This brief review of recent United States and European guideline recommendations for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) through the management of dyslipidemia/cholesterol compares the evaluation and treatment set forth in both guidelines (see the Table). The US 2018 American Heart Association/American College of Cardiology Multisociety Guideline (AHA/ACC)¹ emphasizes lifestyle in ASCVD prevention throughout the life course and expands the role of the clinician-patient risk discussion in decisions on statin initiation in those at borderline or intermediate risk. It recommends statin therapy for those with low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dl or adults 40 to 75 years of age with diabetes mellitus. For lower risk primary prevention, it endorses a 3-pronged approach to facilitate shared decision making. It begins with calculating 10-year ASCVD risk and then personalizing risk assessment with risk enhancing factors and, if needed to resolve uncertainty, a coronary artery calcium score. The 10-year ASCVD risk score uses the validated Pooled Cohort Equations.²

Table 1. A Comparison of Primary Prevention Recommendations From 2018 AHA/ACC Multisociety and 2019 ESC/EAS Guidelines Highlighting Key Areas

Apo B indicates apolipoprotein B; ASCVD, atherosclerotic cardiovascular disease; CAC, coronary artery calcium; CHD, coronary heart disease; CVD, cardiovascular disease; HDL-C, high-density lipoprotein-cholesterol; hsCRP, high-sensitivity C-reactive protein; LDL-C, low-density lipoprotein-cholesterol; LpA, lipoprotein(a); and SCORE, European Systematic Coronary Risk Evaluation.

The European 2019 European Society of Cardiology–European Atherosclerosis Society Dyslipidemia Guideline (ESC/EAS) endorses a 3 stage risk stratification process of clinical evaluation using cardiovascular disease (CVD) risk estimation with the SCORE system (European Systematic Coronary Risk Evaluation).³ For primary prevention, ESC/EAS begins with clinical evaluation designed to identify high- and very high-risk conditions, including diabetes mellitus with estimation of target organ damage, other major risk factors and diabetes mellitus duration, moderate to severe chronic kidney disease, very high levels of individual risk factors, familial hypercholesterolemia, or a high-risk SCORE for fatal CVD.

The second stage uses the 10-year SCORE risk estimate recommended for asymptomatic individuals >40 years of age without CVD or the high-risk conditions mentioned earlier. The SCORE CVD risk estimate uses large representative database sets from Europe to predict CVD death as contrasted with the Pooled Cohort Equation’s use of US data to predict both nonfatal and fatal ASCVD events. Both guidelines acknowledge the usefulness (in the populations in which they have been derived and validated) and limitations of risk scores.^{2, 3}

The third stage is the assessment of risk modifiers. ESC/EAS risk modifiers are more extensive than AHA/CC risk enhancers (see Table). The ESC/EAS recommend, in selected individuals, measuring factors such as apolipoprotein B, lipoprotein(a) (LpA) or high-sensitivity C-reactive protein, assessing family history of premature ASCVD, or using the presence of moderate atherosclerotic plaque on imaging to improve risk stratification and inform treatment decisions.

Thus, in the approaches to primary prevention, there are strong similarities. Both guidelines acknowledge the importance of apolipoprotein B-containing lipoproteins in atherosclerosis and endorse aggressive lowering of LDL-C in those at highest risk. Both underscore a heart-healthy lifestyle and use evidence from randomized controlled trials. Both recommend statins as initial therapy for those at elevated ASCVD risk. Also, both recommend randomized controlled trial–proven non-statins (ezetimibe or PCSK9 inhibitors) in specific individuals at higher risk. The latter include patients with severe hypercholesterolemia, including familial hypercholesterolemia who merit treatment early in life.

Both guidelines require follow-up testing of LDL-C to determine treatment adequacy and assess percent LDL-C lowering. The ESC/EAS is more aggressive with non-statins by recommending their use when patients fail to reach specific targets for LDL-C; more subsequent testing and pharmacologic treatment will likely be needed to get individuals below arbitrary LDL-C goal levels. AHA/ACC focuses on net benefit that considers cost-effectiveness studies. In ESC/EAS, even low-risk individuals have a goal for LDL-C that may require additional testing and treatment, with uncertain marginal gain.

For individuals with elevated triglycerides, both guidelines recommend lifestyle therapy and, if the individuals have high enough risk, statins. ESC/EAS recommends in high-risk patients with diabetes mellitus and with elevated triglycerides despite statin therapy, icosapent ethyl fatty acids at 2 g twice daily. This is based on a randomized controlled trial published after AHA/ACC was released.⁴

ESC/EAS did not list specific factors such as pre-eclampsia and premature menopause for women, as seen in AHA/ACC. Also, in ESC/EAS guidelines, plaque imaging includes carotid and femoral imaging as well as coronary artery calcium scores. The utility of identifying coronary artery calcium equal to 0 is highlighted in AHA/ACC for reclassifying risk downward and deferring statin therapy in many intermediate risk individuals. The absence of carotid plaque does not have comparable negative predictive value.⁵

Both guidelines recommend consideration of apolipoprotein B and LpA risk assessment. AHA/ACC uses these, if measured, as risk-enhancing factors in those at intermediate and borderline risk. ESC/EAS recommends apolipoprotein B in those with high triglycerides, diabetes mellitus, obesity or metabolic syndrome, or very low LDL-C, and indicates it may be preferred over non-HDL-C. ESC/EAS recommends that LpA should be considered in selected patients with a family history of premature CVD and for reclassification in people who are borderline between moderate and high risk. Uniquely, ESC/EAS guideline recommends LpA measurement once in each person’s lifetime to identify those with very high inherited LpA levels (>180 mg/dL or >430 nmol/L) which may impart a lifetime ASCVD risk equivalent to that of heterozygous familial hypercholesterolemia. ESC/EAS do not clearly indicate how clinicians and patients address the mild to moderately high LpA values identified with this screening approach.

There are important similarities between AHA/ACC and ESC/EAS guidelines in primary prevention. Both identify individuals with either severely elevated LDL-C at any age, or diabetes mellitus at 40 to 75 years of age, that merit LDL-C lowering therapy. Both recommend statins as first-line therapy. Both recommend follow-up LDL-C levels for adequacy of effect and as a measure of adherence. However, there are important differences. Although both endorse attainment of specific LDL-C lowering (expressed as a percentage of baseline LDL-C) with statin intensity proportional to individual risk, the ESC/EAS includes specific LDL-C goals or targets at all levels of risk. However, targets can lead to intensified treatment of uncertain net benefit in those who fall just short of arbitrary LDL-C goals and who might benefit instead from a treatment discussion. For example, the net benefit of intensifying LDL-C lowering therapy in a low-risk patient, at 42 years of age with recent diabetes mellitus on a moderate intensity statin and LDL-C just above 100 mg/dl (2.6 mmol/L), to get below goal is not clear. AHA/ACC endorse statins for LDL-C lowering in those primary prevention patients shown to have net benefit with LDL-C lowering therapy proven safe and effective by randomized controlled trials. It puts emphasis on the clinician-patient risk discussion and the option of coronary artery calcium scoring that may focus statin therapy more specifically on those who benefit the most.

Authors were members of the writing group for the 2018 American Heart Association-American College of Cardiology Multisociety Cholesterol Guidelines.

The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.

https://www.ahajournals.org/journal/circ

通过对美国和欧洲有关通过血脂异常/胆固醇进行一级预防动脉粥样硬化性心血管疾病（ASCVD）的最新指南的简要回顾，比较了这两个指南中列出的评估和治疗方法（参见表）。美国2018年美国心脏协会/美国心脏病学会多社会学会（AHA / ACC）¹在整个生命过程中强调生活方式在ASCVD预防中的作用，并扩大临床医生-患者风险讨论在边缘或中度风险人群中他汀类药物起始决策中的作用。对于低密度脂蛋白胆固醇（LDL-C）≥190mg / dl或40至75岁糖尿病的成年人，建议使用他汀类药物治疗。对于较低风险的一级预防，它赞同采用三管齐下的方法来促进共同决策。首先要计算10年的ASCVD风险，然后使用风险增强因素以及（如果需要解决不确定性的话）冠状动脉钙化评分来个性化风险评估。10年ASCVD风险评分使用经过验证的汇总队列方程式。²

表1. 2018 AHA / ACC多社会协会和2019 ESC / EAS指南的主要预防建议比较重点领域

Apo B表示载脂蛋白B；ASCVD，动脉粥样硬化性心血管疾病；CAC，冠状动脉钙；冠心病，冠心病；CVD，心血管疾病；HDL-C，高密度脂蛋白胆固醇；hsCRP，高敏感性C反应蛋白；LDL-C，低密度脂蛋白胆固醇；LpA，脂蛋白（a）；和SCORE，欧洲系统性冠脉风险评估。

欧洲2019年欧洲心脏病学会-欧洲动脉粥样硬化学会血脂异常指南（ESC / EAS）批准了使用SCORE系统（欧洲系统性冠状动脉风险评估）的心血管疾病（CVD）风险评估的临床评估的三阶段风险分层过程。³对于一级预防，ESC / EAS从旨在评估高危和高危疾病的临床评估开始，包括评估目标器官损害的糖尿病，其他主要危险因素和糖尿病病程，中度至重度慢性肾脏病，个别危险因素，家族性高胆固醇血症或致命性CVD的高风险SCORE的水平很高。

第二阶段使用推荐给10岁以上但无CVD或无高危情况的40岁以上无症状个体的10年SCORE风险估计。SCORE CVD风险估计使用来自欧洲的大型代表性数据库集来预测CVD死亡，而Pooled Cohort方程使用美国数据来预测非致命性和致命性ASCVD事件。两项准则都承认其有用性（在已经获得和验证的人群中）和风险评分的局限性。^{2 3}

第三阶段是风险调整因子的评估。ESC / EAS风险调节剂比AHA / CC风险增强剂更广泛（见表）。ESC / EAS建议在选定的个体中测量诸如载脂蛋白B，脂蛋白（a）（LpA）或高敏C反应蛋白之类的因子，评估早产ASCVD的家族史，或在影像学中使用中度动脉粥样斑块改善风险分层并为治疗决策提供依据。

因此，在一级预防的方法中，有很多相似之处。两项指南都承认含载脂蛋白B的脂蛋白在动脉粥样硬化中的重要性，并支持高危人群中LDL-C的大幅降低。两者都强调了心脏健康的生活方式，并使用了来自随机对照试验的证据。两者均建议将他汀类药物作为ASCVD风险升高的患者的初始疗法。此外，双方都建议对风险较高的特定个体进行随机对照试验验证的非他汀类药物（依泽麦布或PCSK9抑制剂）。后者包括患有严重高胆固醇血症的患者，包括值得一生就进行治疗的家族性高胆固醇血症。

两项指南均要求对LDL-C进行后续测试，以确定治疗是否适当并评估LDL-C降低的百分比。当患者未能达到LDL-C的特定指标时，建议使用非他汀类药物，ESC / EAS对非他汀类药物更具攻击性。要使个体低于任意LDL-C目标水平，可能需要进行更多的后续测试和药物治疗。AHA / ACC专注于考虑成本效益研究的净收益。在ESC / EAS中，即使是低风险的个人也有LDL-C的目标，可能需要额外的测试和治疗，而边际收益不确定。

对于甘油三酸酯升高的个体，这两个指南均建议生活方式治疗；如果个体具有足够高的风险，则应推荐他汀类药物。ESC / EAS建议尽管他汀类药物治疗的糖尿病和甘油三酯升高的高危患者，每天两次两次服用2克二十碳五乙酯。这是基于AHA / ACC发布后发布的随机对照试验。⁴

ESC / EAS并未列出妇女的先兆子痫和更年期等具体因素，如AHA / ACC所示。同样，在ESC / EAS指南中，斑块成像包括颈动脉和股骨成像以及冠状动脉钙化评分。在AHA / ACC中突出显示了识别冠状动脉钙等于0的实用性，可用于在许多中度风险个体中将风险降低重新分类并推迟他汀类药物治疗。没有颈动脉斑块没有可比的阴性预测值。⁵

两项指南均建议考虑载脂蛋白B和LpA风险评估。AHA / ACC将这些（如果进行了测量）用作处于中等和临界风险中的风险增强因素。ESC / EAS建议在高甘油三酸酯，糖尿病，肥胖或代谢综合征或极低LDL-C的人群中使用载脂蛋白B，并表明它可能比非HDL-C更受欢迎。ESC / EAS建议在具有早发CVD家族史的某些患者中考虑LpA，并在中度和高危人群之间重新分类。独特的是，ESC / EAS指南建议在每个人的一生中进行一次LpA测量，以发现遗传性LpA水平很高（> 180 mg / dL或> 430 nmol / L）的人，其终身ASCVD风险可能相当于杂合性家族性高胆固醇血症。

在一级预防中，AHA / ACC和ESC / EAS指南之间有重要的相似之处。两者都可以识别出值得降低LDL-C水平的任何年龄段的LDL-C严重升高或40-75岁的糖尿病患者。两者都推荐他汀类药物作为一线疗法。两者均建议随访LDL-C水平，以确保效果是否足够以及是否依从性。但是，有重要的区别。尽管两者都认可达到特定LDL-C降低（以基线LDL-C的百分比表示）且他汀类药物强度与个体风险成正比，但ESC / EAS包括所有风险水平的特定LDL-C目标或指标。但是，对于那些未能达到任意LDL-C目标且可能从治疗讨论中受益的人，目标可能导致加重不确定性净收益的治疗。例如，在低危患者中加强LDL-C降低治疗的净收益，该患者在42岁时患有中等强度他汀类药物和LDL-C刚超过100 mg / dl（2.6 mmol / L）的新近糖尿病，要达到目标还不清楚。AHA / ACC认可他汀类药物可降低那些通过LDL-C降低治疗可带来净收益的一级预防患者，经随机对照试验证明是安全有效的。它着重于临床医生-患者的风险讨论以及冠状动脉钙化评分的选择，这可能会使他汀类药物治疗更具体地集中在受益最大的人群上。达到目标还不清楚。对于那些通过LDL-C降低疗法具有净获益的一级预防患者，AHA / ACC认可他汀类药物可降低LDL-C，经随机对照试验证明是安全有效的。它着重于临床医生-患者的风险讨论以及冠状动脉钙化评分的选择，这可能会使他汀类药物的治疗更具体地集中于受益最大的人群。达到目标还不清楚。AHA / ACC认可他汀类药物可降低那些通过LDL-C降低治疗可带来净收益的一级预防患者，经随机对照试验证明是安全有效的。它着重于临床医生-患者的风险讨论以及冠状动脉钙化评分的选择，这可能会使他汀类药物的治疗更具体地集中于受益最大的人群。

作者是《 2018年美国心脏协会-美国心脏病学会多元社会胆固醇指南》撰写小组的成员。

本文表达的观点不一定是编辑者或美国心脏协会的观点。

https://www.ahajournals.org/journal/circ