Dr. Naghavi

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.

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.