Elsevier

Journal of Cardiac Failure

Volume 14, Issue 9, November 2008, Pages 739-745
Journal of Cardiac Failure

Clinical Investigation
C-Terminal Provasopressin (Copeptin) is Associated With Left Ventricular Dysfunction, Remodeling, and Clinical Heart Failure in Survivors of Myocardial Infarction

https://doi.org/10.1016/j.cardfail.2008.07.231Get rights and content

Abstract

Background

Acute myocardial infarction (AMI) is associated with left ventricular (LV) dysfunction and clinical heart failure. Arginine vasopressin is elevated in heart failure and the C-terminal of provasopressin (Copeptin) is associated with adverse outcome post-AMI. The aim of this study was to describe the association between Copeptin with LV dysfunction, volumes, and remodeling and clinical heart failure post-AMI.

Methods and Results

We studied 274 subjects with AMI. Copeptin was measured from plasma at discharge and subjects underwent echocardiography at discharge and follow-up (median 155 days). Subjects were followed for clinical heart failure for a median of 381 days. Remodeling was assessed as the change (Δ) in LV volumes between echo examinations. Copeptin correlated directly with wall motion index score (WMIS) and inversely with LV ejection fraction (LVEF) at discharge (WMIS, r = 0.276, P < .001; LVEF, r = −0.188, P = .03) and follow-up (WMIS, r = 0.244, P < .001; LVEF, r = −0.270, P < .001) and with ventricular volumes at follow-up (LVEDV, r = 0.215, P = .002; LVESV, r = 0.299, P < .001). Copeptin was associated with ventricular remodeling; ΔEDV; r = 0.171, P = 0.015, ΔESV; r = 0.186, P = .008. Subjects with increasing LVESV had higher levels of Copeptin (median 6.30 vs. 5.75 pmol/L, P = .012). Subjects with clinical heart failure (n = 30) during follow-up had higher Copeptin before discharge (median 13.55 vs. 5.80, P < .001). In a Cox proportional hazards model, Copeptin retained association with clinical heart failure. Kaplan-Meier assessment revealed increased risk in subjects with Copeptin >6.31 pmol/L.

Conclusions

Copeptin is associated with LV dysfunction, volumes, and remodeling and clinical heart failure post-AMI. Measurement of Copeptin may provide prognostic information and the AVP system may be a therapeutic target in post-MI LV dysfunction.

Section snippets

Methods

We studied 274 consecutive AMI patients admitted to the coronary care unit of Leicester Royal Infirmary. The study complied with the declaration of Helsinki and was approved by the local ethics committee; written consent was obtained from all patients before inclusion. Diagnosis was based on symptoms consistent with AMI in conjunction with appropriate, dynamic electrocardiogram changes (ST segment elevation MI [STEMI], n = 230) or ST segment/T wave changes, non–ST-elevation myocardial infarction

Patient Demographic

Patient demographics for our study population are shown in Table 1. Approximately 75% of the population were male, ST-elevation was evident on the admission electrocardiogram in more than 84%, and median creatine kinase was >900 IU. Of the 230 patients presenting with STEMI, 149 (65%) received thrombolytic therapy. No patient received primary percutaneous revascularization, which was unavailable in our unit at the time. Adequate echocardiographic assessment was available in 248 (91%) subjects

Discussion

The present study has several important findings. First, association is seen between Copeptin and LV dysfunction in the very early stages post-AMI. Second, in those subjects who survive the acute event, this relationship is maintained, and hence Copeptin predicts LV dysfunction at follow-up. In addition, Copeptin is associated with the degree of LV remodeling after the acute event and is associated with clinical heart failure events.

One of the most prognostically significant consequences of AMI

Conclusions

The present study demonstrates the association between Copeptin and LV dysfunction in the post-AMI period, Moreover our study shows that Copeptin predicts LV dysfunction and clinical heart failure distant from the infarct period in survivors of the acute event. This study is the first to demonstrate an association between Copeptin and the degree of LV remodeling post-AMI. Pharmacologic manipulation of the AVP system may be a potential therapeutic target in the post-AMI period, and we suggest

References (30)

  • R.M. Califf et al.

    One-year results from the Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) trial. GUSTO-I Investigators

    Circulation

    (1996)
  • A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial infarction. The Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO IIb) Angioplasty Substudy Investigators

    N Engl J Med

    (1997)
  • R. Zahn et al.

    The volume of primary angioplasty procedures and survival after acute myocardial infarction

    N Engl J Med

    (2000)
  • S. Yusuf et al.

    Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation

    N Engl J Med

    (2001)
  • M.S. Sabatine et al.

    Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation

    N Engl J Med

    (2005)
  • Cited by (107)

    • Novel Biomarkers of Heart Failure

      2017, Advances in Clinical Chemistry
      Citation Excerpt :

      Its superiority in comparison to BNP and NT-proBNP was further confirmed in a study which showed association of copeptin with severity of HF, as well as proved copeptin as a potent independent predictor of mortality [190]. Copeptin was also associated to LVEF, remodeling, and clinical HF in survivor of MI [201]. In patients with acute HF, elevated copeptin indicated increased 90-day mortality [126], while its excellent predictive value was also found in patients with chronic, stable coronary disease [186,202].

    View all citing articles on Scopus

    D. Kelly was supported by a BHF project grant; S.Q. Khan was supported by British Heart Foundation Junior Fellowship.

    This study was supported by research grants from the Brandenburg Ministry of Economics, Germany and the European Regional Development Fund (EFRE/ERDF). Drs. Struck and Morgenthaler are employees of BRAHMS, which holds patent rights on and manufactures the Copeptin assay.

    View full text