Evidence map›Paper›PMID 25035343›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2014

Polymorphisms in catechol-O-methyltransferase modify treatment effects of aspirin on risk of cardiovascular disease.

Kathryn T Hall, Christopher P Nelson, Roger B Davis, Julie E Buring, Irving Kirsch, Murray A Mittleman, Joseph Loscalzo, Nilesh J Samani, Paul M Ridker, Ted J Kaptchuk and 1 more

Registry-linked trialOpen access · greenAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03433586 (COMT on Aspirin Platelets Effects), which is not on this map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03433586 phase4unknown statusnot on this mapstarted 2020, after this paper: background citation

COMT on Aspirin Platelets Effects (CAPE)

TypeinterventionalSponsorBrigham and Women's HospitalRan2020 to 2022Enrolled45ConditionsCardiovascular DiseasesArmsAspirin 81 mg, Placebo
3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Article
  6. Article
  7. Catechol-O-Methyltransferase and Cardiovascular Disease: MESA.Journal of the American Heart Association · 2019
    Observational
  8. Drug-Placebo Additivity in Randomized Clinical Trials.Clinical pharmacology and therapeutics · 2019
    Article
  9. Article
  10. Article
  11. Article
  12. The Association Between C-Reactive Protein and Postoperative Delirium Differs by Catechol-O-Methyltransferase Genotype.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2019
    Article
  13. Potential Impact ofJournal of cardiovascular development and disease · 2018
    Article
  14. Pharmacogenomics and the Placebo Response.ACS chemical neuroscience · 2018
    Review
  15. Article
  16. Article
  17. The influence of dopamine-beta-hydroxylase and catecholDiabetology & metabolic syndrome · 2017
    Article
  18. Catechol-O-methyltransferase association with hemoglobin A1c.Metabolism: clinical and experimental · 2016
    Article
  19. Brain white matter structure and COMT gene are linked to second-language learning in adults.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  20. Genetics and the placebo effect: the placebome.Trends in molecular medicine · 2015
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Kathryn T HallFrom the Program in Placebo Studies, Division of General Medicine and Primary Care, Department of Medicine, Beth Israel Deaconess Medical Center (K.T.H., R.B.D., I.K., T.J.K.), Division of Preventative Medicine, Brigham and Women's Hospital (J.E.B., P.M.R., D.I.C.), and Department of Medicine, Brigham and Women's Hospital (J.L.), Harvard Medical School, Boston, MA (K.T.H., R.B.D., I.K., T.J.K, J.E.B., P.M.R., D.I.C, J.L., M.A.M.); Department of Cardiovascular Sciences, Clinical Research Centre, Glenfield General Hospital, University of Leicester, Leicester, United Kingdom (C.P.N., N.J.S.); Department of Psychology, Plymouth University, Plymouth, United Kingdom (I.K.); and Cardiovascular Epidemiology Research Unit, Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School and Harvard School of Public Health Boston, MA (M.A.M.). kthall@bidmc.harvard.edu.
Christopher P NelsonFrom the Program in Placebo Studies, Division of General Medicine and Primary Care, Department of Medicine, Beth Israel Deaconess Medical Center (K.T.H., R.B.D., I.K., T.J.K.), Division of Preventative Medicine, Brigham and Women's Hospital (J.E.B., P.M.R., D.I.C.), and Department of Medicine, Brigham and Women's Hospital (J.L.), Harvard Medical School, Boston, MA (K.T.H., R.B.D., I.K., T.J.K, J.E.B., P.M.R., D.I.C, J.L., M.A.M.); Department of Cardiovascular Sciences, Clinical Research Centre, Glenfield General Hospital, University of Leicester, Leicester, United Kingdom (C.P.N., N.J.S.); Department of Psychology, Plymouth University, Plymouth, United Kingdom (I.K.); and Cardiovascular Epidemiology Research Unit, Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School and Harvard School of Public Health Boston, MA (M.A.M.).
Roger B DavisFrom the Program in Placebo Studies, Division of General Medicine and Primary Care, Department of Medicine, Beth Israel Deaconess Medical Center (K.T.H., R.B.D., I.K., T.J.K.), Division of Preventative Medicine, Brigham and Women's Hospital (J.E.B., P.M.R., D.I.C.), and Department of Medicine, Brigham and Women's Hospital (J.L.), Harvard Medical School, Boston, MA (K.T.H., R.B.D., I.K., T.J.K, J.E.B., P.M.R., D.I.C, J.L., M.A.M.); Department of Cardiovascular Sciences, Clinical Research Centre, Glenfield General Hospital, University of Leicester, Leicester, United Kingdom (C.P.N., N.J.S.); Department of Psychology, Plymouth University, Plymouth, United Kingdom (I.K.); and Cardiovascular Epidemiology Research Unit, Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School and Harvard School of Public Health Boston, MA (M.A.M.).
Julie E BuringFrom the Program in Placebo Studies, Division of General Medicine and Primary Care, Department of Medicine, Beth Israel Deaconess Medical Center (K.T.H., R.B.D., I.K., T.J.K.), Division of Preventative Medicine, Brigham and Women's Hospital (J.E.B., P.M.R., D.I.C.), and Department of Medicine, Brigham and Women's Hospital (J.L.), Harvard Medical School, Boston, MA (K.T.H., R.B.D., I.K., T.J.K, J.E.B., P.M.R., D.I.C, J.L., M.A.M.); Department of Cardiovascular Sciences, Clinical Research Centre, Glenfield General Hospital, University of Leicester, Leicester, United Kingdom (C.P.N., N.J.S.); Department of Psychology, Plymouth University, Plymouth, United Kingdom (I.K.); and Cardiovascular Epidemiology Research Unit, Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School and Harvard School of Public Health Boston, MA (M.A.M.).
Irving KirschFrom the Program in Placebo Studies, Division of General Medicine and Primary Care, Department of Medicine, Beth Israel Deaconess Medical Center (K.T.H., R.B.D., I.K., T.J.K.), Division of Preventative Medicine, Brigham and Women's Hospital (J.E.B., P.M.R., D.I.C.), and Department of Medicine, Brigham and Women's Hospital (J.L.), Harvard Medical School, Boston, MA (K.T.H., R.B.D., I.K., T.J.K, J.E.B., P.M.R., D.I.C, J.L., M.A.M.); Department of Cardiovascular Sciences, Clinical Research Centre, Glenfield General Hospital, University of Leicester, Leicester, United Kingdom (C.P.N., N.J.S.); Department of Psychology, Plymouth University, Plymouth, United Kingdom (I.K.); and Cardiovascular Epidemiology Research Unit, Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School and Harvard School of Public Health Boston, MA (M.A.M.).
Murray A MittlemanFrom the Program in Placebo Studies, Division of General Medicine and Primary Care, Department of Medicine, Beth Israel Deaconess Medical Center (K.T.H., R.B.D., I.K., T.J.K.), Division of Preventative Medicine, Brigham and Women's Hospital (J.E.B., P.M.R., D.I.C.), and Department of Medicine, Brigham and Women's Hospital (J.L.), Harvard Medical School, Boston, MA (K.T.H., R.B.D., I.K., T.J.K, J.E.B., P.M.R., D.I.C, J.L., M.A.M.); Department of Cardiovascular Sciences, Clinical Research Centre, Glenfield General Hospital, University of Leicester, Leicester, United Kingdom (C.P.N., N.J.S.); Department of Psychology, Plymouth University, Plymouth, United Kingdom (I.K.); and Cardiovascular Epidemiology Research Unit, Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School and Harvard School of Public Health Boston, MA (M.A.M.).
Joseph LoscalzoFrom the Program in Placebo Studies, Division of General Medicine and Primary Care, Department of Medicine, Beth Israel Deaconess Medical Center (K.T.H., R.B.D., I.K., T.J.K.), Division of Preventative Medicine, Brigham and Women's Hospital (J.E.B., P.M.R., D.I.C.), and Department of Medicine, Brigham and Women's Hospital (J.L.), Harvard Medical School, Boston, MA (K.T.H., R.B.D., I.K., T.J.K, J.E.B., P.M.R., D.I.C, J.L., M.A.M.); Department of Cardiovascular Sciences, Clinical Research Centre, Glenfield General Hospital, University of Leicester, Leicester, United Kingdom (C.P.N., N.J.S.); Department of Psychology, Plymouth University, Plymouth, United Kingdom (I.K.); and Cardiovascular Epidemiology Research Unit, Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School and Harvard School of Public Health Boston, MA (M.A.M.).
Nilesh J SamaniFrom the Program in Placebo Studies, Division of General Medicine and Primary Care, Department of Medicine, Beth Israel Deaconess Medical Center (K.T.H., R.B.D., I.K., T.J.K.), Division of Preventative Medicine, Brigham and Women's Hospital (J.E.B., P.M.R., D.I.C.), and Department of Medicine, Brigham and Women's Hospital (J.L.), Harvard Medical School, Boston, MA (K.T.H., R.B.D., I.K., T.J.K, J.E.B., P.M.R., D.I.C, J.L., M.A.M.); Department of Cardiovascular Sciences, Clinical Research Centre, Glenfield General Hospital, University of Leicester, Leicester, United Kingdom (C.P.N., N.J.S.); Department of Psychology, Plymouth University, Plymouth, United Kingdom (I.K.); and Cardiovascular Epidemiology Research Unit, Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School and Harvard School of Public Health Boston, MA (M.A.M.).
Paul M RidkerFrom the Program in Placebo Studies, Division of General Medicine and Primary Care, Department of Medicine, Beth Israel Deaconess Medical Center (K.T.H., R.B.D., I.K., T.J.K.), Division of Preventative Medicine, Brigham and Women's Hospital (J.E.B., P.M.R., D.I.C.), and Department of Medicine, Brigham and Women's Hospital (J.L.), Harvard Medical School, Boston, MA (K.T.H., R.B.D., I.K., T.J.K, J.E.B., P.M.R., D.I.C, J.L., M.A.M.); Department of Cardiovascular Sciences, Clinical Research Centre, Glenfield General Hospital, University of Leicester, Leicester, United Kingdom (C.P.N., N.J.S.); Department of Psychology, Plymouth University, Plymouth, United Kingdom (I.K.); and Cardiovascular Epidemiology Research Unit, Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School and Harvard School of Public Health Boston, MA (M.A.M.).
Ted J KaptchukFrom the Program in Placebo Studies, Division of General Medicine and Primary Care, Department of Medicine, Beth Israel Deaconess Medical Center (K.T.H., R.B.D., I.K., T.J.K.), Division of Preventative Medicine, Brigham and Women's Hospital (J.E.B., P.M.R., D.I.C.), and Department of Medicine, Brigham and Women's Hospital (J.L.), Harvard Medical School, Boston, MA (K.T.H., R.B.D., I.K., T.J.K, J.E.B., P.M.R., D.I.C, J.L., M.A.M.); Department of Cardiovascular Sciences, Clinical Research Centre, Glenfield General Hospital, University of Leicester, Leicester, United Kingdom (C.P.N., N.J.S.); Department of Psychology, Plymouth University, Plymouth, United Kingdom (I.K.); and Cardiovascular Epidemiology Research Unit, Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School and Harvard School of Public Health Boston, MA (M.A.M.).
Daniel I ChasmanFrom the Program in Placebo Studies, Division of General Medicine and Primary Care, Department of Medicine, Beth Israel Deaconess Medical Center (K.T.H., R.B.D., I.K., T.J.K.), Division of Preventative Medicine, Brigham and Women's Hospital (J.E.B., P.M.R., D.I.C.), and Department of Medicine, Brigham and Women's Hospital (J.L.), Harvard Medical School, Boston, MA (K.T.H., R.B.D., I.K., T.J.K, J.E.B., P.M.R., D.I.C, J.L., M.A.M.); Department of Cardiovascular Sciences, Clinical Research Centre, Glenfield General Hospital, University of Leicester, Leicester, United Kingdom (C.P.N., N.J.S.); Department of Psychology, Plymouth University, Plymouth, United Kingdom (I.K.); and Cardiovascular Epidemiology Research Unit, Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School and Harvard School of Public Health Boston, MA (M.A.M.).
University of Plymouth · GBGlenfield Hospital · GBUniversity of Leicester · GB

Funding

HARVARD CLINICAL AND TRANSLATIONAL SCIENCE CENTER (UL1)UL1RR025758 · NCRR · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2008 to 2011
$91.4M
Women's Health Study: Continued Follow-upR01CA047988 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI BURING, JULIE E., LEE, I-MIN · 1991 to 2014
$28.2M
Research Training in Complementary and Integrative MedicineT32AT000051 · NCCIH · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI GLORIA Y YEH · 1999 to 2026
$10.2M
Women's Health Study: Continued Follow-UpR01HL080467 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI BURING, JULIE E. · 2005 to 2010
$4.5M
GPx-3 and Peroxide Flux in the Endothelial CellR37HL061795 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LOSCALZO, JOSEPH · 2007 to 2016
$4.3M
Omics and Variable Responses to Placebo and Acupuncture in Irritable Bowel SyndroR01AT004662 · NCCIH · BETH ISRAEL DEACONESS MEDICAL CENTER · PI KAPTCHUK, TED, KOKKOTOU, EFI G. · 2009 to 2013
$2.3M
TRIAL OF VITAMIN E, BETA-CAROTENE &ASPRIN IN WOMENR01HL043851 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI BURING, JULIE E · 1991 to 2000
$1.6M
Mentoring and Research in Placebo Studies, Asian Medicine, and CAMK24AT004095 · NCCIH · HARVARD MEDICAL SCHOOL · PI KAPTCHUK, TED · 2007 to 2016
$1.4M
Integrative Healing Model in IBS (RMI)R21AT002860 · NCCIH · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI KAPTCHUK, TED · 2004 to 2005
$254k
GINSENG'S EFFECTS ON MRNA PROFILES IN A DIABETES-2 MODELF32AT000051 · NCCIH · UNIVERSITY OF TEXAS AUSTIN · PI PAN, SHUJIA J · 1999 to 2001
$96k
NCCIH NIH HHS 3R01AT004662-02S1NCCIH NIH HHS F32 AT000051NCCIH NIH HHS K24 AT004095NCCIH NIH HHS K24AT004095NCCIH NIH HHS R01AT004662NCCIH NIH HHS R21 AT002860NCCIH NIH HHS R21AT002860NCCIH NIH HHS T32 AT000051NCCIH NIH HHS T32AT000051NCI NIH HHS CA047988NCI NIH HHS R01 CA047988NCRR NIH HHS UL1 RR 025758NCRR NIH HHS UL1 RR025758NHLBI NIH HHS HL080467NHLBI NIH HHS R01 HL043851NHLBI NIH HHS R01 HL080467NHLBI NIH HHS R37 HL061795
6 · The paper itself

Abstract

objectiveCatechol-O-methyltransferase (COMT), a key enzyme in catecholamine metabolism, is implicated in cardiovascular, sympathetic, and endocrine pathways. This study aimed to confirm preliminary association of COMT genetic variation with incident cardiovascular disease (CVD). It further aimed to evaluate whether aspirin, a commonly used CVD prevention agent, modified the potential association of COMT with incident CVD. APPROACH AND

resultsWe examined COMT polymorphism rs4680 (MAF [minor allele frequency], 0.47), encoding a nonsynonymous methionine-to-valine substitution, in the Women's Genome Health Study (WGHS), a large population-based cohort of women with randomized allocation to aspirin or vitamin E when compared with placebo and 10-year follow-up. Rs4680 effects were confirmed with COMT polymorphism rs4818 and also examined in Coronary ARtery DIsease Genome-wide Replication and Meta-analysis/The Coronary Artery Disease Genetics Consortium, consortia for genome-wide association studies of coronary artery disease. Among WGHS women allocated to placebo (135 events/n=5811), the rs4680 valine allele was protective against incident CVD relative to the methionine (hazard ratio [HR; 95% confidence interval {CI}], 0.66 [0.51-0.84]; P=0.0007); an association also observed in Coronary ARtery DIsease Genome-wide Replication and Meta-analysis and The Coronary Artery Disease Genetics Consortium (combined P=2.4×10(-5)). In the WGHS, the rs4680 association was abolished by randomized allocation to aspirin, such that valine/valine women experienced higher CVD rates with aspirin allocation when compared with placebo (HR [95% CI], 1.85 [1.05-3.25]; P=0.033), whereas methionine/methionine women experienced lower rates (HR [95% CI], 0.60 [0.39-0.93]; P=0.023). Allocation to vitamin E also conferred higher but nonsignificant CVD rates on valine/valine (HR [95% CI], 1.50 [0.83-2.70]; P=0.180) when compared with significantly lower rates on methionine/methionine (HR [95% CI], 0.53 [0.34-0.84]; P=0.006) women. Rs4818 results were similar.

conclusionsCommon COMT polymorphisms were associated with incident CVD, and this association was modified by randomized allocation to aspirin or vitamin E. Replication of these findings is required.

Indexed as

Polymorphism, Single NucleotideAmino Acid SubstitutionAspirinCardiovascular DiseasesCatechol O-MethyltransferaseFemaleFollow-Up StudiesGenome-Wide Association StudyHumansIncidenceMeta-Analysis as TopicMiddle AgedProportional Hazards ModelsProspective StudiesRandomized Controlled Trials as TopicRisk FactorsAspirinCatechol O-MethyltransferaseCOMT protein, humanVitamin Easpirincatecholaminesvitamin E

Identifiers

PMID25035343
PMCPMC4148908
OpenAlexW2160091096

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.