On the last day of each year, for the last 9 years, the American Heart Association (AHA) releases a list of what the organization considers the "Top 10" advances in heart disease and stroke research. A group of clinical experts and research scientists from within the AHA select advances reported during the previous year based on suggestions from AHA volunteers. The experts choose reports that are likely to have the greatest impact on the treatment and prevention of cardiovascular disease or stroke. As in other years, the list for 2003 covers a wide range of advances.
For the last 3 years, the Journal of Cardiovascular Nursing (JCN) has devoted one issue each year to describing all 10 of these research advances. The articles not only describe the research advance, but place it in the context of previous related research and explain its potential impact on current or future clinical practice and cardiovascular health. For the clinician and research scientist alike, the list provides a perspective of where cardiovascular research has been, as well as a blueprint for future research and therapeutic implications.
In the first article, "New high blood pressure guidelines create new at-risk classification: Changes in blood pressure classification by the JNC 7," Dr Edgar Miller III and Megan Gehn from Johns Hopkins discuss this finding and others from the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. If you thought you were safe with a blood pressure reading of 130/82, you may be surprised to find that you (or your patients) are considered "prehypertensive." The bad news is that prehypertension is a precursor for higher blood pressure that greatly increases the risk of developing heart disease or stroke. The good news is that lifestyle changes can delay or prevent prehypertension from developing into full-blown hypertension.
Four of the Top 10 research advances for 2003 concern new pharmacotherapeutic agents or interventions. In the second article, "New blood thinner offers first potential alternative in 50 years: Ximelagatran," Dr Edith Nutescu and colleagues describe the mechanism of action of ximelagatran, as well as clinical trials supporting its efficacy and safety and its potential to replace warfarin. Anticoagulation therapy with warfarin has been a mainstay of treatment and prevention of multiple cardiovascular diseases. Any clinician who has tried to maintain a patient's warfarin therapy within the therapeutic range while dodging side effects and food and drug interactions will know the difficulties and drawbacks of this drug. Dose adjustments and laboratory anticoagulation monitoring of warfarin are constantly required. Finally, after 50 years, ximelagatran, a drug as effective as or more effective than warfarin and lacking these flaws is about to be approved by the FDA.
The second drug-related research advance highlights eplerenone, a promising new treatment for heart failure. About 5 million people in the United States have heart failure. Standard treatment of heart failure includes, among other drugs, beta-adrenergic receptor antagonists and ACE inhibitors or angiotensin II receptor antagonists to block the harmful effects of activation of the renin-angiotensin-aldosterone system. Yet, heart failure is still characterized by progressively diminishing quality of life, with mortality approaching 50% within 5 years. In 1999, the RALES trial showed that blocking the aldosterone receptor with spironolactone reduced morbidity and mortality in patients with heart failure, but adverse effects forced many patients to discontinue therapy. The fourth article, "New treatment option for heart failure patients: Eplerenone," describes results of the EPHESUS trial of eplerenone, a selective aldosterone receptor antagonist, which improves outcomes without causing many of the adverse effects of spironolactone.
The potential of a third drug, derived from vampire bat saliva, for the treatment of stroke is discussed in the eighth article. Ischemic stroke is sometimes referred to as a brain attack. Brain tissue dies when a clot forms in arteries that supply oxygen to the brain. Tissue plasminogen activator (rtPA) can effectively open arteries and save tissue if it is administered within 3 hours of stroke onset. Drs Grandjean, McMullen, and Newschwander report on findings from animal studies, demonstrating that Desmodus rotundus (vampire) salivary plasminogen activator (DSPA) can successfully break up clots that have been around for a much longer period of time. The thrombus busting activity of DSPA is now being tested in humans up to 9 hours after stroke symptoms appear. Discovery of DSPA has generated excitement owing to its potential to widen the time frame whereby ischemic stroke can be treated successfully.
Synthetic HDL (ETC-216) is the fourth new pharmacotherapeutic intervention that is considered one of the top 10 research advances of 2003. ETC-216 mimics a genetic variation of HDL that appears to protect a subgroup of people living in Italy from atherosclerosis. Controlled studies from investigators at the Cleveland Clinic demonstrate that once-a-week intravenous ETC-216 infusion for 5 weeks removed plaque from clogged arteries. The findings are discussed in the article "A shot of good cholesterol: Synthetic HDL, A new intervention for atherosclerosis."
Automated external defibrillators (AEDs): you are beginning to see them in planes, shopping malls, and many other public places. Every year over 400,000 Americans die of cardiac arrest. After the heart stops beating, the window for resuscitation is very short. Evidence described in the third article in this issue, "Public defibrillators: Increased survival from a structured response system," demonstrates that having available AEDs along with volunteers trained to use them and an integrated emergency response system greatly improves the chances of survival for victims of cardiac arrest.
"Heal thyself: Potential applicability of stem cell therapy in the management of heart disease," the fifth article in this issue, describes stem cell therapy and its potential to repair or replace cardiac tissue damaged by myocardial ischemia. In case of a heart attack, if the myocardium is not reperfused within a limited time frame, the heart muscle cells die and there is loss of cardiac function. Several teams of investigators are examining whether bone marrow stem cells, delivered directly to patients' damaged hearts, can differentiate into viable heart cells and improve myocardial function. The author highlights problems and promises associated with this therapeutic approach.
The article "Drug-coated stents: Preventing restenosis in coronary artery disease" follows up a report on drug-coated stents that first made the "AHA Top 10" research advances list of 2001. In 2001, clinicians and researchers were extremely excited about experimental results demonstrating that drug-coated stents significantly decrease the incidence of reocclusion of coronary arteries after stent placement. Late in 2003, successful outcomes from use of rapamycin (sirolimus)-coated stents in "real world" patients was reported in the journal Circulation. Julie Stanik-Hutt from Johns Hopkins reviews this exciting treatment advance for coronary occlusion.
The seventh article in this issue, "Newly mapped gene for thoracic aortic aneurysm and dissection," describes findings from a new area of research that can potentially prevent or mitigate genetically based cardiovascular disorders. Thoracic aortic aneurysm and dissection (TAAD) is life-threatening. People with this disorder are usually unaware of the problem until the aorta ruptures, resulting in a fatal bleed. Drs Wung and Aouizerat describe progress of investigators who have identified chromosome locations of genes associated with TAAD. Several have been found. The search continues for related genes so that tests can be developed to identify persons at risk for inherited TAAD. With identification, surgery can be performed to correct the problem before fatal consequences occur.
Finally, the last article, "New blood test to measure heart attack risk: C-reactive protein," explains how a new blood test for C-reactive protein can help physicians stratify patients for risk of heart attack and optimize treatment.
The goal of this third special issue of the JCN on the AHA's "Top 10 Research Advances" is to again provide cardiovascular nurses and other healthcare professionals with a review of recent research findings considered by experts to have the most immediate or future impact on treatment and prevention of cardiovascular disease. It is our observation that while some of the studies on the list for 2003 are primarily basic science, over the last 3 years, the list of research advances has become more clinically focused. As editors, we hope this issue meets its goal, and we express our thanks to the team of contributors, who worked hard to make it happen.