Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy
Chasman DI, Shiffman D, Zee RY, Louie JZ, Luke MM, Rowland CM, Catanese JJ, Buring JE, Devlin JJ, Ridker PM
Atherosclerosis · 176 citas
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
- Financiación independiente
- Gobierno
- National Heart, Lung, and Blood Institute
- Gobierno
- National Cancer Institute
- Gobierno
- NCI NIH HHS
- Gobierno
- NHLBI NIH HHS
- Subvenciones
- National Heart, Lung, and Blood Institute (R01‐HL043851); National Cancer Institute (R01CA047988)
Según 4 financiadores declarados.
Publicación
- Publicado
- 2008-07-27 · Atherosclerosis · vol. 203 · número 2 · págs. 371–376
- Editorial
- Elsevier BV
- Citado
- 228 citas · más que el 98% de estudios similares · 9.4× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 33 trabajos
- Acceso
- Acceso abierto (copia en repositorio)
- Áreas de investigación
- Lipoproteins and Cardiovascular Health · Genetic Associations and Epidemiology · Paraoxonase enzyme and polymorphisms
- Palabras clave
- apolipoprotein(a), rs3798220, cardiovascular risk, low-dose aspirin, aspirin therapy, genetic susceptibility, Women's Health Study, gene-diet interaction
- MeSH
- humans, cardiovascular diseases, aspirin, apolipoproteins a, anti-inflammatory agents, non-steroidal, proportional hazards models, risk, genotype, heterozygote, homozygote, polymorphism, genetic, alleles, middle aged, female
10 autores
- Daniel I. Chasman🇺🇸Brigham and Women's Hospital; Harvard University
- Dov Shiffman
- Robert Y.L. Zee🇺🇸Brigham and Women's Hospital; Harvard University
- Judy Z. Louie
- May M. Luke
- Charles M. Rowland
- Joseph J. Catanese
- Julie E. Buring🇺🇸Brigham and Women's Hospital; Harvard University
- James J. Devlin
- Paul M. Ridker🇺🇸Brigham and Women's Hospital; Harvard University
Resumen
El texto original del estudio, en el idioma en que se publicó.
Objective
A minor allele variant (rs3798220) of apolipoprotein(a) has been reported to be associated with elevated plasma lipoprotein(a) [Lp(a)] and increased cardiovascular risk. We investigated whether this allele was associated with elevated Lp(a) and cardiovascular risk in the Women's Health Study, a randomized trial of low-dose aspirin, and whether aspirin reduced cardiovascular risk in minor allele carriers.
Methods and results
Genotypes of rs3798220 were determined for 25,131 initially healthy Caucasian participants. Median Lp(a) levels at baseline were 10.0, 79.5, and 153.9mg/dL for major allele homozygotes, heterozygotes, and minor allele homozygotes, respectively (P<0.0001). During the 9.9 years of follow-up, minor allele carriers (3.7%) in the placebo group had twofold higher risk of major cardiovascular events than non-carriers (age-adjusted hazard ratio (HR)=2.21, 95% CI: 1.39-3.52). Among carriers, risk was reduced more than twofold by aspirin: for aspirin compared with placebo the age-adjusted HR was 0.44 (95% CI: 0.20-0.94); risk was not significantly reduced among non-carriers (age-adjusted HR=0.91, 95% CI: 0.77-1.08). This interaction between carrier status and aspirin allocation was significant (P=0.048).
Conclusions
In the Women's Health Study, carriers of an apolipoprotein(a) variant had elevated Lp(a), doubled cardiovascular risk, and appeared to benefit more from aspirin than non-carriers.
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