Clinical Investigation
Prognostic Value of Serum Tenascin-C Levels on Long-Term Outcome After Acute Myocardial Infarction

https://doi.org/10.1016/j.cardfail.2012.02.009Get rights and content

Abstract

Background

Tenascin-C (TN-C), an extracellular matrix glycoprotein, is not normally expressed in the adult heart but transiently reappears under various pathologic conditions to play important roles in tissue remodeling. It is unclear whether serum TN-C levels add prognostic information independent from traditional prognostic markers.

Methods and Results

We assessed 239 patients with first ST-segment elevation myocardial infarction who underwent successful percutaneous coronary intervention. We measured serum TN-C and plasma B-type natriuretic peptide (BNP) levels on day 5 after admission and compared long-term clinical outcome. During the follow-up period (24.3 ± 13 months), 54 patients experienced primary composite cardiac events (cardiac death or hospitalization for worsening heart failure). Multivariable Cox proportional hazards analysis indicated that serum TN-C (hazard ratio 2.92, 95% confidence interval [CI] 1.55–5.67; P < .001) and plasma BNP levels (hazard ratio 1.84, 95% CI 1.17–2.97; P = .008) were significant independent predictors for cardiac events after adjustment for multiple confounders. The combination of TN-C and BNP resulted in an increase of the c-statistic from 0.821 to 0.877 (P < .001) and an integrated discrimination improvement gain of 14.0% (P < .001).

Conclusions

Serum TN-C level on day 5 after admission is potentially useful for early risk stratification after AMI beyond established prognostic markers.

Section snippets

Study Population

We initially studied a prospective series of 250 patients with first AMI who underwent primary PCI at Yokosuka Kyosai Hospital from January 2005 to February 2008. Inclusion criteria for the study patients were: 1) chest pain >30 minutes in duration and presenting to hospital within 12 hours after onset of symptoms; 2) ST-segment elevation >0.1 mV in 2 contiguous electrocardiographic leads; 3) total occlusion of the infarct-related artery; 4) elevated creatine kinase–MB (CK-MB) isoenzymes within

Patient Characteristics

The 239 patients included in the study comprised 184 men and 55 women with an overall mean age of 67 ± 11 years. Baseline clinical characteristics of the patients are summarized in Table 1.

Comparison of Clinical Characteristics and LV Parameters Between MACE and Non-MACE Groups

Of the 239 patients, 54 patients (22.6%) suffered MACE during the follow-up period. MACE included 23 (9.2%) cardiac deaths and 31 (13%) episodes of heart failure. Clinical characteristics of the study patients suffering MACE and those without are shown in Table 2. There were no significant differences in sex,

Discussion

The major important findings in this are as follows. First, serum TN-C level measured in patients on day 5 after admission for AMI has a prognostic value similar to that of plasma BNP level, the predictive biomarker of prognosis after AMI. Second, the incorporation of a combination of serum TN-C and plasma BNP levels with the established prognostic markers improved risk stratification for MACE and cardiac death, as evidenced by a substantial increase in the C-statistics and IDI values.

Conclusion

Inclusion of serum TN-C level measured on day 5 after admission for AMI is potentially useful in addition to established prognostic markers for early risk stratification of patients after AMI. Identification of this and other biomarkers will lead to more aggressive follow-up and medical intervention as potential strategies to prevent MACE and cardiac deaths.

Disclosures

None.

References (32)

  • G. Orend

    Potential oncogenic action of tenascin-C in tumorigenesis

    Int J Biochem Cell Biol

    (2005)
  • S. Matsuo et al.

    Revised equations for estimated GFR from serum creatinine in Japan

    Am J Kidney Dis

    (2009)
  • M. Tamaoki et al.

    Tenascin-C regulates recruitment of myofibroblasts during tissue repair after myocardial injury

    Am J Pathol

    (2005)
  • K. Damman et al.

    Worsening renal function and prognosis in heart failure: systematic review and meta-analysis

    J Card Fail

    (2007)
  • A.S. Jaffe et al.

    Biomarkers in acute cardiac disease: the present and the future

    J Am Coll Cardiol

    (2006)
  • M.A. Pfeffer et al.

    Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications

    Circulation

    (1990)
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