Hyperlipidemia and coronary disease: correction of the increased thrombogenic potential with cholesterol reduction

L Lacoste, JYT Lam, J Hung, G Letchacovski… - Circulation, 1995 - Am Heart Assoc
L Lacoste, JYT Lam, J Hung, G Letchacovski, CB Solymoss, D Waters
Circulation, 1995Am Heart Assoc
Background Hypercholesterolemia is a risk factor for coronary disease, and platelet
reactivity is increased with hypercholesterolemia, suggesting a prethrombotic risk. The aim
of this study was to measure mural platelet thrombus formation on an injured arterial wall in
a model simulating vessel stenosis and plaque rupture in hypercholesterolemic coronary
disease patients before and after cholesterol reduction. Methods and Results Thirty-two
patients with stable coronary disease were studied. Platelet thrombus formation and serum …
Background Hypercholesterolemia is a risk factor for coronary disease, and platelet reactivity is increased with hypercholesterolemia, suggesting a prethrombotic risk. The aim of this study was to measure mural platelet thrombus formation on an injured arterial wall in a model simulating vessel stenosis and plaque rupture in hypercholesterolemic coronary disease patients before and after cholesterol reduction.
Methods and Results Thirty-two patients with stable coronary disease were studied. Platelet thrombus formation and serum lipids were measured in 16 hypercholesterolemic patients (cholesterol >5.2 mmol/L) before and after a mean of 2.5 months of pravastatin therapy (40 mg/d) and in 16 normocholesterolemic control patients. Thrombus formation was assessed by exposing porcine aortic media to the patient’s flowing venous blood for 3 minutes at a shear rate of 754 or 2546 s−1 at 37°C in an ex vivo superfusion chamber. Quantitative morphometric platelet thrombus formation at baseline was higher in the hypercholesterolemic patients at both the high and low shear rates: 4.8±1.0 and 3.3±0.7 μm2/mm, respectively, compared with normocholesterolemic patients: 2.1±0.5 and 1.6±0.4 μm2/mm (both P<.05). In the hypercholesterolemic patients, pravastatin decreased total cholesterol from 6.5±0.2 to 4.5±0.2 mmol/L and LDL cholesterol from 4.5±0.2 to 2.8±0.1 mmol/L (both P<.05). Platelet thrombus formation at high and low shear rates decreased to 2.0±0.3 and 1.3±0.3 μm2/mm, respectively (both P<.05).
Conclusions Thus, hypercholesterolemia is associated with an enhanced platelet thrombus formation on an injured artery, increasing the propensity for acute thrombosis. Platelet thrombus formation at both high and low shear rates decreased as total and LDL cholesterol levels were reduced with pravastatin. Cholesterol lowering may therefore reduce the risk of acute coronary events in part by reducing the thrombogenic risk.
Am Heart Assoc