Prognostic Utility of Stress Testing and Cardiac Biomarkers in Menopausal Women at Low to Intermediate Risk for Coronary ARTery Disease (SMART Study): 5-Year Outcome

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((R)), 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 1mm 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 (54.45.5 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.