title: Systemic chemokine levels, coronary heart disease, and ischemic stroke events: the PRIME study.
abstract: OBJECTIVE
  To quantify the association between systemic levels of the chemokine regulated on activation normal T-cell expressed and secreted (RANTES/CCL5), interferon-γ-inducible protein-10 (IP-10/CXCL10), monocyte chemoattractant protein-1 (MCP-1/CCL2), and eotaxin-1 (CCL11) with future coronary heart disease (CHD) and ischemic stroke events and to assess their usefulness for CHD and ischemic stroke risk prediction in the PRIME Study.
  
  
  METHODS
  After 10 years of follow-up of 9,771 men, 2 nested case-control studies were built including 621 first CHD events and 1,242 matched controls and 95 first ischemic stroke events and 190 matched controls. Standardized hazard ratios (HRs) for each log-transformed chemokine were estimated by conditional logistic regression.
  
  
  RESULTS
  None of the 4 chemokines were independent predictors of CHD, either with respect to stable angina or to acute coronary syndrome. Conversely, RANTES (HR = 1.70; 95% confidence interval [CI] 1.05-2.74), IP-10 (HR = 1.53; 95% CI 1.06-2.20), and eotaxin-1 (HR = 1.59; 95% CI 1.02-2.46), but not MCP-1 (HR = 0.99; 95% CI 0.68-1.46), were associated with ischemic stroke independently of traditional cardiovascular risk factors, hs-CRP, and fibrinogen. When the first 3 chemokines were included in the same multivariate model, RANTES and IP-10 remained predictive of ischemic stroke. Their addition to a traditional risk factor model predicting ischemic stroke substantially improved the C-statistic from 0.6756 to 0.7425 (p = 0.004).
  
  
  CONCLUSIONS
  In asymptomatic men, higher systemic levels of RANTES and IP-10 are independent predictors of ischemic stroke but not of CHD events. RANTES and IP-10 may improve the accuracy of ischemic stroke risk prediction over traditional risk factors.
authors.affiliation: INSERM U970, The Paris Cardiovascular Research Centre (PARCC), 56 rue Leblanc, Paris, F-75015, France. jean-philippe.empana@inserm.fr
authors.forename: F
authors.initials: F
authors.lastname: Canouï-Poitrine
authors.forename: G
authors.initials: G
authors.lastname: Luc
authors.forename: Z
authors.initials: Z
authors.lastname: Mallat
authors.forename: E
authors.initials: E
authors.lastname: Machez
authors.forename: A
authors.initials: A
authors.lastname: Bingham
authors.forename: J
authors.initials: J
authors.lastname: Ferrieres
authors.forename: J-B
authors.initials: JB
authors.lastname: Ruidavets
authors.forename: M
authors.initials: M
authors.lastname: Montaye
authors.forename: J
authors.initials: J
authors.lastname: Yarnell
authors.forename: B
authors.initials: B
authors.lastname: Haas
authors.forename: D
authors.initials: D
authors.lastname: Arveiler
authors.forename: P
authors.initials: P
authors.lastname: Morange
authors.forename: F
authors.initials: F
authors.lastname: Kee
authors.forename: A
authors.initials: A
authors.lastname: Evans
authors.forename: P
authors.initials: P
authors.lastname: Amouyel
authors.forename: P
authors.initials: P
authors.lastname: Ducimetiere
authors.forename: J-P
authors.initials: JP
authors.lastname: Empana
mesh_terms: D002545:Brain Ischemia / Q000097:blood* / Q000175:diagnosis*; D016022:Case-Control Studies; D018925:Chemokines / Q000097:blood*; D015331:Cohort Studies; D003327:Coronary Disease / Q000097:blood* / Q000175:diagnosis*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020521:Stroke / Q000097:blood* / Q000175:diagnosis*; D011795:Surveys and Questionnaires
chemical_list: D018925:Chemokines