Statins decrease thrombin generation in patients with hypercholesterolemia.
OBJECTIVE
Statins are cholesterol-lowering agents with antithrombotic effect possibly unrelated to their lipid-lowering properties. Traditional global coagulation tests failed, however, to reveal clinically relevant change after treatment. We therefore sought to investigate whether statins were able to modify thrombin generation in hypercholesterolemia.


METHODS
Fifty-one patients who needed treatment with statins were enrolled in this study. Thrombin generation, assessed as endogenous thrombin potential (the amount of thrombin generated after triggering coagulation with small amount of tissue factor) was measured at pre- and two months post-treatment with statins.


RESULTS
The median (inter-quartile range) level of total cholesterol that was 325 mg/dL (278-405) decreased significantly [211 mg/dL (197-247)] at post-treatment (p<0.001); the median level of HDL cholesterol that was 49 mg/dL (43-56) increased significantly [55 mg/dL (47-66)] at post-treatment (p<0.001). The median endogenous thrombin potential (inter-quartile range) before treatment was 2372 nM·min (2008-2617) and decreased to 2,048 nM·min (1764-2375) (p<0.001) after treatment.


CONCLUSIONS
The results support the hypothesis of a direct link between statins and coagulation through their capacity to lower thrombin generation in patients with hypercholesterolemia.


CONCLUSIONS
The antithrombotic properties of statins could be mediated (at least in part) by their endogenous thrombin potential lowering effect. This interesting hypothesis warrants evaluation by clinical trials.
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, IRCCS Cà Granda Ospedale Maggiore Foundation, Milano, Italy. Electronic address: armando.tripodi@unimi.it.
Armando
A
Tripodi
Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy; Department of Pharmacological Sciences and Biomolecular, University of Milan, Milan, Italy.
Fabio
F
Pellegatta
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, IRCCS Cà Granda Ospedale Maggiore Foundation, Milano, Italy.
Veena
V
Chantarangkul
Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy.
Liliana
L
Grigore
Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy.
Katia
K
Garlaschelli
Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy; Department of Pharmacological Sciences and Biomolecular, University of Milan, Milan, Italy.
Andrea
A
Baragetti
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, IRCCS Cà Granda Ospedale Maggiore Foundation, Milano, Italy.
Laura
L
Lemma
Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy; Department of Pharmacological Sciences and Biomolecular, University of Milan, Milan, Italy; IRCCS Multimedica, Milano, Italy.
Alberico
A
Catapano
D001777:Blood Coagulation / Q000502:physiology; D008076:Cholesterol, HDL / Q000097:blood; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000378:metabolism*; D013917:Thrombin / Q000096:biosynthesis*
D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013917:Thrombin
Atherosclerosis; Endogenous thrombin potential; Hypercoagulability; Lipids; Thrombosis