CON Subjects Research Articles

Impaired cardiopulmonary baroreflex function and altered cardiovascular responses to hypovolemia in patients with heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is associated with autonomic dysregulation, which may be related to baroreflex dysfunction. Thus, we tested the hypothesis that cardiac and peripheral vascular responses to baroreflex activation via lower-body negative pressure (LBNP; -10, -20, -30, -40 mmHg) would be diminished in patients with HFpEF (n = 10, 71 ± 7 yr) compared with healthy controls (CON, n = 9, 69 ± 5 yr). Changes in heart rate (HR), mean arterial pressure (MAP, Finapres), forearm blood flow (FBF, ultrasound Doppler), and thoracic impedance (Z) were determined. Mild levels of LBNP (-10 and -20 mmHg) were used to specifically assess the cardiopulmonary baroreflex, whereas responses across the greater levels of LBNP represented an integrated baroreflex response. LBNP significantly increased in HR in CON subjects at -30 and -40 mmHg (+3 ± 3 and +6 ± 5 beats/min, P < 0.01), but was unchanged in patients with HFpEF across all LBNP levels. LBNP provoked progressive peripheral vasoconstriction, as quantified by changes in forearm vascular conductance (FVC), in both groups. However, a marked (40%-60%) attenuation in FVC responses was observed in patients with HFpEF (-6 ± 8, -15 ± 6, -16 ± 5, and -19 ± 7 mL/min/mmHg at -10, -20, -30, and -40 mmHg, respectively) compared with controls (-15 ± 10, -22 ± 6, -25 ± 10, and -28 ± 10 mL/min/mmHg, P < 0.01). MAP was unchanged in both groups. Together, these data provide new evidence for impairments in cardiopulmonary baroreflex function and diminished cardiovascular responsiveness during hypovolemia in patients with HFpEF, which may be an important aspect of the disease-related changes in autonomic cardiovascular control in this patient group.NEW & NOTEWORTHY Data from the current study demonstrate diminished cardiovascular responsiveness during hypovolemia induced by incremental lower-body negative pressure in patients with heart failure with preserved ejection fraction (HFpEF). These diminished responses imply impaired cardiopulmonary baroreflex function and altered autonomic cardiovascular regulation which may represent an important aspect of HFpEF pathophysiology.

Reduced Insulin Clearance Differently Relates to Increased Liver Lipid Content and Worse Glycemic Control in Recent-Onset Type 2 and Type 1 Diabetes.

Diabetes may feature impaired insulin kinetics, which could be aggravated by altered hepatic metabolism and glycemic control. Thus, we examined insulin clearance and its possible determinants in individuals with recent-onset diabetes. Participants of the German Diabetes Study (GDS) with type 1 diabetes (T1D) (n = 306), type 2 diabetes (T2D) (n = 489), or normal glucose tolerance (control [CON]) (n = 167) underwent hyperinsulinemic-euglycemic clamps for assessment of whole-body insulin sensitivity (M value) and insulin clearance (ICCLAMP). Insulin clearance rates were further calculated during intravenous glucose tolerance tests (ICIVGTT) and mixed-meal tests (ICMMT). Hepatocellular lipid content (HCL) was quantified with 1H-MRS. Both T1D and T2D groups had lower ICCLAMP (0.12 ± 0.07 and 0.21 ± 0.06 vs. 0.28 ± 0.14 arbitrary units [a.u.], respectively, all P < 0.05) and ICMMT (0.71 ± 0.35 and 0.99 ± 0.33 vs. 1.20 ± 0.36 a.u., all P < 0.05) than CON. In T1D, ICCLAMP, ICIVGTT, and ICMMT correlated negatively with HbA1c (all P < 0.05). M value correlated positively with ICIVGTT in CON and T2D (r = 0.199 and r = 0.178, P < 0.05) and with ICMMT in CON (r = 0.176, P < 0.05). HCL negatively associated with ICIVGTT and ICMMT in T2D (r = -0.005 and r = -0.037) and CON (r = -0.127 and r = -0.058, all P < 0.05). In line, T2D or CON subjects with steatosis featured lower ICMMT than those without steatosis (both P < 0.05). Insulin clearance is reduced in both T1D and T2D within the first year after diagnosis but correlates negatively with liver lipid content rather in T2D. Moreover, insulin clearance differently associates with glycemic control and insulin sensitivity in each diabetes type, which may suggest specific mechanisms affecting insulin kinetics.

Effect of Instability Training on Compensatory Muscle Activation during Perturbation Challenge in Young Adults.

Balance requires constant adjustments in muscle activation to attain force steadiness. Creating appropriate training can be challenging. The purpose of this study was to examine the effects of 2 weeks of front squat instability training using a water-filled training tube on force steadiness during an instability challenge. Control (CON, n = 13) and experimental (EXP, n = 17) subjects completed pre- and post-testing for EMG variability by completing one set of 10 repetitions with a stable and unstable training tube. Electrodes were placed bilaterally on the anterior deltoid, paraspinal, and vastus lateralis muscles. CON subjects completed 2 weeks of training using a stable training tube, while EXP subjects trained with a water-filled instability tube. EMG data were integrated for each contraction, and force steadiness was computed using the natural log of coefficient of variation. CON results showed no changes in force steadiness for any condition. EXP showed significant reductions in EMG activation variability across all muscles. These results indicate a significant training effect in reducing muscle activation variability in subjects training with a water-filled instability training device. Improvements seen in these healthy subjects support the development of training implements for a more clinical population to help improve force steadiness.

Habitual Vaping And Its Effect On Pulmonary Function In College Age Men And Women.

The use of electronic cigarettes, otherwise known as vaping, has dramatically increased among college students within recent years. Vaping has been marketed as a safer alternative to cigarettes, however, there is minimal research studying potential adverse effects of vaping. PURPOSE: To identify any potential relationships between e-cigarette use and clinical indicators of pulmonary function. METHODS: Pulmonary function of 6 vaping subjects (VAPE) and 13 control subjects (CON) were assessed through performance of a forced vital capacity (FVC) test. Forced expiratory volume in 1 second (FEV1.0) and FVC were measured using a spirometer (ParvoMedics, TrueOne 2400, Sandy, UT). Height and body compositions were measured using a stadiometer and bioelectrical impedance (InBody 720, Cerritos, CA). Subjects completed the International Physical Activity Questionnaire (IPAQ) to assess physical activity levels. Inclusion criteria for potential VAPE subjects required participants to be habitual users of electronic cigarettes for at least 6 months. Exclusion criteria for potential VAPE subjects included regular use of combustible cigarettes or any other combustible inhalant that is not an e-cigarette. Exclusion criteria for potential CON subjects included regular use of any combustible inhalant. Comparisons between groups were made using 2-tailed, unpaired t-tests. RESULTS: FEV1.0/FVC was found to be significantly lower in vape subjects (73.4 ± 7.8%) compared to CON subjects (83.8 ± 5.0%) (p-value <0.05). IPAQ scores, body compositions, and heights between VAPE and CON subjects were not found to significantly differ (p-value >0.05). CONCLUSION: These preliminary data suggest that habitual use of electronic cigarettes appears to correspond with decreases in FEV1.0/FVC percentages, suggesting that vaping may contribute to decreased expiratory lung capacities and potentially increased risk for diagnosis of chronic lung diseases over time. We will ultimately enroll 20 subjects per group.

Metabolomics analysis reveals dysregulation in one carbon metabolism in Friedreich Ataxia.

Friedreich Ataxia (FA) is a rare and often fatal autosomal recessive disease in which a mitochondrial protein, frataxin (FXN), is severely reduced in all tissues. With loss of FXN, mitochondrial metabolism is severely disrupted. Multiple therapeutic approaches are in development, but a key limitation is the lack of biomarkers reflecting the activity of FXN in a timely fashion. We predicted this dysregulated metabolism would present a unique metabolite profile in blood of FA patients versus Controls (Con). Plasma from 10 FA and 11 age and sex matched Con subjects was analyzed by targeted mass spectrometry and untargeted NMR. This combined approach yielded quantitative measurements for 540 metabolites and found 59 unique metabolites (55 from MS and 4 from NMR) that were significantly different between cohorts. Correlation-based network analysis revealed several clusters of pathway related metabolites including a cluster associated with one‑carbon (1C) metabolism composed of formate, sarcosine, hypoxanthine, and homocysteine. Receiver operator characteristics analyses demonstrated an excellent ability to discriminate between Con and FA with AUC values >0.95. These results are the first reported metabolomic analyses of human patients with FA. The metabolic perturbations, especially those related to 1C metabolism, may serve as a valuable biomarker panel of disease progression and response to therapy. The identification of dysregulated 1C metabolism may also inform the search for new therapeutic targets related to this pathway.

Recurrence Plot-based Classification of Ischemic and Dilated Cardiomyopathy Patients.

A large portion of the elderly population are affected by cardiovascular diseases. The early prognosis of cardiomyopathies is still a challenge. The aim of this study was to classify cardiomyopathy patients by their etiology in function of significant indexes extracted from the characterization of the recurrence plot of the systems involved. Thirty-nine cardiomyopathy patients (CMP) classified as ischemic (ICM - 24 patients) and dilated (DCM-15 patients) were considered. In addition, thirty-nine control subjects (CON) were used as reference. The beat-to-beat (BBI) time series, from the electrocardiographic signal, the systolic (SBP), and diastolic (DBP) time series, from the blood pressure signal, and the respiratory time (FLW) from the respiratory flow signal, were extracted. The recurrence plot from each signal considered were calculated and characterized by a total of 12 indexes. The best classifiers were used to build support vector machine models. The optimal model to classify ICM versus DCM patients achieved 92.3% accuracy, 95.8% sensitivity, and 86.6% specificity. When comparing CMP patients and CON subjects, the best model achieved 85.8% accuracy, 92.3% sensitivity, and 80.1% specificity. Our results suggest a more deterministic behavior in DCM patients. Clinical Relevance - This study explores the recurrence plot for the classification of ICM and DCM patients.

FADS Polymorphisms Affect the Clinical and Biochemical Phenotypes of Metabolic Syndrome.

Long-chain polyunsaturated fatty acids (LC-PUFAs) play important roles in human health, from controlling inflammation to lipid and glucose homeostasis. In our previous study, which employed a cluster analysis of a plasma fatty acid (FA) pattern, we identified two clusters of metabolic syndrome (MetS) independent of clinical and biochemical parameters within the whole study group (controls together with metabolic syndrome (MetS) patients). FA desaturase (FADS) genes are the key regulators of LC-PUFA metabolism. The aim of this study was to analyze associations between FADS polymorphisms and clusters of MetS. The study group consisted of 188 controls and 166 patients with MetS. The first cluster contained 71 controls (CON1) and 109 MetS patients (MetS1). The second cluster consisted of 117 controls (CON2) and 57 MetS patients (MetS2). In comparison with MetS2, cluster MetS1 displayed a more adverse risk profile. Cluster CON1 had, in comparison with CON2, higher body weight and increased triacylglycerol levels (p < 0.05). We found that the FADS rs174537 (p < 0.001), rs174570 (p < 0.01), and rs174602 (p < 0.05) polymorphisms along with two inferred haplotypes had statistically significant genotype associations with the splitting of MetS into MetS1 and MetS2. Conversely, we observed no significant differences in the distribution of FADS polymorphisms between MetS and CON subjects, or between CON1 and CON2. These associations between FADS polymorphisms and two clusters of MetS (differing in waist circumference, HOMA-IR, lipolysis, and oxidative stress) implicate the important influence of genetic factors on the phenotypic manifestation of MetS.

Localized Heat Therapy Improves Mitochondrial Respiratory Capacity but Not Fat Oxidation in Human Skeletal Muscle

Exercise training (EX) imposes stress on skeletal muscle, resulting in improved mitochondrial respiratory capacity and fat oxidation. Heat, which is one of the stresses of exercise, has been previously shown to increase mitochondrial respiration in human skeletal muscle. Still, it is unknown how the effects of localized heat therapy (HEAT) compare to the effects of EX, or if HEAT improves fat oxidation capacity. Therefore, the objective of this study was to determine the extent to which 6 weeks of HEAT improve mitochondrial function compared to EX. We hypothesized that HEAT would increase mitochondrial respiratory capacity, fatty acid oxidation and citrate synthase (CS) activity, but to a lesser extent than EX. Subjects were randomized into three groups: HEAT (n=11), EX (n=8), and a sham control group (CON, n=12). Subjects in the HEAT group were exposed to 2 hrs/day, 3 days/wk of short‐wave diathermy, which raised internal muscle temperature by 3.2 ± 0.33° C, while CON subjects experienced no change in muscle temperature during sham diathermy sessions. EX consisted of single‐leg extension exercise on a modified cycle ergometer for 45 min/day, 3 days/week, and resulted in a 1.8 ± 0.42° C increase in muscle temperature. Muscle biopsies were performed at baseline, and after 3 and 6 weeks of intervention. Small muscle fiber bundles (2‐4 mg wet wt.) were permeabilized, and mitochondrial respiration was assessed using high‐resolution respirometry (Oroboros O2k, Innsbruck, Austria). CS and 3‐hydroxyacyl‐CoA dehydrogenase (HAD) activity assays were performed in duplicate on supernatant from homogenized muscle samples. At 6 weeks, EX resulted in 27.9 ± 8.7% and 33.2 ± 11.7% increases in maximal coupled and uncoupled respiration, respectively, which were significantly different from baseline (p&lt;0.05). At 6 weeks, HEAT resulted in 24.8 ± 6.2% and 24.5 ± 6.2% increases in maximal coupled and uncoupled respiration, respectively, which were significantly different from baseline (p&lt;0.05), but not different from EX. Fatty acid oxidation was improved only in EX subjects after 6 weeks (29.5 ± 6.8%), compared to baseline (p&lt;0.05), with no change in HEAT or CON subjects. CS activity increased in EX subjects (25.9 ± 10.5 µmol·min‐1·mg protein‐1 or 19.0 ± 7.4%) compared to all others (p&lt;0.05), but no changes were observed in HEAT or CON subjects. Furthermore, no change in HAD activity occurred in any group. These results suggest that HEAT improves mitochondrial respiratory capacity to a similar extent as EX but does not result in other EX‐induced adaptations like increased fat oxidation and CS activity. Still, HEAT‐induced improvements in respiratory capacity may have therapeutic potential in the context of skeletal muscle disease or disuse, and further investigation is warranted.

Eye Movement Patterns Can Distinguish Schizophrenia From the Major Affective Disorders and Healthy Control Subjects.

Background and hypothesisNo objective tests are currently available to help diagnosis of major psychiatric disorders. This study evaluates the potential of eye movement behavior patterns to predict schizophrenia subjects compared to those with major affective disorders and control groups.Study designEye movements were recorded from a training set of UK subjects with schizophrenia (SCZ; n = 120), bipolar affective disorder (BPAD; n = 141), major depressive disorder (MDD; n = 136), and healthy controls (CON; n = 142), and from a hold-out set of 133 individuals with proportional group sizes. A German cohort of SCZ (n = 60) and a Scottish cohort of CON subjects (n = 184) acted as a second semi-independent test set. All patients met DSMIV and ICD10 criteria for SCZ, BPAD, and MDD. Data from 98 eye movement features were extracted. We employed a gradient boosted (GB) decision tree multiclass classifier to develop a predictive model. We calculated the area under the curve (AUC) as the primary performance metric.Study resultsEstimates of AUC in one-versus-all comparisons were: SCZ (0.85), BPAD (0.78), MDD (0.76), and CON (0.85). Estimates on part-external validation were SCZ (0.89) and CON (0.65). In all cases, there was good specificity but only moderate sensitivity. The best individual discriminators included free viewing, fixation duration, and smooth pursuit tasks. The findings appear robust to potential confounders such as age, sex, medication, or mental state at the time of testing.ConclusionsEye movement patterns can discriminate schizophrenia from major mood disorders and control subjects with around 80% predictive accuracy.

Classification of ischemic and dilated cardiomyopathy patients based on the analysis of the pulse transit time.

Cardiomyopathies diseases affects a great number of the elderly population. An adequate identification of the etiology of a cardiomyopathy patient is still a challenge. The aim of this study was to classify patients by their etiology in function of indexes extracted from the characterization of the pulse transit time (PTT). This time series represents the time taken by the pulse pressure to propagate through the length of the arterial tree and corresponding to the time between R peak of ECG and the mid-point of the diastolic to systolic slope in the blood pressure signal. For each patient, the PTT time series was extracted. Thirty cardiomyopathy patients (CMP) classified as ischemic (ICM - 15 patients) and dilated (DCM - 15 patients) were analyzed. Forty-three healthy subjects (CON) were used as a reference. The PTT time series was characterized through statistical descriptive indices and the joint symbolic dynamics method. The best indices were used to build support vector machine models. The optimal model to classify ICM versus DCM patients achieved 89.6% accuracy, 78.5% sensitivity, and 100% specificity. When comparing CMP patients and CON subjects, the best model achieved 91.3% accuracy, 91.3% sensitivity, and 88.3% specificity. Our results suggests a significantly lower pulse transit time in ischemic patients.Clinical relevance- This study analyzed the suitability of the pulse transit time for the classification of ICM and DCM patients.

Metabolic profiles identify circulating biomarkers associated with heart failure in young single ventricle patients

BackgroundChildren and young adults with single ventricle (SV) heart disease frequently develop heart failure (HF) that is intractable and difficult to treat. Our understanding of the molecular and biochemical reasons underlying this is imperfect. Thus, there is an urgent need for biomarkers that predict outcome and provide a rational basis for treatment, and advance our understanding of the basis of HF.ObjectiveWe sought to determine if a metabolomic approach would provide biochemical signatures of HF in SV children and young adults. If significant, these analytes might serve as biomarkers to predict outcome and inform on the biological mechanism(s) of HF.MethodsWe applied a multi-platform metabolomics approach composed of mass spectrometry (MS) and nuclear magnetic resonance (NMR) which yielded 495 and 26 metabolite measurements respectively. The plasma samples came from a cross-sectional set of young SV subjects, ages 2–19 years with ten control (Con) subjects and 16 SV subjects. Of the SV subjects, nine were diagnosed as congestive HF (SVHF), and 7 were not in HF. Metabolomic data were correlated with clinical status to determine if there was a signature associated with HF.ResultsThere were no differences in age, height, weight or sex between the 3 cohorts. However, statistical analysis of the metabolomic profiles using ANOVA revealed 44 metabolites with significant differences between cohorts including 41 profiled by MS and 3 by NMR. These metabolites included acylcarnitines, amino acids, and bile acids, which distinguished Con from all SV subjects. Furthermore, metabolite profiles could distinguish between SV and SVHF subjects.ConclusionThese are the first data to demonstrate a clear metabolomic signature associated with HF in children and young adults with SV. Larger studies are warranted to determine if these findings are predictive of progression to HF in time to provide intervention.

Alpha-Synuclein Oligomers and Neurofilament Light Chain in Spinal Fluid Differentiate Multiple System Atrophy from Lewy Body Synucleinopathies.

To explore the role of alpha-synuclein (αSyn) oligomers and neurofilament light chain (NFL) in cerebrospinal fluid (CSF) as markers of early multiple system atrophy (MSA) and to contrast findings with Lewy body synucleinopathies. In a discovery cohort of well-characterized early MSA patients (n = 24) and matched healthy controls (CON, n = 14), we utilized enzyme-linked immunosorbent assay to measure NFL and protein misfolding cyclic amplification (PMCA) to detect αSyn oligomers in CSF. We confirmed findings in a separate prospectively enrolled cohort of patients with early MSA (n = 38), Parkinson disease (PD, n = 16), and dementia with Lewy bodies (DLB, n = 13), and CON subjects (n = 15). In the discovery cohort, NFL was markedly elevated in MSA patients, with perfect separation from CON. αSyn-PMCA was nonreactive in all CON, whereas all MSA samples were positive. In the confirmatory cohort, NFL again perfectly separated MSA from CON, and was significantly lower in PD and DLB compared to MSA. PMCA was again nonreactive in all CON, and positive in all but 2 MSA cases. All PD and all but 2 DLB samples were also positive for αSyn aggregates but with markedly different reaction kinetics from MSA; aggregation occurred later, but maximum fluorescence was higher, allowing for perfect separation of reactive samples between MSA and Lewy body synucleinopathies. NFL and αSyn oligomers in CSF faithfully differentiate early MSA not only from CON but also from Lewy body synucleinopathies. The findings support the role of these markers as diagnostic biomarkers, and have important implications for understanding pathophysiologic mechanisms underlying the synucleinopathies. ANN NEUROL 2020;88:503-512.

Cardiorespiratory and Vascular Variability Analysis to Classify Patients with Ischemic and Dilated Cardiomyopathy.

Heart diseases are the leading cause of death in developed countries. Ascertaining the etiology of cardiomyopathies is still a challenge. The objective of this study was to classify cardiomyopathy patients through cardio, respiratory and vascular variability analysis, considering the vascular activity as the input and output of the baroreflex response. Forty-one cardiomyopathy patients (CMP) classified as ischemic (ICM, 24 patients) and dilated (DCM, 17 patients) were analyzed. Thirty-nine elderly control subjects (CON) were used as reference. From the electrocardiographic, respiratory flow, and blood pressure signals, following temporal series were extracted: beat-to-beat intervals (BBI), total respiratory cycle time series (TT), and end- systolic (SBP) and diastolic (DBP) blood pressure amplitudes, respectively. Three-dimensional representation of the cardiorespiratory and vascular activities was characterized geometrically, by fitting a polygon that contains 95% of data, and by statistical descriptive indices. The best classifiers were used to build support vector machine models. The optimal model to classify ICM versus DCM patients achieved 92.7% accuracy, 94.1% sensitivity, and 91.7% specificity. When comparing CMP patients and CON subjects, the best model achieved 86.2% accuracy, 82.9% sensitivity, and 89.7% specificity. These results suggest a limited ability of cardiac and respiratory systems response to regulate the vascular variability in these patients.

The Prevalence of Expiratory Flow Limitation in Youth Elite Male Cyclists.

Twelve ET youth male cyclists (16.3 ± 1.0 yr (13-18 yr), 176.5 ± 6.2 cm, 64.2 ± 5.9 kg) and 12 CON subjects (17.6 ± 2.2 yr (13-18 yr), 177.9 ± 7.1 cm, 74.8 ± 11.2 kg) completed an incremental exercise test to determine peak oxygen consumption (V˙O2peak) on a cycle ergometer. Maximal flow volume loops (MFVL), forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, forced expiratory flow between 25% and 75% of FVC, and peak expiratory flow were assessed before and after exercise, with inspiratory capacity maneuvers and dyspnea ratings measured in the last 20 s of each stage. EFL was quantified as the percentage of the expiratory tidal volume that overlapped with the maximal flow volume loop. V˙O2peak, dyspnea ratings at peak, and ventilation were higher in the ET compared with CON group (P < 0.05). The ET group experienced greater EFL prevalence at V˙O2peak, with 11 of 12 subjects exhibiting EFL compared with 5 of 12 subjects in the CON group (P = 0.014). When matched for absolute ventilation of 20, 40, 60, 80, and 100 L·min, there were no differences in EFL severity between the ET and CON groups (P = 0.473). Elite youth male cyclists have a greater prevalence of EFL at maximal exercise than do CON subjects who are similar in age, height, and lung size. Future research should determine whether EFL in youth ET male cyclists may limit their exercise performance.

Alteration of Angiopoietin-Like Protein 4 Levels in Serum or Urine Correlate with Different Biochemical Markers in Hyperlipidemia-Related Proteinuria.

Angiopoietin-like protein 4 (ANGPTL4) is widely known as a key regulator of lipid metabolism. We investigated the relationship between ANGPTL4 expression in serum or urine and blood lipid or urine protein levels of patients with hyperlipidemia- (HL-) related proteinuria. Sixty-eight patients with HL-related proteinuria (HL-Pro group), 68 patients with HL without proteinuria (HL-NPro group), 46 patients with non-HL-related proteinuria (NHL-Pro group), and 50 healthy control (Con) subjects were selected. There were no significant differences in serum ANGPTL4 levels between the Con group (36.82 ± 17.03 ng/ml) and the HL-Pro group (27.94 (18.90, 53.72) ng/ml). Additionally, the serum ANGPTL4 levels in the HL-Pro group were significantly lower than those in the HL-NPro group (53.32 ± 24.01 ng/ml) (P < 0.001). The urine ANGPTL4/Cr levels in the HL-Pro group (52.01 (45.25, 79.79) μg/g) were significantly higher than those in the HL-NPro group (9.96 (8.35, 12.43) ng/ml) (P < 0.05). A significant alteration in urine ANGPTL4/Cr levels was observed in the NHL-Pro group (69.41 ± 55.36 μg/g) and the Con group (10.08 ± 2.38 μg/g) as well. There was no correlation between serum and urine ANGPTL4 levels of the four groups (P > 0.05). Serum ANGPTL4 levels (HL-Pro/HL-NPro group) were positively correlated with total cholesterol (TC) and triglyceride (TG) levels in hyperlipidemia patients. However, there was no correlation between urinary ANGPTL4 levels and TC or TG (P > 0.05). Urine ANGPTL4 levels were positively correlated with 24hUPro in patients with renal impairment (HL-Pro/NHL-Pro group). To summarize, ANGPTL4 may be considered an accurate predictor of proteinuria with HL. Notably, serum or urine ANGPTL4 levels indicated the degree of proteinuria or hyperlipidemia, respectively, in HL patients.

Acute and daily effects of repeated voluntary hyperpnea on pulmonary function in healthy adults.

Hyperpnea training has been used as a method for both improving exercise performance in healthy persons and improving ventilatory capacity in patients with pulmonary disease. However, voluntary hyperpnea causes acute declines in pulmonary function, but the effects of repeated days of hyperpnea on airway function are not known. The purpose of this study was to determine the effects of repeated normocapnic hyperpnea on daily and post-hyperpnea pulmonary function in healthy adults. Ten healthy adults (21years; 170cm; 66kg) completed ten hyperpnea training sessions within 17-days (TR). Training sessions consisted of 20-minutes of normocapnic hyperpnea with gradually increased minute ventilation over the 10days. Spirometry was assessed at baseline and serially following hyperpnea during each experimental day. A control group (24years; 171cm; 66kg) completed 10days of spirometry with no hyperpnea training (CON). In both CON and TR subjects, baseline pulmonary function was unchanged during the 10days. In TR subjects, pulmonary function was decreased at 5mins after hyperpnea but thereafter increased to pre-hyperpnea values by 30mins. Furthermore, these changes in pulmonary function were consistent during the 10 training days. In TR subjects, maximal voluntary ventilation decreased by 10.4 ± 8.9% (168-150 L min-1) over the 10days (P < 0.05), whereas it was unchanged in CON subjects. These findings demonstrate that voluntary hyperpnea acutely decreases airway function in healthy subjects. However, there does not appear to be a cumulative effect of repeated hyperpnea, as daily pulmonary function was unchanged.

Twelve Weeks of Combined Resistance and Aerobic Exercise Improves Cardiometabolic Biomarkers and Enhances Red Blood Cell Hemorheological Function in Obese Older Men: A Randomized Controlled Trial.

The present study examined the effect of a 12-week combined resistance and aerobic exercise training program on cardiometabolic biomarkers and red blood cell (RBC) hemorheological function in 20 obese older men (mean age: 68.8 ± 0.9 years). Subjects were randomly divided into two groups (exercise intervention [EXP; n = 10] and control [CON; n = 10]). The EXP subjects performed resistance and aerobic exercise training program three times per week for 12 weeks, and the CON subjects maintained their regular lifestyle during the intervention period. Body composition was estimated using bioelectrical impedance analysis equipment. Cardiometabolic biomarkers (glucose, insulin, homeostasis model assessment-estimated insulin resistance (HOMA-IR), HOMA β-cell function, and leptin) and RBC hemorheological parameters (RBC deformability and aggregation) were analyzed. Percent body fat decreased significantly in the EXP group during the intervention period but increased significantly in the CON group. Insulin increased significantly in the CON group over the 12-week period and both insulin and HOMA-IR were significantly higher in the CON group than in the EXP group at post-test. RBC deformability (RBC EI_3Pa) and aggregation (RBC AI_3Pa) improved significantly only in the EXP group. The present study suggests that combined exercise training can be useful for improving cardiometabolic biomarkers and RBC hemorheological parameters in obese older men and may help prevent metabolic syndrome and cardiovascular diseases.

Heat therapy reduces sympathetic activity and improves cardiovascular risk profile in women who are obese with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) affects up to 15% of women and is associated with increased risk of obesity and cardiovascular disease. Repeated passive heat exposure [termed "heat therapy" (HT)] is a lifestyle intervention with the potential to reduce cardiovascular risk in obesity and PCOS. Women with obesity (n = 18) with PCOS [age 27 ± 4 yr, body mass index (BMI) 41.3 ± 4.7 kg/m2] were matched for age and BMI, then assigned to HT (n = 9) or time control (CON; n = 9). HT subjects underwent 30 one-hour hot tub sessions over 8-10 wk, whereas CON subjects did not undergo HT. Muscle sympathetic nerve activity (MSNA), blood pressure, cholesterol, C-reactive protein, and markers of vascular function were assessed at the start (Pre) and end (Post) of 8-10 wk. These measures included carotid and femoral artery wall thickness and flow-mediated dilation (FMD), measured both before and after 20 min of ischemia-20 min of reperfusion (I/R) stress. HT subjects exhibited reduced MSNA burst frequency (Pre: 20 ± 8 bursts/min, Post: 13 ± 5 bursts/min, P = 0.012), systolic (Pre: 124 ± 5 mmHg, Post: 114 ± 6 mmHg; P < 0.001) and diastolic blood pressure (Pre: 77 ± 6 mmHg, Post: 68 ± 3 mmHg; P < 0.001), C-reactive protein (Pre: 19.4 ± 13.7 nmol/L, Post: 15.2 ± 12.3 nmol/L; P = 0.018), total cholesterol (Pre: 5.4 ± 1.1 mmol/L, Post: 5.0 ± 0.8 mmol/L; P = 0.028), carotid wall thickness (Pre: 0.054 ± 0.005 cm, Post: 0.044 ± 0.005 cm; P = 0.010), and femoral wall thickness (Pre: 0.056 ± 0.009 cm, Post: 0.042 ± 0.005 cm; P = 0.003). FMD significantly improved in HT subjects over time following I/R (Pre: 5.6 ± 2.5%, Post: 9.5 ± 1.7%; P < 0.001). No parameters changed over time in CON, and BMI did not change in either group. These findings indicate that HT reduces sympathetic nerve activity, provides protection from I/R stress, and substantially improves cardiovascular risk profiles in women who are obese with PCOS.

Cardiovascular Coupling-Based Classification of Ischemic and Dilated Cardiomyopathy Patients.

Cardiovascular diseases are one of the most common causes of death in elderly patients. The etiology of cardiomyopathies is difficult to discern clinically. The objective of this study was to classify cardiomyopathy patients using coupling analysis, through their cardiovascular behavior and the baroreflex response. A total of thirty-eight cardiomyopathy patients (CMP) classified as ischemic (ICM, 25 patients) and dilated (DCM, 13 patients) were analyzed. Thirty elderly control subjects (CON) were used as reference. Their electrocardiographic (ECG) and blood pressure (BP) signals were studied. To characterize the cardiovascular activity, the following temporal series were extracted: beat-to-beat intervals (from the ECG signal), and end- systolic and diastolic blood pressure amplitudes (from the BP signal). Non-linear characterization techniques like high resolution joint symbolic dynamics, segmented Poincaré plot analysis, normalized shorttime partial directed coherence, and dual sequence method were used to characterize these times series. The best indices were used to build support vector machine models for classification. The optimal model for ICM versus DCM patients achieved 84.2% accuracy, 76.9% sensitivity, and 88% specificity. When CMP patients and CON subjects were compared, the best model achieved 95.5% accuracy, 97.3% sensitivity, and 93.3% specificity. These results suggest a disfunction in the baroreflex mechanism in cardiomyopathies patients.

Leucine Supplementation Partially Protects Leg Lean Mass in Older Adults During Seven Days of Bed Rest (OR18-02-19)

ObjectivesOlder adults are at increased risk of being hospitalized or bedridden and experiencing a host of negative health outcomes including loss of lean body mass. We hypothesized that supplementing daily meals with a small quantity (3–4 g/meal) of leucine will partially preserve lean leg mass and function during bed rest. MethodsMen and women (67.8 ± 1.1 y) were randomized to receive isoenergentic meals supplemented with leucine (LEU, 0.06 g/kg/meal; n = 10) or an alanine control, (CON, 0.06 g/kg/meal; n = 10). Subjects were admitted to the Clinical Research Center for 7 days of bed rest followed by 7 days of rehabilitation. Muscle fiber type and cross-sectional area (CSA) as well as single fiber characteristics were assessed from biopsies of the vastus lateralis obtained prior to (Pre-BR) and after bed rest (Post-BR) and after rehabilitation (Post-RE). Body composition measured using iDEXA was also determined at the same time points. ResultsLeucine-supplementation partially protected leg lean mass during bed rest (–1035 vs. –423 ± 143 g; P = 0.008). Leg lean mass did not differ between the groups Post-RE (P = 0.16). There was no significant effect of time (P = 0.16) or treatment (P = 0.92) on muscle fiber CSA; however, CON subjects, but not LEU subjects, exhibited an increased number of smaller fibers (<2000 um) and fewer larger fibers (>6000 um) Post-BR. Additionally, CON subjects tended to have a greater decrement in fiber width (P = 0.085) that did not return to baseline following rehabilitation. ConclusionsSupplementing older adults with moderate amounts of leucine has the potential to partially negate some of the deleterious effects on muscle health during short bouts of inactivity. Funding SourcesNational Institutes of Health, The Claude D. Pepper Older Americans Independence Center, Sealy Center on Aging and Institute for Translational Sciences-Clinical Research Center.