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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.
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Angiografía por Tomografía Computarizada , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Valor Predictivo de las Pruebas , Humanos , Femenino , Persona de Mediana Edad , Anciano , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/terapia , Medición de Riesgo , Estudios Prospectivos , Isquemia Miocárdica/diagnóstico por imagen , Isquemia Miocárdica/diagnóstico , Factores de Riesgo , Factores de Riesgo de Enfermedad Cardiaca , Factores Sexuales , Factores de Tiempo , Pronóstico , Salud de la Mujer , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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Identifying ischemic heart disease (IHD) in women based on symptoms is challenging. Women are more likely to endorse non-cardiac symptoms. More than 50% of women with suspected ischemia have no obstructive coronary disease (and thus, INOCA) and impaired outcomes during follow-up. We aimed to identify symptoms having predictive capacity for INOCA in women with clinical evidence of coronary ischemia. We included 916 women from the original WISE cohort (NCT00000554) who had coronary angiography performed for suspected ischemia and completed a 65-item WISE symptom questionnaire. Sixty-two percent (n = 567) had suspected INOCA. Logistic regression models using a best subsets approach were examined to identify the best predictive model for INOCA based on Score χ2 and AICc. A 10-variable, best-fit model accurately predicted INOCA (AUC 0.72, 95% CI 0.68, 0.75). The model indicated that age ≤ 55 years, left side chest pain, chest discomfort, neck pain, and palpitations had independent, positive relationship (OR > 1) to INOCA (p < 0.001 to 0.008). An inverse relationship (OR < 1) was observed for impending doom, and pain in the jaw, left or bilateral arm, and right hand, interpreted as INOCA associated with the absence of these symptoms (p ≤ 0.001 to 0.023). Our best-fit model accurately predicted INOCA based on age and symptom presentation ~72% of the time. While the heterogeneity of symptom presentation limits the utility of this unvalidated 10-variable model, it has promise for consideration of symptom inclusion in future INOCA prediction risk modeling for women with evidence of symptomatic ischemia.
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BACKGROUND: Studies on the longitudinal effects of intense physical training on cardiac remodeling are limited, especially in American collegiate football players. HYPOTHESIS: College-level American football training will result in remodeling in a pattern consistent of a sport with moderate static and dynamic demands with increases in both wall and chamber sizes. METHODS: We studied 85 American collegiate football players who underwent transthoracic echocardiogram (TTE) for asymptomatic or mild COVID-19-related illness and compared the changes in echo dimensions to their preparticipation screening TTE. Pre- and posttraining variables were compared using a paired t-test for normally distributed variables. RESULTS: Mean age was 19 years ± 1 and 61% of athletes were Black. Mean follow-up between TTEs was 21 ± 13 months. There was an increase in left atrial volume index (26.4 ± 5.5 to 32.8 ± 8.4 mL/m2 , p < .001), LV end diastolic diameter (5.13 ± 0.4 to 5.27 ± 0.4 cm, p = .003), basal RV diameter (3.28 ± 0.7 to 3.83 ± 0.5 cm, p = <.001), LV mass index (86.7 ± 15.3 to 90.1 ± 15.3, p = .015), and aortic root diameter (3.1 ± 0.4 to 3.2 ± 0.3 cm, p = .03) from pre- to posttraining, with a slightly greater magnitude in athletes with >2 years of training. Presence of left atrial enlargement (≥35 mL/m2 ) increased from 2.9% to 29% pre- to postparticipation in athletes with >2 years training. No significant changes in wall thickness, diastolic function, or right ventricular systolic function were observed. CONCLUSION: American football players college-level training was associated with increases in left and right ventricular chamber sizes, left atrial size, and aortic root diameter.
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Fibrilación Atrial , COVID-19 , Fútbol Americano , Humanos , Adulto Joven , Adulto , Remodelación Ventricular , Ecocardiografía/métodos , Atrios Cardíacos/diagnóstico por imagenRESUMEN
Background: While autoimmune rheumatic diseases (ARDs) have been linked with coronary microvascular dysfunction (CMD), the relationship between ARD and CMD in women with signs and symptoms of ischemia and no obstructive arteries (INOCA) are not well described. We hypothesized that among women with CMD, those with ARD history have greater angina, functional limitations, and myocardial perfusion compromise compared to those without ARD history. Methods: Women with INOCA and confirmed CMD by invasive coronary function testing were included from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) project (NCT00832702). Seattle Angina Questionnaire (SAQ), Duke Activity Status Index (DASI), and cardiac magnetic resonance myocardial perfusion reserve index (MPRI) were collected at baseline. Chart review was performed to confirm self-reported ARD diagnosis. Results: Of the 207 women with CMD, 19 (9%) had a confirmed history of ARD. Compared to those without ARD, women with ARD were younger (p = 0.04). In addition, they had lower DASI-estimated metabolic equivalents (p = 0.03) and lower MPRI (p = 0.008) but similar SAQ scores. There was a trend towards increased nocturnal angina and stress-induced angina in those with ARD (p = 0.05 for both). Invasive coronary function variables were not significantly different between groups. Conclusions: Among women with CMD, women with a history of ARD had lower functional status and worse myocardial perfusion reserve compared to women without ARD. Angina-related health status and invasive coronary function were not significantly different between groups. Further studies are warranted to understand mechanisms contributing to CMD among women with ARDs with INOCA.
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Enfermedad de la Arteria Coronaria , Isquemia Miocárdica , Femenino , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/terapia , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/epidemiología , Isquemia Miocárdica/terapia , Angiografía Coronaria , Isquemia , Factores de RiesgoRESUMEN
Hypertension (HTN) is associated with gut dysbiosis and the depletion of butyrate-producing bacteria in animal models and people. Furthermore, fecal material transfer from donor hypertensive patients increases blood pressure in normotensive recipient animals and ameliorates HTN-associated pathophysiology. These observations have implications in the impaired interactions between the gut and gut microbiota in HTN. Although this concept is supported in animal models, little is known about human HTN. Therefore, our objective for this study was to compare gene expression with transcriptomics and its potential to influence microbiota in subjects with normal and high blood pressure (HBP). Colon samples from reference subjects with normal blood pressure (REF) and HBP were used for RNA-seq to analyze their transcriptomes. We observed the significant downregulation of gene sets governing immune responses (e.g., SGK1 and OASL), gut epithelial function (e.g., KRT20 and SLC9A3R1), gut microbiota (e.g., PPARG and CIDEC) and genes associated with cardiovascular and gut diseases (e.g., PLAUR and NLN) in HBP subjects; the expression of genes within these pathways correlated with blood pressure. Potential drug targets in the gut epithelium were identified using the Drug Gene International Database for possible use in HTN. They include peroxisome proliferator-activated receptor gamma (PPRG), active serum/glucocorticoid regulated kinase 1 (SGK1) and 3 beta-hydroxysteroid isomerase type II inhibitor (HSD3B). Finally, butyrate, a microbiota-derived short-chain fatty acid, restored the disrupted expression of certain functional genes in colonic organoids from HBP subjects. Patients with HBP exhibit a unique transcriptome that could underlie impaired gut-microbiota interactions. Targeting these interactions could provide a promising new therapeutic intervention for hypertension management.
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Butiratos , Hipertensión , Animales , Humanos , Butiratos/metabolismo , Presión Sanguínea/genética , Colon/metabolismo , Expresión Génica , Disbiosis/complicacionesRESUMEN
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.
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Minocycline, an anti-inflammatory antibiotic drug, rebalances impaired gut microbiota, attenuates neuroinflammation and lowers high blood pressure in animal models of hypertension and in hypertensive patients. Our objective in this study was to investigate if antihypertensive effects of minocycline involve the expression of gut epithelial genes relevant to blood pressure homeostasis using human colonic 3-dimensional organoid culture and high-throughput RNA sequencing. The data demonstrates that minocycline could restore impaired expression of functional genes linked to viral and bacterial immunity, inflammation, protein trafficking and autophagy in human hypertensive organoids.
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Study objective: Sudden cardiac death is the most common cause of non-traumatic death in collegiate athletes. Marfan syndrome poses a risk for sudden cardiac death secondary to aortic root dilation leading to aortic dissection or rupture. Arm span to height ratio (ASHR) > 1.05 has been proposed as a screening tool for Marfan syndrome in pre-participation examinations (PPE) for collegiate athletes but limited data exists on the association between ASHR and aortic root diameter (ARD). This study examines the relationship between ASHR and ARD and assesses for predictors of ARD. Design: Retrospective chart review. Setting: National Collegiate Athletic Association Division I University. Participants: 793 athletes across thirteen sports between 2012 and 2022 evaluated with PPE and screening echocardiogram. Interventions: Not applicable. Main outcome measures: (1) Relationships between ASHR, SBP, BSA, and ARD amongst all athletes as well as stratified by ASHR >1.05 or ≤1.05 using univariate analysis. (2) Predictors of ARD using multivariate analysis using linear regression. Results: 143 athletes (18 %) had ASHRs > 1.05. Athletes with ASHR > 1.05 had higher ARD (2.99 cm) than athletes with ASHR ≤ 1.05 (2.85 cm). Weak correlations were noted between ASHR, ARD, and SBP. Multivariate analysis showed that BSA, male sex, and participation in swimming were predictors of ARD. ASHR was not predictive of ARD in regression analysis. Conclusions: These findings showed a tendency towards higher ARD in athletes with ASHR >1.05 but this observation was not statistically significant in multivariate analysis.
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Microvascular dysfunction describes a varied set of conditions that includes vessel destruction, abnormal vasoreactivity, in situ thrombosis, and fibrosis, which ultimately results in tissue damage and progressive organ failure. Microvascular dysfunction has a wide array of clinical presentations, ranging from ischemic heart disease to renal failure, stroke, blindness, pulmonary arterial hypertension, and dementia. An intriguing unifying hypothesis suggests that microvascular dysfunction of specific organs is an expression of a systemic illness that worsens with age and is accelerated by vascular risk factors. Studying relationships across a spectrum of microvascular diseases affecting the brain, retina, kidney, lung, and heart may uncover shared pathologic mechanisms that could inform novel treatment strategies. We review the evidence that supports the notion that microvascular dysfunction represents a global pathologic process. Our focus is on studies reporting concomitant microvascular dysfunction of the heart with that of the brain, kidney, retina, and lung.
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Riñón , Trombosis , Encéfalo , Humanos , Riñón/irrigación sanguínea , Pulmón , Factores de RiesgoRESUMEN
Background: Cardiac 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). Methods: We 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. Results: Concentrations 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). Conclusions: Results of this small pilot study support the suggestion that 18-HEPE is synthesized outside the heart and utilized within the myocardial bed.
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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 < 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.
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Resolvins and maresins, members of the specialized proresolving mediator (SPM) family, are omega-3 fatty acid-derived lipid mediators that attenuate inflammation. We hypothesized that they play a role in the pathophysiology of coronary microvascular dysfunction (CMD) in women with ischemia and no obstructive coronary disease. In a pilot study, we measured the D-series resolvins (D1, D2, D3, and D5), resolvin E1, maresin 1, docosahexaenoic acid, eicosapentaenoic acid (precursor of resolvin E1), and 18-hydroxyeicosapentaenoic acid by mass spectrometry in the peripheral blood of 31 women enrolled in the Women's Ischemia Trial to Reduce Events in Nonobstructive CAD (WARRIOR) trial who had confirmed CMD assessed by coronary flow reserve. We compared SPM levels with 12 gender and age-matched reference subjects. Compared with the reference subject group, those with CMD had significantly lower plasma concentrations of resolvin D1 and maresin 1 and significantly higher levels of docosahexaenoic acid and 18-hydroxyeicosapentaenoic acid. In conclusion, insufficient or ineffective SPM production may play a role in the pathophysiology of CMD. If our results are validated in a larger cohort, omega-3 fatty acid supplementation could be tested as a novel treatment for these patients.
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Ácidos Docosahexaenoicos/sangre , Ácido Eicosapentaenoico/sangre , Ácidos Hidroxieicosatetraenoicos/sangre , Microcirculación/fisiología , Isquemia Miocárdica/sangre , Anciano , Ácido Eicosapentaenoico/análogos & derivados , Ácidos Grasos Insaturados/sangre , Femenino , Humanos , Espectrometría de Masas , Persona de Mediana Edad , Isquemia Miocárdica/etiología , Isquemia Miocárdica/prevención & control , Proyectos PilotoRESUMEN
Background: Left ventricular assist device (LVAD) implantation provides a robust survival advantage, however despite improvements in mortality, the adverse event burden of durable mechanical circulatory support remains high. Bleeding complications are one such significant complication. The uSTOP LVAD BLEED (Utilization of umbilical cord lining Stem cells TO Prevent LVAD associated angiodysplastic BLEEDing) pilot study is designed to evaluate the safety and tolerability of escalating doses of umbilical cord lining stem cells (ULSCs) in LVAD recipients to ameliorate the dysregulation of angiogenic factors seen in this population. Design: This Phase Ia single-ascending dose pilot study will evaluate the IV administration of ULSCs in stable out-patients supported with an LVAD. In a 3 + 3 design, a maximum of 18 patients will receive an IV infusion of ULSCs. Main outcome measures: The primary endpoints are safety and tolerability, secondary exploratory endpoints will include biomarker evaluation of angiogenic dysregulation. Summary: This represents a novel cell type and route of administration in this population, while collecting initial data regarding the magnitude and duration of effects of cell therapy, and assessing the possibility of decreasing bleeding by a strategy of vascular stabilization. Clinical trial registration: ClinicalTrials.gov Identifier: NCT04811261. https://clinicaltrials.gov/ct2/show/NCT04811261.
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Coronary microvascular dysfunction is a ubiquitous pathologic process that is operational in ischemia with no obstructive coronary artery disease and other cardiovascular disorders including heart failure with preserved ejection fraction. It may, in fact, be a manifestation of a multi-systemic condition of small vessel dysfunction that also affects the brain and kidneys. While the pathophysiology driving coronary microvascular dysfunction is multifactorial, chronic inflammation plays an important role. Resolution of inflammation is an active process mediated, in part, by a family of locally active mediators biosynthesized from omega-3 fatty acids, collectively referred to as specialized pro-resolving mediators. Omega-3 fatty acid treatment modulates inflammation and is associated with improved cardiovascular outcomes and attenuation of plaque progression on cardiovascular imaging. Whether omega-3 fatty acid treatment attenuates coronary microvascular dysfunction is unknown.
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Background: There is a paucity of data describing the association between blood pressure (BP) and cardiac remodeling in female collegiate athletes. Methods: This retrospective cohort review describes the BP characteristics and echocardiographic features of female collegiate athletes during preparticipation evaluation. We evaluated data from 329 female athletes at two National Collegiate Athletic Association (NCAA) Division I universities who underwent preparticipation evaluation that included medical history, physical examination, 12-lead electrocardiography, and 2-dimensional transthoracic echocardiography. BP values were divided into categories of normal, elevated, stage 1 and stage 2 hypertension based on 2017 ACC/AHA Guidelines. Left ventricular mass index was calculated and indexed to body surface area and further classified into concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. Results: Normal BP values were noted in 184 (56%) female athletes, 88 (26.7%) had elevated BP and 57 (17.3%) had BP values indicating stage 1 or 2 hypertension. The majority of participants were white (n = 136, 73.9%). There was significantly higher body surface area in female athletes with higher BP values: 1.85 ± 0.18 in the stage 1 and 2 hypertension range, 1.82 ± 0.18 in the elevated BP range versus 1.73 ± 0.16 in the normal BP range (p < 0.001). Conclusions: There was a trend toward higher incidence of concentric and eccentric hypertrophy in athletes with higher than normal BP, however no statistical significance was noted. Elevated BP values were frequent among female collegiate athletes, and there is evidence of cardiac remodeling associated with higher BP values.
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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.