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研究生:張瑀
研究生(外文):Yu Chang
論文名稱:高心血管風險者之阿斯匹靈阻抗之相關因子與臨床結果
論文名稱(外文):Clinical Outcomes and Related Factors of Aspirin Resistance among High CVD Risk Patients
指導教授:白其卉白其卉引用關係
口試委員:王致皓邱弘毅
口試日期:2013-07-16
學位類別:碩士
校院名稱:臺北醫學大學
系所名稱:公共衛生學系暨研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:英文
論文頁數:137
中文關鍵詞:阿斯匹靈阻抗臨床結果初級預防
外文關鍵詞:Aspirin resistanceclinical outcomesprimary prevention
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背景與目的: 根據行政院衛生署至2007年至2011年統計資料,心臟疾病與腦中風佔台灣十大死因的第二以及第三位。阿斯匹靈(Aspirin)是目前臨床常用於預防心臟血管疾病之抗血小板藥物,然而並非所有服藥者均可達到降低未來發生心臟血管疾病風險的效果,此一現象廣義地稱為阿斯匹靈阻抗(Aspirin Resistance)。但是目前其定義、產生原因以及盛行率均不明確。因此本研究將探討於罹患心臟血管疾病高風險者產生阿斯匹靈阻抗的可能原因,以及更進一步追蹤未來不良臨床結果並探討其與阿斯匹靈阻抗之相關性。
材料與方法: 本研究為一世代研究,於2006年10月至2007年5月進行研究對象招募。參與者均來自台北市士林地區民眾或新光吳火獅紀念醫院門診個案。通過收案條件者於簽屬同意書並於完成問卷後,給予兩週隔日服用阿斯匹靈100毫克並於用藥完畢進行血液收集(N=144),依據血小板閉鎖時間(Closure Time)小於165秒為阿斯匹靈阻抗定義。而後須經由病歷追蹤至個案發生心臟血管疾病或最終一次赴醫院接受診療之日期。
結果: 在基線部分,本研究有29.58%參與者表現阿斯匹靈阻抗。雖然基線時之血栓素B2於阿斯匹靈阻抗與阿斯匹靈反應兩組間並無差異,但是阿斯匹靈阻抗者具有顯著較高的血栓素B2 (p=0.04)與血糖值(p=0.01)。經由年齡與性別校正之羅吉斯回歸分析,血小板數目≧244 〖10〗^3μl(OR=2.97, p=0.02)及血糖值≧126 mg/dl(OR=2.26, p=0.03)是為阿斯匹靈阻抗之危險因子;另外,進一步分析糖尿病及血糖控制的影響,在罹患糖尿病且血糖值≧126 mg/dl相較於並無糖尿病且正常血糖值者,有較高的風險發生阿斯匹靈阻抗 (OR=2.35, p=0.04)。在追蹤分析部份,經由年齡與性別校正存活分析發現,糖尿病史 (HR=4.78, p=0.0004)、血小板數≧244 〖10〗^3μl (HR=2.21, p=0.04)、經由Framingham Heart Scores評估為中度或高度危險者(HR=3.05, p=0.04)及血糖值≧126 mg/dl (HR=3.31, p=0.0003)為未來六年罹患心臟血管疾病的預測因子,但是並未發現阿斯匹靈阻抗對於罹病的影響(HR=1.45, p=0.2)。然而在一年內之追蹤結果,阿斯匹靈阻抗呈現具有罹患心血管疾病風險(追蹤一年HR=2.55, p=0.04; 追蹤六個月HR=3.87, p=0.04)。

結論: 近三分之一參與者存在阿斯匹靈阻抗現象。糖尿病、高血糖以及較高的血小板計數是阿斯匹靈阻抗之危險因子。於血糖控制較佳的糖尿病患者中,可能有助於改善阿斯匹靈阻抗。此外,於一年期間追蹤呈現阿斯匹靈阻抗是罹患心血管疾病之預測因子。
Background and Purpose: Cardiovascular diseases (CVDs) are a common cause of mortality and morbidity in the 21st century. Also, in Taiwan, heart disease and stroke are the 2nd and 3rd leading cause of death, respectively. Aspirin is a common antiplatelet drug in the prevention of cardiovascular events among the people at risk for CVDs. However, ‘Aspirin resistance’ may lead to ineffective despite Aspirin treatment. The definition, risk factors and prevalence of Aspirin resistance are still not well-establish. This study was designed to explore possible factors of Aspirin resistance in people at high risk of developing CVDs. Furthermore, we also aimed to observe the association between the occurrence of worse clinical outcomes and Aspirin resistance among Aspirin user.

Methods: A cohort study on the participants in medium or high risk of CVDs were performed in community or in clinics of the Shin Kong Wu Ho-Su Memorial Hospital. At baseline from October 2006 to May 2007, the participants who meet the criterion have to draw the blood before and after be prescribed 100 mg Aspirin in alternate day (totally 7 capsules within 14 days) (N=144). We used cut-off <165 seconds of closure time (CT) to identify the phenomenon of Aspirin resistance. Then, all of the participants were followed-up to the date of CVDs onset or final outpatient department in the hospital according their medical records. Thromboxane B2 (TxB2) and PGF1a were measured.

Results: Among the 144 individuals, there were 29.58% of them with Aspirin resistance (n=42). Although baseline TxB2 was no-different between Aspirin resistance and Aspirin resistance groups after 7 capsules of Aspirin usage, the levels of TxB2 in Aspirin resistance group was significantly higher than Aspirin responsive group (p=0.04). In age- and gender- adjusted logistic regression model, the subjects with platelet counts ≧244 〖10〗^3μl and glucose ≧126 mg/dl had increased the risk of Aspirin resistance (platelet: OR=2.97, p=0.02 and glucose: OR=2.26, p=0.03). Focusing on diabetes and controlled status, we also reported 2.35 of age- and gender- adjusted OR (p=0.04) in subjects with diabetic and glucose ≧126 mg/dl than those without diabetes and with normal glucose level. The risk was not significant in those people with diabetic but well-controlled glucose level (<126 mg/dl). Furthermore, during 6 years follow-up, the subjects with diagnosed diabetes (HR=4.78, p=0.0004), glucose≧126 mg/dl (HR=3.31, p=0.0003), moderated or high Framingham Heart Scores (HR=3.05, p=0.04), platelet count ≧244 〖10〗^3μl (HR=2.21, p=0.04) but not Aspirin resistance (CT<165s) (HR=1.45, p=0.2) were the risk factors of the following CVDs after age and gender adjustment. However, during less than one year follow-up, Aspirin resistance (one-year: HR=2.55, p=0.04 and six-month: HR=3.87, p=0.04) expressed the risk of CVDs onset.

Conclusions: Round one-third of the participants presented Aspirin resistance in our study. Diabetic, hyperglycaemia and higher platelet count was the risk factors of Aspirin resistance. In diabetic patients, well-controlled glucose might improve the resistance. Aspirin resistance was the predictor of CVDs only during the periods of 1 year.
Chapter I Introduction 1
Chapter II Literature Review 3
Section I Introduction of Aspirin 3
1.1 History 3
1.2 Indications and dosage 4
1.3 Mechanism of action of Aspirin in Human Body 4
1.4 Aspirin in Prevention of Cardiovascular Diseases 7
1.5 Adverse Events of Aspirin Usage 10
Section II Aspirin Resistance 12
2.1 Definition of Aspirin Resistance 12
2.2 Prevalence of Aspirin Resistance 13
2.3 The Possible Reasons of Aspirin Resistance 15
2.4 Clinical Outcomes in Aspirin Resistance Patients 22
Section III Study Aims 25
3.1 Study Aim 25
3.2 Study Hypothesis 26
Chapter III Materials and Methods 28
1.1 Study Design 28
1.2 Participants Recruitment 28
1.3 Follow-up Process 37
1.4 Collected Information 39
1.5 Target Outcomes for Follow-up 41
1.6 Target Antipletelet Drugs after 7 Doses Usage of Aspirin for Follow-up 42
1.7 Statistical Analysis 43
1.8 Variable Definitions 44


Chapter IV Results 46
Section I Description for Aspirin Resistance 46
Section II Risk Factors of Aspirin Resistance 47
2.1 Basic Characteristic of Participants by Aspirin Resistance Group and Aspirin
Responsive Group 47
2.2 Risk Factors of Aspirin Resistance 49
Section III Progression Analysis 52
3.1 Progress Risk Factors of Clinical Outcomes among 142 Participants 53
Chapter V Discussion 58
Chapter VI Conclusion 66
Chapter VII Tables and Figures 67
Reference 99
Appendix 114
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