New Marker in Acute Coronary Syndromes
Myeloperoxidase, a protein expressed by polymorphonuclear neutrophils, is a powerful predictor of the risk of cardiovascular events in patients with acute coronary syndrome, said an international collaboration of researchers in the September 23, 2003, issue of the journal Circulation (Circulation. 2003;108:1440–1445).
The scientists, led by Stephanus Baldus, MD, of the University of Hamburg in Germany, for the CAPTURE (c7E3 Anti-Platelet Therapy in Unstable Refractory angina) trial investigators, assessed myeloperoxidase levels in the blood of 1090 patients with acute coronary syndrome in a substudy of the CAPTURE trial itself. During the next 6 months, they recorded the deaths and myocardial infarctions that occurred in the group. They determined that myeloperoxidase is an independent predictor of patients’ 6-month outcomes, as were troponin T, C-reactive protein, vascular endothelial growth factor, and soluble CD 40 ligand. They concluded not only that myeloperoxidase is an important risk indicator but that it extends prognostic information gleaned by measuring more traditional biochemical markers. For example, in patients with low troponin T levels (below 0.01 μg/L) and elevated myeloperoxidase, the risk of cardiovascular events is elevated. The measurement thus identifies a subgroup of patients who might be missed by more traditional marker measurements.
They concluded that myeloperoxidase “may serve as both a marker and mediator of vascular inflammation and further points toward the significance of PMN [polymorphic neutrophils] in the pathophysiology of ACS [acute coronary syndrome].”
Moderate Warfarin Dosages Adequate in Antiphospholipid Syndrome
Moderate dosages of warfarin appeared as effective as higher dosages in preventing thrombosis in patients with antiphospholipid antibodies who had had previous clotting episodes, said researchers from Canada and Chicago in a report in the September 18, 2003, issue of The New England Journal of Medicine (N Engl J Med. 2003;349:1133–1138).
Researchers led by Mark A. Crowther, MD, MSc, of the Department of Medicine at McMaster University in Hamilton, Ontario, randomly assigned 114 patients to receive higher-intensity warfarin to achieve an international normalized ratio (INR) of 3.1 or 4.0 or moderate-intensity warfarin to achieve an INR of 2.0 to 3.0. The patients were followed up for 2.7 years.
Six of the 56 patients on high-intensity warfarin and 2 of 58 patients on moderate-intensity warfarin experienced a recurrent thrombosis. Three patients in the high-intensity group had a major bleeding event, as did 4 patients in the moderate-intensity group. The researchers concluded that the high-intensity warfarin was “not superior” to moderate-intensity warfarin in the prevention of thrombosis.
In an accompanying editorial, Michael D. Lockshin, MD, and Doruk Erkan, MD, of the Hospital for Special Surgery, Joan and Sanford Weill College of Medicine, of Cornell University in New York, noted that 20 years after it was established that this syndrome exists, “we still lack scientifically robust, evidence-based rules for the treatment of the antiphospholipid syndrome” (N Engl J Med. 2003;349;1177–1179). They blamed the dearth of such information on the lack of well-designed prospective studies, as well as the fact that the syndrome itself is complex.
They said that two surprising results came out of this most recent study—the fact that there were few recurrent thrombotic events and that the lower dose of warfarin was as effective as the higher dose. “These results refute recent calls for treatment with even higher doses of anticoagulant agents,” they wrote.
They called for more studies into the different aspects of these important diseases. “An American antiphospholipid syndrome registry funded by the National Institutes of Health, the European Euro-Phospholipid Project and several recently established Canadian and American clinical trial consortia provide opportunities to conduct the correct type of study from the beginning. If these opportunities are taken, we will not have to wait another 20 years to know the best treatment for patients with the antiphospholipid syndrome.”
Atrial Fibrillation, Anticoagulation, and Stroke
Treatment with anticoagulants such as warfarin and aspirin to an INR of 2.0 or greater results in fewer ischemic strokes and deaths among patients with nonvalvular atrial fibrillation, said researchers from the Massachusetts General Hospital and Harvard Medical School in Boston, Kaiser Permanente of Northern California in Oakland, and the University of California, San Francisco, in a report in the September 11, 2003, issue of The New England Journal of Medicine (N Engl J Med. 2003;349:1019–1026).
The researchers, led by Elaine M. Hylek, MD, MPH, of Massachusetts General Hospital, retrospectively studied ischemic strokes in a cohort of 13 559 patients with nonvalvular atrial fibrillation. Medical records provided information on strokes, the use of warfarin or aspirin at admission, INR, and coexisting illnesses. A total of 596 strokes were identified in the group. Of those, 32% occurred while the patient was on warfarin therapy, 27% occurred in patients on aspirin, and 42% occurred in patients who were taking neither drug.
Of those patients on warfarin, the ones with an INR of less than 2.0 at admission had an increased risk of severe stroke and death within 30 days compared to those with an INR of greater than 2.0 on admission. The 30-day mortality rate for patients taking aspirin at the time of stroke was similar to that of patients who were taking warfarin and had an INR of less than 2.0.
The authors concluded that in this patient group, anticoagulation that results in an INR of 2.0 or greater reduces both the frequency of stroke and its severity along with the risk of mortality. “Our findings provide further evidence against the lower INR target levels in patients with atrial fibrillation,” they wrote.
Smoking Causes Nearly 5 Million Deaths Worldwide
Researchers from Harvard School of Public Health in Boston and the University of Queensland in Australia estimated that the annual worldwide death toll from smoking approaches 5 million, according to their article in the September 11, 2003, issue of The Lancet (Lancet. 2003;362:847–852). Deaths in developing countries were estimated to be as high as those in industrialized nations, with 84% of mortality in the developing world occurring in male smokers.
In this study, Majid Ezzati, PhD, an assistant professor at Harvard, and Alan Lopez, PhD, of the University of Queensland, devised methods of estimating the smoking-related deaths in developing nations, where 930 million of the 1.1 billion smokers in the world live. More than three quarters of smoking deaths worldwide occurred among men, but the proportion of male to female deaths was higher in the developing world. Dr Ezzati said in a released statement, “As the hazards of smoking accumulate among those who began smoking in developing countries over the past decade, coupled with population growth and aging, mortality as a result of smoking will rise substantially unless effective intervention and policies that curb and reduce smoking among men and prevent increases among women in these countries are implemented.”