High chemical levels in blood stream indicate need for action to avoid heart attack, death

Researchers working to decode chemical SOS signals sent out by disease-damaged hearts believe they now know better when to aggressively clear clogged arteries and when medical procedures may be unnecessary and even harmful.

The research, led by Uppsala University in Sweden, appears in the Sept. 19 edition of the Journal of the American College of Cardiology.

According to the research, high levels of two proteins in the bloodstream indicate that patients with acute coronary syndromes – chest pain caused by lack of blood to the heart – are at high risk of having potentially fatal heart attacks. Taking aggressive action to treat their blocked arteries will reduce their risk of dying within one year.

On the other hand, patients with low levels of these proteins, also called biomarkers, are not at high risk for deadly heart attacks and may even be harmed by having angioplasty or bypass surgery to treat blocked arteries.

The proteins – troponin-T (TnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) – are just two of the biomarkers being studied by physicians and scientists around the world in an effort to improve treatment for a wide range of illnesses.

"Biomarkers are analyzed in blood samples taken from patients when they are admitted to the hospital," said Stefan James, MD, PhD, senior consultant cardiologist and catheterization laboratory director for Uppsala University Academic Hospital's Department of Cardiology. "With a better understanding of these markers, we will be able to assess risk for individual patients more accurately.

"We will also be able to individualize treatment alternatives," said Dr. James, lead author of the new study. "Thereby, we may avoid costly and potentially hazardous treatments for patients at low risk and still provide lifesaving and symptom-relieving medical and surgical treatments for those at high risk."

For the study, researchers conducted a statistical analysis of data collected as part of the Global Utilization of Strategies To open Occluded arteries-IV trial (GUSTO-IV). Records of 2,340 patients who underwent procedures to clear their blocked arteries within the first 30 days of the international trial were included in the analysis. All of these patients were diagnosed with non-ST segment elevation acute coronary syndromes. Non-ST segment elevation refers to how the heart beat appears when displayed in graph form.

Researchers found that if either TnT or NT-proBNP levels were elevated, patients benefited from aggressive treatment to clear their coronary arteries. But if either level was low or non-existent, patients did not benefit. In this group, undergoing invasive medical procedures resulted in a significant increase of death within one year of treatment. All results were independent of other chemical biomarkers in the blood, including C-reactive protein and interleukin-6.

Although TnT levels are routinely checked in patients seeking care for chest pain, NT-proBNP levels are not. Dr. James said this study shows both levels should be tested.

"I think NT-proBNP adds important information," he said, "and the test should be available for use in both emergency and in outpatient clinics."

Still, Dr. James said, tests and treatments can only do so much to keep people healthy.

"We have developed tools for identifying patients at high risk for heart attack," he said. "With these markers, we are also able to rule out serious heart disease with high accuracy. Now we want patients to take responsibility for their lifestyle and environment. Personally, I am concerned about the health of the next generation – of Americans, particularly. Lack of exercise and junk food may ruin all of our common medical efforts and successes."

Also participating in this research were the University of Alberta in Edmonton, Canada; Duke Clinical Research Institute in Durham, N.C.; and the Thoraxcenter, Erasmus Medical Center, in Rotterdam, the Netherlands.

Suresh Mulukutla, MD, FACC, an assistant professor of medicine at the University of Pittsburgh, was not connected with the research but said it gives physicians one more tool to help ensure that every patient receives the most appropriate treatment.

"This is an important finding because in many centers across the world, if patients present with acute coronary syndromes, they are rushed to the catheterization lab to have their arteries opened with angioplasty or stenting," said Dr. Mulukutla, an interventional cardiologist. "This study suggests that if we use these biomarkers, we may be able to better select patients who would truly benefit from such aggressive procedures. Conversely, we could treat lower-risk patients with more conservative strategies."

Although the study involved a retrospective data analysis, Dr. Mulukutla said, the large numbers of patients involved "argue in favor of the reliability of these results."

Dr. James reports no disclosures with this research, a substudy of the GUSTO-IV trial. Funding comes from a variety of sources, including Centocor Inc. and Eli Lilly and Co.

Also in this issue of JACC

Up to half of all patients with chronic heart failure (CHF) are also anemic, meaning they don't have enough oxygen-carrying red blood cells in their bodies. As a result, these people may experience a greater degree of shortness of breath, fatigue and other health problems. New research shows a less-costly treatment may be as effective as other trial-led therapy for treating anemia in these patients.

To date, treatment has involved a combination of synthetic erythropoietin and iron. Erythropoietin is a hormone produced by the kidneys that stimulates production of red blood cells. Its synthetic, or man-made, form is costly and not appropriate for all patients.

Researchers at The Heart Hospital in London and West Middlesex University Hospital in Isleworth, England, found that treating anemia with intravenous iron alone can be as effective as the dual therapy for some CHF patients. The researchers found the iron-only treatment to increase hemoglobin levels, decrease negative symptoms and increase the ability to exercise for patients in the small study.

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The American College of Cardiology is leading the way to optimal cardiovascular care and disease prevention. The College is a 34,000-member nonprofit medical society and bestows the credential Fellow of the American College of Cardiology upon physicians who meet its stringent qualifications. The College is a leader in the formulation of health policy, standards and guidelines, and is a staunch supporter of cardiovascular research. The ACC provides professional education and operates national registries for the measurement and improvement of quality care. More information about the association is available online at www.acc.org.

The American College of Cardiology (ACC) provides these news reports of clinical studies published in the Journal of the American College of Cardiology as a service to physicians, the media, the public and other interested parties. However, statements or opinions expressed in these reports reflect the view of the author(s) and do not represent official policy of the ACC unless stated so.

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