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| 研究生： |
郭風裕 Kuo, Feng-Yu |
|---|---|
| 論文名稱： |
Statin在末期腎病合併心肌梗塞患者的效果 Impact of Statin on Long Term Outcome among End-stage Renal Disease Patients with Acute Myocardial Infarction (MI) : A Nationwide Case-Control Study |
| 指導教授： |
吳明昌
Wu, Ming-Chang |
| 學位類別： |
博士 Doctor |
| 系所名稱： |
農學院 - 食品科學系所 Department of Food Science |
| 畢業學年度： | 107 |
| 語文別： | 英文 |
| 論文頁數： | 97 |
| 中文關鍵詞： | 死亡率 、全民健保資料庫 、降膽固醇藥物 、心肌梗塞 、末期腎衰竭 |
| 外文關鍵詞： | Mortality, National health insurance database, Acute myocardial infarction, Statin, End-stage renal disease |
| DOI URL： | http://doi.org/10.6346/NPUST201900378 |
| 相關次數： | 點閱：22 下載：0 |
| 分享至: |
| 查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 |
根據世界衛生組織(WHO, World health Organization)的統計資料，人類死亡的因素第一位為心血管疾病，其中以急性心肌梗塞最為嚴重。近幾十年來，由於醫學技術與藥物的進步，心肌梗塞的死亡率已經逐漸下降，其中降膽固醇藥物佔有舉足輕重的地步。降膽固藥物可以明顯降低急性心肌梗塞病人的心肌再梗塞機率及死亡率。而這個數字在臺灣人與西方人皆然。在西方的APPLO STUDY 中，心肌梗塞病人的再復發機率及死亡率三年約20%左右，而根據臺灣健保資料庫的資料，心肌梗塞病人三年的復發機率約在14%左右。降膽固醇藥物在末期腎衰竭接受透析合併心肌梗塞病人是否能降低心肌梗塞再發率並無明顯之研究證實。此研究主要是針對末期腎病接受透析的心肌梗塞病人，使用降膽固醇藥物是否有降低死亡率的效果。
我們蒐集臺灣健保資料庫從2000年到2012年的所有心肌梗塞病人，因末期腎病有接受血液透析的患者，排除復發的心肌梗塞，小於18歲的病人，及資料不全者，共蒐集到8056位病人，其中有2134位有接受降膽固醇藥物治療，5922位病人未接受降膽固醇藥物治療，追蹤其十二年的死亡率。結果發現有使用降膽固醇藥物者，其十二年的死亡率較未使用者低。有使用降膽固醇藥物者中風、腦出血與再心肌梗塞發生機率也較低。在調整過變數(After Propensity match 1:2)後，Cox Proportional Hazard Regression analysis分析發現，降膽固醇藥物可以降低心肌梗塞患者之長期(十二年)死亡率。
According to WHO (World health organization) data, the leading cause of mortality of human being is cardiovascular disease. Acute myocardial infarction (AMI) is the most severe form. In the past decades, owing to improvement of medical technique and medicine, the mortality rate and myocardial infarction rate decreased gradually, in which, lipid lowering agent (Statin) played important role. Use of statin has been associated with reduced risk of myocardial re-infarction rate and overall mortality in patients after AMI. However, in patients with end-stage renal disease (ESRD), receiving hemodialysis, the protective effects of statin seem to be controversial. This study aimed to evaluate the impact of statin use on clinical outcome of AMI in ESRD patients.
Total 8056 subjects with ESRD admitted for first AMI was enrolled from Taiwan National Health Insurance Research Database (NHIRD). In these patients, 2,134 patients underwent therapy with statin and other 5,922 patients did not receive stain therapy.
Statin use resulted in a significantly better 12-year survival rate in overall AMI patients with ESRD than non-statin users, including stroke, intracranial bleeding and myocardial re-infarction rate. In sub-group analysis, benefits of statin in AMI patient with ESRD also existed in patients irrespective of age, diabetes or not, and in male patient, patient not undergoing cardiac revascularization. After propensity matching (1:2 match), Cox Proportional Hazard Regression analysis showed use of statin made a better contribution to AMI long-term survival rate (adjusted Hazard Ratios 0.89, 95% CI: 0.82-0.97; p =0.007).
Statin therapy was shown to have better long term (12-year) outcome among ESRD patients suffered from first episode of AMI, irrespective of age, diabetes mellitus. In subgroup analysis, the benefit also existed in patients not undergoing cardiac revascularization, male patient. Among ESRD patients with acute MI, statin therapy was associated with reduced all-cause mortality.
Contents
摘要 I
Abstract III
謝誌 V
Contents VI
List of Tables VII
List of Figures VIII
1. Introduction 1
2. Literature Review 3
3. Methods and Experimental Design 45
3.1 Data Source 45
3.2 Study Population 46
3.3 Outcome analysis 48
3.4 Statistical Analyses 49
4. Research Results 50
4.1 Baseline characteristics 50
4.2 Impact of statin use on mortality after acute myocardial infarction with ESRD 57
5. Discussion 69
6. Conclusion 74
7. Limitations 75
Reference 76
Appendix 84
Author’s Profile 97
List of Tables
Table 1. Adjusted hazard ratios estimated between eGFR and clinical events 29
Table 2. Kidney function and life expectancy estimated 30
Table 3. Risk ratios estimated of CKD patients with or without ESRD 36
Table 4. Impacts of statin on LDL-C and clinical events 40
Table 4. Impacts of statin on LDL-C and clinical events (continued 1) 41
Table 5. Hazard ratios estimated between all caused mortality and medication use 42
Table 6. Mortality risk estimated of AMI patients with acute kidney injury 44
Table 7. Baseline characteristics of all selected patients 51
Table 7. Baseline characteristics of all selected patients (continued 1) 52
Table 7. Baseline characteristics of all selected patients (continued 2) 53
Table 8. Characteristics of patients with first hospitalized AMI with ESRD after propensity match 54
Table 8. Characteristics of patients with first hospitalized AMI with ESRD after propensity match (continued 1) 55
Table 8. Characteristics of patients with first hospitalized AMI with ESRD after propensity match (continued 2) 56
Table 9. Cox proportional hazard regression before propensity match 58
Table 10. Cox proportional hazard regression after propensity match 59
List of Figures
Figure 1. The cause of atherosclerosis 4
Figure 2. Atherothrombosis: a generalized and progressive process 6
Figure 3. The association between total cholesterol level and clinical events 7
Figure 4. Correlation between LDL-C and incidence rate of CHD in primary and secondary prevention trials 9
Figure 5. Relative risk estimated for LDL-C and coronary heart disease 11
Figure 6. The mortality of acute myocardial infarction 12
Figure 7. The incidence of major adverse cardiovascular events of patients with AMI in 3 years 13
Figure 8. The mortality of patients with AMI in Taiwan 14
Figure 9. The incidence of post-MI for AMI patients in 3 years in Taiwan 15
Figure 10. The incidence of clinical events for AMI patients with or without statin therapy 16
Figure 11. The incidence of fatal or nonfatal stroke for AMI patients with or without statin therapy 17
Figure 12. The incidence of death, MI or re-hospitalization for AMI patients who had controlled LDL-C by using Pravastatin or Atorvastatin 18
Figure 13. The incidence of recurrent MI or coronary death with different LDL-C and CRP levels 19
Figure 14. The study design of AMI patients who had Ezetimibe/simvastatin combined versus Simvastatin therapy 20
Figure 15. The long term trend of LDL concentration for AMI patients who had Ezetimibe/simvastatin combined versus Simvastatin therapy 21
Figure 16. Recurrence rate of cardiovascular events for AMI patients who had Ezetimibe/simvastatin combined versus Simvastatin therapy 22
Figure 17. The adjusted hazard ratios of clinical events and patients with chronic kidney disease who use verse non-use statin 25
Figure 18. Association between eGFR and clinical events (A) death; (B) cardiovascular events; (C) hospitalization. 26
Figure 18. Association between eGFR and clinical events (continued 1) (A) death; (B) cardiovascular events; (C) hospitalization. 27
Figure 18. Association between eGFR and clinical events (continued 2) (A) death; (B) cardiovascular events; (C) hospitalization. 28
Figure 19. Relative risks estimated in CKD patients without dialysis who used statin (A) all caused death; (B) cardiac caused death; (C) cardiovascular events; (D) stroke. 32
Figure 19. Relative risks estimated in CKD patients without dialysis who used statin (continued 1) (A) all caused death; (B) cardiac caused death; (C) cardiovascular events; (D) stroke. 33
Figure 19. Relative risks estimated in CKD patients without dialysis who used statin (continued 2) (A) all caused death; (B) cardiac caused death; (C) cardiovascular events; (D) stroke. 34
Figure 19. Relative risks estimated in CKD patients without dialysis who used statin (continued 3) (A) all caused death; (B) cardiac caused death; (C) cardiovascular events; (D) stroke. 35
Figure 20. Relative risks estimated of kidney failure and clinical events 38
Figure 21. The flow chart of study sample selection from National Health Insurance Research Database in Taiwan 47
Figure 22. Kaplan-Meier survival curves for ESRD patients after AMI with or without statin (log-rank p<0.0001) 60
Figure 23. Kaplan-Meier survival curves for ESRD patients after AMI with or without statin adjustfied for demographic strata (A) Male; (B) Female; (C) under 65 years old; (D) over 65 years old; (E) with PCI; (F) without PCI; (G) with DM; (H) without DM. 61
Figure 23. Kaplan-Meier survival curves for ESRD patients after AMI with or without statin adjustfied for demographic strata (continued 1) (A) Male; (B) Female; (C) under 65 years old; (D) over 65 years old; (E) with PCI; (F) without PCI; (G) with DM; (H) without DM. 62
Figure 23. Kaplan-Meier survival curves for ESRD patients after AMI with or without statin adjustfied for demographic strata (continued 2) (A) Male; (B) Female; (C) under 65 years old; (D) over 65 years old; (E) with PCI; (F) without PCI; (G) with DM; (H) without DM. 63
Figure 23. Kaplan-Meier survival curves for ESRD patients after AMI with or without statin adjustfied for demographic strata (continued 3) (A) Male; (B) Female; (C) under 65 years old; (D) over 65 years old; (E) with PCI; (F) without PCI; (G) with DM; (H) without DM. 64
Figure 23. Kaplan-Meier survival curves for ESRD patients after AMI with or without statin adjustfied for demographic strata (continued 4) (A) Male; (B) Female; (C) under 65 years old; (D) over 65 years old; (E) with PCI; (F) without PCI; (G) with DM; (H) without DM. 65
Figure 23. Kaplan-Meier survival curves for ESRD patients after AMI with or without statin adjustfied for demographic strata (continued 5) (A) Male; (B) Female; (C) under 65 years old; (D) over 65 years old; (E) with PCI; (F) without PCI; (G) with DM; (H) without DM. 66
Figure 23. Kaplan-Meier survival curves for ESRD patients after AMI with or without statin adjustfied for demographic strata (continued 6) (A) Male; (B) Female; (C) under 65 years old; (D) over 65 years old; (E) with PCI; (F) without PCI; (G) with DM; (H) without DM. 67
Figure 23. Kaplan-Meier survival curves for ESRD patients after AMI with or without statin adjustfied for demographic strata (continued 7) (A) Male; (B) Female; (C) under 65 years old; (D) over 65 years old; (E) with PCI; (F) without PCI; (G) with DM; (H) without DM. 68
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校外公開2024/08/10