Critical power: How different protocols and models affect its determination

In cycling, critical power (CP) and work above CP (W’) can be estimated through linear and nonlinearmodels. Despite the concept of CP representing the upper boundary of sustainable exercise, overestimations may be made as the models possess inherent limitations and the protocol design is not always appropriate. Objectives: to measure and compare CP and W’ through the exponential (CPexp), 3- parameter hyperbolic (CP3-hyp), 2-parameter hyperbolic (CP2-hyp), linear (CPlinear), and linear 1/time (CP1/time) models, using different combinations of TTE trials of different durations (approximately 1 to 20 min). Design: repeated measures. Methods: Thirteen healthy young cyclists (26±3yrs; 69.0±9.2kg; 174±10cm; 60.4±5.9mL·kg-1·min-1) performed five TTE trials on separate days. CP and W’ were modeled using two, three, four, and/or five trials. All models were compared against a criterion method (CP3-hyp with five trials; confirmed using the leaving-one-out cross-validation analysis) using smallest worthwhile change (SWC) and concordance correlation coefficient (CCC) analyses. Results: CP was considerably overestimated when only trials lasting less than 10 min were included, independent of the mathematical model used. Following CCC analysis, a number of alternative methods were able to predict our criterion method with almost a perfect agreement. However, the application of other common approaches resulted in an overestimation of CP and underestimation of W’, typically these methods only included TTE trials lasting less than 12 min. Conclusions: Estimations from CP3-hyp were found to be the most accurate, independently of TTE range. Models that include two trials between 12 and 20 min provide good agreement with the criterion method (for both CP and W’)

Repeatability of vascular responsiveness measures derived from near-infrared spectroscopy

Near-infrared spectroscopy (NIRS)-derived measures of tissue oxygen saturation (StO2) have been recently shown to significantly correlate with the widely used method for noninvasively assessing vascular endothelial function, flow-mediated dilation (FMD). The purpose of this study was to examine the intraday and interday reliability of the reperfusion slope of StO2 (slope 2 StO2) and compare it to FMD Ultrasound-derived FMD was quantified following 5\ua0min of distal cuff occlusion of the popliteal artery in nine healthy young men (26\ua0\ub1\ua03\ua0years). An FMD test was performed each of 4\ua0days, with a fifth involving three tests. FMD was calculated as the greatest percent change in diameter from baseline (%FMD). StO2 was measured using NIRS throughout each test, with slope 2 StO2 being calculated as the upslope of 10-sec following cuff release. Reliability was determined using repeatability, intraclass correlation coefficients (ICC), and coefficient of variation (CV). Repeatability of slope 2 StO2 was better than %FMD for both intraday (0.43 and 5.65, respectively) and interday (0.48 and 4.82, respectively) comparisons; approximately 30% of mean values for slope 2 StO2 could be attributed to measurement error, whereas 100% of mean FMD could be for both intraday and interday comparisons. Similarly, ICC and CV values indicated stronger reliability of slope 2 StO2 compared to %FMD for both intraday (ICC 0.92 and 0.36, respectively; CV 9\ua0\ub1\ua04% and 44\ua0\ub1\ua024%, respectively) and interday (ICC 0.94 and 0.25, respectively; CV 14\ua0\ub1\ua05% and 40\ua0\ub1\ua022%, respectively) comparisons. In conclusion, NIRS-derived slope 2 StO2 can be used as a reliable measure of vascular reactivity

Gokyo Khumbu/Ama Dablam Trek 2012

In the expedition Gokyo Khumbu/Ama Dablam Trek 2012, we studied the effects of two 12-day training periods performed both at sea level and at high altitude. The main results on adult women have been published in six original articles. In women, high altitude trekking induced CD69 T cell activation and promoted anti-stress effects of the immune responses and the oxidative balance (1). Low-to-moderate exercise training at s.l. improves the regenerative capacity of skeletal muscle and depicted the epigenetic signature of satellite cells. The cell differentiation was favored by increased [Ca2+]i and fusion index (2). On the contrary, the training in hypobaric-hypoxia induced oxidative stress and impaired the regenerative capacity of satellite cells (6). Although training did not significantly modify muscle phenotype , it induced beneficial adaptations of the oxygen transport-utilization systems witnessed by faster VO2 kinetics at exercise onset (3). The two training periods did not influence the postural stability (4). In young adult women, micturition physiological parameters were affected during adaptation to hypoxia; the correlation with SpO2 strongly suggests a role of hypoxia in these changes (5

Handcycling: training effects of a specific dose of upper body endurance training in females

Purpose: This study aims to evaluate a handcycling training protocol based on ACSM guidelines in a well-controlled laboratory setting. Training responses of a specific dose of handcycling training were quantified in a homogeneous female subject population to obtain a more in depth understanding of physiological mechanisms underlying adaptations in upper body training. Methods: 22 female able-bodied participants were randomly divided in a training (T) and control group (C). T received 7-weeks of handcycling training, 3 × 30 min/week at 65 % heart rate reserve (HRR). An incremental handcycling test was used to determine local, exercise-specific adaptations. An incremental cycling test was performed to determine non-exercise-specific central/cardiovascular adaptations. Peak oxygen uptake (peakVO2), heart rate (peakHR) and power output (peakPO) were compared between T and C before and after training. Results: T completed the training sessions at 65 ± 3 % HRR, at increasing power output (59.4 ± 8.2 to 69.5 ± 8.9 W) over the training program. T improved on handcycling peakVO2 (+18.1 %), peakPO (+31.9 %), and peakHR (+4.0 %). No improvements were found in cycling parameters. Conclusion: Handcycling training led to local, exercise-specific improvements in upper body parameters. Results could provide input for the design of effective evidence-based training programs specifically aimed at upper body endurance exercise in females

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Chapter 6. Cardiovascular Changes

[no abstract available