癌症病患罹患腦中風之風險評估

背景和目的 全世界已有許多關於癌症與腦中風的相關研究報告；但是研究報告的證據不一致，並且不同類型癌症發生腦中風的風險數據有限。我們假設癌症會影響凝血機制，導致腦中風的發生。這項研究旨在評估癌症患者之腦中風發生的風險以及凝血標誌物（coagulation marker）之間的關聯性。方法 使用全民健康保險研究資料庫中的數據，通過傾向分數配對（propensity score matching）來調查癌症患者罹患腦中風的風險；並收集地區教學醫院臨床病歷之數據，以分析凝血標誌物與癌症及腦中風之相關性。結果 全民健康保險研究資料庫(Longitudinal Health Insurance Database 2000；2004-2013)總共篩選1,793名患者；其中惡性腫瘤組有898位和無惡性腫瘤組895位，其中分別有42名（4.68％）和25名（2.79％）腦中風患者（P <0.001）。根據年齡、性別和共病症調整後，腦中風之校正勝算比（adjusted odds ratio）為1.84（95％ confidence interval；CI 1.17-3.30），出血型腦中風為3.92（95％CI 1.30-11.77）及梗塞型腦中風為1.37（95％ CI 0.72-2.59）。癌症患者有較高的風險發生腦中風，其中出血型腦中風之風險大於梗塞型腦中風。 分析曾入住區域教學醫院之2858名腦中風患者的凝血標誌物。腦中風併癌症的患者的D-雙合蛋白(D-Dimer)（P=0.016），纖維蛋白原(fibrinogen)（P=0.009）和纖維蛋白原/血小板比值（fibrinogen/platelet ratio；FPR）（P= 0.014）之中位數顯著高於腦中風且無癌症患者；顯示癌症誘發了凝血功能障礙，增加腦中風之風險。 在這兩個數據庫，消化器官及腹膜癌是與腦中風相關的最常見癌症，於全民健康保險研究資料庫為30.95%，於區域教學醫院為36.90%。結論 這項研究表明，癌症可能會增加腦中風的風險，尤其是消化器官及腹膜癌症。應評估癌症對D-雙合蛋白，纖維蛋白原和纖維蛋白原/血小板比值的影響，這可能是癌症影響凝血功能而導致腦中風風險增加的潛在機制，未來應嘗試發展評估癌症與腦中風關聯性之指標。

Background and PurposeThe association between cancer and stroke has been reported worldwide; however, studies have reported inconsistent evidence and there are limited data on the risk of stroke in different types of cancer. We hypothesized that cancer affects coagulation mechanisms, leading to the occurrence of stroke. This study aimed to estimate the risk of stroke and interaction of coagulation markers in cancer patients.MethodsData from the National Health Insurance Research Database was used to investigate the risk of stroke in cancer patients using propensity score matching, and data from clinical records from a regional teaching hospital in Taiwan were collected to analyze the impact of coagulation markers on the occurrence of stroke for cancer patients.ResultsA total of 1,793 patients were included in the national database. There were 42(4.68%) and 25(2.79%) stroke patients in the malignancy and control groups, respectively (P<0.001). The odds ratio adjusted according to age, sex, and comorbidities was 1.84 (95% confidence interval [CI]: 1.17-3.30) for overall stroke, 3.92(95% CI 1.30-11.77) for hemorrhagic stroke, and 1.37(95% CI 0.72-2.59) for infarction stroke. Coagulation markers were analyzed in 2,858 stroke patients who were admitted to the regional teaching hospital. The median D-Dimer level (528ng/ml vs. 318ng/ml; P=0.016), fibrinogen level (305.5mg/dl vs. 283mg/dl; P=0.009), and fibrinogen/platelet ratio (1.61 vs. 1.42; P=0.014) were significantly higher in cancer patients with stroke than in those without stroke. In both databases, digestive organ and peritoneum cancer were the most common cancers associated with the risk of stroke.ConclusionsThis study indicates that cancer, especially digestive organ cancer, may increase the risk of stroke. The influence of cancer on the regulation of D-Dimer level, fibrinogen level, and fibrinogen/platelet ratio should be evaluated as an underlying mechanism leading to the increased risk of stroke, and attempts should be made to develop indicators for evaluating the association between cancer and stroke.