偏頭痛為周邊動脈阻塞疾病之危險因子:臺灣人口之世代追蹤研究

目前已有許多研究指出偏頭痛(migraine)會增加腦中風的風險，即使在校正多變項包含更年期、停經後使用賀爾蒙、口服避孕藥及使用阿斯匹靈後，偏頭痛仍是中風的顯著危險因子。然而偏頭痛與周邊動脈阻塞疾病（Peripheral artery occlusive disease, PAOD）之相關探討文獻仍相當有限，且研究結果並無一致之結論。因此，本研究利用台灣全民健保資料庫建立的研究族群，探討偏頭痛與周邊動脈阻塞疾病之相關性，以及偏頭痛是否為後續發生周邊動脈阻塞疾病的指標。利用台灣全民健保資料庫抽樣產生的抽樣檔—2005年承保抽樣歸人檔 (Longitudinal Health Insurance Database; LHID 2005)，並從LHID 2005定義出2004-2015新診斷偏頭痛之病患，經篩選標準後以一比一的比例配對出非偏頭痛之族群，同時收集其他相關危險因子作分析。主要試驗指標(Primary outcome)設定為發生周邊動脈阻塞疾病。經篩選配對後，偏頭痛與無偏頭痛組別各納入37288個病人。其中研究組(偏頭痛組)有885人發生周邊動脈阻塞疾病，對照組(非偏頭痛組)有530人發生周邊動脈阻塞疾病，且研究組發生周邊動脈阻塞疾病的調整風險比明顯更高(Adjusted HR 1.65, 95% C.I 1.48-1.84, p<0.001)，累積發生率也顯示偏頭痛與周邊動脈阻塞疾病之關聯性。對於無系統性疾病如高血壓、慢性肝病、慢性腎臟病、冠狀動脈心臟病、腦中風、氣喘或心衰竭之個體，有偏頭痛之患者比無偏頭痛之患者發生周邊動脈阻塞疾病之機率顯著上升(p值皆<0.001)，此結果發現偏頭痛會顯著影響之後發生周邊動脈阻塞疾病的機率，是周邊動脈阻塞疾病的危險因子之一。由於周邊動脈阻塞疾病會導致嚴重肢體缺血甚至永久失能，病人如果有長期偏頭痛應該要被轉介到心血管專科評估是否有周邊動脈阻塞疾病與早期介入治療。此外，也需更進一步的前瞻性研究來評估治療偏頭痛是否會影響之後發生周邊動脈阻塞的機率。

This study evulated the development of preipheral occlusive artery disease (PAOD) in patients with migraine by using the National Health Insurance Research Database in Taiwan. Based on the International Classiifcation of Diseases, Ninth Revision (ICD-9), individuals with diagnostic codes of migraine were enrolled in the study group. One subject without migraine was set as control group and was matched with age and gender to each patient in the study group. The exclusion criteria was diagnosis of PAOD before index date. The outcome was set as the development of PAOD. In addition, other risk factors including age, gender and comorbidities were analyzed in the multivariate model. A total of 37288 patients with migraine and another 37288 non-migraine individuals were enrolled after inclusion and exclusion. The age and gender distributions were identical between the two groups due to matching. In the follow-up period, there were 885 and 530 PAOD events in the study group and control group, respectively. Moreover, the study group had a significantly higher adjusted hazard ratio (1.65, 95% confidential interval: 1.48–1.84, p<0.001). The cumulative incidence analysis revealed a correlation between the diagnosis of migraine and PAOD either. In addition, other potential risk factors related to the existence of PAOD include age, hypertension, chronic kidney disease, diabetes mellitus, coronary artery disease, stroke and asthma. In the subgroup analysis, for patients without systemic disease such as DM or hypertension, the HR of subsequent PAOD was significantly higher in the migraine group than in the control group. In conclusion, the diagnosis of migraine is a significant risk factor for the development of PAOD.