Reproducibility of different methods to measure the endothelial function.

This study compares the reliability and reproducibility of flow-mediated dilatation (FMD) and peripheral arterial tonometry (PAT) to assess endothelial function. Eighteen volunteers with coronary heart disease underwent simultaneous testing of FMD by means of brachial artery ultrasound scanning and PAT with the EndoPAT 2000. The subjects underwent both tests twice with an interval of 30 minutes and the same protocol was repeated 2 days later. The within-day variability was lower for the FMD measurements than for the PAT measurements (10% versus 18%; p < 0.05). The between-day variability was similar (11%). A significant correlation was found between PAT and FMD (r = 0.57, p < 0.001). The typical errors of measurements for FMD were lower than those for PAT. In conclusion, in this study, FMD demonstrated the best reliability for the within- and between-day and separate day measurements when compared to PAT.

Reliability and validity of the ultrasound technique to measure the rectus femoris muscle diameter in older CAD-patients.

BACKGROUND: The increasing age of coronary artery disease (CAD) patients and the occurrence of sarcopenia in the elderly population accompanied by 'fear of moving' and hospitalization in these patients often results in a substantial loss of skeletal muscle mass and muscle strength. Cardiac rehabilitation can improve exercise tolerance and muscle strength in CAD patients but less data describe eventual morphological muscular changes possibly by more difficult access to imaging techniques. Therefore the aim of this study is to assess and quantify the reliability and validity of an easy applicable method, the ultrasound (US) technique, to measure the diameter of rectus femoris muscle in comparison to the muscle dimensions measured with CT scans. METHODS: 45 older CAD patients without cardiac event during the last 9 months were included in this study. 25 patients were tested twice with ultrasound with a two day interval to assess test-retest reliability and 20 patients were tested twice (once with US and once with CT) on the same day to assess the validity of the US technique compared to CT as the gold standard. Isometric and isokinetic muscle testing was performed to test potential zero-order correlations between muscle diameter, muscle volume and muscle force. RESULTS: An intraclass correlation coefficient (ICC) of 0.97 ((95%CL: 0.92 - 0.99) was found for the test-retest reliability of US and the ICC computed between US and CT was 0.92 (95%CL: 0.81 - 0.97). The absolute difference between both techniques was 0.01 ± 0.12 cm (p = 0.66) resulting in a typical percentage error of 4.4%. Significant zero-order correlations were found between local muscle volume and muscle diameter assessed with CT (r = 0.67, p = 0.001) and assessed with US (r = 0.49, p < 0.05). Muscle strength parameters were also significantly correlated with muscle diameter assessed with both techniques (range r = 0.45-r = 0.61, p < 0.05). CONCLUSIONS: Ultrasound imaging can be used as a valid and reliable measurement tool to assess the rectus femoris muscle diameter in older CAD patients.

Muscular strength and diameter as determinants of aerobic power and aerobic power response to exercise training in CAD patients.

OBJECTIVE: Low exercise capacity and skeletal muscle strength are important predictors of all-cause mortality in healthy as well as diseased individuals. Compared to sedentary subjects, CAD patients have a decreased oxygen uptake (peakVO2) and show accompanying increased muscle fatiguability. Despite the known importance of oxygen extraction by peripheral muscles on improving peakVO2 and of the relationship between muscle strength and aerobic capacity, only few studies in CAD patients include measurements of muscle strength before and after cardiac rehabilitation. This study therefore aimed to evaluate how much of the variance in baseline peakVO2 and its response to exercise training can be explained by muscular parameters. METHODS: 260 CAD patients performed maximal incremental cycle ergometer testing and maximal knee muscle strength measurements. The rectus femoris diameter was measured using ultrasound. Zero order correlations were calculated and determinants of baseline and response in peakVO2 were analysed by multiple regression analysis. RESULTS: PeakVO2 and muscle strength and diameter increased significantly after three months of cardiac rehabilitation (P < 0.0001). Zero order correlations showed significant correlations between muscular parameters and baseline peakVO2 (P < 0.0001). 63% of the total variance in baseline peakVO2 could be explained by seven parameters with knee extensor muscular endurance as the strongest predictor (P < 0.0001). 32% of the variation in relative increase in peakVO2 could be explained by 5 determinants of which the increase in muscular endurance was the strongest determinant (P < 0.0001). CONCLUSIONS: Knee extensor muscular endurance and its response after training are the strongest muscular predictors in explaining peakVO2 and its response in CAD patients.

A genetic predisposition score for muscular endophenotypes predicts the increase in aerobic power after training: the CAREGENE study.

BACKGROUND: It is widely accepted that genetic variability might explain a large part of the observed heterogeneity in aerobic capacity and its response to training. Significant associations between polymorphisms of different genes with muscular strength, anaerobic phenotypes and body composition have been reported. Muscular endophenotypes are positively correlated with aerobic capacity, therefore, we tested the association of polymorphisms in twelve muscular related genes on aerobic capacity and its response to endurance training. METHODS: 935 Coronary artery disease patients (CAD) who performed an incremental exercise test until exhaustion at baseline and after three months of training were included. Polymorphisms of the genes were detected using the invader assay. Genotype-phenotype association analyses were performed using ANCOVA. Different models for a genetic predisposition score (GPS) were constructed based on literature and own data and were related to baseline and response VO(2) scores. RESULTS: Carriers of the minor allele in the R23K polymorphism of the glucocorticoid receptor gene (GR) and the ciliary neurotrophic factor gene (CNTF) had a significantly higher increase in peakVO(2) after training (p < 0.05). Carriers of the minor allele (C34T) in the adenosine monophosphate deaminase (AMPD1) gene had a significantly lower relative increase (p < 0.05) in peakVO(2). GPS of data driven models were significantly associated with the increase in peakVO(2) after training. CONCLUSIONS: In CAD patients, suggestive associations were found in the GR, CNTF and the AMPD1 gene with an improved change in aerobic capacity after three months of training. Additionally data driven models with a genetic predisposition score (GPS) showed a significant predictive value for the increase in peakVO(2).

The CAREGENE study: genetic variants of the endothelium and aerobic power in patients with coronary artery disease.

OBJECTIVES: Aerobic phenotypes show a wide variability to similar aerobic training stimuli, which can be partly attributed to heritability. Endothelial function affects aerobic power. Various physiological pathways may influence the endothelial function. Therefore, we aimed to examine whether polymorphisms of the eNos gene, the CAT gene, the VEGF gene, the GPX1 gene, the subunit P22 phox of the NAD(P)H-odixase gene, the PPAR-alpha gene, and the PGC-alpha gene are associated with aerobic power or with its response to physical training in patients with coronary artery disease (CAD). METHODS: 935 biologically unrelated Caucasian patients with CAD who had exercised until exhaustion during graded bicycle testing at baseline and after completion of 3 months of training were included in the CAREGENE study (Cardiac Rehabilitation and GENetics of exercise performance). Polymorphisms were detected using the invader assay and MassARRAY technology. Haplotype analysis was performed on the polymorphisms of the eNos gene, the VEGF gene and the NAD(P)H-oxidase gene. RESULTS: Physical training significantly increased aerobic power by 24.2 +/- 0.6% (P < 0.001). Associations of P < 0.05 were found between aerobic power and the eNOS 273C>T variant and the catalase -262C>T variant and aerobic power response. Haplotypes of the eNOS polymorhisms were predictive of aerobic power and its response to training (P < 0.05). After Bonferroni correction of multiple testing no significant differences remained. CONCLUSION: We believe that genetic factors are very important in the explanation of the great variability of aerobic power and its response. However, after Bonferroni-correction, differences in these polymorphisms remained no longer statistically significant.

Exercise-based cardiac rehabilitation improves endothelial function assessed by flow-mediated dilation but not by pulse amplitude tonometry.

We aimed to investigate the effect of exercise on endothelium-dependent vasodilator function assessed simultaneously in the brachial artery and in the distal arterial bed by flow-mediated dilation and the pulse amplitude tonometry method, respectively, in coronary artery disease patients. The study included 146 patients with stable coronary artery disease (123 men, mean age 62 ± 9 years) who participated in the Cardiac Rehabilitation and Genetics of Exercise performance study. All patients completed a 12-week supervised cardiac rehabilitation programme (three sessions per week at an intensity of 80% of the heart rate reserve). At baseline and upon completion of the training, we measured brachial artery diameters by means of ultrasound scanning (linear array transducer of 12 MHz) and simultaneously assessed pulse amplitudes in the fingertip using a pulse amplitude tonometry device both at rest and after reactive hyperaemia induced by a 5-min forearm cuff occlusion. Peak oxygen uptake significantly increased (+22%; p < 0.0001) and flow-mediated dilation improved from 10.0% to 13.1% (+37%; p < 0.0001), whereas the reactive hyperaemia index of the pulse amplitude tonometry method remained unchanged (p = 0.47) following exercise-based cardiac rehabilitation. However, the basal digital pulse amplitude (+58%; p < 0.001) increased as a result of training, as did the digital pulse amplitude after reactive hyperaemia (+22%; p < 0.05). Exercise-based cardiac rehabilitation is associated with an improvement in endothelial function, as can be measured by flow-mediated dilation but not by the reactive hyperaemia index of the pulse amplitude tonometry method.

Genetic predisposition scores associate with muscular strength, size, and trainability.

INTRODUCTION: The number of studies trying to identify genetic sequence variation related to muscular phenotypes has increased enormously. The aim of this study was to identify the role of a genetic predisposition score (GPS) based on earlier identified gene variants for different muscular endophenotypes to explain the individual differences in muscular fitness characteristics and the response to training in patients with coronary artery disease. METHODS: Two hundred and sixty coronary artery disease patients followed a standard ambulatory, 3-month supervised training program for cardiac patients. Maximal knee extension strength (KES) and rectus femoris diameter were measured at baseline and after rehabilitation. Sixty-five single nucleotide polymorphisms (SNP) in 30 genes were selected based on genotype-phenotype association literature. Backward regression analysis revealed subsets of SNP associated with the different phenotypes. GPS were constructed for all sets of SNP by adding up the strength-increasing alleles. General linear models and multiple stepwise regression analysis were used to test the explained variance of the GPS in baseline and strength responses. Receiver operating characteristic curve analyses were performed to discriminate between high- and low-responder status. RESULTS: GPS were significantly associated with the rectus femoris diameter (P < 0.01) and its response (P < 0.0001), the isometric KES (P < 0.05) and its response (P < 0.01), the isokinetic KES at 60° · s (P < 0.05) and 180° · s (P < 0.001) and their responses to training (P < 0.0001), and the isokinetic KES endurance (P < 0.001) and its change after training (P < 0.0001). The GPS was shown as an independent determinant in baseline and response phenotypes with partial explained variance up to 23%. Receiver operating characteristic analysis showed a significant discriminating accuracy of the models, including the GPS for responses to training, with areas under the curve ranging from 0.62 to 0.85. CONCLUSION: GPS for muscular phenotypes showed to be associated with baseline KES, muscle diameter, and the response to training in cardiac rehabilitation patients.

Measures of exercise capacity in adults with congenital heart disease.

BACKGROUND: Exercise capacity in grown-ups with congenital heart disease (GUCH) is mostly reported by peak oxygen consumption (peak VO(2)). Our aim was to evaluate the maximal character of exercise tests, and to investigate submaximal measures of exercise capacity. METHODS: Adults with Coarctation of the Aorta (COA, n=155), Tetralogy of Fallot (TOF, n=98), dextro-Transposition of the Great Arteries (dTGA, n=68) and Univentricular Heart (UVH, n=10), and 122 healthy adults performed cardiopulmonary exercise testing until exhaustion. Gas exchange was measured breath by breath. The maximal performance of the test was evaluated by respiratory exchange ratio (RER), ventilatory equivalent for oxygen and Borg scale. Oxygen uptake efficiency slope (OUES), VE/VCO(2) slope and VO(2)/WR slope were calculated and ventilatory anaerobic threshold (VAT) was defined. Correlations of these measures with peak VO(2) were calculated. RESULTS: GUCH showed significantly lower peak VO(2) than controls (p<0.001), declining from 80% in COA, 74% in TOF, 64% in dTGA, to 55% in UVH. Compared to suggested criteria, mean peak RER and median Borg scale indicated a maximal effort in GUCH, however these results were significantly lower than controls (p<0.05). OUES, VO(2)/WR slope and VAT were significantly lower in patients compared to controls. OUES (r=0.853) and VAT (r=0.840) correlated best with peak VO(2); VO(2)/WR slope (r=0.551) and VE/VCO(2) slope (r=-0.421) correlated to a lesser degree (p<0.001). CONCLUSION: The investigated GUCH show reduced exercise tolerance compared to controls, related to the underlying heart defect. Different expressions of exercise tolerance clearly reveal the same differences in exercise capacity across groups of GUCH.

Importance of exercise training session duration in the rehabilitation of coronary artery disease patients.

BACKGROUND: In cardiac rehabilitation, 40-60-min exercise training sessions are advised. However, because of the increasing coronary artery disease (CAD) prevalence and higher workload for cardiac rehabilitation centres, it remains unclear whether 40-min exercise training sessions are equally effective as 60-min exercise training sessions. DESIGN: Prospective randomized clinical trial. METHODS: One hundred and thirty-four CAD patients were included in a 7-week rehabilitation programme. All patients exercised 3 days per week, at a heart rate corresponding to 65% of baseline peak oxygen uptake (VO2peak). Patients were randomized in two groups: 40 versus 60-min exercise training sessions. Changes of body anthropometrics, resting haemodynamics, exercise capacity and ventilatory threshold, blood plasma lipid profile and C-reactive protein level were assessed. RESULTS: As a result of rehabilitation, exercise capacity, ventilatory threshold, and blood plasma lipid profile improved significantly in the total population (P<0.05), without differences between subgroups (P>0.05). Body weight and waist circumference decreased significantly in total population (P<0.01), but with a greater magnitude in the 40 versus 60-min exercise session group (P<0.05). CONCLUSIONS: In the early rehabilitation of CAD patients, 40-min exercise training sessions seem to be at least as effective for improving body anthropometrics, blood plasma lipid profile and exercise capacity, as compared with 60-min exercise training sessions.