老年人血脂异常管理中国专家共识
2022年10月

中华内科杂志,第61卷第10期 第1095页-第1118页

刘梅林,张雨濛,付志方,叶平,郭艺芳,汪芳,何青,李建军,严晓伟,廖玉华,周晓芳,拓西平,王朝晖

  摘要

血脂异常是导致动脉粥样硬化性心血管疾病(ASCVD)的重要危险因素,他汀类药物延缓ASCVD的发生、发展并降低心血管事件及死亡的风险。由于对安全性的担忧,老年人调脂药物使用不足、停药率高。本专家共识依据老年人使用调脂药物的临床证据,参考国内外血脂管理指南及专家共识推荐,对我国老年人的血脂异常提出管理建议,旨在促进我国老年ASCVD防治工作。

  正文

动脉粥样硬化性心血管疾病(atherosclerotic cardiovascular disease,ASCVD)是老年人致死、致残的主要疾病1,患病率和死亡率随增龄增加。血脂异常是ASCVD及心血管事件的独立危险因素,大量证据表明,他汀类药物可延缓ASCVD的发生、发展并降低发生心血管事件及死亡的风险。由于对药物安全性的担忧,老年人群用药不足、停药率高2, 3。为促进我国老年人ASCVD的防治工作,相关多学科专家经多次讨论形成本共识。

一、老年人血脂异常的特点

血脂异常与基因、年龄、生活方式及环境等因素相关。我国老年人的总胆固醇(total cholesterol,TC)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)和甘油三酯(triglyceride,TG)总体水平低于西方人群,血脂异常以轻、中度增高为主4。中国慢性病和危险因素监测(China chronic disease and risk factor surveillance,CCDRFS)对163 641名成人的调查显示,70岁以下成人LDL-C和TG水平随年龄增加而升高,70岁以后呈降低趋势(表1)5

二、调脂药物用于老年人ASCVD防治的临床证据
(一)他汀类药物防治老年人ASCVD的临床证据

老年人临床试验和老年亚组分析显示,他汀类药物可降低ASCVD的患病率、死亡率和心血管事件的发生率,尚缺乏75岁以上老年人使用他汀类药物防治ASCVD的大规模随机对照临床试验证据。

1.他汀类药物用于老年人ASCVD一级预防的临床证据:他汀类药物用于ASCVD一级预防获益的证据,75岁以下老年人多来自随机对照研究,75岁及以上老年人多来自亚组分析及荟萃分析。HOPE-3(heart outcomes prevention evaluation-3)研究入选存在心血管疾病危险因素的人群12 705例(包含中国人3 691例),随访5.6年,结果显示服用瑞舒伐他汀10 mg/d使主要终点事件发生风险减少24%,70岁以上亚组分析显示同样获益6。2019年胆固醇治疗研究协作组(Cholesterol Treatment Trialists′ Collaboration,CTT)对28项随机对照研究进行荟萃分析,含82 682例非ASCVD患者,其中75岁以上6 449例,平均随访4.9年,结果显示他汀类药物降低主要血管事件发生风险25%,65~70岁亚组心血管事件发生风险降低39%,70岁以上亚组无显著降低7。2020年哥本哈根研究(Copenhagen general population study,CGPS)对91 131例无ASCVD或糖尿病未服用他汀类药物的人群平均随访7.7年,其中60岁以上35 587例,结果显示,随LDL-C增加,70~79岁老年人心肌梗死(myocardial infarction,MI)(HR=1.25,95%CI 1.12~1.40)和ASCVD(HR=1.12,95%CI 1.04~1.20)风险均增加,80~100岁老年人风险增加更明显(MI HR=1.28,95%CI 1.08~1.52;ASCVD HR=1.16,95%CI 1.05~1.29);经中等强度他汀类药物治疗,70~100岁人群MI或ASCVD 5年的需治疗人数(NNT)最少8。2020年对退伍军人健康管理局(Veterans Health Administration,VHA)326 981例年龄>75岁退伍军人的注册健康资料进行回顾性分析显示,其中57 178例(17.5%)使用他汀类药物治疗,平均随访6.8年,结果显示他汀类药物治疗组全因死亡(HR= 0.75,95%CI 0.74~0.76)、心血管疾病死亡(HR=0.80,95%CI 0.78~0.81)以及ASCVD事件(HR=0.92,95%CI 0.91~0.94)风险均低于对照组9(更多临床证据详见附录表1)。

2. 他汀类药物用于老年人二级预防的临床证据:大量证据表明,老年人服用他汀类药物进行二级预防可获益。2019年CTT 荟萃分析涉及28项随机对照研究,纳入104 123例服用他汀类药物的ASCVD患者,结果显示LDL-C每降低1.0 mmol/L(40 mg/dl)主要血管事件[包括冠状动脉(冠脉)事件、卒中和冠脉血运重建]相对风险减少21%(RR=0.79,95%CI 0.77~0.81);各年龄组(包括>75岁8 034例患者)均可从他汀类药物治疗中获益;他汀类药物减少主要血管事件的获益取决于LDL-C降低的绝对值和基线ASCVD风险,并独立于包括年龄在内的其他心血管危险因素7。Gencer等10 对29项临床试验的荟萃分析显示,21 492例≥75岁患者使用他汀类药物、依折麦布或前蛋白转化酶枯草溶菌素9(PCSK9)抑制剂,LDL-C 每降低1 mmol/L,主要血管事件[包括心血管死亡、MI或其他急性冠脉综合征(ACS)、卒中、冠脉血运重建]的风险降低26%(RR=0.74,95%CI 0.61~0.89),分别减少心血管死亡15%(RR=0.85,95%CI 0.74~0.98)、MI 20%(RR=0.80,95%CI 0.71~0.90)、冠脉血运重建20%(RR=0.80,95%CI 0.60~0.96)、卒中27%(RR=0.74,95%CI 0.61~0.87);75岁以上与75岁以下患者的获益相似(RR=0.85,95%CI 0.78~0.92,P=0.37)(详见附录表2)。

3. 他汀类药物用于特定老年人群的临床试验:研究表明,老年女性(详见附录表3)、糖尿病(详见附录表4)患者使用他汀类药物可降低血管事件及死亡风险。他汀类药物降低非透析慢性肾脏病(chronic kidney disease,CKD)的心血管事件及死亡风险,相对获益随肾功能减退而降低;尚缺乏透析(5D期)患者心血管获益的证据(详见附录表5)。

(二)非他汀类降胆固醇药物用于老年人的临床试验

老年亚组分析显示,胆固醇吸收抑制剂依折麦布和PCSK9抑制剂降低老年患者主要终点事件发生率。IMPROVE-IT(improved reduction of outcomes:vytorin efficacy international trial)研究纳入18 144例ACS患者,平均年龄64岁,随访6年,结果显示辛伐他汀联合依折麦布较单独应用辛伐他汀可进一步降低终点事件发生风险,75岁以上亚组终点事件发生风险低于75岁以下亚组11。FOURIER(further cardiovascular outcomes research with PCSK9 inhibition in subjects with elevated risk)研究12, 13和ODYSSEY(evaluation of cardiovascular outcomes after an acute coronary syndrome during treatment with alirocumab)研究14老年亚组分析结果显示老年ASCVD患者应用PCSK9抑制剂可降低主要终点事件(详见附录表6)。

(三)降TG药物的临床试验

荟萃分析显示,TG每升高1 mmol/L,男性和女性心血管疾病(CVD)风险分别增加14%和37%15。亚洲大样本研究16, 17显示,TG升高增加缺血性CVD风险18。降低TG的主要药物包括贝特类、烟酸类和鱼油制剂。

贝特类药物的临床研究19, 20 未显示一致结果,部分研究显示降低主要终点及冠脉事件。REDUCE-IT(reduction of cardiovascular events with icosapent ethyl-intervention trial)研究显示,使用他汀类药物的高TG血症患者,服用97%纯度的二十碳五烯酸乙酯(Icosapent Ethyl,IPE;即二十碳五烯酸EPA)4 g/d主要终点事件风险较安慰剂组降低25%21。STRENGTH(statin residual risk with epanova in high cardiovascular risk patients with hypertriglyceridemia)研究入选混合性血脂异常、CVD高危患者,在他汀类药物治疗的基础上给予n-3多不饱和脂肪酸[n-3 polyunsaturated fatty acid,n-3 PUFA(Epanova)1 g含 EPA 0.55 g和二十二碳六烯酸(DHA)0.2 g]4 g/d或安慰剂,中位随访时间42个月,两组主要终点事件差异无统计学意义22(详见附录表7、8)。

三、国内外指南及专家共识对老年人血脂管理的推荐

近年,随着老年人临床研究证据的积累,各国血脂管理指南和专家共识不断更新。调脂治疗以LDL-C作为首要干预靶点,非高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)为次要干预靶点。

《2016中国成人血脂异常防治指南》23未推荐老年人群的调脂治疗目标。

《2018 美国心脏病学学会/美国心脏协会(American College of Cardiology/American Heart Association,ACC/AHA)胆固醇管理指南》推荐≤75岁ASCVD患者服用高强度他汀类药物,降低LDL-C>50%(Ⅰ,A);不耐受高强度他汀类药物或出现不良反应者,服用中等强度他汀类药物使LDL-C降低30%~49%(Ⅰ,A);若极高危ASCVD患者服用最大耐受剂量他汀类药物LDL-C ≥1.8 mmol/L(70 mg/dl),推荐联合依折麦布(Ⅱa,B),仍未达标加用PCSK9抑制剂(Ⅱa,A)。>75岁的老年ASCVD患者获益超过风险时可启动中等强度或高强度他汀类药物治疗(Ⅱa,B),已使用高强度者,需评估降低ASCVD风险的获益、药物不良反应和相互作用、患者的虚弱状态并考虑个人意愿,可继续高强度他汀类治疗(Ⅱa,C)24。《2019 ACC/AHA心血管疾病一级预防指南》建议,对于>75岁的患者,根据心血管风险评估决定是否给予他汀类药物治疗25。《2019 欧洲心脏病学会/欧洲动脉粥样硬化协会(European Society of Cardiology/European Atherosclerosis Society,ESC/EAS)血脂异常管理指南》26推荐老年ASCVD患者积极使用他汀类药物,≤75岁老年人使用他汀类药物进行一级预防(Ⅰ,A),>75岁心血管病高危或极高危老年人考虑使用他汀类药物进行一级预防(Ⅱ,B)。推荐极高危ASCVD患者的LDL-C目标<1.4 mmol/L(Ⅰ,A)且较基线值降低≥50%,高危患者LDL-C<1.8 mmol/L(70 mg/dl)且降低幅度≥50%,中危患者LDL-C<2.6 mmol/L(100 mg/dl),低危患者LDL-C<3.0 mmol/L(116 mg/dl)。指南强调老年人使用高强度他汀类药物时发生不良反应的风险增加,应考虑使用低强度他汀类药物;对于有明显肾功能受损和/或潜在药物相互作用的老年人,推荐使用低剂量他汀类药物并根据目标LDL-C水平调整剂量。

《2021 ESC心血管疾病预防指南》推荐老年ASCVD患者使用他汀类药物(Ⅰ,A),≥70岁以上人群使用系统性冠脉风险评估2-老年人(systemic coronary risk estimation 2-older persons,SCORE2-OP)进行风险评估(Ⅰ,B),高危及以上患者可考虑使用他汀类药物进行一级预防(Ⅱb,B),存在明显肾功能受损和/或潜在药物相互作用的患者推荐起始使用低剂量他汀类药物(Ⅰ,C)27

2019年《中国胆固醇教育计划调脂治疗降低心血管事件专家建议》28、2020年《超高危动脉粥样硬化性心血管疾病患者血脂管理中国专家共识》29提出更积极的调脂治疗目标,未提及老年人。

《2021 ACC降低持续性高甘油三酯血症患者ASCVD风险管理的专家共识决策路径》30 建议ASCVD或≥50岁至少合并一项其他ASCVD高危因素的糖尿病患者,经排除继发因素、他汀类药物治疗LDL-C达标、TG持续升高(1.7~5.6 mmol/L)时,可加用鱼油制剂(优先推荐高纯度EPA)。空腹 TG ≥ 5.6 mmol/L,应首先降低TG,首选贝特类、鱼油制剂(优先推荐高纯度EPA)等药物,非处方鱼油产品不能替代处方n-3 PUFA。《2021 ESC心血管疾病预防指南》建议ASCVD高危及以上患者,经他汀类药物及生活方式干预后TG>1.5 mmol/L,可考虑联用n-3 PUFA(Ⅱb,B)27

四、中国老年人血脂异常的管理建议
(一)生活方式治疗

保持健康的生活方式是治疗老年人血脂异常的基本措施。主要包括戒烟、限酒,均衡饮食,减少饱和脂肪酸和胆固醇摄入,增加蔬菜、水果、鱼类、豆类、粗粮、全谷类、坚果及富含植物甾醇、纤维的食物摄入,不提倡老年人过度严格控制饮食和减轻体重。建议老年人坚持规律有氧运动,运动时应注意避免运动导致的损伤和跌倒,有条件者可在运动康复专业医师评估及指导下选择运动方案。

(二)调脂治疗目标及推荐药物

1. 建议老年ASCVD患者积极使用他汀类药物,对于存在心血管病风险的老年人,根据心血管病危险分层制定血脂管理目标(详见表2)。

2.推荐老年ASCVD患者及≤75岁具有多种心血管危险因素的老年人使用他汀类药物。

3. 对于年龄>75岁心血管高风险的老年人应进行预期寿命、虚弱状态、合并疾病、肝肾功能、经济因素等综合评估,权衡调脂治疗的获益风险比、药物相互作用、不良反应以及个人意愿决定是否使用中低剂量他汀类药物。

4. 老年人使用可耐受剂量他汀类药物 LDL-C未达标时,可加用依折麦布或PCSK9抑制剂。

5. TG 升高时,首先应排除或纠正继发因素并进行生活方式干预。对于ASCVD患者或极高危老年人,经他汀类药物治疗后非HDL-C未达标或TG持续升高(2.3~5.6 mmol/L)时,可联用贝特类药物或鱼油制剂(优先推荐高纯度EPA)。空腹 TG ≥ 5.6 mmol/L,应首先降低TG,首选贝特类、鱼油制剂(优先推荐高纯度EPA)治疗。

(三)老年人血脂异常治疗的监测

首先进行生活方式治疗的老年人,应于6~8周复查血脂水平,达标者应继续坚持健康生活方式,3~6个月复查;如持续达标,每6~12个月复查。在服用他汀类药物前后4周复查血脂、肌酶及肝肾功能,服药时应监测有无肌痛、乏力和消化道症状等不良反应,长期使用应定期随诊。服用他汀后出现肌肉或消化道症状的患者,应监测肌酶及肝功能。如血肌酸激酶(CK)升高未超过正常上限4倍且肌肉症状轻微或丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)升高未超过正常上限3倍,可继续服用他汀类药物并复查32。血CK升高超过正常上限4倍或ALT、AST超过正常上限3倍及胆红素升高,应停用或减少他汀类药物剂量,恢复正常后再次评估他汀类药物的获益/风险,决定是否继续服用他汀或换用其他调脂药物;若需继续使用调脂药物,可更换种类或减少剂量后密切观察。如CK升高超过正常上限10倍,应立即停用他汀并入院进行水化治疗。3~6个月未达标者,应调整他汀类药物的剂量或种类,必要时加用依折麦布或PCSK9抑制剂,达标后每6~12个月复查。

五、常用的调脂药物及安全性
(一)他汀类药物

1. 药理特性:目前常用的他汀中洛伐他汀、辛伐他汀、氟伐他汀、阿托伐他汀和匹伐他汀为亲脂性他汀类药物,普伐他汀和瑞舒伐他汀为亲水性他汀类药物(详见表3)。血脂康由粳米接种红曲菌发酵精制而成,含洛伐他汀等13种他汀同系物及不饱和脂肪酸、甾醇和少量的黄酮类物质等。常用剂量为1.2 g/d(0.6 g,2次/d),含洛伐他汀10 mg。洛伐他汀、辛伐他汀与食物同服更容易吸收,瑞舒伐他汀、阿托伐他汀、氟伐他汀和匹伐他汀不受食物影响,普伐他汀与食物同服减少吸收。由于肝内胆固醇的合成在夜间达到高峰,氟伐他汀、洛伐他汀、辛伐他汀半衰期较短,建议晚间服用;阿托伐他汀、匹伐他汀、瑞舒伐他汀半衰期较长,可在任何时间服用。他汀类药物治疗降低LDL-C幅度见表4。

2. 安全性32, 33:尽管老年人服用他汀类药物的安全性和耐受性好,仍应及时识别并处理相关不良反应。通常,他汀类药物的不良反应随剂量增大而增加34,常见的不良反应包括肝功能异常、肌损害等。

(1)肝功能异常:他汀类药物最常见的不良反应是肝功能异常,ALT升高大于正常上限3倍的发生率0.5%~2.0%,严重肝损害发生率0.001%,多发生在用药后的3个月内。老年人使用他汀类药物常规剂量时较少发生肝功能异常,使用大剂量时肝功能异常的发生率增高。

他汀类药物禁用于活动性肝病、失代偿性肝硬化及急性肝衰竭、不明原因转氨酶持续升高和任何原因转氨酶升高超过3倍正常上限的患者。慢性肝病不是使用他汀类药物的禁忌证。他汀类药物与抗肝炎病毒药物合用可增加不良反应,推荐选用不经肝脏细胞色素P450酶(CYP)3A4代谢的他汀类35。国际指南不推荐在他汀类药物治疗期间常规监测肝酶,但我国约有2 000万~3 000万人患慢性乙型肝炎36,故推荐监测肝酶37

(2)肌损害32:他汀类药物相关的肌损害:观察性研究报道服用他汀类药物出现肌肉症状(SAMS)的发生率10%~15%,安慰剂对照研究1%~2%。肌损害表现为肌痛或乏力等症状伴CK增高,发生横纹肌溶解时CK≥正常上限10倍,严重时可超过正常上限40倍。横纹肌溶解是他汀相关的最严重不良反应,表现为严重肌痛、肌肉坏死,肌红蛋白尿可导致急性肾损伤和死亡26。他汀类药物导致横纹肌溶解的发生率约0.01%,有研究显示老年人较普通人群发生横纹肌溶解的风险高4倍38

他汀类药物相关的肌损害通常与大剂量相关,老年、瘦弱女性、肝肾功能异常、多种疾病并存、多种药物合用及围术期容易发生。部分患者在尚无肌酶升高或肌病发生时即可出现肌痛、乏力等症状,而肌酶升高即使无肌肉症状也不能排除他汀类药物的不良反应;应排查其他原因导致的肌酶升高,如创伤、剧烈运动、甲状腺疾病、感染、维生素D缺乏、风湿性多肌痛、原发性肌病、线粒体肌病、他汀类药物相关自身免疫性肌病等。由于老年人的肌无力、肌痛也可见于骨关节、肌肉疾病等,需要进行鉴别诊断。

(3)CKD:老年人的肾功能随年龄增长减退,血肌酐正常时即可能存在肾功能不全,启动调脂治疗前应评估肾功能[如血肌酐(Cr)、估算的肾小球滤过率(eGFR)],用药过程中关注肾功能变化。他汀类药物无明显肾毒性,不会导致肾功能恶化,可导致一过性蛋白尿,可能与肾小管重吸收减少相关39, 40

(4)新诊断糖尿病:他汀类药物增加新诊断糖尿病的风险,更多见于糖尿病早期阶段及代谢综合征者,常与使用大剂量他汀类药物及增龄相关41(详见附录表9)。鉴于他汀类药物对心血管疾病患者的总体获益远超新诊断糖尿病的风险42,推荐老年ASCVD患者服用他汀类药物并监测血糖及糖化血红蛋白的变化。服用他汀类药物时应强化生活方式干预,密切随访,及时发现并进行血糖管理。

(5)神经系统:他汀类药物降低缺血性卒中风险32。现有临床证据未显示他汀类药物增加出血性卒中、认知功能障碍、阿尔茨海默病、血管性痴呆或帕金森病的风险(详见附录表10、11)。若在启动他汀类药物治疗后新发神经系统症状,如认知功能障碍、记忆力减退、睡眠障碍等,应评估是否为他汀类药物的不良反应,必要时停药观察3243

(6)肿瘤:2019年CTT荟萃分析显示,他汀类药物未增加各年龄亚组肿瘤发生率及死亡风险732。有观察性研究显示他汀类药物降低乳腺癌、结肠癌、卵巢癌、胰腺癌等风险44

(二)非他汀类调脂药物

1. 胆固醇吸收抑制剂45:依折麦布通过抑制胆固醇转运蛋白NPC1L1抑制肠道对胆固醇的吸收,降低LDL-C 15%~22%26,常用剂量为5~10 mg/d。依折麦布的安全性和耐受性良好,常见的不良反应如头痛、腹痛、腹泻、腹胀、乏力及肝酶异常。

2. PCSK9抑制剂26:PCSK9抑制剂通过抑制循环中PCSK9 与低密度脂蛋白(LDL)受体(LDLR)的结合,阻止PCSK9介导的LDLR降解,促进LDL-C清除,平均降低LDL-C 60%,减少心血管事件。依洛尤单抗常用剂量为140 mg/2周或420 mg/4周,阿利西尤单抗常用剂量为75~150 mg/2周。常见的不良反应是注射部位不适、过敏反应和流感样症状46

Inclisiran为抑制PCSK9的小干扰RNA(siRNA),通过抑制PCSK9的合成,降低血浆中LDL-C水平47,每年注射2次可有效降低LDL-C,已获美国食品药品监督管理局(FDA)批准上市。ORION1(ClinicalTrials.gov,NCT02597127)研究(含60岁以上患者)显示可进一步降低LDL-C 36.7%~59.7%,安全性良好,常见不良反应如咳嗽、肌肉骨骼疼痛、鼻咽炎、头痛、背痛、腹泻等48

3. 贝特类26:贝特类药物通过激活过氧化物酶体增殖物激活受体α和脂蛋白脂酶降低TG、升高HDL-C,降低TG 20%~50%49。常用非诺贝特,常用剂量200 mg/d。常见不良反应如肌病、转氨酶升高、胃肠道反应及皮疹,可导致血肌酐升高、eGFR下降,通常可逆50,CKD患者使用时应调整剂量。吉非罗齐与他汀类药物联用增加肌病风险,非诺贝特的肌病风险明显降低35

4. 烟酸类2637:烟酸通过抑制二酰甘油酰基转移酶-2减少极低密度脂蛋白(very low-density lipoprotein,VLDL)分泌,降低TG 15%~25%51,临床研究未显示烟酸的心血管获益52, 53。不良反应包括颜面潮红、胃肠道症状、肝损害、尿酸及血糖升高等。禁用于严重或原因未明的肝功能损害、酗酒、活动性消化道溃疡及痛风患者。烟酸与他汀类药物联用时不良反应增加。

5. 鱼油制剂(n-3 PUFA):鱼油制剂3~6 g/d降低TG 30%~50%54。n-3 PUFA疗效与基线TG水平、剂量、种类相关,降低重度升高的TG 30%~60%55, 56, 57、轻中度升高的TG 15%~30%2158, 59。高纯度EPA降低心血管病高危患者的心血管事件。鱼油制剂常见不良反应为嗳气、恶心、鱼腥味等60, 61,大剂量鱼油可能增加发生心房颤动的风险21, 2262, 63

(三)药物的相互作用

老年人常联用多种药物,需关注药物相互作用及不良反应。联用经CYP450酶代谢、影响P-糖蛋白(P-gp)等药物时,发生他汀类药物不良反应的风险增加。抑制剂通过竞争结合位点或降低酶及蛋白活性等机制增加他汀类的生物利用度或减少他汀类的清除而升高他汀类药物血药浓度,诱导剂增加CYP450酶或P-gp活性使他汀类药物代谢加快降低他汀类药物血药浓度(表5)。

他汀类药物与烟酸或贝特类药物合用增加肌病风险。依折麦布与贝特类药物或环孢素合用时生物利用度增加65。贝特类与华法林合用增加抗凝疗效和出血风险,与免疫抑制剂合用可导致肾功能恶化。

六、老年人调脂治疗的注意事项

1.建议充分评估老年人调脂治疗的获益/风险、根据个体特点选择药物。对于75岁以上的老年人,根据生理年龄、心血管危险分层、肝肾功能、伴随疾病、合并用药、营养状态、虚弱状态、预期寿命等,衡量利弊后确定是否使用调脂药物,不推荐虚弱或预期寿命有限的老年人进行调脂治疗。

2. 随年龄增长,老年人生理性改变导致肌肉萎缩、肌力减弱,调脂药物可导致或加重肌肉症状,影响生活质量并增加跌倒风险。女性、体型瘦小、CKD、围术期、血容量低、重症感染、甲状腺功能异常的老年人发生肌病的风险增加。

3. 他汀类药物的不良反应随剂量增大而增加,多数老年人使用中、小剂量他汀类药物即可使LDL-C达标66;应从小或中等剂量开始并根据疗效调整剂量,他汀类不耐受时可减少剂量或换用不同类型的他汀类药物;服用可耐受剂量的他汀类LDL-C不能达标时,可加用依折麦布或PCSK9抑制剂。对于服用小剂量他汀类药物后TC或LDL-C迅速降低的老年人,应排查是否患有肿瘤及其他消耗性疾病。

4. 老年人肝肾功能减退、联用多种药物时,容易发生药物相互作用及不良反应,应选择在体内代谢途径不同的药物。他汀类药物与其他调脂药物合用时,可增加肝脏及肌肉损伤等风险,需关注老年人的个体特点及耐受性,避免大剂量联用并监测药物相互作用及不良反应。

5.调脂药物应坚持长期使用,无特殊原因不应停药。停药后血脂升高甚至反跳,使心血管事件及死亡率明显增加67

总之,调脂治疗是防治老年人ASCVD的重要措施。LDL-C是首要的治疗目标,非HDL-C是次要目标。健康的生活方式是治疗老年人血脂异常的基本措施,他汀类药物是首选的调脂药物。建议充分评估调脂治疗的利弊,根据老年人心血管疾病的危险分层及个体特点合理选择调脂药物。推荐老年人使用低、中剂量的他汀类药物,当使用可耐受剂量的他汀类药物LDL-C不达标时,可加用依折麦布或/和PCSK9抑制剂。当ASCVD或极高危老年患者LDL-C达标而TG升高时,可加用贝特类药物或/和鱼油制剂(优先推荐高纯度EPA)。

执笔人:刘梅林;张雨濛;付志方

共识专家组名单(按姓氏汉语拼音排序):程晓昱(安徽中医药大学第一附属医院老年科);程蕴琳(江苏省人民医院老年科);方宁远(上海交通大学医学院附属仁济医院老年病科);付志方(北京大学第一医院老年科);高海青(山东大学齐鲁医院老年科);郭艺芳(河北省人民医院老年心血管内科);何青(北京医院心内科);李建军(中国医学科学院 北京协和医学院 阜外医院心血管内科);刘朝中(空军总医院心内科);刘丰(广州市第一人民医院老年病科);刘宏斌(解放军总医院心血管内科);刘梅林(北京大学第一医院老年科);廖玉华(华中科技大学同济医学院附属协和医院心内科);吕继成(北京大学第一医院肾内科);齐国先(中国医科大学附属第一医院老年医学科);孙永安(北京大学第一医院神经内科);陶军(中山大学附属第一医院心内科);拓西平(上海长海医院老年病科);汪芳(北京医院心内科);王晓明(空军军医大学西京医院老年病科);王朝晖(华中科技大学同济医学院附属协和医院老年科);叶平(解放军总医院第二医学中心心内科);严晓伟(中国医学科学院 北京协和医学院 北京协和医院心内科);张一娜(哈尔滨医科大学附属第二医院老年科);张雨濛(北京大学第一医院老年科);赵宁(北京大学第一医院药剂科);周晓芳(四川省人民医院老年科)


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