Intensive low-density lipoprotein cholesterol lowering improves fibrin clot properties: Association with lipoproteins and C-reactive protein

Abstract

Objective: Dense fibrin networks resistant to lysis characterize coronary artery disease (CAD) patients. We investigated whether a statin-induced decrease of low-density lipoprotein cholesterol (LDL-C) could improve fibrin clot phenotype in CAD patients.

Methods: We recruited 130 consecutive patients with advanced CAD (baseline LDL-C of 4.4 [IQR, 3.8-4.8] mmol/L), who on statins did not achieve the LDL-C goal based on the 2016 ESC/EAS guidelines. On standard statin treatment and after 6-12 months of high-dose statin treatment (atorvastatin 80 mg/day or rosuvastatin 40 mg/day), plasma fibrin clot permeability (Ks), clot lysis time (CLT), thrombin generation, coagulation and fibrinolytic factors were determined.

Results: After a median high-dose statin therapy of 7 months there was 25% reduction in LDL-C associated with increased Ks and shorter CLT, together with lower thrombin activatable fibrinolysis inhibitor, factor VIII, D-dimer, and C-reactive protein (CRP); thrombin generation was unaltered. The patients who achieved the therapeutic goal (n = 49, 37.7%) had 29.2% increase in Ks and 16.3% shorter CLT compared with the standard therapy, while there were no similar changes in the remaining patients. After adjustment for potential confounders, including CRP, an increase in Ks (by 1 × 10^-9 cm²) and decrease in CLT (by 10 min) were independently predicted by on-treatment LDL-C goal (odds ratio [OR] 6.23, 95% confidence interval [CI] 1.97-20.33 and OR 3.11, 95% CI 1.05-8.99, respectively).

Conclusions: For the first time we showed that a decrease of LDL-C ≤ 1.8 mmol/L, or a reduction of at least 50% if the baseline LDL-C is between 1.8 and 3.5 mmol/L, is associated with favorable alterations to fibrin clot phenotype, with a stronger impact of lipoprotein reduction than CRP lowering, which might suggest that other potent cholesterol-lowering drugs can exert similar antithrombotic actions.

Keywords: Coagulation; Coronary artery disease; Fibrinolysis; Low-density lipoproteins; Statin.