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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| Veröffentlicht in: | Atherosclerosis Jg. 203; H. 2; S. 371 - 376 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Journal Article |
| Sprache: | Englisch |
| Veröffentlicht: |
Amsterdam
Elsevier Ireland Ltd
01.04.2009
Elsevier |
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| ISSN: | 0021-9150, 1879-1484, 1879-1484 |
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| Abstract | 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. |
|---|---|
| AbstractList | 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. Abstract 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 153.9 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). 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. 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 153.9mg/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). 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. 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.OBJECTIVEA 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 153.9mg/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).METHODS AND RESULTSGenotypes 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).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.CONCLUSIONSIn 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. |
| Author | Luke, May M. Catanese, Joseph J. Louie, Judy Z. Chasman, Daniel I. Rowland, Charles M. Devlin, James J. Shiffman, Dov Ridker, Paul M. Zee, Robert Y.L. Buring, Julie E. |
| AuthorAffiliation | 4 Celera, Alameda, CA 94502 3 Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215 1 Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215 2 Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215 |
| AuthorAffiliation_xml | – name: 1 Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215 – name: 2 Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215 – name: 4 Celera, Alameda, CA 94502 – name: 3 Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215 |
| Author_xml | – sequence: 1 givenname: Daniel I. surname: Chasman fullname: Chasman, Daniel I. email: dchasman@rics.bwh.harvard.edu organization: Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, United States – sequence: 2 givenname: Dov surname: Shiffman fullname: Shiffman, Dov organization: Celera, Alameda, CA 94502, United States – sequence: 3 givenname: Robert Y.L. surname: Zee fullname: Zee, Robert Y.L. organization: Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, United States – sequence: 4 givenname: Judy Z. surname: Louie fullname: Louie, Judy Z. organization: Celera, Alameda, CA 94502, United States – sequence: 5 givenname: May M. surname: Luke fullname: Luke, May M. organization: Celera, Alameda, CA 94502, United States – sequence: 6 givenname: Charles M. surname: Rowland fullname: Rowland, Charles M. organization: Celera, Alameda, CA 94502, United States – sequence: 7 givenname: Joseph J. surname: Catanese fullname: Catanese, Joseph J. organization: Celera, Alameda, CA 94502, United States – sequence: 8 givenname: Julie E. surname: Buring fullname: Buring, Julie E. organization: Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, United States – sequence: 9 givenname: James J. surname: Devlin fullname: Devlin, James J. organization: Celera, Alameda, CA 94502, United States – sequence: 10 givenname: Paul M. surname: Ridker fullname: Ridker, Paul M. organization: Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, United States |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21399130$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/18775538$$D View this record in MEDLINE/PubMed |
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| Keywords | 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 |
| Language | English |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3 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. |
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| PublicationTitle | Atherosclerosis |
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| PublicationYear | 2009 |
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| Snippet | A minor allele variant (rs3798220) of apolipoprotein(a) has been reported to be associated with elevated plasma lipoprotein(a) [Lp(a)] and increased... Abstract Objective A minor allele variant (rs3798220) of apolipoprotein(a) has been reported to be associated with elevated plasma lipoprotein(a) [Lp(a)] and... |
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| SubjectTerms | 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 |
| Title | Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy |
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