Epoxyeicosatrienoic Acids (EETs) are cytochrome P450 derivatives of arachidonic acid that have multiple biological activities, including anti-inflammatory, vasodilatory and platelet anti-aggregation. Additionally, manipulation of EET levels in animal studies suggests a protective role in diabetes. Whether EET levels are related to risk of diabetes and cardiovascular complications of diabetes in humans is largely unknown. We measured 4 species of EET in fasting plasma samples from the Cardiovascular Health Study, a cohort of older adults. Using Cox regression models, we examined the associations of baseline EET levels with 1) risk of incident diabetes and 2) risk of incident myocardial infarction and stroke among participants with diabetes. Among 3222 participants without diabetes, increased levels of each plasma EET were associated with greater risk of diabetes (Table). Among participants with diabetes, increased EETs levels were associated with reduced risk of myocardial infarction but increased risk of stroke (Table). The study findings suggest that circulating EETs are not protective of diabetes in humans, and higher levels in the context of diabetes, may have mixed consequences on cardiovascular complications.
R.N. Lemaitre: None. P.N. Jensen: None. M.B. Zeigler: None. A.M. Fretts: None. C. Sitlani: None. I.B. King: None. N. Sotoodehnia: None. B. McKnight: None. R.A. Totah: None.
National Institutes of Health