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CLINICAL RESEARCH: PEDIATRIC CARDIOVASCULAR DISEASE

Childhood Levels of Serum Apolipoproteins B and A-I Predict Carotid Intima-Media Thickness and Brachial Endothelial Function in Adulthood

The Cardiovascular Risk in Young Finns Study

Markus Juonala, MD, PhD^_*,_*, Jorma S.A. Viikari, MD, PhD^_*, Mika Kähönen, MD, PhD^¶,#, Tiina Solakivi, PhD^||, Hans Helenius, MSc, Antti Jula, MD, PhD^_**, Jukka Marniemi, PhD^_**, Leena Taittonen, MD, PhD^,, Tomi Laitinen, MD, PhD, Tapio Nikkari, MD, PhD^|| and Olli T. Raitakari, MD, PhD^,

^_* Department of Medicine, University of Turku, Turku, Finland
Department of Biostatistics, University of Turku, Turku, Finland
Department of Clinical Physiology, University of Turku, Turku, Finland
Cardiovascular Research Center, University of Turku, Turku, Finland
^|| Department of Medical Biochemistry, University of Tampere, Tampere, Finland
^¶ Department of Clinical Physiology, University of Tampere, Tampere, Finland
^# Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland
^_** Department of Health and Functional Capacity, National Public Health Institute, Turku, Finland
Department of Pediatrics, University of Oulu, Oulu, Finland
Vaasa Central Hospital, Vaasa, Finland
Department of Clinical Physiology, University of Kuopio, Kuopio, Finland.

Manuscript received February 6, 2008; revised manuscript received March 18, 2008, accepted March 18, 2008.

^_* Reprint requests and correspondence: Dr. Markus Juonala, P.O. Box 52, 20521 Turku, Finland. (Email: markus.juonala{at}utu.fi).

Objectives: The aim of this study was to determine whether apolipoproteins (apo) B and A-I measured in childhood and adolescence predict atherosclerosis in adulthood.

Background: Exposure to dyslipidemia in childhood predicts the development of atherosclerosis. Apolipoproteins B and A-I might be good markers of atherogenic dyslipidemia, but there is a paucity of information concerning their importance in childhood.

Methods: Apolipoproteins B and A-I, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, blood pressure, obesity, insulin, C-reactive protein, and smoking were assessed in 1980 and 2001 among 879 subjects in the Cardiovascular Risk in Young Finns Study (ages 3 to 18 years at baseline). Carotid artery intima-media thickness (IMT) and brachial artery flow-mediated dilation (FMD) were measured in 2001 at the age of 24 to 39 years.

Results: In subjects ages 12 to 18 years at baseline, apoB and apoB/apoA-I ratio were directly (p < 0.001) related and apoA-I was inversely (p = 0.01) related with adulthood IMT. In subjects ages 3 to 18 years at baseline, apoB (p = 0.02) and the apoB/apoA-I ratio (p < 0.001) were inversely related and apoA-I (p = 0.003) was directly related to adulthood FMD. These relations were not altered when the effects of nonlipid risk factors and adulthood apolipoproteins were taken into account. The apoB/apoA-I ratio measured in adolescence was superior to LDL/HDL ratio (c-values, 0.623 vs. 0.569, p = 0.03) in predicting increased IMT in adulthood (IMT 90th percentile and/or carotid plaque).

Conclusions: Apolipoproteins B and A-I measured in children and adolescents reflect a lipoprotein profile predisposing to the development of subclinical atherosclerosis in adulthood. These markers might have value in pediatric lipid risk assessment.

Key Words: apolipoprotein • flow-mediated dilatation • intima-media thickness

Abbreviations and Acronyms   apo = apolipoprotein   BMI = body mass index   CHD = coronary heart disease   CRP = C-reactive protein   CV = coefficient of variation   FMD = flow-mediated dilation   HDL = high-density lipoprotein   IMT = intima-media thickness   LDL = low-density lipoprotein   ROC = receiver-operating characteristic

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