Cardiovascular risk factors in idiopathic compared to risk-associated venous thromboembolism: A focus on fibrinogen, factor VIII, and high-sensitivity C-reactive protein (hs-CRP).
ABSTRACT There have recently been reports of an increased incidence of arterial cardiovascular events in patients with idiopathic venous thromboembolism (VTE) compared to patients with risk-associated VTE. The aim of our study was to evaluate whether elevated clotting factors, which have been linked to chronic sub-clinical inflammation and arterial thromboembolic disease, have a higher prevalence in idiopathic VTE compared to secondary VTE. Plasma fibrinogen, factor VIII, and high-sensitivity C-reactive protein (hs-CRP) levels were determined in a cohort of sex- and age-matched patients with unprovoked VTE (n=101), patients with secondary VTE (n=101), and controls (n=202). Fibrinogen and hs-CRP levels were higher in patients with idiopathic VTE (fibrinogen: median/range: 331/214-524 mg/dl; hs-CRP: median/interquartile range: 1.8/0.8-3.7 mg/l) than in those with risk-associated VTE (299/162-458 mg/dl, p=0.004; 1.5/0.8-2.2 mg/l, p=0.05) and controls (302/185-644 mg/dl, p=0.001; 1.2/0.5-2.2 mg/l, p=0.02). Fibrinogen levels in the upper tertile of the controls were seen in 53% of patients with unprovoked VTE, compared to 35% of patients with secondary VTE. According to their hs-CRP levels (>3 mg/l), 26% of patients with idiopathic VTE were categorised as being at high risk for cardiovascular disease, as opposed to just 9% of those with risk-associated VTE. Factor VIII activity was significantly higher in patients with both idiopathic and secondary VTE than in controls, with the highest median value in patients with idiopathic VTE. Our data show that markers of inflammation, such as hs-CRP, fibrinogen, and factor VIII, are at higher levels in patients with idiopathic compared to secondary VTE, supporting the hypothesis that idiopathic VTE and arterial thromboembolism share common risk factors.