Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy

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...

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Published in:Atherosclerosis Vol. 203; no. 2; pp. 371 - 376
Main Authors: Chasman, Daniel I., Shiffman, Dov, Zee, Robert Y.L., Louie, Judy Z., Luke, May M., Rowland, Charles M., Catanese, Joseph J., Buring, Julie E., Devlin, James J., Ridker, Paul M.
Format: Journal Article
Language:English
Published: Amsterdam Elsevier Ireland Ltd 01.04.2009
Elsevier
Subjects:
Alleles
Anti-Inflammatory Agents, Non-Steroidal - therapeutic use
Apolipoproteins A - blood
Apolipoproteins A - genetics
Aspirin
Aspirin - therapeutic use
Atherosclerosis (general aspects, experimental research)
Biological and medical sciences
Blood and lymphatic vessels
Blood. Blood coagulation. Reticuloendothelial system
Cardiology. Vascular system
Cardiovascular
Cardiovascular disease
Cardiovascular Diseases - blood
Cardiovascular Diseases - genetics
Female
Genetics
Genotype
Heterozygote
Homozygote
Humans
Lipoproteins
Lp(a)
Medical sciences
Middle Aged
Pharmacology. Drug treatments
Polymorphism, Genetic
Proportional Hazards Models
Risk
Cardiovascular disease
Genetics
Aspirin
Lipoproteins
Lp(a)
Prostaglandin-endoperoxide synthase
Enzyme
Low dose
Enzyme inhibitor
Acetylsalicylic acid
Antiplatelet agent
Lipoprotein a
Vascular disease
Non steroidal antiinflammatory agent
Apolipoprotein A
Analgesic
Treatment
Atherosclerosis
Antipyretic
Oxidoreductases
Salicylates
Polymorphism
ISSN:0021-9150, 1879-1484, 1879-1484
Online Access:Get full text
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Summary: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. Genotypes of rs3798220 were determined for 25,131 initially healthy Caucasian participants. Median Lp(a) levels at baseline were 10.0, 79.5, and 153.9 mg/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). 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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Dov Shiffman, Judy Z. Louie, May M. Luke, Charles M. Rowland, Joseph J. Catanese, and James J. Devlin disclose that they are employees of Celera.
ISSN:0021-9150
1879-1484
1879-1484
DOI:10.1016/j.atherosclerosis.2008.07.019