Pro-inflammatory interleukin-1 genotypes potentiate the risk of coronary artery disease and cardiovascular events mediated by oxidized phospholipids and lipoprotein(a).
J Am Coll Cardiol
; 63(17): 1724-34, 2014 May 06.
Article
em En
| MEDLINE
| ID: mdl-24530664
ABSTRACT
OBJECTIVES:
The aim of this study was to assess the influence of pro-inflammatory interleukin (IL)-1 genotype status on the risk for coronary artery disease (CAD), defined as >50% diameter stenosis, and cardiovascular events mediated by oxidized phospholipids (OxPLs) and lipoprotein (Lp) (a).BACKGROUND:
OxPLs are pro-inflammatory, circulate on Lp(a), and mediate CAD. Genetic variations in the IL-1 region are associated with increased inflammatory mediators.METHODS:
IL-1 genotypes, OxPL on apolipoprotein B-100 (OxPL/apoB), and Lp(a) levels were measured in 499 patients undergoing coronary angiography. The composite genotype termed IL-1(+) was defined by 3 single-nucleotide polymorphisms in the IL-1 gene cluster associated with higher levels of pro-inflammatory cytokines. All other IL-1 genotypes were termed IL-1(-).RESULTS:
Among IL-1(+) patients, the highest quartile of OxPL/apoB was significantly associated with a higher risk for CAD compared with the lowest quartile (odds ratio [OR] 2.84; p = 0.001). This effect was accentuated in patients age ≤60 years (OR 7.03; p < 0.001). In IL-1(-) patients, OxPL/apoB levels showed no association with CAD. The interaction was significant for OxPL/apoB (OR 1.99; p = 0.004) and Lp(a) (OR 1.96; p < 0.001) in the IL-1(+) group versus the IL-1(-) group in patients age ≤60 years but not in those age >60 years. In IL-1(+) patients age ≤60 years, after adjustment for established risk factors, high-sensitivity C-reactive protein, and Lp(a), OxPL/apoB remained an independent predictor of CAD. IL-1(+) patients above the median OxPL/apoB presented to the cardiac catheterization laboratory a mean of 3.9 years earlier (p = 0.002) and had worse 4-year event-free survival (death, myocardial infarction, stroke, and need for revascularization) compared with other groups (p = 0.006).CONCLUSIONS:
Our study suggests that IL-1 genotype status can stratify population risk for CAD and cardiovascular events mediated by OxPL. These data suggest a clinically relevant biological link between pro-inflammatory IL-1 genotype, oxidation of phospholipids, Lp(a), and genetic predisposition to CAD and cardiovascular events.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfolipídeos
/
Doença da Artéria Coronariana
/
DNA
/
Interleucina-1
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Lipoproteína(a)
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Polimorfismo de Nucleotídeo Único
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
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Male
/
Middle aged
País/Região como assunto:
America do norte
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article