title: Importance of substantial weight loss for altering gene expression during cardiovascular lifestyle modification.
abstract: OBJECTIVE
  To examine relationships between weight loss through changes in lifestyle and peripheral blood gene expression profiles.
  
  
  METHODS
  A prospective nonrandomized trial was conducted over 1 year in participants undergoing intensive lifestyle modification to reverse or stabilize progression of coronary artery disease. Cardiovascular risk factors, inflammatory biomarkers, and gene expression as a function of weight loss were assessed in 89 lifestyle participants and 71 retrospectively matched controls undergoing usual care.
  
  
  RESULTS
  Substantial weight loss (-15.2 ± 3.8%) in lifestyle participants (n = 33) was associated with improvement in selected cardiovascular risk factors and significant changes in peripheral blood gene expression from pre- to post-intervention: 132 unique genes showed significant expression changes (false discovery rate corrected P-value <0.05 and fold-change ≥1.4). Altered molecular pathways were related to immune function and inflammatory responses involving endothelial activation. In contrast, participants losing minimal weight (-3.1 ± 2.5%, n = 32) showed only minor changes in cardiovascular risk factors and markers of inflammation and no changes in gene expression compared to non intervention controls after 1 year.
  
  
  CONCLUSIONS
  Weight loss (≥10%) during lifestyle modification is associated with down-regulation of genetic pathways governing interactions between circulating immune cells and the vascular endothelium and may be required to successfully reduce CVD risk.
authors.affiliation: Integrative Cardiac Health Program, Windber Research Institute, Windber, Pennsylvania, USA.
authors.forename: Darrell L
authors.initials: DL
authors.lastname: Ellsworth
authors.affiliation: Integrative Cardiac Health Program, Windber Research Institute, Windber, Pennsylvania, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Mamula
authors.affiliation: Integrative Cardiac Health Program, Windber Research Institute, Windber, Pennsylvania, USA.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Blackburn
authors.affiliation: Almac Diagnostics, Almac Group Limited, Craigavon, UK.
authors.forename: Fionnuala A
authors.initials: FA
authors.lastname: McDyer
authors.affiliation: Almac Diagnostics, Almac Group Limited, Craigavon, UK.
authors.forename: Gera L
authors.initials: GL
authors.lastname: Jellema
authors.affiliation: Bioinformatics Department, ChipDX LLC, New York, New York, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: van Laar
authors.affiliation: Integrative Cardiac Health Program, Windber Research Institute, Windber, Pennsylvania, USA.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Costantino
authors.affiliation: Integrative Cardiac Health Program, Walter Reed National Military Medical Center, Bethesda, Maryland, USA.
authors.forename: Renata J M
authors.initials: RJ
authors.lastname: Engler
authors.affiliation: Integrative Cardiac Health Program, Walter Reed National Military Medical Center, Bethesda, Maryland, USA.
authors.forename: Marina N
authors.initials: MN
authors.lastname: Vernalis
mesh_terms: D000368:Aged; D000072038:Cardiac Rehabilitation; D002318:Cardiovascular Diseases / Q000235:genetics*; D005247:Feeding Behavior; D005260:Female; D015870:Gene Expression; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018570:Risk Assessment; D040242:Risk Reduction Behavior; D015431:Weight Loss / Q000235:genetics*