Page 167 - Haematologica July

Coagulation & its Disorders
C-reactive protein and risk of venous thromboembolism: results from a population-based case-crossover study
Gro Grimnes,1,2 Trond Isaksen,1,2 Ynse Ieuwe Gerardus Vladimir Tichelaar,1,3 Jan Brox,1,2 Sigrid Kufaas Brækkan1,2 and John-Bjarne Hansen1,2
1K.G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway; 2Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway and 3Department of Vascular Medicine, Academic Medical Center, University of Amsterdam,
ABSTRACT
Long-term, low-grade inflammation does not seem to be a risk fac- tor for venous thromboembolism. The impact of acute inflamma- tion, regardless of cause, on risk of venous thromboembolism is scarcely studied. We aimed to investigate the impact of acute inflam- mation, assessed by C-reactive protein, on short-term risk of venous thromboembolism. We conducted a case-crossover study of patients with venous thromboembolism (n=707) recruited from a general pop- ulation. Information on triggers and C-reactive protein levels were retrieved from hospital records during the 90 days before the event (hazard period) and in four preceding 90-day control periods. Conditional logistic regression was used to obtain β coefficients for change in natural log (ln) transformed C-reactive protein from control to hazard periods and to determine corresponding odds ratios for venous thromboembolism. Median C-reactive protein was 107 mg/L in the hazard period, and ranged from 7 mg/L to 16 mg/L in the control periods. The level of C-reactive protein was 58% (95% CI 39-77%) higher in the hazard period than in the control periods. A one-unit increase in ln-C-reactive protein was associated with increased risk of venous thromboembolism (OR 1.79, 95% CI 1.48-2.16). The risk esti- mates were only slightly attenuated after adjustment for immobiliza- tion and infection. In stratified analyses, ln-C-reactive protein was associated with increased risk of venous thromboembolism in cases with (OR 1.55, 95% CI 1.01-2.38) and without infection (OR 1.77, 95% CI 1.22-2.57). In conclusion, we found that acute inflammation, assessed by C-reactive protein, was a trigger for venous thromboem- bolism.
Introduction
Venous thromboembolism (VTE), consisting of deep vein thrombosis (DVT) and pulmonary embolism (PE), is a multicausal disease associated with substantial morbidity and mortality.1 Contrary to arterial thrombotic disease, there has been no decline in the incidence of VTE during the last decades.2,3 Thus, there is an unmet need for improved risk stratification and prevention of VTE.
Chronic inflammation is recognized as part of the pathophysiological process in arterial thrombosis,4 but its role in venous thrombosis has been less clear.5,6 Inflammatory biomarkers such as high-sensitivity C-reactive protein (hs-CRP) can predict long-term risk of arterial cardiovascular disease, but have not been associ- ated with risk of VTE in prospective studies with long-term follow up.7-9 However, in studies with shorter follow up time, inflammatory markers such as hs-CRP and neutrophil to lymphocyte ratio were associated with increased risk of VTE.10,11
Several conditions associated with increased risk of VTE, including cancer, acute infections, autoimmune diseases and obesity, share the feature of inflammation.12-
Ferrata Storti Foundation
the Netherlands
Haematologica 2018 Volume 103(7):1245-1250
Correspondence:
gro.grimnes@uit.no
Received: December 21, 2017. Accepted: April 18, 2018. Pre-published: April 19, 2018.
doi:10.3324/haematol.2017.186957
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/7/1245
©2018 Ferrata Storti Foundation
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