血脂異常之第二型糖尿病患者有無併發症對服用 Statin 類藥物與心血管疾病發病危險性之探討

Statin and Risk of Cardiovascular Diseases among Type 2 Diabetes Mellitus Patients with Lipid Abnormality and Complication

鄭舒云(Shu-Yun Cheng)

指導教授 ： 邱弘毅

臺北醫學大學/公共衛生暨營養學院/公共衛生學研究所/碩士(2011年)

摘要

背景：
低密度脂蛋白、總膽固醇、三酸甘油脂增加及高密度脂蛋白膽固醇的下降，都會是糖尿病患者罹患心血管疾病的危險因子之一。糖尿病患者其降血脂藥物Statin 類對於心血管疾病的影響，目前已在不少臨床詴驗中及綜合分析研究被證實。然而，糖尿病患者合併不同程度併發症者，對於服用不同與降血脂藥物 Statin類的天數及劑量，對於心血管疾病具有保護作用，目前仍舊不是很清楚。因此，本研究使用全民健康保隩資料庫，來探討 Statin 類降血脂藥物使用情況在不同糖尿病併發症患者身上對於其罹患心血管疾病的風隩評估。

材料與方法：
本研究是選取 2005 年承保抽樣百萬歸人檔，1999 年至 2006 年總計 8 年的健保申請資料庫。在 2001-2005 年間 81,105 糖尿病患者中有 51,166 位有血脂異常，排除使用其他藥物、未使用任何降血脂藥物、第一型糖尿病患者及心血管疾病病史者等，使用 Statin 類總計有 6071 人，其中無任何糖尿病併發症者有 2705人，有糖尿病相關併發症者 3366 人，再依其使用血脂藥物的情形，分為使用天
數小於 180 天者共 3732 人及大於等於 180 天者 2339 人，帄均劑量小於等於 20 mg 5300 人(每日低平均劑量)、大於 20 mg 771 人(每日高平均劑量)；研究對象總劑量小於 3600 mg 有 4207 人及總劑量大於等於 3600 mg 有 1864 人。Statin 類藥物使用的 Index date 為第一次被診斷為糖尿病及血脂異常後，第一次開立 Statin
類處方的第一天，並以 Index date 觀察一年以內心血管疾病發病之狀況。
以 t 檢定、卡方檢定/Fisher‘s Exact Test 比較糖尿病使用降血脂藥物 Statin類多寡，各變項之間是否有無差異；Cox proportional hazard model 在校正了危險因子之後，比較服用降血脂藥物 Statin 類的相關指標與罹患心血管疾病的風險比；趨勢檢定以驗證血脂用藥 Statin 類對於罹患心血管疾病的劑量效應是否有達
到統計上顯著意義。

結果：
研究對象 6071 糖尿病人當中，不論有無併發症，使用血脂用藥的天數及平均劑量都沒有顯著的差異。小於 55 歲、男性中服用 Statin 類的服藥天數、平均劑量及總劑量與心血管疾病的保護效果都沒達到統計上的顯著意義。而大於等於55 歲、女性及有併發症者服藥情形分別會降低發生中風、心臟衰竭的風險。第二型糖尿病病人在調整過相關的因子後，無任何糖尿病相關併發症且服藥天數小於 180 天者、一種以上糖尿病併發症且服藥天數大於等於 180 天者及無併發症且服用天數大於等於 180 天者，比起有糖尿病併發症且服用天數小於 180 天者，可分別降低 56%-35%發生中風的風險，服用時間短但高劑量及服用時間長但低劑量的保護效果接近，比起服用短且低劑量者都可減少 0.5 倍發生中風的風險，其中以服藥時間長且高劑量者保護效果最佳，調整後有 0.18 倍的保護效果。除了中風之外，對於缺血型中風及心臟衰竭大多有一致的結果。並將總劑量依中位數及第三分位數區分為三組，結果指出對於全部中風、缺血型中風、心臟衰竭及週邊血管疾病調整前後其劑量效應都達到統計上顯著意義。

結論：
本研究結果指出，糖尿病有無合併症者，其血脂藥物 Statin 類的服藥天數、平均劑量及總劑量之間沒有顯著的差異。糖尿病相關併發症罹患心血管疾病比例較高，但服藥血脂藥物 Statin 類天數大於 180 天以上及帄均劑量較大者，則與無併發症的發病情形會十分接近，並以長時間高劑量者對於心血管疾病的保護效果最佳，另外血脂藥物 Statin 類的劑量效應也都達到顯著，因此糖尿病合併血脂異
常者，不論有無併發症都應該長期服用血脂藥物 Statin 類來控制血脂異常的問題。

關鍵字

血脂藥物 Statin 類(HMG-CoA 還原沒抑制劑) ； 糖尿病 ； 併發症 ； 心血管疾病 ； 台灣健保資料庫

並列摘要

Background：
Increasing LDL, total cholesterol, triglycerides or decreasing HDL-C had been reported highly correlated with risk of cardiovascular disease among diabetes patients. The
effects of statins therapy on reducing mortality and cardiovascular morbidity in diabetic patients had been demonstrated in numerous randomized clinical trials and
meta-analysis. There were few studies to investigate the effect of taking statins on the risk of cardiovascular diseases among diabetes with complications. Therefore, the
purpose of this study was to investigate that taking statins in diabetic patients with complications might reduce the risk of cardiovascular disease by using national
health insurance database.

Materials and Methods
This is a retrospective cohort study using 1999-2006 the National Health Insurance (NHI) claim data. In 2001-2005 we recruited 51,166 diabetic patients with lipid abnormality through 81,105 diabetes patients. Those who using drug, without using any lipid lower drug, with type 1 diabetes mellitus and with any cardiovascular diseases history were excluded in this study. A total of 6071 diabetic patients using statins were analyzed in our study. Among them, there were 2705 patients without diabetic complication and 3366 patients with diabetic complications. According to patients’ behavior of using statins：Duration less than 180 days was 3732 patients, the others was 2339 patients. Average daily dose less than and equal 20 mg was 5300 patients(low dose), the average daily dose＞20 mg was 771 patients (high dose). Total dose less than 3600mg was 4207 patients, while more than and equal to 3600mg were 1864 patients. The first time of statins prescription will be defiened as index date. We observed incidence of cardiovascular disease within one year after index date.

Result：
Patients (N=6071) with and without diabetic complications did not have significant difference in statins taking behavior. Study subjects who were less than 55 years old
or men subjects did not have protective effects of statins on cardiovascular disease risk . While, older(≧55)subjects, female and diabetes with complications have
reduce stroke and heart failure risk through statins taking. After adjustment for tranditional risk factors of type 2 diabetes, subjects without diabetes-related complications, taking statins more than 180 days or taking high doseage(>20 mg) could reduce 56%-35% of stroke incidence. Both short duration with high dose patients and long duration with low dose patients could also decrease 50% stroke risk than short duration with low dose patients. Taking statins with long-term use andwith high dose had the best protective effects on stroke risk (HR=0.18). Stroke,
ischemic stroke, heart failure and peripheral vascular disease have significant dose-respense reduced effects through taking statins.

Conclusion
Type 2 Diabetes Mellitus Patients with or without complications has no significant difference in statins using behavior. Patients with complications have higher risk of cardiovascular disease. However, when they take statins more than 180 days and with high dose they will have similar risk of cardiovascular disease with those who
without complication.Our study showed that diabetic patients with lipid abnormality and complication who took use statins at least 180 days or total dosage greater than
and equal to 3600mg will have significant reduced risk of lipid-abnormal related diseases.

並列關鍵字

Statins ； HMG-CoA reductase inhibitor ； Diabetes ； Complications ； Cardiovascular disease ； National Health Insurance Research

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