Circulating tissue inhibitor of matrix metalloproteinase-1 is associated with aldosterone-induced diastolic dysfunction

J Hypertens. 2015 Sep;33(9):1922-30; discussion 1930. doi: 10.1097/HJH.0000000000000619.

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).

Conclusion: Excess of aldosterone induces cardiac diastolic dysfunction, which is reversible by adrenalectomy. TIMP-1 is associated with the aldosterone-induced diastolic dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Neoplasms / blood*
  • Adrenal Cortex Neoplasms / complications
  • Adrenal Cortex Neoplasms / surgery
  • Adrenalectomy
  • Adrenocortical Adenoma / blood*
  • Adrenocortical Adenoma / complications
  • Adrenocortical Adenoma / surgery
  • Adult
  • Aldosterone / blood
  • Diastole
  • Echocardiography, Doppler
  • Essential Hypertension
  • Female
  • Heart Ventricles / diagnostic imaging*
  • Humans
  • Hyperaldosteronism / blood*
  • Hyperaldosteronism / etiology
  • Hyperaldosteronism / surgery
  • Hypertension / blood
  • Hypertension / diagnostic imaging
  • Hypertension / pathology
  • Male
  • Matrix Metalloproteinase 2 / blood
  • Middle Aged
  • Tissue Inhibitor of Metalloproteinase-1 / blood*
  • Treatment Outcome

Substances

  • Tissue Inhibitor of Metalloproteinase-1
  • Aldosterone
  • Matrix Metalloproteinase 2