Evidence map›Paper›PMID 26286125›Full record

ArticleJournal of thrombosis and haemostasis : JTH2015

Coagulation factor XII genetic variation, ex vivo thrombin generation, and stroke risk in the elderly: results from the Cardiovascular Health Study.

N C Olson, S Butenas, L A Lange, E M Lange, M Cushman, N S Jenny, J Walston, J C Souto, J M Soria, G Chauhan and 5 more

Open access · bronzeAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 2 pooled it
0.5field-weighted citation impact, top 32% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 2 syntheses or guidelines pooled it, 16 citations in OpenAlex.

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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

15 authors at 7 institutions in 3 countries.

N C OlsonDepartment of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, VT, USA.
S ButenasDepartment of Biochemistry, University of Vermont College of Medicine, Burlington, VT, USA.
L A LangeDepartment of Genetics, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
E M LangeDepartment of Genetics, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
M CushmanDepartment of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, VT, USA.
N S JennyDepartment of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, VT, USA.
J WalstonDivision of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J C SoutoDepartment of Hematology, Institute of Biomedical Research (IIB-Sant Pau), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
J M SoriaUnit of Genomics of Complex Diseases, Institute of Biomedical Research (IIB-Sant Pau), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
G ChauhanINSERM U897, University of Bordeaux, Bordeaux, France.
S DebetteINSERM U897, University of Bordeaux, Bordeaux, France.
W T LongstrethDepartment of Neurology, University of Washington, Seattle, WA, USA.
S SeshadriDepartment of Neurology, Boston University School of Medicine, Boston, MA, USA.
A P ReinerDepartment of Epidemiology, University of Washington, Seattle, WA, USA.
R P TracyDepartment of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, VT, USA.
University of Vermont · USBoston University · USHospital de Sant Pau · ESUniversity of North Carolina at Chapel Hill · USUniversity of Washington · USInserm · FRJohns Hopkins Medicine · US

Funding

Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8M
UC Davis Alzheimer's Disease Core CenterP30AG010129 · NIA · UNIVERSITY OF CALIFORNIA DAVIS · PI MEYER, OANH L · 1991 to 2020
$28.3M
PRECURSORS OF STROKE INCIDENCE AND PROGNOSISR01NS017950 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Hugo Javier Aparicio, Jose Rafael Romero · 1985 to 2026
$22.9M
Genome-Wide Association Analysis in Essential Hypertension (FEHGAS study)R01HL086694 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ARAVINDA CHAKRAVARTI · 2007 to 2026
$21.2M
EPIDEMIOLOGY OF DEMENTIA IN THE FRAMINGHAM STUDYR01AG008122 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI AU, RHODA, SESHADRI, SUDHA · 1989 to 2015
$14.4M
Epidemiology of Venous Thrombosis & Pulmonary EmbolismR01HL059367 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI TANG, WEIHONG · 1998 to 2024
$11.8M
Exceptional Survival: Trajectories to Functional Aging (CHS All Stars)R01AG023629 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NEWMAN, ANNE B. · 2004 to 2016
$9.5M
The ARIC and Neurocognitive Longitudinal StudyR01HL070825 · NHLBI · UNIVERSITY OF MISSISSIPPI MEDICAL CENTER · PI MOSLEY, THOMAS H · 2002 to 2004
$5.1M
CHS Events Follow-up StudyU01HL080295 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M · 2005 to 2008
$4.6M
HEMOSTASIS &THROMBOSIS PROGRAM FOR ACADEMIC TRAINEEST32HL007594 · NHLBI · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI KELM, ROBERT J · 1985 to 2015
$4.6M
Collaborative GWAS of Dementia, AD and related MRI and Cognitive EndophenotypesR01AG033193 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI SESHADRI, SUDHA · 2009 to 2016
$4.4M
Thrombosis Genetics, MI and Stroke in Older AdultsR01HL071862 · NHLBI · UNIVERSITY OF WASHINGTON · PI REINER, ALEXANDER P · 2003 to 2012
$4.3M
NCRR NIH HHS UL1 RR025005NCRR NIH HHS UL1RR025005NHGRI NIH HHS U01 HG004402NHGRI NIH HHS U01HG004402NHLBI NIH HHS 5T32HL007894NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201100005CNHLBI NIH HHS HHSN268201100005GNHLBI NIH HHS HHSN268201100005INHLBI NIH HHS HHSN268201100006CNHLBI NIH HHS HHSN268201100007CNHLBI NIH HHS HHSN268201100008CNHLBI NIH HHS HHSN268201100008INHLBI NIH HHS HHSN268201100009CNHLBI NIH HHS HHSN268201100009INHLBI NIH HHS HHSN268201100010CNHLBI NIH HHS HHSN268201100011CNHLBI NIH HHS HHSN268201100011INHLBI NIH HHS HHSN268201100012CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS N01-HC-25195NHLBI NIH HHS N02 HL064278NHLBI NIH HHS R01 HL059367NHLBI NIH HHS R01 HL070825NHLBI NIH HHS R01 HL071862NHLBI NIH HHS R01 HL084099NHLBI NIH HHS R01 HL086694NHLBI NIH HHS R01HL086694NHLBI NIH HHS R01 HL087641NHLBI NIH HHS R01HL087641NHLBI NIH HHS R01HL59367NHLBI NIH HHS R01HL70825NHLBI NIH HHS R01 HL71862,NHLBI NIH HHS T32 HL007594NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01HL080295NIA NIH HHS P30 AG010129NIA NIH HHS R01 AG008122NIA NIH HHS R01 AG023629NIA NIH HHS R01AG023629NIA NIH HHS R01 AG033193NIA NIH HHS R01AG033193NINDS NIH HHS R01 NS017950NINDS NIH HHS R01 NS087541NINDS NIH HHS R01 NS17950PHS HHS U0149505
6 · The paper itself

Abstract

backgroundThe relationships of thrombin generation (TG) with cardiovascular disease risk are underevaluated in population-based cohorts.

objectivesTo evaluate the relationships of TG influenced by the contact and tissue factor coagulation pathways ex vivo with common single-nucleotide polymorphisms (SNPs) and incident cardiovascular disease and stroke. PATIENTS/

methodsWe measured peak TG (pTG) in baseline plasma samples of Cardiovascular Health Study participants (n = 5411), both with and without inhibitory anti-factor XIa antibody (pTG/FXIa(-) ). We evaluated their associations with ~ 50 000 SNPs by using the IBCv2 genotyping array, and with incident cardiovascular disease and stroke events over a median follow-up of 13.2 years.

resultsThe minor allele for an SNP in the FXII gene (F12), rs1801020, was associated with lower pTG in European-Americans (β = - 34.2 ± 3.5 nm; P = 3.3 × 10(-22) ; minor allele frequency [MAF] = 0.23) and African-Americans (β = - 31.1 ± 7.9 nm; P = 9.0 × 10(-5) ; MAF = 0.42). Lower FXIa-independent pTG (pTG/FXIa(-) ) was associated with the F12 rs1801020 minor allele, and higher pTG/FXIa(-) was associated with the ABO SNP rs657152 minor allele (β = 16.3 nm; P = 4.3 × 10(-9) ; MAF = 0.37). The risk factor-adjusted ischemic stroke hazard ratios were 1.09 (95% confidence interval CI 1.01-1.17; P = 0.03) for pTG, 1.06 (95% CI 0.98-1.15; P = 0.17) for pTG/FXIa(-) , and 1.11 (95% CI 1.02-1.21; P = 0.02) for FXIa-dependent pTG (pTG/FXIa(+) ), per one standard deviation increment (n = 834 ischemic strokes). In a multicohort candidate gene analysis, rs1801020 was not associated with incident ischemic stroke (β = - 0.02; standard error = 0.08; P = 0.81).

conclusionsThese results support the importance of contact activation pathway-dependent TG as a risk factor for ischemic stroke, and indicate the importance of F12 SNPs for TG ex vivo and in vivo.

Indexed as

AgedAge FactorsBlack or African AmericanBlood CoagulationBrain IschemiaFactor XIIFemaleGene FrequencyGenetic Predisposition to DiseaseHumansIncidenceMalePhenotypePolymorphism, Single NucleotideProspective StudiesRisk AssessmentFactor XIIThrombincardiovascular diseasesepidemiologyfactor XIIasingle nucleotide polymorphismsthrombin

Identifiers

PMID26286125
PMCPMC4946166
OpenAlexW2144114993

What OpenQuestion holds

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Registered trials

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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.