Therapy with high-dose statins reduces soluble P-selectin: The impact on plasma fibrin clot properties

Objective: Studies on the effect of statins on platelets in patients with coronary artery disease (CAD) yielded inconsistent results. We sought to investigate whether high-dose statin therapy reduces plasma concentrations of soluble P-selectin (sP-selectin), a well-established platelet activation marker and if such changes can affect fibrin clot properties, which are unfavorably altered in CAD patients.Methods: We studied 130 consecutive patients with advanced CAD who did not achieve the target LDL cholesterol on statins. At baseline and after 6-12 months of treatment with atorvastatin 80 mg/day or rosuvastatin 40 mg/ day, soluble plasma sP-selectin, along with plasma fibrin clot permeability (Ks), clot lysis time (CLT), thrombin generation and fibrinolysis proteins were determined.Results: Before high-intensity statin treatment, lower Ks and longer CLT values were associated with increased sPselectin (beta -0.27 [95% CI -0.44 to -0.10] and beta 0.21 [95% CI 0.01 to 0.41]; both p < 0.05, respectively) also after adjustment for potential confounders. sP-selectin, alongside fibrin features and other variables at baseline showed no association with lipid profile. On high-dose statin therapy, there was 32% reduction in sP-selectin levels (p < 0.001). On-treatment change (Delta) in sP-selectin correlated with Delta Ks and Delta CLT (r = -0.32, p < 0.001 and r = 0.22, p = 0.011, respectively), but not with cholesterol and C-reactive protein lowering. We did not observe any associations between post-treatment sP-selectin levels and lipids, fibrin clot properties or thrombin generation.Conclusions: High-dose statin therapy reduces markedly sP-selectin levels in association with improved fibrin clot phenotype, which highlights the contribution of platelet-derived proteins to a prothrombotic state in hypercholesterolemia and statin-induced antithrombotic effects.

Automated summary

This study aimed to investigate the effects of high-dose statin therapy on platelets in patients with coronary artery disease (CAD). The results showed that high-dose statin therapy significantly reduced the levels of soluble P-selectin and improved fibrin clot properties. These findings have important implications for understanding the mechanism of action of statins in the treatment of CAD.