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LDL-c-linked SNPs are associated with LDL-c and myocardial infarction despite lipid-lowering therapy in patients with

Anton P van de Woestijne1, Yolanda van der Graaf, Paul I W de Bakker

  • 1Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.

European Journal of Clinical Investigation
|November 21, 2013
PubMed

Insights

Genetic variations linked to LDL-c influence vascular disease risk, particularly in patients on lipid-lowering therapy. These single-nucleotide polymorphisms (SNPs) increase LDL-c levels and may raise heart attack risk in treated individuals.

Area of Science:

  • Cardiovascular Genetics
  • Pharmacogenomics
  • Lipid Metabolism

Background:

  • Single-nucleotide polymorphisms (SNPs) are known to affect plasma low-density lipoprotein cholesterol (LDL-c) and coronary artery disease risk in the general population.
  • The relevance of these SNP associations in patients with existing vascular disease and their independence from lipid-lowering therapy remains unclear.

Purpose of the Study:

  • To investigate whether common LDL-c-associated SNPs are associated with plasma LDL-c levels and vascular event risk in patients with established vascular disease.
  • To determine if these associations are modified by lipid-lowering medication use.

Main Methods:

  • A prospective cohort study genotyped 5482 patients with vascular disease for four SNPs (rs11206510 (PCSK9), rs1122608 (LDLR), rs579459 (ABO), and rs599839 (SORT1)) known to associate with LDL-c and vascular risk.
  • Associations between LDL-c-increasing alleles, plasma LDL-c levels, and the risk of new vascular events were analyzed.

Main Results:

  • All tested SNPs significantly correlated with plasma LDL-c levels.
  • The association of rs579459 with LDL-c was not observed in patients using lipid-lowering medication.
  • In patients with high genetic risk (7-8 risk alleles), 59% on lipid-lowering medication failed to reach LDL-c target (<2.5 mM) compared to 45% with fewer risk alleles.
  • LDL-c-increasing alleles did not elevate vascular event risk in untreated patients.
  • However, in patients on lipid-lowering medication, each additional LDL-c-increasing allele was associated with a 14% increased risk of myocardial infarction.

Conclusions:

  • In patients with vascular disease, the studied SNPs consistently increase plasma LDL-c levels.
  • LDL-c-increasing alleles may increase myocardial infarction risk in patients undergoing lipid-lowering therapy, but not in those not receiving such treatment.
Abstract

Keywords:
LDL-cholesterolSNPsecondary preventionstatin

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