Dual-high Lp(a) and inflammatory-lipid index carries an 8-fold MACE risk in 1,910 ACS patients with type 2 diabetes (Front Cardiovasc Med 2026)

Background And Aims: Lipoprotein(a) [Lp(a)] and inflammation are critical drivers of residual risk. We aimed to evaluate the combined prognostic value of Lp(a) and a novel Inflammatory-Lipid Index [defined as hs-CRP × (ApoB/ApoA1)] in patients with acute coronary syndrome (ACS) and type 2 diabetes mellitus (T2DM).

Methods And Results: A total of 1,910 patients with ACS and T2DM were analyzed over a median follow-up of 5.5 years. Multivariable Cox regression confirmed that both Lp(a) and the Inflammatory-Lipid Index were independent predictors of major adverse cardiovascular events (MACE). Restricted cubic splines revealed significant non-linear, positive correlations between these markers and MACE risk (both P for non-linearity <0.001). Patients were stratified into four subgroups based on median values. Those in the dual-high group [high Lp(a) and high Inflammatory-Lipid Index] had the highest risk, with a MACE incidence of 57.7% and an 8-fold higher risk compared to the dual-low reference (HR: 8.01; 95% CI: 4.41-14.56; P < 0.001). Formal interaction analysis showed that the multiplicative interaction term was not statistically significant, whereas additive interaction analysis suggested an excess joint risk on the additive scale. Addition of both biomarkers to the conventional risk model improved predictive performance and reclassification (C-statistic: 0.741; NRI: 0.569; IDI: 0.053; all P < 0.001). In a sensitivity analysis using 3-point MACE, the overall pattern of association remained similar.

Conclusions: Concomitant elevation of Lp(a) and the Inflammatory-Lipid Index identifies a particularly high-risk phenotype among ACS patients with T2DM. This dual-biomarker approach significantly enhances cardiovascular risk stratification beyond traditional factors.