研究目的：在冠心症、敗血症與缺血性中風發生前服用statin，對於疾病的預後有改善的效果。而突發性心跳停止的病患會有類似敗血症的的生理學反應。本文研究至急診時以心跳停止來表現的病患，是否在心跳停止前服用statin能改善其預後。

研究方法：本研究資料來源為『全民健康保險資料庫』全人口檔。以2004年至2011年資料庫篩選出在急診接受心肺復甦術的患者為分析對象，將病患分為在接受心肺復甦前30天連續使用statin與完全沒有使用statin兩群進行分析 。

研究結果：在使用傾向分數配對後的族群中，接受statin治療的患者，其一年存活率是沒有接受治療者的1.41倍（風險比=1.41，95%信賴區間=1.16-1.71，P≤0.01）。在次族群分析中，發現有糖尿病、慢性腎臟病與較高Charlson Comorbidity Index者，對於statin的治療特別的有反應。若在住院後停用statin，則其保護作用可能會變得不明顯。

結論：在心跳停止發先前30日使用statin，對於發生心跳停止的病患其預後有幫助，而此效果可以延續至一年，但若在住院後停用，則此保護作用可能會消失。

關鍵字：心跳停止、statin、一年存活

Background: Pretreatment with statins is associated with improved outcomes in severe sepsis, acute coronary syndrome, and stroke. Patients with cardiac arrest experience sepsis-like syndrome and ischemia reperfusion injuries in the heart and brain. The aim of this study was to investigate the effects of statin use before cardiac arrest on outcomes in patients presenting to emergency departments with cardiac arrest.

Methods: Medical records of 142,131 adult patients who experienced non-traumatic cardiac arrest and were resuscitated between 2004 and 2011 were retrieved from the Taiwan National Health Insurance Research Database (NHIRD). Patients were grouped into 2 groups: the “statin group” comprised patients who had received statin treatment for at least 30 days prior to the cardiac arrest event; the “non-statin group” comprised patients who had no statin use within 30 days before the event.

Results: Patients with prior statin treatment had better 1-year survival (4.8% vs. 3.2%; adjusted odds ratio 1.41, 95% confidence interval 1.16-1.71; p = 0.001) than patients in the propensity score-matched non-statin group. A favorable outcome effect of statin on one-year survival was observed in the presence of diabetes mellitus, chronic kidney disease, and Charlson Comorbidity Index score greater than 5 in the subgroup analysis. The beneficial effects of statins may become insignificant if statin use is discontinued after hospital admission.

Conclusion: Statin use before cardiac arrest is associated with one-year survival in cardiac arrest patients except for those with statin discontinuation after admission in a propensity score-matched nationwide cohort study.

致謝 i
中文摘要 ii
Abstract iii
目錄 v
第一章 緒論 1
第一節 研究背景與動機 1
第二節 研究目的 8
第三節 研究之重要性 9
第二章 文獻探討 10
第一節 到院前心跳停止病患之流行病學 10
第二節 敗血症及到院前心跳停止病患之生理狀態及statin可能之作用 15
第三節 急性冠心症及突發性心跳停止之關聯性及statin可能在兩者之作用 22
第四節 statin對於神經之保護作用 31
第三章 研究方法 37
第一節 研究設計 38
第二節 研究架構 40
第三節 研究假說 41
第四節 研究對象 42
第五節 研究方式工具及操作型定義 43
第六節 資料蒐集 47
第七節 資料處理與統計方法 48
第四章 研究結果 49
第一節 病患篩選描述性統計分析 50
第二節 Statin的使用對於心跳停止病患預後影響之推論性統計分析 58
第三節 次分組分析 (subgroup analysis) 62
第四節心跳停止前後使用分析 65
第五章 討論 66
第一節 研究結果分析 66
第二節 假說驗證 71
第三節 研究限制 72
第六章 結論與建議 74
第一節 結論 74
第二節 建議 76
參考文獻 77

一、中文部分
1. 衛生福利部104年主要死因統計結果分析
http://dep.mohw.gov.tw/DOS/lp-1777-113.html

2. 朱育增 (2010)。回顧與探討次級資料適用之共病測量方法。台灣衛誌 Vol 29, No 1
 
二、英文部分
1. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Després JP, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee.. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation. 2015 Jan 27;131(4):e29-322.

2. Ma MH, Chiang WC, Ko PC, Huang JC, Lin CH, Wang HC, Chang WT, Hwang CH, Wang YC, Hsiung GH, Lee BC, Chen SC, Chen WJ, Lin FY. Outcomes from out-of-hospital cardiac arrest in Metropolitan Taipei: does an advanced life support service make a difference? Resuscitation. 2007 Sep;74(3):461-9.

3. Kuo CW, See LC, Tu HT, Chen JC. Adult out-of-hospital cardiac arrest based on chain of survival in Taoyuan County, northern Taiwan. J Emerg Med. 2014 Jun;46(6):782-90. doi: 10.1016/j.jemermed.2013.08.026.

4. McNally B, Robb R, Mehta M, Vellano K, Valderrama AL, Yoon PW, Sasson C, Crouch A, Perez AB, Merritt R, Kellermann A; Centers for Disease Control and Prevention.. Out-of-hospital cardiac arrest surveillance --- Cardiac Arrest Registry to Enhance Survival (CARES), United States, October 1, 2005--December 31, 2010. MMWR Surveill Summ. 2011 Jul 29;60(8):1-19

5. Kim YJ, Ahn S, Sohn CH, Seo DW, Lee YS, Lee JH, Oh BJ, Lim KS, Kim WY. Long-term neurological outcomes in patients after out-of-hospital cardiac arrest. Resuscitation. 2016 Apr;101:1-5. doi: 10.1016/j.resuscitation.2016.01.004. Epub 2016 Jan 28.

6. Grunau B, Reynolds JC, Scheuermeyer FX, Stenstrom R, Pennington S, Cheung C, Li J, Habibi M, Ramanathan K, Barbic D, Christenson J. Comparing the prognosis of those with initial shockable and non-shockable rhythms with increasing durations of CPR: Informing minimum durations of resuscitation. Resuscitation. 2016 Apr;101:50-6.

7. Rea TD, Pearce RM, Raghunathan TE, Lemaitre RN, Sotoodehnia N, Jouven X, Siscovick DS. Incidence of out-of-hospital cardiac arrest. Am J Cardiol. 2004 Jun 15;93(12):1455-60.

8. Kronick SL, Kurz MC, Lin S, Edelson DP, Berg RA, Billi JE, Cabanas JG, Cone DC, Diercks DB, Foster JJ, Meeks RA, Travers AH, Welsford M. Part 4: Systems of Care and Continuous Quality Improvement: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015 Nov 3;132(18 Suppl 2):S397-413.

9. Kudenchuk PJ, Brown SP, Daya M, Rea T, Nichol G, Morrison LJ, Leroux B, Vaillancourt C, Wittwer L, Callaway CW, Christenson J, Egan D, Ornato JP, Weisfeldt ML, Stiell IG, Idris AH, Aufderheide TP, Dunford JV, Colella MR, Vilke GM, Brienza AM, Desvigne-Nickens P, Gray PC, Gray R, Seals N, Straight R, Dorian P; Resuscitation Outcomes Consortium Investigators.. Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. N Engl J Med. 2016 May 5;374(18):1711-22.

10. Driver BE, Debaty G, Plummer DW, Smith SW. Use of esmolol after failure of standard cardiopulmonary resuscitation to treat patients with refractory ventricular fibrillation. Resuscitation. 2014 Oct;85(10):1337-41.

11. Srivatsa UN, Ebrahimi R, El-Bialy A, Wachsner RY. Electrical storm: case series and review of management. J Cardiovasc Pharmacol Ther. 2003 Sep;8(3):237-46.

12. Dumas F, Cariou A, Manzo-Silberman S, Grimaldi D, Vivien B, Rosencher J, Empana JP, Carli P, Mira JP, Jouven X, Spaulding C. Immediate percutaneous coronary intervention is associated with better survival after out-of-hospital cardiac arrest: insights from the PROCAT (Parisian Region Out of hospital Cardiac ArresT) registry. Circ Cardiovasc Interv. 2010 Jun 1;3(3):200-7.

13. Dumas F, Grimaldi D, Zuber B, Fichet J, Charpentier J, Pène F, Vivien B, Varenne O, Carli P, Jouven X, Empana JP, Cariou A. Is hypothermia after cardiac arrest effective in both shockable and nonshockable patients?: insights from a large registry. Circulation. 2011 Mar 1;123(8):877-86.

14. O’Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, Ettinger SM, Fang JC, Fesmire FM, Franklin BA, Granger CB, Krumholz HM, Linderbaum JA, Morrow DA, Newby LK, Ornato JP, Ou N, Radford MJ, Tamis-Holland JE, Tommaso CL, Tracy CM, Woo YJ, Zhao DX. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127:529–555.

15. Task Force on the Management of ST-Segment Elevation Acute Myocardial 
Infarction of the European Society of Cardiology, Steg PG, James SK, Atar D, Badano LP, Blomstrom-Lundqvist C, Borger MA, Di Mario C, Dickstein K, Ducrocq G, Fernandez-Aviles F, Gershlick AH, Giannuzzi P, Halvorsen S, Huber K, Juni P, Kastrati A, Knuuti J, Lenzen MJ, Mahaffey KW, Valgimigli M, van ‘t Hof A, Widimsky P, Zahger D. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012;33:2569–2619. 


16. Stenestrand U, Wallentin L; Swedish Register of Cardiac Intensive Care (RIKS-HIA). Early statin treatment following acute myocardial infarction and 1-year survival. JAMA. 2001 Jan 24-31;285(4):430-6.

17. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, Brown L, Warnica JW, Arnold JM, Wun CC, Davis BR, Braunwald E. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996 Oct 3;335(14):1001-9.

18. Adrie C, Adib-Conquy M, Laurent I, Monchi M, Vinsonneau C, Fitting C, Fraisse F, Dinh-Xuan AT, Carli P, Spaulding C, Dhainaut JF, Cavaillon JM. Successful cardiopulmonary resuscitation after cardiac arrest as a "sepsis-like" syndrome. Circulation. 2002 Jul 30;106(5):562-8.

19. Ridker PM, Cannon CP, Morrow D, Rifai N, Rose LM, McCabe CH, Pfeffer MA, Braunwald E; Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) Investigators. C-reactive protein levels and outcomes after statin therapy. N Engl J Med. 2005 Jan 6;352(1):20-8.

20. Hackam DG, Mamdani M, Li P, Redelmeier DA. Statins and sepsis in patients with cardiovascular disease: a population-based cohort analysis. Lancet. 2006 Feb 4;367(9508):413-8.

21. Almog Y, Shefer A, Novack V, Maimon N, Barski L, Eizinger M, Friger M, Zeller L, Danon A. Prior statin therapy is associated with a decreased rate of severe sepsis. Circulation. 2004 Aug 17;110(7):880-5.

22. Sironi L, Cimino M, Guerrini U, Calvio AM, Lodetti B, Asdente M, Balduini W, Paoletti R, Tremoli E. Treatment with statins after induction of focal ischemia in rats reduces the extent of brain damage. Arterioscler Thromb Vasc Biol. 2003 Feb 1;23(2):322-7.

23. Yeh PS, Lin HJ, Bai CH, Hsieh FI, Ke DS, Li YH; Taiwan Stroke Registry. Effect of in-hospital initiation of lipid-lowering therapy on six-month outcomes in patients with acute ischemic stroke or transient ischemic attack. Am J Cardiol. 2010 May 15;105(10):1490-4.

24. Neumar RW, Nolan JP, Adrie C, Aibiki M, Berg RA, Böttiger BW, Callaway C, Clark RS, Geocadin RG, Jauch EC, Kern KB, Laurent I, Longstreth WT Jr, Merchant RM, Morley P, Morrison LJ, Nadkarni V, Peberdy MA, Rivers EP, Rodriguez-Nunez A, Sellke FW, Spaulding C, Sunde K, Vanden Hoek T. Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A consensus statement from the International Liaison Committee on Resuscitation (American Heart Association, Australian and New Zealand Council on Resuscitation, European Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Asia, and the Resuscitation Council of Southern Africa); the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; and the Stroke Council. Circulation. 2008 Dec 2;118(23):2452-83.

25. Ong ME, Shin SD, De Souza NN, Tanaka H, Nishiuchi T, Song KJ, Ko PC, Leong BS, Khunkhlai N, Naroo GY, Sarah AK, Ng YY, Li WY, Ma MH; PAROS Clinical Research Network. Outcomes for out-of-hospital cardiac arrests across 7 countries in Asia: The Pan Asian Resuscitation Outcomes Study (PAROS). Resuscitation. 2015 Nov;96:100-8.

26. Ma MH, Chiang WC, Ko PC, Yang CW, Wang HC, Chen SY, Chang WT, Huang CH, Chou HC, Lai MS, Chien KL, Lee BC, Hwang CH, Wang YC, Hsiung GH, Hsiao YW, Chang AM, Chen WJ, Chen SC. A randomized trial of compression first or analyze first strategies in patients with out-of-hospital cardiac arrest: results from an Asian community. Resuscitation. 2012 Jul;83(7):806-12.

27. Ma MH, Chiang WC, Ko PC, Huang JC, Lin CH, Wang HC, Chang WT, Hwang CH, Wang YC, Hsiung GH, Lee BC, Chen SC, Chen WJ, Lin FY. Outcomes from out-of-hospital cardiac arrest in Metropolitan Taipei: does an advanced life support service make a difference? Resuscitation. 2007 Sep;74(3):461-9.

28. Shao F, Li CS, Liang LR, Li D, Ma SK. Outcome of out-of-hospital cardiac arrests in Beijing, China. Resuscitation. 2014 Nov;85(11):1411-7.

29. Kuo CW, See LC, Tu HT, Chen JC. Adult out-of-hospital cardiac arrest based on chain of survival in Taoyuan County, northern Taiwan. J Emerg Med. 2014 Jun;46(6):782-90.

30. Nichol G, Thomas E, Callaway CW, Hedges J, Powell JL, Aufderheide TP, Rea T, Lowe R, Brown T, Dreyer J, Davis D, Idris A, Stiell I; Resuscitation Outcomes Consortium Investigators. Regional variation in out-of-hospital cardiac arrest incidence and outcome. JAMA. 2008 Sep 24;300(12):1423-31.

31. Schewe JC, Kappler J, Heister U, Weber SU, Diepenseifen CJ, Frings B, Hoeft A, Fischer M. Outcome of out-of-hospital cardiac arrest over a period of 15 years in comparison to the RACA score in a physician staffed urban emergency medical service in Germany. Resuscitation. 2015 Nov;96:232-8.

32. S?holm H, Kjaergaard J, Bro-Jeppesen J, Hartvig-Thomsen J, Lippert F, K?ber L, Nielsen N, Engsig M, Steensen M, Wanscher M, Karlsen FM, Hassager C. Prognostic Implications of Level-of-Care at Tertiary Heart Centers Compared With Other Hospitals After Resuscitation From Out-of-Hospital Cardiac Arrest. Circ Cardiovasc Qual Outcomes. 2015 May;8(3):268-76.

33. von Vopelius-Feldt J, Coulter A, Benger J. The impact of a pre-hospital critical care team on survival from out-of-hospital cardiac arrest. Resuscitation. 2015 Nov;96:290-5.

34. Blom MT, Beesems SG, Homma PC, Zijlstra JA, Hulleman M, van Hoeijen DA, Bardai A, Tijssen JG, Tan HL, Koster RW. Improved survival after out-of-hospital cardiac arrest and use of automated external defibrillators. Circulation. 2014 Nov 18;130(21):1868-75.

35. Adrie C, Laurent I, Monchi M, Cariou A, Dhainaou JF, Spaulding C. Postresuscitation disease after cardiac arrest: a sepsis-like syndrome? Curr Opin Crit Care. 2004 Jun;10(3):208-12. Review.

36. Adrie C, Adib-Conquy M, Laurent I, Monchi M, Vinsonneau C, Fitting C, Fraisse F, Dinh-Xuan AT, Carli P, Spaulding C, Dhainaut JF, Cavaillon JM. Successful cardiopulmonary resuscitation after cardiac arrest as a "sepsis-like" syndrome. Circulation. 2002 Jul 30;106(5):562-8.

37. Kandasamy K, Prawez S, Choudhury S, More AS, Ahanger AA, Singh TU, Parida S, Mishra SK. Atorvastatin prevents vascular hyporeactivity to norepinephrine in sepsis: role of nitric oxide and α₁-adrenoceptor mRNA expression. Shock. 2011 Jul;36(1):76-82.

38. Kruger P, Bailey M, Bellomo R, Cooper DJ, Harward M, Higgins A, Howe B, Jones D, Joyce C, Kostner K, McNeil J, Nichol A, Roberts MS, Syres G, Venkatesh B; ANZ-STATInS Investigators–ANZICS Clinical Trials Group. A multicenter randomized trial of atorvastatin therapy in intensive care patients with severe sepsis. Am J Respir Crit Care Med. 2013 Apr 1;187(7):743-50.

39. Hackam DG, Mamdani M, Li P, Redelmeier DA. Statins and sepsis in patients with cardiovascular disease: a population-based cohort analysis. Lancet. 2006 Feb 4;367(9508):413-8

40. Liappis AP, Kan VL, Rochester CG, Simon GL. The effect of statins on mortality in patients with bacteremia. Clin Infect Dis. 2001 Oct 15;33(8):1352-7.

41. Almog Y, Shefer A, Novack V, Maimon N, Barski L, Eizinger M, Friger M, Zeller L, Danon A. Prior statin therapy is associated with a decreased rate of severe sepsis. Circulation. 2004 Aug 17;110(7):880-5.

42. Ridker PM, Cannon CP, Morrow D, Rifai N, Rose LM, McCabe CH, Pfeffer MA, Braunwald E; Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) Investigators. C-reactive protein levels and outcomes after statin therapy. N Engl J Med. 2005 Jan 6;352(1):20-8.

43. Endorsed by the Latin American Society of Interventional Cardiology; PCI WRITING COMMITTEE, Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, Chambers CE, Ellis SG, Guyton RA, Hollenberg SM, Khot UN, Lange RA, Mauri L, Mehran R, Moussa ID, Mukherjee D, Ting HH; STEMI WRITING COMMITTEE, O''Gara PT, Kushner FG, Ascheim DD, Brindis RG, Casey DE Jr, Chung MK, de Lemos JA, Diercks DB, Fang JC, Franklin BA, Granger CB, Krumholz HM, Linderbaum JA, Morrow DA, Kristin Newby L, Ornato JP, Ou N, Radford MJ, Tamis-Holland JE, Tommaso CL, Tracy CM, Joseph Woo Y, Zhao DX; ACC/AHA TASK FORCE MEMBERS, Halperin JL, Levine GN, Anderson JL, Albert NM, Al-Khatib SM, Birtcher KK, Bozkurt B, Brindis RG, Cigarroa JE, Curtis LH, Fleisher LA, Gentile F, Gidding S, Hlatky MA, Ikonomidis J, Joglar J, Kovacs RJ, Magnus Ohman E, Pressler SJ, Sellke FW, Shen WK, Wijeysundera DN. 2015 ACC/AHA/SCAI focused update on primary percutaneous coronary intervention for patients with ST-elevation myocardial Infarction: An update of the 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention and the 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Catheter Cardiovasc Interv. 2016 May;87(6):1001-19.

44. Noc M. Urgent coronary angiography and percutaneous coronary intervention as a part of postresuscitation management. Crit Care Med. 2008 Nov;36(11 Suppl):S454-7. Review.

45. Fonarow GC, Wright RS, Spencer FA, Fredrick PD, Dong W, Every N, French WJ; National Registry of Myocardial Infarction 4 Investigators. Effect of statin use within the first 24 hours of admission for acute myocardial infarction on early morbidity and mortality. Am J Cardiol. 2005 Sep 1;96(5):611-6.

46. Aronow HD, Topol EJ, Roe MT, Houghtaling PL, Wolski KE, Lincoff AM, Harrington RA, Califf RM, Ohman EM, Kleiman NS, Keltai M, Wilcox RG, Vahanian A, Armstrong PW, Lauer MS. Effect of lipid-lowering therapy on early mortality after acute coronary syndromes: an observational study. Lancet. 2001 Apr 7;357(9262):1063-8.

47. Spencer FA, Allegrone J, Goldberg RJ, Gore JM, Fox KA, Granger CB, Mehta RH, Brieger D; GRACE Investigators. Association of statin therapy with outcomes of acute coronary syndromes: the GRACE study. Ann Intern Med. 2004 Jun 1;140(11):857-66.

48. Mytas D, Zairis M, Karanasos A, Kosma L, Arsenos P, Tentolouris C, Pitsavos C, Foussas S, Stefanadis C, Cokkinos D. Effect of statin pretreatment on the outcome of ST-segment elevation myocardial infarction in patients without prior history of coronary artery disease. Hellenic J Cardiol. 2013 Nov-Dec;54(6):422-8.

49. Iwakura K, Ito H, Kawano S, Okamura A, Kurotobi T, Date M, Inoue K, Fujii K. Chronic pre-treatment of statins is associated with the reduction of the no-reflow phenomenon in the patients with reperfused acute myocardial infarction. Eur Heart J. 2006 Mar;27(5):534-9. Epub 2006 Jan 9.

50. Daskalopoulou SS, Delaney JA, Filion KB, Brophy JM, Mayo NE, Suissa S. Discontinuation of statin therapy following an acute myocardial infarction: a population-based study. Eur Heart J. 2008 Sep;29(17):2083-91.

51. Choi JC, Lee JS, Park TH, Cho YJ, Park JM, Kang K, Lee KB, Lee SJ, Ko Y, Lee J, Kim JT, Yu KH, Lee BC, Cha JK, Kim DH, Lee J, Kim DE, Jang MS, Kim BJ, Han MK, Bae HJ, Hong KS. Effect of pre-stroke statin use on stroke severity and early functional recovery: a retrospective cohort study. BMC Neurol. 2015 Jul 30;15:120.

52. Deplanque D, Masse I, Lefebvre C, Libersa C, Leys D, Bordet R. Prior TIA, lipid-lowering drug use, and physical activity decrease ischemic stroke severity. Neurology. 2006 Oct 24;67(8):1403-10.

53. Laufs U, Gertz K, Huang P, Nickenig G, Böhm M, Dirnagl U, Endres M. Atorvastatin upregulates type III nitric oxide synthase in thrombocytes, decreases platelet activation, and protects from cerebral ischemia in normocholesterolemic mice. Stroke. 2000 Oct;31(10):2442-9

54. Gertz K, Laufs U, Lindauer U, Nickenig G, Böhm M, Dirnagl U, Endres M. Withdrawal of statin treatment abrogates stroke protection in mice. Stroke. 2003 Feb;34(2):551-7.

55. https://health.gov.taipei/Portals/0/%E9%86%AB%E8%AD%B7%E7%AE%A1%E7%90%86%E8%99%95/%E6%80%A5%E8%A8%BA%E6%AA%A2%E5%82%B7%E5%88%86%E9%A1%9E.pdf

56. Lee CC, Tsai MS, Fang CC, et al. Effects of pre-arrest comorbidities on 90-day survival of patients resuscitated from out-of-hospital cardiac arrest. Emerg Med J 2011;28(5):432-6.
57. Herlitz J, M. Eek, J. Engdahl, et al. M. Factors at resuscitation and outcome among patients suffering from out of hospital cardiac arrest in relation to age. Resuscitation 2003;58 (3): 309–317.

58. Cheng SH, Chiang TL. The effect of universal health insurance on health care utilization in Taiwan. Results from a natural experiment. JAMA. 1997 Jul 9;278(2):89-93.

59. Tsai MS, Chiang WC, Lee CC, Hsieh CC, Ko PC, Hsu CY, Su CP, Chen SY, Chang WT, Yuan A, Ma MH, Chen SC, Chen WJ. Infections in the survivors of out-of-hospital cardiac arrest in the first 7 days. Intensive Care Med. 2005 May;31(5):621-6.

60. Dandona P, Aljada A, Chaudhuri A, Bandyopadhyay A. The potential influence of inflammation and insulin resistance on the pathogenesis and treatment of atherosclerosis-related complications in type 2 diabetes. J Clin Endocrinol Metab. 2003 Jun;88(6):2422-9.

61. Wissenberg M, Lippert FK, Folke F, Weeke P, Hansen CM, Christensen EF, Jans H, Hansen PA, Lang-Jensen T, Olesen JB, Lindhardsen J, Fosbol EL, Nielsen SL, Gislason GH, Kober L, Torp-Pedersen C. Association of national initiatives to improve cardiac arrest management with rates of bystander intervention and patient survival after out-of-hospital cardiac arrest. JAMA. 2013 Oct 2;310(13):1377-84.

62. Weisfeldt ML, Everson-Stewart S, Sitlani C, Rea T, Aufderheide TP, Atkins DL, Bigham B, Brooks SC, Foerster C, Gray R, Ornato JP, Powell J, Kudenchuk PJ, Morrison LJ; Resuscitation Outcomes Consortium Investigators. Ventricular tachyarrhythmias after cardiac arrest in public versus at home. N Engl J Med. 2011 Jan 27;364(4):313-21.

63. Layon AJ, Gabrielli A, Goldfeder BW, Hevia A, Idris AH. Utstein style analysis of rural out-of-hospital cardiac arrest [OOHCA]: total cardiopulmonary resuscitation (CPR) time inversely correlates with hospital discharge rate. Resuscitation. 2003 Jan;56(1):59-66.

64. Ellis JJ, Erickson SR, Stevenson JG, Bernstein SJ, Stiles RA, Fendrick AM. Suboptimal statin adherence and discontinuation in primary and secondary prevention populations. J Gen Intern Med. 2004 Jun;19(6):638-45.

65. Chan PS, Nallamothu BK, Krumholz HM, Spertus JA, Li Y, Hammill BG, Curtis LH; American Heart Association Get with the Guidelines–Resuscitation Investigators. Long-term outcomes in elderly survivors of in-hospital cardiac arrest. N Engl J Med. 2013 Mar 14;368(11):1019-26.