Association Between High-Density Lipoprotein Characteristics and Hemostatic Parameters in the Netherlands...

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.

Using baseline measurements from 6245 participants in NEO study (the Netherlands Epidemiology of Obesity), we performed adjusted linear regression analyses to estimate associations between 34 parameters of XLHDL (very large HDL), LHDL (large HDL), MHDL (medium HDL), and SHDL (small HDL) particles, as well as ApoA1 (apolipoprotein A1), quantified using a high-throughput ¹H-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.

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.

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.