Puccetti Luca, Pasqui Anna Laura, Pastorelli Marcello, Bova Giovanni, Di Renzo Michela, Leo Alessandro, Cercignani Michela, Palazzuoli Alberto, Auteri Alberto, Bruni Fulvio
Department of Clinical Medicine and Immunological Sciences, Internal Medicine Division, Policlinico Le Scotte, V. le Bracci, 53100, Siena, Italy.
Thromb Haemost. 2003 Sep;90(3):476-82. doi: 10.1160/TH03-02-0111.
Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular events by cholesterol lowering as well as by non-lipid related actions. Among them, the modulation of platelet activity could play a relevant role in vascular protection. Furthermore withdrawal of statins has been associated with increased cardiovascular event rate. The aim of our study was to evaluate platelet activity after cerivastatin discontinuation in eighteen subjects that did not accept other drugs and in sixteen subjects continuing treatment with simvastatin. Fourteen subjects at the end of the discontinuation period decided to receive other drugs (simvastatin) and they were evaluted six weeks later. We measured complete lipid profile by the chromogenic method (LDL-C was calculated); oxidized-LDL (ox-LDL; ELISA), platelet P-selectin (P-sel) expression (flow cytometry detection), platelet aggregation (% change of transmitted light), intracellular citrullin production (iCit; HPLC) as an indicator of intracellular NO synthase activity at baseline and 7, 14, 28, 60 days after statin discontinuation. P-sel expression and platelet aggregation were increased at 14 days (p < 0.001 and p < 0.05) in association with raised ox-LDL (r = 0.30, p < 0.05) and decreased iCit (r = 0.53, p < 0.01). Increased LDL-C was related to P-sel and platelet aggregation at 28 days (r = 0.30, p < 0.05). Subjects continuing statin treatment had no significant changes of P-sel at 28 (p = 0.221) and 60 days (p = 0.238). Subjects treated with simvastatin after 60 days of diet showed a significant reduction of P-sel and platelet aggregation after six weeks of treatment (p < 0.01). Our data suggest a platelet hyperactivation state in the second week after statin discontinuation which is partially related to raised LDL-C. Such a finding could participate in the increased cardiovascular event rate after statin discontinuation.
羟甲基戊二酰辅酶A还原酶抑制剂（他汀类药物）通过降低胆固醇以及非脂质相关作用来减少心血管事件。其中，血小板活性的调节可能在血管保护中发挥重要作用。此外，停用他汀类药物与心血管事件发生率增加有关。我们研究的目的是评估在18名不接受其他药物的受试者和16名继续使用辛伐他汀治疗的受试者中，停用西立伐他汀后血小板的活性。在停药期结束时，14名受试者决定接受其他药物（辛伐他汀），并在六周后对他们进行评估。我们通过比色法测量完整血脂谱（计算低密度脂蛋白胆固醇）；氧化型低密度脂蛋白（ox-LDL；酶联免疫吸附测定法）、血小板P-选择素（P-sel）表达（流式细胞术检测）、血小板聚集（透过光的变化百分比）、细胞内瓜氨酸生成（iCit；高效液相色谱法），作为基线以及停用他汀类药物后第7、14、28、60天细胞内一氧化氮合酶活性的指标。在第14天时，P-sel表达和血小板聚集增加（p < 0.001和p < 0.05），同时ox-LDL升高（r = 0.30，p < 0.05）且iCit降低（r = 0.53，p < 0.01）。在第28天时，升高的低密度脂蛋白胆固醇与P-sel和血小板聚集相关（r = 0.30，p < 0.05）。继续接受他汀类药物治疗的受试者在第28天（p = 0.221）和第60天（p = 0.238）时P-sel无显著变化。在饮食控制60天后接受辛伐他汀治疗的受试者在治疗六周后P-sel和血小板聚集显著降低（p < 0.01）。我们的数据表明，在停用他汀类药物后的第二周存在血小板过度激活状态，这与升高的低密度脂蛋白胆固醇部分相关。这一发现可能与停用他汀类药物后心血管事件发生率增加有关。
