Background: Carotid intima-media thickness (cIMT) is commonly used as a surrogate for atherosclerosis. Since cIMT is correlated with hypertension and microalbuminuria, we tested the hypothesis that there is a genetic basis for the observed relationship between cIMT, blood pressure (BP), and renal function within high risk families.
Methods: Six hundred and three nondiabetic individuals from 149 Hispanic American families (HA) were ascertained via a hypertensive parent. Phenotyping included cIMT, BP, anthropometrics, and renal function, which was assessed by urine microalbumin, blood urea nitrogen (BUN), serum creatinine (Cr), and Cr clearance (Ccr). A variance components approach was used to estimate trait heritabilities and decompositions of their phenotypic correlations.
Results: Significant heritabilities (P<0.0001 for each) were found for cIMT, body mass index, BP, and the renal function traits. There were significant phenotypic correlations within family members, with positive correlations between cIMT and systolic BP (SBP), and urine microalbumin and Ccr, and negative correlations among cIMT, BUN, and Cr; these remained significant after correction for BP, but not after correction for urine microalbumin. Partitioned into genetic and environmental correlations, genetic correlations were significant between cIMT and each of SBP, urine microalbumin, Ccr, BUN, and Cr, respectively, while there were significant environmental correlations between cIMT and each of BUN, Cr, and Ccr. The genetic and environmental correlations were unchanged when adjusted for BP, but were no longer significant when adjusted for urine microalbumin.
Conclusions: There is substantial genetic contribution to SBP, renal function, and cIMT in these high risk Hispanic families. Subclinical atherosclerosis shares common genetic determinants with SBP and, independently, with measures of renal function.