Abstract
BACKGROUND: Atrial fibrillation (AF) confers a high risk of thromboembolism and cardiovascular events, which persists despite optimal oral anticoagulation (OAC). The non-high-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C) ratio (NHHR) integrates pro- and anti-atherogenic lipid fractions and has been linked to adverse outcomes in high-risk patient populations. The prognostic value of NHHR in anticoagulated AF patients is uncertain. We aimed to evaluate NHHR as a marker of residual thromboembolic and cardiovascular risk in this population. METHODS: Consecutive AF outpatients initiating OAC between January 2016 and November 2021 were enrolled in this prospective cohort study. NHHR was calculated from baseline non-HDL-C and HDL-C levels, and patients were stratified into two groups. Primary outcomes were thromboembolic events (i.e., composite of ischaemic stroke (IS), transient ischaemic attack (TIA), or systemic embolism) and major adverse cardiovascular events (MACE), comprising myocardial infarction, IS, TIA, or cardiovascular death. Secondary outcomes included cardiovascular and all-cause death. Restricted cubic spline (RCS) models assessed non-linear associations, and multivariable Cox models evaluated associations between NHHR and outcomes. RESULTS: 1694 patients (52.8% female; age 76 years [IQR 69-82]; follow-up 1.86 years [SD 0.4]) were included. During follow-up, 97 (5.7%) experienced a thromboembolic event and 126 (7.4%) experienced MACE. RCS analysis showed significant linear associations between continuous NHHR and primary outcomes (p-overall < 0.001). High NHHR was independently associated with increased risk of thromboembolic events (adjusted Hazard Ratio [aHR] 2.15; 95% CI 1.41-3.29; p < 0.001) and MACE (aHR 1.69; 95% CI 1.15-2.48; p = 0.007), compared to the low NHHR group. No significant associations were observed for secondary outcomes. CONCLUSIONS: In anticoagulated AF patients, high NHHR was independently associated with increased residual thromboembolic and cardiovascular risk. NHHR may improve cardiovascular risk stratification in patients with AF, although external validation in more ethnically diverse cohorts is warranted.