ACC/AHA心血管预防指南放弃降脂目标值

美国心脏病学会(ACC)和美国心脏协会(AHA)11月12日发布了最新版降低心血管风险临床实践指南，要点包括：不再推荐具体的血脂治疗目标值，建议同时评估10年和终生心血管疾病风险，以及在估算心血管疾病风险时将卒中纳入考虑范围。

撰写这部指南的是曾经名为成人治疗专家组(ATP)Ⅳ的血脂专家组。这部调脂治疗指南将不可避免地受到巨大关注，原因是它不再推荐将低密度脂蛋白胆固醇(LDL-C)降到特定的数值，而改为根据心血管疾病和卒中风险的增加程度使用已被证明可降低这些风险的药物。

专家组总结：“这部指南采用他汀治疗强度——而非LDL-C或非HDL-C目标值——作为治疗目标，基于来自随机对照试验的大量证据确定了中至高强度他汀治疗可安全降低动脉粥样硬化性心血管事件风险的4类人群。”

指南编撰委员会主席、西北大学心血管内科的Neil J. Stone博士指出，这部调脂治疗指南带来了“对LDL和非HDL胆固醇治疗目标的新视角”，确定了可将中至高强度他汀治疗作为一级或二级预防的4类患者。“尽管进行了广泛的文献复习，但我们未能找到确凿证据来支持继续使用特定的LDL-C和非HDL-C治疗目标。”

既往的指南推荐心血管高危者将LDL降至100 mg/dl以下，并建议极高危患者将LDL降至70 mg/dl或更低。

这一系列的临床实践指南最初是由国立心肺血液研究所(NHLBI)主持修订的，今年上半年改由AHA和ACC负责。ACC主席、加州大学洛杉矶分校David Geffen 医学院的John Gordon Harold博士在新闻发布会上介绍，在2011年以来的最佳临床试验和流行病学研究的基础上，除了血脂管理之外，这部“千呼万唤始出来”的指南还聚焦于评估心血管风险、改变生活方式以降低心血管风险，以及成人超重和肥胖的管理。

调脂治疗

Stone博士指出，现有证据支持在心脏健康生活方式的基础上采用“适当强度”的他汀治疗以降低风险。推荐接受“高强度”他汀治疗(使LDL降低至少50%)或“中强度”他汀治疗(使LDL降低约30%~49%)的4个“主要的他汀获益人群”包括：

·临床动脉粥样硬化性心血管疾病(ASCVD)。

·LDL-C明显升高至≥190 mg/dl，包括家族性高脂血症。

·糖尿病，年龄40~75岁，无临床性ASCVD，LDL水平介于70~189 mg/dl。

·无临床性ASCVD或糖尿病，年龄40~75岁，LDL水平介于70~189 mg/dl，估计10年ASCVD风险≥7.5%(通过计算整体心血管风险评分来判断，使用风险评估指南工作组提出的、已被纳入指南的公式)。

“我们认为，某些人群，如那些曾发生动脉粥样硬化事件和LDL-C水平极高的患者……从高强度他汀治疗中获益最大，如果他们能耐受的话。”Stone博士指出：“对于风险评分≥7.5%但尚未发生心肌梗死(MI)或卒中的患者，分析得出了强有力证据，表明治疗可以阻止或预防这些事件，在高危患者中甚至可以降低总死亡率。”

采用特定目标值常常可能导致某些人群治疗不足或治疗过度，例如加用增益价值尚未得到证实的药物。现有数据不支持采用某个具体的目标值，而是支持临床医生“对最可能获益的患者运用恰当强度的他汀治疗以降低动脉粥样硬化风险”，非他汀治疗“在心脏病发作和卒中的预防中，相比其不良反应，并不能提供可接受的CVD风险降低的获益”。

心血管风险评估

编撰委员会共同主席、西北大学预防医学系主任Lloyd-Jones博士指出，评估成人心血管风险的指南包括整体风险评估工具，后者“可以提供定量的临床评估以指导临床治疗”。


Donald Lloyd-Jones博士

指南建议，在评估10年风险的同时还应评估终生风险。10年风险方程式可预测MI和卒中的风险，而先前的风险方程式只关注冠心病事件风险。Lloyd-Jones博士指出，“我们很快意识到，假如不把卒中风险纳入到评估算法中，就会遗漏相当一部分的风险”，这在女性和黑人患者中尤为重要。

估计终生风险在识别10年风险较低“但具有不健康的生活方式或危险因素，实质上发生心血管疾病的远期风险较高”的年轻患者方面可能尤其有用。

针对非西班牙裔白人和针对黑人的风险方程式以NHLBI资助的人群研究的数据为基础，包括年轻成人冠状动脉风险发展研究(CARDIA)、社区动脉粥样硬化风险研究(ARIC)、心血管健康研究(CHS)，以及Framingham心脏研究。

使用这些方程式要求输入年龄、性别、种族、总胆固醇和HDL-C水平、血压、降压治疗状态，以及目前吸烟和糖尿病状态。这些被确定为10年风险的最佳预测因素。

研究者还考虑了其他风险标记物，但由于支持证据不足而未将其纳入方程式。在获得足够多的相关数据并开发出针对西班牙裔、亚裔，拉丁美洲裔等人群的风险预测方程式之前，将暂时对这些族裔的人群使用白人男性和女性的风险方程式。

基于对新型风险标记物相关文献的复习，工作组认为，假如上述方程式未能得出确切结果，“可以考虑”用4个标记物来优化风险评估：一级亲属早发心血管疾病家族史、冠状动脉钙化评分、高敏C-反应蛋白(CRP)检测值，以及踝肱指数检测值。

没有足够证据支持使用其他的标记物，而且“我们明确反对进行颈动脉内膜中层厚度测量”，原因是有证据表明，该检测并不能带来额外获益。

该指南还介绍了如何将风险评估融入临床实践，包括一份可用来计算风险的Excel电子表格。另外，可将风险方程式编制到电子健康档案中去。

退伍军人健康管理局全国心脏病学代理主任、科罗拉多大学内科学教授John Rumsfeld博士认为，新指南关于调脂治疗的建议是“对航向的修正”，而不是方向上的根本性变化。

“这部指南是基于对证据的客观评价，而且证据很明确：没有证据支持以特定的血脂水平为治疗目标。然而，有明确且强有力的证据显示，应当对心脏病和卒中风险升高者使用他汀类药物。新的治疗方法更加以患者为中心；治疗对象是最可能从长期用药中获益的个体；它关注的是用有确切效果的药物降低这些个体的风险；新方法还能通过减少反复检查和使用额外的、效果未获证实的药物而降低了患者的负担。”

早在1年前，退伍军人事务部(VA)医疗系统就已不再将LDL-C降至100 mg/dl以下作为全国绩效评价指标，而是采用了类似新指南推荐意见的绩效评价指标，强调对风险增高的患者使用他汀类药物。

“从治疗达标到降低风险的变化会减少使用未经证实的药物过度治疗患者的情况，并可减少反复血液检测和服用额外药物给患者和医疗系统带来的负担。”尽管临床医生可以一开始会对这部新指南感到惊讶，但Rumsfeld博士相信他们将会乐意接受这种观念的改变。临床医生“很快会发现新方式反映了现有证据，并且可以简化临床治疗”。

管理生活方式以降低心血管风险

编撰委员会的另一位共同主席、科罗拉多大学内科学教授Robert H. Eckel博士指出，另外两项指南推荐意见分别关注了生活方式管理和超重、肥胖管理。生活方式管理指南方面推荐了心脏健康膳食模式：包括水果、蔬菜和全谷物，限制饱和脂肪、反式脂肪和钠盐摄入，并且以相应的体力活动作为膳食建议的补充。



关于体力活动的建议主要基于2008年健康与人类服务部(DHHS)的报告，后者支持每周至少3~4天进行30~40分钟的中至高强度体力活动。

对于能从较低血压中获益的人，新指南建议每天钠摄入量不超过2,400 mg (之前推荐美国成人每天钠摄入量不超过3,600 mg)，同时指出每天钠摄入量≤1,500 mg与更大幅度的血压降低有关。

成人超重和肥胖的管理

编撰委员会共同主席、路易斯安那州立大学的Donna Ryan博士介绍，关于成人超重和肥胖的管理建议是与肥胖学会共同制定的，涉及5个主要领域，包括体重管理的治疗算法，以帮助初级保健医生确定体重管理方案。新指南可以帮助初级保健医生确定哪些患者需要减重、需要减轻多少体重、减重的益处、最佳膳食、生活方式干预的效果，以及减肥手术的获益和风险。

建议包括将体重指数(BMI)作为“快速、方便的首要筛选步骤”使用，以确定可能发生肥胖相关健康问题的患者，并且将腰围作为ASCVD风险、2型糖尿病和全因死亡的指示剂。

由于理想的减肥饮食尚未确定，临床医生应推荐热量摄入较低的饮食，而且饮食类型“应当真正根据患者的喜好和健康状况来确定”，例如对超重的高血压患者采取低热量、低钠饮食。

另一项建议是采取综合性减重措施，包括饮食和体力活动，进行至少6个月的咨询——理想情况下应当由经过训练的专业人士通过现场小组或个别辅导进行至少1年的咨询。

减肥手术可以作为BMI≥35 kg/m2且有合并症的患者，或者BMI≥40 kg/m2的患者的减重选择。虽然药物治疗是一个“关键”领域，但新指南并未就药物减重提出建议，原因是在开始制定新指南时，西布曲明(已被撤市)和奥利司他是唯一在美国获准用于减肥的药物。

Stone博士、Lloyd-Jones博士和Rumsfeld博士无利益冲突披露。

Eckel博士报告称与默克、辉瑞、雅培、Amylin、礼来、Esperion、foodminds、强生、诺和诺德、Vivus、葛兰素史克、赛诺菲-安万特/Regeneron等公司有利益关系。

Ryan博士报告称与Alere Wellbeing、Amylin、Arena制药、卫材、诺和诺德、NutriSystem、Orexigen、武田和Vivus等公司有利益关系。她是Scientific Intake的首席医疗官。

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By: ELIZABETH MECHCATIE, Cardiology News Digital Network

A move away from specific cholesterol treatment targets, assessment of both 10-year and lifetime cardiovascular disease risk, and inclusion of stroke in cardiovascular disease risk estimates are among the highlights of updated clinical practice guidelines on reducing cardiovascular risk released Nov. 12 by the American College of Cardiology and American Heart Association.

Written by the blood cholesterol expert panel that was originally the Adult Treatment Panel (ATP) IV, the cholesterol treatment guideline will inevitably receive the most attention, with the shift from recommending treatment of cholesterol to a specific LDL cholesterol target to treatment based on an increased risk for cardiovascular disease and stroke with medications proven to reduce those risks.
 
"Rather than LDL-C or non–HDL-C targets, this guideline used the intensity of statin therapy as the goal of treatment," identifying four groups of individuals "for whom an extensive body" of evidence from randomized controlled trials demonstrated a reduction in atherosclerotic CVD events "with a good margin of safety from moderate- or high-intensity statin therapy," the panel concluded.

While these guidelines are a change from previous guidelines, "clinicians have become accustomed to change when that change is consistent with the current evidence," they added.

The cholesterol treatment guideline provides "a new perspective on LDL and non-HDL treatment goals," with the identification of the four groups of patients for whom moderate- or high-intensity statin treatment is recommended, for primary or secondary prevention, explained Dr. Neil J. Stone, chair of the writing committee.

"Despite an extensive review, we were unable to find solid evidence to support continued use of specific LDL-cholesterol or non-HDL treatment targets," he said in a telephone briefing.

The previous guidelines recommended treating to an LDL goal of below 100 mg/dL in people at high cardiovascular risk, but also recommended a goal of 70 mg/dL or lower for patients at very high risk.

The four sets of clinical practice guidelines were initially commissioned by the National Heart, Lung, and Blood Institute (NHLBI) in 2008, and were transitioned to the AHA and ACC earlier this year. On the basis of evidence from the best clinical trials and epidemiologic studies through 2011, the "long-awaited" guidelines focus on assessment of cardiovascular risk, lifestyle modifications to reduce cardiovascular risk, and management of overweight and obesity in adults, in addition to management of blood cholesterol, Dr. John Gordon Harold, ACC president, said during the briefing.

The 2013 guidelines "will provide updated guidance to primary care providers, nurses, pharmacists, and speciality medicine providers on how to best manage care of individuals at risk of cardiovascular diseases," based on evidence available through 2011, said Dr. Harold of the David Geffen School of Medicine at the University of California and Cedars-Sinai Heart Institute, Los Angeles.

Cholesterol treatment

In the cholesterol treatment guideline, Dr. Stone said that based on an extensive literature review, the evidence supported the use of the "appropriate intensity" of statin therapy in addition to a heart-healthy lifestyle to reduce risk, with the identification of four "major statin benefit groups" for whom "high intensity" statin treatment (lowering LDL by at least 50%) or "moderate intensity" statin treatment (lowering LDL by roughly 30%-49%) is recommended. Those groups are patients with:
 
· Clinical atherosclerotic cardiovascular disease (ASCVD).
· A primary elevation of LDL-cholesterol of 190 mg/dL or higher, including those with familial hypercholesterolemia.
· Diabetes, aged 40-75 years with no clinical ASCVD and LDL levels of 70-189 mg/dL.
· No clinical ASCVD or diabetes, aged 40-75 years, with an LDL of 70-189 mg/dL and an estimated 10-year risk of ASCVD of at least 7.5% (determined by calculating the global cardiovascular risk assessment score, using formulas developed by the Risk Assessment guideline work group and included in that guideline).

"The idea was that certain groups such as those with [a prior atherosclerotic event] and those with very high LDL-cholesterol, especially these familial forms ... benefit most, if they can tolerate it, from high-intensity statin therapy."

For those with a score of 7.5% or more, who have not had an MI or stroke, analyses provide strong evidence that treatment can forestall or prevent these events, and in those at high risk, "even can reduce total mortality," said Dr. Stone, Robert Bonow Professor in the division of medicine-cardiology at Northwestern University, Chicago.

Often, the use of a specific target might lead to undertreatment in certain groups, or overtreatment when, for example, additional medications that are not proven to add incremental or additional benefit are added to treatment. Rather than supporting a target, the data indicated that clinicians "use the appropriate intensity of statin therapy to reduce this atherosclerotic risk in those most likely to benefit," and that nonstatin therapies "didn’t provide an acceptable CVD risk reduction benefit compared to their adverse effects in the routine prevention of heart attack and stroke," Dr. Stone noted.

Assessment of cardiovascular risk

The guideline on assessing cardiovascular risk in adults includes the global risk assessment tool, which "provides a quantitative clinical assessment to guide clinical care," said Dr. Donald M. Lloyd-Jones, one of the cochairs in the work group that wrote this guideline.

The guideline recommends lifetime risk alongside 10-year risk, said Dr. Lloyd-Jones, chair and professor of preventive medicine at Northwestern University, Chicago. The 10-year risk equations predict the risk of MI and stroke, while previous risk equations focused only on the risk of coronary heart disease events. "We realized quickly that we were leaving a lot of risk on the table by not also including stroke in our risk assessment algorithm," which is particularly important in female and black patients, he said.

Estimating lifetime risk may be particularly useful for identifying younger patients who have a low 10-year risk "but who have unhealthy lifestyles or risk factors that will put them at substantial risk for developing cardiovascular disease in the longer term," he added.

The risk equations for non-Hispanic white men and women and for black men and women are based on data from NHLBI-funded population-based studies, including the Coronary Artery Risk Development in Young Adults Study (CARDIA), the Atherosclerosis Risk in Communities Study (ARIC), and the Cardiovascular Health Study (CHS), as well as the Framingham Heart Study.

These require input of age, sex, race, total and HDL cholesterol levels, blood pressure, blood pressure treatment status, and current smoking and diabetes status, which were identified as the best predictors for 10-year risk, Dr. Lloyd-Jones said.

Other risk markers were considered, but were not included because there was not sufficient information to warrant their inclusion in the equations. Until risk-predictor equations are developed for Hispanics, Latinos, and Asian-Americans, as relevant data become available, the risk equations for white men and women should be used for other races and ethnic groups in the United States, he said.

Based on review of the literature on newer risk markers, the work group determined that four markers "may be considered" in refining risk estimates, if there is uncertainty after performing the risk equations: family history of premature cardiovascular disease in a first degree relative, coronary artery calcium score, measurement of high sensitivity of C-reactive protein (CRP), and measurement of ankle-brachial index.

The evidence for using other markers was insufficient, and "we explicitly recommend against performing carotid intimal medial thickness measurement," because of evidence that there is no additional benefit of this test, Dr. Lloyd-Jones said.

The guideline provides information on how to incorporate risk assessment into clinical practice settings, and includes an Excel spreadsheet that can be used to calculate risk, said Dr. Lloyd-Jones. Risk equations can also be programmed into electronic health records.

Dr. John Rumsfeld, acting national director of cardiology for the Veterans Health Administration, views the change in cholesterol treatment recommendations as "a course correction," rather than a radical change in direction.

"These guidelines are based on an objective review of the evidence – and that evidence is clear: There is no evidence for treating to specific target numbers for cholesterol. Yet, there is clear and strong evidence for the use of statin medications for people at elevated risk for heart disease and stroke," he said.

"The new treatment approach is more patient centered; it is about treating those who are most likely to benefit from taking a chronic medication; it is about reducing their risk with proven medicines; and it also reduces patient burden by lessening the need for repeat testing and taking additional, unproven medications," he said in an interview.

Over a year ago, the VA health care system dropped its national performance measure for treating to an LDL-cholesterol below 100 mg/dL, based on an independent review of the evidence. Using an approach that is similar to that recommended in the new guideline, the VA implemented a performance measure that emphasized the use of statin medication in patients at elevated risk.

"The change from treating targets to treating risk leads to fewer patients being overtreated with unproven medications, and reduces the burden on patients of repeated blood testing and additional medications to take," said Dr. Rumsfeld, also professor of medicine at the University of Colorado, Denver. In addition, the change reduces repeat blood tests and extra medication use, reducing costs to the health care system, he pointed out.

"Instead of repeated laboratory testing, and uptitrating medications or adding additional medications for patients to take with possible side effects, this approach emphasizes initiating treatment with proven medications for those at risk," he said.

Although clinicians may be initially surprised by the guidelines, he said he believes they will be well received. Clinicians "will quickly see that the approach reflects current evidence, and that the approach simplifies care," said Dr. Rumsfeld, who served as one of the expert reviewers of the guidelines.

Lifestyle management to reduce cardiovascular risk

The other two guidelines are on lifestyle management, and on overweight and obesity. The lifestyle management guideline includes recommendations for a dietary patterns that are heart healthy, including those with fruits, vegetables, and whole grains; limiting saturated fat, trans fat, and sodium intake; and for a physical activity level that complements dietary recommendations," said Dr. Robert H. Eckel, cochair of the writing committee, and professor of medicine at the University of Colorado, Denver.

The physical activity recommendations are based largely on a 2008 Department of Health and Human Services report, which provided support for 30-40 minutes of moderate to vigorous activity at least 3-4 days a week.

For people who could benefit from a lower blood pressure, the guideline recommends a sodium intake of no more than 2,400 mg per day (a reduction from the current average of about 3,600 mg a day among U.S. adults), but points out that sodium intake of 1,500 mg a day or less has been associated with greater reductions in blood pressure.

Management of overweight and obesity in adults

The guidelines on the management of overweight and obesity in adults, developed with the Obesity Society, provide recommendations in five major areas and include a treatment algorithm on weight management, to help primary care providers address weight management in their patients, said Dr. Donna Ryan, cochair of the writing committee and professor emeritus at Louisiana State University’s Pennington Biomedical Research Center, Baton Rouge.

The guidelines help primary care providers identify which patients need to lose weight and how much weight loss is needed, as well as the benefits of weight loss, the best diet, the effectiveness of lifestyle interventions, and the benefits and risks of bariatric surgery.

The recommendations include the use of body mass index as "a quick and easy first screening step" to identify patients who may be at risk for obesity-related health problems, and weight circumference as an indicator of ASCVD risk, type 2 diabetes, and all-cause mortality, Dr. Ryan said.

Since the ideal weight loss diet has not been identified, providers should recommend a diet that results in reduced caloric intake, and the type of diet "should really be determined by the patient’s preferences and their health status," such as a reduced calorie, reduced sodium diet for an overweight, hypertensive patient.

Another recommendation is a comprehensive approach to weight loss that involves diet and physical activity, with counseling for 6 months or more – which ideally should be on-site group or individual counseling sessions with a trained professional for at least 1 year.

Bariatric surgery may be an option for patients with a BMI of 35 kg/m2, with comorbidities, or a BMI of 40. Although a "critical" area, recommendations on pharmacotherapy are not included, because at the time the guidelines were being developed, sibutramine (which has since been taken off the market) and orlistat were the only medications approved for weight loss in the United States.

Dr. Stone, Dr. Lloyd-Jones, and Dr. Rumsfeld had no disclosures.

Dr. Eckel disclosed ties to Merck, Pfizer, Abbott, Amylin, Eli Lilly, Esperion, Foodminds, Johnson & Johnson, Novo Nordisk, Vivus, GlaxoSmithKline, and Sanofi-Aventis/Regeneron.

Dr. Ryan disclosed ties to Alere Wellbeing, Amylin, Arena Pharmaceuticals, Eisai, Novo Nordisk, Nutrisystem, Orexigen, Takeda, and Vivus. She is chief medical officer of Scientific Intake.