European Heart Journal Advance Access originally published online on September 9, 2008
European Heart Journal 2008 29(20):2578-2579; doi:10.1093/eurheartj/ehn395
Adiponectin and prognostic outcome in patients with coronary artery disease
Department of Clinical and Experimental Medicine
Clinica Medica 4, University Hospital
University of Padova
via Giustiniani, 2
35126 Padova
Italy
Fax: +39 049 880 2252
Email: maurizio.cesari{at}unipd.it
Department of Clinical and Experimental Medicine
Clinica Medica 4, University Hospital
University of Padova
via Giustiniani, 2
35126 Padova
Italy
von Eynatten et al. prospectively evaluated the prognostic impact of total and high-molecular weight adiponectin in 1051 German patients with stable coronary heart disease (CHD) at baseline after a median follow-up of 4.7 years,1 and found no association with incidence of secondary cardiovascular (CV) events. This finding is paradoxical because adiponectin can exert anti-atherogenic, anti-inflammatory, and insulin-sensitizing effects,2 and contrast with findings in CHD patients with no or limited adjustment for potential confounders.3,4
We performed a study on 712 very similar (for age, gender, prevalence of diabetes mellitus, overweight, and history of hypertension) coronary artery disease (CAD) Italian patients, which was eventually published.5 Compared with that of von Eynatten et al., our cohort showed more CV deaths and composite CV events (comprising CV death, non-fatal myocardial infarction, acute coronary syndromes, stroke, and vascular surgery) (45 and 119, respectively) even despite a slightly shorter follow-up (median 3.8 years), thus providing a high statistical power to our study.
Noteworthy, at univariate Kaplan–Meier analysis, we found a higher CV death rate among those with a high plasma adiponectin than in those with a low plasma adiponectin, suggesting a paradoxical detrimental role of adiponectin on CV outcome. Nonetheless, a comparison of the two groups evidenced an unbalanced distribution of several covariates that can affect outcome, including major CV risk factors, rate of previous CV events, and ongoing medical treatment.
We therefore undertook a hierarchical multivariate Cox regression analysis where these potential confounders were considered. At variance with von Eynatten et al. who considered only the number of major epicardial coronary vessel affected, we could estimate the CAD burden by a modified Duke prognostic index score that furnishes an accurate estimation of the severity of the CAD extension. Moreover, at variance with von Eynatten et al. who considered only the use of angiotensin-converting enzyme-inhibitors and lipid-lowering drugs, we considered all the ongoing CV drugs.
This refined examination showed that the independent predictors of CV death were low left ventricular ejection fraction (LVEF) and calcium channel blockers treatment, while the strongest predictors of the composite CV end-point were the Duke prognostic index score followed by LVEF and age. However, no impact of plasma adiponectin on either CV death or the composite CV end-point was detected, thus confirming von Eynatten et al.'s findings.1
Moreover, we exploited the use of the propensity score,6 a novel statistical technique which allows to consider all potentially relevant co-variables, without the limitations of variables adjustment imposed to the multivariate models by the limited number of cardiovascular deaths and/or events observed. Hence, we could consider the complete ongoing treatment. This additional analysis fully confirmed the results obtained with the multivariate analysis, thus confirming that in high-risk patients when potential confounders are taken into due consideration adiponectin do not carry any additional prognostic information over conventional CV risk factors.
These two independent studies testify that, when assessing the usefulness of novel biomarkers of CV disease in high-risk patients, the overall risk profile, LVEF, CAD atherosclerotic burden, medical history, and concurrent medical treatment should be carefully considered before jumping to conclusions that might affect clinical practice.
References
- von Eynatten M, Hamann A, Twardella D, Nawroth PP, Brenner H, Rothenbacher D. Atherogenic dyslipidaemia but not total- and high-molecular weight adiponectin are associated with the prognostic outcome in patients with coronary heart disease. Eur Heart J (2008) 29:1307–1315.
[Abstract/Free Full Text] - Zhu W, Cheng KK, Vanhoutte PM, Lam KS, Xu A. Vascular effects of adiponectin: molecular mechanisms and potential therapeutic intervention. Clin Sci (Lond) (2008) 114:361–374.[Medline]
- Pilz S, Mangge H, Wellnitz B, Seelhorst U, Winkelmann BR, Tiran B, Boehm BO, Marz W. Adiponectin and mortality in patients undergoing coronary angiography. J Clin Endocrinol Metab (2006) 91:4277–4286.
[Abstract/Free Full Text] - Cavusoglu E, Ruwende C, Chopra V, Yanamadala S, Eng C, Clark LT, Pinsky DJ, Marmur JD. Adiponectin is an independent predictor of all-cause mortality, cardiac mortality, and myocardial infarction in patients presenting with chest pain. Eur Heart J (2006) 27:2300–2309.
[Abstract/Free Full Text] - Maiolino G, Cesari M, Sticchi D, Zanchetta M, Pedon L, Altezza K, Pessina A.C, Rossi GP. Plasma adiponectin for prediction of cardiovascular events and mortality in high-risk patients. J Clin Endocrinol Metab (2008) 93:3333–3340.
[Abstract/Free Full Text] - D'Agostino RB Jr. Propensity scores in cardiovascular research. Circulation (2007) 115:2340–2343.
[Free Full Text]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||