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Reduced High-Molecular-Weight Adiponectin and Elevated High-Sensitivity C-Reactive Protein Are Synergistic Risk Factors for Metabolic Syndrome in a Large-Scale Middle-Aged to Elderly Population: the Shimanami Health Promoting Program Study

Departments of Basic Medical Research and Education (Y.T.), Molecular and Genetic Medicine (H.O., H.M.), and Geriatric Medicine (R.T.-I., M.Y., J.N., T.M., K.K.), Ehime University Graduate School of Medicine, Ehime 791-0295, Japan; and Department of Internal Medicine (R.K.), Seiyo-city Nomura Hospital, Ehime 797-1212, Japan

Address all correspondence and requests for reprints to: Yasuharu Tabara, Ph.D., Department of Basic Medical Research and Education, Ehime University Graduate School of Medicines, Toon, Ehime 791-0295, Japan. E-mail: tabara{at}m.ehime-u.ac.jp.

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 that inversely associates with metabolic syndrome. Among several molecular isoforms, high-molecular-weight (HMW) complex is considered the active form. Increased serum high-sensitivity C-reactive protein (hsCRP) concentration also associates with metabolic syndrome, and adiponectin could modulate plasma C-reactive protein 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 one of the novelties of this study.

Design: We analyzed 1845 community-dwelling middle-aged to elderly subjects (62 ± 13 yr). Plasma HMW adiponectin levels were measured by ELISA. 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% confidence interval 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.