Prognostic value of plasma midregional pro‐adrenomedullin and C‐terminal‐pro‐endothelin‐1 in chronic heart failure outpatients

Abstract

AimsThe identification of chronic heart failure (CHF) patients at high risk of adverse outcome remains a challenge. New peptides are emerging that may give additional information. In CHF patients, endothelin (ET) levels predict mortality risk. Adrenomedullin has been shown to predict mortality in ischaemic heart failure, but not in unselected or nonischaemic CHF patients. Moreover, ADM and ET have never been assessed in one model. The aim of the present study was to assess the prognostic value of midregional-pro-adrenomedullin (MR-proADM) and C-terminalpro-endothelin-1 (CT-proET-1) in outpatients with CHF. Methods and resultsWe measured plasma MR-proADM and CT-proET-1 levels in 786 consecutive CHF outpatients and compared them with B-type natriuretic peptide (BNP) levels. At 24-month follow-up, 233 patients had died. A stepwise forward Cox regression model with age, sex, estimated glomerular filtration rate, NYHA . II, left ventricular ejection fraction (LVEF), MR-proADM, CT-proET-1, and BNP as possible predictors revealed that MR-proADM levels [hazard ratio (HR) ¼ 1.77, P , 0.001] in addition to age (HR ¼ 1.02, P ¼ 0.004), ejection fraction (HR ¼ 0.98, P ¼ 0.004), and NYHA . II (HR ¼ 1.86, P , 0.001) were predictors of death at 24 months. When the analysis was repeated dependent on NYHA-stage, MR-proADM (HR ¼ 2.12, P , 0.001) and LVEF (HR ¼ 0.96, P ¼ 0.006) were significant markers, but only in patients with mild/moderate CHF. ConclusionOur data suggest that MR-proADM may be an important prognostic humoral marker, especially in mild/moderately symptomatic and non-ischaemic CHF patients.--

Prognostic Value of Emerging Neurohormones in Chronic Heart Failure during Optimization of Heart Failure–Specific Therapy

“…Adrenomedullin, a strong peripheral vasodilator, and its counterpart endothelin, a powerful vasoconstrictor, both play a prominent role in cardiovascular disease, but reliable measurements of these constituents are hampered by their instability and binding to plasma proteins. C-terminal proendothelin-1 precursor fragment (CT-proET-1) and midregional proadrenomedullin (MR-proADM) were studied in patients who had suffered myocardial infarction (18 -19 ), as well as in patients with advanced stages of HF (20 ). In both settings CT-proET-1 and MR-proADM were predictors of adverse outcome.…”

Acute coronary syndrome – the present and future role of biomarkers1)

“…Adrenomedullin exhibits protective effects on the heart and the vasculature [44]. The stable midregional part of its prohormone, MR-proADM, is elevated in various cardiovascular pathologies and has been shown to be strongly predictive of mortality in populations with cardiovascular disease, especially heart failure [45] but also AMI [46].…”

Regional circulatory distribution of novel cardiac bio-markers and their relationships with haemodynamic measurements

“…Plasma concentrations of biomarkers reflect the net balance between production and clearance but cannot distinguish between these two. Little is known about sites of production or disposal of many biomarkers or their relationships with haemodynamics, which could help explain their associations with adverse outcome (6)(7)(8)(9)(10).…”

“…The biomarkers were chosen to reflect different pathways potentially involved in heart failure: mid-regional pro-atrial natriuretic peptide (MR-proANP), a stable fragment of the ANP prohormone which reflects atrial pressure or transmural stress (11)(12); mid-regional pro-adrenomedullin (MR-proADM), a vasodilator peptide that may also offer cytoprotection (13)(14)(15); C-terminal pro-endothelin-1 (CT-proET-1), which mirrors the production of endothelin, a potent vasoconstrictor reflecting endothelial dysfunction (16)(17);Cterminal pro-arginine vasopressin (CT-proAVP or copeptin), a measure of AVP production (18); ultrasensitive procalcitonin (hsPCT), a marker of infection (19)(20)(21)(22); and galectin-3, a measure of tissue injury and fibrosis (23)(24). All of these markers regional circulatory bio-marker distribution Page 5 of 18 are elevated in heart failure and, in some way, reflect the severity of disease and prognosis (6)(7)(8)(9). and right heart catheterisation were enrolled (seven patients had significant valvular disease, nine had ischemic heart disease (IHD), one had both severe mitral regurgitation and IHD, two had an atrial septal defect and one had complete heart block with superior vena cava obstruction).…”