Association between plasma total homocysteine and parental history of cardiovascular disease in children with familial hypercholesterolemia.

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 rho, -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] micromol/L versus 5.6 [4.7, 6.8] micromol/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.