title: Biomarkers of cardiomyocyte injury and stress identify left atrial and left ventricular remodelling and dysfunction: A population-based study.
abstract: OBJECTIVE
  The validation of effective screening tools for the identification of patients with subclinical myocardial remodelling is a major clinical need. Thus, we explored the associations of circulating biomarkers of cardiomyocyte injury and stress with subclinical cardiac remodelling and dysfunction, and with biomarkers reflecting collagen turnover.
  
  
  METHODS
  We randomly recruited 727 subjects from a general population (51.2% women; mean age 51.3 years). Measurements included echocardiographic left atrial (LA) and left ventricular (LV) structure and function, quantification of high sensitivity cardiac Troponin T (hs-cTnT), NT-proBNP, and biomarkers of collagen types I and III turnover.
  
  
  RESULTS
  In unadjusted and adjusted analyses, the prevalence of LA enlargement (LAE), LV hypertrophy (LVH) and LV diastolic dysfunction (LVDD) increased with higher hs-cTnT (P ≤ 0.031). NT-proBNP was independently associated with LVDD (P=0.009). Both biomarkers combined yielded significant integrated discrimination and net reclassification improvements (P ≤ 0.014 and P ≤ 0.009, respectively) for LAE, LVH and LVDD, over the conventional risk factors, and were independently and positively associated with biomarkers of collagen type I turnover. In a sensitivity analysis, after excluding participants with previous cardiac diseases, our findings remained consistent.
  
  
  CONCLUSIONS
  Our population-based study suggested that subclinical LV and LA remodelling were associated with hs-cTnT, and that, in combination with NT-proBNP, hs-cTnT showed incremental diagnostic utility over the conventional risk factors. Both biomarkers were associated with biomarkers of collagen type I turnover. Thus, biomarkers of cardiomyocyte microinjury and hemodynamic stress may stimulate fibrosis-related mechanisms and facilitate the diagnosis of subclinical LA and LV remodelling and dysfunction in the general population.
authors: Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, IdiSNA-Navarra Institute for Health Research, Pamplona, Spain.
authors: Susana
authors: S
authors: Ravassa
authors: The Studies Coordinating Centre, Research Unit of Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium.
authors: Tatiana
authors: T
authors: Kuznetsova
authors: Department of Biochemistry, University of Navarra Clinic, University of Navarra, IdiSNA-Navarra Institute for Health Research, Pamplona Spain.
authors: Nerea
authors: N
authors: Varo
authors: The Studies Coordinating Centre, Research Unit of Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium.
authors: Lutgarde
authors: L
authors: Thijs
authors: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Scotland, UK.
authors: Christian
authors: C
authors: Delles
authors: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Scotland, UK.
authors: Anna
authors: A
authors: Dominiczak
authors: Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, IdiSNA-Navarra Institute for Health Research, Pamplona, Spain; Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, University of Navarra, IdiSNA-Navarra Institute for Health Research, Pamplona, Spain. Electronic address: jadimar@unav.es.
authors: Javier
authors: J
authors: Díez
authors: The Studies Coordinating Centre, Research Unit of Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium; Department of Epidemiology, University of Maastricht, Maastricht, The Netherlands. Electronic address: jan.staessen@med.kuleuven.be.
authors: Jan A
authors: JA
authors: Staessen
mesh_terms: D000328:Adult; D064752:Atrial Remodeling / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism*; D004452:Echocardiography; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D011159:Population Surveillance; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors; D018487:Ventricular Dysfunction, Left / Q000453:epidemiology / Q000378:metabolism* / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000502:physiology*; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D015415:Biomarkers
keywords: Collagen metabolism; Diastolic dysfunction; Left atrial remodelling; Left ventricular remodelling; NT-proBNP; hs-cTnT