Decrease in plasma cyclophilin A concentration at 1 month after myocardial infarction predicts better left ventricular performance and synchronicity at 6 months: a pilot study in patients with ST elevation myocardial infarction

Abstract

Background: Cyclophilin A (CyPA) concentration increases in acute coronary syndrome. In an animal model of acute myocardial infarction, administration of angiotensin-converting-enzyme inhibitor was associated with lower left ventricular (LV) CyPA concentration and improved LV performance. This study investigated the relationships between changes in plasma CyPA concentrations and LV remodeling in patients with ST-elevation myocardial infarction (STEMI).

Methods and results: We enrolled 55 patients who underwent percutaneous coronary intervention for acute STEMI. Plasma CyPA, matrix metalloproteinase (MMP), interleukin-6 and high-sensitivity C-reactive protein concentrations were measured at baseline and at one-month follow-up. Echocardiography was performed at baseline and at one-, three-, and six-month follow-up. Patients with a decrease in baseline CyPA concentration at one-month follow-up (n = 28) had a significant increase in LV ejection fraction (LVEF) (from 60.2 ± 11.5% to 64.6 ± 9.9%, p < 0. 001) and preserved LV synchrony at six months. Patients without a decrease in CyPA concentration at one month (n = 27) did not show improvement in LVEF and had a significantly increased systolic dyssynchrony index (SDI) (from 1.170 ± 0.510% to 1.637 ± 1.299%, p = 0.042) at six months. Multiple linear regression analysis showed a significant association between one-month CyPA concentration and six-month LVEF. The one-month MMP-2 concentration was positively correlated with one-month CyPA concentration and LV SDI. Conclusions : Decreased CyPA concentration at one-month follow-up after STEMI was associated with better LVEF and SDI at six months. Changes in CyPA, therefore, may be a prognosticator of patient outcome.

Keywords: Acute myocardial infarction; Cyclophilin A; Left ventricular dyssynchrony; Left ventricular ejection fraction; Matrix metalloproteinase..

Figure 1

Changes in plasma CyPA concentration in patients with a decrease and without a decrease in plasma CyPA levels between baseline and 1 month. Group A comprised patients with a decrease in plasma CyPA concentration at 1 month. Group B comprised patients without a decrease in plasma CyPA concentration at 1 month. A1 vs. A4, (p < 0.001). B1 vs. B4 (p < 0.001) (paired-samples t-test). A4 vs. B4 (p = 0.021, Student's t-test).

Figure 2

Relationship between quartiles of 1-month cyclophilin A (CyPA) concentration and 1-month matrix metalloproteinase-2 (MMP-2) concentration. Trend analysis showed that 1-month MMP-2 concentration was positively correlated with quartiles of 1-month CyPA concentration (Jonckheere-Terpstra test, p = 0.026).

Figure 3

Evaluation of plasma CyPA concentration at 1 month as a predictor of 6-month LVEF in STEMI patients after primary balloon angioplasty. The area under the curves (AUC) for plasma 1-month CyPA concentration as a predictor of 6-month LVEF was 0.734 (95% CI, 0.618-0.869, p = 0.001).

Figure 4

Evaluation of plasma MMP-2 concentration at 1 month as a predictor of 6-month SDI in STEMI patients after primary balloon angioplasty. The area under the curves (AUC) for plasma 1-month MMP-2 concentration as a predictor of 6-month SDI were 0.682 (95% CI, 0.547-0.817, p = 0.015).