Biomarkers in Clinical Trials

In contemporary cardiovascular practice, the most common and useful applications of biomarkers focus on disease diagnosis, with troponins for myocardial infarction and natriuretic peptides for heart failure representing the most notable examples. Identification of additional cardiovascular diagnostic markers has proved challenging, however, because high quality studies for diagnostic indications are difficult to perform, and most putative cardiovascular biomarkers demonstrate inadequate cardiac specificity. Cardiovascular biomarker research has increasingly focused on the lower-hanging fruit of risk assessment, at least in part because prognostic biomarker studies are relatively easy to embed within ongoing clinical trials or epidemiology studies. Here also, success has been mixed; although numerous biomarkers have been associated with adverse outcomes across a variety of cardiovascular disease states, few meet appropriately rigorous criteria to support routine measurement for risk prediction in clinical practice.1 Moreover, risk assessment alone is of limited value to clinicians. To move beyond simple fortune telling and to take advantage of the potential value of circulating biomarkers as modifiable indices of specific biological pathways, additional applications have been investigated. These emerging roles include the use of biomarkers to guide therapeutic selection and the profiling of chronic disease course or response to treatment with individual biomarkers or panels of distinct markers. If biomarkers are selected that provide a reliable representation of a biological pathway mediating disease risk, it remains possible that the measurement of changes in these biomarkers will yield useful insight into the expected effects of different therapies.Article see p 695In the current issue of Circulation , Sobel et al report findings from a combination of 2 large biomarker substudies of the Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) trial, in which they consider several of these potential applications for cardiovascular biomarkers.2 In an ambitious study in which they performed serial …