title: Tissue inhibitor of matrix metalloproteinases 4 (TIMP4) in a population of young adults: relations to cardiovascular risk markers and carotid artery intima-media thickness. The Cardiovascular Risk in Young Finns Study.
abstract: OBJECTIVE
  The tissue inhibitor of metalloproteinases 4 (TIMP4) is present in significant amounts in human atherosclerotic coronary artery lesions, but its relations with the early pathogenesis of atherosclerotic changes have not been clarified. We studied the associations of circulating TIMP4 with pre-clinical markers of atherosclerosis and traditional cardiovascular risk factors by using longitudinal data on carotid artery intima-media (cIMT) thickness in a population-based cohort of asymptomatic young adult Finns.
  
  
  METHODS
  Data on cIMT, plasma TIMP4, lipids, CRP, blood pressure, BMI, smoking status and daily alcohol intake were obtained from 980 24-39 year-old participants in 2001. The 6-year follow-up in cIMT measurements were performed in 2007 for 769 participants.
  
  
  RESULTS
  Plasma TIMP4 concentrations (mean ± SD) were 2.3 ± 1.7 ng/mL in men and 2.5 ± 1.8 ng/mL in women. Age, LDL-cholesterol, BMI and systolic blood pressure were directly associated with TIMP4 concentration. In a multivariable model, the independent determinants of TIMP4 included systolic blood pressure (p = 0.008) and daily smoking (p = 0.009), both being inversely associated with TIMP4. These two baseline variables explained 1.5% of the variation in TIMP4. TIMP4 was significantly and inversely associated with cIMT measured 6 years later (beta =- 0.0135, p = 0.01) explaining 0.7% of the variability of cIMT.
  
  
  CONCLUSIONS
  In young apparently healthy adults, circulating TIMP4 concentration was independently and inversely associated with cIMT, a marker of vascular structure and function.
authors.affiliation: Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, 20520 Turku, Finland. mervi.oikonen@utu.fi
authors.forename: Mervi
authors.initials: M
authors.lastname: Oikonen
authors.forename: Maria
authors.initials: M
authors.lastname: Wendelin-Saarenhovi
authors.forename: Niina
authors.initials: N
authors.lastname: Siitonen
authors.forename: Annele
authors.initials: A
authors.lastname: Sainio
authors.forename: Markus
authors.initials: M
authors.lastname: Juonala
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.forename: Leo-Pekka
authors.initials: LP
authors.lastname: Lyytikäinen
authors.forename: Ilkka
authors.initials: I
authors.lastname: Seppälä
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.forename: Jorma S A
authors.initials: JS
authors.lastname: Viikari
authors.forename: Hannu
authors.initials: H
authors.lastname: Järveläinen
authors.forename: Olli T
authors.initials: OT
authors.lastname: Raitakari
mesh_terms: D000328:Adult; D050197:Atherosclerosis / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000378:metabolism / Q000473:pathology; D002339:Carotid Arteries / Q000473:pathology*; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D012307:Risk Factors; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D017539:Tunica Intima / Q000473:pathology*; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D015415:Biomarkers; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4