Cardiology in 2011—Amazing Opportunities, Huge Challenges

Abstract

THE HEART HAS ALWAYS HELD A SPECIAL FASCINATION for humans: it has been the seat of the soul; the home of emotions; and the pump that when beating, symbolizes life, and when silent, signifies death. Perhaps no other organ in the body has been so closely scrutinized. Therefore it is appropriate that as scientists and clinicians from around the globe gather at the 2011 American Heart Association (AHA) Scientific Sessions, we devote this theme issue of JAMA to cardiovascular disease (CVD). It is our hope that readers will clearly see that cardiovascular medicine remains a vital and rapidly changing discipline, filled with innovation yet also confronting significant challenges. Only 50 years ago, atherosclerosis was thought to be inevitable, a natural consequence of the aging process. However, carefully performed epidemiologic studies from the Framingham Heart Study and others identified the major CVD risk factors including hypertension, elevated cholesterol levels, smoking, and diabetes. These seminal works changed the view of CVD from a preordained fate to a preventable disorder. Much has been learned since that time regarding the etiology of CVD, yet multiple mysteries persist. For example, although the onset of CVD is directly related to the burden of CVD risk factors, Canto and colleagues, in their report in this issue of JAMA, found, paradoxically, that inhospital mortality following an initial myocardial infarction (MI) was inversely associated with the number of baseline risk factors. This interesting finding either could represent residual confounding or may indicate that patients without traditional risk factors who have an acute coronary event may harbor novel but as-yet uncharacterized and deadly CVD risk factors. Another “known but unknown” in CVD risk centers on blood pressure. Although it is known that high blood pressure can lead to CVD and stroke, the optimal therapeutic target for blood pressure control remains unclear. In their study of patients following a stroke, Ovbiagele and colleagues found a U-shaped association between longitudinal blood pressure levels and risk for recurrent events. The higher risk at lower levels of blood pressure could be the result of residual confounding, but these observational data raise the possibility that there may be harm if blood pressure management is too aggressive or too lenient. Cholesterol management is another important and modifiable risk factor. Scientists have unraveled the complexities of cholesterol metabolism and identified several therapeutic targets for manipulation. Statins effectively lower low-density lipoprotein (LDL) cholesterol levels and subsequently reduce CVD events when used in select primary and secondary populations. In this issue of JAMA, Nicholls and colleagues report on the first large experience with evacetrapib, a novel, potent, and selective inhibitor of cholesteryl ester transfer protein (CETP). In their clinical trial, the authors found that this new drug, when added to a statin regimen, further favorably improved lipid profiles by not only decreasing LDL levels but also by substantially increasing high-density lipoprotein (HDL) cholesterol levels. Although these findings are promising, subsequent larger outcome trials will be needed to confirm that these modifications in lipid profile translate into lower long-term CVD risk. The past few decades have seen the emergence of a number of acute and chronic interventions that prevent events, improve the quality of life, and save lives for patients with CVD. The tradition of exploration of novel concepts in CVD therapy continues in the research on the potential for pleuripotent stem cells to repair and replace damaged myocardium. To date, animal models have demonstrated that stem cell infusions following experimental infarction can restore ventricular function, yet the role of this intervention in humans remains controversial. In this issue, Traverse and colleagues report the primary findings of the LateTIME trial, the first of a series of human clinical stem cell trials sponsored by the National Heart, Lung, and Blood Institute (NHLBI). Their clinical trial was designed to specifically address the optimal timing of stem cell