title: Early childhood hospitalisation with infection and subclinical atherosclerosis in adulthood: the Cardiovascular Risk in Young Finns Study.
abstract: OBJECTIVE
  Most infections occur in pre-school children but the severity of the inflammatory response to common pathogens varies considerably. We examined the relationship between early childhood infections of sufficient severity to warrant hospitalisation, and markers of subclinical atherosclerosis in adulthood.
  
  
  METHODS
  We investigated whether infection-related hospitalisation (IRH) in early childhood (0-5 years) was associated with adverse non-invasive phenotypes of atherosclerosis (carotid artery distensibility and intima-media thickness (IMT), and brachial artery flow-mediated dilation (FMD)) in adulthood in participants from the Cardiovascular Risk in Young Finns study. Analyses were adjusted for age, sex, and socioeconomic status and cardiovascular risk factors in childhood and adulthood. 1043 participants had lifetime IRH data with a mean age at adult follow-up of 33 years.
  
  
  RESULTS
  Brachial FMD levels were significantly lower among individuals with early child IRH (mean ± SEM 8.15 ± 0.37 vs. 9.10 ± 0.16%, p = 0.03). These individuals had a 1.84% (95% CI 0.64-3.04, p = 0.002) greater decrease in FMD over a 6-year interval between two adult follow-ups at mean ages 27 and 33 years. Childhood IRH was associated with increased asymmetrical dimethylarginine (ADMA) in adulthood (0.62 ± 0.01 vs. 0.59 ± 0.01 μmol/l, p = 0.04), adjusted for age, sex, adult body mass index, and serum creatinine. Early childhood IRH was associated with lower carotid distensibility levels (1.95 ± 0.06 vs. 2.09 ± 0.02%/10 mmHg, p = 0.02), but not with carotid intima-media thickness (0.601 ± 0.006 vs. 0.596 ± 0.003 mm). All findings remained unchanged after adjustments for age, sex and conventional cardiovascular risk factors in childhood or adulthood.
  
  
  CONCLUSIONS
  Infection-related hospitalisation in the pre-school period was associated with adverse adult atherosclerotic phenotypes and increased ADMA. Infection may contribute to causal pathways leading to the development of endothelial dysfunction and early atherosclerosis.
authors.affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital, 50 Flemington Road, Parkville 3052, Australia; Department of Paediatrics, University of Melbourne, Grattan Street, Melbourne, Victoria 3010, Australia; Department of Paediatrics, Monash University, 246 Clayton Road, Clayton, Victoria 3186, Australia. Electronic address: david.burgner@mcri.edu.au.
authors.forename: David P
authors.initials: DP
authors.lastname: Burgner
authors.affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital, 50 Flemington Road, Parkville 3052, Australia; Department of Paediatrics, University of Melbourne, Grattan Street, Melbourne, Victoria 3010, Australia.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Sabin
authors.affiliation: Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland; Menzies Institute for Medical Research, University of Tasmania, 17 Liverpool Street, Hobart, Tasmania 7000, Australia.
authors.forename: Costan G
authors.initials: CG
authors.lastname: Magnussen
authors.affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital, 50 Flemington Road, Parkville 3052, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Cheung
authors.affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital, 50 Flemington Road, Parkville 3052, Australia.
authors.forename: Cong
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Clinical Physiology, University of Tampere School of Medicine and Tampere University Hospital, Teiskontie 35, 33520 Tampere, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.affiliation: Department of Paediatrics, University of Tampere School of Medicine and Tampere University Hospital, Teiskontie 35, 33520 Tampere, Finland.
authors.forename: Nina
authors.initials: N
authors.lastname: Hutri-Kähönen
authors.affiliation: Department of Clinical Chemistry, University of Tampere School of Medicine and Tampere University Hospital, Teiskontie 35, 33520 Tampere, Finland; Fimlab Laboratories, University of Tampere School of Medicine and Tampere University Hospital, Teiskontie 35, 33520 Tampere, Finland.
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.affiliation: Hospital for Children and Adolescents, University of Helsinki, Stenböckinkatu 9, 00029 HUS Helsinki, Finland.
authors.forename: Eero
authors.initials: E
authors.lastname: Jokinen
authors.affiliation: Department of Clinical Physiology, Kuopio University Hospital and University of Eastern Finland, Kotkankallionkatu 14, 70600 Kuopio, Finland.
authors.forename: Tomi
authors.initials: T
authors.lastname: Laitinen
authors.affiliation: Department of Medicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland; Division of Medicine, Turku University Hospital, Kiinamyllynkatu 4-8, 20520 Turku, Finland.
authors.forename: Jorma S A
authors.initials: JS
authors.lastname: Viikari
authors.affiliation: Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland; Division of Medicine, Turku University Hospital, Kiinamyllynkatu 4-8, 20520 Turku, Finland.
authors.forename: Olli T
authors.initials: OT
authors.lastname: Raitakari
authors.affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital, 50 Flemington Road, Parkville 3052, Australia; Department of Medicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland; Division of Medicine, Turku University Hospital, Kiinamyllynkatu 4-8, 20520 Turku, Finland. Electronic address: mataju@utu.fi.
authors.forename: Markus
authors.initials: M
authors.lastname: Juonala
mesh_terms: D000328:Adult; D017668:Age of Onset; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D058070:Asymptomatic Diseases; D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000503:physiopathology; D002340:Carotid Artery Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology; D059168:Carotid Intima-Media Thickness; D002648:Child; D002675:Child, Preschool; D003141:Communicable Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000628:therapy; D005260:Female; D005387:Finland / Q000453:epidemiology; D006760:Hospitalization; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008297:Male; D010641:Phenotype; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D059289:Vascular Stiffness; D014664:Vasodilation; D055815:Young Adult
chemical_list: D015415:Biomarkers; C018524:N,N-dimethylarginine; D001120:Arginine
keywords: Asymmetric dimethylarginine; Atherosclerosis; Child; Infection