Association of MR-proadrenomedullin with cardiovascular risk factors and subclinical cardiovascular disease q Johannes Tobias Neumann a,1 , Stergios Tzikas b,1 , Anne Funke-Kaiser a , Sandra Wilde a , Sebastian Appelbaum a , Till Keller a , Francisco Ojeda-Echevarria a , Tanja Zeller a , Isabella Zwiener c , Christoph R. Sinning a , Annika Jagodzinski a , Renate B. Schnabel a , Karl J. Lackner d , Thomas Münzel b , Stefan Blankenberg a , Philipp S. Wild b, e,1 , Karsten Sydow a, * , 1 a Department of General and Interventional Cardiology, Hamburg University Heart Center, Martinistraße 52, 20246 Hamburg, Germany b Department of Medicine 2, University Medical Center Mainz, Mainz, Germany c Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Center Mainz, Germany d Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Mainz, Germany e Center for Thrombosis and Haemostasis, University Medical Center Mainz, Mainz, Germany article info Article history: Received 15 November 2012 Received in revised form 20 February 2013 Accepted 3 March 2013 Available online 19 March 2013 Keywords: Biomarker Adrenomedullin Cardiovascular disease Cardiovascular risk factors Reference values abstract Aims and background: Midregional proadrenomedullin (MR-proADM) is a protein, which exerts various effects on the cardiovascular system. Recent studies underscored its prognostic implications in patients with acute dyspnea and cardiovascular diseases. Therefore, we aimed to determine the distribution of MR-proADM in the general population and to reveal potential associations of MR-proADM with car- diovascular risk factors and measures of subclinical cardiovascular disease. Methods and results: MR-proADM plasma concentrations were determined in individuals of the population-based cohort of the Gutenberg Health Study (N ¼ 5000) using a commercially available fluoroimmunoassay. Individuals were enrolled between April 2007 and October 2008. Subclinical car- diovascular disease was assessed using echocardiographic and functional measures of myocardial and vascular function. The mean age of the study population was 55.5  10.9 years. In the overall population we determined a median MR-proADM plasma concentration of 0.44 nmol/L in men and women. MR- proADM concentrations were elevated in individuals with hypertension, diabetes, dyslipidemia, known cardiovascular disease, heart failure, peripheral artery disease, atrial fibrillation, and history of myocardial infarction and stroke. In men, we observed a positive association of MR-proADM with reduced ejection fraction, intraventricular septal diameter, wall thickness, and echocardiographic mea- sures of diastolic dysfunction. Conclusions: In this study, we present age-dependent reference values for MR-proADM in a represen- tative population sample. Elevated MR-proADM plasma concentrations were strongly associated with classical cardiovascular risk factors and manifest cardiovascular diseases. Furthermore, we revealed a gender-specific association with echocardiographic measures of hypertension. MR-proADM seems to be a promising prognostic biomarker for subclinical and manifest cardiovascular disease. Ó 2013 Elsevier Ireland Ltd. All rights reserved. Abbreviations: CVD, cardiovascular disease; ADM, adrenomedullin; MR-proADM, midregional proadrenomedullin; LV, left ventricular; MI, myocardial infarction; NT- proBNP, n-terminal pro-brain natriuretic peptide; CVRF, cardiovascular risk factors; GHS, Gutenberg Health Study; CAD, coronary artery disease; ECG, electrocardiogram; LDL, low-density lipoprotein; HDL, high-density lipoprotein; BMI, body mass index; NYHA, New York Heart Association; EDTA, ethylenediaminetetraacetic acid; EF, ejection fraction; IVSD, intraventricular septal diameter; IMT, intima-media-thickness; FMD, flow-mediated dilation; PAT, peripheral artery tone; SD, standard deviation; eGFR, estimated glomerular filtration rate; AF, atrial fibrillation; BP, blood pressure; CRP, c-reactive protein; ACC, A. carotis communis/common carotid artery; MV, mitralvalve; CI, confidence interval; DDPEF, diastolic dysfunction with preserved ejection fraction; SHFNDF, systolic heart failure with normal diastolic function; HFPEF, heart failure with preserved ejection fraction; PDFREF, preserved diastolic function with reduced ejection fraction. q Previous presentation of the manuscript: none. * Corresponding author. Tel.: þ49 40 7410 53979; fax: þ49 40 7410 59277. E-mail address: sydow@uke.de (K. Sydow). 1 These authors contributed equally to this work. Contents lists available at SciVerse ScienceDirect Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis 0021-9150/$ e see front matter Ó 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.atherosclerosis.2013.03.006 Atherosclerosis 228 (2013) 451e459