Risk Factor and Prediction Modeling for Sudden Cardiac Death in Women With Coronary Artery Disease

Background: To our knowledge, the risk of sudden cardiac death (SCD) and the assessment of risk factors in prediction models have not been evaluated in women with coronary artery disease (CAD). We sought to evaluate the incidence of SCD as well as its risk factors and their predictive accuracy among a population of women with CAD. Methods: The Heart and Estrogen/progestin Replacement Study evaluated the effects of hormone replacement therapy on cardiovascular events among 2763 postmenopausal women with CAD. Sudden cardiac death was defined as death resulting from a cardiac origin that occurred within 1 hour of symptom onset. The associations between candidate predictor variables and SCD were evaluated in a Cox proportional hazards model. The C-index was used to compare the predictive value of the clinical risk factors with left ventricular ejection fraction (LVEF) alone and in combination. The net reclassification improvement was also computed. Results: Over a mean follow-up of 6.8 years, SCD comprised 136 of the 254 cardiac deaths. The annual SCD event rate was 0.79% (95% confidence interval, 0.67-0.94). The following variables were independently associated with SCD in the multivariate model: myocardial infarction, heart failure, an estimated glomerular filtration rate of less than 40 mL/min/1.73 m(2), atrial fibrillation, physical inactivity, and diabetes. The incidences of SCD among women with 0 (n = 683), 1 (n = 1224), 2 (n = 610), and 3 plus (n = 246) risk factors at baseline were 0.3%, 0.5%, 1.2%, and 2.9% per year, respectively. The combination of clinical risk factors and LVEF (C-index, 0.681) were better predictors of SCD than LVEF alone (C-index, 0.600) and resulted in a net reclassification improvement of 0.20 (P < .001). Conclusions: Sudden cardiac death comprised the majority of cardiac deaths among postmenopausal women with CAD. Independent predictors of SCD, including myocardial infarction, congestive heart failure, an estimated glomerular filtration rate of less than 40 mL/min/1.73 m(2), atrial fibrillation, physical inactivity, and diabetes, improved SCD prediction when they were considered in addition to LVEF.