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.

Background— The electrical activity of the atrioventricular node (AVN) is functionally heterogeneous, but how this relates to distinct cell types and the 3-dimensional structure of the AVN is unknown. To address this, we have studied the expression of Na v 1.5 and other Na + channel isoforms in the AVN. Methods and Results— The rat AVN was identified by Masson’s trichrome staining together with immunolabeling of marker proteins: connexin40, connexin43, desmoplakin, atrial natriuretic peptide, and hyperpolarization-activated and cyclic nucleotide–gated channel 4. Na + channel expression was investigated with immunohistochemistry with isoform-specific Na + channel antibodies. Na v 1.1 was distributed in a similar manner to Na v 1.5. Na v 1.2 was not detected. Na v 1.3 labeling was present in nerve fibers and cell bodies (but not myocytes) and was abundant in the penetrating atrioventricular (AV) bundle and the common bundle but was much less abundant in other regions. Na v 1.5 labeling was abundant in the atrial and ventricular myocardium and the left bundle branch. Na v 1.5 labeling was absent in the open node, penetrating AV bundle, AV ring bundle, and common bundle but present at a reduced level in the inferior nodal extension and transitional zone. Na v 1.6 was not detected. Conclusions— Our findings provide molecular evidence of multiple electrophysiological cell types at the AV junction. Impaired AV conduction as a result of mutations in or loss of Na v 1.5 must be the result of impaired conduction in the AVN inputs (inferior nodal extension and transitional zone) or output (bundle branches) rather than the AVN itself (open node and penetrating AV bundle).

Abstract Background: Among premenopausal women presenting with ischemia, hypothalamic hypoestrogenemia (HHE) has been associated with angiographic coronary artery disease (CAD). Further, serum amyloid-alpha (SAA), a marker of systemic inflammation strongly predicts future adverse cardiovascular events. We sought to relate inflammatory markers to HHE and understand if inflammation mediates relations between HHE and CAD. Methods: We assessed premenopausal women not on exogenous hormones undergoing coronary angiography for suspected ischemia. HHE was defined as estradiol<50 pg/ml, luteinizing hormone<10 IU/l and follicle stimulating hormone<10 IU/l. Serum inflammatory markers, reproductive hormones, and angiographic CAD were measured. Results: Overall, 40 (31%) of the 127 women had HHE with similar age and body mass index compared to no HHE (p=0.48 and p=0.77, respectively). Women with HHE had lower estradiol compared to no HHE (30.4+11.7 vs 112.5+62.4 pg/ml, p<0.0001). There were no significant differences between high sensitivity C-reactive protein (hsCRP) (0.86 ± 1.45 vs 0.65 ± 1.17, p=0.5211) and interleukin 6 (IL-6) (4.95 ± 6.06 vs 3.90 ± 3.90, p=0.2358). However, HHE women had significantly higher SAA compared to no HHE (4.44+13.5 vs 0.94+2.37, p=0.0495). Conclusion: Among premenopausal women undergoing coronary angiography for suspected myocardial ischemia, SAA levels were significantly elevated in women with HHE, suggesting that inflammation may serve as a mediator between HHE and CAD. Further investigation relative to inflammation as a treatment target in this cohort may be warranted.

Background Recurrent hospitalization is prevalent in women with signs and symptoms of ischemia and no obstructive coronary artery disease. We hypothesized that rates of angina hospitalization might have changed over time, given advances in diagnostic and therapeutic approaches. Methods and Results We evaluated 551 women enrolled in the WISE (Women's Ischemia Syndrome Evaluation) study with no obstructive coronary artery disease (CAD) for a follow‐up period of 9.1 years. We analyzed angina hospitalization rates using the Kaplan‐Meier method. Univariate analysis and multivariable Cox proportional hazard models were developed for prediction of angina hospitalization in women with signs and symptoms of angina and no CAD. A total of 223 women had nonobstructive CAD (>20–50% <stenosis) and 328 had no CAD (<20% stenosis). Among women with either no or nonobstructive CAD, the mean age was 56±11 years, 56% had hypertension, 46% dyslipidemia, 51% were smokers, and 10% had prior myocardial infarction. The rates of angina hospitalization for a maximum of 9.1 years showed near‐linear increases in both groups (P=0.03). Hypertension, dyslipidemia, nonobstructive CAD, use of nitrates, statins, and angiotensin‐converting enzyme inhibitors were univariate predictors of angina hospitalization. Adjusted multivariate hazard ratios for angina hospitalization were significant for use of nitrates 2.58 (1.80–3.69, P<0.0001), statins 1.80 (1.20–2.70, P=0.004), and angiotensin‐converting enzyme inhibitors/angiotensin II receptor blockers 1.81 (1.22–2.68, P=0.003). Conclusions Angina hospitalization rates continued at a relatively constant rate in all women with no obstructive CAD despite medical advances. Clinical trials aimed at reducing angina hospitalization rates and identifying the pathophysiological mechanisms contributing to angina symptoms in women with no CAD and women with no obstructive CAD.

Background Previous studies have reported an association between the timing of menarche and cardiovascular disease (CVD). However, emerging studies have not examined the timing of menarche in relation to role of estrogen over a lifetime and major adverse cardiac events (MACE). Methods and Results A total of 648 women without surgical menopause undergoing coronary angiography for suspected ischemia in the WISE (Women's Ischemia Syndrome Evaluation) study were evaluated at baseline and followed for 6 years (median) to assess major adverse CVD outcomes. MACE was defined as the first occurrence of all‐cause death, nonfatal myocardial infarction, nonfatal stroke, or heart failure hospitalization. Age at menarche was self‐reported and categorized (≤10, 11, 12, 13, 14, ≥15 years) with age 12 as reference. Total estrogen time and supra–total estrogen time were calculated. Cox regression analysis was performed adjusting for CVD risk factors. Baseline age was 57.9 ± 12 years (mean ± SD), body mass index was 29.5 ± 6.5 kg/m2, total estrogen time was 32.2 ± 8.9 years, and supra–total estrogen time was 41.4 ± 8.8 years. MACE occurred in 172 (27%), and its adjusted regression model was J‐shaped. Compared with women with menarche at age 12 years, the adjusted MACE hazard ratio for menarche at ≤10 years was 4.53 (95% CI 2.13‐9.63); and at ≥15 years risk for MACE was 2.58 (95% CI, 1.28‐5.21). Conclusions History of early or late menarche was associated with a higher risk for adverse CVD outcomes. These findings highlight age at menarche as a potential screening tool for women at risk of adverse CVD events. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000554.

BACKGROUND:Currently as many as one-half of women with suspected myocardial ischemia have no obstructive coronary artery disease (CAD), and abnormal coronary reactivity (CR) is commonly found. OBJECTIVES:The authors prospectively investigated CR and longer-term adverse cardiovascular outcomes in women with and with no obstructive CAD in the National Heart, Lung, and Blood Institute-sponsored WISE (Women's Ischemia Syndrome Evaluation) study. METHODS:Women (n = 224) with signs and symptoms of ischemia underwent CR testing. Coronary flow reserve and coronary blood flow were obtained to test microvascular function, whereas epicardial CR was tested by coronary dilation response to intracoronary (IC) acetylcholine and IC nitroglycerin. All-cause mortality, major adverse cardiovascular events (MACE) (cardiovascular death, myocardial infarction, stroke, and heart failure), and angina hospitalizations served as clinical outcomes over a median follow-up of 9.7 years. RESULTS:The authors identified 129 events during the follow-up period. Low coronary flow reserve was a predictor of increased MACE rate (hazard ratio [HR]: 1.06; 95% confidence interval [CI]: 1.01 to 1.12; p = 0.021), whereas low coronary blood flow was associated with increased risk of mortality (HR: 1.12; 95% CI: 1.01 to 1.24; p = 0.038) and MACE (HR: 1.11; 95% CI: 1.03 to 1.20; p = 0.006) after adjusting for cardiovascular risk factors. In addition, a decrease in cross-sectional area in response to IC acetylcholine was associated with higher hazard of angina hospitalization (HR: 1.05; 95% CI: 1.02 to 1.07; p < 0.0001). There was no association between epicardial IC-nitroglycerin dilation and outcomes. CONCLUSIONS:On longer-term follow-up, impaired microvascular function predicts adverse cardiovascular outcomes in women with signs and symptoms of ischemia. Evaluation of CR abnormality can identify those at higher risk of adverse outcomes in the absence of significant CAD. (Women's Ischemia Syndrome Evaluation [WISE]; NCT00000554).

Objective . In a separate, contemporary cohort, we sought to confirm findings of the original Women’s Ischemia Syndrome Evaluation (WISE). Background . The original WISE observed a high prevalence of both invasively determined coronary endothelial and coronary microvascular dysfunction (CMD) that predicted adverse events in follow-up. Methods . We comparatively studied the WISE-Coronary Vascular Dysfunction (CVD) cohort (2009-2011), with signs and symptoms of ischemia but without significant CAD, to the original WISE (1997-2001) cohort. CMD was defined as coronary flow reserve (CFR) ≤2.5, or endothelial dysfunction as epicardial coronary artery constriction to acetylcholine (ACH), or <20% epicardial coronary dilation to nitroglycerin (NTG). Results . In WISE (n=181) and WISE-CVD (n=235) women, mean age in both was 54 years, and 83% were white (WISE) vs 74% (WISE-CVD, p=0.04). Use of hormone replacement therapy was less frequent in WISE-CVD vs WISE (46% vs 57%, p=0.026) as was presence of hypertension (40% vs 52%, p=0.013), hyperlipidemia (20% vs 46%, p<0.0001), and smoking (46% vs 56%, p=0.036). Similar rates were observed in WISE-CVD and WISE cohorts for CMD (mean CFR 2.7±0.6 vs 2.6±0.8, p=0.35), mean change in diameter with intracoronary ACH (0.2±10.0 vs 1.6±12.8 mm, p=0.34), and mean change in diameter with intracoronary NTG (9.7±13.0 vs 9.8±13.5 mm, p=0.94), respectively. Conclusions . This study confirms prevalence of CMD in the contemporary WISE-CVD cohort similar to that of the original WISE cohort, despite a lower risk factor burden in WISE-CVD. Because these coronary functional abnormalities predict major adverse cardiac events, clinical trials of therapies targeting these abnormalities are indicated.

Background Information regarding the pathogenesis of ischemic heart disease (IHD) in women is limited. Sex-specific responses to atherosclerosis and coronary arterial remodelling in women versus men have been hypothesized, but limited study exists. Methods Case-matched study of 174 women with suspected ischemia referred for coronary angiography: 87 with non-obstructive coronary artery disease (CAD) (no luminal diameter stenosis >20% in any coronary artery) and 87 age and ethnicity matched women with obstructive CAD. Groups were compared with regard to atheroma burden and coronary arterial remodelling assessed by coronary artery intravascular ultrasound (IVUS). Results IVUS revealed more extensive atheroma with obstructive CAD vs. those without obstructive CAD, with greater percent atheroma volume (PAV) (36.1%±9.8% vs. 25.4%±9.1%, P<0.0001), total atheroma volume (TAV) (140.8±58.7 vs. 98.8±46.9 mm3, P<0.0001) and percentage of images containing plaque (70.0%±30.5% vs. 35.7%±32.6%, P<0.0001). Adjusting for risk factors, PAV (35%±1% vs. 28%±1%, P=0.0008), TAV (131±7 vs. 115±7 mm3, P=0.110) and percentage of images containing plaque (66%±4% vs. 45%±5%, P=0.0008) remained greater with obstructive CAD. Obstructive CAD was associated with smaller lumen volumes (251.9±92.8 vs. 289.7±91.8 mm3, P=0.005), but surprisingly, the external elastic membrane (EEM) volume was very similar comparing the groups (392.7±128.1 vs. 388.6±113.7 mm3, P=0.910). Conclusions Our findings suggest that women referred to angiography for suspected ischemia, have differing patterns of coronary arterial response to injury with regard to accumulation of atherosclerosis and compensatory remodelling related to the presence and absence of obstructive CAD. Preservation and cultivation of compensatory arterial remodelling may be a novel CAD therapeutic target.

Background The association between migraine headache and cardiovascular events has been inconsistent. This study determines the long-term risk of cardiovascular events among women with and without a history of migraine headache who were under evaluation for suspected myocardial ischemia in the Women's Ischemia Syndrome Evaluation (WISE). Methods The WISE is a National Heart, Lung and Blood Institute-sponsored prospective, multicenter study that aims to improve myocardial ischemia evaluation in women. A total of 936 women presenting with symptoms of myocardial ischemia underwent structured data collection and coronary angiography. Information pertaining to migraine headache was available in 917 women. All-cause mortality data were available on all women for a median of 9.5 years, and nonfatal cardiovascular event data were available on 888 women for a median of 6.5 years. Results A total of 224 (24.4%) women reported a history of migraine headache. Compared with women who did not report a history of migraine headache, women with a history of migraine headache had an increased adjusted risk of cardiovascular event (cardiovascular death, nonfatal myocardial infarction, heart failure, or stroke) (hazard ratio 1.83; 95% confidence interval, 1.22-2.75) at a median follow-up of 6.5 years. This result was driven mainly by a twofold increase in the risk of stroke (hazard ratio 2.33; 95% confidence interval, 1.16-4.68). Conclusion Among women being evaluated for ischemic heart disease, those reporting a history of migraine headache had increased risk of future cardiovascular events on long-term follow-up. This risk was primarily driven by a more-than twofold increase in the risk of stroke.

Women with signs and symptoms of ischemia, no obstructive coronary artery disease (CAD) and preserved left ventricular ejection fraction (EF) often have diastolic dysfunction and experience elevated rates of major adverse cardiac events (MACE), including heart failure (HF) hospitalization with preserved ejection fraction (HFpEF). We evaluated the predictive value of inflammatory biomarkers for long-term HF hospitalization and all-cause mortality in these women.We performed a cross-sectional analysis to investigate the relationships between inflammatory biomarkers [serum interleukin-6 (IL-6), C-reactive protein (hs-CRP) and serum amyloid A (SAA)] and median of 6 years follow-up for all-cause mortality and HF hospitalization among women with signs and symptoms of ischemia, non-obstructive CAD and preserved EF. Multivariable Cox regression analysis tested associations between biomarker levels and adverse outcomes.Among 390 women, mean age 56 ± 11 years, median follow up of 6 years, we observed that there is continuous association between IL-6 level and HF hospitalization (adjusted hazard ratio [AHR] 2.5 [1.2-5.0], p = 0.02). In addition, we found significant association between IL-6, SAA levels and all-cause mortality AHR (1.8 [1.1-3.0], p = 0.01) (1.5 [1.0-2.1], p = 0.04), respectively.In women with signs and symptoms of ischemia, non-obstructive CAD and preserved EF, elevated IL-6 predicted HF hospitalization and all-cause mortality, while SAA level was only associated with all-cause mortality. These results suggest that inflammation plays a role in the pathogenesis of development of HFpEF, as well all-cause mortality.

BackgroundSudden cardiac death (SCD) is often the first presentation of ischemic heart disease; however, there is limited information on SCD among women with and without obstructive coronary artery disease (CAD). We evaluated SCD incidence in the WISE (Women's Ischemia Syndrome Evaluation) study. Methods and ResultsOverall, 904 women with suspected ischemic heart disease with preserved ejection fraction and core laboratory coronary angiography were followed for outcomes. In case of death, a death certificate and/or a physician or family narrative of the circumstances of death was obtained. A clinical events committee rated all deaths as cardiovascular or noncardiovascular and as SCD or non‐SCD. In total, 96 women (11%) died over a median of 6 years (maximum: 8 years). Among 65 cardiovascular deaths, 42% were SCD. Mortality per 1000 person‐hours increased linearly with CAD severity (no CAD: 5.8; minimal: 15.9; obstructive: 38.6; P<0.0001). However, the proportion of SCD was similar across CAD severity: 40%, 58%, and 38% for no, minimal, and obstructive CAD subgroups, respectively (P value not significant). In addition to traditional risk factors (age, diabetes mellitus, smoking), a history of depression (P=0.018) and longer corrected QT interval (P=0.023) were independent SCD predictors in the entire cohort. Corrected QT interval was an independent predictor of SCD in women without obstructive CAD (P=0.033). ConclusionsSCD contributes substantially to mortality in women with and without obstructive CAD. Corrected QT interval is the single independent SCD risk factor in women without obstructive CAD. In addition to management of traditional risk factors, these data indicate that further investigation should address mechanistic understanding and interventions targeting depression and corrected QT interval in women.

Background— The WISE study (Women’s Ischemia Syndrome Evaluation) was a prospective cohort study of 936 clinically stable symptomatic women who underwent coronary angiography to evaluate symptoms and signs of ischemia. Long-term mortality data for such women are limited. Methods and Results— Obstructive coronary artery disease (CAD) was defined as ≥50% stenosis on angiography by core laboratory. We conducted a National Death Index search to assess the mortality of women who were alive at their final WISE contact date. Death certificates were obtained. All deaths were adjudicated as cardiovascular or noncardiovascular by a panel of WISE cardiologists masked to angiographic data. Multivariate Cox proportional hazards regression was used to identify significant independent predictors of mortality. At baseline, mean age was 58±12 years; 176 (19%) were non-white, primarily black; 25% had a history of diabetes mellitus, 59% hypertension, 55% dyslipidemia, and 59% had a body mass index ≥30. During a median follow-up of 9.5 years (range, 0.2–11.5 years), a total of 184 (20%) died. Of these, 115 (62%) were cardiovascular deaths; 31% of all cardiovascular deaths occurred in women without obstructive CAD (<50% stenosis). Independent predictors of mortality were obstructive CAD, age, baseline systolic blood pressure, history of diabetes mellitus, history of smoking, elevated triglycerides, and estimated glomerular filtration rate. Conclusions— Among women referred for coronary angiography for signs and symptoms of ischemia, 1 in 5 died from predominantly cardiac pathogeneses within 9 years of angiographic evaluation. A majority of the factors contributing to the risk of death seem to be modifiable by existing therapies. Of note, 1 in 3 of the deaths in this cohort occurred in women without obstructive CAD, a condition often considered benign and without guideline-recommended treatments. Clinical trials are needed to provide treatment guidance for the group without obstructive CAD.

hristopher B. Arant, MD,* Timothy R. Wessel, MD,* Marian B. Olson, MS,‡ . Noel Bairey Merz, MD, FACC,¶ George Sopko, MD,# William J. Rogers, MD, FACC, arry L. Sharaf, MD, FACC,§ Steven E. Reis, MD, FACC,‡ Karen M. Smith, MD, FACC,* . Delia Johnson, PHD,‡ Eileen Handberg, PHD,* Sunil Mankad, MD, FACC,† arl J. Pepine, MD, MACC* ainesville, Florida; Pittsburgh, Pennsylvania; Providence, Rhode Island; Birmingham, Alabama; os Angeles, California; and Bethesda, Maryland

Introduction: Data regarding the association between migraine headaches (MH) and cardiovascular (CV) events in women have been inconsistent. The aim of this study was to determine the long-term risk of CV events among women with and without MH who were evaluated for suspected ischemic heart disease (IHD) in the Women’s Ischemia Syndrome Evaluation (WISE) Study. Methods: Women reporting a history of MH were identified from the WISE cohort. Extended follow-up data were available for a median follow-up of 6 years. Cox proportional adjusted hazard ratios (HR) were constructed for time to first adverse CV event (CV death, non-fatal myocardial infarction [MI], heart failure hospitalization, or non-fatal stroke) among women with and without MH. Additionally, HR were determined for each event separately, as well as, all-cause death, angina hospitalization, death or MI, and CV death or MI. Results: Data on self reported MH were available on 917 women. A total of 224 (24.4%) reported a history of MH. Compared to those who did not report a history of migraines, women with a history of MH had an increased adjusted* risk of CV events (HR 1.83 CI 1.22-2.75, p=0.004) at a median follow up of 6-years. This result was mainly due to an increase in the risk of stroke (HR 2.33 CI 1.16-4.68, p=0.018) (Table 1). Conclusion: Among women being evaluated for IHD, those who reported a history of MH had an increased risk of future CV event. This finding was primarily driven by the more than 2-fold increased risk of stroke.

BACKGROUND Women with polycystic ovary syndrome (PCOS) have greater cardiac risk factor clustering but the link with mortality is incompletely described. OBJECTIVE To evaluate outcomes in 295 postmenopausal women enrolled in the National Institutes of Health-National Heart, Lung, and Blood Institute (NIH-NHLBI) sponsored Women's Ischemia Syndrome Evaluation (WISE) study according to clinical features of PCOS. MATERIALS AND METHODS A total of 25/295 (8%) women had clinical features of PCOS defined by a premenopausal history of irregular menses and current biochemical evidence of hyperandrogenemia, defined as the top quartile of androstenedione (≥701 pg/mL), testosterone (≥30.9 ng/dL), or free testosterone (≥4.5 pg/mL). Cox proportional hazard model estimated death (n = 80). RESULTS Women with clinical features of PCOS had an earlier menopause (p = 0.01), were more often smokers (p < 0.04), and trended toward more angiographic coronary artery disease (CAD) (p = 0.07) than women without these features. Cumulative 10-year mortality was 28% for women with (n = 25) versus 27% without clinical features of PCOS (n = 270) (p = 0.85). PCOS was not a significant predictor (p = NS) in prognostic models including diabetes, waist circumference, hypertension, and angiographic CAD. CONCLUSION From this longer-term follow up of a relatively small cohort of postmenopausal women with suspected ischemia, the prevalence of PCOS is similar to the general population, and clinical features of PCOS are not associated with CAD or mortality. These findings question whether identification of clinical features of PCOS in postmenopausal women who already have known cardiovascular disease provides any additional opportunity for risk factor intervention.

Studies suggest that the prognosis of women with signs and symptoms of ischemia and nonobstructive coronary artery disease (CAD) is not benign. [1]2][3] The Women's Ischemia Syndrome Evaluation (WISE) 4 demonstrated that the WISE CAD severity score, a measure of coronary atherosclerotic burden, is a useful predictor of mortality in women with nonobstructive CAD.However, the prognostic value of ischemia variables is less well described.We evaluated the associaton of ischemia and prior infarct with outcomes using the WISE database, which consisted of women with signs and symptoms of ischemia and nonobstructive CAD enrolled from 1996 to 2000 and followed up for up to 8.5 years.

Objective: Studies have linked vasomotor symptoms (VMS) to markers of cardiovascular disease (CVD) risk, yet few have considered clinical cardiovascular events. Data suggest that associations may depend upon the age that symptoms occur. We examined associations between VMS and cardiovascular events and endothelial function, considering age of symptom onset. Methods: The Women's Ischemia Syndrome Evaluation enrolled women referred for coronary angiography for suspected myocardial ischemia. A total of 254 women aged more than 50 years, postmenopausal, with both ovaries, not taking hormone therapy underwent a baseline evaluation, were followed annually (median = 6.0 y), and the National Death Index was searched to ascertain CVD mortality (median = 9.3 y). A subset of participants underwent brachial artery ultrasound for flow-mediated dilation (FMD). Receiver-operating curve analysis was used to determine vasomotor symptom groups (symptoms beginning < age 42 [early onset], beginning ≥42 [later onset], never) which were examined in relation to cardiovascular events and FMD in Cox proportional hazard and linear regression models. Results: Women reporting early onset VMS (HR = 3.35, 95% CI = 1.23-7.86, P = 0.005) and women who never had VMS (HR = 2.17, 95% CI = 1.02-4.62, P = 0.05) had higher CVD mortality than women with later onset symptoms (multivariable models). Women with early onset VMS had lower FMD than women with later onset symptoms (b = −4.31, SE = 2.10, P = 0.04, multivariable). Conclusions: Women with signs and symptoms of ischemia who had VMS beginning early in midlife had higher CVD mortality and reduced endothelial function relative to women with later onset symptoms. Future research should evaluate the vascular phenotype of women with early midlife VMS.

This paper evaluated long-term associations between psychosocial factors and premature mortality among women with suspected coronary artery disease (CAD). We tracked total mortality events over a median 9.3 years in a cohort of 517 women [baseline mean age = 58.3 (11.4) years]. Baseline evaluations included coronary angiography, psychosocial testing, and CAD risk factors. Measures included the Spielberger Trait Anxiety Scale, Beck Depression Inventory, self-rated health, and Social Network Index. Cox regression analysis was used to assess relationships. Covariates included age, CAD risk factors, and CAD severity. BDI scores (HR 1.09, 95 % CI 1.02–1.15), STAI scores (HR .86, 95 % CI .78–.93), and very good self-rated health (relative to the poor self-rated health group; HR .33, 95 % CI .12–.96) each independently predicted time to mortality outcomes in the combined model. SNI scores (HR .91, 95 % CI .81–1.06) and other self-rated health categories (i.e., fair, good, and excellent categories) were not significant mortality predictors after adjusting for other psychosocial factors. These results reinforce and extend prior psychosocial research in CAD populations.