European Heart Journal Advance Access published online on June 9, 2008
European Heart Journal, doi:10.1093/eurheartj/ehn245
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Association of adiponectin with adverse outcome in coronary artery disease patients: results from the Atherogene study
Institute of Cardiology
Catholic University of the Sacred Heart
Largo Agostino Gemelli, 8
00168, Rome
Italy
Tel: +39 06 30154187
Fax: +39 06 3055535
Email: giu.ferrante{at}hotmail.it
Cardiovascular Department
Royal Brompton Hospital
London
UK
Institute of Cardiology
Catholic University of the Sacred Heart
Rome
Italy
Cardiovascular Department
Royal Brompton Hosptial
London
UK
Institute of Cardiology
Catholic University of the Sacred Heart
Rome
Italy
We read with interest the article by Schnabel et al.1 in which the authors assessed the prognostic value of baseline levels of adiponectin in patients with manifest coronary artery disease (CAD). They conclude that adiponectin concentration is predictive of cardiovascular death or non-fatal myocardial infarction (MI) at a median follow-up of 2.5 years.
Several considerations are worth noting before accepting these conclusions.
First, the overall study population is markedly heterogeneous due to the inclusion of patients with stable angina (SA) and various sub-sets of patients with acute coronary syndromes (ACS) (e.g. ST-elevation and non-ST elevation MI). While baseline adiponectin levels were almost comparable in both SA and ACS patients, the levels of B-type natriuretic peptide (BNP) and of C-reactive protein (CRP) were more than two-fold higher in patients with ACS than in SA. Both BNP and CRP are known to be associated with adverse outcome in ACS patients2,3 with BNP also having a prognostic role in patients with SA.4,5 The BNP levels in the present study were only 38 pg/mL (11.94–99.81) in patients with SA, a range comparable with 36.1 pg/mL (11.3–94.6), a value found in patients with SA who did not have cardiovascular events in a previous study4 and overlapping with the values of the first and partially the second lower quartiles of BNP, which were not associated with increased risk of cardiovascular events.5 Secondly, despite continuous levels of adiponectin predicting cardiovascular events in the overall population after adjusting for the presence of ACS (model 2 regression), adiponectin was not significantly associated with the outcome (models 1–4) in patients with ACS, while only in patients with SA predicted the outcome.
Thirdly, the authors did not report the cardiovascular event rate according to SA and ACS, but it is likely that the patients with SA in this study (who had low BNP values) had a better prognosis compared with patients with ACS.
Taken together, these finding raise the strong possibility that an association between adiponectin and prognosis in patients with ACS might not exist, and that the main result of this study may have been driven by the patients with SA. As patients with ACS represent a large part of patients with CAD in clinical practice, the conclusion, therefore, that adiponectin predicts outcome in patients with CAD may be not accurate.
Moreover, the independent predictive value of adiponectin in SA patients might be a spurious finding, as patients with SA and high levels of BNP (>100 pg/mL) were not included in this study. Furthermore, even in the present cohort of SA patients, a hazard ratio = 1.035 may not represent a clinically significant increase in adverse events if the baseline absolute risk of events is low anyway.
Finally, continuous levels of adiponectin did not independently predict the outcome in the overall population and the independent predictive value of a one-quartile adiponectin level increase has not been verified after entering BNP, CRP, and creatinine as covariates in the Cox proportional hazard regression model.
References
- Schnabel R, Messow CM, Lubos E, Espinola-Klein C, Rupprecht HJ, Bickel C, Sinning C, Tzikas S, Keller T, Genth-Zotz S, Lackner KJ, Münzel TF, Blankenberg S. Association of adiponectin with adverse outcome in coronary artery disease patients: results from the AtheroGene study. Eur Heart J (2008) 29:649–657.
[Abstract/Free Full Text] - De Lemos JA, Morrow DA, Bentley JH, Omland T, Sabatine MS, McCabe CH, Hall C, Cannon CP, Braunwald E. The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. N Engl J Med (2001) 345:1014–1021.
[Abstract/Free Full Text] - Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi AG, Pepys MB, Maseri A. The prognostic value of C-reactive protein and serum amyloid A protein in severe unstable angina. N Engl J Med (1994) 331:417–424.
[Abstract/Free Full Text] - Schnabel R, Lubos E, Rupprecht HJ, Espinola-Klein C, Bickel C, Lackner KJ, Cambien F, Tiret L, Münzel T, Blankenberg S. B-type natriuretic peptide and the risk of cardiovascular events and death in patients with stable angina: results from the AtheroGene study. J Am Coll Cardiol (2006) 47:552–558.
[Abstract/Free Full Text] - Kragelund C, Grønning B, Køber L, Hildebrandt P, Steffensen R. N-terminal pro-B-type natriuretic peptide and long-term mortality in stable coronary heart disease. N Engl J Med (2005) 352:666–675.
[Abstract/Free Full Text]
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