Contribution of cardiac and extra-cardiac disease burden to risk of cardiovascular outcomes varies by ejection fraction in heart failure

Wolsk, E., Claggett, B., Køber, L., Pocock, S., Yusuf, S., Swedberg, K., McMurray, J. J.V. , Granger, C. B., Pfeffer, M. A. and Solomon, S. D. (2018) Contribution of cardiac and extra-cardiac disease burden to risk of cardiovascular outcomes varies by ejection fraction in heart failure. European Journal of Heart Failure, 20(3), pp. 504-510. (doi: 10.1002/ejhf.1073) (PMID:29193462)

Abstract

Aims: Patients with heart failure (HF) often have multiple co-morbidities that contribute to the risk of adverse cardiovascular (CV) and non-CV outcomes. We assessed the relative contribution of cardiac and extra-cardiac disease burden and demographic factors to CV outcomes in HF patients with reduced (HFrEF) or preserved (HFpEF) left ventricular ejection fraction (LVEF). Methods and results: We utilized data from the CHARM trial, which enrolled HF patients across the ejection fraction spectrum. We decomposed the previously validated MAGGIC risk score into cardiac (LVEF, New York Heart Association class, systolic blood pressure, time since HF diagnosis, HF medication use), extra-cardiac (body mass index, creatinine, diabetes mellitus, chronic obstructive pulmonary disease, smoker), and demographic (age, gender) categories, and calculated subscores for each patient representing the burden of each component. Cox proportional hazards models were used to estimate the population attributable risk (PAR) associated with each component to the outcomes of death, CV death, HF, myocardial infarction, and stroke relative to patients with the lowest risk score. PARs for each component were depicted across the spectrum of LVEF. In 2675 chronic HF patients from North America [HFrEF (LVEF ≤40%): n = 1589, HFpEF (LVEF >40%): n = 1086] with data available for calculation of the MAGGIC score, the highest risk of death and CV death was attributed to cardiac burden. This was especially evident in HFrEF patients (PAR: 76% cardiac disease vs. 58% extra-cardiac disease, P < 0.05). Conversely, in HFpEF patients, extra-cardiac burden accounted for a greater proportion of risk for death than cardiac burden (PAR: 15% cardiac disease vs. 49% extra-cardiac disease, P < 0.05). For HF hospitalization, the contribution of both cardiac and extra-cardiac burden was comparable in HFpEF patients (PAR: 42% cardiac disease vs. 53% extra-cardiac disease, P = NS). In addition, demographic burden was especially high in HFpEF patients, with 62% of deaths attributable to demographic characteristics. Conclusion: In North American HF patients enrolled in the CHARM trials, the relative contribution of cardiac and extra-cardiac disease burden to CV outcomes and death differed depending on LVEF. The high risk of events attributable to non-cardiac disease burden may help explain why cardiac disease-modifying medication proven to be efficacious in HFrEF patients has not proven beneficial in HFpEF.

• Item Type: Articles
• Additional Information: The CHARM programme was funded by AstraZeneca. E.W. was supported by an unrestricted grant from Independent Research Fund Denmark (DFF – 4183-00550).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McMurray, Professor John and Kober, Professor Lars
• Authors: Wolsk, E., Claggett, B., Køber, L., Pocock, S., Yusuf, S., Swedberg, K., McMurray, J. J.V., Granger, C. B., Pfeffer, M. A., and Solomon, S. D.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: European Journal of Heart Failure
• Publisher: Wiley
• ISSN: 1388-9842
• ISSN (Online): 1879-0844
• Published Online: 30 November 2017
• Copyright Holders: Copyright © 2017 European Society of Cardiology
• First Published: First published in European Journal of Heart Failure 20(4):504-510
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher