Evaluating Incident Atrial Fibrillation and Incident Heart Failure as Time-varying Covariates for Time-to-Event Analysis Among Adults 55 Years and Older in the Multi-Ethnic Study of Atherosclerosis (MESA)

Abstract

Objectives

Heart failure (HF) and atrial fibrillation (AF) frequently coexist, exacerbate each other and are associated with increased morbidity and mortality rates. However, no previous study has specifically calculated the risk of experiencing either event following the occurrence of the other and also considered competing risks. The aim of this study was to examine the bidirectional relationship of AF and HF in a multiethnic population, taking competing risks into account.

Methods

Two Fine and Gray regression models of the subdistribution functions were implemented to evaluate the bidirectional association between AF and HF and were adjusted for a common set of covariates. Competing events were defined as HF/AF and/or cardiac death vs noncardiac death. For each model, common covariates for AF and HF were pre-identified in the literature, and either HF or AF was used as a time-dependent covariate.

Results

In the Multi-Ethnic Study of Atherosclerosis (MESA), 4016 study participants (mean age 67.2 ± 7.6 years and 48.8% male participants), free of clinically recognized cardiovascular disease at baseline, were assessed for AF and HF. After a median (IQR) follow-up of 6034 (3994–6313) days, 1044 incident AFs, 302 incident HFs and 1298 events of death occurred. Deaths were distributed as 313 cardiac deaths and 985 noncardiac deaths, and the incidence of AF was about 3.5 higher than that of HF. We found that HF was associated with a composite outcome of AF and/or cardiac death (HR 2.91, 95%CI [2.49–3.40]; P < 0.001) and that AF was associated with a composite outcome of HF and/or cardiac death (HR 2.05, 95%CI [1.79–2.35]; P < 0.001).

Conclusion

AF and HF exacerbate the incidence of each other and are strongly and independently associated, suggesting that their joint association should be taken into consideration in future studies. From a clinical perspective, the occurrence of either of these events greatly increases the risk for the other (ClinicalTrials.gov Identifier: NCT00005487).