INTRODUCTION

It is estimated that in excess of 20,000 proteincoding genes are responsible for the presence of more than million proteins found in biological matrices.1 The measurement of these proteins, commonly in plasma, serum, urine, saliva, and tissue samples, has provided critical advancements in medical science through the development of diagnostic and prognostic assays for patients presenting with, or at risk of, a multitude of diseases. The use of protein measurements has been particularly beneficial for the assessment of cardiovascular disease, with the notable inclusion of natriuretic peptides and troponin isoforms in clinical decision making for heart failure (HF) and acute coronary syndromes (ACS), respectively. Clinical measurements of endogenous biological substances, such as proteins, lipids, and metabolites, are commonly referred to as biomarkers and provide pathophysiologic information through an associative or direct mechanistic interaction with the diseased system, organ, or tissue. The relationships of protein biomarkers with disease allow physicians to assess the presence, severity, and/ or prognosis of a condition with improved precision and accuracy.

The progression in medical diagnosis and treatment of HF has been heavily influenced by the inclusion of protein biomarker analyses, with measurement of natriuretic peptides commonly used in hospitals worldwide. HF is a major worldwide epidemic associated with high morbidity, mortality, and health care costs affecting more than 23 million people, especially those aged 65 years or older ; therefore, any improvements in diagnosis, prognosis, and therapeutic monitoring using protein measurements provide direct improvements in patient care and outcome, as well as economic burden. Difficulties in HF diagnoses exist because of the multifactorial pathophysiology (eg, cardiac stress and injury, neurohormonal activation, and endothelial congestion), and because the signs and symptoms may not arise during early stages of the disease.