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

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

Methods: Two Fine and Gray regression models of the sub-distribution 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 versus non-cardiac 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 AF, 302 incident HF, and 1298 events of deaths occurred. Deaths were distributed as 313 cardiac deaths and 985 non-cardiac deaths, and incidence of AF was about 3.5 higher than 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: Each of 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) LAY SUMMARY: This paper investigates the interplay of heart failure and atrial fibrillation, two types of heart disease. Several reports indicate that these conditions often happen together, make each other worse, and are linked to more illness and death, but their mutual influence has not been formally measured. We examined MESA participants free of heart disease before joining our study and evaluated the degree to which developing either heart failure or atrial fibrillation raises the chance of getting the other condition. We found that AF and HF exacerbate the respective incidence of each other and are strongly and independently associated, suggesting that both diseases should be taken into consideration together in future studies.