Abstract
Despite its beneficial role on insulin resistance and atherosclerosis, adiponectin has been frequently reported as an independent positive predictor of cardiovascular mortality. Very few information is available regarding adiponectin isoforms and mortality, in particular in advanced aging. Baseline serum levels of Total Adiponectin and its circulating isoforms (HMW-, MMW-, LMW-Adiponectin) were measured in 97 old patients (mean age: 79 years). Patients were followed up for all-cause mortality (study end-point) for an average of 76.4 ± 37.3 months. A positive association was observed for LMW-Ad and all-cause mortality (HR: 1.13, 95% CI: 1.05-1,22, p: 0.002). After multivariate adjustment for age, sex and a previous history of myocardial infarction, higher levels of LMW-Ad were significantly associated with all-cause mortality (HR: 1.11, 95% CI: 1.02-1.21; p: 0.017). Interestingly neither total adiponectin neither the other two circulating isoforms (MMW- and HMW-Ad) showed any significant association with the study end-point. Our data suggest that the association between high serum adiponectin levels and increased mortality rate in elderly is contingent to an unbalanced circulating levels of adiponectin isoforms. The present results support the hypothesis that high levels of Low Molecular Weight adiponectin are a biomarker for mortality risk in very old patients.
Highlights
Adiponectin, the most abundant adipose-tissue hormone with pleiotropic actions in a plethora of tissues, is an independent positive predictor of mortality in the general population, especially in cardiovascular setting [1]
We previously reported that total adiponectin (Tot-Ad) level was higher in older adults with previous coronary heart disease (CHD) but, among circulating isoforms, only LMW-Ad was significantly associated with CHD in elderly patients [4]
Among Adiponectin isoforms, only LMW-Ad levels were significantly higher in subjects who died during follow up (2.3μg/ml vs 1.4μg/ml, respectively, p:0.024) (Table 1)
Summary
Adiponectin, the most abundant adipose-tissue hormone with pleiotropic actions in a plethora of tissues, is an independent positive predictor of mortality in the general population, especially in cardiovascular setting [1]. Adiponectin exerts many insulin-sensitizing, anti-inflammatory and endothelial protective effects [1]. Because of such paradox, it is logical to suspect that total adiponectin (Tot-Ad) level may not be a marker of cardiovascular mortality risk. While biological activities among these three isoforms are a matter of controversy, previous studies have indicated that HMW-, MMW- and LMW-Ad have different biological properties. HMW-Ad is known to have strong vasculoprotective and insulin-sensitizing properties, the majority of studies measured only Tot-Ad circulating. We previously reported that Tot-Ad level was higher in older adults with previous coronary heart disease (CHD) but, among circulating isoforms, only LMW-Ad was significantly associated with CHD in elderly patients [4]. We used a long follow-up to investigate a possible independent association between adiponectin circulating isoforms and total mortality in a group of very old patients
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