LAUSR

AIMS Multimorbidity, the coexistence of two or more chronic conditions, is synonymous with heart failure(HF). How risk related to comorbidities compare at individual and population levels is unknown. The aim of this study is to examine the risk related to comorbidities, alone and in combination, both at individual and population levels. METHODS Using two clinical trials in HF- the Prospective comparison of ARNI(Angiotensin Receptor Neprilysin Inhibitor) with ACEI(Angiotensin Converting Enzyme Inhibitor) to Determine Impact on Global Mortality and morbidity in HF trial(PARADIGM-HF) and the Aliskiren trial to Minimize OutcomeS in Patients with HF trial(ATMOSPHERE), we identified the ten most common comorbidities and examined 45 possible pairs. We calculated population attributable fractions(PAF) for all-cause death and relative excess risk due to interaction with Cox proportional hazard models. RESULTS Of 15 066 patients in the study, 14 133(93.7%) had at least one and 11 867(78.8%) had at least two of the ten most prevalent comorbidities. The greatest individual risk among pairs was associated with peripheral artery disease(PAD) in combinations with stroke(HR 1.73;95% CI 1.28-2.33) and anaemia(1.71;1.39-2.11). The combination of CKD and hypertension had the highest PAF(5.65%;95% CI 3.66 to 7.61). Two pairs demonstrated significant synergistic interaction(atrial fibrillation with CKD and coronary artery disease respectively) and one an antagonistic interaction(anaemia & obesity). CONCLUSIONS In HF, the impact of multimorbidity differed at the individual-patient and population level, depending on the prevalence of and the risk related to each comorbidity, and the interaction between individual comorbidities. Patients with co-existent PAD and stroke were at greatest individual risk whereas, from a population perspective, co-existent CKD and hypertension mattered most This article is protected by copyright. All rights reserved.