Pulmonary Hypertension in Systemic Sclerosis

The main cause of death in systemic sclerosis is interstitial lung disease, followed by pulmonary hypertension (PH). Pulmonary hypertension is the result of microvasculopathy which is caused by a disrupted healing process of endothelin damage and is featured by vasoconstriction, proliferation of arterial wall, inflammation, and fibrosis. Reclassification of pulmonary hypertension has led to five distinctive groups. In systemic sclerosis, patients may suffer from pulmonary artery hypertension (PAH, group 1), pulmonary hypertension due to interstitial lung disease (group 3), cardiac disease (group 2), and/or thromboembolic pulmonary hypertension (group 4). Patients endure declining performance during exercise, but symptoms may be variable and nonspecific. Diagnosis is made by right heart catheterization. To select patients for this invasive procedure, several screening tools are discussed, including N-terminal pro-brain natriuretic peptide levels, uric acid levels, spirometry and diffusing capacity for carbon monoxide (DCLO), echocardiography (ECG), and the DETECT algorithm. Depending on features such as disease duration, presence of anti-centromere antibodies, and DCLO, three different flow charts for screening are presented. Based on pathophysiology, several medical treatments have been developed like prostanoids, endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and stimulation of the nitric oxide pathway. Combination therapy as well as lung transplantation and supportive therapy is discussed

Leg blood flow measurements using venous occlusion plethysmography during head-up tilt

We tested whether venous occlusion plethysmography (VOP) is an appropriate method to measure calf blood flow (CBF) during head-up tilt (HUT). CBF measured with VOP was compared with superficial femoral artery blood flow as measured by Doppler ultrasound during incremental tilt angles. Measurements of both methods correlated well (r = 0.86). Reproducibility of VOP was fair in supine position and 30° HUT (CV: 11%–15%). This indicates that VOP is an applicable tool to measure leg blood flow during HUT, especially up to 30° HUT

Combined aerobic and resistance exercise training decreases peripheral but not central artery wall thickness in subjects with type 2 diabetes

Objective Little is known about the impact of exercise training on conduit artery wall thickness in type 2 diabetes. We examined the local and systemic impact of exercise training on superficial femoral (SFA), brachial (BA), and carotid artery (CA) wall thickness in type 2 diabetes patients and controls. Methods Twenty patients with type 2 diabetes and 10 age- and sex-matched controls performed an 8-week training study involving lower limb-based combined aerobic and resistance exercise training. We examined the SFA to study the local effect of exercise, and also the systemic impact of lower limb-based exercise training on peripheral (i.e. BA) and central (i.e. CA) arteries. Wall thickness (WT), diameter and wall:lumen(W:L)-ratios were examined using automated edge detection of ultrasound images. Results Exercise training did not alter SFA or CA diameter in type 2 diabetes or controls (all P > 0.05). BA diameter was increased after training in type 2 diabetes, but not in controls. Exercise training decreased WT and W:L ratio in the SFA and BA, but not in CA in type 2 diabetes. Training did not alter WT or W:L ratio in controls (P > 0.05). Conclusion Lower limb-dominant exercise training causes remodelling of peripheral arteries, supplying active and inactive vascular beds, but not central arteries in type 2 diabetes

Exercise Improves Insulin Sensitivity in the Absence of Changes in Cytokines.

PURPOSE: The benefits of aerobic exercise training on insulin sensitivity in subjects with the metabolic syndrome (MetS) are, at least in part, associated with changes in cytokines. Recent studies identified novel cytokines (e.g. fractalkine, omentin and osteopontin) that are strongly involved in glucose homeostasis and therefore potentially contribute in the exercise-induced changes in insulin sensitivity. Therefore, we aim to examine changes in skeletal muscle RNA expression and plasma levels of novel cytokines after exercise training, and correlate these changes to the exercise-induced changes in insulin sensitivity. METHODS: Women with the metabolic syndrome (MetS, n=11) and healthy women (n=10) participated in a 6-month aerobic exercise training intervention (3/week, 45min per session at 65%-85% of individual heart rate reserve). Before and after training, we examined insulin sensitivity (M-value during hyperinsulinemic euglycaemic clamp), circulating blood levels of cytokines (venous blood sample; leptin, adiponectin, omentin, fraktalkin, osteopontin). Skeletal muscle RNA-expression of these cytokines (muscle biopsy) was examined in two subgroups (MetS n=6; healthy women n=6). RESULTS: At baseline, plasma levels of omentin (85.8±26.2ng/ml) and adiponectin (5.0±1.7μg/ml) levels were significantly higher in controls compared to MetS (51.1±27.1; 3.6±1.1 respectively), and leptin levels were lower in controls (18.7±11.5ng/ml vs 53.0±23.5). M-value was significantly higher in controls (8.1±1.9mg/kg/min) than in MetS (4.0±1.7). Exercise training significantly improved M-values in both groups (P0.05). CONCLUSION: Whilst exercise training successfully improves insulin sensitivity in MetS and healthy women, we found no change in plasma and mRNA expression levels of novel cytokines

Upregulation of skeletal muscle inflammatory genes links inflammation with insulin resistance in women with the metabolic syndrome

Contains fulltext : 119217.pdf (publisher's version ) (Closed access)The metabolic syndrome, a combination of interrelated metabolic risk factors, is associated with insulin resistance and promotes the development of cardiovascular diseases and type 2 diabetes mellitus. There is a close link between inflammation and metabolic disease, but the responsible mechanisms remain elusive. The aim of this study was to identify differentially expressed genes in insulin-resistant skeletal muscle tissue of women with the metabolic syndrome compared with healthy control women. Women with the metabolic syndrome (n = 19) and healthy control women (n = 20) were extensively phenotyped, insulin sensitivity was measured using a hyperinsulinaemic euglycaemic clamp, and a skeletal muscle biopsy was obtained. Gene expression levels were compared between the two groups by microarrays. The upregulated genes in skeletal muscle of the women with the metabolic syndrome were primarily enriched for inflammatory response-associated genes. The three most significantly upregulated of this group, interleukin 6 receptor (IL6R), histone deacetylase 9 (HDAC9) and CD97 molecule (CD97), were significantly correlated with insulin resistance. Taken together, these findings suggest an important role for a number of inflammatory-related genes in the development of skeletal muscle insulin resistance

Dataset for: IMPROVEMENTS IN FITNESS ARE NOT OBLIGATORY FOR EXERCISE TRAINING-INDUCED IMPROVEMENTS IN CV RISK FACTORS

Objectives The purpose of this study was to assess whether changes in physical fitness relate to changes in cardiovascular risk factors following standardized, center-based and supervised exercise training programs in subjects with increased cardiovascular risk. Methods We pooled data from exercise training studies of subjects with increased cardiovascular risk (n=166) who underwent 8-52 weeks endurance training. We determined fitness (i.e. peak oxygen uptake) and traditional cardiovascular risk factors (body mass index, blood pressure, total cholesterol, high density lipoprotein cholesterol), before and after training. We divided subjects into quartiles based on improvement in fitness, and examined whether these groups differed in terms of risk factors. Associations between changes in fitness and in cardiovascular risk factors were further tested using Pearson correlations. Results Significant heterogeneity was apparent in the improvement of fitness and individual risk factors, with non-responder rates of 17% for fitness, 44% for body mass index, 33% for mean arterial pressure, 49% for total cholesterol and 49% for high-density lipoprotein cholesterol. Neither the number, nor the magnitude, of change in cardiovascular risk factors differed significantly between quartiles of fitness change. Changes in fitness were not correlated with changes in cardiovascular risk factors (all P>0.05). Conclusions Our data suggest that significant heterogeneity exists in changes in peak oxygen uptake after training, whilst improvement in fitness did not relate to improvement in cardiovascular risk factors. In subjects with increased cardiovascular risk, improvements in fitness are not obligatory for training-induced improvements in cardiovascular risk factors

Impact of physical fitness and daily energy expenditure on sleep efficiency in young and older humans

Item does not contain fulltextBACKGROUND: Physical activity is known to influence sleep efficiency. Relatively little is known about the relationship between physical activity and sleep efficiency in young and older humans and the impact of exercise training on sleep efficiency in healthy older individuals. OBJECTIVES: To determine the relationship between physical fitness and daily energy expenditure with sleep efficiency in young and older subjects, and assess the effect of 12-month exercise training on sleep efficiency in healthy older participants. METHODS: The relationship between physical fitness (maximal cycling test) and daily energy expenditure (accelerometry) with sleep efficiency (accelerometry) was examined cross-sectionally in 12 healthy young adults (27 +/- 5 years) and 21 healthy older participants (69 +/- 3 years). Subsequently, the effect of 12-month exercise training (n = 11) or control period (n = 10) on sleep efficiency in older participants was examined using a randomized controlled trial. RESULTS: Daily energy expenditure and sleep efficiency did not differ between young and older subjects. A significant correlation was found between energy expenditure and sleep efficiency (r = 0.627, p = 0.029) in young adults, but not in older participants (r = -0.158, p = 0.49). Physical fitness did not correlate with sleep efficiency in either group. Exercise training significantly improved physical fitness (15.0%, p < 0.001), but failed to alter sleep characteristics such as sleep efficiency, sleep onset latency and awakenings. CONCLUSIONS: We found that young adults with higher daily energy expenditure have greater sleep efficiency, whilst this relationship is diminished with advanced age. In contrast, we found no correlation between physical fitness and sleep characteristics in healthy young or older participants, which may explain the lack of improvement in sleep characteristics in older participants with 12-month exercise training. Exercise training may be more successful in subjects with existing sleep disturbances to improve sleep characteristics rather than in healthy older subjects