de Laat-Kremers R, Di Castelnuovo A, van der Vorm L, Costanzo S, Ninivaggi M, Cerletti C, Huskens D, De Curtis A, Gialluisi A, Bai C, de Gaetano G, Yin D, Donati MB, de Laat B, and Iacoviello L
The coagulation system can be assessed by the thrombin generation (TG) assay, and increased TG peak height, endogenous thrombin potential (ETP), and velocity index are associated with an increased risk of thrombosis. Obesity had been reported to increase TG and is associated with dyslipidemia, which also predisposes to atherosclerotic cardiovascular disease (CVD). However, the effect of the blood lipid profile on TG has not been studied extensively. To gain more insight into the associations of TG, body mass index (BMI) and lipid profile, we studied TG in relation to these parameters in a large Italian population cohort, the Moli-sani study ( N = 22,546; age ≥ 35 years; 48% men). TG was measured in plasma samples collected at the enrollment of subjects in the Moli-sani study. TG was triggered with 1 or 5 pM tissue factor, and TG parameters lag time, peak, ETP, time-to-peak (TTP) and velocity index (VI). Additionally, thrombomodulin was added to assess the function of the activated protein C system during TG. In both women and men, overweight (BMI 25-30 kg/m 2 ) and obesity (BMI > 30 kg/m 2 ) were significantly associated with higher ETP, peak and VI (all p < 0.001). High total cholesterol, triglycerides and LDL-cholesterol levels were significantly associated with increased ETP and peak (all p < 0.001). Linear regression analysis revealed that the ETP is positively associated with both plasma LDL and HDL cholesterol levels, whereas the velocity index is positively associated with HDL cholesterol. Additionally, ETP, peak and VI were significantly associated with the plasma triglycerides content. In conclusion, our study shows significant associations of high BMI and blood lipid levels with increased TG parameters, and this hypercoagulability may partly explain the increased risk of CVD in individuals with obesity and/or dyslipidemia., Competing Interests: Synapse Research Institute is a non-for-profit organization, member of Diagnostica Stago SAS. RdLK, LvdV, MN, DH, CB, DY, and BdL are employees of Synapse Research Institute. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 de Laat-Kremers, Di Castelnuovo, van der Vorm, Costanzo, Ninivaggi, Cerletti, Huskens, De Curtis, Gialluisi, Bai, de Gaetano, Yin, Donati, de Laat, Iacoviello and the Moli-sani Investigators.)