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

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 aldosteroneproducing 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.