Hyperlipidemia and coronary disease. Correction of the increased thrombogenic potential with cholesterol reduction.

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 degrees 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 micron 2/mm, respectively, compared with normocholesterolemic patients: 2.1 +/- 0.5 and 1.6 +/- 0.4 micron 2/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 micron 2/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.

Cigarette smoking acutely increases platelet thrombus formation in patients with coronary artery disease taking aspirin.

BACKGROUND: Smoking is associated with an increased risk of myocardial infarction and sudden death. Platelet activation and thrombosis at sites of vessel stenosis and injury or plaque disruption play a crucial role in these acute coronary events. Thus, the aim of this study was to determine whether cigarette smoking acutely increases platelet thrombus formation on an injured arterial surface at local shear rates typical of a stenotic artery. METHODS AND RESULTS: Twelve habitual smokers with stable coronary disease, on aspirin 325 mg/d, were studied immediately before and 5 minutes after smoking two cigarettes each. Ex vivo platelet thrombus formation on porcine arterial media (simulating deep arterial injury) was measured after exposure to the patient's circulating venous blood for 3 minutes in cylindrical flow chambers at 37 degrees C. The flow chambers were designed to produce shear rates of 754 or 2546 s-1, the latter being typical of the high shear rates produced by vessel stenosis. Plasma catecholamine, thromboxane B2, and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) levels and whole blood platelet aggregation responses to thrombin were also measured before and after smoking. Compared with before smoking, morphometrically measured platelet thrombus formation on arterial media at shear rates of 754 and 2546 s-1 increased by an average of 48% (P = .19) and 64% (P = .014), respectively, after smoking. Plasma epinephrine increased by more than twofold after smoking (P = .026). Plasma thromboxane B2 and 6-keto-PGF1 alpha levels did not change. Smoking also increased whole blood platelet aggregation to thrombin (P < or = .05). CONCLUSIONS: These results suggest that smoking-enhanced platelet thrombosis may be an important contributory mechanism for acute coronary events in smokers that is not prevented by aspirin treatment. Catecholamine release and heightened platelet aggregation response to in vivo agonists may contribute to the prothrombotic effects of smoking.