摘要:心血管的疾病(CVD),包括冠心病(CHD)及中風(stroke),是國人罹病和死亡的主要原因。 特別是在現今的社會中,高血壓、高血脂、冠心病、及中風的人口節節上升。雖然過去的研 究已經知道和高血壓相關的許多心血管疾病,但是根據大規模的研究顯示,血壓達到良好控 制的比率仍然偏低。要控制好血壓有賴於生活型態的調整,以及多種藥物的組合使用,目前 研發新的電氣燒灼技術可以電燒腎臟血管的交感神經,達到血壓控制的效果,可是目前研究 仍少且不普及。另一方面,高血壓相關疾病如舒張性心衰竭,在目前所做的研究仍不足,藥 物的使用仍然是依臨床的經驗,而沒有大規模資料庫可以作為研究。血脂異常(dyslipidemia)早就廣為人知是動脈血管粥狀硬化發展過程中最重要的危險因 子。台灣的流行病學研究顯示,高膽固醇血症(hypercholesterolemia,血中總膽固醇〉250毫 克/分升)的盛行率在1970年代是4.3%-5.5% ;在1980年代是12.99% ;在1990年代則上升 到17.1%。而高三酸甘油醋血症(hypertriglyceridemia,血中三酸甘油醋〉200毫克/分升)的盛行 率在1970年代是6.5%-11.1% ;在1990年代則上升到13.0%。血中高密度膽固醇(HDL-C)值 過低也是許多台灣人的獨立冠心病危險因子。以statins降低低密度脂蛋白膽固醇(LDL-C)在 過去二十年已成為血脂異常標準治療的大部分,目前還有更有效的藥物即將進入市場。但是, 令人非常困窘的是台灣的血脂異常治療指引多為參考西方人的標準,因為過去有關降脂葯物 治療(LLT)效果的研究多是在高加索人進行,有關心血管事件終點的大規模研究在亞洲人極 為少見,在台灣更付闕如。為了讓台灣的血脂異常指導方針能植基於我們本土的流行病學資 料、臨床和基礎醫學的研究數據,本聯盟執行之病人登錄研究試圖確定台灣血脂異常及血管 動脈硬化病人接受降脂治療之狀況,並藉由大規模登錄台灣接受初級和次級心血管疾病防治 之病人,來探討降脂治療對心血管疾病罹病率或死亡率之影響,及該達成的目標值為何。此 外,國内企業和研究人員也開發出許多新的診斷和治療器材,需要本聯盟來幫助他們實現其 “概念驗證”,或進行通過註冊所需的臨床試驗。我們的計晝乃建立台灣的高血壓及高血脂兩種最重要的危險因子及動脈血管粥狀硬化疾病相 關的生物檢體資料庫以及臨床試驗聯盟,希望能用合作的方式,在台灣的主要22家醫學中 心,建立一個電子資料庫的收集平台,使用共通的資料登記軟體,收集臨床病患的共通條件, 主要的目的是希望能完成高品質的臨床試驗,並吸引國外重要的臨床試驗在台灣進行,同時 也扶植本土的心血管疾病藥物或器材的的臨床試驗或研究發展。另外我們也希望能使用嚴格 的管控,病患願意將其生物檢體提供研究,由各個醫院登入病患的資料到電子系統中心,定 期由中心控管品質,生物檢體以相同嚴格的條件存放在各家醫院中,資料庫中的病患資料, 優先提供給加入的成員使用,並可以作為日後國内或國際的臨床研究使用,也可以提供給生 物科技產業研發新的技術、新的藥物,進而促進整體國民的健康。本年度計晝,我們擬繼續收集登錄病人,並包括病人終點事件的收集,以期分析瞭解血 壓與血脂的控制與心血管事件的關係。我們亦將自資料庫中透過PI提出七項高血壓及高血脂 有關的研究;和2項新的研究以尋找可靠的血液生物標記物,來檢測具心血管疾風險的病患中 是否已發生認知功能障礙或血管性失智症,及預測中風患者發生血管性失智症的風險。
Abstract: Cardiovascular disease (CVD) including hypertension, hyperlipidemia, and the associated diseases, such as coronary heart disease (CHD), stroke, heart failure remains to be the most important health and public problems for the modern country. Although the influence and impact of hypertension is well-known, the adequate control rate is low and some hypertension-associated disease still lack adequate medical treatment. Successful treatment of raised blood pressure has proven elusive despite availability of various drugs, combination pharmaceutical products, and resources to assist patients’ adherence and lifestyle changes. Recently developed endovascular catheter technology enables selective denervation of the human kidney for better treatment of resistant hypertension. On the other hand, there was over half of patient with heart failure have diastolic heart failure (DHF). Hypertension could result in left ventricular hypertrophy and further diastolic dysfunction. Large randomized trials in selected patients with HF have led to major advances in the medical treatment of systolic HF. On the contrary, few randomized trials have been carried out with regard to medical management of DHF, despite its high prevalence and mortality. Therefore, treatment of DHF is still empirical and there is a scarcity of evidence-based recommendation towards the disease.On the other hand, dyslipidemia has long been recognized to be the most important risk factor in the development of atherosclerosis in human beings. In Taiwan, the rates for hypercholesterolemia (^250mg/dl) were 4.3% and 5.5% in 1970; 12.99% in 1980; and 17.1% in 1990. Those for hypertriglyceridemia (^200 mg/dl) were 6.5% and 11.1% in 1970 and 13.0% in 1990. Low serum HDL-C was an isolated and independent coronary risk factor among a good number of Taiwanese people. Lowering of low-density lipoprotein cholesterol (LDL-C) with statins has in the last decade become the most important part of the standard treatment regimen in patients with dyslipidemia. Even more potent drugs have been developed recently and will get into the market soon. However, most embarrassing is the insufficient data for clinical use in Taiwan. It is necessary to have rationalized and balanced guideline for the management of dyslipidemia in Taiwan, based on our local epidemiological, clinical and basic research data. Because all the previous trials were conducted in Caucasians and no large-scaled end-point research about the lipid lowering therapy (LLT) was published in Asians before, the registry study run by this consortium attempts to define the status of lipid lowering therapy in Taiwan, the effect of LLT on CVD morbidity and mortality in a large population of patients receiving primary or secondary prevention therapy, and the adequate target level of lipid for Taiwanese people. In addition, there have been many new diagnostic or therapeutic instruments, developed by domestic companies or researchers, needing to run clinical trials for “proof of concept” or registration.To achieve the above goals, it is important to conduct multicenter trials for the treatment of hypertension and hyperlipidemia associated diseases, which take the advantage of more efficient screening and enrollment of cases. Specifically, we can prospectively set up a biospecimen bank with clarified disease phenotype through the conduction of these trials. The biospecimen bank and the clinical information collected from these studies could also provide a platform for further investigation of cardiac diseases. We would then coordinate 22 large medical centers in Taiwan and form a hypertension/hyperlipidemia Consortium and biospecimen banks, recruiting patients with hypertension, resistant hypertension, hyperlipidemia and atherosclerosis-related cardiovascular diseases. Through this platform, we would like to promote and attract more important worldwide and domestic clinical trials to be run by this consortium.This year, we propose to collect endpoints of the registered patients to analyze relationship between treatment status of hypertension and hyperlipidemia, and the outcome. We will from the data bank initiate 7 proposals by PIs to explore the status of current management of hypertension and hyperlipidemia in Taiwan, and 2 new proposals to find new reliable blood biomarkers to detect cognitive dysfunction and dementia among patients with risks for cardiovascular diseases or to predict the risks of vascular dementia among patients with stroke.