Hyperhomocyst(e)inemia in Utah siblings with early coronary disease

Abstract

To test the hypothesis that plasma homocyst(e)ine (H|e|) level is a risk factor for early familial coronary heart disease (EFCHD), H(e) was measured in frozen samples from 33 men and 4 women with EFCHD and in 30 male and 18 female control participants matched for age and sex from the University of Utah Cardiovascular Genetics Research Clinic, Salt Lake City, Utah. To test for familial correlation, these participants were selected to include 13 males sibling pairs with EFCHD, 13 male sibling pairs as control subjects, and 13 spouse pairs as control subjects (all matched for age). Compared with control subjects, mean H(e) levels were significantly higher in persons with EFCHD for both men (14.31 vs. 11.09 nmol/mL; P=0.022) and women (9.51 vs 7.40; P=0.020). Most of the difference came from a few cases in 3 EFCHD sibling pairs. This observation was confirmed by a commingling analysis, which detected significant bimodality of plasma H(e) levels among the men with EFCHD (P=0.02). One sibling pair with early coronary heart disease despite normal plasma lipids, lipoproteins, and apolipoproteins, showed concordant elevations of H(e) levels greater than any levels seen among control subjects. Strong familial correlation of plasma H(e) was observed among all 26 male sibling pairs (r=0.52; P<0.01) and was present separately in male siblings with EFCHD (r=0.44) and control siblings (r=0.60). There was no significant familial correlation in spouse pairs (r=-0.15, NS). H(e) was an independent predictor of EFCHD (P=0.014) in a multivariate analysis of the men that included smoking, blood lipids, anthropometrics, and presence or absence of diabetes as other potential predictors of EFCHD. These data suggest that hyperhomocyst(e)inemia is an inherited abnormality that might explain some occurrence of early familial coronary heart disease.