title: The impact of long-term changes in metabolic status on cardiovascular biomarkers and microvascular endothelial function in middle-aged men: a 25-year prospective study.
abstract: BACKGROUND
  The aim of this analysis was to examine long-term effects of changes in metabolic status on microvascular endothelial function and cardiovascular diseases (CVD) biomarkers among physically active middle-aged men.
  
  
  METHODS
  Metabolically healthy men (n = 101, mean age 59.7 years), free of symptoms and treatment, have been prospectively observed for their lifestyle and CVD risk factors (observation period 24.7 years). At the latest follow-up (2011/2012) a set of CVD biomarkers was measured using enzyme-linked immunosorbent assay. Microvascular endothelial function was evaluated by means of the reactive hyperemia index (RHI) using Endo-PAT2000 system. At follow-up the participants were divided into metabolically healthy (0-1 metabolic parameters) and metabolically unhealthy (≥2 metabolic parameters) groups. Metabolic syndrome was defined according to the NCEP ATP III definition.
  
  
  RESULTS
  Traditional metabolic risk factors were significantly associated with hsCRP, ox-LDL, Il-6, leptin and adiponectin/leptin ratio. Reactive hyperemia index was negatively related to body mass (p < 0.01), waist circumference (p < 0.05), triglycerides (p < 0.01), TG/HDL ratio (p < 0.01), uric acid (p < 0.05), sICAM-1 (p < 0.05) and Il-6 (p < 0.05), and positively to HDL-C (p < 0.01) and leisure-time physical activity (p < 0.01). Men who maintained metabolically healthy status (n = 47) through the observation had significantly lower hsCRP and uric acid (p < 0.05), higher adiponectin/leptin ratio (p < 0.05), higher mean RHI and lower prevalence of endothelial dysfunction (p < 0.05) as compared to the metabolically unhealthy group (n = 54). Regular physical activity level was significantly higher among metabolically healthy individuals during the whole observation.
  
  
  CONCLUSIONS
  Even subtle changes in metabolic profile influence inflammatory biomarkers and microvascular endothelial function. Leptin, adiponectin/leptin ratio and hsCRP are significant predictors of metabolic profile. Interleukine-6 and sICAM-1 may be used as indicators of early endothelial dysfunction in asymptomatic men. High leisure-time physical activity level is an important contributor of metabolically healthy profile through middle adulthood.
authors.affiliation: Department of Preventive Medicine, Medical University of Lodz, Zeligowskiego 7/9, 90-752 Lodz, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kwaśniewska
authors.affiliation: Department of Preventive Medicine, Medical University of Lodz, Zeligowskiego 7/9, 90-752 Lodz, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Kozińska
authors.affiliation: Department of Epidemiology and Biostatistics, Medical University of Lodz, Zeligowskiego 7/9, 90-752 Lodz, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Dziankowska-Zaborszczyk
authors.affiliation: Department of Geriatrics, Medical University of Lodz, Zeromskiego 113, Lodz, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kostka
authors.affiliation: Department of Sports Medicine, Medical University of Lodz, Pomorska 251, 92-213 Lodz, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Jegier
authors.affiliation: Department of Preventive Medicine, Medical University of Lodz, Zeligowskiego 7/9, 90-752 Lodz, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Rębowska
authors.affiliation: Central Clinical Hospital, Medical University of Lodz, Pomorska 251, 92-213 Lodz, Poland.
authors.forename: Milena
authors.initials: M
authors.lastname: Orczykowska
authors.affiliation: Department of Sports Medicine, Medical University of Lodz, Pomorska 251, 92-213 Lodz, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Leszczyńska
authors.affiliation: Department of Preventive Medicine, Medical University of Lodz, Zeligowskiego 7/9, 90-752 Lodz, Poland ; Department of Epidemiology, Cardiovascular Disease Prevention and Health Promotion, Institute of Cardiology, Niemodlinska 33, 04-635 Warsaw, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Drygas
keywords: Biomarkers; Disorders; Endothelial; Metabolic syndrome; Physical activity; Reactive hyperemia