Risk factors for heart failure in women with ischemia and no obstructive coronary artery disease.

Study objective: Women with ischemia and no obstructive coronary artery disease (INOCA) are at increased risk for heart failure (HF) hospitalizations, which is predominantly HF with preserved ejection fraction (HFpEF). We aimed to identify predictors for the development of heart failure HF in a deeply phenotyped cohort of women with INOCA and long-term prospective follow-up. Design setting and participants: Women enrolled in the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) were evaluated for baseline characteristics including clinical history, medications, physical exam, laboratory data and angiographic data. Using a multivariate Cox analysis, we assessed the association between baseline characteristics and the occurrence of HF hospitalizations in 493 women with evidence of ischemia but no obstructive coronary disease, no prior history of HF, and available follow-up data. Results: During a median follow-up of 6-years, 18 (3.7%) women were hospitalized for HF. Diabetes mellitus and tobacco use were associated with HF hospitalization. In a multivariate analysis adjusting for known HFpEF predictors including age, diabetes, hypertension, tobacco use, and statin use, novel predictive variables included higher resting heart rate, parity and IL-6 levels and lower coronary flow reserve (CFR) and poor functional status. Conclusions: There is a considerable incidence of HF hospitalization at longer term follow-up in women with INOCA. In addition to traditional risk factors, novel risk variables that independently predict HF hospitalization include multi-parity, high IL-6, low CFR, and poor functional status. These novel risk factors may be useful to understand mechanistic pathways and future treatment targets for prevention of HFpEF.