PCSK9 R46L, low-density lipoprotein cholesterol levels, and risk of ischemic heart disease: 3 independent studies and meta-analyses
Benn M, Nordestgaard BG, Grande P, Schnohr P, Tybjaerg-Hansen A
Journal of the American College of Cardiology · 252 citas
Cómo se estudió
- Diseño
- Metaanálisis (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiación independiente
- Organización sin fines de lucro
- Hjerteforeningen
- Gobierno
- Sundhed og Sygdom, Det Frie Forskningsråd
- Universidad u hospital
- Gentofte Hospital
- Universidad u hospital
- Rigshospitalet
- Gobierno
- Danish Medical Research Council
- Organización sin fines de lucro
- Henry Hansen and Wife's Grant
- Organización sin fines de lucro
- Chief Physician Johan Boserup and Lise Boserup's Fund
- Organización sin fines de lucro
- Danish Heart Foundation
- Organización sin fines de lucro
- Ingeborg and Leo Dannin's Grant
- Sin clasificar
- Research Fund
Según 10 financiadores declarados.
Publicación
- Publicado
- 2010-06-01 · J Am Coll Cardiol · vol. 55 · número 25 · págs. 2833–2842
- Editorial
- Elsevier BV
- Citado
- 314 citas · más que el 99% de estudios similares · 15.8× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 24 trabajos
- Acceso
- Lectura gratuita
- Áreas de investigación
- Lipoproteins and Cardiovascular Health · Genetic Associations and Epidemiology · Paraoxonase enzyme and polymorphisms
- Palabras clave
- PCSK9, LDL cholesterol, ischemic heart disease, myocardial infarction, mortality, genetic association, cardiovascular risk, hypolipidemic effect, Copenhagen City Heart Study, Copenhagen General Population Study, statins, LDL cholesterol lowering
- MeSH
- humans, myocardial ischemia, genetic predisposition to disease, serine endopeptidases, proprotein convertases, severity of illness index, incidence, confidence intervals, proportional hazards models, odds ratio, risk assessment, survival analysis, follow-up studies, gene expression regulation, polymorphism, genetic, alleles, adult, aged, middle aged, female, male, cholesterol, ldl, clinical trials as topic, genetic variation, proprotein convertase 9
5 autores
- Marianne Benn🇩🇰University of Copenhagen; Herlev Hospital; Rigshospitalet
- Børge Grønne Nordestgaard🇩🇰University of Copenhagen; Herlev Hospital; Bispebjerg Hospital
- Peer Grande🇩🇰University of Copenhagen; Rigshospitalet
- Peter Schnohr🇩🇰University of Copenhagen; Bispebjerg Hospital
- Anne Tybjærg-Hansen🇩🇰 · autor de correspondenciaUniversity of Copenhagen; Herlev Hospital; Bispebjerg Hospital; Rigshospitalet
Resumen
El texto original del estudio, en el idioma en que se publicó.
Objectives
The aim of this study was to examine the effect of PCSK9 R46L on low-density lipoprotein cholesterol (LDL-C), risk of ischemic heart disease (IHD), and mortality.
Background
The 46L allele has been associated with reductions in LDL-C and risk of IHD, but results vary between studies.
Methods
We determined the association of R46L genotype with LDL-C, risk of IHD, myocardial infarction (MI), and mortality in the prospective CCHS (Copenhagen City Heart Study) (n = 10,032) and validated the results in: 1) the cross-sectional CGPS (Copenhagen General Population Study) (n = 26,013); and 2) the case-control CIHDS (Copenhagen Ischemic Heart Disease Study) (n = 9,654). We also performed meta-analyses of present and previous studies (n = 66,698).
Results
In carriers (2.6%) versus noncarriers, the 46L allele was associated with reductions in LDL-C of 0.35 to 0.55 mmol/l (11% to 16%) from 20 to 80+ years in the general population (CCHS and CGPS; p values <0.0001). Observed risk reductions for IHD in 46L allele carriers were: 6% in the CCHS study (hazard ratio [HR]: 0.94; 95% confidence interval [CI]: 0.68 to 1.31), 46% in the CGPS study (odds ratio [OR]: 0.54; 95% CI: 0.39 to 0.77), 18% in the CIHDS study (OR: 0.82; 95% CI: 0.55 to 1.21), and 30% in the studies combined (OR: 0.70; 95% CI: 0.58 to 0.86). In the CCHS study, HR for mortality was 1.18 (95% CI: 0.93 to 1.50). In meta-analyses, 46L allele carriers had a 12% (0.43 mmol/l) reduction in LDL-C and a 28% reduction in risk of IHD (HR: 0.72; 95% CI: 0.62 to 0.84), similar to results in the CCHS, CGPS, and CIHDS studies combined. However, the observed 12% (0.43 mmol/l) reduction in LDL-C theoretically predicted an only 5% reduction in risk of IHD (HR: 0.95; 95% CI: 0.92 to 0.97).
Conclusions
The PCSK9 46L allele was associated with reductions in LDL-C from 20 to 80+ years in the general population. The reduction in risk of IHD was larger than predicted by the observed reduction in LDL-C alone. This could be because genotype is a better predictor of lifelong exposure to LDL-C than LDL-C measured in adult life.
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