Abstract

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. 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. 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. 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.

Highlights

  • The number of maintenance dialysis patients in the United States is currently over 400,000 and still growing fast [1]

  • Whereas conventional lipid profile cannot predict mortality in maintenance hemodialysis (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

  • Similar to individuals with chronic heart failure (CHF), the conventional cardiovascular disease (CVD) risk factors such as hypercholesterolemia are not associated with mortality in these patients; in both dialysis and CHF patients, a low, rather than a high, serum total cholesterol (TC) or LDL cholesterol (LDL-C) is associated with higher mortality, a phenomenon known as lipid paradox or reverse epidemiology [3,4,5,6]

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Summary

Introduction

The number of maintenance dialysis patients in the United States is currently over 400,000 and still growing fast [1]. Half of all dialysis patients die of cardiovascular disease (CVD) [1]. Conventional serum levels of LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) predict incident atherosclerotic CVD [2]. Similar to individuals with chronic heart failure (CHF), the conventional CVD risk factors such as hypercholesterolemia are not associated with mortality in these patients; in both dialysis and CHF patients, a low, rather than a high, serum total cholesterol (TC) or LDL-C is associated with higher mortality, a phenomenon known as lipid paradox or reverse epidemiology [3,4,5,6]. Novel CVD biomarkers including novel lipid measures are needed to more reliably risk-stratify dialysis or CHF patients

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