Elevated Fasting Plasma Cortisol Is Associated with Ischemic Heart Disease and Its Risk Factors in People with Type 2 Diabetes: The Edinburgh Type 2 Diabetes Study

Context: Increased activity of the hypothalamic-pituitary-adrenal (HPA) axis may underlie the metabolic syndrome, but whether circulating cortisol levels predict cardiovascular end points is less clear. People with type 2 diabetes are at increased cardiovascular disease risk and thus are suitable to study associations of plasma cortisol with cardiovascular risk. Objective: We aimed to assess whether altered HPA axis activity was associated with features of the metabolic syndrome and ischemic heart disease in people with type 2 diabetes. Design and Setting: We conducted a cross-sectional cohort study in the general community, including 919 men and women aged 67.9 (4.2) yr with type 2 diabetes (the Edinburgh Type 2 Diabetes Study). Intervention: We measured fasting morning plasma cortisol. Main Outcome Measurement: Associations between cortisol levels, features of the metabolic syndrome, obesity, and ischemic heart disease were determined. Results: Elevated plasma cortisol levels were associated with raised fasting glucose and total cholesterol levels (P < 0.001). These findings remained significant after adjustment for potential confounding factors (P < 0.001). Elevated cortisol levels were associated with prevalent ischemic heart disease (>800 vs. <600 nmol/liter; odds ratio, 1.58; P = 0.02). This association remained significant after adjustment for duration and control of diabetes and other cardiovascular risk factors (P = 0.03). Conclusions: The previously described associations between HPA axis activation and features of the metabolic syndrome are present among people with type 2 diabetes. Elevated plasma cortisol is also associated with a greater prevalence of ischemic heart disease, independent of conventional risk factors. Understanding the role of cortisol in the pathogenesis of ischemic heart disease merits further exploration. (J Clin Endocrinol Metab 95: 1602-1608, 2010)