Elevated blood levels of the inflammatory marker myeloperoxidase may be a very early signal of cardiovascular damage that can lead to unexpected heart disease and infarctions years later in seemingly healthy adults, according to an article in the July 10 issue of the Journal of the American College of Cardiology.

“We were surprised to find that many years before a cardiovascular event actually occurs, myeloperoxidase is increased,” said Matthijs Boekholdt, MD, PhD, a resident in cardiology at Academic Medical Center in Amsterdam, the Netherlands. “This could open up completely new areas of research and diagnosis. As we learn more about these processes, we hope to be able to identify ‘vulnerable blood’ as a reliable tool for detecting vulnerable patients.”

Not only does myeloperoxidase change low-density-lipoprotein cholesterol into a harmful oxidized form that can cause atherosclerosis, peroxide activity damages the arteries directly, causing cell death and erosion of the endothelium, a process that can create unstable plaques. Myeloperoxidase also decreases the protective effects of high-density-lipoprotein cholesterol and reduces the availability of nitric oxide.

Earlier studies in patients with chest pain and heart disease have shown that elevated levels of myeloperoxidase identify those at highest risk for myocardial infarction.

“The novelty of the present study is that it is the first large-scale study to examine the relationship of myeloperoxidase to cardiovascular risk in apparently healthy individuals,” Boekholdt said.

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

After an average of eight years, 1,138 participants had been admitted to hospital or died from coronary artery disease, including myocardial infarction. Researchers matched these patients with study participants who remained healthy throughout follow-up, selecting those of the same gender and similar ages and enrollment times.

Average blood levels of myeloperoxidase were significantly higher in those who developed heart disease than in those who remained healthy. In fact, when myeloperoxidase 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 coronary artery disease or have a myocardial infarction. When traditional risk factors-blood pressure, low-density lipoprotein and high-density lipoprotein cholesterol levels, body mass index, smoking and diabetes?were taken into account, a level in the highest fourth increased the risk of heart disease by 1.36 times.

Equally important, elevated levels signaled increased risk even in those with acceptable levels of low- and high-density cholesterol, and C-reactive protein.
The search for blood tests to help identify patients at risk for infarction is a very important one, said Christopher Cannon, MD, who did not participate in the study and is an associate professor of medicine at Harvard Medical School, Boston, MA. “One fascinating aspect of this study is that this marker of inflammation precedes by nearly a decade the development of clinical coronary disease,” he said. “This suggests myeloperoxidase could be used to catch the disease in a very early stage and help in true prevention of coronary artery disease.