The association of stroke rate with low density lipoprotein and statin exposure in patients with atrial fibrillation (AF)

Abstract

Abstract Background There are limited data on the association between cholesterol levels and stroke risk in atrial fibrillation (AF). Objective To quantify the association of stroke rate in AF with low-density lipoprotein (LDL) levels and statin use. Methods Using linked administrative databases in Ontario, Canada, we conducted a population-based retrospective cohort study of patients aged ≥66 years, diagnosed with AF between 2009–2019. We used cause-specific hazard regression to determine the association of statin use with stroke rate. We developed a second cause-specific regression model for patients with at least one lipid profile measurement in the year before AF diagnosis to study the association of LDL levels with stroke rate, while adjusting for statin use. LDL levels were modeled using restricted cubic splines (RCS). Both models were adjusted for age, sex, heart failure, hypertension, diabetes, stroke or transient ischemic attack, and vascular disease at baseline, plus anticoagulation as a time-varying covariate. Results We studied 261,659 qualifying patients (median age 78 years, 49% female), of whom 3,954 (1.5%) developed a stroke during one-year follow-up. A total of 142,834 (54.6%) patients were treated with statins and 145,775 (55.7%) had lipid measurements before AF diagnosis. The adjusted RCS analyses (see Figure) indicated increasing hazard ratios (HRs) for stroke with increasing low-density lipoprotein (LDL) values above 1.5mmol/L. Statin use was associated with a lower stroke rate relative to non-users (hazard ratio 0.87, 95% confidence interval 0.81–0.93, p-value <0.0001). Conclusion LDL levels above 1.5mmol/L were independently associated with higher stroke rates in patients with AF, while statins were associated with lower stroke rates independent of anticoagulation. This suggests that LDL measurements may improve stroke risk stratification in AF, while statins may offer an underutilized pathway to lower stroke risk in AF. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): 1) Heart and stroke foundation of Canada HR for Stroke and LDL level