A propensity-matched study of the effect of diabetes on the natural history of heart failure: variations by sex and age

Background: Poor prognosis in heart failure ( HF) patients with diabetes is often attributed to increased comorbidity and advanced disease. Further, this effect may be worse in women. Objective: To determine whether the effect of diabetes on outcomes and the sex- related variation persisted in a propensity score- matched HF population, and whether the sex- related variation was a function of age. Methods: Of the 7788 HF patients in the Digitalis Investigation Group trial, 2218 had a history of diabetes. Propensity score for diabetes was calculated for each patient using a non- parsimonious logistic regression model incorporating all measured baseline covariates, and was used to match 2056 ( 93%) diabetic patients with 2056 non- diabetic patients. Results: All- cause mortality occurred in 135 ( 25%) and 216 ( 39%) women without and with diabetes ( adjusted HR = 1.67; 95% CI = 1.34 to 2.08; p<0.001). Among men, 535 ( 36%) and 609 ( 41%) patients without and with diabetes died from all causes ( adjusted HR = 1.21; 95% CI = 1.07 to 1.36; p = 0.002). Sex diabetes interaction (overall adjusted p<0.001) was only significant in patients >= 65 years ( 15% absolute risk increase in women; multivariable p for interaction = 0.005), but not in younger patients ( 2% increase in women; p for interaction = 0.173). Risk- adjusted HR ( 95% CI) for all- cause hospitalisation for women and men were 1.49 ( 1.28 to 1.72) and 1.21 ( 1.11 to 1.32), respectively, also with significant sex - diabetes interaction ( p = 0.011). Conclusions: Diabetes- associated increases in morbidity and mortality in chronic HF were more pronounced in women, and theses sex- related differences in outcomes were primarily observed in elderly patients.