Effects of second-generation antipsychotics and long-term atherogenic indices trajectories on metabolic syndrome in patients with schizophrenia

Abstract

Background: Atherogenic indices (AIs) predict metabolic abnormalities, yet their longitudinal patterns and interaction with antipsychotics in schizophrenia-related metabolic syndrome (MetS) remain unclear.

Methods: This longitudinal study composed of 469 MetS-free participants identified AIs trajectories from three follow-up assessments (2019-2021). Group-based trajectory modeling characterized atherogenic index of plasma (AIP), atherogenic coefficient (AC), and Castelli risk index II (CRI-II). Cox models evaluated combined effects of AIs trajectories and antipsychotic use at baseline on incident MetS (2022-2024).

Results: Over a median follow-up of 2.05 years, 155 participants developed MetS. Higher levels of AIP, AC, and CRI-II were linked to elevated MetS risk. AIP demonstrated superior predictive capacity (AUC = 0.632). Three AI trajectories-low-stable, moderate-stable, and high-stable-were identified. Compared to their low-stable trajectories, high-stable trajectories of AIP (HR 1.869, 95 % CI 1.062-3.290), AC (HR 1.921, 95 % CI 1.136-3.247), and CRI-II (HR 2.145, 95 % CI 1.271-3.620) were associated with significantly elevated MetS risk. A significant interaction was noted between olanzapine use and AIP trajectories (P for interaction = 0.004). Participants using olanzapine with a high-stable AIP exhibited the highest risk of incident MetS (HR: 3.266, 95 % CI: 1.461-7.300) compared to those using first-generation antipsychotics alongside classified into the low-stable AIP group.

Conclusions: Elevated AIs in schizophrenia patients are associated with increased MetS risk, with SGAs like olanzapine potentially amplifying this risk.

Keywords: Antipsychotics; Atherogenic indices; MetS; Trajectory.