The Interaction Effect of Cardiac and Noncardiac Co-morbidities on Mortality Rates in Patients With Heart Failure

Abstract

The prevalence of heart failure (HF) and co-morbidities are increasing. The prognostic impact of interaction between co-morbidity and HF remains unknown. The purpose of the present study was to examine if HF interacts with co-morbidity burden to increase mortality. We conducted a cohort study of all adult Danish patients (aged ≥18 years) with a hospital inpatient or outpatient clinic diagnosis of HF (n=252,726) between 1995 and 2016. We matched each patient with up to 3 members of the general population without a history of HF (n=744,372). Noncardiac co-morbidities were assessed using the Charlson co-morbidity index and were defined by 4 categories of co-morbidity: 0 (none), 1 (low), 2 to 3 (moderate), and ≥4 (severe). Cardiac co-morbidities were assessed individually. Among patients with HF with severe co-morbidity, 42% of the mortality rate during 30 days of follow-up was explained by the interaction with co-morbidity. The interaction effect was also substantial in patients with moderate (31%) and low co-morbidity burden (16%). During 31 to 365 days of follow-up, interaction effects were 1% for low co-morbidity, 8% for moderate co-morbidity, and 22% for severe co-morbidity. Beyond 1 year of follow-up, no interaction effect was observed. With the exception of cardiomyopathy, cardiac co-morbidities did not interact substantially with HF during the first year of follow-up. During longer follow-up, pulmonary hypertension, cardiomyopathy, and endocarditis showed interaction. In conclusion, noncardiac co-morbidities had biological interaction with HF that increased short-term mortality substantially beyond the individual effects of HF and co-morbidity.