Lushun Yuan, Jihee Han, Shuzhen Cheng, Frits R Rosendaal, D. O. Mook-Kanamori, J Wouter Jukema, Hans Vink, Bernard M. van den Berg, Ton J Rabelink, Astrid van Hylckama Vlieg, Uwe J F Tietge, Ko Willems van Dijk, Ruifang Li-Gao
BACKGROUND: Recent evidence points to connections between HDLs (high-density lipoproteins), the coagulation system, and venous thromboembolism occurrence. However, uncertainty remains regarding the impact of specific HDL characteristics on the coagulation system. This study investigated associations between HDL characteristics and hemostatic parameters in a large middle-aged Dutch population. METHODS: H-nuclear magnetic resonance metabolomics platform, and coagulation parameters. These included coagulation factor (F) VIII, FIX, FXI, and fibrinogen, along with 5 parameters of the thrombin generation potential. In addition, the associations between HDL characteristics and parameters of platelet activation and endothelial glycocalyx health were tested in a subpopulation. RESULTS: Our findings revealed a particle size-dependent association between HDL parameters and coagulation parameters. Particularly, per 1-SD increase in the levels of components within XLHDL (very large HDL), we observed lower levels in FIX and FXI activities, endogenous thrombin potential, and peak height (median β [interquartile range], FIX: 3.26% [-3.50% to -3.18%]; FXI: -0.96% [-1.21% to -0.89%]; endogenous thrombin potential: -22.11 [-27.07 to -21.47] nmol/L·min; and peak height: -2.28 [-2.70 to -2.19] nmol/L), indicating an antithrombotic effect. In contrast, per 1-SD increase in the levels of components within MHDL and SHDL, we observed an increase in endogenous thrombin potential, peak height, and activities of FVIII, FIX, and FXI, indicating a prothrombotic effect. HDL characteristics were not associated with platelet activation parameters or with glycocalyx-related parameters. CONCLUSIONS: Our study provides evidence for a size-dependent relationship between HDL components and coagulation parameters. These findings contribute to a better understanding of the potential role of HDL in the pathogenesis of venous thromboembolism.