Plasma Adiponectin for Prediction of Cardiovascular Events and Mortality in High-risk Patients

Context: The prognostic value of plasma levels of adiponectin, an adipocytokine with antiatherogenic, antiinflammatory, and insulin-sensitizing effects, is contentious.

Objective: The objective of the study was to investigate whether plasma adiponectin levels predict cardiovascular (CV) events and mortality in high-risk coronary artery disease (CAD) patients. DESIGN, SETTING, PARTICIPANTS, AND MAIN OUTCOME MEASURE: We measured plasma adiponectin and examined its impact on the incidence of CV deaths and events at follow-up in the context of all potentially relevant background covariates in 712 high-risk patients of the Genetic and ENvironmental factors in Coronary Atherosclerosis study who underwent coronary angiography for suspected CAD. Based on the population plasma adiponectin median (6.38 microg/ml, interquartile range 4.2-10.2), we split the patients in a high- and a low-plasma adiponectin subgroup. After a median follow-up of 3.8 years (interquartile range 3.3-4.3 yr), outcome data were obtained in 100% of the patients and 45 CV deaths (6.4%) were recorded. Kaplan-Meier analysis unexpectedly showed a higher CV death rate in high-plasma adiponectin than low-plasma adiponectin patients. By contrast, multivariate Cox regression analysis, in which potential confounders, including ongoing medical treatment, were considered, showed no impact of plasma adiponectin on CV death. Similar negative results were obtained using the propensity score that considered all relevant covariables and medical treatment rate, which differed between the high- and low-plasma adiponectin group.

Conclusions: In high-risk CAD patients, plasma adiponectin above the median (6.38 microg/ml) implies a paradoxical higher risk of CV death. However, when relevant covariates that differ between high- and low-plasma adiponectin groups are considered, this association wanes, indicating that the clustering of plasma adiponectin with other covariates can abolish its impact on CV prognosis.