Prognostic Value of Tissue Inhibitor of Metalloproteinase in Acute Aortic Dissection

ABSTRACT

Background:

Increases in levels of matrix metalloproteinase (MMP) and tissue inhibitor of matrix metalloproteinase (TIMP) occur in acute aortic dissection (AAD); however, their association with prognosis in AAD remains largely unknown. We studied the use of MMP and TIMP in predicting long-term outcomes in medically controlled AAD patients.

Methods:

A total of 82 patients were enrolled (15 Stanford Type A and 67 type B, age 65.1±13.3). AAD was diagnosed by enhanced CT, with serial imaging studies during follow-up. Blood tests for MMP-2, MMP-9, TIMP-1, and TIMP-2 were performed within a week after symptom onset.

Results:

A poor outcome due to death or aortic surgical repair occurred in 17 patients, classified as an unfavorable group. The remaining 65 patients were classified into a favorable group. By multivariate analysis maximum dissection diameter (MDD), TIMP-1, and TIMP-2 were significantly associated with an unfavorable outcome (P < 0.001, P < 0.001, and P = 0.038, respectively). The ratio of TIMP-1 to TIMP-2 (cut-off value > 3.34) had significant predictive power (sensitivity 88.2%, specificity 80.0%). Patients with MDD ≥ 46.8 mm and a TIMP-1/TIMP-2 ratio ≥ 3.34 had a significantly poorer outcome (log rank P < 0.0001). Similarly, in Cox regression analysis AAD patients with MDD ≥46.8 mm and a TIMP- 1/TIMP-2 ratio ≥ 3.34 had the highest risk for an unfavorable outcome (P < 0.001, hazard ratio 45.6, 95% confidence interval 5.96 to 348.42).

Conclusion:

In AAD a higher TIMP-1/TIMP-2 ratio was significantly associated with an increased risk of death or surgical repair.

Keywords:

Aortic dissection, risk factors, follow-up studies, matrix metalloproteinase, tissue inhibitor of matrix metalloproteinase.