Small Apolipoprotein(a) Size Predicts Mortality in End-Stage Renal Disease

Abstract

Background— The high mortality rate in end-stage renal disease has engendered interest in nontraditional atherosclerotic cardiovascular disease (ASCVD) risk factors that are more prevalent in end-stage renal disease, such as elevated lipoprotein(a) [Lp(a)] levels. Previous studies suggest that high Lp(a) levels and small apolipoprotein(a) [apo(a)] isoform size are associated with ASCVD, but none have investigated the relationship between Lp(a) level, apo(a) size, and mortality. Methods and Results— An inception cohort of 864 incident dialysis patients was followed prospectively. Lp(a) was measured by an apo(a) size-independent ELISA and apo(a) size by Western blot after SDS-agarose gel electrophoresis. Comorbid conditions were determined by medical record review. Time to death was ascertained through dialysis clinic and Health Care Financing Administration follow-up. Survival analyses were performed with adjustment for baseline demographic, comorbid conditions, albumin, and lipids. Median follow-up was 33.7 months, with 346 deaths, 162 transplantations, and 10 losses to follow-up during 1999 person-years of follow-up. Cox regression analysis showed no association between Lp(a) level and mortality. However, an association between small apo(a) isoform size and mortality was found (hazard ratio, 1.36; P =0.004) after adjusting for age, race, sex, comorbidity score, cause of renal disease, and congestive heart failure. The association was somewhat lower in white patients (hazard ratio 1.34; P =0.019) than in black patients (1.69; P =0.04). No interaction by age, race, sex, diabetes, ASCVD, or Lp(a) level was present. Conclusions— Small apo(a) size, but not Lp(a) level, independently predicts total mortality risk in dialysis patients.