Abstract 20318: Elevated Levels of Lipoprotein(a) Are Causally Associated With Chronic Kidney Disease
Introduction: It remains unknown whether circulating Lipoprotein(a) [Lp(a)] levels and isoform size of apolipoprotein(a) [apo(a)] bound to Lp(a) are causally relevant to CKD.
Methods: We conducted measurements for Lp(a) levels and apo(a) isoform size in 10,765 participants enrolled in the Pakistan Risk of Myocardial Infarction Study (PROMIS). 1,420 participants were diagnosed to have CKD based on estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2. Lp(a) levels were measured using a high-sensitivity immunoturbidimetric assay, whereas apo(a) isoform size was measured using a validated qPCR assay that assesses CNV repeats in the exon-4 of the LPA gene. We compared the Odds Ratio (OR) for CKD conferred by observed increases in Lp(a) levels with equivalent differences caused by genetic variation due to rs10455872, a variant known to regulate Lp(a) levels. Data on 72,369 participants were available for rs10455872 in association with CKD through combined analyses of PROMIS and the CKDGEN consortium.
Results: Per standard deviation increase in log-Lp(a) levels was associated with increased risk of CKD in PROMIS independent of age, sex, type-2 diabetes, history of hypertension, and tobacco use (OR: 1.08; 95% CI. 1.01 - 1.14), whereas no significant association was observed between apo(a) isoform size and CKD risk. Per copy of the minor allele at rs10455872 was associated with an increase in Lp(a) levels in PROMIS participants (P-value 1.2x10-8). Genetically elevated Lp(a) levels by the minor allele at rs10455872 were associated with increased risk of CKD (OR: 1.02: p-value 3.5x10-3), which was directionally consistent with the OR observed for circulating Lp(a) concentration.
Conclusions: Elevated levels of Lp(a) may have a causal but modest effect on the risk of developing CKD.
Author Disclosures: J. Lin: None. W. Zhao: None. D.J. Rader: None. M. Reilly: None. D. Saleheen: None.
- © 2014 by American Heart Association, Inc.