Arno Schmidt-Trucksäss

The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation: Endorsed by the Association for Research into Arterial Structure and Physiology (ARTERY) Society

While risk scores are invaluable tools for adapted preventive strategies, a significant gap exists between predicted and actual event rates. Additional tools to further stratify the risk of patients at an individual level are biomarkers. A surrogate endpoint is a biomarker that is intended as a substitute for a clinical endpoint. In order to be considered as a surrogate endpoint of cardiovascular events, a biomarker should satisfy several criteria, such as proof of concept, prospective validation, incremental value, clinical utility, clinical outcomes, cost-effectiveness, ease of use, methodological consensus, and reference values. We scrutinized the role of peripheral (i.e. not related to coronary circulation) noninvasive vascular biomarkers for primary and secondary cardiovascular disease prevention. Most of the biomarkers examined fit within the concept of early vascular aging. Biomarkers that fulfill most of the criteria and, therefore, are close to being considered a clinical surrogate endpoint are carotid ultrasonography, ankle-brachial index and carotid-femoral pulse wave velocity; biomarkers that fulfill some, but not all of the criteria are brachial ankle pulse wave velocity, central haemodynamics/wave reflections and C-reactive protein; biomarkers that do no not at present fulfill essential criteria are flow-mediated dilation, endothelial peripheral arterial tonometry, oxidized LDL and dysfunctional HDL. Nevertheless, it is still unclear whether a specific vascular biomarker is overly superior. A prospective study in which all vascular biomarkers are measured is still lacking. In selected cases, the combined assessment of more than one biomarker may be required.

Stromelysin-1 and Interleukin-6 Gene Promoter Polymorphisms Are Determinants of Asymptomatic Carotid Artery Atherosclerosis

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 −174 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 intima-media thickness (IMT) by high-resolution ultrasonography. Univariately, stromelysin genotype was significantly (P =0.015) associated with IMT, and this relation remained (P =0.033) 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 (P =0.036) 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 (P <0.003). 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.

Using snakes to detect the intimal and adventitial layers of the common carotid artery wall in sonographic images

This study presents an innovative automatic system for detecting the intima-media complex of the far wall of the common carotid artery by applying the snake techniques. Cohens snake was modified and some criteria were added for our applications. In addition, the oscillating problem of using snakes was solved by properly choosing the time step from analysis of the frequency response of the filters. A time-diminishing gravity window, external forces, and a cost function assist the snake in selecting the optimal shape of intimal and adventitia layers. We compared the proposed snake and ziplock snake with respect to the manual extraction contour. The results show that the system can automatically detect the intimal and adventitial layers without any manual correction.

Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular risk factors: recommendations from the EACPR (Part II)

In a previous paper, as the first of a series of three on the importance of characteristics and modalities of physical activity (PA) and exercise in the management of cardiovascular health within the general population, we concluded that, in the population at large, PA and aerobic exercise capacity clearly are inversely associated with increased cardiovascular disease risk and all-cause and cardiovascular mortality and that a dose–response curve on cardiovascular outcome has been demonstrated in most studies. More and more evidence is accumulated that engaging in regular PA and exercise interventions are essential components for reducing the severity of cardiovascular risk factors, such as obesity and abdominal fat, high BP, metabolic risk factors, and systemic inflammation. However, it is less clear whether and which type of PA and exercise intervention (aerobic exercise, dynamic resistive exercise, or both) or characteristic of exercise (frequency, intensity, time or duration, and volume) would yield more benefit for each separate risk factor. The present paper, therefore, will review and make recommendations for PA and exercise training in the management of cardiovascular health in individuals with cardiovascular risk factors. The guidance offered in this series of papers is aimed at medical doctors, health practitioners, kinesiologists, physiotherapists and exercise physiologists, politicians, public health policy makers, and individual members of the public. Based on previous and the current literature overviews, recommendations from the European Association on Cardiovascular Prevention and Rehabilitation are formulated regarding type, volume, and intensity of PA and regarding appropriate risk evaluation during exercise in individuals with cardiovascular risk factors.

Structural, Functional, and Hemodynamic Changes of the Common Carotid Artery With Age in Male Subjects

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 (42.4+/-16.5 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 (r=0.60, P<0.001; and r=0.46, P<0.001, respectively). The absolute diastolic/systolic diameter change diminished by 0.10 mm/10 y (r=-0. 73, P<0.001) and peak expansion velocity dropped by 0.12 cm/s per 10 years (r=-0.62, P<0.001) highly significantly with age. The peak blood flow velocity decreased continuously with age (r=-0.67, P<0. 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.

Physical performance and cardiovascular and metabolic adaptation of elite female wheelchair basketball players in wheelchair ergometry and in competition

Spinal cord injury leads to a pronounced reduction of cardiovascular, pulmonary, and metabolic ability. Physical activity, up to and including high-performance sports, has obtained importance in the course of rehabilitation and the postclinical phase. Thirteen elite female wheelchair basketball players from the German National Basketball Team and 10 female sedentary spinal cord-injured persons were examined in the study. Heart volume was measured by an echocardiography. All subjects underwent a graded exercise test on a wheelchair ergometer. Additionally, heart rate, lactate, and player points were measured during a competitive basketball game in wheelchair basketball players. Cardiac dimensions were larger for spinal cord-injured wheelchair basketball players (620.3 ml; 9.6 ml x kg(-1)) in comparison with spinal cord-injured persons (477.4 ml; 8.2 ml x kg(-1)) but did not exceed the heart volume of untrained nonhandicapped persons. In contrast, athletes with amputations or those having had poliomyelitis reached training-induced cardiac hypertrophy in relation to body mass (713.7 ml; 13.2 ml x kg(-1)), as observed in nonhandicapped athletes. During graded wheelchair ergometry, wheelchair basketball players showed a higher maximal work rate (59.9 v 45.5 W), maximal oxygen consumption (33.7 v 18.3 ml x min(-1) x kg(-1)), and maximal lactate (9.1 v 5.47 mmol x l(-1)) without a difference in maximal heart rate and workload at AT4 than did spinal cord-injured persons. The average heart rate during the wheelchair basketball game was 151 x min(-1), and the lactate concentration was 1.92 mmol x l(-1). Female athletes with a less severe handicap and higher maximal oxygen consumption during the graded exercise test reached a higher game level in the evaluation. During the competitive basketball game, high cardiovascular stress was observed, indicating a fast aerobic metabolism; the anaerobic lactic acid capacity played a subordinate role. Wheelchair basketball is an effective and suitable sport to enhance physical performance and to induce positive physiological adaptations.

Assessment of carotid wall motion and stiffness with tissue Doppler imaging.

In this study, the wall motion of the common carotid artery was characterized by measuring wall-motion velocity (Wv) with tissue Doppler imaging (TDI) in 78 male and female subjects (16-75 y) with no history of cardiovascular disease. The near and far arterial wall showed essentially different Wv patterns. To assess the vascular systolic distension, the Wv of the near and far arterial walls were measured and a Wv index was calculated by subtracting the far Wv from the near Wv. Aging was associated with a 2.0-2.5-fold decrease of peak Wv index. Corrected for carotid diameter and blood pressure, the peak Wv index and mean systolic acceleration to the peak Wv correlated highly with arterial distensibility (r = 0.81 resp. r = 0.75) and compliance (r = 0.73 resp. r = 0.68). This study demonstrates the feasibility of TDI in the characterization of wall motion patterns and in the assessment of common carotid artery stiffness.

Carotid intima-media thickness as a biomarker of subclinical atherosclerosis

Intima-media thickness of the carotid artery (CIMT) and its increase is associated with several cardiovascular risk factors and manifest cardiovascular diseases. CIMT is suggested to be an important biomarker of subclinical atherosclerosis. CIMT is measured in B-mode ultrasound images of the carotid tree as a typical double line of the arterial wall. CIMT is best visible in the measurement segment of the distal common carotid artery with lowest measurement variability. The measurement is most reliable over a one centimeter-segment with automatic or semi-automatic reading methods, which minimises reading errors. Further structured training of sonographer and reader is important for valid and reproducible results. CIMT is an accepted predictor for future cardiovascular events independent of age, gender and cardiovascular risk factors. Measurement seems to be best applicable in patients with intermediate risk in order to readjust cardiovascular risk. Plaques in the carotid tree and thickening of the CIMT are different atherosclerotic processes. From childhood to early adulthood CIMT is the only atherosclerotic marker of the carotid tree; plaques occur later in life. Both parameters contribute independently to risk assessment for future cardio-vascular events. Aims of this review are to outline measurement procedures, reproducibility, prognostic value and ability to discriminate healthy subject and patients with manifest disease in a practical and scientifically contemporary manner.

Daily walking performance as an independent predictor of advanced heart failure : Prediction of exercise capacity in chronic heart failure

PURPOSE The purpose of this study was to use an accelerometer to measure daily walking performance in patients with chronic heart failure (CHF) to investigate if this parameter is a determinant of New York Heart Association class and indicative of maximal and functional exercise capacity. METHODS Fifty patients with CHF were instructed to wear an accelerometer for 7 consecutive days while going about their daily business. Maximal and functional exercise capacity was assessed by cardiopulmonary (VO(2peak)) and 6-minute walk testing, respectively. RESULTS Patients in New York Heart Association I, II, and III reached an average total walking time (TWT) of 160.6 +/- 35.8 minutes, 133.9 +/- 59.0 minutes, and 76.1 +/- 22.5 minutes per day of which 19%, 19%, and 9% where spent in the fast walking mode (>83 m/minute), respectively. The TWT correlated strongly with VO(2peak) (r = 0.72; P <.001) and 6-minute walk testing distance (r = 0.68; P <.001). The TWT and time spent in fast walking mode were the strongest determinants in discriminating moderate CHF. CONCLUSION Daily walking performance is a clear determinant of maximal and functional exercise capacities in patients with CHF. Walking intensity in particular is an independent predictor in discriminating patients with advanced heart failure. Monitoring of daily walking performance might aid in detecting disease progression and improve clinical outcome.

Retinal vessel diameter, obesity and metabolic risk factors in school children (JuvenTUM 3)

BACKGROUND The prevalence of childhood obesity is high and its association with future cardiovascular disease in adulthood is well established. The cross-sectional data presented analyze the prevalence of obesity and the association between metabolic risk factors, physical inactivity and retinal vessel diameter in young school children. METHODS The examination included 578 school children aged 11.1±0.6 years from secondary schools in the District of Munich, Germany. Anthropometric measurements and blood sampling were conducted using standard protocols for children. Physical activity was evaluated by use of a questionnaire. Retinal microvascular diameters and the arteriolar to venular ratio (AVR) were assessed with a non-mydriatic vessel analyser (SVA-T) using a computer-based program. RESULTS In our population, 128 (22.2%) children were overweight (ow) or obese (ob). The mean retinal arteriolar and venular calibres were 208.0±15.6 μm and 236.2±16.2 μm, respectively, with a mean AVR of 0.88±0.01. Girls had significantly wider arteriolar and venular diameters compared to boys (p<0.001). ow and ob children had a lower AVR compared to normal weight (nw) children (mean(95% CI); nw: 0.89(0.88-0.89); ow: 0.87(0.86-0.88); ob: 0.85(0.83-0.87); p≤0.05). Wider venular diameters were independently associated with higher BMI and higher hsCRP. Blood pressure was associated with retinal vessel constriction. Higher physical inactivity and BMI were independently associated with a reduced AVR (p=0.032 and p<0.001, respectively). CONCLUSIONS Cardiometabolic risk factors and physical inactivity are associated with retinal microvascular alterations in young children, comparable to associations in adults. Retinal vessel imaging seems to be a feasible assessment for the detection of microvascular impairments in children at risk of developing cardiovascular disease in adulthood.