Novel lipoprotein subfraction and size measurements in prediction of mortality in maintenance hemodialysis patients

Abstract

Background and objectives: Conventional lipid profiles usually cannot predict cardiovascular outcomes in chronic disease states. We hypothesized that novel lipoprotein subfraction concentrations and LDL particle size measurements better predict mortality in maintenance hemodialysis (MHD) patients.

Design, setting, participants, & measurements: Mortality-predictability of LDL particle diameter and lipoprotein subfraction concentrations, measured by novel ion mobility, was examined in a cohort of 235 hemodialysis patients who were followed for up to 6 years using Cox models with adjustment for important covariables.

Results: Patients were 54 ± 14 years old (mean ± SD) and included 45% women with total, LDL and HDL cholesterol levels of 143 ± 42, 76 ± 29, and 37 ± 12 mg/dl, respectively. Over 6 years, 71 patients (31%) died. Conventional lipid profile was not associated with mortality. The death hazard ratio (HR, 95% confidence interval) of the highest versus lowest quartiles of very small and large LDL particle concentrations were 2.43 (1.03 to 5.72) and 0.38 (0.15 to 0.96), respectively. Across increasing quartiles of LDL particle diameter, death HRs were 1.00, 0.93 (0.46 to 1.87), 0.43 (0.21 to 0.89), and 0.45 (0.31 to 1.00), respectively.

Conclusions: Whereas conventional lipid profile cannot predict mortality in MHD patients, larger novel LDL particle diameter or higher large LDL particle concentrations appear predictive of greater survival, whereas higher very small LDL particle concentration is associated with higher death risk. Examining lipoprotein subfraction modulation in chronic diseases is indicated.

Figure 1.

Schematic diagram of different aspects of LDL and HDL measurements.

Figure 2.

Bar diagram of hazard ratio of death according to categories (above median [AM] or below median [BM]) of LDL-C and LDL-P diameter after full adjustment. Median values for LDL-C and LDL-Pd are 73 mg/dl and 216.5 A, respectively. Full adjustment means adjustment for case mix (age, gender, race/ethnicity, diabetes mellitus, dialysis vintage, modified Charlson comorbidity score, and dialysis dose [single pool Kt/V]), lipids (triglyceride, LDL, and HDL particle concentration), malnutrition-inflammation complex syndrome (serum or blood levels of phosphorus, albumin, creatinine, calcium, ferritin, hemoglobin, normalized protein catabolic rate [also known as normalized protein nitrogen appearance], and body mass index), and inflammation (CRP, IL6, and TNF-α).

Figure 3.

Kaplan-Meier proportion of surviving MHD patients after 5 years of observation according to the categories of LDL cholesterol concentration and LDL particle diameter in 235 MHD patients.