頁籤選單縮合
題 名 | 動脈硬化性疾病與Statin之治療--從基礎研究到臨床應用=Atherosclerostic Disease and Statins Therapy--From Bench to Bedside |
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作 者 | 黃耀星; 胡淑寶; 阮仲洲; | 書刊名 | Medical Journal of South Taiwan |
卷 期 | 4:2 2008.09[民97.09] |
頁 次 | 頁61-72 |
分類號 | 415.384 |
關鍵詞 | 動脈粥狀硬化; 血脂異常症; 心血管疾病; 低密度膽固醇; Atherosclerosis; Statins; Dyslipidemia; Cardiovascular disease; LDL-cholesterol; |
語 文 | 中文(Chinese) |
中文摘要 | 動脈硬化是一種慢性炎症的觀念,始於100多年前的Virchow R(1856)及Rokitansky。在100年後由Ross等以「傷害引起的反應」(Response-to-injury)的學說,建立其病理變化,而阻礙血小板功能可防止平滑肌之增生。過去30年來,對atherogensis之細胞及分子機轉之研究有長足進步。對動脈硬化及高膽固醇異常的不斷持續的研究,到了19世紀末葉,由Brown MS及Goldstein JL(1985)發現LDL-受體及其作用機轉,並陳述虛血性心臟病盛行率可能急速減少及Akira Endo等發現Statin而告一段落。在19世紀中期,由於冠狀動脈疾病之死亡率佔歐美各國首位,認知該疾病的形成與膽固醇(尤高LDL-C)有關,觸發這方面的研究,科學家們欲找出可以阻礙肝細胞內HMGCoA還原酶的化合物,於是研發Statin之風氣瀰漫全球。在1985年Brown MS及Goldstein JL兩位大師是當年醫學及生理學諾貝爾獎得主。其得獎理由為除了發現LDL-Receptor及作用機轉外,闡明解釋了代表發現LDL-Receptor的「脂蛋白質代謝之分子機轉」並陳述:將開發出強的高膽固醇治療(藥),虛血性心臟病盛行率可能急遽減少。Brown MS大師傑作“Heart Attacks: Gone with the Century?”(1996)值得一看。在1973年日本人Akira Endo終於由京都郊外土壤生長的米中,分離出Penicillium Citrinum(又叫ML236B、Com-pactin或Mevastatin),是世界第一個Statin的原型。後來陸續在'80及'81年代研發出Pravastatin、Lovastatin及Simvastatin出來。本文也簡介日本動脈硬化學會2007年出版之「動脈硬化疾病預防準則」。該準則之修訂是因過去5年來在日本所做的一些流行病學調查及大型研究結果,陸續發表。而以此實證醫學(EBM)為背景來修改。對臨床醫師實地擬定動脈硬化疾病對策時很有助益。新的準則建議:將hyperlipidemia改為Dyslipidemia(脂質異常症)。如遇到Dyslipidemia病患時,在給藥前先做生活形態調適,然後依照是一次或二次預防,再依病患有高LDL-C等以及以外之危險因子之多寡,將病患分類及層級化。依照病患是屬於低、中或高危險群,來擬定降脂管理目標值。著者等過去的研究也證實,Atrovastatin對國人高膽固醇病患,除可降低LDL-C外,也可調降血小板的CD40 Ligand及P-Selectin之表達(2004)。阻礙上游CD40/CD40補體之結合,可阻礙或延緩發炎及動脈硬化之進展。因此,Atrovastatin的抗發炎作用是其不可分的功能之一。已進入Statin的年代,Statin類藥物已被普遍使用於降膽固醇,其他發展中的Statin新用途有:治療心衰竭(NYHA Ⅱ-Ⅳ),做心導管或冠狀動脈攝影前,先做Statin治療,可防止打造影劑引起之腎病變(CIN),及應用在不整脈治療等。過去一年來,對動脈硬化及血栓形成方面的研究成果,除了強調預防醫學外,有生化影像,如PET、PET/MRI等之熔和應用及血管內超音波(IVUS)之發展。在診斷方面也有長足進步。但是,CETP阻礙劑(提升HDL-C)的開發失敗,期待以後有所進展。本文所提到的Statins類藥物名稱等,與著者等無利益衝突。 |
英文摘要 | Atherosclerosis is associated with chronic inflammation and adhesion between endothedial cell and circulating leukocytes play a key role in inflammatory process. After decades of controversy, there has no longer serious debates from the fact that increasing serum cholesterol (LDL-C) as an important cause of cardiovascular (CV) disease and lowering cholesterol reduces risk.About one and half centuies ago, two renown physician R. Virchow and Rokitonsky had heately debated about inflammation and atherosclerosis. However, recent studies demonstrated that inflammation is critical in the disability of atherosclerotic plaque leading to aute CV events. The underlying mech-anisms triggering the inflammatory response of atherosclerosis remained unknown, however, multiple inflammatory markers, eg. tissue thromboplastin, VCAM-1 had been found highly expression in hyperchole- sterolemia. In addition, inflammatory markers, e.g. hs-CRP, IL-6, ICAM-1, TNF-α and CD40L had been found in associated with coronary artery disease (CAD). Among them, CRP was well correlated with CV events.The Japan Atherosclerosis Society (JAS) guideline (GL) for Diagnosis and Prevention of Altherosclerotic Cardiovascular Disease for Japanese have been published in 2007. Briefly, motivated by good results of last GL published in 2002 and emerging of new EBM from large scale epidemiological and clinical researches in Japan, new GL was published. In 2007 GL, the term hypercholesterolemia was replaced by dyslipidemia. The diagnostic values for each dyslipidemia was defined as high low density lipoproteinemia, LDL-C ≧ 140mg/dl; in hypertriglyceridemia, TG ≧ 160mg/dl and in hypo- high density lipo-protein cholesterolemia, HDL-C<40mg/dl. As regarding to categorized a dys-chronic inflammation and adhesion between lipidemic patient, one should classified as endothedial cell and circulating leukocytes primary or secondary prevention. Beside serum LDL-Cholesterol levels, the following risk factors needed to put into considerations, e. g. gender / aging, diabetes mellitus, hypertension, smoking and patient's family history of CV disease. Subsequently, grading of patient according to regulation of GL. As in primary prevention, before starting phar-macological therapy, life style modification should be performed.In our previous studies, we demonstrated that atorvastatin 10mg/day for 8 weeks, not only decreased the cholesterol levels, but also down regulation of CD 40 ligand and P-selection on platelets in patients with dyslipidemia. Thus, the interference of CD40- CD40L can be recognized as an integral part of the anti-inflammatory activity of atorvastatin. Currently, there are several pharmaco logical strategies for preventing recurrent myocardial infarction or death, this class of drug, include statins, angiotensin converting enzyme inhibitors, ARBs and fibric acid derivatives., e.g. PPAR-γ agonist and probably aspirin.In conclusion, atherosclerosis previously viewed as an aging process which medical science was powerless alter, however, now we can learn more in depth via prism of inflammation, atherosclerosis is widely viewed as a chronic inflammatory disease. In this statin era, this class of drug has been widely used. Statins can modified and/or retared the progression of atherosclerosis, stabilized of atherosclerotic plaque changes. |
本系統中英文摘要資訊取自各篇刊載內容。