Risk Stratification for CV Disease Gets Personal

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Stratifying cardiac disease risk is evolving along with the advancements in imaging technology, which help risk stratification become more highly individualized, taking us further toward personalized medicine.

PET imaging

Dedicated cardiac PET scanners, through improved hardware and software, enable faster imaging and higher resolution compared with conventional SPECT imaging. While cardiac PET was typically confined to those patients who could not be optimally scanned with SPECT, it is now securing its place in cardiology as a valuable tool in the fight against heart disease.

An important advance in the last several years has been demonstrating the ability to measure myocardial blood flow reserve with rubidium-82 (Rb-82) PET, which "increases PET's capability to identify patients at risk for developing cardiac events," says Daniel S. Berman, director of cardiac imaging at Cedars-Sinai Heart Institute in Los Angeles. Cardiac PET excels at identifying perfusion defects, particularly in specific patient populations that might be suboptimally imaged with SPECT. But rather than comparing one region of the heart with another, as with SPECT, measuring absolute blood flow reserve allows each region to be compared to itself and to determine how much blood flow can increase in that region in a given vessel.

Myocardial blood flow with 13N-ammonia and 15O-water as PET flow tracers has been validated. For example, Herzog et al found that myocardial blood flow reserve measured by 13N-ammonia added prognostic predictive value over perfusion findings alone (J Am Coll Cardiol 2009;54;150-156). In fact, an abnormal coronary flow reserve in patients with normal perfusion "allowed further discrimination of patients with high annual event rates from those with low annual event rates."

Herzog et al concluded that coronary flow reserve is a strong predictor of disease progression once disease is present. "This may be due to the fact that impaired coronary flow reserve may indicate extension of the disease beyond the epicardial coronary arteries down to the microcirculation, representing a more advanced disease stage that is, thus, more prone to deterioration."

However, both 13N-ammonia and 15O-water require an onsite cyclotron and have short physical half-lives (10 and two minutes, respectively). Rb-82 does not rely on a cyclotron and already is commonly used to assess perfusion.

El Fakhri et al determined that myocardial blood flow reserve measurement using Rb-82 was accurate and reproducible, with a good intra- and interobserver reliability, compared with 13N-ammonia (J Nucl Med 2009;50:1062-1071).

In another study, Anagnostopoulos et al found that the myocardial blood flow and coronary vasodilator reserve as measured by Rb-82 were inversely and non-linearly correlated to stenosis severity (Eur J Nucl Med Mol Imaging 2008;35:1593–1601). They concluded, "Quantitative Rb-82 PET can be a clinically useful tool for an accurate functional assessment of CAD [coronary artery disease]."

Imaging inflammation

Inflammation is known to play an important role in atherosclerosis and researchers are seeking ways to better use FDG-PET to stratify patients with greater risk as determined by their inflammation as shown by uptake of FDG.  

Rogers et al found that FDG accumulation was increased in patients with recent acute coronary syndromes, both within the culprit lesion as well as in the ascending aorta and left main coronary artery (J Am Coll Cardiol Img 2010;3:388-397). Their finding, they concluded, "suggests inflammatory activity within atherosclerotic plaques in acute coronary syndromes and supports intensification of efforts to refine PET methods for molecular imaging of coronary plaques."

Yoo et al used FDG-PET imaging to assess whether seemingly healthy individuals have inflammation as measured by FDG uptake (J Nucl Med 2011;52:10-17). Researchers noted that 40 percent of deaths from cardiovascular disease occur in patients with low cholesterol levels. Subjects were stratified by levels of high-sensitivity C-reactive protein (hsCRP), a marker for inflammation, and low-density lipoprotein cholesterol (LDL-C). They found that high levels of FDG uptake in the carotid arteries were associated with higher levels of hsCRP, despite any level of LDL-C.

Previously, Yoo and colleagues showed that patients with impaired glucose tolerance or type 2 diabetes had higher uptake of FDG-PET, representing inflammation, compared with healthy subjects, again