Context: the prognostic value of plasma levels of adiponectin, an adipocytokine with anti-atherogenic, anti-inflammatory and insulin-sensitizing effects, is contentious.

Objective: to investigate if plasma adiponectin levels predict cardiovascular (CV) events and mortality in high-risk 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 GENICA study who underwent coronary angiography for suspected CAD. Based on the population plasma adiponectin median (6.38 µg/mL, IQR 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 (IQR 3,3–4,3 years) outcome data were obtained in 100% of the patients and 45 (6.3%) CV deaths were recorded. Kaplan-Meier analysis unexpectedly showed a higher CV death rate in high-plasma adiponectin than in low-plasma adiponectin patients. By contrast, multivariate Cox regression analysis, where 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 co variables 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 µg/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.