title: Can emerging biomarkers of myocardial remodelling identify asymptomatic hypertensive patients at risk for diastolic dysfunction and diastolic heart failure?
abstract: OBJECTIVE
  Hypertension is one of the main drivers of the heart failure (HF) epidemic. The aims of this study were to profile fibro-inflammatory biomarkers across stages of the hypertensive heart disease (HHD) spectrum and to examine whether particular biochemical profiles in asymptomatic patients identify a higher risk of evolution to HF.
  
  
  RESULTS
  This was a cross-sectional observational study involving a population of 275 stable hypertensive patients divided into two different cohorts: Group 1, asymptomatic hypertension (AH) (n= 94); Group 2, HF with preserved ejection fraction  (n= 181). Asymptomatic hypertension patients were further subdivided according to left atrial volume index ≥34 mL/m(2) (n= 30) and <34 mL/m(2) (n= 64). Study assays involved inflammatory markers [interleukin 6 (IL6), interleukin 8 (IL8), monocyte chemoattractant protein 1 (MCP1), and tumour necrosis factor α], collagen 1 and 3 metabolic markers [carboxy-terminal propeptide of collagen 1, amino-terminal propeptide of collagen 1, amino-terminal propeptide of collagen 3 (PIIINP), and carboxy-terminal telopeptide of collagen 1 (CITP)], extra-cellular matrix turnover markers [matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), and tissue inhibitor of metalloproteinase 1 (TIMP1)], and the brain natriuretic peptide. Data were adjusted for age, sex, systolic blood pressure, and creatinine. Heart failure with preserved ejection fraction  was associated with an increased inflammatory signal (IL6, IL8, and MCP1), an increased fibrotic signal (PIIINP and CITP), and an increased matrix turnover signal (MMP2 and MMP9). Alterations in MMP and TIMP enzymes were found to be significant indicators of greater degrees of asymptomatic left ventricular diastolic dysfunction.
  
  
  CONCLUSIONS
  These data define varying fibro-inflammatory profiles throughout different stages of HHD. In particular, the observations on MMP9 and TIMP1 raise the possibility of earlier detection of those at risk of evolution to HF which may help focus effective preventative strategies.
authors: UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors: Patrick
authors: P
authors: Collier
authors: Chris J
authors: CJ
authors: Watson
authors: Victor
authors: V
authors: Voon
authors: Dermot
authors: D
authors: Phelan
authors: Aftab
authors: A
authors: Jan
authors: George
authors: G
authors: Mak
authors: Ramon
authors: R
authors: Martos
authors: John A
authors: JA
authors: Baugh
authors: Mark T
authors: MT
authors: Ledwidge
authors: Kenneth M
authors: KM
authors: McDonald
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood; D003430:Cross-Sectional Studies; D003971:Diastole; D015150:Echocardiography, Doppler; D005260:Female; D006325:Heart Atria; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology; D006801:Humans; D006973:Hypertension; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers; D018932:Chemokine CCL2; D015850:Interleukin-6; D016209:Interleukin-8; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9