Effects of antipsychotics on triglyceride trajectories and its implications in CVD: A longitudinal cohort study

BACKGROUND: Although the association between short-term antipsychotics exposure and triglycerides (TG) levels has been confirmed, the effects of long-term antipsychotics exposure on TG trajectories and its implications in cardiovascular disease (CVD) remains largely unknown. METHODS: A total of 39,988 participants with at least 3 TG measurements between January 2014 and February 2021 were included in this longitudinal study, with a median follow-up was 4.48 years. A latent class growth mixed model (LCGMM) was used to identify TG trajectories. Based on the LCGMM parameters, we calculated the area under the curve (AUC) and estimated the effect of antipsychotics on AUC and TG trajectory slopes. The primary outcome was CVD events. We also investigated and compared the association between antipsychotics and CVD in subgroups stratified by TG trajectory and TG levels. FINDINGS: A total of 11,543 CVD events were documented and the incidence density was 64.64 per 1000 person-years. We identified two TG trajectories labeled as inverse-U shape (30.77%, n=12306) and low-decreasing (69.23%, n=27682). The antipsychotic exposure increased total AUC by 13% and increased the slopes of TG trajectories before age 48 years. In the inverse-U and low-decreasing group, the adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for antipsychotics associated with CVD were 1.40 (1.21-1.62) and 1.29 (1.14-1.45), respectively, and the difference between the two trajectory groups become larger with the increase of the antipsychotic exposure. The association of antipsychotics with CVD (HR=1.72, 95%CI: 1.36-2.19) in inverse-U trajectory and high TG group was stronger than that in other subgroups. INTERPRETATION: Long-term antipsychotic exposure increased the TG burden and TG increase rate early in life. The strength of the association between antipsychotics and CVD risk in the inverse-U group was stronger than that in the low-decreasing group. FUNDING: The National Key Research and Development Program of China, Shandong Province Major Science and Technology Innovation Project, and National Natural Science Foundation of China.