Abstract

Introduction: Chronic inflammatory related disease (ChrIRD) is a novel outcome capturing non-cancer, non-cardiovascular clinical events driven by subclinical inflammation. Derangements in triglyceride-rich, low-density, and high-density lipoprotein particle (TRLp, LDLp, HDLp) subclass concentrations known to associate with inflammation and future cardiovascular disease have not been extensively evaluated in ChrIRD. Hypothesis: Lipoprotein particle subclasses may predict future ChrIRD in a similar direction and magnitude as with CVD. Methods: We measured 17 lipoprotein subclass particle concentrations by NMR spectroscopy in the Multi-Ethnic Study of Atherosclerosis (MESA). MESA is a US cohort including 6,759 White (38.6%), Chinese (11.9%), Black (27.6%), and Hispanic (22%) men and women initially aged 45-84 years and free of CVD. Participants were contacted at least annually to ascertain clinical events. Incident CVD (MI, Stroke, PAD, CV Death) and ChrIRD death/hospitalization risk per-quartile of lipoprotein marker levels were evaluated using disease-specific multivariable Cox regression models adjusted for traditional risk factors. Results: Disparate risk associations with ChrIRD and CVD were observed (Figure). Elevated small HDLp, total LDLp, and small TRLp, and were inversely associated with ChrIRD events. Additionally, larger TRLp size was associated higher ChrIRD risk. Metrics of HDL, LDL, and TRL associations with incident CVD as expected. In contrast, Very large TRLp was inverse with both clinical outcomes (HR [95% CI] CVD: 0.83 [0.75-0.96] ptrend=0.09, ChrIRD: 0.85 [0.69-0.99], ptrend =0.02). Conclusions: TRL, LDL, and HDL particles differentially associate with CVD and ChrIRD. Established predictors of CVD, including total TRL and LDL particles, small LDL, and large /medium TRL, may be inert or even protective in development of ChrIRD events due to distinct pathophysiologic contributions that warrant further investigation.

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