Cerebral Small-Vessel Disease in Individuals with a Family History of Coronary Heart Disease: The Atherosclerosis Risk in Communities Study

Introduction: The degree to which a family history of coronary heart disease (FHCHD) is associated with silent cerebral small-vessel disease (cSVD) among healthy adults, independent of prevalent CHD and traditional risk factors, is unknown. Methods: The Atherosclerosis Risk in Communities (ARIC) study is a community-based cohort study with self-reported family history data and brain magnetic resonance imaging (ages 68-88). The association between markers of cSVD (lacunar infarcts and cerebral microbleeds), or log-transformed white matter hyperintensity (WMH) volume, and FHCHD, or the number of affected relatives was examined using separate adjusted logistic or linear regression models, respectively. Race interaction terms were evaluated. Results: Of 1,639 participants without prevalent CHD (76 +/- 5 years, 62% female, 29% black), 686 (42%) had FHCHD. There were higher odds of lacunar infarct (OR 1.40, 95% CI 1.07-1.84) among those with parental FHCHD and higher odds of microhemorrhages (lobar OR 1.86, 95% CI 1.13-3.06; subcortical OR 1.47, 95% CI 1.01-2.15) among those with sibling FHCHD. A greater number of any relative affected was associated with higher odds of lacunar infarct (OR 1.24, 95% CI 1.04-1.47) and lobar microhemorrhages (OR 1.31, 95% CI 1.05-1.64) but not subcortical microhemorrhages (OR 1.09, 95% CI 0.92-1.28). Odds of having a lacunar infarct were higher among blacks (p-interaction 0.04) with paternal FHCHD (OR 2.20, CI 1.35-3.58) than whites with paternal FHCHD (OR 1.17, CI 0.87-1.56). There was no association with WMH. Discussion/Conclusion: Markers of cSVD, specifically lacunar infarcts and microhemorrhages, appear to be associated with FHCHD, potentially representing shared mechanisms in different vascular beds, and perhaps a genetic propensity for vascular disease.