title: Plasma levels of intermedin (adrenomedullin-2) in healthy human volunteers and patients with heart failure.
abstract: Intermedin/adrenomedullin-2 (IMD) is a member of the adrenomedullin/CGRP peptide family. Less is known about the distribution of IMD than for other family members within the mammalian cardiovascular system, particularly in humans. The aim was to evaluate plasma IMD levels in healthy subjects and patients with chronic heart failure. IMD and its precursor fragments, preproIMD(25-56) and preproIMD(57-92), were measured by radioimmunoassay in 75 healthy subjects and levels of IMD were also compared to those of adrenomedullin (AM) and mid-region proadrenomedullin(45-92) (MRproAM(45-92)) in 19 patients with systolic heart failure (LVEF<45%). In healthy subjects, plasma levels (mean+SE) of IMD (6.3+0.6 pg ml(-1)) were lower than, but correlated with those of AM (25.8+1.8 pg ml(-1); r=0.49, p<0.001). Plasma preproIMD(25-56) (39.6+3.1 pg ml(-1)), preproIMD(57-92) (25.9+3.8 pg ml(-1)) and MRproAM(45-92) (200.2+6.7 pg ml(-1)) were greater than their respective bioactive peptides. IMD levels correlated positively with BMI but not age, and were elevated in heart failure (9.8+1.3 pg ml(-1), p<0.05), similarly to MRproAM(45-92) (329.5+41.9 pg ml(-1), p<0.001) and AM (56.8+10.9 pg ml(-1), p<0.01). IMD levels were greater in heart failure patients with concomitant renal impairment (11.3+1.8 pg ml(-1)) than those without (6.5+1.0 pg ml(-1); p<0.05). IMD and AM were greater in patients receiving submaximal compared with maximal heart failure drug therapy and were decreased after 6 months of cardiac resynchronization therapy. In conclusion, IMD is present in the plasma of healthy subjects less abundantly than AM, but is similarly correlated weakly with BMI. IMD levels are elevated in heart failure, especially with concomitant renal impairment, and tend to be reduced by high intensity drug or pacing therapy.
authors.affiliation: School of Medicine, Dentistry and Biomedical Sciences, The Queen's University of Belfast, Northern Ireland, UK. Electronic address: d.bell@qub.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Bell
authors.affiliation: Peterborough City Hospital, Peterborough, England, UK.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Gordon
authors.affiliation: Hillingdon Hospitals NHS Trust, London, England, UK.
authors.forename: Anita
authors.initials: A
authors.lastname: Lavery
authors.affiliation: Southeastern Health and Social Care Trust, Northern Ireland, UK.
authors.forename: Katie
authors.initials: K
authors.lastname: Megaw
authors.affiliation: Belfast Health and Social Care Trust, Belfast City Hospital, Northern Ireland, UK.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Kinney
authors.affiliation: School of Medicine, Dentistry and Biomedical Sciences, The Queen's University of Belfast, Northern Ireland, UK; Belfast Health and Social Care Trust, Belfast City Hospital, Northern Ireland, UK.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Harbinson
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D058406:Cardiac Resynchronization Therapy; D016022:Case-Control Studies; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D036361:Peptide Hormones / Q000097:blood*; D055815:Young Adult
chemical_list: C484330:ADM2 protein, human; D015415:Biomarkers; D036361:Peptide Hormones
keywords: Adrenomedullin; Cardiac resynchronization therapy; Healthy subjects; Heart failure; Human; Intermedin/adrenomedullin-2; Plasma levels; Renal function