A Diagnostics & Imaging Week

A study published in the July 10 issue of the Journal of the American College of Cardiology (JACC) reports that European researchers have uncovered a new clue to the mystery of how a seemingly healthy person can actually be at high risk for heart disease or a heart attack.

The culprit is myeloperoxidase (MPO), a protein secreted by white blood cells that signals inflammation and also releases a bleach-like substance that damages the cardiovascular system.

Although MPO is intended to kill harmful bacteria, it may instead inflame the body’s arteries and cripple protective substances in the blood, according to the study. Long before conventional risk factors set off alarms, elevated MPO levels signal that harmful plaque has been building up.

“We were surprised to find that many years before a cardiovascular event actually occurs, MPO is increased,” said Matthijs Boekholdt, MD, PhD, a resident in cardiology at Academic Medical Center (Amsterdam, the Netherlands). “As we learn more about these processes, we hope to be able to identify ‘vulnerable blood’ as a reliable tool for detecting vulnerable patients.”

Boekholdt and colleagues recruited healthy people living in Norfolk, UK, between 1993 and 1997, as part of a larger community-based research program known as the European Prospective Investigation Into Cancer and Nutrition (EPIC). They took baseline blood samples from each participant and froze the samples for future analysis.

After an average of eight years, 1,138 EPIC-Norfolk participants had been admitted to the hospital or died from the effects of coronary artery disease (CAD), including heart attack. The average blood levels of MPO were “significantly higher” in those who developed heart disease than in those who remained healthy.

When MPO levels were divided into four groups, patients in the highest fourth were 1.49 times as likely as those in the lowest fourth to develop CAD or have a heart attack.

When traditional risk factors blood pressure, LDL and HDL cholesterol levels, body mass index, smoking and diabetes were taken into account, an MPO level in the highest fourth increased the risk of heart disease by 1.36 times. Elevated MPO levels signaled increased risk even in those with acceptable levels of LDL cholesterol, HDL cholesterol or C-reactive protein, a well-known marker of inflammation.

“[This] is the first large-scale study to examine the relationship of MPO to cardiovascular risk in apparently healthy individuals,” Boekholdt said. “MPO levels help to identify individuals at increased risk for CAD when traditional risk screening fails.”

One of the study’s authors, Stanley Hazen, MD, PhD, is named as a co-inventor on pending patents filed by the Cleveland Clinic Foundation (Cleveland) relating to the use of MPO as a biomarker for cardiovascular disease.

PET/CT false positives found

Researchers at the University of Texas Medical School (UTMS; Houston) have found evidence suggesting that the software used in an unspecified model of positron-emission tomography/computerized axial tomography (PET/CT) scanner may generate a false-positive rate of as much as 40%.

While the researchers have come up with a patch for the software, no such fix is currently commercially available.

In an article appearing in the June 15 issue of the Journal of Nuclear Medicine (JNM), K. Lance Gould, MD, professor of cardiology at UTMS, and five others noted that “cardiac PET combined with CT is rapidly expanding despite artifactual defects and false-positive results due to misregistration of PET and CT attenuation correction data – the frequency, cause, and correction of which remain undetermined.”

Their data show that 103 of the 259 patients who participated in the study had false-positive results.

Of the 259 patients, scans for 59 — about 23% — indicated severe false abnormalities that indicated a need for immediate surgical intervention. “These falsely positive results could lead to unnecessary procedures for nonexistent heart problems or for problems that could be treated without surgery,” Gould said.

Gould said that images of PET/CT, appropriately interpreted, produce “absolutely perfect images of blood flow in the heart” and are “the best way to assess and directly manage heart disease.” He suggested that the misregistration problems he encountered were particularly severe for imaging of the front and side areas of the heart, which accounted for 76% of the 103 bad readings. The apex of the heart accounted for 8% of the false-positives, and the lower portion was the source of the balance of 16% of the erroneous readings.

Gould also co-authored a 2004 paper appearing in JNM that examined a similar problem with PET cardiac imaging that involved misregistration “between attenuation and emission images caus[ing] artifactual abnormalities ... that result in false-positive defects.”

According to that article, scans for roughly 21% of 1,177 came back with false positives, with patient characteristics such as body mass index, displacement of the diaphragm and heart size correlating most often with the misregistrations.

The abstract from the current study indicates that the researchers were checking for myocardial perfusion with a 16-slice scanner that employed helical attenuation correction.

Despite the expense associated with such equipment, Gould said that the software involved fails to account for movement in the lungs and heart while the patient is breathing.

Many perfusion tests involve stress tests during the perfusion, which may involve running or walking on a treadmill. Gould said that the failure of the PET and CT images to align properly causes “the images [to] have big holes or gaps where the processing is incorrect,” leading a diagnostician to conclude that the patient “has severe disease.”

Gould crafted a fix for the software problem with Tinsu Pan, PhD, associate professor of imaging physics at the M.D. Anderson Cancer Center (Houston), consisting of a rewrite of the software to correct for breathing motions and bringing the PET and CT images into alignment.