ABSTRACT
BACKGROUND: The cell adhesion molecule P-selectin has an important role in the pathophysiology of thrombosis. The effect on venous thromboembolism (VTE) of increased circulating concentrations of soluble P-selectin (sP-selectin) and their association with the P-selectin variant Thr715Pro is still uncertain. METHODS: This study was a case-control study of 116 patients with confirmed recurrent VTE and at least 1 event of unprovoked deep venous thrombosis or pulmonary embolism, and 129 age- and sex-matched healthy individuals. We measured sP-selectin by ELISA and P-selectin gene (SELP) variation by genotyping and sampled blood after a mean interval of 2.55 years after the most recent VTE event. RESULTS: The mean (SD) sP-selectin concentration was higher in patients than in controls: 47.3 (15.0) microg/L vs 36.8 (11.0) microg/L, P <0.001. The unadjusted odds ratio (OR) for sP-selectin >55.1 microg/L, representing the 95th percentile for controls, was 8.5 (95% CI, 3.7-23.3; P <0.001) and increased after adjustment for factor V Leiden, the prothrombin G20210A variant, increased factor VIII, and hyperhomocysteinemia (OR, 10.6; 95% CI, 4.1-31.2; P <0.001). Pro715 carriers were more prevalent among controls than patients (21.7% vs 14.7%). sP-selectin concentrations were lower in this subgroup than in noncarriers: 31.3 (7.9) microg/L vs 44.1 (14.1) microg/L; P <0.001). CONCLUSIONS: Increased sP-selectin concentrations are associated with VTE and genotype status. sP-selectin concentrations are lower in individuals carrying the P-selectin Pro715 variant than in those without this variant.
Subject(s)
P-Selectin/blood , P-Selectin/genetics , Thromboembolism/diagnosis , Venous Thrombosis/diagnosis , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , Genetic Predisposition to Disease , Genotype , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Probability , Pulmonary Embolism/diagnosis , Pulmonary Embolism/genetics , ROC Curve , Solubility , Thromboembolism/genetics , Venous Thrombosis/geneticsABSTRACT
BACKGROUND AND OBJECTIVES: The metabolic syndrome, defined by abdominal obesity, elevation of blood pressure, fasting glucose and triglycerides and low levels of high-density lipoprotein cholesterol is associated with atherosclerotic disease. It induces a pro-inflammatory and prothrombotic state. Despite its high prevalence, data on the association with venous thromboembolism (VTE) are scarce. The aim of our study was to elucidate the association of the metabolic syndrome with the risk of VTE. DESIGN AND METHODS: We conducted a case-control study to investigate the presence of the metabolic syndrome defined according to guidelines of the National Cholesterol Education Program, in high-risk patients with objectively confirmed recurrent VTE, who had had at least one unprovoked event of deep venous thrombosis or pulmonary embolism. Age and sex-matched healthy individuals served as controls. RESULTS: A total of 116 patients and 129 controls were enrolled. The prevalence of the metabolic syndrome was statistically significantly higher in patients (40/116, 35%) than in controls (26/129, 20%, p=0.012). The unadjusted odds ratio (OR) of the metabolic syndrome for VTE was 2.1 (95% CI [1.2-3.7], p=0.012) and remained statistically significant after adjustment for established thrombosis risk factors, sex and age (OR=2.2, 95% CI [1.1-4.3], p=0.020). Individuals with the metabolic syndrome (n=66) had significantly higher levels of high-sensitivity C-reactive protein (median, [interquartile range]: 0.312 mg/dL, [0.142-0.751] vs. 0.153 mg/dL, [0.073-0.330], p<0.001), fibrinogen (390 mg/dL, [342-432] vs. 343 mg/dL, [310-394], p<0.001) and factor VIII activity (182%, [157-216] vs. 159%, [133-199], p=0.005) compared to those without (n=179). INTERPRETATION AND CONCLUSIONS: The metabolic syndrome may contribute to the development of VTE and is associated with a two-fold increased risk of VTE.
