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.

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.

Hypotension associated with prone body position: a possible overlooked postural hypotension.

Conditions related to the dysregulation of blood pressure (BP), such as orthostatic hypotension, have been shown to be significantly associated with cardiovascular disease. Recently, the prone body position has been recognized as a possible postural factor leading to BP dysregulation. We conducted a cross-sectional study to investigate the BP response to a change in body position from supine to prone. The study subjects consisted of 271 middle-aged healthy males, randomly selected from the employees of a large manufacturing enterprise in Ehime Prefecture, Japan. Brachial BP and heart rate were measured in a sitting, supine and prone position, in that order, and each difference was defined as a postural change. The postural changes in aortic hemodynamics were also assessed using a SphygmoCor system. The basal BP measured in the sitting position was significantly decreased in the supine position (132+/-18 to 130+/-17 mmHg, p<0.001). A further reduction was observed after the postural change from supine to prone (130+/-17 to 125+/-16 mmHg, p<0.001). The heart rate was increased with the supine-to-prone postural change (4.1+/-5.8 beats/min, p<0.001), while it showed a significant decrease with the sitting-to-supine postural change (-7.6+/-5.6 beats/ min, p<0.05). The impact of BP reduction was more prominent in the aortic artery (-3.3+/-6.7%) than the brachial artery (-3.0+/-6.3%, p=0.020). Multiple regression analysis showed that basal systolic BP was a solely significant determinant of the prone-hypotension (beta=-0.309, p<0.001). In conclusion, these results indicate that lying in a prone posture could lead to unregulated postural hypotension, which has the possibility of being a novel predictor of cardiovascular frailty.

Effect of genetic polymorphism of OATP-C (SLCO1B1) on lipid-lowering response to HMG-CoA reductase inhibitors.

The effect of genetic polymorphism of human organic anion transporting polypeptide C (OATP-C) on the lipid-lowering response to 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors was assessed. A retrospective study was conducted on 66 patients who underwent treatment of hyperlipidemia with HMG-CoA reductase inhibitors in a municipal hospital in a community-based cohort of Ehime prefecture in the southern part of Japan. Plasma lipid concentrations before and after administration were analyzed in patients in relation to the 521T/C (Val-174-->Ala) polymorphism in the OATP-C gene (TT: n=44 (66.7%), TC: n=20 (30.3%), CC: n=0 (0.0%), undetermined: n=2 (3.0%)). Total cholesterol level was significantly lowered after treatment with HMG-CoA reductase inhibitors in all patients (p<0.001); moreover, subjects with the 521C allele showed an attenuated total-cholesterol-lowering effect compared with those homozygous for the 521T allele (-22.3+/-8.7% vs. -16.5+/-10.5%, p<0.05). These data suggest that the 521T/C polymorphism of the OATP-C gene modulates the lipid-lowering efficacy of HMG-CoA reductase inhibitors.