Lipoprotein (a) concentrations, apolipoprotein (a) phenotypes, and peripheral arterial disease in three independent cohorts

Cardiovasc Res. 2014 Jul 1;103(1):28-36. doi: 10.1093/cvr/cvu107. Epub 2014 Apr 22.

Abstract

Aims: The relevance of lipoprotein(a) [Lp(a)] concentrations and low-molecular-weight (LMW) apo(a) phenotypes in peripheral arterial disease (PAD) has only been investigated by few studies. Therefore, we analysed this association in three independent cohorts and performed a Mendelian Randomization approach using instrumental variable regression.

Methods and results: Lp(a) concentrations, apo(a) phenotypes, and one SNP in the LPA gene (rs10455872) were measured in the CAVASIC study, including 241 male patients with intermittent claudication and 246 age- and diabetes-matched controls as well as in the two population-based studies KORA F3 (n = 3184) and KORA F4 (n = 3080). In KORA F3/F4, 109/80 persons suffered from intermittent claudication, 200/144 from PAD, and 128/103 showed an ankle-brachial index (ABI) <0.9. In CAVASIC, adjusted logistic regression analyses revealed significant associations between an increase of log-Lp(a) per one standard deviation (SD) (OR = 1.28, P = 0.02) as well as LMW apo(a) phenotypes and symptomatic PAD (OR = 1.65, P = 0.03). Linear regression models with continuous ABI showed a significant association in the combined analyses of KORA F3/F4: an increase in log-Lp(a) per one SD (β = -0.006, P = 0.005) and the presence of LMW apo(a) phenotypes (β = -0.011, P = 0.02) or the minor allele of rs10455872 (ß = -0.016, P = 0.03) were associated with a decrease in ABI in the fully adjusted linear and instrumental variable regression models.

Conclusion: Analyses in three independent populations showed significant associations of Lp(a) concentrations, LMW apo(a) phenotypes, and rs10455872 with PAD. This points to a causal relationship between Lp(a) and PAD since the genetically determined apo(a) phenotypes and SNP alleles are indeed associated with PAD.

Keywords: Ankle-brachial index; Apolipoprotein(a) phenotypes; Causality; Lp(a) concentrations; Mendelian randomization; Peripheral arterial disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Ankle Brachial Index
  • Apoprotein(a) / blood*
  • Apoprotein(a) / chemistry
  • Apoprotein(a) / genetics*
  • Cohort Studies
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Intermittent Claudication / blood
  • Intermittent Claudication / genetics
  • Intermittent Claudication / physiopathology
  • Linear Models
  • Lipoprotein(a) / blood*
  • Lipoprotein(a) / genetics*
  • Male
  • Middle Aged
  • Molecular Weight
  • Peripheral Arterial Disease / blood*
  • Peripheral Arterial Disease / genetics*
  • Peripheral Arterial Disease / physiopathology
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Risk Factors

Substances

  • Lipoprotein(a)
  • Apoprotein(a)