易损斑块筛查的黄金时代并没有来临

Screening for Vulnerable Plaque: Not Ready for Prime Time

（北京武警总医院 韩玮 翻译）

休斯敦心肌梗死预防协会(SHAPE)的Morteza Naghavi 指出基于传统危险因素的易损病人的筛查结果令人失望，这是SHAPE 建议对无症状人群筛查的一部分。

心脏病医生面临两个主要问题，一个是对健康人群中获得准确的危险因素评价，他举了两个不同的吸烟、肥胖的例子，邱吉尔和Jim Fixx，邱吉尔一直活到90岁而没有严重的心血管事件，而Fixx 53岁即死于严重心肌梗死。另一个问题是发现那些对治疗反映不佳的人群。

为了对患者进行危险分层，Naghavi 提出了一个详细的检查：选择那些没有心肌梗死、冠心病、糖尿病病史或其他症状而因心脏病急诊入院的患者，根据NCEP 指南对他们进行危险分层，仅12%进入到高危组，大约一半不需要治疗，大约70%归为低危组。

这样的发现促使SHAPE 专门进行功能和结构评价的联合分析，比如冠状动脉钙化积分和颈动脉内膜厚度测定，该方法更有助于发现易损患者，“这可能早期发现疾病并根据严重程度进行治疗”。

Naghavi说越来越多的IVUS和其他影像学政局支持无症状患者中局限的病变也可能引起严重的问题，我们不应该再继续等待而是要有所作为。最后他认为对心血管疾病筛查的费用支持不足，心血管疾病是美国的首要死因，大于癌症和事故死亡的人群的总和，而癌症筛查每个患者的联邦费用支持是1000美元，而胆固醇和血压的筛查仅为每个患者50美元。

深入理解易损斑块

比利时Aalst心血管中心的Bernard De Bruyne教授认为易损斑块筛查方法不成熟、费用昂贵且缺乏证据，但他相信易损斑块的概念，那些高危且没有得到最佳治疗的患者应针对局限性的斑块进行治疗，但他强调如何准确识别这样的斑块以及进一步进行有效治疗还有很长的路要走。

De  Bruyne说易损斑块的概念是很松散的，很多方面都没有被很好的认识。例如很多人认为薄纤维冒是引起急性血栓的惟一病理学基础，但也有很多的其他的方面。例如女性和糖尿病患者中斑块侵蚀是30%的ACS 的致病原因。另一个易损斑块的概念是多数易损斑块是非狭窄性和不引起显著血流动力学改变的斑块，但有理由相信很多AMI 患者血管狭窄也是致病原因。最近一个对ACS患者进行详细的定量冠状动脉造影分析的研究中，血栓周围血管都有显著的狭窄，随着时间的延长狭窄导致的冲击力可以导致斑块破裂。另外当病变接近管腔时病变周围较低的剪切力也可以导致斑块不稳定。总的来说，血流动力学、流体学和和生物学特性都参与了易损斑块。

应用最多的评价易损斑块的无创性技术是虚拟组织成像技术，最近IBIS2 研究的结果显示虚拟组织成像技术并不一定是临床终点的可靠替代指标，但这一方向是正确的。无创技术的关键是要知道易损斑块的自然发展病程，而这大多数仍是未知数。

另一个重要的方面是将影像学结果和临床终点结合，以及找到有效的治疗方法，这意味着证明局部治疗比最佳的药物治疗更为安全和有效，但不幸的是对于轻度狭窄不良事件的发生率本来就很低，因此要找到有效的治疗任重道远。

（来源：www.tctmd.com）

Screening for Vulnerable Plaque: Not Ready for Prime Time

Key Points:

Structural assessment can aid in risk stratification, but the link to clinical outcome is lacking.

By TCT Daily Staff

Traditional risk factor-based screening to identify vulnerable patients fails miserably, contended Morteza Naghavi, MD, of the Society for Heart Attack Prevention and Eradication (SHAPE) in Houston, and proponent of the SHAPE guidelines that recommend screening asymptomatic people.

Cardiologists face two major problems, Naghavi said. One is obtaining an accurate risk assessment for apparently healthy people. He illustrated the dilemma by pointing to the different fates of a cigar-smoking, overweight Winston Churchill and the runner Jim Fixx, who was very fit. Churchill did not suffer a major event until age 90, while Fixx died of a massive MI at age 53.

The other problem involves patients who do not respond to treatment, as illustrated by the case of the late journalist Tim Russert.

To make his point about risk stratification, Naghavi proposed a thought experiment: Take a group of patients who arrive at the ER with no prior MI, CAD, diabetes, or other symptoms. Turn back the clock 24 hours, and run them through the existing NCEP guidelines for risk stratification, and only about 12% fall into the high-risk category and about half would not even qualify for treatment. Approximately 70% of people would have been categorized as low risk, Naghavi said.

This kind of analysis inspired the SHAPE task force to focus on combining functional assessments with structural assessments, such as the evidence-based coronary calcium score and carotid intima medial thickness measurement. This approach is better able to identify people who are most vulnerable, said Naghavi. "You identify the disease and you treat based on the severity of the disease," he added.

There is growing evidence from IVUS and a variety of other imaging techniques that local disease in asymptomatic people often causes trouble, Naghavi said. "Should we wait? Or should we do something about it?" he asked.

Finally, Naghavi lamented the relative lack of awareness of and economic support for screening for cardiovascular disease, which is the number one killer in the United States, ahead of cancer and accidental deaths combined. Yet the federal budget allocates about $1,000 per patient for cancer screening compared to just $50 per patient for cholesterol and blood pressure screening.

Broadening the understanding of vulnerable plaque

According to Bernard De Bruyne, MD, PhD, of the Cardiovascular Center in Aalst, Belgium, screening for vulnerable plaque is "premature, too costly, and unproven." Nonetheless, he said, he believes in the concept of vulnerable plaque. People who are at high risk and not being protected by optimal medical treatment should be targeted for treatment of local plaque. But, he emphasized, we are still a long way from accurate identification of such plaque and even farther from identification to effective treatment.

To begin with, the definition of "vulnerable plaque" is very loose, De Bruyne said, and many aspects of the phenemenon are underappreciated. For example, many people believe that thin cap fibroatheroma is the only pathological substrate for acute thrombotic occlusion. But there are many other culprits, he observed. For example, erosion of an atheroma is responsible for up to 30% of cases of ACS in women and diabetics. Another misconception is that vulnerable plaque is mostly non-stenotic and hemodynamically insignificant, he said. But there is good reason to suspect that in many patients with AMI, the stenosis is not benign. In a recent study in which careful quantitative coronary angiography was performed on patients with ACS, the vast majority were found to have significant stenosis underneath their thrombus. It is important to realize that these lesions induce a gradient, said De Bruyne, and that over time this force can contribute to plaque fatigue and rupture. In addition, when the lesion encroaches on the lumen, an area of low shear stress develops around the lesion that promotes plaque destabilization. In short, De Bruyne said, there is "cross-talk" among the hemodynamic, rheological, and biological contributors to vulnerable plaque.

The noninvasive technique that has been most used to assess vulnerable plaque is virtual histology, De Bruyne said. Recent promising results with an inhibitor of progression of the necrotic core in the IBIS 2 (Integrated Biomarker and Imaging) study do not mean that virtual histology is anywhere near being a reliable surrogate for clinical endpoints — but it is a step in the right direction, he said. Noninvasive techniques are critical to unraveling the natural history of vulnerable plaque, which remains largely unknown.

It is also crucial to match imaging data with clinical outcomes. And then, of course, to find effective treatment, which means proving that local treatment is safer and more effective than the best medical therapy available. Unfortunately, with mild stenosis, the rate of events is typically low, so that achieving a favorable treatment-to-benefit ratio may be difficult.

Despite his many caveats, however, in a nod to Naghavi’s project, De Bruyne said he keeps a copy of the SHAPE guidelines on his desk when seeing patients.

Disclosures:

Dr. Naghavi reports being a founder and shareholder of Endothelix Inc. and Volcano Corp.
Dr. De Bruyne reports no relevant conflicts of interest.

（source：www.tctmd.com）