Abstract
BACKGROUND: Atrial fibrillation (AF) significantly increases stroke, heart failure, and mortality risk. Elevated lipoprotein(a) (Lp[a]) is implicated in AF pathogenesis, but its relationship with systemic inflammation (assessed by high-sensitivity C-reactive protein [hs-CRP]) remains unclear.
OBJECTIVE: We investigated whether the Lp(a)-AF association is independent of baseline inflammatory status.
METHODS: In this retrospective cohort study, we analyzed 365,899 United Kingdom (UK) Biobank participants without baseline AF. Lp(a) was modeled as a continuous exposure (per 50 nmol/L increase) and categorically (≥125 nmol/L). Systemic inflammation was defined as hs-CRP ≥2 mg/L. Multivariable Cox proportional hazards models (adjusted for age, sex, cardiovascular risk factors, and comorbidities) and Fine-Gray competing risk analyses estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident AF.
RESULTS: Over a median 13.5-year follow-up, 25,048 (6.8%) incident AF cases occurred. Elevated Lp(a) (7.44% vs 6.77%, log-rank P < .001) and hs-CRP (8.49% vs 5.96%, log-rank P < .001) were associated with higher incident AF. Cox proportional hazard model adjusted for covariates, higher Lp(a) (≥125 nmol/L) was associated with increased AF risk regardless of hs-CRP levels for AF (hs-CRP ≥2 mg/L: HR, 1.12; 95% CI, 1.06-1.19; P < .001; hs-CRP <2 mg/L: HR, 1.09; 95% CI, 1.04-1.15; P = .001). Results remained consistent in propensity score matched cohorts and sensitivity analyses.
CONCLUSION: Lp(a) is an independent risk factor for AF, irrespective of baseline inflammatory status, as measured by hs-CRP.