title: Dyslipidemia and chronic inflammation markers are correlated with telomere length shortening in Cushing's syndrome.
abstract: BACKGROUND
  Cushing's syndrome (CS) increases cardiovascular risk (CVR) and adipocytokine imbalance, associated with an increased inflammatory state. Telomere length (TL) shortening is a novel CVR marker, associated with inflammation biomarkers. We hypothesized that inflammatory state and higher CVR in CS might be related to TL shortening, as observed in premature aging.
  
  
  OBJECTIVE
  To evaluate relationships between TL, CVR and inflammation markers in CS.
  
  
  METHODS
  In a cross-sectional study, 77 patients with CS (14 males, 59 pituitary-, 17 adrenal- and 1 ectopic-origin; 21 active disease) and 77 age-, gender-, smoking-matched controls were included. Total white blood cell TL was measured by TRF-Southern technique. Clinical data and blood samples were collected (lipids, adrenal function, glucose). Adiponectin, interleukin-6 (IL6) and C-reactive protein (CRP) were available in a subgroup of patients (n=32). Correlations between TL and clinical features were examined and multiple linear regression analysis was performed to investigate potential predictors of TL.
  
  
  RESULTS
  Dyslipidemic CS had shorter TL than non-dyslipidemic subjects (7328±1274 vs 7957±1137 bp, p<0.05). After adjustment for age and body mass index, cured and active CS dyslipidemic patients had shorter TL than non-dyslipidemic CS (cured: 7187±1309 vs 7868±1104; active: 7203±1262 vs 8615±1056, respectively, p<0.05). Total cholesterol and triglycerides negatively correlated with TL (r-0.279 and -0.259, respectively, p<0.05), as well as CRP and IL6 (r-0.412 and -0.441, respectively, p<0.05). No difference in TL according the presence of other individual CVR factors (hypertension, diabetes mellitus, obesity) were observed in CS or in the control group. Additional TL shortening was observed in dyslipidemic obese patients who were also hypertensive, compared to those with two or less CVR factors (6956±1280 vs 7860±1180, respectively, p<0.001). Age and dyslipidemia were independent negative predictors of TL.
  
  
  CONCLUSIONS
  TL is shortened in dyslipidemic CS patients, further worse if hypertension and/or obesity coexist and is negatively correlated with increased inflammation markers. Increased lipids and a "low" grade inflammation may contribute to TL shortening and consequently to premature ageing and increased morbidity in CS.
authors: Sant Pau Biomedical Research Institute, Endocrinology/Medicine Departments, Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Center for Biomedical Network Research on Rare Diseases (CIBERER Unit 747), ISCIII, Barcelona, Spain.
authors: Anna
authors: A
authors: Aulinas
authors: Universitat Autònoma de Barcelona. Department of Genetics and Microbiology and Center for Biomedical Network Research on Rare Diseases (CIBERER Unit 745), ISCIII, Bellaterra, Barcelona, Spain.
authors: María-José
authors: MJ
authors: Ramírez
authors: Center for Biomedical Network Research on Rare Diseases (CIBERER Unit 747), ISCIII, Barcelona, Spain; Hospital Universitari Mutua Terrassa, Endocrinology Department, Terrassa, Barcelona, Spain.
authors: María-José
authors: MJ
authors: Barahona
authors: Sant Pau Biomedical Research Institute, Endocrinology/Medicine Departments, Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Center for Biomedical Network Research on Rare Diseases (CIBERER Unit 747), ISCIII, Barcelona, Spain.
authors: Elena
authors: E
authors: Valassi
authors: Sant Pau Biomedical Research Institute, Endocrinology/Medicine Departments, Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Center for Biomedical Network Research on Rare Diseases (CIBERER Unit 747), ISCIII, Barcelona, Spain.
authors: Eugenia
authors: E
authors: Resmini
authors: Sant Pau Biomedical Research Institute, Endocrinology/Medicine Departments, Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Center for Biomedical Network Research on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), ISCIII, Barcelona, Spain.
authors: Eugènia
authors: E
authors: Mato
authors: Sant Pau Biomedical Research Institute, Endocrinology/Medicine Departments, Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Center for Biomedical Network Research on Rare Diseases (CIBERER Unit 747), ISCIII, Barcelona, Spain.
authors: Alicia
authors: A
authors: Santos
authors: Sant Pau Biomedical Research Institute, Endocrinology/Medicine Departments, Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Center for Biomedical Network Research on Rare Diseases (CIBERER Unit 747), ISCIII, Barcelona, Spain.
authors: Iris
authors: I
authors: Crespo
authors: Sant Pau Biomedical Research Institute, Endocrinology/Medicine Departments, Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Center for Biomedical Network Research on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), ISCIII, Barcelona, Spain.
authors: Olga
authors: O
authors: Bell
authors: Universitat Autònoma de Barcelona. Department of Genetics and Microbiology and Center for Biomedical Network Research on Rare Diseases (CIBERER Unit 745), ISCIII, Bellaterra, Barcelona, Spain.
authors: Jordi
authors: J
authors: Surrallés
authors: Sant Pau Biomedical Research Institute, Endocrinology/Medicine Departments, Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Center for Biomedical Network Research on Rare Diseases (CIBERER Unit 747), ISCIII, Barcelona, Spain.
authors: Susan M
authors: SM
authors: Webb
mesh_terms: D052242:Adiponectin / Q000097:blood; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D003480:Cushing Syndrome / Q000097:blood / Q000235:genetics*; D050171:Dyslipidemias / Q000097:blood / Q000235:genetics*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D059506:Telomere Shortening
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D015850:Interleukin-6; D008055:Lipids; D002097:C-Reactive Protein