Objective: In western countries, one of the most important modifiable targets for the prevention of cardiovascular diseases is metabolic syndrome. Adiponectin is an adipose tissue-specific plasma protein which inversely associates with metabolic syndrome. Among several molecular isoforms, high molecular-weight (HMW) complex is considered the active form. Increased serum C-reactive protein (hsCRP) concentration also associate with metabolic syndrome, and adiponectin could modulate plasma CRP levels. Here, through cross-sectional investigation, we investigated whether reduced HMW adiponectin and increased hsCRP levels in plasma are synergistically associated with metabolic syndrome. Measurement of HMW complex of adiponectin is on of novelties of this study.

Design: We analyzed 1,845 community-dwelling middle-aged to elderly subjects (62±13 years). Plasma HMW adiponectin levels were measured by enzyme-linked immunosorbent assay. Clinical parameters were obtained from the subjects' personal health records, evaluated at their annual medical check-up.

Results: Each component of metabolic syndrome, except for raised blood pressure, showed significantly lower plasma HMW adiponectin concentrations for both men and women (p<0.001). In contrast, plasma hsCRP levels were significantly higher in subjects with metabolic disorders (p<0.001). After adjusting for other confounding factors, HMW adiponectin (log normalized, odds ratio 0.084 (95% C.I. 0.050–0.142), p<0.001) and hsCRP (3.009 [2.175–4.163], p<0.001) were identified as independent determinants of metabolic syndrome. In addition to the direct associations, we also observed a synergistic effect between these two molecules (F=11.8, p<0.001).

Conclusions: Reduced HMW adiponectin and elevated hsCRP are synergistically associated with the accumulation of metabolic disorders. The combination of these markers would be useful for identifying at-risk populations.