Relation of total homocysteine and lipid levels in children to premature cardiovascular death in male relatives

We assessed the relative importance of lipid, apo B, lipoprotein(a) [Lp(a)], and total homocysteine (tHcy) levels in children in relation to premature cardiovascular disease in family members. Parents of 381 girls and 375 boys age 8-12 y completed family history questionnaires. Nonfasting serum lipids and lipoproteins and plasma tHcy and cysteine levels were measured in the children. Serum folate and vitamin B-12 levels were determined in a random subsample of 23% of the children, who participated in a food frequency interview. Children whose parents reported hypercholesterolemia had higher total and non-HDL cholesterol and apo B levels than the rest, but these levels were not associated with cardiovascular disease. tHcy levels were similar in girls and boys. tHcy was higher in children whose father, grandfather, or uncle died at age less than or equal to 55 y of myocardial infarction or sudden cardiac arrest (n = 42) than in control children [5.92 mu mol/L (95% confidence interval [CI] of 5.47-6.36) versus 5.25 mu mol/L (95% CI, 5.16-5.34)], also after adjustment for socioeconomic group. Intake and serum levels of vitamin B-12 and folate were within recommended or reference ranges. In a stepwise multiple regression analysis, serum folate (negative correlation), plasma creatinine, and sugar intake as percent of dietary energy (positive correlations) were significantly associated with tHcy (multiple r = 0.44, adjusted r(2) = 18%; 95% CI, 5-30%). Our data show that a modest elevation in tHcy in children was related to premature cardiovascular death in their male relatives and may partly account for the contribution of family history to risk of cardiovascular disease. tHcy may be modifiable through the diet, even in children with apparently adequate vitamin nutriture.