Abnormally high prevalence of major components of the metabolic syndrome in subjects with early-onset idiopathic venous thromboembolism

Abstract

Background

Although patients with idiopathic VTE are at higher than normal risk of asymptomatic atherosclerosis and of cardiovascular events, the impact of cardiovascular risk factors on VTE is poorly understood.

Objective

To assess the prevalence of the metabolic syndrome and of its components in patients with early-onset idiopathic VTE.

Methods

As many as 323 patients referred to our Thrombosis Ward for a recent (< 6-months) early-onset idiopathic venous thromboembolism (VTE), were compared with 868 gender- and age-matched subjects, in whom a history of venous thrombosis had been excluded, referred during the same period time to our Ward. All had undergone a clinical assessment for smoking habits and for the presence of the components of the metabolic syndrome.

Results

The metabolic syndrome was detected in 76/323 cases (23.5%) and in 81/868 controls (9.3%) (p < 0.001; OR:2.990; 95%C.I.:2.119-4.217). Smoking was more common in patients with idiopathic VTE than in controls. In addition to the metabolic syndrome as a whole, its major individual determinants (arterial hypertension, impaired fasting glucose plasma levels, abdominal obesity, hypertriglyceridemia, low HDL-cholesterol) significantly correlated with idiopathic VTE (p always < 0.05). The prevalence of thrombotic events was lower in females than in males (p = 0.000; OR:2.217), the latter being most often hypertensives, smokers, hypertriglyceridemics, carriers of a metabolic syndrome and of impaired fasting glucose than females. In a multivariate analysis, arterial hypertension, impaired fasting glucose, abdominal obesity, and hypercholesterolemia independently predicted idiopathic venous events.

Conclusions

Both metabolic syndrome as a whole and its major components individually considered, independently predict early-onset idiopathic VTE.

Introduction

Venous thromboembolism (VTE) is a common disorder in developed Countries, with an annual incidence of 1-2 events/1,000 people in the general population.[1] Because of its high prevalence, morbidity and mortality, it can be considered a major health concern. Several inherited and acquired risk factors have been identified in its pathogenesis.[2] However, there is still a large number of VTE patients in whom no established risk factor can be identified (idiopathic VTE). Arterial and venous thrombosis have been considered as distinct entities because of thrombi composition and different response to antiplatelet or anticoagulant drugs.[3] However, patients with idiopathic VTE show a higher incidence of cardiovascular disorders as compared to patients with episodes of secondary VTE.[4] Likewise, when compared to patients with secondary VTE or controls, a higher prevalence of asymptomatic atherosclerotic lesions in patients with idiopathic VTE have been reported.[5] Recent studies suggest that cardiovascular risk factors may contribute to idiopathic VTE and that VTE may be an early symptomatic event in patients at high cardiovascular risk.[6] The metabolic syndrome is a cluster of risk factors for atherosclerosis, including abdominal obesity, impaired fasting glucose plasma levels (IFG), arterial hypertension and dyslipidemia (high triglycerides and low HDL-cholesterol).[7], [8] This clinical condition is an emerging public health problem that affects approximately 23% of the population in the USA.[9] In Europe the prevalence varies, with a higher prevalence in the sixth decade of life.[10] An association between the metabolic syndrome and the risk of developing cardiovascular and cerebrovascular events has been documented.[11] Such association is at least in part accounted for by blood hypercoagulability that may occur as a result of abnormally high plasma levels of plasminogen activator inhibitor-1 (PAI-1), fibrinogen, factor (F) VII and FVIII, and von Willebrand factor as well as of endothelial activation, as expressed by increased circulating adhesion molecules (i.e. Inter-Cellular Adhesion Molecule 1 and Vascular Cell Adhesion Molecule 1).[12], [13], [14], [15], [16], [17], [18], [19] As to the VTE risk, the plausibility for an association with cardiovascular events is supported by common background mechanisms such as activation of platelets and of blood coagulation.[20] A variety of conditions (antiphospholipid syndrome, hyperhomocysteinemia) predisposes to both venous and arterial events.[21], [22], [23], [24] Although two recent studies argue for a relationship between subclinical atherosclerosis and the risk of future VTE,[25], [26] the link between cardiovascular risk factors and VTE remains elusive [3].

Ageno[6][Ageno W., 2006] reported an association between idiopathic VTE and the metabolic syndrome in subjects with mean ages ~ 60 yrs and Cihan confirmed these findings.[27] We have evaluated this issue in patients with a recent (< 6 months) history of idiopathic VTE occurring at younger age (< 50 yrs) and compared them with healthy gender- and age-matched subjects, referred during the same period time to our Thrombosis Ward.