title: Circulating tissue inhibitor of matrix metalloproteinase-1 is associated with aldosterone-induced diastolic dysfunction.
abstract: OBJECTIVE
  To test if collagen markers are associated with aldosterone-induced diastolic dysfunction.
  
  
  BACKGROUND
  Although primary aldosteronism is associated with more prominent cardiac remodeling and diastolic dysfunction, the reversibility of diastolic function is unclear. In addition, there is no known biomarker associated with aldosterone-induced diastolic dysfunction.
  
  
  METHODS
  We enrolled 27 patients with aldosterone-producing adenoma (APA) preparing for adrenalectomy, and 27 patients with essential hypertension prospectively from October 2006 to March 2010 at a tertiary referral center. Plasma matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were measured, and echocardiography including tissue Doppler images was performed in both groups and 1 year after receiving adrenalectomy in the APA group.
  
  
  RESULTS
  The baseline plasma TIMP-1 level (88.4 ± 38.7 vs. 63.6 ± 32.5 ng/ml; P = 0.014), left ventricular mass index (LVMI), and E/E' ratio (11.5 ± 2.9 vs. 9.0 ± 2.1; P < 0.001) were significantly higher in the APA group. The baseline plasma TIMP-1 level significantly correlated with the E/E' ratio, LVMI, interventricular septum, and left atrial diameter. The plasma MMP-2 level did not correlate with the left ventricular structure parameters, except for interventricular septum thickness. After adrenalectomy, LVMI and E/E' ratio improved significantly. The postadrenalectomy plasma TIMP-1 levels, but not MMP-2 levels, also decreased. The change of plasma TIMP-1 levels was negatively associated with the postadrenalectomy E/E' ratio after adjustment for age, sex, BMI, and mean blood pressure (β-coefficient = - 3.6, P = 0.004).
  
  
  CONCLUSIONS
  Excess of aldosterone induces cardiac diastolic dysfunction, which is reversible by adrenalectomy. TIMP-1 is associated with the aldosterone-induced diastolic dysfunction.
authors.affiliation: aGraduate Institute of Clinical Medicine, College of Medicine, National Taiwan University bDepartment of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine cDepartment of Obstetrics and Gynecology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei dDepartment of Internal Medicine, Taoyuan General Hospital, Taoyuan eDivision of Cardiovascular Medical Center, Far Eastern Memorial Hospital, New Taipei City fDepartment of Internal Medicine, Postal Hospital, Taipei gDepartment of Urology, Buddhist Tzu Chi General Hospital, New Taipei City hInstitute of Pharmacology, National Taiwan University Medical College, Taipei, Taiwan.
authors.forename: Chi-Sheng
authors.initials: CS
authors.lastname: Hung
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Chou
authors.forename: Xue-Ming
authors.initials: XM
authors.lastname: Wu
authors.forename: Yi-Yao
authors.initials: YY
authors.lastname: Chang
authors.forename: Vin-Cent
authors.initials: VC
authors.lastname: Wu
authors.forename: Ying-Hsien
authors.initials: YH
authors.lastname: Chen
authors.forename: Yuan-Shian
authors.initials: YS
authors.lastname: Chang
authors.forename: Yao-Chou
authors.initials: YC
authors.lastname: Tsai
authors.forename: Ming-Jai
authors.initials: MJ
authors.lastname: Su
authors.forename: Yi-Lwun
authors.initials: YL
authors.lastname: Ho
authors.forename: Ming-Fong
authors.initials: MF
authors.lastname: Chen
authors.forename: Kwan-Dun
authors.initials: KD
authors.lastname: Wu
authors.forename: Yen-Hung
authors.initials: YH
authors.lastname: Lin
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000097:blood* / Q000150:complications / Q000601:surgery; D000315:Adrenalectomy; D018246:Adrenocortical Adenoma / Q000097:blood* / Q000150:complications / Q000601:surgery; D000328:Adult; D000450:Aldosterone / Q000097:blood; D003971:Diastole; D015150:Echocardiography, Doppler; D000075222:Essential Hypertension; D005260:Female; D006352:Heart Ventricles / Q000000981:diagnostic imaging*; D006801:Humans; D006929:Hyperaldosteronism / Q000097:blood* / Q000209:etiology / Q000601:surgery; D006973:Hypertension / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D008875:Middle Aged; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D000450:Aldosterone; D020778:Matrix Metalloproteinase 2