Advertisement

Association of MR-proadrenomedullin with cardiovascular risk factors and subclinical cardiovascular disease

      Highlights

      • MR-proADM was measured in the general population.
      • We determined its association with CVRF and measures of subclinical CVD.
      • Elevated MR-proADM was strongly associated with CVRF and manifest CVD.
      • Association with echocardiographic measures of hypertension is gender-specific.

      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 cardiovascular 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 = 5000) using a commercially available fluoroimmunoassay. Individuals were enrolled between April 2007 and October 2008. Subclinical cardiovascular 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 measures of diastolic dysfunction.

      Conclusions

      In this study, we present age-dependent reference values for MR-proADM in a representative 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.

      Keywords

      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 (mitral valve), 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)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Thygesen K.
        • Mair J.
        • Mueller C.
        • et al.
        Recommendations for the use of natriuretic peptides in acute cardiac care: a position statement from the Study Group on Biomarkers in Cardiology of the ESC Working Group on Acute Cardiac Care.
        Eur Heart J. 2011 Feb 2;
        • Kitamura K.
        • Kangawa K.
        • Kawamoto M.
        • et al.
        Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma.
        Biochem Biophysical Res Commun. 1993 Apr 30; 192 ([Research Support, Non-U.S. Gov't]): 553-560
        • Kitamura K.
        • Kangawa K.
        • Kojima M.
        • Ichiki Y.
        • Matsuo H.
        • Eto T.
        Complete amino acid sequence of porcine adrenomedullin and cloning of cDNA encoding its precursor.
        FEBS Lett. 1994 Feb 7; 338 ([Research Support, Non-U.S. Gov't]): 306-310
        • Morgenthaler N.G.
        • Struck J.
        • Alonso C.
        • Bergmann A.
        Measurement of midregional proadrenomedullin in plasma with an immunoluminometric assay.
        Clin Chem. 2005 Oct; 51 ([Comparative Study]): 1823-1829
        • Struck J.
        • Tao C.
        • Morgenthaler N.G.
        • Bergmann A.
        Identification of an Adrenomedullin precursor fragment in plasma of sepsis patients.
        Peptides. 2004 Aug; 25 ([Comparative Study]): 1369-1372
        • Ishiyama Y.
        • Kitamura K.
        • Ichiki Y.
        • et al.
        Hemodynamic effects of a novel hypotensive peptide, human adrenomedullin, in rats.
        Eur J Pharmacol. 1993 Sep 14; 241: 271-273
        • Jougasaki M.
        • Wei C.M.
        • Aarhus L.L.
        • Heublein D.M.
        • Sandberg S.M.
        • Burnett Jr., J.C.
        Renal localization and actions of adrenomedullin: a natriuretic peptide.
        Am J Physiol. 1995 Apr; 268: F657-F663
        • Kitamura K.
        • Kangawa K.
        • Eto T.
        Adrenomedullin and PAMP: discovery, structures, and cardiovascular functions.
        Microsc Res Tech. 2002 Apr 1; 57: 3-13
        • Bhandari S.S.
        • Davies J.E.
        • Struck J.
        • Ng L.L.
        The midregional portion of proadrenomedullin is an independent predictor of left ventricular mass index in hypertension.
        Metabolism. 2010 Jan; 59: 7-13
        • Al-Omari M.A.
        • Khaleghi M.
        • Mosley Jr., T.H.
        • et al.
        Mid-regional pro-adrenomedullin is associated with pulse pressure, left ventricular mass, and albuminuria in African Americans with hypertension.
        Am J Hypertens. 2009 Aug; 22: 860-866
        • Khan S.Q.
        • O'Brien R.J.
        • Struck J.
        • et al.
        Prognostic value of midregional pro-adrenomedullin in patients with acute myocardial infarction: the LAMP (Leicester Acute Myocardial Infarction Peptide) study.
        J Am Coll Cardiol. 2007 Apr 10; 49 ([Comparative Study]): 1525-1532
        • Klip I.T.
        • Voors A.A.
        • Anker S.D.
        • et al.
        Prognostic value of mid-regional pro-adrenomedullin in patients with heart failure after an acute myocardial infarction.
        Heart. 2011 Jun; 97: 892-898
        • Wild P.S.
        • Schnabel R.B.
        • Lubos E.
        • et al.
        Midregional proadrenomedullin for prediction of cardiovascular events in coronary artery disease: results from the AtheroGene study.
        Clin Chem. 2011 Jan; 58: 226-236
        • Tzikas S.
        • Keller T.
        • Ojeda F.M.
        • et al.
        MR-proANP and MR-proADM for risk stratification of patients with acute chest pain.
        Heart. 2012 Dec 4;
        • Brouwers F.P.
        • de Boer R.A.
        • van der Harst P.
        • et al.
        Influence of age on the prognostic value of mid-regional pro-adrenomedullin in the general population.
        Heart. 2012 Jul 21;
        • Christ-Crain M.
        • Morgenthaler N.G.
        • Struck J.
        • Harbarth S.
        • Bergmann A.
        • Muller B.
        Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: an observational study.
        Crit Care. 2005; 9 ([Comparative Study Evaluation Studies]): R816-R824
        • Maisel A.
        • Mueller C.
        • Nowak R.M.
        • et al.
        Midregion prohormone adrenomedullin and prognosis in patients presenting with acute dyspnea: results from the BACH (Biomarkers in Acute Heart Failure) trial.
        J Am Coll Cardiol. 2011 Aug 30; 58: 1057-1067
        • Potocki M.
        • Breidthardt T.
        • Reichlin T.
        • et al.
        Midregional pro-adrenomedullin in addition to b-type natriuretic peptides in the risk stratification of patients with acute dyspnea: an observational study.
        Crit Care. 2009; 13: R122
        • Masson S.
        • Latini R.
        • Carbonieri E.
        • et al.
        The predictive value of stable precursor fragments of vasoactive peptides in patients with chronic heart failure: data from the GISSI-heart failure (GISSI-HF) trial.
        Eur J Heart Fail. 2010 Apr; 12: 338-347
        • von Haehling S.
        • Filippatos G.S.
        • Papassotiriou J.
        • et al.
        Mid-regional pro-adrenomedullin as a novel predictor of mortality in patients with chronic heart failure.
        Eur J Heart Fail. 2010 May; 12: 484-491
        • Tzikas S.
        • Keller T.
        • Wild P.S.
        • et al.
        Midregional pro-atrial natriuretic peptide in the general population.
        Clin Chem Lab Med. 2012 Nov 23; : 1-9
        • Schnabel R.B.
        • Schulz A.
        • Wild P.S.
        • et al.
        Noninvasive vascular function measurement in the community: cross-sectional relations and comparison of methods.
        Circ Cardiovasc Imaging. 2011 Jul; 4: 371-380
        • Wild P.S.
        • Sinning C.R.
        • Roth A.
        • et al.
        Distribution and categorization of left ventricular measurements in the general population: results from the population-based Gutenberg Heart Study.
        Circ Cardiovasc Imaging. 2010 Sep; 3: 604-613
        • Wild P.S.
        • Zeller T.
        • Beutel M.
        • et al.
        The gutenberg health study.
        Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2012 Jun; 55: 824-830
        • Sinning C.
        • Wild P.S.
        • Echevarria F.M.
        • et al.
        Sex differences in early carotid atherosclerosis (from the community-based Gutenberg-Heart Study).
        Am J Cardiol. 2011 Jun 15; 107: 1841-1847
        • Smith J.G.
        • Newton-Cheh C.
        • Hedblad B.
        • et al.
        Distribution and correlates of midregional proadrenomedullin in the general population.
        Clin Chem. 2009 Aug; 55: 1593-1595
        • Bhandari S.S.
        • Davies J.E.
        • Struck J.
        • Ng L.L.
        Influence of confounding factors on plasma mid-regional pro-adrenomedullin and mid-regional pro-A-type natriuretic peptide concentrations in healthy individuals.
        Biomarkers. 2011 May; 16: 281-287
        • Elmas E.
        • Lang S.
        • Dempfle C.E.
        • et al.
        Diagnostic performance of mid-regional pro-adrenomedullin as an analyte for the exclusion of left ventricular dysfunction.
        Int J Cardiol. 2008 Aug 1; 128: 107-111
        • Mori T.
        • Kai H.
        • Kajimoto H.
        • et al.
        Enhanced cardiac inflammation and fibrosis in ovariectomized hypertensive rats: a possible mechanism of diastolic dysfunction in postmenopausal women.
        Hypertens Res. 2011 Apr; 34: 496-502
        • Duzenli M.A.
        • Ozdemir K.
        • Sokmen A.
        • et al.
        The effects of hormone replacement therapy on myocardial performance in early postmenopausal women.
        Climacteric. 2010 Apr; 13: 157-170
        • Bhuiyan M.S.
        • Fukunaga K.
        Characterization of an animal model of postmenopausal cardiac hypertrophy and novel mechanisms responsible for cardiac decompensation using ovariectomized pressure-overloaded rats.
        Menopause. 2010 Jan–Feb; 17: 213-221