Effect of prothrombotic genotypes on the risk of venous thromboembolism in patients with and without ischemic stroke. The Tromsø Study
Author(s): ,
Ludvig B. Rinde
Affiliations:
K. G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway
Correspondence: Ludvig B. Rinde, K. G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, University of Tromsø The Arctic University of Norway, N‐9037, Norway|Tel.: +47 9713 4760|E‐mail ludvig.b.rinde@uit.no
,
Vania M. Morelli
Affiliations:
K. G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway
,
Birgit Småbrekke
Affiliations:
K. G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway
,
Ellisiv B. Mathiesen
Affiliations:
K. G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway. Brain and Circulation Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway
,
Maja‐Lisa Løchen
Affiliations:
Epidemiology of Chronic Diseases Research Group, Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway
,
Inger Njølstad
Affiliations:
K. G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway. Epidemiology of Chronic Diseases Research Group, Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway
,
Tom Wilsgaard
Affiliations:
Epidemiology of Chronic Diseases Research Group, Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway
,
Erin Smith
Affiliations:
K. G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway. Department of Pediatrics and Rady's Children's Hospital, University of California, San Diego, La Jolla, USA
,
Frits R. Rosendaal
Affiliations:
K. G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
,
Kelly A. Frazer
Affiliations:
K. G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway. Department of Pediatrics and Rady's Children's Hospital, University of California, San Diego, La Jolla, USA
,
Sigrid K. Brækkan
Affiliations:
K. G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway. Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
John‐Bjarne Hansen
Affiliations:
K. G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway. Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
ISTH Academy. Rinde L. May 1, 2019; 273600
Ludvig Rinde
Ludvig Rinde
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Journal Abstract
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Background
Patients with ischemic stroke have a transiently increased risk of subsequent venous thromboembolism (VTE). Prothrombotic genotypes may augment VTE risk under conditions of high thrombosis risk related to stroke.
Aims
To investigate the effect of prothrombotic genotypes in patients with ischemic stroke on the risk of VTE in a population‐based case–cohort study.
Methods
Cases with incident VTE (n = 664) and a randomly selected age‐weighted subcohort (n = 1817) were sampled from three surveys of the Tromsø Study (1994–2008). Participants were genotyped for ABO (rs8176719), F5 (rs6025), F2 (rs1799963), FGG (rs2066865) and F11 (rs2036914) single‐nucleotide polymorphisms (SNPs). Cox regression models were used to calculate hazard ratios (HRs) for incident VTE according to individual SNPs and categories of risk alleles (5‐SNP score; 0–1, 2, 3–4 and ≥ 5) in participants with and without ischemic stroke.
Results
There were 192 patients with incident stroke, of whom 43 developed VTE during a median of 15.2 years of follow‐up. The risk alleles of individual SNPs augmented the elevated VTE risk brought about by ischemic stroke. In stroke patients, a one‐category increase in the genetic risk score was associated with a 50% higher relative risk of overall VTE (HR 1.5, 95% confidence interval [CI] 1.3–1.8) and an 80% higher relative risk of provoked VTE (HR 1.8, 95% CI 1.5–2.1). Stroke patients with ≥ 5 risk alleles had a 12‐fold (HR 11.7, 95% CI 4.1–33.3) higher relative risk of VTE than stroke‐free participants with 0–1 risk alleles.
Conclusions
Prothrombotic genotypes increased the risk of VTE in stroke patients, and the risk increased with an increasing number of risk alleles.
Keyword(s)
epidemiology, genetics, risk factors, stroke, venous thromboembolism
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