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. The gene discussed is APOE; the disease is stroke disorder.