In humans, this same phenotype is vulnerable to plaque rupture, the cause of most heart attacks and strokes.21 Prior studies have shown that deletion of 11‐β‐hydroxysteroid dehydrogenase type 2 (11βHSD2) in ApoE−/− mice, which results in chronic cortisol‐mediated activation of MRs, promotes formation of larger plaques with a similar unstable phenotype.45 Because of significant hypertension in the 11βHSD2‐knockout mouse, the direct, blood pressure–independent effects of Aldo in this model are difficult to interpret. This evidence concerns the gene APOE and myocardial infarction.