Elevated Hemoglobin A1c Is Associated With Leaky Plaque Neovasculature as Detected by Dynamic Contrast-Enhanced Magnetic Resonance Imaging

Background: Patients with diabetes have accelerated atherosclerosis progression, but the underlying mechanisms are not fully understood. Dynamic contrast-enhanced magnetic resonance imaging has allowed in vivo characterization of plaque neovasculature, which plays a critical role in plaque progression. We aimed to evaluate the impact of diabetes on carotid plaque neovasculature as assessed by dynamic contrast-enhanced magnetic resonance imaging. Methods: Patients with recent ischemic stroke and ipsilateral carotid plaque underwent multicontrast magnetic resonance imaging for characterizing plaque morphology and dynamic contrast-enhanced magnetic resonance imaging for pharmacokinetic parameters of plaque neovasculature, including transfer constant (K-trans, reflecting flow, endothelial surface area, and permeability) and fractional plasma volume (nu(p)). Results: Sixty-five patients were enrolled, including 30 patients with diabetes (years since diagnosis: median 5.0 [interquartile range, [3.0-12.0]) and 35 patients without diabetes. Subjects with diabetes had a greater plaque burden and a higher prevalence of high-risk characteristics. Additionally, carotid plaques in the subjects with diabetes showed higher K-trans than those in the subjects without diabetes (0.100 +/- 0.048 min(-1) versus 0.067 +/- 0.042 min(-1), P=0.005) but nu(p) was numerically lower in the subjects with diabetes (5.2 +/- 3.7% versus 6.2 +/- 4.3%, P=0.31). The association of diabetes with high K-trans (beta=0.033, P=0.005) was independent of patient and plaque characteristics and remained largely intact after adjusting for serum lipids, glucose, or hs-CRP (high-sensitivity C-reactive protein). However, it became nonexistent after adjusting for hemoglobin A1c (beta=-0.010, P=0.49). Conclusions: Dynamic contrast-enhanced magnetic resonance imaging of carotid plaques suggested that plaque neovasculature in patients with diabetes is leaky, indicating enhanced capability of bringing blood constituents and facilitating extravasation of inflammatory cells, erythrocytes, and plasma proteins. Leaky plaque neovasculature correlated with hemoglobin A1c and may play a role in accelerated atherosclerosis progression in diabetes.