Abstract-The functional 5A/6A polymorphism of the stromelysin-1 promoter has been implicated as a potential genetic marker for the progression of angiographically determined atherosclerosis in patients with coronary artery disease. Recently, a novel interleukin-6 (IL-6) gene functional G/C polymorphism at Ϫ174 in the promoter has also been reported. In this study, we analyzed the relation of these two polymorphisms with carotid artery atherosclerosis in 109 randomly selected, middle-aged men without exercise-induced ischemia. Atherosclerosis was quantified as intimamedia thickness (IMT) by high-resolution ultrasonography. Univariately, stromelysin genotype was significantly (Pϭ0.015) associated with IMT, and this relation remained (Pϭ0.033) after adjustments for age, cardiorespiratory fitness, body mass index, smoking, LDL cholesterol, and systolic blood pressure and for sonographers. The 5A/6A polymorphism independently explained 7% of the variance in carotid bifurcation IMT. The IL-6 polymorphism was also significantly associated (Pϭ0.036) with increased IMT, with men homozygous for the G allele having IMT that was 11% greater than men homozygous for the C allele. Men who were homozygous for both the 6A and G alleles had an covariate adjusted IMT that was 36% greater than men who were homozygous for neither allele (PϽ0.003). These data suggest that genetic factors that predispose to reduced matrix remodeling (stromelysin 6A allele) and to increased inflammation (IL-6 G allele) combine to increase susceptibility for intima-media thickening in the carotid bifurcation, a predilection site for atherosclerosis. Key Words: stromelysin-1 Ⅲ interleukin-6 Ⅲ DNA polymorphism Ⅲ B-mode ultrasonography Ⅲ carotid atherosclerosis Ⅲ population sample

cross-sectional study, central and peripheral arteries were investigated noninvasively in high-performance athletes and in untrained subjects. The diastolic inner vessel diameter (D) of the thoracic and abdominal aorta, the subclavian artery (Sub), and common femoral artery (Fem) were determined by duplex sonography in 18 able-bodied professional tennis players, 34 able-bodied elite road cyclist athletes, 26 athletes with paraplegia, 17 below-knee amputated athletes, and 30 able-bodied, untrained subjects. The vessel cross-sectional areas (CSA) were set in relation to body surface area (BSA), and the cross-section index (CS-index ϭ CSA/BSA) was calculated. Volumetric blood flow was determined in Sub and Fem via a pulsed-wave Doppler system and was set in relation to heart rate to calculate the stroke flow. A significantly increased D of Sub was found in the racket arm of able-bodied tennis players compared with the opposite arm (19%). Fem of able-bodied road cyclist athletes and of the intact limb in below-knee amputated athletes showed similar increases. D of Fem was lower in athletes with paraplegia (37%) and in below-knee amputated athletes proximal to the lesion (21%) compared with able-bodied, untrained subjects; CS-indexes were reduced 57 and 31%, respectively. Athletes with paraplegia demonstrated a larger D (19%) and a larger CS-index in Sub (54%) than able-bodied, untrained subjects. No significant differences in D and CS-indexes of the thoracic and abdominal aorta were found between any of the groups. The changes measured in Sub and Fem were associated with corresponding alterations in blood flow and stroke flow in all groups. The study suggests that the size and blood flow volume of the proximal limb arteries are adjusted to the metabolic needs of the corresponding extremity musculature and underscore the impact of exercise training or disuse on the structure and the function of the arterial system. tennis players; road cyclists; vascular remodeling; duplex sonography IN HIGH-PERFORMANCE ABLE-BODIED athletes, a 20-25% increase in the left ventricular diameter and a 70-80% increase in the left ventricular muscle mass compared with untrained subjects is considered the physiological limit (28) of left ventricular adaptation. Training-induced cardiac adaptations, the so-called athlete's heart, are not as profound in high-performance disabled athletes (8,17). Along with a reduced training energy expenditure, this can be attributed to the smaller skeletal muscle mass involved in exercise training.The changes in arterial vessels resulting from physical training were influenced similar to training-induced cardiac adaptations by the type, amount, and intensity of the muscular exertions (14). In animals that had undergone regular muscular exercise training, training-induced functional and dimensional adaptations of the coronary vascular system have been found (21, 35). Exercise-induced functional changes in vascular function have also been observed in humans. The present available data suggest that these vasc...

Abstract-Aging of the common carotid artery (CCA) is associated with different principal structural, functional, and hemodynamic changes, which are often influenced by several atherosclerotic risk factors, so that it is difficult to estimate the exclusive effect of aging on this process. Studies dealing with vascular aging of the CCA usually assess only single, dimensional, or functional parameters, although it is likely that there are interactions and probably differences between them. Moreover, regional vascular blood flow characteristics are often not taken into consideration. Therefore, the aim of the study was to assess the age-related multiparametric changes of the CCA properties with ultrasound in 69 male subjects between the ages of 16 and 75 (42.4Ϯ16.5 years), who were screened for the absence of major atherosclerotic risk factors or existing vascular disease. As a result, the intima media thickness (0.052 mm/10 y) and diastolic diameter (0.17 mm/10 y) increased nearly linearly with age (rϭ0. 60, PϽ0.001; and rϭ0.46, PϽ0.001, respectively). The absolute diastolic/systolic diameter change diminished by 0.10 mm/10 y (rϭϪ0.73, PϽ0.001) and peak expansion velocity dropped by 0.12 cm/s per 10 years (rϭϪ0.62, PϽ0.001) highly significantly with age. The peak blood flow velocity decreased continuously with age (rϭϪ0.67, PϽ0.00) by 9.3 cm/s per 10 years. According to multiple regression analysis, peak blood flow velocity seems to reflect the changes of several structural and functional parameters in one; intima-media thickness was determined by diastolic arterial diameter and age as independent variables. The data indicate that a multiparametric assessment may contribute to a better understanding of vascular aging and might be the basis for further studies to evaluate the association of atherosclerotic risk factors and/or major vascular disease with local changes in the CCA. Key Words: carotid artery Ⅲ aging Ⅲ arterial stiffness Ⅲ ultrasound V ascular aging is associated with different principal structural and functional changes; ie, intima-media thickening, 1,2 arterial dilation, 3,4 and the deterioration of elastic wall properties with vascular stiffening 5-7 belong to this process. Each of these has an impact on vascular blood flow and the local and/or systemic hemodynamics interact with the structure and function of the artery. For example, both the elevation of blood pressure and stroke volume increase the wall shear rate and may thus lead to a midterm increase in the thickness of the intima-media 8 or structural adaptation in the form of a greater vascular diameter. 9 Although these interactions are known, very few studies take all these structural, functional, and hemodynamic parameters into consideration, which might be of interest to enable a better understanding of the relation of aging to the named arterial changes. Furthermore, only little data exist on the differences in the progression of these alterations.It is well known that atherosclerotic risk factors such as a high cholesterol level, hyperten...

Commercially available health technologies such as smartphones and smartwatches, activity trackers and eHealth applications, commonly referred to as wearables, are increasingly available and used both in the leisure and healthcare sector for pulse and fitness/activity tracking. The aim of the Position Paper is to identify specific barriers and knowledge gaps for the use of wearables, in particular for heart rate and activity tracking, in clinical cardiovascular healthcare to support their implementation into clinical care. The widespread use of heart rate and fitness tracking technologies provides unparalleled opportunities for capturing physiological information from large populations in the community, which has previously only been available in patient populations in the setting of healthcare provision. The availability of low-cost and high-volume physiological data from the community also provides unique challenges. While the number of patients meeting healthcare providers with data from wearables is rapidly growing, there are at present no clinical guidelines on how and when to use data from wearables in primary and secondary prevention. Technical aspects of heart rate tracking especially during activity need to be further validated. How to analyze, translate, and interpret large datasets of information into clinically applicable recommendations needs further consideration. While the current users of wearable technologies tend to be young, healthy and in the higher sociodemographic strata, wearables could potentially have a greater utility in the elderly and higher risk population. Wearables may also provide a benefit through increased health awareness, democratization of health data and patient engagement. Use of continuous monitoring may provide opportunities for detection of risk factors and disease development earlier in the causal pathway, which may provide novel applications in both prevention and clinical research. However, wearables may also have potential adverse consequences due to unintended modification of behaviour, uncertain use and interpretation of large physiological data, a possible increase in social inequality due to differential access and technological literacy, challenges with regulatory bodies and privacy issues. In the present position paper, current applications as well as specific barriers and gaps in knowledge are identified and discussed in order to support the implementation of wearable technologies from gadget-ology into clinical cardiology.

Aims/hypothesis IL-6 is a cytokine with various effects on metabolism. In mice, IL-6 improved beta cell function and glucose homeostasis via upregulation of glucagon-like peptide 1 (GLP-1), and IL-6 release from muscle during exercise potentiated this beneficial increase in GLP-1. This study aimed to identify whether exercise-induced IL-6 has a similar effect in humans. Methods In a multicentre, double-blind clinical trial, we randomly assigned patients with type 2 diabetes or obesity to intravenous tocilizumab (an IL-6 receptor antagonist) 8 mg/kg every 4 weeks, oral sitagliptin (a dipeptidyl peptidase-4 inhibitor) 100 mg daily or double placebos (a placebo saline infusion every 4 weeks and a placebo pill once daily) during a 12 week training intervention. The primary endpoints were the difference in change of active GLP-1 response to an acute exercise bout and change in the AUC for the concentration-time curve of active GLP-1 during mixed meal tolerance tests at baseline and after the training intervention. Results Nineteen patients were allocated to tocilizumab, 17 to sitagliptin and 16 to placebos. During the acute exercise bout active GLP-1 levels were 26% lower with tocilizumab (multiplicative effect: 0.74 [95% CI 0.56, 0.98], p = 0.034) and 53% higher with sitagliptin (1.53 [1.15, 2.03], p = 0.004) compared with placebo. After the 12 week training intervention, the active GLP-1 AUC with sitagliptin was about twofold that with placebo (2. 03 [1.56, 2.62]; p < 0.001), while GLP-1 AUC values showed a small non-significant decrease of 13% at 4 weeks after the last tocilizumab infusion (0.87 [0.67, 1.12]; p = 0.261). Conclusions/interpretation IL-6 is implicated in the regulation of GLP-1 in humans. IL-6 receptor blockade lowered active GLP-1 levels in response to a meal and an acute exercise bout in a reversible manner, without lasting effects beyond IL-6 receptor blockade. Trial registration Clinicaltrials.gov NCT01073826.