Association Between High-Density Lipoprotein Characteristics and Hemostatic Parameters in the Netherlands Epidemiology of Obesity (NEO) Study-Brief Report

Abstract

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: 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.

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.

Keywords: antioxidants; cardiovascular diseases; thrombin; triglycerides; venous thromboembolism.

Figure 1.

Associations between HDL (high-density lipoprotein) characteristics and levels of coagulation parameters including endogenous thrombin potential (ETP), peak height, factor (F) VIII, FIX, FXI, and fibrinogen in the total population. A, After adjustment for age, sex, race, menopausal status, lipid-lowering drugs, C-reactive protein, total body fat, and body mass index, differences in the total population between HDL characteristics and levels of coagulation parameters were observed. The effect size with a 95% CI was depicted by a dot with a horizontal line. After multiple testing correction, nonsignificant associations were shown in gray, significant positive associations in red, and significant negative associations in blue. B, Particle size–dependent differences in the total population between HDL components and levels of coagulation parameters were illustrated. The median effect size and interquartile range of HDL components (ie, particle number and lipid content including total lipid, total cholesterol, free cholesterol, cholesterol ester, phospholipid, and triglyceride) for each particle size were shown. Detailed abbreviations of HDL characteristics are shown in Table S1. ApoA1 indicates apolipoprotein A1; HDL2C, total cholesterol in HDL2; HDL3C, total cholesterol in HDL3; HDLC, total cholesterol in HDL; HDLCE, cholesteryl esters in HDL; HDLD, average diameter for HDL particles; HDLFC, free cholesterol in HDL; HDLL, total lipids in HDL; HDLP, concentration of HDL particles; HDLPL, phospholipids in HDL; HDLTG, total triglycerides in HDL; LHDL, large HDL; MHDL, medium HDL; SHDL, small HDL; and XLHDL, very large HDL.

Figure 2.

Particle size–dependent differences between HDL (high-density lipoprotein) components and levels of coagulation parameters. After adjustment for age, race, menopausal status, lipid-lowering drugs, C-reactive protein, total body fat, and body mass index, as well as sex for the total population, the median effect size and interquartile range of the associations between HDL components (ie, particle number and lipid content including total lipid, total cholesterol, free cholesterol, cholesterol ester, phospholipid, and triglyceride) and coagulation parameters (ie, endogenous thrombin potential [ETP], peak height, factor (F) VIII, FIX, FXI, and fibrinogen) for each particle size in men, women, and the total population were shown. The red line represents women, the green line represents men, and the black line represents the total population.