Wallaschofski Henri, Lohmann Tobias, Hild Eva, Kobsar Anna, Siegemund Annelie, Spilcke-Liss E, Hentschel Betina, Stumpf Christian, Daniel Werner G, Garlichs Christian D, Eigenthaler Martin
Department of Gastroenterology, Endocrinology and Nutrition, University of Greifswald, Friedrich-Loeffler-Strasse 23a, 17487 Greifswald, Germany.
Thromb Haemost. 2006 Jul;96(1):38-44. doi: 10.1160/TH05-09-0634.
Prolactin and leptin are newly recognised platelet co-stimulators due to potentiation of ADP-induced platelet aggregation. Elevated leptin levels have recently been found to be a risk factor for ischemic stroke in both men and women, and especially in combination with increased blood pressure for hemorrhagic stroke in men. Until now an association between hyperprolactinemia and ischemic stroke has not been investigated systematically. We determined plasma prolactin and leptin levels as well as platelet P-selectin expression in 36 patients with ischemic stroke or transient ischemic attack and detected a significant correlation between increased prolactin values and enhanced ADP stimulated P-selectin expression on platelets. In contrast, no correlation of leptin values with platelet P-selectin expression was found. Next we determined plasma prolactin and leptin as well as acquired and congenital risk factors of thrombophilia in patients with first-ever non-hemorrhagic stroke with or without atrial fibrillation. Excluding patients with such preexisting risk factors, 21 patients with and 59 patients without atrial fibrillation were identified. Patients without atrial fibrillation revealed significantly higher plasma prolactin levels than patients with atrial fibrillation. Furthermore, the influence of aspirin or clopidogrel on prolactin stimulated P-selectin expression in vitro was tested, showing that aspirin was without effect, whereas clopidogrel significantly inhibited platelet P-selectin expression. In conclusion, hyperprolactinemia might be a novel risk factor for stroke mediating its thrombogenic effect through enhanced platelet reactivity, and this might correspond to a higher efficacy of antiplatelet combination therapy with clopidogrel compared to aspirin therapy alone.
由于可增强ADP诱导的血小板聚集，催乳素和瘦素是新发现的血小板共刺激因子。最近发现，瘦素水平升高是男性和女性缺血性中风的危险因素，尤其是男性中，瘦素水平升高与血压升高共同作用会增加出血性中风的风险。到目前为止，尚未系统研究高催乳素血症与缺血性中风之间的关联。我们测定了36例缺血性中风或短暂性脑缺血发作患者的血浆催乳素和瘦素水平以及血小板P-选择素表达，发现催乳素值升高与ADP刺激的血小板P-选择素表达增强之间存在显著相关性。相比之下，未发现瘦素值与血小板P-选择素表达之间存在相关性。接下来，我们测定了首次发生非出血性中风且伴有或不伴有心房颤动患者的血浆催乳素和瘦素以及获得性和先天性血栓形成倾向危险因素。排除具有此类既往危险因素的患者后，确定了21例伴有心房颤动的患者和59例不伴有心房颤动的患者。不伴有心房颤动的患者血浆催乳素水平显著高于伴有心房颤动的患者。此外，测试了阿司匹林或氯吡格雷对体外催乳素刺激的P-选择素表达的影响，结果显示阿司匹林无作用，而氯吡格雷显著抑制血小板P-选择素表达。总之，高催乳素血症可能是中风的一个新危险因素，通过增强血小板反应性介导其血栓形成作用，这可能对应于与单独使用阿司匹林治疗相比，氯吡格雷抗血小板联合治疗具有更高的疗效。
