title: Effects of ACE inhibition versus non-ACE inhibitor antihypertensive treatment on myocardial fibrosis in patients with arterial hypertension. Retrospective analysis of 120 patients with left ventricular endomyocardial biopsies.
abstract: OBJECTIVE
  In experimental arterial hypertension, left ventricular hypertrophy (LVH) becomes pathologic with impaired myocardial function if myocardial fibrosis occurs. Myocardial fibrosis is associated with activated circulating or local renin-angiotensin-aldosterone systems. The primary objective of this retrospective study was to determine whether patients with arterial hypertension treated with angiotensin-converting enzyme inhibitors (ACEI) have less myocardial fibrosis than patients on non-ACEI treatment.
  
  
  METHODS
  We examined left ventricular (LV) endomyocardial biopsies of 97 consecutive patients with hypertensive heart disease due to primary hypertension treated with either any ACEI for at least 6 months (n = 34; HTN + ACEI) or non-ACEI antihypertensive drugs (n = 63; HTN). Normal hearts designated for heart transplantation served as controls (n = 23; CTR). Myocyte diameter (MyoD) and collagen volume fraction (CVF) were measured by morphometry, and pro-matrix metalloproteinases (proMMPs) 2 and 9 by zymography. In a subset of 35 patients, LV myocardial stiffness was determined by left heart catheterization with calculation of stiffness constant k.
  
  
  RESULTS
  In HTN + ACEI or HTN, MyoD (21.8 +/- 0.3 micro m and 22.4 +/- 0.3 micro m, respectively) and CVF (5.3 +/- 0.6% and 7.6 +/- 0.7%, respectively) were increased (p < 0.01) compared with CTR (16.0 +/- 0.4 micro m and 0.5 +/- 0.2%, respectively). In HTN + ACEI, CVF was significantly lower (p < 0.02) and proMMP 2 was higher (0.063 +/- 0.013 OD/mg) compared with HTN (0.037 +/- 0.006 OD/mg; p < 0.05) while no significant difference of MyoD was evident. We found no correlation between CVF and MyoD (r = 0.13; p = 0.47), a positive correlation between k and CVF (r = 0.71; p < 0.00001), and no correlation between k and MyoD (r = 0.22; p = 0.24).
  
  
  CONCLUSIONS
  In patients with hypertensive heart disease, myocyte hypertrophy and myocardial fibrosis are present. Myocardial fibrosis and not myocyte hypertrophy determines myocardial stiffness. ACEI appear to diminish myocardial fibrosis associated with enhanced collagen degradation irrespective of LVH regression.
authors.affiliation: Division of Cardiology, Center of Internal Medicine, Philipps University of Marburg, Germany. brilla@t-online.de
authors.forename: Christian G
authors.initials: CG
authors.lastname: Brilla
authors.forename: Heinz
authors.initials: H
authors.lastname: Rupp
authors.forename: Bernhard
authors.initials: B
authors.lastname: Maisch
mesh_terms: D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001706:Biopsy; D048429:Cell Size / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D004699:Endocardium / Q000473:pathology; D004719:Endomyocardial Fibrosis / Q000473:pathology / Q000517:prevention & control*; D004792:Enzyme Precursors / Q000378:metabolism; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000473:pathology / Q000517:prevention & control; D008297:Male; D020781:Matrix Metalloproteinase 1; D020780:Matrix Metalloproteinase 9; D008875:Middle Aged; D032342:Muscle Cells / Q000473:pathology; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000473:pathology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004792:Enzyme Precursors; D003094:Collagen; D007703:Peptidyl-Dipeptidase A; D017364:Collagenases; C120487:pro-matrix metalloproteinase 9; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1