Peripheral artery disease (PAD) is the atherosclerosis of lower extremity arteries and is also associated with atherothrombosis of other vascular beds, including the cardiovascular and cerebrovascular systems. The presence of diabetes mellitus greatly increases the risk of PAD, as well as accelerates its course, making these patients more susceptible to ischemic events and impaired functional status compared to patients without diabetes. To minimize these cardiovascular risks it is critical to understand the pathophysiology of atherosclerosis in diabetic patients. This, in turn, can offer insights into the therapeutic avenues available for these patients. This article provides an overview of the epidemiology of PAD in diabetic patients, followed by an analysis of the mechanisms by which altered metabolism in diabetes promotes atherosclerosis and plaque instability. Outcomes of PAD in diabetic patients are also discussed, with a focus on diabetic ulcers and critical limb ischemia.

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Background Cardiovascular disease is an important cause of morbidity and mortality in sickle cell disease (SCD). We sought to characterize sickle cell cardiomyopathy using multi-modality non-invasive cardiovascular testing and identify potential causative mechanisms. Methods and Results Stable adults with SCD (n=38) and healthy controls (n=13) prospectively underwent same day multi-parametric cardiovascular magnetic resonance (cine, T2* iron, vasodilator first pass myocardial perfusion, and late gadolinium enhancement (LGE) imaging), transthoracic echocardiography, and applanation tonometry. Compared to controls, patients with SCD had severe dilation of the left ventricle (124±27 vs 79±12 ml/m2), right ventricle (127±28 vs 83±14 ml/m2), left atrium (65±16 vs 41±9 ml/m2), and right atrium (78±17 vs 56±17 ml/m2), p<0.01 for all. SCD patients also had a 21% lower myocardial perfusion reserve index than control subjects (1.47±0.34 vs 1.87±0.37, p=0.034). A significant subset of SCD patients (25%) had evidence of LGE while only one patient had evidence of myocardial iron overload. Diastolic dysfunction was present in 26% of SCD patients compared to 8% in controls. Estimated filling pressures (E/e’, 9.3±2.7 vs 7.3±2.0, p=0.0288) was higher in SCD patients. Left ventricular dilation and the presence of LGE were inversely correlated to hepatic T2* times (i.e. hepatic iron overload due to frequent blood transfusions, p<0.05 for both); whereas, diastolic dysfunction and increased filling pressures were correlated to aortic stiffness (augmentation pressure and index, p<0.05 for all). Conclusions Sickle cell cardiomyopathy is characterized by 4-chamber dilation and in some patients myocardial fibrosis, abnormal perfusion reserve, diastolic dysfunction, and only very rarely myocardial iron overload. Left ventricular dilation and myocardial fibrosis are associated with increased blood transfusion requirements while left ventricular diastolic dysfunction is predominantly correlated with increased aortic stiffness.

When used to treat complex ISR, including in-stent occlusions, laser atherectomy with adjunctive balloon angioplasty may be associated with improved patency.