title: A stepwise approach to assess the impact of clustering cardiometabolic risk factors on carotid intima-media thickness: the metabolic syndrome no-more-than-additive.
abstract: BACKGROUND
  Cardiovascular risk factors cluster in the metabolic syndrome (MS), but it is not known whether the risk associated with the syndrome is higher than the sum of its parts. In this study, we explored the relationship between clustering cardiometabolic risk factors and carotid intima-media thickness (c-IMT).
  
  
  RESULTS
  Cardiovascular parameters and c-IMT were determined in 240 middle-aged healthy participants, divided into groups according to their number of MS components. Higher number of MS components were associated with higher mean c-IMT. Analysis of synergy revealed that c-IMT increase at component clustering fitted an additive model. Redefinition of cutpoints for MS traits, optimized to detect high c-IMT, did not improve the interaction between components. When metabolic factors were rendered independent, a synergistic interaction between factors in increasing the likelihood of having a high c-IMT was detected. Synergic as well was the interaction between metabolic factors with other risk factors that are not consequence of insulin resistance, such as low-density lipoprotein-cholesterol level and smoking habit.
  
  
  CONCLUSIONS
  A stepwise approach reveals that the lack of synergy in the interactions between MS components is attributable to their mutual interdependence, possibly owing to the common pathophysiological background. Indeed, if MS is a unique clinical entity, it should be no more than the sum of its parts.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Padova Medical School, Padova, Italy. gianpaolofadini@hotmail.com
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Fadini
authors.forename: Anna
authors.initials: A
authors.lastname: Coracina
authors.forename: Sandro
authors.initials: S
authors.lastname: Inchiostro
authors.forename: Antonio
authors.initials: A
authors.lastname: Tiengo
authors.forename: Angelo
authors.initials: A
authors.lastname: Avogaro
authors.forename: Saula Vigili
authors.initials: SV
authors.lastname: de Kreutzenberg
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000209:etiology*; D002340:Carotid Artery Diseases / Q000150:complications / Q000000981:diagnostic imaging / Q000209:etiology*; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging*; D016000:Cluster Analysis; D005163:Factor Analysis, Statistical; D005260:Female; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications* / Q000000981:diagnostic imaging; D008875:Middle Aged; D018570:Risk Assessment; D012307:Risk Factors; D017539:Tunica Intima / Q000000981:diagnostic imaging; D017540:Tunica Media / Q000000981:diagnostic imaging; D014463:Ultrasonography