While there is certainly no crystal ball to see who is most likely to have a heart attack, the Cleveland Clinic (Cleveland, Ohio) has developed a new blood test that may be one approach to doing so and could become a standard in emergency rooms and primary care offices. According to a study published in The New England Journal of Medicine (NEJM), the test can identify those in danger of experiencing a heart attack within 30 days to six months. The groundbreaking work, done by researchers at the Cleveland Clinic, indicates that myeloperoxidase (MPO), which they described as an "abundant leukocyte enzyme," is elevated in "culprit lesions that have fissured or ruptured in patients with sudden death from cardiac causes." Steven Nissen, MD, one of the study authors, told Cardiovascular Device Update that the test "seems to be a better predictor [of adverse outcome] than all of the other tests that are out there."

Reported in the Oct. 23 edition of NEJM, the study authors said results identified patients at risk for cardiac events in the absence of myocardial necrosis, which indicates damage has already occurred to the heart. "We looked at more than 600 sequential patients who came to the emergency room with chest pain," said Stanley Hazen, MD, PhD, head of the section of preventive cardiology at the Cleveland Clinic, in a statement. "We found that adding MPO testing to current laboratory-based risk assessments increased our ability to predict future cardiac risks over the next 30 days to six months from 50% to 95% of the time." The study included 604 patients who arrived at the emergency room following the onset of chest pain.

Specifically, according to the study abstract, results demonstrated initial plasma myeloperoxidase levels predicted the risk of myocardial infarction, even in patients who are negative for troponin T at base line. According to the study, myeloperoxidase levels at presentation also predicted the risk of major adverse cardiac events, described as myocardial infarction, the need for revascularization or death within 30 days and six months after presentation of symptoms. In patients without evidence of myocardial necrosis, defined as those who were negative for troponin, the baseline myeloperoxidase levels independently predicted the risk of major adverse coronary events at 30 days and at six months.

Emergency room physicians often have difficulty diagnosing the source of chest pains when patients present with that symptom, and they must make rapid decisions but have only three diagnostic tools to help them determine acute coronary distress. One is the electrocardiogram, which measures the electrical activity of the heart, but identifies less than half of patients with ACS. Existing tests measure other proteins, including troponin, myoglobin and C-reactive protein (CK-MB), but those proteins only become present in the blood after damage to the heart has already been done. Thus, the Cleveland Clinic said its test "is especially valuable for identifying at-risk patients not recognized by current diagnostic laboratory testing."

Nissen told CDU he conducted a study about five or six years ago to "explore the sensitivity of troponin measurements as a means to detect adverse outcomes" of coronary heart disease. They stored samples of the patients' blood, and ultimately conducted this most recent test. Previous studies have linked inflammation to increased risk of cardiovascular disease. Inflammation of the arteries is what led the researchers to look at myeloperoxidase, which is an "inflammatory enzyme activated in patients with coronary diseases." Myeloperoxidase is actually used by the white blood cell to kill bacteria. "In this case, it's a defense mechanism," Nissen said.

The focus on cardiac diagnostic tests has increased in recent years, with market leader Biosite Diagnostics (San Diego, California) seeing sales of its Triage (troponin I, CK-MB and myoglobin) and BNP (B-type natriuretic peptide) tests post compound annual growth rates in excess of 100%. Biosite this year introduced the Cardiac ProfilER, a package that measures all four markers at the point of care in a single $45 test.

diaDexus (South San Francisco, California) was granted marketing clearance by the FDA in July for its PLAC test to be used as an aid in predicting an individual's risk for coronary heart disease. That test measures the level of lipoprotein-associated phospholipase A2 (Lp-PLA2) in blood and is meant to be used as an additional diagnostic tool to clinical evaluation and patient risk assessment.

Ischemia Technologies (Denver, Colorado) secured FDA clearance to market its Ischemia Modified Albumin test in the U.S. in February. IMA is an in vitro test based on the fact that albumin is modified by exposure to ischemic tissue. Albumin binds to certain metals at one end of a molecule, the N-terminus. Peter Crosby, president and chief executive officer of Ischemia Technologies, told CDU that misdiagnosis of chest pain can not only harm the patient, it also can be an expensive proposition for hospitals and physicians. "Misdiagnosis of chest pain in the No. 1 reason for malpractice suits," Crosby said earlier this year.

i-STAT (East Windsor, New Jersey) in September secured FDA marketing clearance for its i-STAT System Cardiac Troponin I test, which can provide indication of heart damage within 10 minutes by measuring the level of troponin in drops of blood. At the time, i-STAT described it as "the first product in the market that offers central laboratory-grade performance at the patient's bedside." Also, when assessing cardiac diagnostic tests, it is important to note that troponin becomes elevated in the bloodstream only about five to six hours after the initial event, resulting in damage to the heart. Also, about 5% of patients with myocardial infarction do not have elevated troponin.

SYNx Pharma (Toronto, Ontario) and LifeSign (Somerset, New Jersey) introduced a new cardiac marker testing product at this year's American Association for Clinical Chemistry (Washington) annual meeting that features three cartridges with differing combinations of troponin I, myoglobin and CK-MB. SYNx is marketing the product as Nexus DX MI in Europe, while LifeSign sells it in the U.S. as LifeSign MI.

Eric Topol, MD, another of the Cleveland Clinic authors of the NEJM article, said that several major drug companies, among them Abbott Laboratories (Abbott Park, Illinois), have expressed interest in commercializing MPO tests.

Women's symptoms early, different

Researchers at the University of Arkansas for Medical Sciences (UAMS; Little Rock, Arkansas) have reported in a new study that female heart attack victims remembered having unusual fatigue or other new symptoms as much as a month beforehand, suggesting a new way to stop heart attacks before they happen. "New or different fatigue, sleep problems, shortness of breath, indigestion and anxiety could be early warning signs of heart disease," said Jean McSweeney, PhD, RN, of the UAMS College of Nursing. "The appearance of these new symptoms, in conjunction with women's standard cardiovascular risk factors, should help providers recognize women who should be thoroughly checked for heart disease," said McSweeney, lead researcher in the study published by Circulation, the journal of the American Heart Association (AHA; Dallas, Texas).

In the three-year study of women in Arkansas, North Carolina and Ohio, the most common early symptoms women remembered were unusual fatigue (70%), sleep disturbance (48%), shortness of breath (42%), indigestion (39%), and anxiety (35%). The symptoms stopped after their heart attacks. Only 30% of the women in the survey remembered chest discomfort, which they usually described as aching, tightness, or pressure, but not pain. About 95% of the women remembered having these symptoms more than a month before their heart attacks. The AHA called the study, funded by the National Institute of Nursing Research, "one of the first comprehensive examinations of issues that might allow prevention of imminent heart attack in women."

In earlier studies, McSweeney and her colleagues found that women who remembered these symptoms in the month before their heart attacks either ignored these signs or were misdiagnosed when they sought medical help. Women also tend to have different symptoms during heart attacks. Rather than the chest pain that men typically experience, women are more likely to have shortness of breath (58%), weakness (55%), unusual fatigue (43%), cold sweat (39%), and dizziness (39%). "Lack of chest pain may be a major reason why women have more unrecognized heart attacks than men or are mistakenly diagnosed and discharged from emergency departments," McSweeney said. "Many clinicians still consider chest pain the primary symptom of a heart attack." The Arkansas-North Carolina-Ohio group was made up primarily of Caucasian women, so McSweeney and her colleagues are now studying ethnic minorities.

Diabetes in young key heart attack risk

Young adults, ages 18-44, who get Type 2 diabetes are 14 times more likely to suffer a heart attack and up to 30 times more likely to have a stroke than their peers without diabetes. Young women account for almost all the increase in heart attack risk, while young men are twice as likely to suffer a stroke as young women. These results come from a study by two researchers at Kaiser Permanente's Center for Health Research (CHR; Portland, Oregon), funded by the American Diabetes Association (Alexandria, Virginia) and appearing in the November issue of Diabetes Care.

"This means that huge numbers of people are going to get heart disease, heart attacks and strokes years, sometimes even decades, before they should," said Teresa Hillier, MD, an endocrinologist and investigator at CHR and lead author of the article. "Young adults are increasingly likely to be overweight and diabetic. Our study is the first to look at the health outcomes of young adults who get diabetes, and the greatly increased risks of heart attack and stroke are very alarming." To conduct the study, Dr. Hillier and her colleague used electronic medical records to identify 7,844 individuals who were newly diagnosed with Type 2 diabetes from 1996 to 1998 (1,600 were under age 45 and 6,244 were 45 or older).

Among other findings:

People with early-onset Type 2 diabetes are 80% more likely to need insulin therapy within two years than people with usual-onset Type 2 diabetes.

People with early-onset diabetes were significantly more obese on average than people with usual-onset diabetes (BMI 37 vs. 33).

Younger adults with diabetes were more than twice as likely as older adults with diabetes to develop any heart disease compared to their peers without diabetes.

Volume/mortality relationship seen in SAH

A study published in the Journal of Neurosurgery found a strong relationship between in-hospital mortality following subarachnoid hemorrhage (SAH), the deadliest form of stroke, and the volume of such cases seen at the treating hospital. The study, considered the most comprehensive to date evaluating the volume-mortality relationship in SAH cases, showed patients treated at high-volume SAH centers had a 40% better chance of leaving the hospital alive than patients treated at low volume centers. Study authors attributed this finding, in part, to differences in the availability of specialized personnel, equipment and protocols at low- and high-volume SAH centers.

SAH is bleeding into the compartment around the brain. The most common cause is a ruptured brain aneurysm, a weak spot in a brain artery that has ballooned out. Other origins of hemorrhagic stroke are vascular malformations, high blood pressure that leads to the rupture of a tiny artery or vein, and drugs that create a dysfunction of the clotting system.

The study found that the in-hospital mortality rate of low-volume hospitals (those treating less than 10 a year) was 38.7% compared to only 27% in high-volume centers (those treating more than 35 a year). The large difference in mortality suggests that there may be significant benefits to centralizing SAH care for these catastrophic strokes, the researchers said. "The 40% reduction in relative risk seen at high-volume SAH centers represents one of the largest impacts demonstrated in any medical study examining mortality differences at low- and high-volume centers," said DeWitte Cross, MD, lead author and director of interventional neuroradiology at the Mallinckrodt Institute of Radiology at Washington University's Barnes-Jewish Hospital (St. Louis, Missouri). "This is the most comprehensive study of its kind to date involving patients from 18 states, representing nearly 60% of the U.S. population. Its findings suggest that centralizing treatment of this disease in high-volume centers may mean significantly more patients will survive their SAH."

Study authors point to a variety of factors likely to account for the large difference in mortality. Compared to their low-volume counterparts, high-volume hospitals tend to have more specialists on staff, rely on more sophisticated and less-invasive imaging equipment and use a defined team approach to treatment. In addition, they benefit from experienced neuro-intensive care units and offer both surgical and endovascular treatment. For example, the study showed that only 2% of low-volume hospitals offered endovascular treatment.

"The patterns of care for patients with SAH are complex and indicate that opportunities may exist to improve outcomes through development of high-volume, multi-disciplinary centers," said Cross.

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