Abstract
BackgroundThe atherogenic index of plasma (AIP) has been widely investigated in relation to cardiovascular disease (CVD). However, its association with major adverse cardiovascular events (MACE) among individuals with metabolic syndrome (MetS) remains unclear. We aimed to evaluate the association of AIP with incident MACE and its component endpoints among individuals with MetS.MethodsWe analyzed data from 131,736 UK Biobank participants with MetS who were free of MACE at baseline. The primary outcome was MACE, defined as the first occurrence of acute myocardial infarction (AMI), cardiovascular death (CV death), unstable angina (UA), stroke, or heart failure (HF). Cumulative incidence was estimated using Kaplan-Meier methods, and the association between baseline AIP and MACE was explored with multivariable Cox proportional hazards models. Additionally, nonlinearity in this association was examined with restricted cubic splines (RCS). The incremental predictive value of AIP for MACE was evaluated using the change in C-index ($$:varDelta:$$C-index), the net reclassification index (NRI), and the integrated discrimination improvement (IDI). Robustness of the findings was evaluated in prespecified subgroup and sensitivity analyses.ResultsDuring a median of 13.4 years of follow-up, 19,140 of the 131,736 participants with MetS experienced MACE (14.5%). Each standard deviation (SD) increase in AIP was associated with higher risks across multiple cardiovascular endpoints in this population. In fully adjusted models, AIP was associated with MACE (hazard ratio (HR), 1.07; 95% confidence interval (CI), 1.05,1.08), AMI (1.16; 1.12,1.19), and UA (1.16; 1.13,1.19), with no clear evidence of association for stroke (1.03; 1.00,1.06), CV death (1.01; 0.97,1.05), or HF (1.01; 0.98,1.03). Kaplan-Meier curve analysis demonstrated significant differences in the incidences of MACE, AMI, UA, CV death, and HF across AIP groups in the entire cohort (all log-rank P < 0.05), whereas stroke showed no significant difference (log-rank P > 0.05). RCS analyses indicated U-shaped associations for MACE, AMI, HF, and CV death and a J-shaped association for UA (all P for nonlinearity < 0.05), whereas the association with stroke was linear (P for nonlinearity > 0.05). Moreover, AIP improved reclassification metrics (NRI/IDI) and discriminative ability (C-index). Sensitivity analyses corroborated these primary findings.ConclusionsThis observational study showed that higher AIP was associated with increased risks of MACE and its component endpoints, highlighting its potential as a biomarker for risk stratification among individuals with MetS.Graphical abstract