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新血脂标志物不能有效预测心血管风险
作者:MARY ANN MOON 来源:EGMN 爱唯医学网   日期:2012-06-27 10:21
本文摘要:6月20日在《美国医学会杂志》上发表的一项研究显示,用新血脂标志物代替传统胆固醇测定或在后者基础上加测新血脂标志物,并不能提高预测心血管风险的能力。

    新兴危险因素协作组——6月20日在《美国医学会杂志》上发表的一项研究显示,用新血脂标志物代替传统胆固醇测定或在后者基础上加测新血脂标志物,并不能提高预测心血管风险的能力(JAMA 2012;307:2499-506)。

    总胆固醇和HDL胆固醇测定是已得到认可的预测心血管疾病(CVD)风险的方法。一些专家提议用更能反映动脉粥样硬化过程的其他指标(如总胆固醇/HDL胆固醇比值或总胆固醇-HDL胆固醇的差值)来代替现行的风险预测方法,以简化对CVD风险的预测。还有一些专家提议在现行风险预测方法上增加测定载脂蛋白B、载脂蛋白A-I、脂蛋白(a)或脂蛋白相关磷脂酶A2,以提高风险预测的能力。

    在这项研究中,英国剑桥大学公共卫生与初级保健科的Emanuele Di Angelantonio博士及其同事回顾了1968~2007年发表的探讨各种血脂指标与CVD预后的前瞻性队列研究。研究者选择15个国家的37项研究,以评价各种风险预测方法的准确性。这些研究共入选165,544例基线无CVD的患者,中位随访时间为10年。致死性和非致死性心血管事件为15,126起,其中10,132起为冠心病事件,4,994起为卒中事件。

    在整个研究人群和临床相关亚组(如糖尿病患者或甘油三酯升高的患者)中,用其他血脂标志物代替总胆固醇和HDL胆固醇测定均不能提高预测CVD风险的能力。事实上,用载脂蛋白B和A-1测定代替总胆固醇和HDL胆固醇测定反而明显降低了鉴别风险的能力。

    在现有风险评价基础上增加对多种新血脂标志物的测定仅能够轻微提高预测能力。所有的新血脂标志物均不能明显改变根据现行临床风险临界水平进行的分类。

    单纯根据传统危险因素进行筛查后,有13,622例患者被归类为中危患者。根据成人治疗组第三次指南,不建议对此类患者进行他汀治疗。研究者建立了一个统计学模型,在这些中危患者中对各种血脂标志物进行了评价。结果显示,测定脂蛋白(a)后,仅555例(4.1%)被重新界定为高危,测定脂蛋白相关磷脂酶A2后,仅365例(2.7%)被归入高危组,测定载脂蛋白B和A-I后,仅154例(1.1%)被归入高危组。换言之,对于CVD中危患者,每测定801例的脂蛋白(a)、每测定973例的脂蛋白相关磷脂酶A2及每测定4,541例的载脂蛋白B和A-I,才能在10年内预防1起额外的CVD事件。

    在随刊述评中,德克萨斯大学达拉斯西南医学中心人类营养中心的Scott M. Grundy博士指出,目前没有能够降低脂蛋白(a)和脂蛋白相关磷脂酶A2等新血脂标志物水平的治疗,这从另一方面表明没有理由常规检测这些血脂标志物(JAMA 2012;307:2540-2)。

    该研究获英国心脏基金会等多家机构资助。Di Angelantonio博士与默沙东等多家公司存在联系。Grundy博士声明无经济利益冲突。

 

Newer Lipid Markers Useless for CVD Risk Prediction

BY MARY ANN MOON

Using newer lipid markers to either replace or supplement conventional cholesterol measurements doesn’t improve cardiovascular risk prediction, according to a report from the Emerging Risk Factors Collaboration in the June 20 issue of JAMA.

Some experts have advocated simplifying and perhaps improving cardiovascular disease risk prediction by replacing the currently accepted measurements of total and HDL cholesterol with other measurements (such as the ratio of total:HDL cholesterol, or the difference of total minus HDL cholesterol) because these are believed to better reflect the underlying atherosclerotic process. Others have proposed adding measures of apolipoprotein B, apolipoprotein A-I, lipoprotein (a), or lipoprotein-associated phospholipase A2 to the current risk prediction formulas to improve risk prediction.

To examine whether any of these alternative methods of risk prediction would improve on the currently accepted method, researchers in the Emerging Risk Factors Collaboration reviewed the literature from 1968 through 2007 for prospective cohort studies that obtained numerous lipid measures and reported CVD outcomes, said Dr. Emanuele Di Angelantonio, head of the collaboration’s writing group, and his colleagues.

To assess the accuracy of each method of risk prediction, the researchers selected 37 studies involving 165,544 subjects in 15 countries who had no CVD at baseline and were followed for a median of 10 years. There were 15,126 incident fatal and nonfatal cardiovascular events, including 10,132 coronary heart disease and 4,994 stroke events.

Replacing total and HDL cholesterol measures with any other lipid markers did not improve CVD risk prediction in the study population as a whole, or in clinically relevant subgroups such as diabetes patients or people with elevated triglycerides. In fact, using apolipoprotein B and A-I measures instead of total and HDL cholesterol measures significantly worsened risk discrimination, said Dr. Di Angelantonio of the department of public health and primary care at the University of Cambridge (England), and his associates.

Adding information on various “emerging” lipid markers to existing risk assessments only improved prediction slightly. And none of the newer lipid markers significantly changed classification of subjects “across the clinical risk cutoff levels that are currently used to inform treatment decisions,” the investigators said (JAMA 2012;307:2499-506).

The researchers then created a statistical model that assessed various lipid markers specifically in 13,622 patients who were judged to be at intermediate risk after screening by conventional risk factors alone. Such patients would not be recommended for statin therapy according to Adult Treatment Panel III guidelines.

Using lipoprotein (a) measures would reclassify only 555 of these subjects (4.1%) to a higher-risk group, using lipoprotein-associated phospholipase A2 would reclassify only 365 subjects (2.7%) to a higher-risk group, and using a combination of apolipoprotein B and A-I would reclassify only 154 subjects (1.1%) to a higher-risk group. “In other words, such targeted assessment of [and initiation of statin therapy in] individuals at intermediate CVD risk could help prevent [one] extra CVD outcome over 10 years for every 801 assessed for lipoprotein (a), every 973 assessed for lipoprotein-associated phospholipase A2, and every 4,541 assessed for the combination of apolipoprotein B and A-I,” Dr. Di Angelantonio and his associates said.

Dr. Scott M. Grundy of the center for human nutrition at the University of Texas Southwestern Medical Center, Dallas, agreed. He noted that at present, there are no treatments known to reduce elevated levels of such “emerging” lipid markers as lipoprotein (a) and lipoprotein-associated phospholipase A2 – which is another compelling argument against routine measurement of these lipids.

Although several agents are being tested in clinical trials, none has shown proven efficacy, he wrote in an editorial comment (JAMA 2012;307:2540-2) accompanying Dr. Di Angelantonio’s report. This fact, added to the finding by Dr. Di Angelantonio and colleagues that these measures don’t enhance CVD risk prediction, shows that “there is no reason for clinical measurement” of these biomarkers,” Dr. Grundy concluded.

This study was funded by the British Heart Foundation, the U.K. Medical Research Council, and the U.K. National Institute of Health Research, Cambridge Biomedical Research Centre. Dr. Di Angelantonio reported ties to Merck Sharp and Dohme, John Wiley & Sons, and Pfizer, and his associates reported ties to numerous industry sources. Dr. Grundy reported no financial conflicts of interest.

(责任编辑:董明满)
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