METHODS AND RESULTS: This is a prospective cohort study using data from the Heart and
Estrogen/
progestin Replacement Study (HERS), a randomized, blinded, placebo-controlled trial of 4.1 years' duration, and subsequent open-label observational follow-up for 2.7 years (HERS II), performed at 20 US clinical centers between 1993 and 2000. Of the 2763 postmenopausal women with established
coronary disease in the HERS trial, we studied the 2391 women with no
heart failure at baseline by self-report and physical examination. The primary outcome of this analysis was incident
heart failure defined by hospital admission or death from
heart failure. During the 6.3+/-1.4-year follow-up, 237 women (10%) developed
heart failure. Nine predictors were identified: diabetes (defined as a self-reported history of diabetes on treatment),
atrial fibrillation,
myocardial infarction,
creatinine clearance <40 mL/min, systolic blood pressure >120 mm Hg, current smoking, body mass index >35 kg/m2,
left bundle-branch block, and
left ventricular hypertrophy. Randomization to
estrogen/
progestin was not associated with
heart failure (hazard ratio=1.0; 95% CI, 0.7 to 1.3). Diabetes was the strongest risk factor (adjusted hazard ratio=3.1; 95% CI, 2.3 to 4.2). Diabetic women with elevated body mass index or depressed
creatinine clearance were at highest risk, with annual incidence rates of 7% and 13%, respectively. Among diabetic women,
hyperglycemia was associated with
heart failure risk (adjusted hazard ratio=3.0; 95% CI, 1.2 to 7.5 for fasting
glucose >300 mg/dL compared with fasting
glucose 80 to 150 mg/dL).
CONCLUSIONS: