Financiado en parte por Sanofi, Regeneron Pharmaceuticals, Fresenius Medical Care North America
Elevated lipoprotein(a) and risk of aortic valve stenosis in the general population
Kamstrup PR, Tybjærg-Hansen A, Nordestgaard BG
Journal of the American College of Cardiology · 471 citas
Etiquetas de revisión
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Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiado por la industria
- Empresa
- Sanofi
- Organización sin fines de lucro
- Hjerteforeningen
- Empresa
- Regeneron Pharmaceuticals
- Empresa
- Fresenius Medical Care North America
- Universidad u hospital
- Gentofte Hospital
- Universidad u hospital
- Herlev Hospital
- Organización sin fines de lucro
- Danish Heart Foundation
- Organización sin fines de lucro
- Johan and Lise Boserup's Fund
- Organización sin fines de lucro
- IMK Almene Fund
- Gobierno
- Danish Council for Independent Research Medical Sciences
Según 10 financiadores declarados.
Publicación
- Publicado
- 2013-10-23 · J Am Coll Cardiol · vol. 63 · número 5 · págs. 470–477
- Editorial
- Elsevier BV
- Citado
- 595 citas · más que el 100% de estudios similares · 18.9× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 32 trabajos
- Acceso
- Lectura gratuita
- Áreas de investigación
- Cardiac Valve Diseases and Treatments · Lipoproteins and Cardiovascular Health · Genetic Associations and Epidemiology
- Palabras clave
- lipoprotein(a), aortic stenosis, rs10455872, rs3798220, genetic risk, calcific aortic valve disease, Mendelian randomization, cardiovascular risk factors, Copenhagen City Heart Study, Copenhagen General Population Study, general population cohort
- MeSH
- humans, aortic valve stenosis, lipoprotein(a), severity of illness index, population surveillance, incidence, prevalence, risk assessment, risk factors, prospective studies, aged, middle aged, denmark, female, male, hyperlipoproteinemias, biomarkers
3 autores
- Pia R. Kamstrup🇩🇰Herlev Hospital; Copenhagen University Hospital
- Anne Tybjærg‐Hansen🇩🇰University of Copenhagen; Frederiksberg Hospital; Herlev Hospital; Copenhagen University Hospital; Rigshospitalet
- Børge Grønne Nordestgaard🇩🇰 · autor de correspondenciaUniversity of Copenhagen; Frederiksberg Hospital; Herlev Hospital; Copenhagen University Hospital
Resumen
El texto original del estudio, en el idioma en que se publicó.
Objectives
The purpose of this study was to determine whether elevated lipoprotein(a) levels and corresponding LPA risk genotypes (rs10455872, rs3798220, kringle IV type 2 repeat polymorphism) prospectively associate with increased risk of aortic valve stenosis (AVS).
Background
The etiologic basis of AVS is unclear. Recent data implicate an LPA genetic variant (rs10455872), associated with Lp(a) levels, in calcific AVS.
Methods
We combined data from 2 prospective general population studies, the Copenhagen City Heart Study (1991 to 2011; n = 10,803) and the Copenhagen General Population Study (2003 to 2011; n = 66,877), following up 77,680 Danish participants for as long as 20 years, during which time 454 were diagnosed with AVS. We conducted observational and genetic instrumental variable analyses in a Mendelian randomization study design.
Results
Elevated Lp(a) levels were associated with multivariable adjusted hazard ratios for AVS of 1.2 (95% confidence interval [CI]: 0.8 to 1.7) for 22nd to 66th percentile levels (5 to 19 mg/dl), 1.6 (95% CI: 1.1 to 2.4) for 67th to 89th percentile levels (20 to 64 mg/dl), 2.0 (95% CI: 1.2 to 3.4) for 90th to 95th percentile levels (65 to 90 mg/dl), and 2.9 (95% CI: 1.8 to 4.9) for levels greater than 95th percentile (>90 mg/dl), versus levels less than the 22nd percentile (<5 mg/dl; trend, p < 0.001). Lp(a) levels were elevated among carriers of rs10455872 and rs3798220 minor alleles, and of low number of KIV-2 repeats (trend, all p < 0.001). Combining all genotypes, instrumental variable analysis yielded a genetic relative risk for AVS of 1.6 (95% CI: 1.2 to 2.1) for a 10-fold Lp(a) increase, comparable to the observational hazard ratio of 1.4 (95% CI: 1.2 to 1.7) for a 10-fold increase in Lp(a) plasma levels.
Conclusions
Elevated Lp(a) levels and corresponding genotypes were associated with increased risk of AVS in the general population, with levels >90 mg/dl predicting a threefold increased risk.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.
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