Systems-Based Approaches to Cardiovascular Biomarker Discovery

The pace of discovery of cardiovascular biomarkers seems to be slowing. Although important advances in the identification of molecular biomarkers have been made during the past decade, it is becoming apparent that their clinical relevance is limited and that advanced discovery methods are needed.There are >27 000 articles on cardiac biomarkers in PubMed. However, only a small number of these biomarkers are in clinical use. In patients with heart failure (HF), numerous biomarkers have been evaluated (Table), but only brain natriuretic peptide and its precursor molecules have been widely applied.1 In patients with stable coronary artery disease, C-reactive protein (CRP) is a potential prognostic biomarker. Although there is conflicting evidence about the ability of CRP to augment the predictive accuracy of traditional clinical risk factors,2,3 targeting patients with elevated CRP for lipid lowering therapy with rosuvastatin was associated with improved cardiovascular outcomes in 1 randomized controlled trial.4 However, a recent meta-analysis of 83 studies including >60 000 patients has questioned its value.5 The key hurdle to the introduction of new “omic” biomarkers has been the inability to demonstrate their clinical relevance and validity. This refers not only to meeting analytic validity and independent evaluation criteria, but also to the biomarkers' capacity to guide the improvement of patient outcomes. We believe that a more integrated, unbiased approach is essential to discover novel diagnostic and prognostic models of heart disease.View this table:Table. Examples of Biomarkers in Heart FailureBiomarker discovery research has traditionally emphasized the study of individual molecular indicators of clinical condition. A major limitation of this approach is that the informational complexity underpinning many clinical states are not adequately taken into account.The relevance of hypothesis-driven, reductionist approaches to biomarker discovery is indisputable. However, an overreliance on this strategy may limit the translation of fundamental …