(Circulation. 1997;96:1803-1808.)
© 1997 American Heart Association, Inc.
Articles |
Association Between Plasma Total Homocysteine and Parental History of Cardiovascular Disease in Children With Familial Hypercholesterolemia
From the Lipid Clinic, Medical Department A, National Hospital, Oslo (S.T.), and the Department of Clinical Biology, Division of Pharmacology, University of Bergen, Bergen (H.R., P.M.U.), Norway
Correspondence to Dr Serena Tonstad, Preventive Cardiology, Ulleval Hospital, Oslo N-0407, Norway. E-mail serena.tonstad{at}rh.uio.no
Background Recently, we reported a relation between plasma total homocysteine (tHcy) in children and cardiovascular disease (CVD) in their male relatives, suggesting that tHcy may partly explain the increased risk related to a family history of CVD. Because individuals with familial hyperlipidemias have an exceptionally high risk of premature CVD, we explored the relationship between tHcy and parental history of CVD in children with familial hypercholesterolemia (FH).
Methods and Results Study subjects were 91 boys and 64
girls (age range, 7 to 17 years) with FH who were treated with a
standard lipid-lowering diet at a tertiary care lipid clinic. We
conducted a cross-sectional analysis of demographics, the diet,
tHcy level, presence of the C677T mutation in the
methylenetetrahydrofolate reductase
gene (a common genetic cause of elevated tHcy) in children, and the
prevalence of parental CVD. tHcy increased after puberty and was
inversely related to parental educational level. Intakes of folate,
vitamin C, and fruits and vegetables were inversely associated with
tHcy, as were serum folate and vitamin B12 (Spearman's
, -0.2 to -0.4; P<.05). tHcy was increased in children
whose parent with FH had experienced CVD compared with children without
parental CVD (median [interquartile range], 6.6 [5.3, 8.0]
µmol/L versus 5.6 [4.7, 6.8] µmol/L; P=.01). This
difference remained significant in multivariate
regression analysis. Homozygosity for the C677T mutation was
associated with a higher tHcy level and tended to be more frequent in
the group with than in the group without a parental history of CVD
(18% versus 8%; P=.07).
Conclusions These findings suggest that a moderately elevated tHcy level may partly account for the contribution of the family history to risk of CVD in FH. Dietary recommendations for FH should include nutrients that affect homocysteine metabolism.
Key Words: genetics • homocysteine • risk factors • pediatrics • hypercholesterolemia
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