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. 2025 May;27(5):2790-2799.
doi: 10.1111/dom.16286. Epub 2025 Mar 4.

Joint association of remnant cholesterol and lipoprotein-associated phospholipase A2 with composite adverse events: A 12-year follow-up study from Asymptomatic Polyvascular Abnormalities Community study

Yuhe Liu  1 , Liang Zhang  2 , Yuehao Xu  3 , Tianyun Zhou  4 , Wenqian Wu  1 , Kangnan Zhang  1 , Rongdi Xu  1 , Wangyang Chen  5 , Weifang Xu  6 , Yong Zhou  1 , Xingdong Zheng  1 , Baofu Chen  2
Affiliations

Joint association of remnant cholesterol and lipoprotein-associated phospholipase A2 with composite adverse events: A 12-year follow-up study from Asymptomatic Polyvascular Abnormalities Community study

Yuhe Liu et al. Diabetes Obes Metab. 2025 May.

Abstract

Aims: To explore the association of remnant cholesterol (RC) and lipoprotein-associated phospholipase A2 (Lp-PLA2) with composite adverse events in a large-scale prospective study.

Methods: All data were collected from the Asymptomatic Polyvascular Abnormalities Community study between 2010 and 2022. Serum cholesterol levels and Lp-PLA2 were determined by enzyme-linked immunosorbent assay. The participants were categorized into four groups based on their RC and Lp-PLA2 levels: low-RC/Lp-PLA2-, high-RC/Lp-PLA2-, low-RC/Lp-PLA2+ and high-RC/Lp-PLA2+. The composite endpoint was a combination of first-ever stroke, myocardial infarction or all-cause mortality. Cox regression analyses were performed to evaluate associations of RC and Lp-PLA2 with composite adverse events.

Results: Of the 1864 eligible participants, the average age was 60.6 years, and 74.3% were male. Over a follow-up of 12 years, we identified 500 composite adverse events, including 210 major adverse cardiovascular events and 342 all-cause deaths. When compared with the group of low-RC/Lp-PLA2-, the hazard ratios with 95% confidence intervals in the group of high-RC/Lp-PLA2+ for stroke, myocardial infarction, major adverse cardiovascular event, all-cause death and composite endpoints were 1.37 (0.87-2.16), 0.72 (0.28-1.82), 1.29 (0.85-1.95), 1.61 (1.10-2.38) and 1.43 (1.07-1.91), respectively. A significant interaction between RC and Lp-PLA2 status has been found for all-cause death and composite endpoint (p for interaction <0.05). In addition, joint association of RC and Lp-PLA2 with all-cause death was modified by sex and age of <60 versus ≥60 years (p for interaction: 0.035 and 0.01, respectively).

Conclusions: Elevated RC and Lp-PLA2 levels were associated with an increased risk of composite adverse events, with these associations significantly influenced by sex and age. Our study highlights the synergistic effect of RC and Lp-PLA2 on the composite adverse events.

Keywords: lipoprotein‐associated phospholipase A2; prospective study; remnant cholesterol.

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Conflict of interest statement

The authors declare no competing financial/non‐financial interests.

Figures

FIGURE 1
FIGURE 1
Cumulative risk of outcomes during a follow‐up of 12 years in the study population. Kaplan–Meier cumulative risk curves for stroke (A), MI (B), MACE (C), all‐cause death (D) and composite endpoint (E) in participants with RC and Lp‐PLA2 levels. Lp‐PLA2, lipoprotein‐associated phospholipase A2; MACE, Major adverse cardiovascular events; MI, myocardial infarction; RC, remnant cholesterol.
FIGURE 2
FIGURE 2
Restricted cubic spline curves for the association of RC and Lp‐PLA2 with the risk of all‐cause death and composite endpoint. Lp‐PLA2, lipoprotein‐associated phospholipase A2; RC, remnant cholesterol.
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