Publications by Year: 2015

OBJECTIVE: Hypertensive patients with CKD present an increased risk for cardiovascular mortality. Among the proteins synthesized and released from adipose tissue, resistin is a cytokine whose physiologic role has been the subject of much research and controversy. We and others have demonstrated that serum resistin levels are higher in patients with CKD and correlate directly with inflammatory markers, including TNF-α and hsCRP. Since inflammation has been consistently linked to atherosclerosis, death, and cardiovascular (CV) events, our goal was to investigate the interaction between resistin levels and long term all-cause and CV mortality in elderly non-obese and non-diabetic with hypertension. DESIGN AND METHOD: We studied 80 patients (52 men/28 women) 70.9 ± 8.6 years of age with hypertension and CKD. Exclusion criteria was obesity and diabetes mellitus, active infection, acute illness, chronic inflammatory disease or cancer, and immunosuppresive, anti-inflammatory or anti-lipidemic drugs. Demographic data, clinical information and blood samples were collected prospectively. The patients were observed for 5 years. RESULTS: During the follow-up 28 of 80 (35%) patients died: 16 (57%) deaths due to CV events and 12 (43%) of other causes. Patients who died were older and had higher DBP, compared to survivors, but had no differences in BMI, smoking, SBP and HR. Deceased patients had higher WBC, hsCRP, BUN, creatinine, cystatin C, phosphate, magnesium and potassium levels and lower eGFR, Hct/Hg, T3, T4, total cholesterol, LDL-C, albumin and sodium levels compared to survivors. No significant differences in platelet count, TNF-α, fibrinogen, oxLDL, ADMA, HgA1C and HOMA-index were revealed between the groups. eceased patients had significantly higher resistin levels than survivors at baseline (p = 0.025), but adiponectin, visfatin and leptin did not differ between the two groups. Five variables, namely resistin, sodium, cholesterol, T3 and WBC remained significantly associated with survival and were used in the multivariate Cox regression analysis, which revealed that only resisitin, cholesterol and WBC maintained their discriminatory ability, as independent predictors of mortality both by forward and backward stepwise analysis. CONCLUSIONS: Elevated serum resistin was a significant independent biomarker of CV and all-cause mortality in elderly, non-diabetic CKD patients with hypertension.
Dalamaga M, Christodoulatos GS. Adiponectin as a biomarker linking obesity and adiposopathy to hematologic malignancies. Horm Mol Biol Clin Investig. 2015;23(1):5-20.Abstract
Higher body mass index and adiposopathy have been associated with increased risk of hematologic malignancies such as leukemia, multiple myeloma, myeloproliferative disorders, Hodgkin's and non-Hodgkin's lymphoma, and myelodysplastic syndromes. Adiponectin is a multimeric protein of the white adipose tissue presenting anti-inflammatory, insulin-sensitizing, anti-atherogenic, cardioprotective, and anti-neoplastic properties. Its anti-neoplastic actions are manifested via two mechanisms: (i) direct action on tumor cells by enhancing receptor-mediated signaling pathways and (ii) indirect action by regulating inflammatory responses, influencing cancer angiogenesis, and modulating insulin sensitivity at the target tissue site. In the bone marrow milieu, adiponectin and its main receptors are expressed by the majority of bone marrow stromal cell populations influencing hematopoietic stem cells function. Adiponectin may represent a molecular mediator relating adiposopathy with leukemogenesis and myelomagenesis. Several epidemiological studies conducted to date relate hypoadiponectinemia to the risk of myeloid-derived hematopoietic cancer and multiple myeloma. Adiponectin may be a promising biomarker with potential diagnostic and prognostic utility in determining the likelihood of myeloma and leukemia progression in certain cohorts of monoclonal gammopathy of undetermined significance patients and in myeloid hematologic malignancies, respectively. This review summarizes experimental and epidemiologic data regarding the role of adiponectin in hematologic malignancies in the context of adiposopathy. Enhancement of endogenous adiponectin, adiponectin replacement, or manipulation of adiponectin receptor sensitivity may be an attractive goal for prevention and an effective therapeutic strategy against hematopoietic cancer, specifically in overweight/obese individuals. Further studies are required to elucidate the role of the bone marrow microenvironment adiponectin in complex interactions involved in preleukemic and leukemic states.
Nikolaou V, Papadavid E, Ekonomidi A, Dalamaga M, Marinos L, Stratigos A, Papadaki T, Antoniou C. Association of clinicopathological characteristics with secondary neoplastic lymphoproliferative disorders in patients with lymphomatoid papulosis. Leuk Lymphoma. 2015;56(5):1303-7.Abstract
Lymphomatoid papulosis (LyP) refers to an indolent cutaneous lymphoma. The association of prognostic clinicopathological risk factors with a second hematologic malignancy has not yet been determined. We investigated the prognostic effect of clinicopathological characteristics on the occurrence of a second lymphoma, as well as the first-line treatment, in 24 patients diagnosed with LyP using logistic regression models. We showed that lymphoma occurrence was associated with a lower mean age at onset of LyP symptoms, histological types B and C, head-located LyP lesions and a higher frequency of LyP recurrences. In multivariate analyses, histologic type A was associated with a lower risk of second lymphoma (odds ratio [OR] = 0.12, 95% confidence interval [CI] 0.014-0.98; p = 0.045) adjusting for age of LyP first symptomatology, and an important increased lymphoma-free survival rate (long-rank test; p = 0.06). Clinicopathological characteristics are important in defining the clearance or persistence of LyP lesions and may predict the occurrence of a second lymphoma.