APOE ε4 and ischemic heart disease in American Indian/Indigenous tribal Elders

Objective: American Indian/Indigenous (AI) populations have the highest rate of ischemic heart disease (IHD) of any racial or ethnic group in the United States. While modifiable cardiovascular risk factors represent a well-established source of elevated IHD in AI, little is known regarding genetic IHD influences, in particular APOE ε4, which has an ancestry-dependent prevalence and effect on human disease. We sought to quantify the prevalence and association between APOE ε4 and IHD in AI communities. Methods: We performed a cross-sectional, community-based study including tribal Elders (ages >54 years) at the Bois Forte Band of Chippewa in the state of Minnesota. We collected data pertaining to demographics, cardiovascular risk factors, APOE ε4 genotype, and ischemic heart disease (defined as history of myocardial infarction, coronary artery bypass graft, angiogram showing coronary artery disease, percutaneous transluminal coronary angioplasty, or thrombolytic therapy). Findings: One-hundred-eighty-one participants were included. Their median age and interquartile range were 67 (61, 73) years, AI ancestry was 75 % (50 %, 100 %), 126 (70 %) were females, 46 (25 %) were APOE ε4 heterozygous, and 5 (2.8 %) were APOE ε4 homozygous. Each APOE ε4 allele increased the odds of IHD in AI tribal Elders 2.38-fold (95 % CI: 0.94–6.89; p = 0.06), which is comparable to a two-point rise in hemoglobin A1C. Conclusions: APOE ε4 appears to play an important role in the risk of IHD in AI populations, given its high prevalence and strong association with IHD.