HDL particle concentration, but not HDL cholesterol, is inversely associated with mortality after liver transplantation

BACKGROUND: Liver transplant recipients (LTRs) are at increased risk of long-term mortality in part due to cardiometabolic complications. Dyslipidemia is common after transplantation, but conventional lipid measurements, such as high-density lipoprotein cholesterol (HDL-C), may capture different aspects of HDL compared with its particle concentration and size. Nuclear magnetic resonance (NMR) spectroscopy allows quantification of HDL particle concentration (HDL-P), subclasses (small, medium, and large), and size, which might better reflect the impact of HDL on morbidity and mortality. OBJECTIVE: To assess whether the HDL-P concentration is associated with mortality in LTRs in comparison with HDL-C. METHODS: We conducted a prospective cohort study within the TransplantLines biobank at the University Medical Center Groningen (NCT03272841). A total of 367 LTRs were included. Total HDL-P, subclasses, size, and HDL-C were quantified by NMR spectroscopy. The primary outcome was all-cause mortality. Associations between HDL markers and mortality were assessed using Cox proportional hazards regression models with adjustment for demographic, metabolic, inflammatory, and transplant-related factors. RESULTS: Over a median follow-up of 7.8 years (2530 person-years), 78 deaths occurred. Total and small HDL-P were inversely and independently associated with all-cause mortality; whereas large HDL-P and HDL size were positively associated with mortality. HDL-C was not associated with mortality. The inverse association of total HDL-P remained after adjustment for HDL-C. CONCLUSION: NMR-derived total HDL particle concentration, rather than HDL-C, is independently associated with all-cause mortality in LTRs. The opposing directionalities across HDL subclasses suggest that HDL-P captures dimensions of HDL not reflected by HDL-C itself and, hence, could represent a potentially important mortality biomarker in LTRs.