ABSTRACT
OBJECTIVE: Data on C-reactive protein (CRP) as a risk indicator of venous thromboembolism are conflicting. A recent study reported higher CRP levels in homozygous carriers of a novel CRP gene polymorphism at the 3' UTR (CRP +1444C>T). We investigated, whether homozygosity for CRP +1444C>T is associated with an increased risk of spontaneous venous thromboembolism (VTE). METHODS AND RESULTS: CRP +1444C>T genotype and plasma levels were assessed in 128 patients with deep venous thrombosis (DVT, 70 females/58 males), 105 with pulmonary embolism (PE, 58 females/47 males) and 122 healthy individuals (60 females/62 males). CRP +1444TT was significantly associated with increased CRP plasma levels in healthy individuals. CRP +1444TT was more frequent (14%) among controls than DVT patients (9%, p=0.26) or PE patients (6%, p=0.05), respectively. No significant deviation from Hardy-Weinberg equilibrium was observed in patients (p=0.8) or controls (p=0.3), respectively. CRP +1444C>T was not significantly associated with CRP levels in patients with VTE. CONCLUSIONS: Homozygous carriers of the CRP 3' UTR +1444C>T polymorphism do not have a significantly increased risk of VTE. Our data support the assumption that a clinically relevant association between CRP and VTE is missing.
Subject(s)
C-Reactive Protein/genetics , Genetic Predisposition to Disease , Polymorphism, Genetic , Pulmonary Embolism/genetics , Venous Thrombosis/genetics , Austria , C-Reactive Protein/metabolism , Female , Homozygote , Humans , Male , Middle AgedABSTRACT
BACKGROUND: The post-thrombotic syndrome (PTS) is a frequent complication of deep vein thrombosis (DVT). Patients with recurrent ipsilateral DVT have an increased risk of PTS; other risk factors are unknown. OBJECTIVES: To establish risk factors of PTS and its impact on venous thrombotic disease. PATIENTS: We prospectively followed 406 patients after a first symptomatic DVT for a median of 60 months. Patients with recurrent DVT, a natural inhibitor deficiency, the lupus anticoagulant, cancer, long-term anticoagulation, an observation time < 18 months and DVT-recurrence prior PTS-assessment were excluded. Study outcomes were occurrence of PTS and recurrent symptomatic DVT. RESULTS: PTS was assessed after 44 +/- 23 months (mean +/- SD) using a clinical classification score. PTS developed in 176 of 406 patients (43.3%). Severe PTS was rare (1.4%). Proximal DVT was the strongest risk factor of PTS [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.3-3.7]. Male gender (OR 1.6, 95% CI 1.0-2.8) and elevated D-dimer levels (OR 1.9, 95% CI 1.0-3.9) were weaker risk factors. Factor V Leiden, factor II G20210A or high factor VIII did not confer an increased risk of PTS. At 4 years, the cumulative probability of recurrence was 7.4% (95% CI 3.2-11.7) among patients with PTS when compared with 1.6% (95% CI 0-3.5; P < 0.02) among patients without PTS. The risk of recurrence was 2.6-fold (95% CI 1.2-5.9) increased when PTS was present. CONCLUSIONS: Proximal DVT, male gender, and high D-dimer levels are independently associated with the development of PTS in patients with a first DVT. Patients with PTS have an increased risk of recurrent venous thromboembolism.
Subject(s)
Postphlebitic Syndrome/epidemiology , Thrombosis/epidemiology , Adult , Female , Fibrin Fibrinogen Degradation Products/analysis , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Postphlebitic Syndrome/etiology , Probability , Prospective Studies , Recurrence , Risk Factors , Sex Factors , Thromboembolism/complications , Thromboembolism/epidemiology , Thromboembolism/pathology , Thrombosis/complications , Thrombosis/pathology , Venous Thrombosis/complications , Venous Thrombosis/epidemiology , Venous Thrombosis/pathologyABSTRACT
High factor IX (FIX) is a risk factor of deep vein thrombosis. The impact of high FIX on the risk of recurrent venous thrombosis is unknown. We prospectively followed 546 patients after anticoagulation for a first spontaneous venous thromboembolism. Patients with a natural coagulation inhibitor deficiency, lupus anticoagulant or cancer were excluded. At 3 years, the likelihood of recurrence was 23% among patients with high FIX (exceeding the 75th percentile) compared with 11% among patients with lower levels. Among patients with high FIX, the relative risk of recurrence was 2.2 (95% CI: 1.3-3.6) before and was 1.6 (95% CI: 1.0-2.8) after adjustment for age, gender, duration of anticoagulation, FV Leiden, FII G20210A, high FVIII and hyperhomocysteinemia. Compared with patients with low factor IX (< 138 IU dL(-1)) and low FVIII (= 234 IU dL(-1)), the relative risk of recurrence was 1.5 among patients with high FIX and low FVIII, 2.7 among patients with low FIX and high FVIII and 6.6 among patients with high FIX and high FVIII. High levels of FIX confer an increased risk of recurrent venous thromboembolism and enhance the risk of recurrence among patients with high FVIII.