Getting to the Heart of the Matter: Advanced Coronary Analysis of the Obese Patient
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A growing epidemic
The prevalence of obesity is increasing significantly worldwide. The International Obesity Task Force, a global non-governmental agency that studies the spread of the epidemic, estimates that 1.7 billion people—one out of every five worldwide—are overweight or obese. The World Health Organization (WHO) has projected there will be more than 700 million obese adults in the world by 2015.
In Europe, WHO says, the prevalence of obesity has tripled in many countries since the 1980s. By 2010, it is projected that 150 million adults and 15 million children will be obese. For men, the prevalence of obesity ranged from 5.4 percent to 22.8 percent, and from 7.1 percent to 35.6 percent among women, largely based by country. Men and women with a BMI of 35 kg/m2 had about 20 times the risk of developing diabetes of those of normal weight. To obesity, the organization attributes 2 to 8 percent of Europe’s total healthcare costs and 10 to 13 percent of deaths in different parts of the region.
The WHO predicts that approximately 130 million adults in the United States will be obese by 2015 (more than 80 percent of the U.S. adult population will be overweight). Studies done in the U.S. indicate that, in comparison with people of normal weight, obese people had 36 percent higher annual healthcare costs.
In Asia, obesity has hit epidemic proportions as well. The number of obese Chinese doubled to 60 million between 1992 and 2002, while some 200 million are at least overweight; among children, the obesity rate has reached 8.1 percent, according to a recent study from China’s Ministry of Health. Interestingly, clinical studies have shown that Asians can suffer the ill effects of obesity at a much lower BMI; a WHO study has suggested that the threshold for Asians could be a BMI of 23 for overweight, and 26 for obesity. For Westerners, a BMI above 25 is considered overweight, while one above 30 is obese.
With more incidence of obesity, there is increased risk for many diseases and conditions including type 2 diabetes, high blood pressure, breathing problems, heart disease and several types of cancer. India and China already have 32.7 million and 22.6 million diabetes sufferers, respectively. By 2030, the WHO forecasts, Asia could have as many as 190 million cases, with India and China having over 100 million between them. In China, 160 million people suffer from hypertension.
Correcting for attenuation artifact
Utilizing SPECT imaging alone in overweight and obese patients has been a clinical challenge due to attenuation artifacts that are commonly found since the information from the heart has to pass more attenuating tissue in this patient population. As obesity becomes more and more of an epidemic, it is increasingly more of an issue to include strategies that improve these attenuation artifacts that reduce test accuracy. “In our SPECT images, we are seeing defects within the heart that are not true perfusion defects, just attenuation artifacts and this is reducing the specificity of our SPECT-alone read outs dramatically if the patients are obese,” says Frank M. Bengel, MD, director of cardiovascular nuclear medicine at Johns Hopkins Medical Institutions in Baltimore.
Adding CT to the mix provides a transmission map that allows for attenuation correction (AC) of SPECT images. As a complement to a SPECT/CT study, calcium scoring can help to identify coronary artery calcifications.
Calcium scoring studies have a two-fold benefit: they can increase diagnostic accuracy of SPECT, and improve the prognostic risk assessment of the whole test. Increased diagnostic accuracy comes from increased confidence that a probably normal SPECT study is truly normal and vice versa. “If you can see there is no calcium in the coronaries of the patient; if you are unsure about the SPECT readout, a negative coronary calcium score can give you better confidence to call it negative,” Bengel says. The second benefit—prognostic risk assessment—is that due to integrated information provided from the calcium score as well as the perfusion study, patients can be more precisely subdivided into different risk groups.
Attenuation correction offers an advantage over SPECT alone, but not over PET/CT. According to Bengel, the hope is SPECT/CT utilization will increase specificity and decrease the gap in accuracy between the two hybrid technologies. “We are getting closer to the diagnostic accuracy of SPECT/CT, but PET/CT is probably still the most accurate technique for advanced coronary analysis in an obese subset,” he adds.
At Johns Hopkins, the practice is to preferably use PET/CT for patients who are above 300 pounds—due to the large number of equivocal studies seen with SPECT and SPECT/CT compared to PET. However, he maintains that SPECT/CT is still the clinical workhorse for advanced coronary analysis in obese patients, due to the limited availability of PET/CT scanners and additional reimbursement limitations for cardiac PET.
In the future, SPECT/CT might be used as a first-line test, and if equivocal results are encountered, PET/CT will be available in select academic and high-end centers as a second-line test, he adds, but this is an algorithm that has yet to tested in prospective studies, Bengel concludes.
PET/CT helps identify silent risk
Although mortality from cardiovascular disease has diminished in recent years, sudden cardiac death (SCD) remains the most common cause of death in the United States, claiming an estimated 350,000 lives annually. Most SCD events occur in people who do not have previous symptoms or signs of cardiac disease and, as such, would not have been considered to be at an increased risk for SCD.
Atherosclerosis, a preventable and treatable condition, if undetected, can be a contributing factor to SCD; obese individuals have a higher risk for the condition. According to the American Heart Association, overweight or obese individuals are predisposed to or associated with coronary heart disease (CHD), heart failure or SCD. The challenge in preventing SCD is in analyzing the coronary arteries for the presence of vulnerable, rupture-prone, non-calcified plaque.
“The basic issues that we deal with are that we know that half of myocardial infarction occurs due to rupture-prone plaque; not only is it non-calcified, but it is inflamed,” says Daniel S. Berman, MD, president of the Society of Cardiovascular Computed Tomography (SCCT), professor at the University of California, Los Angeles School of Medicine and chief of cardiac imaging and nuclear cardiology at the S. Mark Taper Foundation Imaging Center at Cedars-Sinai Medical Center in Los Angeles. Two major techniques that have been in development for the evaluation of vulnerable, rupture prone plaques are coronary CT angiography, which is being quite commonly used, and PET/CT imaging.
The utilization of PET/CT to evaluate the coronary arteries is still new. With CT, after coronary contrast agent injection, the lumen of the vessel wall is visible. Yet, because of CT’s ability to see soft tissue, it has the potential to quantify the amount of non-calcified and calcified plaque—but it does not reveal details about inflammation. Some characteristics of plaque that can be identified are, for example, if a non-calcified plaque is large, it might be a sign of vulnerability. If it is causing external bulging due to extensive amounts of lipids, then it is more likely to be rupture-prone.
PET/CT provides an additional opportunity to evaluate plaque metabolism using 18F fluoro-2-deoxyglucose (18F FDG). The theory behind 18F is that approximately 90 percent of white blood cells that are inside vulnerable plaque are a specific type that ingest foreign material and burn a lot of glucose, Berman says. When the coronary arteries show an increase in glucose metabolism, this is generally considered to be a sign of vulnerable, rupture-prone, non-calcified plaque.
In carotid arteries and the aorta, PET/CT is useful in characterizing plaque formation since the hybrid scanner enables the collection of both metabolic and anatomical information in a single exam. “Our group is studying the same phenomenon in the same way, with a slightly different twist,” Berman says.
The twist is related to a problem encountered when imaging the coronary arteries. To use the highest resolution PET scanner available, coupled with a combination of respiration and cardiac gating, adjustments must be made for vertical heart movement during the cardiac cycle. 18F FDG is taken up in the myocardium and if the artery is over the heart, plaque might be obscured. Berman’s group is developing a new imaging technique utilizing coronary CT angiography (CCTA) to find the non-calcified, rupture-prone plaque, then injecting 18F FDG and imaging with PET scanner. Then, the two images, CCTA and PET, will be fused together to define the area of plaque and determine its level of glucose metabolism.
Roughly speaking, approximately 20 percent of patients who have significant three vessel CAD will have a coronary event over time. “Because of this, we often take these patients to bypass surgery or we perform angiography, but in so doing, we are treating 80 percent of patients who were not going to have event at all,” Berman notes. “Plaque imaging may provide an opportunity for assessing risk beyond what we are able to do by either looking at degree of stenosis of the lumen or the degree of ischemia caused by a lesion. It also could allow us to take certain patients who were candidates for interventional revascularization and instead use medical management.”
Going forward, the development of new tracers that will allow specific identification of vulnerable, rupture-prone plaque will enable better detection of patients at risk—thus increasing the clinical utility of cardiac PET/CT. For example, perhaps tracers could be directed towards activated white blood cells or apoptosis agents or agents looking at oxidized LDL, Berman concludes. Time will tell.