Skin autofluorescence, a non-invasive marker for AGE accumulation, is associated with the degree of atherosclerosis.

INTRODUCTION: Advanced glycation endproducts (AGEs) may be involved in the development of atherosclerosis, beyond diabetes and renal disease. Skin autofluorescence (AF) is a non-invasive marker for AGEs. We examined whether skin AF is increased in (subclinical) atherosclerosis and associated with the degree of atherosclerosis independent of diabetes and renal function. METHODS: A cross-sectional study of 223 patients referred for primary (n = 163) or secondary (n = 60) prevention between 2006 and 2012 was performed. Skin AF was measured using the AGE-Reader. Ultrasonography was used to assess plaques in carotid and femoral arteries and computed tomography for the calculation of the coronary artery calcium score (CACS; in primary prevention only). Primary prevention patients were divided into a group with subclinical atherosclerosis defined as >1 plaque or CACS>100 (n = 67; age 53 year [interquartile range 48-56]; 49% male) and without (controls; 96; 43 [38-51]; 55%). Secondary prevention were patients with peripheral arterial disease (60; 64 [58-70]; 73%). RESULTS: Skin AF was higher in subclinical and clinical atherosclerosis compared with controls (skin AF 2.11 [interquartile range 1.83-2.46] and 2.71 [2.15-3.27] vs. 1.87 [1.68-2.12] respectively; P = 0.005 and <0.001). In a multivariate analysis, the association of skin AF with the atherosclerosis categories was independent of age, sex, diabetes, presence of the metabolic syndrome, Framingham Risk Score, and renal function. Skin AF correlated with most cardiovascular risk factors, Framingham risk score, and IMT and CACS. CONCLUSIONS: Skin AF is increased in documented subclinical and clinical atherosclerosis, independent of known risk factors such as diabetes and renal disease. These data suggest that AGEs may be associated with the burden of atherosclerosis and warrant a prospective study to investigate its clinical usability as a risk assessment tool for primary prevention.

Coronary artery calcification score and carotid intima­media thickness in patients with hemophilia.

BACKGROUND/OBJECTIVES: The traditional view that patients with hemophilia are protected against cardiovascular disease is under debate. The aim of the present study was to evaluate the presence and extent of atherosclerosis by coronary artery calcification score (CACS) and carotid intima media thickness (IMT) in patients with hemophilia, and to evaluate their cardiovascular risk profile. METHODS: Sixty-nine patients (51 with hemophilia A; 18 with hemophilia B) were studied [median age: 52 years (interquartile range [IQR] 43­64)]. Cardiovascular risk factors and prior major adverse cardiovascular events (MACEs) were recorded. CACS was derived from electron-beam or dual-source computed tomography, and carotid IMT was assessed by ultrasound measurements and compared with age-specific reference values. RESULTS: The median CACS in all patients was 35 (IQR 0­110) and the geometric mean IMT was 0.80 mm (95% confidence interval [CI] 0.76­0.84); neither was different from the reference values. Patients with a previous MACE (n = 9) had significantly higher CACS and IMT than patients without a previous MACE:CACS median 1013 (IQR 530­1306) vs. 0 (IQR 0­67), and IMT geometric mean 1.09 mm (95% CI 0.95­1.26) vs. 0.76 mm (95% CI 0.73­0.79), both P < 0.001. A higher calculated 10-year cardiovascular risk was related to higher IMT and CACS. CONCLUSION: Patients with hemophilia are not protected against the development of atherosclerosis as measured by CACS and IMT. The extent of atherosclerosis is related to the traditional cardiovascular risk factors. This suggests that traditional cardiovascular risk factors should be monitored and treated in patients with hemophilia.