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LDL ‐c‐linked SNP s are associated with LDL ‐c and myocardial infarction despite lipid‐lowering therapy in patients with established vascular disease
Author(s) -
Woestijne Anton P.,
Graaf Yolanda,
Bakker Paul I. W.,
Asselbergs Folkert W.,
Borst Gert Jan,
Algra Ale,
Spiering Wilko,
Visseren Frank L. J.
Publication year - 2014
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/eci.12206
Subject(s) - medicine , single nucleotide polymorphism , myocardial infarction , coronary artery disease , population , snp , pcsk9 , prospective cohort study , cholesterol , allele , gastroenterology , endocrinology , ldl receptor , lipoprotein , cardiology , genotype , biology , genetics , environmental health , gene
Background Several single‐nucleotide polymorphisms ( SNP s) are associated with both plasma low‐density lipoprotein cholesterol ( LDL ‐c) level and coronary artery disease in the general population. It is unclear whether these associations also apply to patients with vascular disease and whether the associations are independent of lipid‐lowering therapy. Design Single‐nucleotide polymorphisms associated with plasma LDL ‐c and vascular risk in the general population (rs11206510 ( PCSK 9 ), rs1122608 ( LDLR ), rs579459 ( ABO ) and rs599839 ( SORT 1 )) were genotyped in a prospective cohort study of 5482 patients with vascular disease. We determined the association between LDL ‐c‐associated alleles and plasma LDL ‐c levels and the risk of new vascular events. Results All tested SNP s were associated with LDL ‐c plasma levels with a magnitude between +0·06 (95% CI 0·02–0·10) mM and +0·14 (95% CI 0·09–0·18) mM per LDL ‐c‐increasing allele. The associations were independent of the use of lipid‐lowering medication, except for rs579459, for which the association was not present in patients using lipid‐lowering medication. In patients with 7–8 risk alleles for these SNP s, 59% of the patients treated with lipid‐lowering medication did not reach the LDL ‐c target of <2·5 mM compared with 45% in patients with 3 or fewer risk alleles. LDL ‐c‐increasing alleles were not associated with increased risk of vascular events in patients not using lipid‐lowering medication ( HR s: 1·01; 95% CI: 0·93–1·09). In patients using lipid‐lowering medication, the risk of myocardial infarction increased with 14% ( HR s: 1·14; 95% CI: 1·01–1·28) per allele. Conclusions In patients with established vascular disease, the studied SNP s increase LDL ‐c plasma levels. LDL ‐c‐increasing alleles may be associated with increased risk of myocardial infarction in patients treated with lipid‐lowering medication, but not in patients not treated with lipid‐lowering medication.