Increased plasma thrombin potential is associated with stable coronary artery disease: An angiographically-controlled study.

INTRODUCTION: Coagulation plays a crucial role in coronary artery disease (CAD) contributing to both atherosclerotic plaque development and acute thrombotic complications, like myocardial infarction (MI). Coagulation biomarkers have been linked with ischemic heart disease, but results are still controversial. MATERIALS AND METHODS: D-dimer and thrombin generation, two "overall" coagulation assays, were evaluated in 775 subjects with or without angiographically-proven CAD (170 CAD-free and 605 CAD, 355 of whom with history of previous MI). Subjects taking anticoagulant drugs or with any acute illness were excluded. D-dimer plasma concentration was determined by an immuno-turbidimetric assay. Thrombin generation was assessed as the ability of plasma to generate thrombin triggered by the addition of tissue factor ex-vivo by means of a chromogenic method. RESULTS: Both D-dimer and thrombin generation parameters were associated with several traditional cardiovascular risk factors. Lag-time, time-to-peak, peak height, and Endogenous Thrombin Potential (ETP), as well as D-dimer levels, were higher in CAD patients than in CAD-free subjects. After adjustment for all the traditional risk factors, only ETP levels remained significantly associated with CAD (the highest versus the lowest tertile: OR 2.61 with 95%CI 1.14-5.99), but without improvement of C-statistic. The association of D-dimer vanished after adjustment for inflammatory markers. No difference of either D-dimer or thrombin generation parameters was found between CAD patients with or without previous MI history. CONCLUSIONS: Our results suggest that an increased plasma thrombin potential is characteristic in patients with clinically stable CAD, irrespective of previous MI history and independent of traditional cardiovascular risk factors.

Low levels of serum paraoxonase activities are characteristic of metabolic syndrome and may influence the metabolic-syndrome-related risk of coronary artery disease.

Low concentrations of plasma high-density lipoprotein (HDLs) are characteristic in metabolic syndrome (MS). The antioxidant ability of HDLs is, at least in part, attributable to pleiotropic serum paraoxonase (PON1). Different PON1 activities have been assessed in 293 subjects with (n = 88) or without MS (n = 205) and with (n = 195) or without (n = 98) angiographically proven coronary artery disease (CAD). MS subjects had low PON1 activities, with a progressively decreasing trend by increasing the number of MS abnormalities. The activity versus 7-O-diethyl phosphoryl,3-cyano,4-methyl,7-hydroxycoumarin (DEPCyMC), which is considered a surrogate marker of PON1 concentration, showed the most significant association with MS, independently of both HDL and apolipoprotein A-I levels. Subjects with MS and low DEPCyMCase activity had the highest CAD risk (OR 4.34 with 95% CI 1.44-13.10), while no significant increase of risk was found among those with MS but high DEPCyMCase activity (OR 1.45 with 95% CI 0.47-4.46). Our results suggest that low PON1 concentrations are typical in MS and may modulate the MS-related risk of CAD.