Progression of asymptomatic peripheral artery disease over 1 year.

The pathophysiology and time course of an individual converting from asymptomatic peripheral artery disease (PAD) to symptomatic claudication is unclear. The objectives of this study were: (1) to characterize the extent of atherosclerotic disease in individuals with an abnormal ankle-brachial index (ABI), but without claudication; and over 1 year of follow-up to (2) evaluate the progression of PAD using ultrasound imaging, (3) determine changes in the ABI and leg pain symptoms, and (4) correlate PAD progression with changes in the ABI and leg symptoms. We hypothesized that PAD progression would be associated with the development of claudication and changes in the ABI, 6-minute walk distance (6-MWD), and walking quality of life. Individuals with a reduced ABI but without typical intermittent claudication noted on community screening were invited to undergo baseline and 1-year follow-up assessment, including duplex ultrasound. The initial and repeat evaluations included measurement of the ABI, lower extremity duplex arterial mapping, and assessment of leg pain and functional status. Of the 50 people studied, 44 (88%) had significant atherosclerotic lesions in the lower extremity arteries, affecting 80 legs. A total of 33 of 50 individuals (66%) returned for the 1-year follow-up visit. On ultrasound examination, two of 18 normal legs developed PAD, and in 48 legs with PAD at baseline, 17 legs (35%) developed new or progressive lesions. Thirteen legs developed new claudication. Overall, there was no significant worsening in the ABI, 6-MWD, or the Walking Impairment Questionnaire (WIQ). However, legs with new lesions or lesion progression were significantly more likely to develop claudication, and the 13 legs (seven subjects) developing claudication showed a significant decline in the 6-MWD. In conclusion, these data indicate that a significant number of people with asymptomatic PAD show progression over 1 year, that such individuals are more likely to develop claudication, and that those developing claudication have a significant decrease in their 6-MWD.

Effect of darbepoetin alfa on endothelial progenitor cells and vascular reactivity in chronic kidney disease.

Endothelial progenitor cells (EPCs) are thought to be important for maintaining normal vascular function. We conducted a prospective study evaluating the effect of the erythropoiesis-stimulating agent darbepoetin alfa on EPCs and vascular function in patients with chronic kidney disease (CKD), with or without diabetes. Thirty subjects with CKD (20 subjects with type II diabetes mellitus and 10 without diabetes mellitus) received weekly subcutaneous administration of darbepoetin alfa for 4 weeks. EPCs were measured at baseline and 2 and 4 weeks after drug administration. Vascular function was measured with brachial ultrasound and cell activity was measured with a cell proliferation assay. Cells expressing CD133, CD34, CD146 and CD146/31 were significantly elevated (all p < 0.05), flow-mediated vasodilatation increased 2.1%, 95% CI: (0.4%, 3.8%) and colony-forming units increased twofold, 95% CI: (1.7, 2.3) after 4 weeks of treatment with darbepoetin alfa. Subjects with diabetes exhibited an increase in a subset of EPCs (CD133( +) and 34(+), p < 0.01 and p = 0.06, respectively), vasodilatation and proliferation. In conclusion, the administration of darbepoetin alfa for 4 weeks increased a subset of EPCs, improved endothelial function and increased cell proliferation, including those with diabetes, which is consistent with a favorable improvement in vascular health.

Relationship of microparticles to progenitor cells as a measure of vascular health in a diabetic population.

OBJECTIVE: Quantitative measures are needed to identify diabetic patients at higher risk for CV events. Cell-derived microparticles (MPs) are submicron membrane vesicles released from activated cells that are indicative of cell damage. Progenitor cells (PCs) including proangiogenic cells (PACs), often termed endothelial progenitor cells (EPCs), are mediators of reparative capacity. We examined whether the relationship of MPs to PCs/PACs could be used as an improved and clinically feasible index of vascular pathology. METHODS AND RESULTS: Plasma samples were collected from patients with early-stage (ES, Diagnosis < 1 year) and long-term (LT, Diagnosis > 5 years,) Type 2 diabetes and compared with age related healthy subjects (H). PC and MP subtypes were measured by a combination of flow cytometry and ELISA-based methods. The ratio of procoagulant MPs/CD34(+) PCs proved a valuable index to distinguish between subject groups (P = 0.01). This index of compromised vascular function was highest in the LT group despite intensive statin therapy and was more informative than a range of soluble protein biomarkers. CONCLUSIONS: This is the first report of a relationship between MPs and PCs in Type 2 diabetes. This ratio may provide a quantitative and clinically feasible measurement of vascular dysfunction and cardiovascular risk in patients with diabetes. © 2010 International Clinical Cytometry Society.

Evaluation of diabetic foot ulcer healing with hyperspectral imaging of oxyhemoglobin and deoxyhemoglobin.

OBJECTIVE: Foot ulceration remains a major health problem for diabetic patients and has a major impact on the cost of diabetes treatment. We tested a hyperspectral imaging technology that quantifies cutaneous tissue hemoglobin oxygenation and generated anatomically relevant tissue oxygenation maps to assess the healing potential of diabetic foot ulcers (DFUs). RESEARCH DESIGN AND METHODS: A prospective single-arm blinded study was completed in which 66 patients with type 1 and type 2 diabetes were enrolled and followed over a 24-week period. Clinical, medical, and diabetes histories were collected. Transcutaneous oxygen tension was measured at the ankles. Superficial tissue oxyhemoglobin (oxy) and deoxyhemoglobin (deoxy) were measured with hyperspectral imaging from intact tissue bordering the ulcer. A healing index derived from oxy and deoxy values was used to assess the potential for healing. RESULTS: Fifty-four patients with 73 ulcers completed the study; at 24 weeks, 54 ulcers healed while 19 ulcers did not heal. When using the healing index to predict healing, the sensitivity was 80% (43 of 54), the specificity was 74% (14 of 19), and the positive predictive value was 90% (43 of 48). The sensitivity, specificity, and positive predictive values increased to 86, 88, and 96%, respectively, when removing three false-positive osteomyelitis cases and four false-negative cases due to measurements on a callus. The results indicate that cutaneous tissue oxygenation correlates with wound healing in diabetic patients. CONCLUSIONS: Hyperspectral imaging of tissue oxy and deoxy may predict the healing of DFUs with high sensitivity and specificity based on information obtained from a single visit.

Effect of statin treatment on aortic valve and coronary artery calcification.

BACKGROUND AND AIM OF THE STUDY: Conflicting data exist regarding statins and the progression of aortic valve disease. Hence, further information is required to determine if statin treatment has a beneficial effect on aortic valve calcification, and whether the inflammatory status of the patient affects aortic valve disease progression. The study aim was to evaluate the concomitant effect of statin treatment on aortic valve and coronary artery calcification and to compare results with the inflammatory status of the patient. METHODS: Sixty-one patients with moderate to severe aortic stenosis (AS) were enrolled in this single-center, prospective observational study evaluating progression of aortic valve calcification. Patients underwent baseline and one-year echocardiography and electron-beam computed tomography. Blood samples were withdrawn at baseline and at one year for measurement of inflammatory biomarkers. RESULTS: There was no significant reduction in calcium accumulation in the aortic valve of the statin group compared to the non-statin group, but there was trend towards less progression of calcification for the statin group. A significant inhibition of the coronary artery calcification volume score was observed for the statin group compared to the non-statin group. On echocardiography, statin treatment had no significant impact on aortic valve stenosis. Patients with serum LDL level >130 mg/dl showed less progression of coronary artery calcification when treated with statin drugs. The level of high-sensitivity C-reactive protein (hsCRP) significantly correlated with the progression of calcification for both the aortic valve and coronary arteries. CONCLUSION: Whilst there was no significant benefit of statin treatment on aortic valve calcification over one year, there was a decreased progression of coronary artery calcification. The baseline level of hsCRP was predictive of progression of both aortic valve and coronary artery calcification, and may identify a high-risk population requiring aggressive control, either with statins or emerging drugs targeted at the inflammatory process of atherosclerosis.

Aortic valve calcium content does not predict aortic valve area.

BACKGROUND AND AIM OF THE STUDY: Aortic stenosis (AS) is a common clinical problem which frequently necessitates aortic valve replacement (AVR). The traditional view of progressive AS is a 1:1 inverse relationship between valve calcium content and aortic valve area (AVA). However, this assumption has been based on subjective estimates of calcification on chest X-radiographic images. The study aim was to evaluate the relationship between AVA as measured with echocardiography compared to calcium quantification using electron beam computed tomography (EBT). METHODS: Sixty-one patients with an AVA between 0.7 and 2.0 cm2 underwent an EBT scan to evaluate the aortic valve calcium content. RESULTS: The mean (+/- SD) aortic valve Agatston calcium score was 1,458.4 +/- 1,362.2, and for the aortic valve volume score was 1,178.8 +/- 1,066.0. The aortic valve Agatston score did not correlate strongly with AVA (r = -0.34, 95% CI -0.54, -0.09; p = 0.007). The data pattern appeared curvilinear, with the poorest correlation noted for those patients with moderate and severe aortic valve calcification. CONCLUSION: The study findings support the hypothesis that the aortic valve orifice area decreases not only due to calcium accumulation but also to sclerotic processes.