ASSOCIATION BETWEEN PLASMA TOTAL HOMOCYSTEINE AND PARENTAL HISTORY OFCARDIOVASCULAR-DISEASE IN CHILDREN WITH FAMILIAL HYPERCHOLESTEROLEMIA

Background Recently, we reported a relation between plasma total homoc ysteine (tHcy) in children and cardiovascular disease (CVD) in their m ale relatives, suggesting that tHcy may partly explain the increased r isk related to a family history of CVD. Because individuals with famil ial 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 Resul ts 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 ter tiary care lipid clinic. We conducted a cross-sectional analysis of de mographics, the diet, tHcy level, presence of the C677T mutation in th e methylene tetrahydrofolate 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 educatio nal level. Intakes of folate, vitamin C, and fruits and vegetables wer e inversely associated with tHcy, as were serum folate and vitamin B-1 2 (Spearman's rho, -0.2 to -0.4; P<.05). tHcy was increased in childre n whose parent with FH had experienced CVD compared with children with out parental CVD (median [interquartile range], 6.6 [5.3, 8.0] mu mol/ L versus 5.6 [4.7, 6.8] mu mol/L; P=.01). This difference remained sig nificant in multivariate regression analysis. Homozygosity for the C67 7T mutation was associated with a higher tHcy level and tended to be m ore frequent in the group with than in the group without a parental hi story of CVD (18% versus 8%; P=.07). Conclusions These findings sugges t that a moderately elevated tHcy level may partly account for the con tribution of the family history to risk of CVD in FH. Dietary recommen dations for FH should include nutrients that affect homocysteine metab olism.