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Background  Local ancestry in relation to clinical cardiovascular events ( CVEs ) among African Americans can provide insight into their genetic susceptibility to the disease.    Methods and Results  We examined local European ancestry ( LEA ) association with  CVEs  among 3000 African Americans from the Atherosclerosis Risk in Communities Study ( ARIC ). We estimated  LEA  using  L ocal  A ncestry Inference in ad M ixed  P opulations using  L inkage  D isequilibrium ( LAMP ‐ LD ) and examined its association with myocardial infarction, stroke, coronary heart disease and its composite and cardiovascular disease composite using logistic regression. Genome‐wide significance was achieved by 121  LEA  regions in relation to  myocardial infarction  and 2 in relation to the cardiovascular disease composite. The  LEA  region downstream of 4q32.1 was significantly associated with 2 times higher odds of myocardial infarction ( P =1.45×10 −6 ). The  LEA  region upstream of 6q11.1 was associated with 0.37 times lower odds of fatal coronary heart disease ( P =7.34×10 −4 ), whereas the  LEA  region downstream of 21q21.1 was associated with 1.55 times higher odds of composite coronary heart disease ( P= 3.45×10 −4 ). Association of  LEA  with stroke was observed in the region upstream of 6p22.3 with a 1.57 times higher odds of stroke ( P =9.69×10 −4 ). Likewise, the  LEA  region on 4q32.3 was associated with a 1.53 times higher odds of composite cardiovascular disease ( P= 3.04×10 −4 ). We also found 20 of the  LEA  regions at previously significant cardiovascular disease single‐nucleotide polymorphisms to be associated with  CVE  in our study.    Conclusions  Future studies are needed to replicate and/or determine the causal variants driving our associations and explore clinical applications for those consistently associated with  CVEs .

Local Ancestry and Clinical Cardiovascular Events Among African Americans From the Atherosclerosis Risk in Communities Study