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

Jakub Siudut; Michał Ząbczyk; Paweł Wołkow; Maciej Polak; Anetta Undas; Jacek Jawień

doi:10.1016/j.vph.2022.106977

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

Vascul Pharmacol. 2022 Jun:144:106977. doi: 10.1016/j.vph.2022.106977. Epub 2022 Mar 10.

Authors

Jakub Siudut¹, Michał Ząbczyk¹, Paweł Wołkow², Maciej Polak³, Anetta Undas¹, Jacek Jawień⁴

Affiliations

¹ Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland; Krakow Center for Medical Research and Technologies, John Paul II Hospital, Krakow, Poland.
² Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland; Centre for Medical Genomics-OMICRON, Krakow, Poland.
³ Department of Epidemiology and Population Studies, Institute of Public Health, Jagiellonian University Medical College, Krakow, Poland.
⁴ Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland. Electronic address: jacek.jawien@uj.edu.pl.

PMID: 35283275
DOI: 10.1016/j.vph.2022.106977

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

C-Reactive Protein
Cholesterol, LDL
Fibrin / metabolism
Fibrinolysis
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors* / pharmacology
Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
Thrombin / metabolism
Thrombosis* / drug therapy
Thrombosis* / prevention & control

Substances

Cholesterol, LDL
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Fibrin
C-Reactive Protein
Thrombin