C-reactive protein and risk of venous thromboembolism in the general population.
OBJECTIVE
To examine the robustness of the association between C-reactive protein (CRP) levels and increased risk of venous thromboembolism (VTE) and to examine whether genetically elevated CRP levels cause VTE.


RESULTS
In the prospective Copenhagen City Heart Study, we observed 10 388 participants for longer than 16 years, of whom 484 developed a VTE. In the cross-sectional Copenhagen General Population Study, we studied 36 616 participants, of whom 903 previously had a VTE. Levels of CRP greater than 3 mg/L versus less than 1 mg/L were associated with a 2.3- and 2.4-fold increased risk of VTE in the Copenhagen City Heart Study and the Copenhagen General Population Study, respectively. CRP levels in tertiles, quintiles, and octiles associated with a stepwise increase in VTE risk. CRP genotypes associated with an increase in plasma CRP levels up to 59% but did not associate consistently with risk of VTE in either study. The causal odds ratio for VTE for a doubling in genetically elevated CRP on instrumental variable analyses was lower than the odds ratio for VTE observed for a doubling in plasma CRP on logistic regression ([odds ratio and 95% CI] 0.80 [0.56 to 1.12] versus 1.17 [1.08 to 1.27]; P=0.04).


CONCLUSIONS
We observed 47,000 participants from the general population, of whom 1387 developed VTE. Although elevated CRP levels robustly associated with increased risk of VTE, this may not necessarily be a causal association because genetically elevated CRP did not associate with VTE risk.
Zacho
Jeppe
J
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Tybjaerg-Hansen
Anne
A
Nordestgaard
Børge G
BG
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D003430:Cross-Sectional Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D015854:Up-Regulation; D054556:Venous Thromboembolism / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*
D015415:Biomarkers; D018836:Inflammation Mediators; D002097:C-Reactive Protein