Hypercoagulable state in hypercholesterolemic subjects assessed by platelet-dependent thrombin generation: in vitro effect of cerivastatin.
BACKGROUND
Hypercholesterolemia is an important risk factor to develop acute thrombotic complications of atherosclerosis like to myocardial infarction and ischemic stroke. Platelets and coagulation factors are strictly involved in the genesis of such thrombotic events and their hyperactivity in hypercholesterolemic patients has been previously reported. Moreover some cholesterol-lowering molecules (statins) seem to be able of reducing platelet activity.


METHODS
We performed platelet-dependent thrombin generation (colorimetric method) to assess the coagulative potential of 40 caucasian hypercholesterolemic subjects with respect to normal controls and to the grade of hypercholesterolemia. Moreover we observed the effect of platelets from hypercholesterolemics on thrombin generation in plasma from normal subjects. The effect of Cerivastatin on thrombin generation was evaluated too.


RESULTS
Our data show an increased thrombin generation both in mild and high hypercholesterolemic subjects with respect to controls (424.6+/-30.5 vs. 197.1+/-27.4 mIU/ml). No significant difference in the amount of thrombin generation was found between mild and high hypercholesterolemics (399.6+/-20.7 vs. 440.2+/-21.4 mIU/ml). Platelets directly influence thrombin generation and they present an intrinsic hyperactivity that can be modulated by Cerivastatin (223.6+/-24.8 vs. 424.6+/-30.5 mIU/ml).


CONCLUSIONS
Mild hypercholesterolemia is associated with an increased thrombinic potential that may be considered an added risk factor to develop thrombotic events. Platelets directly influences this hypercoagulative state and Cerivastatin is able to reduce thrombin generation by way of a direct interaction with platelets.
Puccetti
L
L
Institute of Medical Semeiotics, Centro per lo Studio delle Malattie Dismetaboliche e della Aterosclerosi, University of Siena, Italy.
Bruni
F
F
Di Renzo
M
M
Bova
G
G
Cercignani
M
M
Iadanza
A
A
Auteri
A
A
Pasqui
A L
AL
D001778:Blood Coagulation Disorders / Q000097:blood / Q000209:etiology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications*; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D011725:Pyridines; D013917:Thrombin / Q000096:biosynthesis*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011725:Pyridines; C086276:cerivastatin; D013917:Thrombin