Early carotid atherosclerosis and family history of vascular disease: specific effects on arterial sites have implications for genetic studies.

Abstract

Carotid artery intima-media thickness (IMT) is an intermediate phenotype for atherosclerosis. In a community population (n=5400), we determined whether a parental history of myocardial infarction (MI) or stroke is associated with increased IMT and whether associations differ at specific sites in the carotid arterial tree. Using regression modeling, the proportion of IMT that remains unexplained after controlling for vascular risk factors was determined. A parental history of stroke was associated with both increased common carotid artery (CCA) and increased internal carotid artery (ICA)-IMT, but in young individuals (<or=60 years of age), the association was stronger with ICA-IMT, with an odds ratio (95% CI) for ICA-IMT in the highest quartile of 2.31 (1.67 to 3.21), P<0.001, compared with 1.53 (1.07 to 2.20), P=0.019, for CCA-IMT. In contrast, a parental history of MI was associated with increased CCA-IMT both overall and in young individuals but not with ICA-IMT, with an odds ratio (95% CI) for increased CCA-IMT of 2.51 (1.94 to 3.25), P<0.001, compared with 1.03 (0.78 to 1.35), P=0.861, for ICA-IMT. IMT has a significant familial component that is independent of conventional risk factors. Associations for stroke and MI differ at specific sites in the carotid arterial tree. Although commonly used aggregate CCA/ICA-IMT measures may be appropriate for candidate gene studies investigating stroke risk, these results suggest that CCA-IMT alone may be a better marker for MI risk.