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Aging and disease    2018, Vol. 9 Issue (5) : 946-951     DOI: 10.14336/AD.2017.1117
Short Communication |
Low Molecular Weight Adiponectin Increases the Mortality Risk in Very Old Patients

Stefano Rizza1,2, *, Marina Cardellini1,2, Alessio Farcomeni3, Pasquale Morabito1, Daniele Romanello1, Giovanni Di Cola1,2, Maria Paola Canale1,2, Massimo Federici1,2

1Department of Systems Medicine, University of Rome Tor Vergata and
2Center for Atherosclerosis, Policlinico Tor Vergata.
3Department of Public Health and Infectious Diseases Sapienza, University of Rome, Italy
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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.

Keywords adiponectin      isoforms      mortality      aging     
Corresponding Authors: Stefano Rizza   
About author: These authors contributed equally to this work.
Issue Date: 23 October 2017
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Rizza Stefano
Cardellini Marina
Farcomeni Alessio
Morabito Pasquale
Romanello Daniele
Di Cola Giovanni
Canale Maria Paola
Federici Massimo
Cite this article:   
Rizza Stefano,Cardellini Marina,Farcomeni Alessio, et al. Low Molecular Weight Adiponectin Increases the Mortality Risk in Very Old Patients[J]. Aging and disease, 2018, 9(5): 946-951.
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All-cause deaths (n°54)Survivors (n°43)p
Age (years)80.4±3.878.5±3.3<0.05
Gender (male)39(72.2)21(48.8)<0.056
BMI (kg/m2)26.8±3.527.0±4.30.841
Systolic blood pressure (mmHg)144.8±21.4146.5±21.40.712
Diastolic blood pressure (mmHg)75.6±12.477.6±10.00.427
Total cholesterol (mg/dl)183.3±38.3188.3±39.80.572
High-density-lipoprotein cholesterol (mg/dl)48.7±13.254.3±14.70.085
Low-density-lipoprotein cholesterol (mg/dl)118.3±32.8116.5±34.70.813
Triglycerides (mg/dl)123.8±61.6110.3±37,30.220
Current or former smokers (yes)32(59.2)16(37.2)<0.05
Diabetes (yes)20(37.0)11(25.5)0.229
Stable CHD (yes)24(44.4)10(23.2)<0.050
Tumor necrosis factor-α (pg/ml)12.9±15.011.9±14.10.757
High sensitivity C-reactive protein (mg/l)5.0±5.63.3±3.80.083
Estimated glomerul filtration rate (ml*sec-¹)57.1±19.959.5±19.00.595
Total-Adiponectin (µg/ml)4.7±4.24.6±4.10.896
HMW-Ad (µg/ml)1.7±1.82.3±2.30.222
MMW-Ad (µg/ml)1.0±1.01.1±1.30.831
LMW-Ad (µg/ml)2.5±2.51.4±1.4<0.05
Pharmacological Therapy
Metformin* (%)75720.889
Sulphonylurea* (%)25360.504
Glitazone* (%)10270.210
Angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist (%)77830.826
Diuretic (%)35250.309
Calcium antagonist (%)35340.975
Beta-blocker (%)50420.424
Aspirin (%)60630.723
Statin (%)57550.942
Table 1  Baseline clinical and laboratory characteristics of patients divided upon follow-up mortality. Data are displayed as n (%) or mean (±SD).
HRCI (95%)p
Model 1
Gender (male)2.041.17-3.580.012
Age (year)1.101.01-1.190.019
Stable CHD (yes)1.450.80-2.640.220
Total-Adiponectin (µg/ml)0.990.93-1.050.663
Model 2
Gender (male)2.031.16-3.550.013
Age (year)1.101.01-1.190.026
Stable CHD (yes)1.450.80-2.650.220
HMW-Ad (µg/ml)0.910.80-1.040.173
Model 3
Gender (male)2.051.16-3.640.014
Age (year)1.101.02-1.190.014
Stable CHD (yes)1.350.73-2.490.337
MMW-Ad (µg/ml)1.040.82-1.320.723
Model 4
Gender (male)1.911.08-3.350.025
Age (year)1.101.02-1.200.013
Stable CHD (yes)1.220.67-2.210.51
LMW-Ad (µg/ml)1.111.02-1.210.017
Table 2  Multivariate analysis models for all-cause mortality with all Adiponectin isoforms.
[1] Ortega-Moreno L, Copetti M, Fontana A, De Bonis C, Salvemini L, Trischitta et al. (2016). Evidence of a causal relationship between high serum adiponectin levels and increased cardiovascular mortality rate in patients with type 2 diabetes. Cardiovasc Diabetol, 15:17.
[2] Inoue T, Kotooka N, Morooka T, Komoda H, Uchida T, Aso Yet al. (2007). High-molecular-weight adiponectin as a predictor of long-term clinical outcome in patients with coronary artery disease. Am J Cardiol, 100: 569-74.
[3] Kizer JR, Benkeser D, Arnold AM, Djousse L, Zieman SJ, Mukamal KJ, et al. (2013). Total and high-molecular-weight adiponectin and risk of coronary heart disease and ischemic stroke in older adults. J Clin Endocrinol Metab, 98:255-63.
[4] Rizza S, Gigli F, Galli A, Micchelini B, Lauro D, Lauro Ret al. (2010). Adiponectin Isoforms in Elderly Patients with or without CHD. JAGS, 58: 702-706
[5] Jia Z, Liu Y, Cui S (2014). Adiponectin induces breast cancer cell migration and growth factor expression. Cell Biochem Biophys 70(2): 1239-45.
[6] Fayad R, Pini M, Sennello JA, Cabay RJ, Chan L, Xu Aet al. (2007). Adiponectin deficiency protects mice from chemically induced colonic inflammation. Gastroenterology 132(2): 601-14.
[7] Kaur K, Saxena A, Larsen B, Truman S, Biyani N, Fletcher Eet al. (2015). Mucus mediated protection against acute colitis in adiponectin deficient mice. J Inflamm (Lond), 12:3 5.
[8] Van Himbergen TM, Alexa SB, Ai M, Seshadri S, Otokozawa S, Au Ret al. (2012). Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and alzheimer disease results from the framingham heart study. Arch Neurol, 69, 564-600
[9] Matsumoto Y, Toyomasu K, Uchimura N, Ishitake T (2013). Low-molecular-weight adiponectin is more closely associated with episodes of asthma than high-molecular-weight adiponectin. Endocr J, 60:119-25
[10] Tsukada T, Fushida S, Harada S, Terai S, Yagi Y, Kinoshita Jet al. (2011). Adiponectin receptor-1 expression is associated with good prognosis in gastric cancer. J Exp Clin Cancer Res, 30: 107
[11] Rider JR, Fiorentino M, Kelly R, Gerke T, Jordahl K, Sinnott JAet al. (2015). Tumor expression of adiponectin receptor-2 and lethal prostate cancer. Carcinogenesis, 36(6): 639-47.
[12] Ping Li, Li Yang, Cui-li Ma, Liu B, Zhang X, Ding Ret al. (2015). Low-molecular-weight adiponectin is more closely associated with disease activity of rheumatoid arthritis than other adiponectin multimeric forms. Clin Rheumatol, 34:1025-1030
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