Novel biomarkers for prediction of poor treatment response in heart failure to guide therapy

• Published in: The Lancet (British edition) 2014-02, Vol.383, p.S32-S32
• Main Authors: Huy, Thong Cao, Dr, Quinn, Paulene A, MPhil, Sandhu, Jatinderpal K, MPhil, Voors, Adriaan A, Prof, Lang, Chim C, Prof, Jones, Donald J L, PhD, Ng, Leong Loke, Prof
• Format: Article
• Language: English
• Subjects: Cardiovascular diseases; Internal Medicine; Liquid chromatography; Mass spectrometry; Peptides; Proteins
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(14)60295-6

Abstract Background Heart failure is a complex clinical syndrome that occurs at the end stage of heart disease. It is a major health problem in western countries with an overall population prevalence of 2–3% which rises sharply to 10–20% at 75 years of age. Despite advances in therapy for heart failure, improvment of clinical outcomes remains a challenge for physicians: half of patients die within 4 years of diagnosis and 40% of patients, who have been admitted to hospital are dead or re-admitted to hospital within 1 year. The aim of this study was to find plasma proteins that predict differences in clinical response from standard therapy in patients with heart failure. Methods Patients with heart failure who met inclusion and exclusion criteria were recruited. Uptitration of angiotensin-converting-enzyme-inhibitors and β blockers was done over 6 months. Patients were followed up for clinical events such as death and admission to hospital for heart failure within the next 24 months. We compared plasma proteins in 50 patients who responded to standard treatment (responders) with 50 patients who died or were re-admitted to hospital (non-responders). Plasma samples were pooled and depleted of 14 high abundance proteins and then reduced and alkylated, before digestion with trypsin to peptides. Peptides were analysed on two-dimensional liquid chromatography coupled to a tandem mass spectrometry in high definition mode which used a high pH reverse phase liquid chromatography in the first step before separation with conventional low pH reverse phase columns in the second step. Findings 434 proteins were identified in the plasma of patients with heart failure. 137 proteins in both responders and non-responders were significantly overexpressed or underexpressed (p