Apolipoproteins and lipoprotein(a) as factors modulating fibrin clot properties in patients with severe aortic stenosis

Abstract

Background and aims: Large amounts of clot-bound lipoproteins were reported in proteomic analysis of plasma clot but their impact on fibrin clot properties is unknown. We investigated a contribution of lipid profile and apolipoproteins (apo) to the prothrombotic plasma fibrin clot phenotype in patients with aortic stenosis (AS).

Methods: In 138 patients with isolated severe AS, we determined serum apoA-I, A-II, B, C-II, C-III, E, oxidized low-density lipoprotein (OxLDL) and lipoprotein(a) concentrations. Plasma fibrin clot permeability (Ks), maximal absorbance (MaxAbs_CLT2018 and MaxAbs_Lys50), and fibrinolytic capacity were studied using 3 plasma-based lysis assays (CLT2018, CLT, and Lys50), and compared with well-matched patients without AS (control group).

Results: After adjustment for confounding factors, including statin use, only low-density lipoprotein cholesterol (LDL-C) and apoB levels were inversely associated with Ks. Triglycerides, apoC-II, and C-III were associated with MaxAbs_CLT2018 and MaxAbs_Lys50, explaining 56-64% of their variability. CLT2018 and CLT showed associations with total cholesterol, LDL-C, triglycerides, and OxLDL as well as with apoB, C-II, C-III, and E. ApoA-I, C-II, and C-III but not serum lipids were associated with Lys50. Only CLT2018 was associated with lipoprotein(a). ApoC-III, B, A-I, and E along with estimated glomerular filtration rate and OxLDL predicted hypofibrinolysis in multiple regression analysis. AS patients had higher lipoprotein(a) (+34.9%) and apoA-I (+25.9%) levels and less compact fibrin clots (-13.3% lower MaxAbs_CLT2018, -53.2% lower MaxAbs_Lys50, and +28.3% higher Ks) displaying higher susceptibility to lysis (-17.9% lower Lys50) in comparison with control group.

Conclusions: Apolipoproteins and OxLDL contribute to prothrombotic fibrin clot phenotype in severe AS. Moreover, apolipoproteins better than serum lipids predicted hypofibrinolysis, which provides additional argument for a role of elevated lipoproteins in the prothrombotic state.

Keywords: Aortic stenosis; Apolipoproteins; Fibrinolysis; Lipoproteins; Oxidized low-density lipoproteins; lipoprotein(a).