title: Diastolic function parameters are improved by the addition of simvastatin to enalapril-based treatment in hypertensive individuals.
abstract: OBJECTIVE
  Diastolic dysfunction (DD) is a frequent condition in hypertensive patients whose presence increases mortality and whose treatment remains unclear. The aim of this study was to investigate in a prospective, double-blinded, placebo-controlled randomized design the additive effect of simvastatin on DD in enalapril-treated hypertensive patients with average cholesterol levels.
  
  
  METHODS
  Hypertensive patients with DD and LDL-cholesterol <160 mg/dL underwent a run-in phase to achieve a systolic blood pressure (SBP) <135 mmHg and diastolic blood pressure (DBP) <85 mmHg with enalapril. Hydrochlorothiazide was added when need to achieve blood pressure control. Four weeks after reaching the optimum anti-hypertensive regimen patients were randomized to receive 80 mg simvastatin (n=27) or placebo (n=28) for a period of 20 weeks. Echocardiograms were performed before and after treatment with measurement of maximum left atrial volume (LAV), conventional and tissue Doppler velocities in early diastole (E, e') and late diastole (A, a').
  
  
  RESULTS
  After 20 weeks, the simvastatin group presented reduction in SBP (-4±2 mmHg, p=0.02), increase in E/A ratio (1.0±0.05 to 1.2±0.06, p=0.03) and decrease of LAV indexed to body surface area (24.5±0.9 to 21.1±0.8 ml/m(2), p=0.048), as compared with placebo arm. No change in systolic function and no correlation between the E/A ratio, LAV and changes in blood pressure or lipid profile were observed.
  
  
  CONCLUSIONS
  The addition of simvastatin to enalapril in hypertensive patients with average cholesterol levels improves parameters of diastolic function independently of changes in blood pressure or cholesterol.
authors.affiliation: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Adenalva L S
authors.initials: AL
authors.lastname: Beck
authors.forename: Maria E B
authors.initials: ME
authors.lastname: Otto
authors.forename: Luciana B O
authors.initials: LB
authors.lastname: D'Avila
authors.forename: Fernando M
authors.initials: FM
authors.lastname: Netto
authors.forename: Marinez K
authors.initials: MK
authors.lastname: Armendaris
authors.forename: Andrei C
authors.initials: AC
authors.lastname: Sposito
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D001938:Brazil; D016009:Chi-Square Distribution; D002784:Cholesterol / Q000097:blood; D003971:Diastole / Q000187:drug effects*; D004232:Diuretics / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015150:Echocardiography, Doppler; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012044:Regression Analysis; D019821:Simvastatin / Q000627:therapeutic use*; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D015415:Biomarkers; D004232:Diuretics; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006852:Hydrochlorothiazide; D004656:Enalapril; D002784:Cholesterol; D019821:Simvastatin