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Background: In women with low to intermediate risk of coronary artery disease (CAD), prognostic detection strategies have been controversial. We present the follow-up data of the SMART trial in peri/postmenopausal women at low to intermediate risk of CAD., Objectives: To determine the value of contrast stress echocardiography (CSE), stress electrocardiogram (sECG), and serum biomarkers for prediction of cardiovascular events (CE) in peri/postmenopausal women at low to intermediate risk of CAD., Materials and Methods: From January 2004 to August 2007, 400 peri/postmenopausal women were prospectively enrolled. All women had detailed risk factor assessment, and underwent simultaneous CSE (Definity ® , Lantheus Medical Imaging) and sECG. Laboratories included brain natriuretic peptide (BNP), atrial natriuretic peptide, endothelin, and high sensitivity C-reactive protein. Wall motion score index was based on a 16-segment model. Abnormal CSE was defined as new or worsening wall motion abnormality at stress, while abnormal sECG was ≥1 mm horizontal/downsloping ST segment depression/elevation (80 mseconds duration). Self-reported outcome data were collected from a mailed Women's Heart Clinic Questionnaire. CE outcomes included all-cause mortality, nonfatal myocardial infarction (MI), heart failure, chest pain hospitalization or development of typical angina (CP), and revascularization (REVASC). Adjusted Cox proportional hazard ratios (HR; 95% confidence intervals) were reported., Results: A total of 366 women (54.4 ± 5.5 years, Framingham risk 6.5% ± 4.4%) completed simultaneous CSE and sECG. Forty-two (11.5%) had abnormal CSE, while sECG was abnormal in 22 (6%) women. Follow-up (4.4 ± 1.2 years) was available in 315/366 (86%) women (78% exercise-CSE, 22% dobutamine-CSE). In those who completed follow-up, CSE was abnormal in 33 women (10.5%) and sECG was abnormal in 21 (6.7%). In 33 women with abnormal CSE, sECG was abnormal in 7 (21.2%) and normal in 26 (79%), p = 0.0004. CE occurred in 27 (8.6%) women: 8 all-cause mortality, 2 nonfatal MI, 13 CP, and 4 REVASC. CE occurred in 21% versus 7% of women with abnormal versus normal CSE, p = 0.014 and 38% versus 6% of women with abnormal versus normal sECG, p < 0.0001. Rest BNP was higher in women with CE versus those without (p = 0.018). Abnormal sECG and abnormal CSE were associated with CE, while only abnormal sECG was an independent predictor of CE (adjusted HR 10.3 [1.9-61.4], p = 0.007). Of the laboratory results, only BNP was associated with CE (adjusted HR 2.9 [1.1-7.3], p = 0.028)., Conclusions: sECG and rest BNP were independent predictors of subsequent CE within 5 years in peri/postmenopausal women at low to intermediate risk of CAD.

Aims: This multisite prospective trial, Stress Echocardiography in Menopausal Women At Risk for Coronary Artery Disease (SMART), aimed to evaluate the prognostic value of contrast stress echocardiography (CSE), coronary artery calcification (CAC), and cardiac biomarkers for prediction of cardiovascular events after 2 and 5 years in early menopausal women experiencing chest pain symptoms or risk factors. This report describes the study design, population, and initial test results at study entry., Methods: From January 2004 through September 2007, 366 early menopausal women (age 54±5 years, Framingham risk score 6.51%±4.4 %, range 1%-27%) referred for stress echocardiography were prospectively enrolled. Image quality was enhanced with an ultrasound contrast agent. Tests for cardiac biomarkers [high-sensitivity C-reactive protein (hsCRP), atrial natriuretic protein (ANP), brain natriuretic protein (BNP), endothelin (ET-1)] and cardiac computed tomography (CT) for CAC were performed., Results: CSE (76% exercise, 24% dobutamine) was abnormal in 42 women (11.5%), and stress electrocardiogram (ECG) was positive in 22 women (6%). Rest BNP correlated weakly with stress wall motion score index (WMSI) (r=0.189, p<0.001). Neither hsCRP, ANP, endothelin, nor CAC correlated with stress WMSI. Predictors of abnormal CSE were body mass index (BMI), diabetes mellitus, family history of premature coronary artery disease (CAD), and positive stress ECG. Twenty-four women underwent clinically indicated coronary angiography (CA); 5 had obstructive (≥50%), 15 had nonobstructive (10%-49%), and 4 had no epicardial CAD., Conclusions: The SMART trial is designed to assess the prognostic value of CSE in early menopausal women. Independent predictors of positive CSE were BMI, diabetes mellitus, family history of premature CAD, and positive stress ECG. CAC scores and biomarkers (with the exception of rest BNP) were not correlated with CSE results. We await the follow-up data.