Diastolic dysfunction of aging is independent of myocardial structure but associated with plasma advanced glycation end-product levels

PLoS One. 2012;7(11):e49813. doi: 10.1371/journal.pone.0049813. Epub 2012 Nov 26.

Abstract

Background: Heart failure is associated with abnormalities of myocardial structure, and plasma levels of the advanced glycation end-product (AGE) N(ε)-(carboxymethyl)lysine (CML) correlate with the severity and prognosis of heart failure. Aging is associated with diastolic dysfunction and increased risk of heart failure, and we investigated the hypothesis that diastolic dysfunction of aging humans is associated with altered myocardial structure and plasma AGE levels.

Methods: We performed histological analysis of non-ischemic left ventricular myocardial biopsies and measured plasma levels of the AGEs CML and low molecular weight fluorophores (LMWFs) in 26 men undergoing coronary artery bypass graft surgery who had transthoracic echocardiography before surgery. None had previous cardiac surgery, myocardial infarction, atrial fibrillation, or heart failure.

Results: The patients were aged 43-78 years and increasing age was associated with echocardiographic indices of diastolic dysfunction, with higher mitral Doppler flow velocity A wave (r = 0.50, P = 0.02), lower mitral E/A wave ratio (r = 0.64, P = 0.001), longer mitral valve deceleration time (r = 0.42, P = 0.03) and lower early diastolic peak velocity of the mitral septal annulus, e' (r = 0.55, P = 0.008). However, neither mitral E/A ratio nor mitral septal e' was correlated with myocardial total, interstitial or perivascular fibrosis (picrosirius red), immunostaining for collagens I and III, CML, and receptor for AGEs (RAGE), cardiomyocyte width, capillary length density, diffusion radius or arteriolar dimensions. Plasma AGE levels were not associated with age. However, plasma CML levels were associated with E/A ratio (r = 0.44, P = 0.04) and e' (r = 0.51, P = 0.02) and LMWF levels were associated with E/A ratio (r = 0.49, P = 0.02). Moreover, the mitral E/A ratio remained correlated with plasma LMWF levels in all patients (P = 0.04) and the mitral septal e' remained correlated with plasma CML levels in non-diabetic patients (P = 0.007) when age was a covariate.

Conclusions: Diastolic dysfunction of aging was independent of myocardial structure but was associated with plasma AGE levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aging*
  • Blood Chemical Analysis
  • Collagen / metabolism
  • Coronary Artery Disease / complications
  • Diastole
  • Echocardiography
  • Glycation End Products, Advanced / blood*
  • Hemodynamics
  • Humans
  • Lysine / analogs & derivatives
  • Lysine / blood
  • Lysine / metabolism
  • Male
  • Middle Aged
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / blood
  • Receptors, Immunologic / metabolism
  • Ventricular Dysfunction, Left / blood*
  • Ventricular Dysfunction, Left / etiology
  • Ventricular Dysfunction, Left / pathology*

Substances

  • Glycation End Products, Advanced
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • N(6)-carboxymethyllysine
  • Collagen
  • Lysine

Grant support

This work was funded by grants from the National Health and Medical Research Council of Australia and from the National Heart Foundation of Australia. D.J.C. (Grant ID 395508) and D.J.K. (Grant ID 566867) are recipients of Senior Research Fellowships from the National Health and Medical Research Council of Australia. St Vincent’s Institute of Medical Research is supported in part by the Victorian Government’s Operational Infrastructure Support Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.