title: Overweight across the life course and adipokines, inflammatory and endothelial markers at age 60-64 years: evidence from the 1946 birth cohort.
abstract: OBJECTIVE
  There is growing evidence that early development of obesity increases cardiovascular risk later in life, but less is known about whether there are effects of long-term excess body weight on the biological drivers associated with the atherosclerotic pathway, particularly adipokines, inflammatory and endothelial markers. This paper therefore investigates the influence of overweight across the life course on levels of these markers at retirement age.
  
  
  METHODS
  Data from the Medical Research Council National Survey of Health and Development (n=1784) were used to examine the associations between overweight status at 2, 4, 6, 7, 11, 15, 20, 26, 36, 43, 53 and 60-64 years (body mass index (BMI)⩾25 kg m(-2) for adult ages and gender-specific cut-points for childhood ages equivalent to BMI⩾25 kg m(-2)) and measurements of adipokines (leptin and adiponectin), inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6)) and endothelial markers (E-selectin, tissue plasminogen activator (t-PA) and von Willebrand factor) at 60-64 years. In addition, the fit of different life course models (sensitive periods/accumulation) were compared using partial F-tests.
  
  
  RESULTS
  In age- and sex-adjusted models, overweight at 11 years and onwards was associated with higher leptin, CRP and IL-6 and lower adiponectin; overweight at 15 years and onwards was associated with higher E-selectin and t-PA. Associations between overweight at all ages earlier than 60-64 with leptin, adiponectin, CRP and IL-6 were reduced but remained apparent after adjustment for overweight at 60-64 years; whereas those with E-selectin and t-PA were entirely explained. An accumulation model best described the associations between overweight across the life course with adipokines and inflammatory markers, whereas for the endothelial markers, the sensitive period model for 60-64 years provided a slightly better fit than the accumulation model.
  
  
  CONCLUSIONS
  Overweight across the life course has a cumulative influence on adipokines, inflammatory and possibly endothelial markers. Avoidance of overweight from adolescence onwards is likely important for cardiovascular disease prevention.
authors: Population Health Research Institute, St George's University of London, London, UK.
authors: E T
authors: ET
authors: Murray
authors: MRC Unit for Lifelong Health and Ageing at University College London, London, UK.
authors: R
authors: R
authors: Hardy
authors: Institute of Cardiovascular Science, University College London, London, UK.
authors: A
authors: A
authors: Hughes
authors: School of Clinical Sciences, University of Bristol, Bristol, UK.
authors: A
authors: A
authors: Wills
authors: British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
authors: N
authors: N
authors: Sattar
authors: National Centre for Cardiovascular Prevention and Outcomes, University College London, London, UK.
authors: J
authors: J
authors: Deanfield
authors: MRC Unit for Lifelong Health and Ageing at University College London, London, UK.
authors: D
authors: D
authors: Kuh
authors: Population Health Research Institute, St George's University of London, London, UK.
authors: P
authors: P
authors: Whincup
mesh_terms: D052242:Adiponectin / Q000097:blood; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000375:Aging; D015415:Biomarkers / Q000097:blood*; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood* / Q000517:prevention & control; D002648:Child; D002675:Child, Preschool; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000517:prevention & control; D019040:E-Selectin / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000453:epidemiology; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D019040:E-Selectin; D015850:Interleukin-6; D020738:Leptin; D014841:von Willebrand Factor; D002097:C-Reactive Protein