Longitudinal depressive symptom trajectories and the risk of new-onset atrial fibrillation

Abstract Background Depression is an established risk factor for both new-onset and recurrent atrial fibrillation (AF). However, the dynamic nature of depressive symptoms makes the relationship more complex, and this is rarely captured in existing studies which often use a single time point measure of depressive symptoms. It remains unclear how the risk of AF is dependent on depressive symptom trajectories over time. Purpose To examine how sex-specific trajectories of depressive symptoms over time are associated with incident AF. Methods We included 8401 participants from a large population-based study, who were followed from 1999 to 2020. AF was assessed with electrocardiogram. Repeated measures of depressive symptoms were assessed through Centre for Epidemiology Studies Depression (CES-D) scale. First, we evaluated depressive symptom trajectories using a linear mixed-effects model where time was modelled non-linearly using natural cubic splines. Then we employed a joint model framework to integrate the longitudinal depressive symptom trajectories with time to incident AF. We assessed the instantaneous depressive symptoms effect on AF hazard. Thereafter, we assessed the risk of the cumulative burden of depressive symptoms, calculated as the area under the curve, on AF. Models were adjusted for age, smoking, alcohol intake, BMI, dyslipidaemia, hypertension, psychoanaleptics intake and history of; diabetes, heart failure, and coronary heart disease. We examined these associations for the overall sample and stratified by sex. Associations are presented as hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs). Results Mean (standard deviation) age was 61.42 (±7.49) in the total population and 61.73 (±7.74) in women, 61.03 (±7.11) in men. We identified a strong non-linear trajectory of depressive symptoms in the total sample. Similar patterns were observed in women and men, with women showing steeper temporal changes than men. The joint model showed the current value of depression to be significantly associated with incident AF (HR: 1.12, 95% CI: 1.02 – 1.23) in the total population. The association attenuated in women, albeit non-significant (HR: 1.09, 95% CI: 0.95 – 1.27), but was not observed in men (HR: 1.00, 95% CI: 0.86 – 1.17), (P for sex interaction = 0.019). Cumulative burden of depression was also significantly associated with incident AF (HR: 1.12, 95% CI: 1.02 – 1.21). The association was attenuated in women, albeit non-significant (HR: 1.07, 95% CI: 0.92 – 1.24) but was not observed in men (HR: 0.97, 95% CI: 0.83 – 1.13), (P for sex interaction = 0.034). Conclusion Both the short-term and the long-term burden of depressive symptoms are risk factors for AF. Our results suggest that depressive symptoms might have a larger impact on women. However, the limited sample size warrants replication in larger samples.For image description, please refer to the figure legend and surrounding text. For image description, please refer to the figure legend and surrounding text.