) study

Abstract Background High and low levels of high-density lipoprotein cholesterol (HDL-C) are associated with lower and higher cardiovascular risk, respectively. Emerging data in the general population and those with coronary artery disease have shown an increased risk of adverse outcomes with high (&amp;gt;1.8mmolL [70 mg/dL]) HDL-C levels. However, there are limited data on the risk of adverse of outcomes in women with suspected ischemic heart disease and high HDL-C levels. Purpose To investigate relationships between high (&amp;gt;1.8mmol/L [70 mg/dL]), average (1.3 - 1.8 mmol/L [ 50 - 70 mg/dL]), and low (&amp;lt;1.3 mmol/L [50 mg/dL]) HDL-C levels with major adverse cardiac events (MACE) (death, myocardial infarction, stroke, and heart failure hospitalization), and 10-year all-cause mortality in women referred for coronary angiography for suspected myocardial ischemia. Methods Participants (N= 935) enrolled in the Women’s Ischemia Syndrome Evaluation (WISE) study from 1997-2001 underwent baseline testing that included fasting lipids, detailed demographic, and clinical data. A total of 607 women with available HDL-C values were included in this analysis. The adjudicated MACE outcome median follow-up was 5.9 years (range, 0 - 9.3), and the all-cause mortality median follow-up was 8.4 years (range, 0 - 11.3). Associations between HDL-C level and outcomes were obtained via multivariate cox regression and adjusted for age, race, BMI, waist circumference, menopausal status, hypertension, diabetes, family history of CAD, history of stroke, smoking history, alcohol use, statin use, and CAD status. The U-shaped curve was obtained using continuous HDL-C with the cubic spline analysis before adjusting for covariates listed above. Results The mean age of the cohort 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 increased MACE risk compared to average HDL-C (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 increased risk of all-cause mortality (HR 3.64, CI 1.84 - 7.20, p &amp;lt;0.001; HR 2.81, CI 1.67 - 4.71, p &amp;lt;0.001, respectively, Figure). Conclusions High and low HDL-C levels are associated with an increased MACE and all-cause mortality in women presenting with suspected ischemia undergoing coronary angiography. Our results highlight the need for additional prospective studies to discern the mechanisms behind high HDL-C levels and elevated risk of adverse outcomes in women.

Epicardial fat is associated with adverse ventricular remodeling and diastolic dysfunction in women with ischemia but no obstructive coronary artery disease

Abstract Background Epicardial fat is a metabolically active adipose tissue depot located between the myocardium and visceral pericardium. Increased epicardial fat is associated with the development of atherosclerosis and obstructive coronary artery disease (CAD). However, information regarding relations between epicardial fat—which covers 80% of the heart surface—and cardiac function, is limited. Purpose To evaluate relations between epicardial fat and cardiac morphology and function in all four chambers of the heart. Methods To accomplish our objective, we studied 113 participants from the Women’s Ischemia Syndrome Evaluation cohort who underwent invasive measurement of left ventricular end-diastolic pressure and coronary reactivity, and comprehensive rest-stress cardiac magnetic resonance imaging (cMRI) per standardized protocols. Epicardial fat area was measured from a single high resolution steady-state free precession cine cMRI in the horizontal long axis plane (Figure 1A). Left ventricular (LV) mass, bi-ventricular volumes, and ejection fractions, were assessed using a stack of short axis cine images covering both ventricles (Figure 1B). LV concentricity was defined as the mass-to-end-diastolic volume ratio. Strain and strain rate were assessed in all four chambers by feature tracking (Figure 1C). Left atrial (LA) volume was assessed using three orthogonal long-axis cines, while right atrial (RA) area was assessed using a single horizontal long axis cine (Figure 1D). Participants were stratified by the median epicardial fat area, defined as "Low" epicardial fat (&amp;lt;13 cm2, n=48) and "High" epicardial fat (≥13 cm2, n=65). Results Participant characteristics are reported in Table 1. Notably, the majority (58%) had "High" epicardial fat and body mass index (BMI) was greater in the "High" epicardial fat group. After adjusting for BMI, however, bi-ventricular stroke index remained lower in the "High" epicardial fat group, as did bi-atrial ejection fraction (fractional area change, RA). Moreover, compared to the "Low" epicardial fat group, LV concentricity and LA booster strain were higher in the "High" epicardial fat group (Figure E-F), while LV longitudinal strain and LV early circumferential diastolic strain rate were lower (Figure G-H). No other major differences were observed between groups, including coronary reactivity or myocardial perfusion reserve. Conclusions Together, these data suggest that higher BMI is associated with increased epicardial fat that is related to adverse cardiac remodeling, along with systolic and diastolic dysfunction, across multiple cardiac chambers. Further studies would be useful to define specific mechanism contributing to these observations.Figure 1Table 1

Abstract 14700: Associations of Left Ventricular Structure With Cumulative Systolic Blood Pressure Load: A Report From Women’s Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction Study

Background: Recent studies have identified cumulative systolic blood pressure load to be associated with increased risk of adverse cardiovascular disease (CVD) outcomes. Similarly, associations between left ventricular (LV) structure and CVD events have long been recognized. Purpose: The purpose of this study was to assess the association between cumulative systolic blood pressure (CuSBP) load and LV structure in women with suspected ischemia with no obstructive coronary arteries (INOCA). Methods: Women enrolled in the Women’s Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction (WISE-CVD) study (NCT00832702) underwent cardiac magnetic resonance imaging (CMRI) for LV structure and those (n= 225) who had at least 2 blood pressure (BP) measures recorded at a single site before their baseline CMRI were included in this analysis. Cumulative systolic BP (CuSBP) was defined as systolic BP (SBP) ≥ 130 divided by all SBP readings and each mean value multiplied by the years. LV remodeling index was defined as the ratio between LV mass and LV end diastolic volume (LVEDV). Results: The mean age was 55±10 years, body mass index (BMI) 26.3 ± 5.5 kg/m 2 , 36% had a history of hypertension, number of BP medications was mean 2.7 ± 1.6 [median 2 (range 0, 8)], and SBP and DBP were 126 ± 15 and 66 ± 10 mmHg respectively. Age, BMI and history of hypertension were significantly associated with higher CuSBP load. In univariate analyses, LV end diastolic volume and LV end systolic volume decreased, and LV remodeling index increased across CuSBP quartiles while LV mass index did not significantly differ among the quartiles (Figure 1) . In multivariable regression analysis, the association between CuSBP and LV mass index and LV remodeling index remained significant. Conclusions: Among women with suspected INOCA, higher CuSBP load was associated with greater LV mass index and concentric LV remodeling independent of age. Changes in LV volumes may represent age-related changes in LV structure.

Left ventricular ejection fraction and long-term outcomes in women presenting with signs and symptoms of ischaemia

BackgroundAlthough women are known to have a relatively higher left ventricular ejection fraction (LVEF) compared with men, a sex-neutral LVEF threshold continues to be used for clinical management. We sought...

Fitness attenuates long-term cardiovascular outcomes in women with ischemic heart disease and metabolic syndrome

BackgroundThe prevalence of metabolic syndrome continues to increase steadily while fitness remains relatively low. The contribution of fitness on longer-term cardiovascular outcomes and mortality in individuals with cardiovascular disease and metabolic syndrome remains unknown. DesignWomen's Ischemia Syndrome Evaluation (WISE) prospective cohort (enrolled 1996–2001) of women undergoing invasive coronary angiography with signs/symptoms of ischemic heart disease. MethodsInvestigated the association of fitness, defined as >7METs measured by self-reported Duke Activity Status Index (DASI), and both metabolic syndrome (ATPIII criteria) and dysmetabolism (ATPIII criteria and/or treated diabetes) with long-term cardiovascular outcomes and all-cause mortality risk. ResultsAmong the 492 women followed for a median of 8.6 years (range 0–11 years), 19.5% were fit-metabolically healthy (reference), 14.4% fit-metabolic syndrome, 29.9% unfit-metabolically healthy, and 36.2% unfit-metabolic syndrome. Compared to reference, MACE risk was 1.52-fold higher in fit-metabolic syndrome women (HR 1.52, 95% CI 1.03–2.26) and 2.42-fold higher in unfit-metabolic syndrome women (HR 2.42, 95% CI 1.30–4.48). Compared to reference, mortality risk was 1.96-fold higher in fit-dysmetabolism (HR 1.96, 95% CI 1.29–3.00) and 3-fold higher in unfit-dysmetabolism women (HR 3.0, 95% CI 1.66–5.43). ConclusionsIn a high risk cohort of women with signs/symptoms of ischemic heart disease, unfit-metabolically healthy and fit-metabolically unhealthy women were at higher risk of long-term MACE and mortality compared to fit-metabolically healthy women; and women who were unfit and metabolically unhealthy were at the highest risk. Our study demonstrates that metabolic health and fitness play an important role in long term outcomes that warrants further investigation. Registrationhttps://www.clinicaltrials.gov/ct2/show/NCT00000554 (NCT00000554)

Latest from the WISE: Contributions to the Understanding of Ischemia and Heart Failure among Women with No Obstructive Coronary Arteries.

Since 1996, the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) has been investigating pathophysiological processes underlying ischemic heart disease in women and related outcomes. Recent findings have focused on women with signs and symptoms of ischemia and no obstructive coronary arteries (INOCA) and their elevated risk for heart failure with preserved ejection fraction (HFpEF). This review summarizes the latest WISE findings related to INOCA and pre-HFpEF characteristics, addressing our understanding of contributions from traditional vs nontraditional risk factors in women.

Abstract 15367: Depression Symptom Patterns as Predictors of Metabolic Syndrome and Cardiac Events in Symptomatic Women With Suspected Myocardial Ischemia: The Women’s Ischemia Syndrome Evaluation (WISE &amp; WISE-CVD) Projects

Introduction: Ischemic Heart Disease (IHD) risk in women includes biomedical, behavioral, and psychosocial contributors. Among psychosocial contributors, recent studies suggest that depression, especially somatic symptoms of depression such as anhedonia and low energy, may play a disproportionate role in the development of both IHD risk factors and major adverse cardiovascular events (MACE). Methods: We examined relationships between cognitive/somatic symptoms of depression and metabolic syndrome (MetS) in two independent cohorts of women with suspected IHD. In the Women’s Ischemia Syndrome Evaluation (WISE, NCT00000554), we also examined depression and MetS as predictors of all-cause mortality and MACE over a median 9.3-year follow-up. The sample from WISE included 641 women with suspected ischemia with or without obstructive coronary artery disease (CAD). The WISE-Coronary Vascular Dysfunction (WISE-CVD, NCT00832702) consisted of 359 women with suspected ischemia and no obstructive CAD (INOCA). Somatic, cognitive, and total depressive symptoms were measured via the Beck Depression Inventory (BDI). MetS was assessed according to the AHA’s ATP-III criteria. Results: (See attached table) In both the WISE and WISE-CVD samples, somatic symptoms of depression were associated with MetS diagnosis and MetS severity, while cognitive symptoms were not. Within the WISE sample, using Cox Proportional Hazard Regression, both somatic symptoms and MetS diagnosis were significant predictors of all-cause mortality and MACE, while cognitive symptoms were not. Conclusions: In two independent samples of women undergoing coronary angiography for suspected myocardial ischemia, somatic symptoms of depression were uniquely associated with both MetS and all-cause mortality and MACE, and both somatic symptoms of depression and MetS independently predicted all-cause mortality and MACE.

Pericardial fat from a single horizontal long axis cardiac magnetic resonance cine image: a validation study against three-dimensional cardiac computed tomography

Abstract Background Excess fat accumulation around the heart (i.e., pericardial fat) is positively associated with cardiovascular disease. Pericardial fat is composed of two distinct depots: (1) epicardial fat, which is a metabolically active adipose tissue located between the heart and the pericardium, and (2) paracardial fat, which is the fat deposit in the mediastinum outside of the parietal pericardium. Both depots are visible on the horizontal long axis cardiac magnetic resonance (CMR) cine (i.e., four chamber view), offering an attractive opportunity to quantify pericardial fat from standard CMR cine images. Purpose To validate pericardial fat area measured from a single horizontal long axis CMR cine against whole-heart volumetric non-contrast cardiac computed tomography (CT) measurements. Methods To accomplish our goal, we leveraged 25 cases from the Women's Ischemia Syndrome Evaluation – Coronary Vascular Dysfunction Continuation cohort who underwent both cardiac MRI and cardiac CT within a median of 35 days apart. For MRI, pericardial fat area was measured from a single high resolution steady state free precession cine image in the horizontal long axis imaging plane using commercially available software (CVI42 V5.13.5, Circle Cardiovascular Imaging, Figure 1A). For CT, pericardial fat volume was measured using a fully automated deep learning algorithm (QFAT 2.0, Figure 1A). Results Fat area measured from a single horizontal long axis cine image was closely related to fat volume measured by three-dimensional cardiac CT, with strong correlations for epicardial fat (R2=0.72, p&amp;lt;0.01, Figure 1B), paracardial fat (R2=0.80, p&amp;lt;0.01, Figure 1C), and pericardial fat (R2=0.91, p&amp;lt;0.01, Figure 1D). Conclusions Measuring pericardial fat area, and its constituent parts, from a single horizontal long axis cine image is both feasible and strongly related to reference standard pericardial fat volume by cardiac CT. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): National Institutes of Health

Depression Symptom Patterns as Predictors of Metabolic Syndrome and Cardiac Events in Symptomatic Women with Suspected Myocardial Ischemia: The Women's Ischemia Syndrome Evaluation (WISE and WISE-CVD) Projects

Background: Ischemic heart disease (IHD) risk in women includes biomedical, behavioral, and psychosocial contributors. The purpose of this study was to build upon previous research suggesting that in women, somatic symptoms (SS) of depression may be important to the development of IHD risk factors and major adverse cardiovascular events (MACE). Based on previous findings, we hypothesized that: (1) SS would be associated with robust biomedical predictors of heart disease and functional capacity, while cognitive symptoms (CS) of depression would not, and (2) SS would independently predict adverse health outcomes while CS would not. Methods: We examined the relationships between symptoms of depression (SS/CS), metabolic syndrome (MetS), inflammatory markers (IM), coronary artery disease (CAD) severity, and functional capacity in two independent cohorts of women with suspected IHD. In the Women's Ischemia Syndrome Evaluation (WISE), we also examined these variables as predictors of all-cause mortality (ACM) + MACE over a median 9.3-year follow-up. The WISE sample included 641 women with suspected ischemia with or without obstructive CAD. The WISE-Coronary Vascular Dysfunction (WISE-CVD) sample consisted of 359 women with suspected ischemia and no obstructive CAD. All study measures were collected uniformly at baseline. Depressive symptoms were measured via the Beck Depression Inventory. MetS was assessed according to Adult Treatment Panel III (ATP-III) criteria. Results: In both studies, SS was associated with MetS (Cohen's d = 0.18, 0.26, P &lt; 0.05, respectively), while CS was not. Within WISE, using Cox Proportional Hazard Regression, SS (Hazard ratio [HR] = 1.08, 95% confidence interval [CI] = 1.01–1.15; HR = 1.07, 95% CI = 1.00–1.13) and MetS (HR = 1.89, 95% CI = 1.16–3.08; HR = 1.74, 95% CI=1.07–2.84) were independent predictors of ACM + MACE after controlling for demographics, IM, and CAD severity, while CS was not. Conclusions: In two independent samples of women undergoing coronary angiography due to suspected ischemia, SS but not CS of depression were associated with MetS, and both SS and MetS independently predicted ACM and MACE. These results add to previous studies suggesting that SS of depression may warrant specific attention in women with elevated cardiovascular disease (CVD) risk. Future research evaluating the biobehavioral basis of the relationship between depression, MetS, and CVD is needed.

Trans-myocardial omega-3 fatty acid gradient in coronary microvascular dysfunction

BackgroundCardiac remodeling is a process mediated, in part, by 18-hydroxyeicosapentaenoic acid (HEPE), a metabolite of the omega-3 polyunsaturated fatty acid, eicosapentaenoic acid (EPA). We hypothesized that trans-myocardial levels of 18-HEPE could inform the pathophysiologic processes involved in heart failure with preserved ejection fraction (HFpEF). MethodsWe measured the concentration of 18-HEPE and EPA in trans-myocardial plasma samples from 10 subjects enrolled in The Women's Ischemia Syndrome Evaluation [WISE] Mechanisms of Coronary Microvascular Dysfunction Leading to Pre-HFpEF project. ResultsConcentrations of 18-HEPE were significantly lower in coronary venous compared to the aortic plasma (270.5 pg/mL [212.8–480.8] vs. 430.5 pg/mL [299.5–655.8], p = 0.0039). There was a significant correlation between the concentrations of coronary venous EPA and aortic 18-HEPE (r = 0.94, p = 0.0002), and aortic EPA and aortic 18-HEPE (r = 0.82, p = 0.0058). ConclusionsResults of this small pilot study support the suggestion that 18-HEPE is synthesized outside the heart and utilized within the myocardial bed.

Body weight and physical fitness in women with ischaemic heart disease: does physical fitness contribute to our understanding of the obesity paradox in women?

AimsBody mass index (BMI) defined obesity is paradoxically associated with lower all-cause mortality in patients with known cardiovascular disease. This study aims to determine the role of physical fitness in the obesity paradox in women with ischaemic heart disease (IHD).Methods and ResultsWomen undergoing invasive coronary angiography with signs/symptoms of IHD in the Women’s Ischemia Syndrome Evaluation (WISE) prospective cohort (enrolled 1997–2001) were analysed. This study investigated the longer-term risk of major adverse cardiovascular events (MACE) and all-cause mortality associated with BMI and physical fitness measured by Duke Activity Status Index (DASI). Overweight was defined as BMl ≥25 to 30 kg/m2, obese as BMI ≥30 kg/m2, unfit as DASI scores <25, equivalent to ≤7 metabolic equivalents. Among 899 women, 18.6% were normal BMI-fit, 11.4% overweight-fit, 10.4% obese-fit, 15.3% normal BMI-unfit, 23.8% overweight-unfit, and 30.4% obese-unfit. In adjusted models compared to normal BMI-fit, normal BMI-unfit women had higher MACE risk [hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.17–2.32; P = 0.004]; whereas obese-fit and overweight-fit women had lower risk of mortality (HR 0.60, 95% CI 0.40–0.89; P = 0.012 and HR 0.62, 95% CI 0.41–0.92; P = 0.018, respectively).ConclusionTo address the paradox of body weight and outcomes in women, we report for the first time that among women with signs/symptoms of IHD overweight-fit and obese-fit were at lower risk of long-term all-cause mortality; whereas normal BMI-unfit were at higher risk of MACE. Physical fitness may contribute to the obesity paradox in women, warranting future studies to better understand associations between body weight, body composition, and physical fitness to improve cardiovascular outcomes in women.

Prognostic significance of anemia in women with suspected ischemia, an insight from the women ischemia syndrome evaluation study (WISE)

Abstract Background Anemia is associated with adverse cardiovascular outcomes in patients with myocardial infarction and congestive heart failure. Anemia is more prevalent in women. We investigated the prognosis of anemia in women with suspected ischemic heart disease. Purpose To study if hemoglobin levels at baseline in women with symptoms of ischemia predicts long term all-cause mortality and major adverse cardiac events. Methods We studied 885 women enrolled in WISE (1997–2001) undergoing clinically indicated coronary angiography for suspected ischemia. Anemia was defined as hemoglobin (Hb) level &amp;lt;12g/dL. Major adverse cardiovascular event (MACE) included all-cause death, nonfatal myocardial infarction, stroke and heart failure hospitalization. Cox regression models and Kaplan-Meier methods were was used. Results Overall, 885 women, mean age 58.4±11.7 years, 21.1% and anemia were followed for 6.8 years. Anemic women had higher creatinine, history of diabetes mellitus, hypertension and CHF (p&amp;lt;0.05), but not obstructive coronary artery disease compared to non-anemia women (p=0.97). Anemic women had higher all-cause mortality and MACE (Figure). In multivariate analysis, anemia was independently associated with increased MACE risk (hazard ratio (HR): 1.5, 95% confidence interval [1.11- 2.01, p=0.007]) but not all-cause mortality (HR: 1.2 [0.84–1.72, p=0.30]). Conclusions Among women evaluated for symptoms of ischemia, anemia is associated with and independently predicts MACE. Further research targeting anemia treatment in women to mitigate these adverse outcomes is warranted. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): NIH USA

Anemia and Long-term cardiovascular outcomes in women with suspected ischemia – The Women's Ischemia Syndrome Evaluation (WISE)

BackgroundAnemia is associated with adverse cardiovascular outcomes in patients with ischemic heart disease and is more prevalent in women as compared to men. Prior studies have evaluated short-term outcomes in women with stable angina and relatively low rates of obstructive coronary artery disease (CAD). We investigated the long-term clinical significance of baseline anemia in this cohort. MethodsWe studied 885 women enrolled in the Women's Ischemia Syndrome Evaluation (WISE) undergoing clinically indicated coronary angiography for suspected ischemia. Anemia at enrollment was defined as hemoglobin (Hgb) level < 12 g/dL. Major adverse cardiovascular events (MACE) included cardiovascular death, non-fatal myocardial infarction, heart failure hospitalization, stroke, and vascular events. Cox regression models and Kaplan-Meier methods were used. ResultsOverall, the women, mean age 58.4 ± 11.7 years, were followed for an average of seven years (range 0–11 years). Anemia was present in 21.1%. They had higher creatinine levels with more frequent history of diabetes mellitus, hypertension, and HF (p < 0.05) but similar obstructive coronary artery disease compared to non-anemic women. Anemic women had higher long-term all-cause mortality and MACE rate. In multivariable analysis, anemia was independently associated with increased MACE risk (hazard ratio (HR): 1.5, 95% confidence interval [1.117–2.017, p = 0.007]) but not all-cause mortality (HR:1.2 [0.841, 1.727, p = 0.309]). ConclusionsAmong women evaluated for symptoms of ischemia, anemia is associated with and independently predicts long-term MACE. Further research targeting anemia management in women to mitigate these adverse outcomes is warranted.

Somatic Versus Cognitive Depressive Symptoms as Predictors of Coronary Artery Disease among Women with Suspected Ischemia: The Women's Ischemia Syndrome Evaluation.

Background:Depression is an established predictor of coronary artery disease (CAD) progression and mortality. “Somatic” symptoms of depression such as fatigue and sleep impairment overlap with symptoms of CAD and independently predict CAD events. Differentiating between “somatic” and “cognitive” depressive symptoms in at-risk patients may improve our understanding of the relationship between depression and CAD.Methods:The study utilized data from the Women’s Ischemia Syndrome Evaluation. Participants (N = 641; mean age = 58.0 [11.4] years) were enrolled to evaluate chest pain or suspected myocardial ischemia. They completed a battery of symptom and psychological questionnaires (including the Beck Depression Inventory [BDI]) at baseline, along with quantitative coronary angiography and other CAD diagnostic procedures. The BDI provided scores for total depression and for cognitive and somatic depressive symptom subscales.Results:Two hundred and fourteen (33.4%) women met criteria for obstructive CAD. Logistic regression models were used to examine relationships between depression symptoms and obstructive CAD. Neither BDI total scores (odds ratio [OR] =1.02, 95% confidence interval [CI], 0.99–1.05, P = 0.053) nor BDI cognitive scores (OR = 1.02, 95% CI, 1.00–1.04, P = 0.15) predicted CAD status. BDI somatic symptom scores, however, significantly predicted CAD status and remained statistically significant after controlling for age, race, and education (OR = 1.06, 95% CI, 1.01–1.12, P = 0.02).Conclusion:Among women with suspected myocardial ischemia, somatic but not cognitive depressive symptoms predicted an increased risk of obstructive CAD determined by coronary angiography. Consistent with prior reports, these results suggest a focus on somatic rather than cognitive depressive symptoms could offer additional diagnostic information.