Lacoste L, Lam J Y, Hung J, Letchacovski G, Solymoss C B, Waters D
Department of Medicine, Montreal Heart Institute, Quebec, Canada.
Circulation. 1995 Dec 1;92(11):3172-7. doi: 10.1161/01.cir.92.11.3172.
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.
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).
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.
高胆固醇血症是冠心病的危险因素，高胆固醇血症会使血小板反应性增加，提示存在血栓前风险。本研究的目的是在一个模拟高胆固醇血症冠心病患者血管狭窄和斑块破裂的模型中，测量胆固醇降低前后受损动脉壁上的壁内血小板血栓形成情况。
研究了32例稳定型冠心病患者。对16例高胆固醇血症患者（胆固醇>5.2 mmol/L）在平均2.5个月的普伐他汀治疗（40 mg/d）前后以及16例正常胆固醇血症对照患者进行了血小板血栓形成和血脂测量。通过在体外灌注室中，于37℃以754或2546 s-1的剪切速率将猪主动脉中膜暴露于患者流动的静脉血3分钟来评估血栓形成。在高剪切速率和低剪切速率下，高胆固醇血症患者基线时的定量形态学血小板血栓形成均较高：分别为4.8±1.0和3.3±0.7平方微米/毫米，而正常胆固醇血症患者分别为2.1±0.5和1.6±0.4平方微米/毫米（均P<.05）。在高胆固醇血症患者中，普伐他汀使总胆固醇从6.5±0.2 mmol/L降至4.5±0.2 mmol/L，低密度脂蛋白胆固醇从4.5±0.2 mmol/L降至2.8±0.1 mmol/L（均P<.05）。高剪切速率和低剪切速率下的血小板血栓形成分别降至2.0±0.3和1.3±0.3平方微米/毫米（均P<.05）。
因此，高胆固醇血症与受损动脉上血小板血栓形成增强有关，增加了急性血栓形成的倾向。随着普伐他汀降低总胆固醇和低密度脂蛋白胆固醇水平，高剪切速率和低剪切速率下的血小板血栓形成均减少。因此，降低胆固醇可能部分通过降低血栓形成风险来降低急性冠状动脉事件的风险。
