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

Abstract

ABSTRACT So-called metabolic syndrome (MetS) is, in Western countries, one of the most promising modifiable targets for preventing cardiovascular disease. Elements of MetS include abdominal obesity, elevated blood pressure, hypertriglyceridemia, and impaired glucose tolerance. Numerous epidemiologic studies have found significant associations between MetS and both coronary artery disease and stroke. Adiponectin is an adipose tissue-specific plasma protein that is able to suppress atherosclerotic vascular changes. Levels of adiponectin reportedly are reduced in obese individuals and those with MetS. One of several molecular isoforms of adiponectin, high-molecular-weight (HMW) complex, is thought to be the active form. Adiponectin may influence plasma levels of C-reactive protein (CRP), a marker of inflammation reflecting early-stage atherosclerosis. Increased serum levels of high-sensitivity CRP (hsCRP) also are associated with MetS. This study measured plasma HMW adiponectin concentrations using an enzyme-linked immunosorbent assay, as well as levels of hsCRP, in 1845 middle-aged to elderly subjects dwelling in the community. Significantly reduced plasma levels of HMW adiponectin were documented, in both men and women, for each component of MetS other than elevated blood pressure. Plasma levels of hsCRP were significantly higher in those with metabolic disorders. Levels of high-density lipoprotein-cholesterol correlated positively with adiponectin levels. There was an inverse association between body mass index and hsCRP. After adjusting for possible confounding factors by logistic regression analysis, concentrations of both HMW adiponectin and hsCRP were identified as independent determinants of MetS. In addition to these direct associations there was a synergistic effect between these substances. Both HMW adiponectin and hsCRP were independently associated with insulin resistance. These findings demonstrate that reduced concentrations of HMW adiponectin and elevated levels of hsCRP are synergistically associated with the accumulation of metabolic disorders as exemplified by MetS. Estimating concentrations of these marker substances might help to identify populations at increased risk.