Abstract

Background: Elevated remnant-like particle (RLP)-cholesterol (RLP-C) and high-sensitivity C-reactive protein (hsCRP) are each associated with atherosclerotic cardiovascular disease (ASCVD) individually. Whether a serum marker of systemic inflammation modifies RLP-C associated ASCVD risk is unknown. The purpose of this study was to evaluate the interplay of nuclear magnetic resonance (NMR)-derived RLP-C and hsCRP and their association with ASCVD risk in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: Lipoprotein particles were measured using NMR spectroscopic analysis among MESA participants. RLP-C includes very-low-density lipoprotein (VLDL)-cholesterol and intermediate-density lipoprotein (IDL)-cholesterol. Four groups were created as follows: Group 1: RLP-C ≤ median (≤29.14 mg/dL) and hsCRP < 2 mg/dL; Group 2: RLP-C ≤ median (≤29.14 mg/dL) and hsCRP≥ 2 mg/dL; Group 3: RLP-C > median (>29.14 mg/dL) and hsCRP level < 2 mg/dL; and Group 4: RLP-C > median (>29.14 mg/dL) and hsCRP level ≥ 2 mg/dL. Kaplan-Meier survival curves and multivariable adjusted Cox proportional hazard models were used to examine the relationship between RLP-C and hsCRP with incident ASCVD. Results: A total of 6,720 MESA participants (mean age 62.2 y, SD 10.2, 53% female) who had baseline NMR-derived RLP-C and hsCRP measurements were included. At a median follow-up of 15.6 years, a total of 1,032 ASCVD events were observed. In the fully adjusted model, compared to those in the reference group (Group 1), participants in Group 2, Group 3, and Group 4 demonstrated a 24% (95%CI, 1.02 - 1.50), 22% (1.01 - 1.46), and 47% (1.22 - 1.77) increased risk of incident ASCVD events, respectively (p <0.001). Conclusion: We found an independent association of NMR-derived RLP-C and hsCRP with incident ASCVD in an ethnically and geographically diverse population. Notably, the combination of increased RLP-C and hsCRP was associated with a markedly increased risk of future ASCVD events.

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