Proteins give early clue to coronary artery disease

Levels of blood proteins may help to predict the risk posed by coronary artery disease and help doctors to decide on the best course of treatment.

Researchers have found that raised levels of myeloperoxidase, an enzyme secreted from activated neutrophils, monocytes, and tissue macrophages, are independently associated with an increased risk of coronary artery disease (JAMA 2001;286:2136-42).

Dr Stanley Hazen from the Cleveland Clinic Foundation, Ohio, and colleagues collected data for 158 patients with known coronary artery disease and for 175 controls. They measured levels of leucocyte myeloperoxidase and blood myeloperoxidase for each patient. The researchers found that levels of both leucocyte and blood myeloperoxidase were significantly higher in patients with established coronary artery disease than in the controls (P<0.001). Multivariate analysis showed that the Framingham risk score, white blood cell counts, and myeloperoxidase levels were all significantly associated with coronary artery disease.

“If these findings are confirmed in other populations and prove to be predictive of coronary events, MPO [myeloperoxidase] levels may be helpful to identify patients with CAD [coronary artery disease] who might otherwise not be identified by routine screening methods,” the researchers concluded.

In a second study, another group of researchers found that raised levels of circulating interleukin 6 are an independent marker of increased mortality in patients with unstable coronary artery disease. The researchers suggested that patients with raised levels of interleukin 6 may be candidates for early surgical intervention (JAMA 2001;286:2107-13).

Dr Agneta Siegbahn from Uppsala University Hospital in Sweden and colleagues evaluated 3269 patients with unstable coronary artery disease for whom levels of interleukin 6 were available. These patients were randomly assigned to receive early treatment with coronary angioplasty or non-invasive treatment. Those receiving non-invasive treatment, and 666 patients for whom invasive treatment was contraindicated, were randomised to low molecular weight heparin or placebo for 90 days.

Overall, patients with higher levels of interleukin 6 were nearly 3.5 times more likely to die than those with lower levels. Although surgery reduced mortality by about 5% in the patients with high levels of interleukin 6, it had no effect on mortality among those with lower levels of the protein.

“In this study, we found that plasma IL-6 [interleukin 6] level is an independent marker for identifying patients with unstable CAD with increased risk of death over 6 to 12 months,” the researchers wrote. “IL-6 was ‘predictive’ independent of other risk indicators, including the biochemical markers troponin T and C-reactive protein.”

“Despite the interesting observations in [these] studies … major questions need to be resolved before measurements of [these blood proteins] are incorporated into the routine assessment of patients with CAD,” Dr David Vorchheimer and Dr Valentin Fuster of the Mount Sinai School of Medicine in New York city wrote in an editorial in the same issue of JAMA. “For now, such preliminary reports should not distract physicians or patients from treatments that have been unequivocally proven effective in treating CAD.”