Cardiovascular
Identifying mediators of the effect of cigarette smoking on atrial fibrillation in the Atherosclerosis Risk in Communities (ARIC) Study Oluseye Ogunmoroti* Oluseye Ogunmoroti Ogunmoroti Ogunmoroti Ogunmoroti Ogunmoroti Emory University
Background: The biological pathways linking cigarette smoking to atrial fibrillation (AF) remain unclear. We quantify AF risk mediation by cigarette smoking-related comorbidities (coronary heart disease [CHD], hypertension [HTN], diabetes mellitus [DM] and obesity) to identify potential intervention targets.
Methods: We analyzed data from 11,580 adults aged 45-64 years at enrollment. Cigarette smoking status was assessed at baseline (1987-1989) by self-report questionnaire and categorized as current, former and never. At visit 3 (1993-1995), the presence of CHD, HTN, DM and obesity was determined using standardized methods. Incident AF was ascertained via ECG, hospital discharge records and death certificates through the end of 2019. Using confounder-adjusted causal mediation analysis, we estimated the risk ratios for the total (TE), natural direct (NDE) and natural indirect (NIE) effects of cigarette smoking on AF, under a no exposure-mediator interaction assumption.
Results: The analytical sample was 44% men and overall mean age (SD) was 54 (6) years at baseline. After a median (IQR) follow-up of 27 (19, 31) years, 2,800 AF cases (24%) were identified. The TE of current smoking (vs. never smoking) on AF was 1.18 (95% CI: 1.08, 1.30) which was similar to the NDE across mediators: CHD 1.18 (1.09, 1.28), HTN 1.19 (1.10, 1.29), DM 1.19 (1.10, 1.28), and obesity 1.19 (1.10, 1.28). The NIE was 1.00 − 1.01 across mediators yielding low proportions mediated: 3% (CHD), 4.8% (HTN), 0.4% (DM), and 0.01% (obesity). The estimates for former smoking were highly imprecise.
Conclusion: The mediation of the effect of cigarette smoking on AF through CHD, HTN, DM, and obesity was minimal. These findings indicate that most of the effect of cigarette smoking on AF is direct, underscoring the importance of smoking cessation. Future research should explore the time-varying nature of these variables along with additional pathways for mediation to identify novel targets for AF prevention.