title: Elevated plasma levels of TNF-alpha and interleukin-6 in patients with diastolic dysfunction and glucose metabolism disorders.
abstract: BACKGROUND
  Diabetes mellitus (DM) has reached epidemic proportions and is an important risk factor for heart failure (HF). Left ventricular diastolic dysfunction (LVDD) is recognized as the earliest manifestation of DM-induced LV dysfunction, but its pathophysiology remains incompletely understood. We sought to evaluate the relationship between proinflammatory cytokine levels (TNF-alpha, IL-6) and tissue Doppler derived indices of LVDD in patients with stable coronary artery disease.
  
  
  METHODS
  We enrolled 41 consecutive patients (mean age 65+/-10 years) submitted for coronary angiography. Echocardiographic assessment was performed in all patients. Pulsed tissue Doppler imaging was performed at the mitral annulus and was characterized by the diastolic early relaxation velocity Em. Conventional transmitral flow was measured with pw-doppler. Early (E) transmitral flow velocity was measured. LVDD was defined as E/Em ratio >or= 15, E/Em 8-14 was classified as borderline. Plasma levels of TNF-alpha and IL-6 were determined in all patients. A standardized oral glucose tolerance test was performed in subjects without diabetes.
  
  
  RESULTS
  Patients with E/Em ratio >or= 15, classified as LVDD and those with E/Em ratio 8-14 (classified as borderline) had significantly higher IL-6 (P = 0,001), TNF-alpha (P < 0,001) and NT-pro- BNP (P = 0,001) plasma levels compared to those with normal diastolic function. TNF-alpha and IL-6 levels remains significantly elevated after adjustment for sex, age, left ventricular ejection function, body mass index, coronary heart disease, smoking, hypertension and diabetes mellitus with linear regression analysis. Furthermore, in subjects LVDD or borderline LV diastolic function, 75% had diabetes or IGT, respectively. When subjects without diabetes were excluded, both IL-6 (P = 0,006) and TNF-alpha (P = 0,002) remained significantly elevated in subjects with E/Em ratio >or= 15.
  
  
  CONCLUSIONS
  This study reveals that increased plasma levels of IL-6 and TNF-alpha were associated with LVDD. These findings suggest a link between low-grade inflammation and the presence of LVDD. An active proinflammatory process may be of importance in the pathogenesis of diastolic dysfunction.
authors.affiliation: Helios Clinics Wuppertal, Heart Center, Germany. wilfried.dinh@helios-kliniken.de
authors.forename: Wilfried
authors.initials: W
authors.lastname: Dinh
authors.forename: Reiner
authors.initials: R
authors.lastname: Füth
authors.forename: Werner
authors.initials: W
authors.lastname: Nickl
authors.forename: Thomas
authors.initials: T
authors.lastname: Krahn
authors.forename: Peter
authors.initials: P
authors.lastname: Ellinghaus
authors.forename: Thomas
authors.initials: T
authors.lastname: Scheffold
authors.forename: Lars
authors.initials: L
authors.lastname: Bansemir
authors.forename: Alexander
authors.initials: A
authors.lastname: Bufe
authors.forename: Michael Coll
authors.initials: MC
authors.lastname: Barroso
authors.forename: Mark
authors.initials: M
authors.lastname: Lankisch
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D044882:Glucose Metabolism Disorders / Q000097:blood* / Q000150:complications; D054144:Heart Failure, Diastolic / Q000097:blood* / Q000150:complications; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000097:blood*; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000150:complications
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha