Abstract

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 hazard ratio {AHR} =1.67; 95% confidence interval {CI} =1.34-2.08; p<0.0001). Among men, 535 (36%) and 609 (41%) patients without and with diabetes died from all causes (AHR =1.21; 95% CI =1.07-1.36; p=0.002). Sex-diabetes interaction (overall adjusted p <0.0001) 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 hospitalization for women and men were respectively 1.49 (1.28-1.72) and 1.21 (1.11-1.32), 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.