Biomedical subjects

Barry L Sharaf

Publications and source records attributed to Barry L Sharaf.

At least 19 recordsLinked to original sources

PubMed2006

The economic burden of angina in women with suspected ischemic heart disease: results from the National Institutes of Health--National Heart, Lung, and Blood Institute--sponsored Women's Ischemia Syndrome Evaluation.

BACKGROUND: Coronary angiography is one of the most frequently performed procedures in women; however, nonobstructive (ie, < 50% stenosis) coronary artery disease (CAD) is frequently reported. Few data exist regarding the type and intensity of resource consumption in women with chest pain after coronary angiography. METHODS AND RESULTS: A total of 883 women referred for coronary angiography were prospectively enrolled in the National Institutes of Health--National Heart, Lung, and Blood Institute--sponsored Women's Ischemia Syndrome Evaluation (WISE). Cardiovascular prognosis and cost data were collected. Direct (hospitalizations, office visits, procedures, and drug utilization) and indirect (out-of-pocket, lost productivity, and travel) costs were estimated through 5 years of follow-up. Among 883 women, 62%, 17%, 11%, and 10% had nonobstructive and 1-vessel, 2-vessel, and 3-vessel CAD, respectively. Five-year cardiovascular death or myocardial infarction rates ranged from 4% to 38% for women with nonobstructive to 3-vessel CAD (P < 0.0001). Five-year rates of hospitalization for chest pain occurred in 20% of women with nonobstructive CAD, increasing to 38% to 55% for women with 1-vessel to 3-vessel CAD (P < 0.0001). The volume of repeat catheterizations or angina hospitalizations was 1.8-fold higher in women with nonobstructive versus 1-vessel CAD after 1 year of follow-up (P < 0.0001). Drug treatment was highest for those with nonobstructive or 1-vessel CAD (P < 0.0001). The proportion of costs for anti-ischemic therapy was higher for women with nonobstructive CAD (15% versus 12% for 1-vessel to 3-vessel CAD; P = 0.001). For women with nonobstructive CAD, average lifetime cost estimates were $767,288 (95% CI, $708,480 to $826,097) and ranged from $1,001,493 to $1,051,302 for women with 1-vessel to 3-vessel CAD (P = 0.0003). CONCLUSIONS: Symptom-driven care is costly even for women with nonobstructive CAD. Our lifetime estimates for costs of cardiovascular care identify a significant subset of women who are unaccounted for within current estimates of the economic burden of coronary heart disease.

Aged↗

PubMed2006

Persistent chest pain predicts cardiovascular events in women without obstructive coronary artery disease: results from the NIH-NHLBI-sponsored Women's Ischaemia Syndrome Evaluation (WISE) study.

AIMS: Women with chest pain but without obstructive coronary artery disease (CAD) are considered at low risk for cardiovascular (CV) events, but half continue to experience debilitating chest pain over many years. This study compared CV outcomes in women with persistent chest pain (PChP) vs. those without PChP. METHODS AND RESULTS: We studied 673 Women's Ischaemia Syndrome Evaluation (WISE) participants with chest pain undergoing coronary angiography for suspected myocardial ischaemia and at least 1 year of follow-up. PChP was defined as self-reported continuing chest pain after 1 year. Events occurring after that year were recorded for a median of 5.2 years. We compared CV event rates for women with and without PChP in subgroups with and without obstructive CAD. The median age was 58 years, 20% were racial minorities, 45% had PChP, 39% had obstructive CAD. Among women without CAD, those with PChP had more than twice the rate of composite CV events (P = 0.03), that included non-fatal myocardial infarctions (P = 0.11), strokes (P = 0.03), congestive heart failure (P = 0.38), and CV deaths (P = 0.73), compared with those without PChP. In women with CAD, there was no difference in composite CV events in those with and without PChP (P = 0.72). CONCLUSION: Among women undergoing coronary angiography for suspected myocardial ischaemia, PChP in women with no obstructive CAD predicted adverse CV outcomes. Such women might benefit from additional evaluation and aggressive risk factor modification therapy.

Aged↗

PubMed2006

Phytoestrogens and lipoproteins in women.

OBJECTIVES: We undertook a study to evaluate relationships among blood phytoestrogen levels, lipoprotein levels, estrogen levels, and angiographically defined coronary artery disease in women. BACKGROUND: Evidence for a beneficial role and the potential mechanism(s) of plant estrogens (phytoestrogens) on blood lipoproteins in humans is controversial. METHODS: We evaluated 483 women enrolled in the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation with coronary risk factors undergoing coronary angiography for evaluation for suspected ischemia for blood phytoestrogen levels (daidzein and genistein), lipoprotein levels [total cholesterol, triglycerides, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol (HDL-C)], estrogen levels (estradiol, bioavailable estradiol, estrone), and angiographic coronary artery disease using core laboratories. RESULTS: Higher blood levels of the phytoestrogen daidzein were associated with lower triglycerides (P = 0.01), higher HDL-C (P = 0.05) levels, and a beneficial total cholesterol to HDL-C ratio (P = 0.02). This beneficial association was evident among the subgroup of women with low [<184 pmol/liter (<50 pg/ml)] blood estradiol levels, regardless of age and lipoprotein levels. The phytoestrogen associations with lipoproteins were incrementally related to the magnitude of daidzein level and independent of other lipoprotein modulators. There were no detectable relationships between the phytoestrogen levels and angiographic coronary artery disease. CONCLUSIONS: Higher blood phytoestrogen daidzein levels are associated with beneficial lipoprotein levels in women with low estrogen levels, possibly by an estrogen receptor mechanism. These results suggest a potential explanation for the variable lipoprotein results observed in prior randomized controlled trials and call for investigation regarding subgroups of subjects who may preferentially benefit from dietary intake of food products, such as soy.

Adult↗

PubMed2006

Insights from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study: Part II: gender differences in presentation, diagnosis, and outcome with regard to gender-based pathophysiology of atherosclerosis and macrovascular and microvascular coronary disease.

Coronary heart disease is the leading cause of death and disability in the U.S., but recent advances have not led to declines in case fatality rates for women. The current review highlights gender-specific issues in ischemic heart disease (IHD) presentation, evaluation, and outcomes with a special focus on the results derived from the National Institutes of Health-National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) study. In the second part of this review, we will assess new evidence on gender-based differences in vascular wall or metabolic alterations, atherosclerotic plaque deposition, and functional expression on worsening outcomes of women. Additionally, innovative cardiovascular imaging techniques will be discussed. Finally, we identify critical areas of further inquiry needed to advance this new gender-specific IHD understanding into improved outcomes for women.

Atherosclerosis↗

PubMed2006

Insights from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study: Part I: gender differences in traditional and novel risk factors, symptom evaluation, and gender-optimized diagnostic strategies.

Despite a dramatic decline in mortality over the past three decades, coronary heart disease is the leading cause of death and disability in the U.S. Importantly, recent advances in the field of cardiovascular medicine have not led to significant declines in case fatality rates for women when compared to the dramatic declines realized for men. The current review highlights gender-specific issues in ischemic heart disease presentation, evaluation, and outcomes with a special focus on the results published from the National Institutes of Health-National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) study. We will present recent evidence on traditional and novel risk markers (e.g., high sensitivity C-reactive protein) as well as gender-specific differences in symptoms and diagnostic approaches. An overview of currently available diagnostic test evidence (including exercise electrocardiography and stress echocardiography and single-photon emission computed tomographic imaging) in symptomatic women will be presented as well as data using innovative imaging techniques such as magnetic resonance subendocardial perfusion, and spectroscopic imaging will also be discussed.

Female↗

PubMed2006

Hypertension, menopause, and coronary artery disease risk in the Women's Ischemia Syndrome Evaluation (WISE) Study.

OBJECTIVES: We evaluated whether the relationship between hypertension, other cardiac risk factors, and coronary artery disease (CAD) is modulated by menopausal status and/or age. BACKGROUND: The relative contribution of age versus menopausal status in the development of CAD in women remains unclear. METHODS: We compared systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and traditional cardiac risk factors for CAD in premenopausal (n = 123) and postmenopausal (n = 482) women undergoing coronary angiography for suspected ischemia. To assess the relative contribution of age versus menopausal status, we fit a hypertension-menopausal status interaction term and adjusted for age. RESULTS: There were similar relationships with regard to traditional coronary risk factors and angiographic CAD in premenopausal versus postmenopausal women, with few exceptions. Twenty percent of premenopausal women had angiographic CAD versus 31% of postmenopausal women (p = 0.02). Premenopausal women had lower mean (standard deviation) SBP (132 [25] vs. 139 [20] mm Hg; p < 0.0001) and lower PP (54 [18] vs. 62 [18] mm Hg; p < 0.0001) compared to postmenopausal women; however, multivariable analyses revealed that SBP was a risk factor for CAD in premenopausal (p = 0.002) but not postmenopausal women (p = 0.13), and regression slopes were significantly different (p = 0.04). This interaction effect remained after age adjustment, suggesting independent risk contribution from both age and menopausal status. A similar slope difference was observed for PP (p = 0.03) but not for DBP. CONCLUSIONS: Among women undergoing angiography for suspected ischemia, elevated SBP and PP are potent risk factors in premenopausal women. The results suggest that identification of hypertension in premenopausal women dictates additional CAD risk factor assessment and management.

Adult↗

PubMed2006

Impaired coronary vascular reactivity and functional capacity in women: results from the NHLBI Women's Ischemia Syndrome Evaluation (WISE) Study.

OBJECTIVES: We investigated the relationship between coronary vascular reactivity and functional capacity as assessed from the Duke Activity Status Index (DASI) in a cohort of women evaluated for suspected ischemia. BACKGROUND: Reduced functional capacity and impaired vascular reactivity are associated with poor prognosis, but an association between vascular reactivity and functional capacity is unknown. METHODS: A total of 190 women enrolled in the National Heart, Lung, and Blood Institute (NHLBI)-sponsored Women's Ischemia Syndrome Evaluation (WISE) study had baseline clinical assessment and coronary artery flow velocity response to adenosine (CFVR(ado)). We compared these results with self-reported DASI metabolic equivalents (METs). RESULTS: Mean age was 55 +/- 11 years (range 21 to 83 years), and only 18% had coronary stenosis > or =50%. Women with a CFVR(ado) <2.5 (n = 98) had mean DASI of 15.1 +/- 13.6, compared to women (n = 92) with CFVR(ado) > or =2.5, whose mean DASI was 21.0 +/- 15.2 (p = 0.004). This relationship was maintained after adjusting for age and presence of coronary artery disease. CFVR(ado) of > or =2.5 was associated with a DASI of >20 (odds ratio 3.03, 95% confidence interval 1.56 to 5.90, p = 0.001). CONCLUSIONS: Women with reduced CFVR(ado) were significantly more likely to have reduced functional capacity. Impairment in coronary vascular function and reduced levels of activity may both play a role in the poorer prognosis observed in the WISE study women; however, the relationship between the two is still unclear.

Adenosine↗

PubMed2006

Migraines, angiographic coronary artery disease and cardiovascular outcomes in women.

PURPOSE: There are conflicting data regarding the association between migraines and cardiovascular events. We evaluated the relationship between migraine headaches, angiographic coronary artery disease, and cardiovascular events in women. SUBJECTS AND METHODS: The Women's Ischemia Syndrome Evaluation (WISE) study is a National Heart, Lung and Blood Institute (NHLBI)-sponsored prospective, multicenter study aiming to improve ischemia evaluation in women. A total of 944 women presenting with chest pain or symptoms suggestive of myocardial ischemia were enrolled and underwent complete demographic, medical, and psychosocial history, physical examination, and coronary angiography testing. A smaller subset of 905 women, representing a mean age of 58 years, answered questions regarding a history of migraines. We prospectively followed 873 women for 4.4 years for cardiovascular events and all-cause mortality. RESULTS: Women reporting a history of migraines (n=220) had lower angiographic coronary severity scores, and less severe (> or = 70% luminal stenosis) angiographic coronary artery disease compared to women without a history of migraines (n=685). These differences remained statistically significant after adjustment for age and other important cardiac risk factors. On prospective follow-up of a median of 4.4 years, women with a history of migraines were not more likely to have a cardiovascular event (hazard ratio [HR] 1.2; 95% confidence interval [CI], 0.93-1.58) and migraines did not predict all-cause mortality (HR 0.96; 95% CI, 0.49-1.99). CONCLUSION: Among women undergoing coronary angiography for suspected ischemia, those reporting migraines had less severe angiographic coronary artery disease. We could not support an association between migraines and cardiovascular events or death. Further research studying the common pathophysiology underlying migraines and cardiovascular disease is warranted.

Coronary Artery Disease↗

PubMed2005

Electrocardiographic predictors of cardiovascular outcome in women: the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) study.

OBJECTIVES: We sought to analyze the value of infrequently measured parameters of the 12-lead electrocardiogram (ECG) in predicting cardiovascular events in women with suspected myocardial ischemia who were referred for cardiac catheterization. BACKGROUND: Routinely analyzed ECG parameters have low predictive value for cardiovascular events in women with preserved left ventricular function and suspected myocardial ischemia. The predictive value of ECG parameters for cardiovascular disease has not been fully determined. METHODS: Women enrolled in the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) study who had complete digital 12-lead ECG and quantitative angiography data were studied. Clinical and ECG predictors of cardiovascular disease events, defined as death, congestive heart failure, and non-fatal myocardial infarction, were determined. RESULTS: Of 143 women with ECG and angiographic data (mean age 59 +/- 13 years, left ventricular ejection fraction 64.1 +/- 8.6%), 13% had events during a mean follow-up period of 3.3 +/- 1.6 years. Independent predictors of event occurrences included a wider QRS-T angle (i.e., the spatial electrical angle between the QRS complex and the T-wave; p = 0.0005), wider QRS complex (p = 0.004), longer QTrr (i.e., age- and gender-adjusted QT interval; p = 0.0004), a more depressed ST-segment in precordial lead V5 (p = 0.0002), and a higher coronary artery disease severity score (p = 0.02). CONCLUSIONS: Several 12-lead ECG parameters, such as the QRS-T angle and the QRS and QTrr duration, are predictive of future cardiovascular events in women with suspected myocardial ischemia.

Aged↗

PubMed2005

Exercise treadmill testing using a modified exercise protocol in women with suspected myocardial ischemia: findings from the National Heart, Lung and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE).

BACKGROUND: Exercise testing, a major diagnostic modality in individuals with suspected coronary artery disease (CAD), has in general demonstrated less overall diagnostic accuracy in women compared to men. As part of the WISE, a modified protocol was examined with the intention of improving reliability of exercise testing. METHODS: Criteria for entry in the WISE study include clinically indicated coronary angiography. Exercise testing was performed using a protocol modified to be more appropriate for women. The study population consisted of 96 women, mean age of 55.8 y (range 34-77), who completed exercise treadmill test (ETT). Most (78%) were postmenopausal; 96% had >or =2 risk factors for CAD. RESULTS: By core laboratory angiography, 29/96 women had stenosis > or =50% in at least one coronary artery. Of these 29 women, 9 had abnormal ETT, yielding overall sensitivity of 31%. The remaining 20 women had normal (12/29, 41%) or nondiagnostic (8/29, 28%) studies. Among the 67 women with minimal or no coronary stenosis, 35 had no ischemic ST-segment changes during ETT, yielding overall specificity of 52%. Analysis with exclusion of women with nondiagnostic studies yielded sensitivity and specificity of 43% and 66%, respectively. The presence of coronary artery stenosis and inability to perform ETT, but not results of testing, predicted the outcomes of myocardial infarction, heart failure, and death. CONCLUSIONS: Exercise treadmill test appears to be of limited diagnostic value in women with suspected myocardial ischemia referred for coronary angiography. Sensitivity and specificity remain poor even with modified exercise protocol and core laboratory angiographic analysis. These findings merit consideration in view of current guidelines that recommend exercise testing in women with suspected CAD.

Adult↗

PubMed2005

Inflammation, endothelial cell activation, and coronary microvascular dysfunction in women with chest pain and no obstructive coronary artery disease.

BACKGROUND: Coronary artery microvascular dysfunction is prevalent in women with chest pain in the absence of obstructive coronary artery disease (CAD) and is manifested by attenuated coronary flow reserve (CFR). Markers of inflammation and endothelial cell activation have been found to be elevated in patients with chest pain but without CAD. The relationship between inflammation, endothelial activation, and CFR is not known. METHODS: Ninety-four women with chest pain in the absence of obstructive angiographic CAD underwent catheterization-based assessment of CFR and measurement of levels of inflammatory markers (n = 78) and endothelial cell activation in the NHLBI WISE study. RESULTS: Coronary flow reserve did not correlate with levels of C-reactive protein (high-sensitivity C-reactive protein) (rs = -0.07, P = .53), interleukin (IL)-6 (rs = -0.12, P = .31), IL-18 (rs = 0.14, P = .23), tumor necrosis factor alpha (rs = -0.09, P = .43), transforming growth factor beta1 (rs = 0.02, P = .84), and soluble intracellular adhesion molecule-1 (rs = 0.04, P = .68). Median levels of markers of inflammation and endothelial cell activation did not differ between the 57 women with abnormal CFR (< 2.5) and the 37 women with normal coronary microvascular function (high-sensitivity C-reactive protein 0.32 vs 0.25 mg/dL, P = .80; IL-6 2.89 vs 2.39 pg/mL, P = .63; IL-18 218 vs 227 pg/mL, P = .59; tumor necrosis factor alpha 2.7 vs 2.4 pg/mL, P = .43; transforming growth factor beta1 9928 vs 12436 pg/mL, P = .76; soluble intracellular adhesion molecule-1 286 vs 287 pg/mL, P = .95). Multivariable models demonstrated no evidence of associations between markers of inflammation and of endothelial cell activation and CFR. CONCLUSIONS: Coronary microvascular dysfunction is not associated with markers of inflammation and endothelial cell activation in women with chest pain in the absence of obstructive CAD. These results suggest that inflammation and endothelial cell activation may not play a pathophysiological role in coronary microvascular dysfunction.

Biomarkers↗

PubMed2004

Relationship of physical fitness vs body mass index with coronary artery disease and cardiovascular events in women.

CONTEXT: Individual contributions of obesity and physical fitness (physical activity and functional capacity) to risk of coronary heart disease in women remain unclear. OBJECTIVE: To investigate the relationships of measures of obesity (body mass index [BMI], waist circumference, waist-hip ratio, and waist-height ratio) and physical fitness (self-reported Duke Activity Status Index [DASI] and Postmenopausal Estrogen-Progestin Intervention questionnaire [PEPI-Q] scores) with coronary artery disease (CAD) risk factors, angiographic CAD, and adverse cardiovascular (CV) events in women evaluated for suspected myocardial ischemia. DESIGN, SETTING, AND PARTICIPANTS: The National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) is a multicenter prospective cohort study. From 1996-2000, 936 women were enrolled at 4 US academic medical centers at the time of clinically indicated coronary angiography and then assessed (mean follow-up, 3.9 [SD, 1.8] years) for adverse outcomes. MAIN OUTCOME MEASURES: Prevalence of obstructive CAD (any angiographic stenosis >or=50%) and incidence of adverse CV events (all-cause death or hospitalization for nonfatal myocardial infarction, stroke, congestive heart failure, unstable angina, or other vascular events) during follow-up. RESULTS: Of 906 women (mean age, 58 [SD, 12] years) with complete data, 19% were of nonwhite race, 76% were overweight (BMI >or=25), 70% had low functional capacity (DASI scores <25, equivalent to <or=7 metabolic equivalents [METs]), and 39% had obstructive CAD. During follow-up, 337 (38%) women had a first adverse event, 118 (13%) had a major adverse event, and 68 (8%) died. Overweight women were more likely than normal weight women to have CAD risk factors, but neither BMI nor abdominal obesity measures were significantly associated with obstructive CAD or adverse CV events after adjusting for other risk factors (P =.05 to.88). Conversely, women with lower DASI scores were significantly more likely to have CAD risk factors and obstructive CAD (44% vs 26%, P<.001) at baseline, and each 1-MET increase in DASI score was independently associated with an 8% (hazard ratio, 0.92; 95% confidence interval, 0.85-0.99; P =.02) decrease in risk of major adverse CV events during follow-up. CONCLUSIONS: Among women undergoing coronary angiography for suspected ischemia, higher self-reported physical fitness scores were independently associated with fewer CAD risk factors, less angiographic CAD, and lower risk for adverse CV events. Measures of obesity were not independently associated with these outcomes.

Body Mass Index↗

PubMed2004

Hemoglobin level is an independent predictor for adverse cardiovascular outcomes in women undergoing evaluation for chest pain: results from the National Heart, Lung, and Blood Institute Women's Ischemia Syndrome Evaluation Study.

OBJECTIVES: This study was designed to investigate the relationship between hemoglobin level (Hgb) and adverse cardiovascular outcomes in women with suspected ischemia. BACKGROUND: Low Hgb levels correlate with increased cardiovascular morbidity and mortality in patients presenting with acute myocardial infarction (MI) or congestive heart failure (CHF). However, the prognostic significance of Hgb in women with suspected ischemia is unclear. METHODS: As part of the National Heart, Lung, and Blood Institute (NHLBI)-sponsored Women's Ischemia Syndrome Evaluation (WISE), we prospectively studied 936 women referred for coronary angiography to evaluate suspected ischemia. We compared Hgb levels with cardiovascular risk factors, core lab interpreted angiograms, inflammatory markers, and adverse cardiovascular outcomes. RESULTS: Of women enrolled, 864 (mean age 58.4 +/-11.6 years) had complete Hgb, angiogram, and follow-up (mean 3.3 +/- 1.7 years) data. The mean Hgb was 12.9 g/dl (range 7.7 to 16.4 g/dl) and 184 women (21%) were anemic (Hgb <12 g/dl). Anemic women had higher creatinine and were more likely to be nonwhite and have a history of diabetes, hypertension, and CHF (p < 0.05). However, we found no difference in EF or severity of coronary artery disease. Anemic women had a higher risk of death from any cause (10.3% vs. 5.4%; p = 0.02) and total adverse outcomes (26% vs. 16%, p < 0.01). In a multivariable model, decreasing Hgb was associated with significantly higher risk of adverse outcomes (hazard ratio = 1.20, p = 0.002). Also, anemic women had shorter survival time free of adverse outcome (p < 0.001). CONCLUSIONS: Our findings extend previous reports, linking lower hemoglobin levels with higher risk for adverse cardiovascular outcomes, to women evaluated for suspected ischemia in the absence of acute MI or CHF.

Adolescent↗

PubMed2004

Metabolic syndrome modifies the cardiovascular risk associated with angiographic coronary artery disease in women: a report from the Women's Ischemia Syndrome Evaluation.

BACKGROUND: The metabolic syndrome, which is characterized by a constellation of fasting hyperglycemia, hypertriglyceridemia, low HDL cholesterol, hypertension, and/or abdominal obesity, is a risk factor for the development of coronary artery disease (CAD) and cardiovascular events. The interrelationship between metabolic status and CAD on cardiovascular risk in women is not known. METHODS AND RESULTS: We evaluated interrelationships between angiographic CAD, the metabolic syndrome, and incident cardiovascular events among 755 women from the Women's Ischemia Syndrome Evaluation (WISE) study who were referred for coronary angiography to evaluate suspected myocardial ischemia; 25% of the cohort had the metabolic syndrome at study entry. Compared with women with normal metabolic status, women with the metabolic syndrome had a significantly lower 4-year survival rate (94.3% versus 97.8%, P=0.03) and event-free survival from major adverse cardiovascular events (death, nonfatal myocardial infarction, stroke, or congestive heart failure; 87.8% versus 93.5%, P=0.003). When the subjects were stratified by the presence or absence of angiographically significant CAD at study entry, in women with angiographically significant CAD, the metabolic syndrome resulted in significantly higher risk of cardiovascular events than in women with normal metabolic status (hazard ratio 4.93, 95% CI 1.02 to 23.76; P=0.05), whereas it did not result in increased 4-year cardiovascular risk in women without angiographically significant CAD (hazard ratio 1.41, 95% CI 0.32 to 6.32; P=0.65). CONCLUSIONS: These data suggest that in women with suspected myocardial ischemia, the metabolic syndrome modifies the cardiovascular risk associated with angiographic CAD. Specifically, the metabolic syndrome was found to be a predictor of 4-year cardiovascular risk only when associated with significant angiographic CAD.

Adult↗

PubMed2004

Abnormal coronary vasomotion as a prognostic indicator of cardiovascular events in women: results from the National Heart, Lung, and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE).

BACKGROUND: Coronary vascular dysfunction has been linked to atherosclerosis and adverse cardiovascular outcomes in men, but these relationships have not been firmly established in women. METHODS AND RESULTS: As part of the Women's Ischemia Syndrome Evaluation (WISE) sponsored by the National Heart, Lung, and Blood Institute, 163 women referred for clinically indicated coronary angiography underwent coronary reactivity assessment with quantitative coronary angiography and intracoronary Doppler flow before and after intracoronary administration of acetylcholine, adenosine, and nitroglycerin and were then followed up for clinical outcomes. History of hypertension was present in 61%, dyslipidemia in 54%, diabetes in 26%, and current tobacco use in 21% of women enrolled. Seventy-five percent had no or only mild epicardial coronary artery disease (CAD). Over a median follow-up of 48 months, events occurred in 58 women. On bivariate analysis, women with an event had significantly less change in coronary cross-sectional area (DeltaCSA) in response to acetylcholine (P=0.0006) and nitroglycerin (P=0.04). In addition, women with abnormal coronary dilator response to acetylcholine had less time free from cardiovascular events (P=0.004). In multivariable analysis, after controlling for age, hypertension, diabetes, dyslipidemia, tobacco use, and CAD severity, %DeltaCSA with acetylcholine (P=0.001) independently predicted events. When the outcome was restricted to only death, myocardial infarction, congestive heart failure, and stroke, %DeltaCSA with acetylcholine remained a significant predictor (P=0.006). CONCLUSIONS: In women in this study, impaired coronary vasomotor response to acetylcholine was independently linked to adverse cardiovascular outcomes regardless of CAD severity.

Acetylcholine↗

PubMed2004

Validation of the accuracy of pretest and exercise test scores in women with a low prevalence of coronary disease: the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) study.

BACKGROUND: Recently revised American College of Cardiology/American Heart Association guidelines have suggested that exercise test scores be used in decisions concerning patients with suspected coronary artery disease (CAD). Pretest and exercise test scores derived for use in women without known CAD have not been tested in women with a low prevalence of CAD. METHODS: Within the Women's Ischemia Syndrome Evaluation (WISE) study, we evaluated 563 women undergoing coronary angiography for suspected myocardial ischemia. The prevalence of angiographic CAD was 26%. Overall, 189 women underwent treadmill exercise testing. Prognostic end points included death, myocardial infarction, stroke, and revascularization. RESULTS: Each score stratified women into 3 probability groups (P <.001) according to the prevalence of coronary disease: Pretest: low 20/164 (12%), intermediate 53/245 (22%), high 75/154 (49%); Exercise test: low 11/83 (13%), intermediate 22/74 (30%), high 17/32 (53%). However, the Duke score did not stratify as well: low 7/46 (15%), intermediate 36/126 (29%), high 6/17 (35%); P =.44. When pretest and exercise scores were considered together, the best stratification with the exercise test score was in the intermediate pretest group (P <.03). The Duke score did not stratify this group at all (P =.98). Pretest and exercise test scores also stratified women according to prognostic end points: pretest--low 7/164 (4.3%), intermediate 28/245 (11.4%), high 27/154 (17.5%), P <.01; exercise test--low 4/83 (4.8%) and intermediate-high 17/106 (16%), P =.014. CONCLUSION: Both pretest and exercise test scores performed better than the Duke score in stratifying women with a low prevalence of angiographic CAD. The exercise test score appears useful in women with an intermediate pretest score, consistent with American College of Cardiology/American Heart Association guidelines.

Coronary Angiography↗

PubMed2004

Determination of menopausal status in women: the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) Study.

PURPOSE: Accurate classification of menopausal status is important to epidemiological research evaluating the role of reproductive hormones in disease processes. Algorithms relying on repeat hormone assays are unfeasible in large epidemiological studies. This paper summarizes the development of the Women's Ischemia Syndrome Evaluation (WISE) Hormonal menopausal status algorithm for determining premenopausal, perimenopausal, and postmenopausal status using menstrual and reproductive history and reproductive hormone levels obtained at a single clinic visit. METHODS: The authors compared the accuracy of this algorithm with two currently used self-report algorithms: Menstrual, based only on months since last menstrual period, and Historical, which adds age and surgical history. RESULTS: The study population consisted of 515 women (329 clearly postmenopausal) enrolled in the WISE study who were undergoing coronary angiography for suspected ischemia. A subgroup of 186, not clearly postmenopausal, was classified by these three algorithms. Results were evaluated against individualized expert consensus classification. The Menstrual and Historical classifications differed significantly (p < 0.0001) from expert consensus, with 32%-26% discordant classifications, respectively. For the WISE Hormonal classification, discordance was 4%. CONCLUSIONS: The authors conclude that inaccurate classifications of menopausal status occur frequently in self-report algorithms. Use of the relatively simple WISE algorithm can improve the accuracy of menopausal status classification for epidemiological research.

Adult↗

PubMed2003

Hypoestrogenemia of hypothalamic origin and coronary artery disease in premenopausal women: a report from the NHLBI-sponsored WISE study.

OBJECTIVES: We sought to evaluate hypoestrogenemia of hypothalamic origin and its association with angiographic coronary artery disease (CAD) in premenopausal women. BACKGROUND: Coronary artery disease in premenopausal women appears to have a particularly poor prognosis. Primate animal data suggest that premenopausal CAD is strongly determined by psychosocial stress-induced central disruption of ovulatory cycling and resulting hypoestrogenemia. METHODS: We assessed reproductive hormone blood levels and angiographic CAD using core laboratories in 95 premenopausal women with coronary risk factors who were enrolled in the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation and were undergoing coronary angiography for evaluation for suspected ischemia. RESULTS: Premenopausal women with angiographic CAD (n = 13) had significantly lower estradiol, bioavailable estradiol, and follicle-stimulating hormone (FSH) (all p < 0.05) than women without angiographic CAD (n = 82), even after controlling for age. Hypoestrogenemia of hypothalamic origin, defined as estradiol <184 pmol/l (50 pg/ml), FSH <10 IU/l, and luteinizing hormone <10 IU/l, was significantly more prevalent among the women with CAD than those without CAD (9/13 [69%] vs. 24/82 [29%], respectively, p = 0.01). Hypoestrogenemia of hypothalamic origin was the most powerful predictor of angiographic CAD in a multivariate model (odds ratio [OR] 7.4 [confidence interval (CI) 1.7 to 33.3], p = 0.008). Anxiolytic/sedative/hypnotic and antidepressant medication use were independent predictors of hypoestrogenemia of hypothalamic origin in a multivariate model (OR 4.6 [CI 1.3 to 15.7], p = 0.02, OR 0.10 [CI 0.01 to 0.92], p = 0.04, respectively). CONCLUSIONS: Among premenopausal women undergoing coronary angiography for suspected myocardial ischemia, disruption of ovulatory cycling characterized by hypoestrogenemia of hypothalamic origin appears to be associated with angiographic CAD.

Adult↗