Clinical Practice 2022 Taiwan lipid guidelines for primary prevention 06

台灣2022年血脂治療指引部分更新
 中間有些跳過. 節錄片段
非藥物治療. 飲食控制
幾項觀察性和隨機臨床研究表明，較低的 ASCVD 風險與健康飲食模式之間存在關聯，例如地中海飲食、DASH（停止高血壓的飲食方法）飲食、健康的台灣飲食方法 (TEA) 和台灣素食。 45e48 台灣人飲食模式研究還發現油炸食品、甜食和甜味飲料、高脂肪和含糖糕點、脂肪和內臟肉類是心血管代謝疾病的危險食物。 47,49 基於這些研究，保護心臟的飲食模式包括：食物包括全穀類、蔬菜、新鮮水果、堅果和種子、茶和富含不飽和脂肪酸的非熱帶植物油（如大豆油、葵花籽油、橄欖油）；omega-3 脂肪酸的來源（例如魚、堅果、豆類）；優質蛋白質食品（低度加工豆製品、魚、蛋、瘦動物蛋白）；低反式脂肪、油炸食品、肥肉、加工肉類或魚製品（例如，香腸、培根、火腿和熱狗）和添加/精製糖。50e54 薈萃分析表明，低碳水化合物飲食可能有助於減肥並改善 HDL-C 和 TG 水平。55 然而，LDL-C 和總膽固醇 (TC) 升高的潛在後果是一個主要問題。在過去的幾十年裡，雞蛋消費與 ASCVD 發展之間的適度關聯已經確定，但仍存在爭議。雞蛋不僅飽和脂肪酸含量低，而且富含蛋白質和各種微量營養素，已被證明可以促進大的 LDL-C 的形成，從而減少動脈粥樣硬化。 56,57 由於可能仍然存在適度的劑量反應關係，應根據個人的LDL-C目標和營養狀況個體化攝入適量的雞蛋。此外，由於之前觀察到飽和脂肪酸含量會增加 LDL-C 水平，食用乳製品的影響也存在爭議。 58 最近的薈萃分析顯示食用乳製品對 CV 結果有積極或中性影響，而台灣人前瞻性研究顯示保護關聯。 47 乳製品，包括發酵的和最好是脫脂或低脂產品，可以作為健康飲食的一部分適量食用。 59

膳食補充劑 一些膳食補充劑被認為對健康有益。魚油或海洋 omega-3 脂肪酸補充劑在二十碳五烯酸 (EPA) 和二十二碳六烯酸 (DHA) 的作用下會產生劑量依賴性的 TG 降低，但 TC、LDL-C 或 HDL-C 沒有明顯變化.60,61 紅曲米 (RYR) 提取物已被用作降低膽固醇的保健品。在水稻發酵過程中，主要的生物活性化合物莫納可林 K 是 3-羥基-3-甲基戊二酰輔酶 A (HMG-CoA) 還原酶的弱可逆抑製劑。在一項薈萃分析研究中，使用 1200 毫克/天至 4800 毫克/天的 RYR，與安慰劑相比，LDL-C 降低了 18.4 毫克/分升。 62 然而，市場上的 RYR 產品質量參差不齊，RYR 可能存在藥理相互作用的潛在風險，其安全性結果尚未得到廣泛研究。可可製品中的類黃酮可抑制膽固醇的吸收。一項薈萃分析表明，食用黑巧克力 2-12 周可顯著降低 TC 和 LDL-C（分別為 6.2 和 5.9 mg/dL）。 63 儘管如此，令人擔憂的是，黑巧克力產品含有不同量的飽和脂肪並添加糖。維生素 D 可能通過調節維生素 D 受體的轉錄活性和抑制 HMG-CoA 還原酶表達的胰島素誘導基因 2 活性來影響循環膽固醇水平。64,65 臨床研究表明補充維生素 D 有利於降低 TC、LDL- C、TG但對HDLC水平無影響。

Non-pharmacological therapy

Diet

Several observational and randomized clinical studies have demonstrated association between a lower risk of ASCVD and healthy dietary patterns, such as Mediterranean diet, DASH (Dietary Approaches to Stop Hypertension) diet, healthy Taiwanese eating approach (TEA), and Taiwanese vegetarian diet.45e48 Taiwanese dietary pattern studies also identified fried foods, sweets and sweetened beverages, high fat and sugar-containing pastry, fatty and organ meats as risky foods for cardiometabolic diseases.47,49 Based on these studies, a cardioprotective dietary pattern includes: rich plant-based foods including whole grains, vegetables, fresh fruits, nuts and seeds, tea, and unsaturated fatty acid-rich non-tropical plant oils (e.g., soybean oil, sunflower oil, olive oil); sources of omega-3 fatty acids (e.g., fish, nuts, legumes); good protein foods (low degree processed soy product, fish, egg, and lean animal protein); low in trans-fats, fried foods, fatty meat, processed meats or fish products (e.g., sausage, bacon, ham and hot dogs), and added/refined sugars.50e54 Meta-analysis indicated that low-carbohydrate diets may help weight loss and improve HDL-C and TG levels.55 However, the potential consequence of elevated LDL-C and total cholesterol (TC) is a major concern. In the past decades, the modest association between eggs consumption and the development of ASCVD has been established but remains controversial. Eggs are not only low in saturated fatty acid but also rich in protein and various micronutrients, which have been shown to promote the formation of large LDL-C, which is less atherogenic.56,57 Since there may still be a moderate doseeresponse relationship, the appropriate amount of egg consumption should be individualized based on individual’s LDL-C target and nutrition status. Besides, the effect of dairy consumption is also controversial due to previous observation relating the saturated fatty acid content to increase LDL-C levels.58 Recent meta-analyses revealed either positive or neutral effects on CV outcomes from consumption of dairy products, while a Taiwanese prospective study showed protective association.47 Dairy, including fermented and preferably no-fat or low-fat products, may be consumed moderately as part of a healthy diet.59

Dietary supplements Some dietary supplements are considered to be beneficial for health. Fish oil, or marine omega-3 fatty acid supplementation, yields a dose-dependent reduction in TG from the effect of eicosapentenoic acid (EPA) and docosahexenoic acid (DHA), but no overt changes in TC, LDL-C or HDL-C.60,61 Red yeast rice (RYR) extract has been applied as a cholesterol-lowering nutraceutical. During the rice fermentation, the main bioactive compound, monacolin K, is a weak reversible inhibitor of 3-hydroxy-3- methylglutaryl-coenzyme A (HMG-CoA) reductase. In a metaanalysis study, using RYR from 1200 mg/day to 4800 mg/ day, LDL-C was lowered with 18.4 mg/dL compared to placebo.62 However, the quality of RYR products in the market varied and RYR may possess a potential risk of pharmacological interactions and its safety outcomes have not been extensively studied yet. The flavonoids in cocoa products inhibit cholesterol absorption. A meta-analysis showed that consumption of dark chocolate for 2e12 weeks significantly reduced TC and LDL-C (6.2 and 5.9 mg/ dL), respectively.63 Nonetheless, it is a concern that dark chocolate products contained varied amount of saturated fats and added sugar. Vitamin D may affect circulating cholesterol levels by modulating the transcription activity of vitamin D receptor and insulin-induced gene-2 activity which inhibits HMG-CoA reductase expression.64,65 Clinical study indicated that vitamin D supplementation has benefits on reducing TC, LDL-C, and TG but no influence on HDLC level.64 A meta-analysis of 14 randomized controlled trials showed that consumption of green tea or its extracts resulted in a moderate reduction in TC and LDL-C concentrations, but no change in HDL-C.66 However, a longitudinal cohort study with 6-year follow-up showed that frequent tea consumption, including black tea and green tea, was associated with a slower age-related decrease in HDL-C concentrations.67

Clinical Practice 2022 Taiwan lipid guidelines for primary prevention 05

台灣2022年血脂治療指引部分更新

沒有高風險的受試者 在沒有 DM、CKD 和 LDL-C 190 mg/dL 的受試者中，應評估 ASCVD 的其他危險因素。這些包括：(1) 高血壓，(2) 男性年齡大於 45 歲或女性大於 55 歲或絕經期女性，(3) 早發 CAD 家族史（男性小於 55 歲或女性小於 65 歲）女性），(4) 高密度脂蛋白膽固醇 (HDL-C) 男性低於 40 mg/dL 或女性低於 50 mg/dL 和 (5) 吸煙。 35 因為向心性肥胖、糖尿病前期和甘油三酯 (TG)在一些研究中也被認為是 ASCVD 危險因素，包括所有這些項目的代謝綜合徵在本指南中被視為第六個獨立危險因素。代謝綜合徵是根據修改後的亞洲人國家膽固醇教育計劃成人治療小組 III 定義的。 36，37 滿足以下三個或更多標準的患者被認為患有代謝綜合徵：(1) 男性腰圍大於 90 厘米或女性大於 80 厘米，(2) 血壓為 130/ 85 毫米汞柱或更高或使用抗高血壓藥物，(3) 空腹血糖水平為 100 mg/dL 或更高或使用抗糖尿病藥物，(4) 空腹 TG 水平為 150 mg/dL 或更高或使用降脂劑以增加 TG，以及 ( 5) HDL-C 男性低於 40 mg/dL 或女性低於 50 mg/dL（表 1）。基於上述風險因素評估，一級預防對象可分為以下風險類別。高風險表示受試者患有 DM、CKD 或 LDL-C 190 mg/dL。在那些沒有 DM、CKD 或 LDL-C 190 mg/dL 的人中，中度風險表示受試者有 2 個或更多風險因素，低風險表示有 1 個風險因素，最小風險表示沒有風險因素。高風險受試者需要立即降脂治療以達到推薦的LDL-C目標。對於沒有高風險的受試者，建議首先改變生活方式 3 個月，然後再考慮降脂治療。表 2 總結了初級預防的總體風險類別。

建議
對於一級預防，患有 DM、非透析性 CKD 或 LDL-C 190 mg/dL 的受試者處於 ASCVD 的高風險中，需要立即進行降脂治療。（COR I，LOE A）在沒有 DM、CKD 或 LDL-C 190 mg/dL 的受試者中，ASCVD 的風險應根據風險因素分類為最小、低或中等。（COR I，LOE C）

Subjects without high risk In subjects without DM, CKD, and LDL-C
190 mg/dL, other risk factors of ASCVD should be evaluated. These include: (1) hypertension, (2) age greater than 45 years in men or greater than 55 years in women or menopausal women, (3) family history of premature CAD (less than 55 years in men or less than 65 years in women), (4) high-density lipoprotein cholesterol (HDL-C) less than 40 mg/dL in men or less than 50 mg/dL in women and (5) smoking.35 Because central obesity, prediabetes and triglyceride (TG) are also considered to be ASCVD risk factors in some studies, metabolic syndrome that include all these items is regarded as the sixth independent risk factor in this guideline. Metabolic syndrome is defined according to the modified National Cholesterol Education Program Adult Treatment Panel III for Asians.36,37 Patients who meet three or more of the following criteria are considered to have metabolic syndrome: (1) waist circumference greater than 90 cm in men or greater than 80 cm in women, (2) blood pressure of 130/ 85 mmHg or higher or use of antihypertensive medication, (3) fasting glucose level of 100 mg/dL or higher or use of antidiabetic drug, (4) fasting TG level of 150 mg/dL or higher or use of lipid-lowering agent for increased TG, and (5) HDL-C less than 40 mg/dL in men or less than 50 mg/dL in women (Table 1). Based on the above-mentioned risk factor evaluation, the subjects with primary prevention can be classified into the following risk categories. High risk indicates subjects with DM, CKD or LDL-C
190 mg/dL. In those without DM, CKD or LDL-C
190 mg/dL, moderate risk indicates subjects with 2 or more risk factors, low risk indicates with 1 risk factor and minimal risk indicates no risk factor. Subjects with high risk need immediate lipid lowering therapy to reach the recommended LDL-C target. Lifestyle modification first is recommended for 3 months before considering lipid lowering therapy in the subjects without high risk. The overall risk categories for primary prevention are summarized in Table 2.

Recommendation
For primary prevention, subjects with DM, nondialysis CKD, or LDL-C
190 mg/dL are at high risk of ASCVD and immediate lipid lowering therapy is necessary. (COR I, LOE A) In subjects without DM, CKD, or LDL-C
190 mg/dL, the risk of ASCVD should be classified as minimal, low, or moderate according to the risk factors. (COR I, LOE C)

Clinical Practice 2022 Taiwan lipid guidelines for primary prevention 04

Risk calculator
風險計算
對於初級預防，人口研究衍生的 ASCVD 風險估計計算器，例如 Framingham 風險評分，通常用於決定受試者是否應該接受降脂治療。近年來，美國心髒病學會 (ACC) 和美國心臟協會 (AHA) 開發了合併隊列方程。 15,16 歐洲心髒病學會 (ESC) 和歐洲動脈粥樣硬化學會 (EAS) 使用 SCORE（系統性冠狀動脈風險評估）用於 ASCVD 風險評估。17,18 英國國家健康與護理卓越研究所 (NICE) 指南使用 QRISK2 作為 ASCVD 風險評估工具。19 儘管存在多種特定於人群的風險評估工具，但目前可用的模型均未派生來自或在東亞人中前瞻性驗證。用於估計 10 年 ASCVD 事件風險的 AHA/ACC 合併隊列方程適用於 40 至 79 歲的黑人和非西班牙裔白人男性和女性。15 該風險預測因子可能高估了中國人群的 ASCVD 風險。 20 Framingham 風險評分也高估了華人的 ASCVD 風險。 21 在台灣，1990 年代的金山社區心血管隊列研究開發了一個基於點的預測模型來預測 CAD 的 10 年風險。 22 然而，沒有指出定義高風險的明確分界點。一些檢查，如踝肱指數、脈搏波速度、頸動脈超聲和冠狀動脈鈣化評分，已被用於 ASCVD 風險評估。這些檢查的可及性是當地診所的一個主要問題。冠狀動脈鈣化評分檢查的成本和輻射暴露問題也是重要的考慮因素。基本上，該指南不鼓勵在無症狀受試者中常規篩查亞臨床動脈粥樣硬化的存在。目前階段，使用風險因素的數量是台灣風險分層的一種更方便的方法。風險類別 高風險（DM、CKD 和 LDL-C ‡ 190 mg/dL） 本初級預防指南決定保留常規目標方法，並根據 CV 風險因素的存在定制 LDL-C 治療目標。由於 ASCVD 是導致 DM 和 CKD 人群顯著死亡率的一個主要問題，因此這兩組患者被認為處於高風險中。2017 年台灣高危患者血脂指南描述了 DM 的診斷和糖尿病血脂異常的管理策略。10 對於 CKD，白蛋白尿是用於檢測和定義 CKD 的重要生物標誌物。白蛋白尿是指尿中白蛋白排泄增加。未計時尿樣中的尿白蛋白與肌酐比值 (UACR) 已取代 24 小時尿白蛋白排泄量，成為測量白蛋白尿的首選方法。23e26 白蛋白尿定義為 UACR 30 mg/g，可進一步分為微量白蛋白尿(UACR 30e300 mg/g) 和大量白蛋白尿 (UACR > 300 mg/g)。國家腎臟基金會腎臟疾病結果質量倡議 (KDOQI) 指南將 CKD 定義為腎臟損傷 (UACR 30 mg/g) 或腎小球濾過率 (GFR) < 60 mL/min/1.73 m2 至少三個月。27，28 GFR 通常根據腎臟疾病飲食改良 (MDRD)29 或慢性腎髒病流行病學協作 (CKD-EPI) 方程式從血清肌酐水平估算。 30 建議對 DM 和非糖尿病患者立即進行降脂治療-透析 CKD。定義為 LDLC 190 mg/dL 的嚴重高膽固醇血症具有 ASCVD 和早發 CV 事件的高風險。與一般人群相比，這些人患 CAD 的風險高 5 到 6 倍，男性患 CAD 的時間早 10-20 年，女性早 20-30 年。 31 早期開始降脂治療可以顯著降低這些受試者的發病率和死亡率。 32 LDL-C 190 mg/dL 顯著增加了 FH 存在的可能性。大約 7% 的 LDLC 190 mg/dL 的受試者可能符合 FH 的診斷標準。33 應考慮對這組受試者進行基因檢測以診斷 FH。先前的研究表明，與 LDL-C <130 mg/dL 且未檢測到 FH 基因突變的參考組相比，LDL-C 190 mg/dL 且未檢測到 FH 突變的受試者患 CAD 的風險高 6 倍，而那些LDL-C 190 mg/dL 和 FH 突變的風險增加了 22 倍。 34 因為 LDL-C 190 mg/dL 是一個非常獨特的高風險組，具有明顯的長期臨床結果，它被歸類為作為高風險。就像 DM 和 CKD 一樣，建議立即進行降脂治療並強化 LDL-C 控制，因為這些患者的 CV 風險非常高。與 LDL-C <130 mg/dL 且未檢測到 FH 基因突變的參考組相比，LDL-C 190 mg/dL 且未檢測到 FH 突變的受試者患 CAD 的風險高 6 倍，而那些同時具有 LDL-C 和190 mg/dL 和 FH 突變表明風險增加 22 倍。34 由於 LDL-C 190 mg/dL 是一個非常獨特的高風險組，具有明顯的長期臨床結果，因此它被歸類為高風險。就像 DM 和 CKD 一樣，建議立即進行降脂治療並強化 LDL-C 控制，因為這些患者的 CV 風險非常高。與 LDL-C <130 mg/dL 且未檢測到 FH 基因突變的參考組相比，LDL-C 190 mg/dL 且未檢測到 FH 突變的受試者患 CAD 的風險高 6 倍，而那些同時具有 LDL-C 和190 mg/dL 和 FH 突變表明風險增加 22 倍。34 由於 LDL-C 190 mg/dL 是一個非常獨特的高風險組，具有明顯的長期臨床結果，因此它被歸類為高風險。就像 DM 和 CKD 一樣，建議立即進行降脂治療並強化 LDL-C 控制，因為這些患者的 CV 風險非常高。34 因為 LDL-C 190 mg/dL 是一個非常獨特的高風險組，具有明顯的長期臨床結果，所以它被歸類為高風險。就像 DM 和 CKD 一樣，建議立即進行降脂治療並強化 LDL-C 控制，因為這些患者的 CV 風險非常高。34 因為 LDL-C 190 mg/dL 是一個非常獨特的高風險組，具有明顯的長期臨床結果，所以它被歸類為高風險。就像 DM 和 CKD 一樣，建議立即進行降脂治療並強化 LDL-C 控制，因為這些患者的 CV 風險非常高。

For primary prevention, population study-derived ASCVD risk estimate calculators, such as the Framingham risk score, are commonly used to decide whether a subject should receive lipid-lowering therapy or not. In recent years, the American College of Cardiology (ACC) and the American Heart Association (AHA) developed the pooled cohort equation.15,16 The European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) used SCORE (Systematic COronary Risk Evaluation) for ASCVD risk assessment.17,18 The UK National Institute for Health and Care Excellence (NICE) guidelines used the QRISK2 as the ASCVD risk assessment tool.19 Although several populationspecific risk assessment tools exist, none of the currently available models are derived from or prospectively validated in East Asians. The AHA/ACC pooled cohort equation for estimating the 10-year risk of ASCVD event is applicable to black and non-Hispanic white men and women 40 through 79 years of age.15 This risk predictor may overestimate the ASCVD risk in the Chinese population.20 The Framingham risk score also overestimated the ASCVD risk for ethnic Chinese.21 In Taiwan, a point-based prediction model to predict the 10-year risk of CAD was developed from the Chin-Shan Community Cardiovascular Cohort study in 1990s.22 However, the definite cut-off point to define high risk was not indicated. Some examinations, such as ankle-brachial index, pulse wave velocity, carotid ultrasound, and coronary calcium score, have been used in ASCVD risk assessment. The accessibility of these examinations is a major problem in local clinics. Concerns of cost and radiation exposure for examination of coronary calcium score are also important considerations. Basically, this guideline does not encourage to routinely screen the presence of subclinical atherosclerosis in asymptomatic subjects. At current stage, using the numbers of risk factors is a more convenient way for risk stratification in Taiwan. Risk category High risk (DM, CKD and LDL-C ‡ 190 mg/dL) This primary prevention guideline decides to keep a conventional target approach and the LDL-C treatment targets are tailored according to the presence of CV risk factors. Since ASCVD is a major problem contributing to significant mortality in populations with DM and CKD, these 2 groups of patients are considered at high risk. The diagnosis of DM and management strategy of diabetic dyslipidemia was described in the 2017 Taiwan Lipid Guidelines for High Risk Patients.10 For CKD, albuminuria is an important biomarker which is used to detect and define CKD. Albuminuria refers to increased urinary excretion of albumin. The urine albumin-to-creatinine ratio (UACR) in an untimed urine specimen has replaced 24-h urine albumin excretion as the preferred method for measuring albuminuria.23e26 Albuminuria is defined as a UACR
30 mg/g and can be further categorized into microalbuminuria (UACR 30e300 mg/g) and macroalbuminuria (UACR > 300 mg/g). The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines defined CKD as kidney damage (UACR
30 mg/g) or a glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 for at least three months.27,28 The GFR is usually estimated from the serum creatinine level according to equations of the Modification of Diet in Renal Disease (MDRD)29 or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).30 Immediate lipid lowering therapy is recommended for DM and non-dialysis CKD. Severe hypercholesterolemia, defined as having an LDLC
190 mg/dL, carries a high risk of ASCVD and premature CV events. These individuals have a 5 to 6-fold higher risk of CAD and develop CAD 10e20 years earlier in men and 20e30 years earlier in women than general population.31 Early initiation of lipid-lowering therapy can significantly reduce morbidity and mortality in these subjects.32 LDL-C
190 mg/dL significantly increases the likelihood for the presence of FH. Approximately 7% of the subjects with LDLC
190 mg/dL may fulfill the diagnostic criteria of FH.33 Genetic testing should be considered for this group of subjects for diagnosis of FH. Previous study demonstrated that, compared with a reference group with LDL-C <130 mg/dL without detected FH genetic mutation, subjects with LDL-C
190 mg/dL without detected FH mutation had a 6-fold higher risk for CAD, whereas those with both LDL-C
190 mg/dL and an FH mutation demonstrated a 22-fold increased risk.34 Because LDL-C
190 mg/dL is a very unique and high risk group with a distinct long-term clinical outcome, it is classified as high risk. Just like DM and CKD, immediate lipid lowering therapy with intensive LDL-C control is recommended because the CV risk is so high in these patients.

Clinical Practice 2022 Taiwan lipid guidelines for primary prevention 03

Recommendation
臨床證據明顯的動脈粥狀硬化疾病, 需要立即降低 LDL-C. 
臨床證據不明顯, 單純是為了初級預防疾病, 建議依照危險等級分類. 來決定降血脂策略
Clinically significant ASCVD needs immediate and intensive reduction of LDL-C. (COR I, LOE A) For primary prevention in subjects without clinically significant ASCVD, risk stratification is necessary to determine the lipid lowering strategy. (COR I, LOE B)

Clinical Practice 2022 Taiwan lipid guidelines for primary prevention 02

台灣2022年血脂治療指引部分更新

一級預防的定義 由於這是一項一級預防指南，因此應首先描述具有臨床意義的 ASCVD 的定義。已經證明動脈粥樣硬化早在 2 歲時就起源於兒童期。一系列病理學研究，從在朝鮮戰爭和越南戰爭中陣亡的士兵的屍檢到最近的青年動脈粥樣硬化的病理生物學決定因素 12 和 Bogalusa 心臟研究 13，表明冠狀動脈脂肪條紋在生命早期形成，晚期纖維斑塊存在於青少年的比例。在過去的幾十年裡，令人信服的證據表明，吸煙、血脂異常、高血壓、胰島素抵抗、肥胖和 DM 等 CV 危險因素在整個生命週期中加速了動脈粥樣硬化過程。14 “一級預防”的主要目的是指通過消除或改變危險因素來預防有臨床意義的 ASCVD。具有臨床意義的 ASCVD 包括： (1) 冠心病，如負荷試驗陽性心絞痛和/或影像學檢查冠狀動脈主動脈直徑狹窄>50%；(2)ACS，如心肌梗死、不穩定型心絞痛；(3)腦血管病，如短暫性腦缺血發作、缺血性腦卒中、影像學檢查發現頸動脈狹窄>50%；(4)影像學檢查顯示大肢動脈直徑狹窄>50%的PAD；(5) 主動脈粥樣硬化疾病，如腹主動脈瘤的影像學檢查。有臨床意義的 ASCVD 血脂異常的治療應參考 2017 年台灣高危患者血脂指南及其重點更新中的建議。該一級預防指南闡述了在沒有臨床意義的 ASCVD 的受試者中控制血脂的一般原則。危險分層是確定一級預防降脂策略的第一步。

Definition of primary prevention Since this is a primary prevention guideline, the definitions of clinically significant ASCVD should be described first. It has been demonstrated that atherosclerosis originates in childhood as early as 2 years of age. A series of pathology studies, from autopsies of soldiers killed in the Korean and Vietnam Wars to the more recent Pathobiological Determinants of Atherosclerosis in Youth12 and Bogalusa Heart studies,13 demonstrated that coronary fatty streaks develop early in life and advanced fibrous plaques are present in a proportion of adolescents. During the past decades, convincing evidence has emerged that CV risk factors, such as cigarette smoking, dyslipidemia, hypertension, insulin resistance, obesity, and DM, accelerate the atherosclerotic process throughout the life span.14 The major purpose of “primary prevention” refers to prevention of clinically significant ASCVD by removing or modifying risk factors. The clinically significant ASCVD include: (1) CAD, such as angina with positive stress test and/or major coronary artery diameter stenosis >50% by imaging studies; (2) ACS, such as myocardial infarction and unstable angina; (3) cerebrovascular disease, such as transient ischemic attack, ischemic stroke, and carotid artery stenosis >50% by imaging studies; (4) PAD with major extremity artery diameter stenosis >50% by imaging studies; and (5) aortic atherosclerotic disease, such as abdominal aortic aneurysm by imaging studies. Treatment of dyslipidemia for clinically significant ASCVD should be referred to the recommendations in the 2017 Taiwan Lipid Guidelines for High Risk Patients and its focused update. This primary prevention guideline addresses the general principles of lipid control in subjects without clinically significant ASCVD. Risk stratification is the first step to determine the lipid lowering strategy in primary prevention.

Clinical Practice 2022 Taiwan lipid guidelines for primary prevention 01

台灣2022年血脂治療指引部分更新
早期開始他汀類藥物治療以降低 LDL-C 可以獲得與未經治療的低 LDL-C 水平患者相似的 CV 風險。8
很明顯，在生命早期維持足夠的 LDL-C 水平是預防 ASCVD 的有效干預措施。然而，台灣LDL-C的控制率令人失望。即使在患有 ASCVD 的患者中，也只有 54% 的患者可以達到 <100 mg/dL 的 LDL-C 水平。9

台灣血脂與動脈粥樣硬化學會與台灣其他七個主要學會聯合發布了台灣血脂高危指南風險患者 2017.10 推薦高危患者的最佳血脂目標和治療策略，
包括冠心病（CAD）、急性冠脈綜合徵（ACS）、缺血性卒中、外周動脈疾病（PAD）、糖尿病（DM） , 慢性腎病 (CKD) 和家族性高膽固醇血症 (FH)。

2017年台灣高危患者血脂指南在台灣獲得好評，成為高危患者血脂異常治療的標準指南。2017年指南未提及對不具有上述高危特徵的受試者進行血脂異常管理。

在 2005 年至 2008 年台灣進行的營養與健康調查中，高膽固醇血症定義為膽固醇水平 240 毫克/分升，男性佔 12.5%，女性佔 10%。 11 台灣血脂與動脈粥樣硬化學會決定向前推進一級預防並針對沒有臨床顯著 ASCVD 但可能攜帶其他各种血管危險因素的受試者制定了新的血脂指南。

2020年11月至2021年3月，台灣脂質與動脈粥樣硬化學會召開顧問委員會會議，來自台灣家庭醫學會、台灣心髒病學會、台灣中風學會、台灣糖尿病協會、台灣糖尿病教育者協會的專家和意見領袖、台灣腎病學會及台灣血脂教育者協會出席顧問委員會會議並提出重要建議。

科學證據是該指南的主要考慮因素。然而，我們認識到台灣可能沒有足夠的數據來支持血脂異常管理各個方面的一級預防建議。許多建議是專家意見經過討論後達成的共識。

與2017年台灣高危患者血脂指南類似，本指南使用推薦等級 (COR) 和證據等級 (LOE) 來描述推薦強度及其相關科學證據。10 COR 包括 3 個等級，包括 I 級（推薦有用、指示和必要） 、IIa 類（建議可能有用且有指示性，但其證據強度低於 I 類）、IIb 類（可以考慮這些建議，但其效果不太確定）和 III 類（建議指的是治療是有害的，禁忌的，不應該這樣做）。LOE 也有 3 個級別，包括 LOE A（建議得到多項隨機臨床試驗的支持）、LOE B（建議僅來自有限的隨機試驗或觀察性研究）、
Introduction Cardiovascular (CV) disease, including atherosclerotic cardiovascular disease (ASCVD), is one of the major leading causes of death in Taiwan.1 Multiple evidences from laboratory, epidemiological, and genetic studies indicate that increased circulating low-density lipoprotein cholesterol (LDL-C) causes accelerated deposition of cholesterol in the arterial wall leading to vascular inflammation and atherosclerosis.2,3 The causal link of LDL-C and ASCVD was further proved in many clinical trials showing that intensive reduction of LDL-C is an effective therapy to attenuate the progression of coronary atherosclerosis and improve CV outcomes.4e7 Recent study demonstrated that, in individuals without established coronary atherosclerosis, early initiation of statin therapy to decrease LDL-C could obtain a similar CV risk as those with untreated low LDL-C levels.8 It is clear that maintaining an adequate LDL-C level earlier in life is an effective intervention for prevention of ASCVD. However, the control rate of LDL-C is disappointing in Taiwan. Even in patients with ASCVD, only 54% of them could achieve an LDL-C level <100 mg/dL.9 The Taiwan Society of Lipids and Atherosclerosis, in association with seven other major societies in Taiwan, published the Taiwan Lipid Guidelines for High Risk Patients in 2017.10 The optimal lipid target and treatment strategy were recommended for high risk patients, including those with coronary artery disease (CAD), acute coronary syndrome (ACS), ischemic stroke, peripheral artery disease (PAD), diabetes mellitus (DM), chronic kidney disease (CKD), and familial hypercholesterolemia (FH). The 2017 Taiwan Lipid Guidelines for High Risk Patients received critical acclaim in Taiwan and became the standard guidance for dyslipidemia treatment in high risk patients. The management of dyslipidemia for subjects without the above-mentioned high risk features was not mentioned in the 2017 guidelines. In the Nutrition and Health Surveys in Taiwan performed from 2005 to 2008, hypercholesterolemia defined as a cholesterol level
240 mg/dL was found in 12.5% in men and 10% in women.11 The Taiwan Society of Lipids and Atherosclerosis decided to move forward to primary prevention and developed a new lipid guideline targeting the subjects without clinically significant ASCVD, but may carry other various vascular risk factors. Advisory board meetings were held by the Taiwan Society of Lipids and Atherosclerosis from November 2020 to March 2021. Experts and opinion leaders from the Taiwan Association of Family Medicine, Taiwan Society of Cardiology, Taiwan Stroke Society, Taiwan Diabetes Association, Taiwan Association of Diabetes Educators, Taiwan Society of Nephrology and Taiwan Association of Lipid Educators attended the advisory board meetings and gave important suggestions. Scientific evidence is the major consideration of the guideline. However, we recognized that there may be insufficient data in Taiwan to support the recommendations in every aspect of dyslipidemia management for primary prevention. Many recommendations were consensus from the expert opinions after discussion. Similar to the 2017 Taiwan Lipid Guidelines for High Risk Patients, this guideline uses class of recommendation (COR) and level of evidence (LOE) to describe the intensities of the recommendations and their related scientific evidence.10 The COR includes 3 levels, including class I (the recommendations are useful, indicated, and necessary), class IIa (the recommendations maybe useful and indicated, but their intensity of evidence are less than class I), class IIb (the recommendations could be considered but their effects are less well established) and class III (the recommendations refer to the treatment that is harmful, contraindicated, and should not be done). The LOE also has 3 levels, including LOE A (the recommendations are supported by multiple randomized clinical trials), LOE B (the recommendations are from limited randomized trials or observational studies only), LOE C (the recommendations are from experts’ consensus).