Clinical Utility of the Cardiorespiratory Optimal Point in Patients with Heart Failure.

INTRODUCTION: We assessed the cardiorespiratory optimal point (COP)-the minimal V̇E /V̇O 2 in a given minute of an incremental cardiopulmonary exercise test-in patients with heart failure (HF) and aimed to determine 1) its association with patient and disease characteristics, 2) changes after an exercise-based cardiac rehabilitation program (CR), and 3) the association with clinical outcomes. METHODS: We studied 277 HF patients (67 (58-74) yr, 30% female, 72% HF with restricted ejection fraction) between 2009 and 2018. Patients participated in a 12- to 24-wk CR program, and COP was assessed pre- and post-CR. Patient and disease characteristics and clinical outcomes (mortality and cardiovascular-related hospitalization) were extracted from patient files. The incidence of clinical outcomes was compared across COP tertiles (low, <26.0; moderate, 26.0-30.7; high, >30.7). RESULTS: Median COP was 28.2 (24.9-32.1) and was reached at 51% ± 15% of V̇O 2peak . Lower age, female sex, higher body mass index, the absence of a pacemaker or the absence of chronic obstructive pulmonary disease, and lower N-terminal prohormone brain natriuretic peptide concentrations were associated with a lower COP. Participation in CR reduced COP (-0.8; 95% confidence interval, -1.3 to -0.3). Low COP had a reduced risk (adjusted hazard ratio, 0.53; 95% confidence interval, 0.33-0.84) for adverse clinical outcomes as compared with high COP. CONCLUSIONS: Classic cardiovascular risk factors are associated with a higher, more unfavorable, COP. CR-based exercise training reduces COP, whereas a lower COP is associated with a better clinical prognosis. As COP can be established during a submaximal exercise test, this may offer novel risk stratification possibilities for HF care programs.

Cardiorespiratory Optimal Point Is a Submaximal Exercise Test Variable and a Predictor of Mortality Risk: THE BALL STATE ADULT FITNESS LONGITUDINAL LIFESTYLE STUDY (BALL ST).

PURPOSE: The cardiorespiratory optimal point (COP) is the minimum ventilatory equivalent for oxygen. The COP can be determined during a submaximal incremental exercise test. Reflecting the optimal interaction between the respiratory and cardiovascular systems, COP may have prognostic utility. The aim of this investigation was to determine the relationship between COP and all-cause mortality in a cohort of apparently healthy adults. METHODS: The sample included 3160 apparently healthy adults (46% females) with a mean age of 44.0 ± 12.5 yr who performed a cardiopulmonary exercise test. Cox proportional hazards models were performed to assess the relationship between COP and mortality risk. Prognostic peak oxygen uptake (V˙ o2peak ) and COP models were compared using the concordance index. RESULTS: There were 558 deaths (31% females) over a follow-up period of 23.0 ± 11.9 yr. For males, all Cox proportional hazards models, including the model adjusted for traditional risk factors and V˙ o2peak , had a positive association with risk for mortality ( P < .05). For females, only the unadjusted COP model was associated with risk for mortality ( P < .05). The concordance index values indicated that unadjusted COP models had lower discrimination compared with unadjusted V˙ o2peak models ( P < .05) and V˙ o2peak did not complement COP models ( P ≥ .13). CONCLUSIONS: Cardiorespiratory optimal point is related to all-cause mortality in males but not females. These findings suggest that a determination of COP can have prognostic utility in apparently healthy males aged 18-85 yr, which may be relevant when a maximal exercise test is not feasible or desirable.

Cardiorespiratory optimal point during exercise testing is related to cardiovascular and all-cause mortality.

Cardiorespiratory optimal point (COP) during exercise may be a potentially clinically useful cardiopulmonary exercise testing (CPET) variable, but its prognostic relevance for adverse cardiovascular disease (CVD) outcomes is unknown. We aimed to assess the association of COP during exercise with fatal mortality outcomes and the extent to which COP could improve the prediction of CVD mortality. Cardiorespiratory optimal point, the minimum value of the ventilatory equivalent for oxygen (VE/VO2) in a given minute of a CPET, was defined in 2,205 men who underwent CPET. Hazard ratios (HRs) (95% confidence intervals [CIs]) for outcomes and measures of risk discrimination for CVD mortality were calculated. During a median follow-up of 28.8 years, 402 fatal CHDs, 607 fatal CVDs, and 1,348 all-cause mortality events occurred. COP was continually associated with each outcome in a dose-response manner. On adjustment for established and emerging risk factors, the HRs (95% CIs) for fatal CHD, fatal CVD, and all-cause mortality were 3.05 (1.94-4.81), 2.82 (1.91-4.18) and 2.46 (1.85-3.27), respectively, per standard deviation increase in COP. After further adjustment for high sensitivity C-reactive protein, the HRs were 2.82 (1.78-4.46), 2.57 (1.73-3.81), and 2.27 (1.70-3.02), respectively. Addition of COP to a CVD mortality risk prediction model containing established risk factors was associated with a C-index change of 0.0139 (0.0040 to 0.0238; p = 0.006) at 25 years. COP during exercise is directly associated with fatal cardiovascular and all-cause mortality events in dose-response fashions. COP during exercise may improve the prediction of the long-term risk for CVD mortality.

Cardiorespiratory fitness is not associated with risk of venous thromboembolism: a cohort study.

Objectives. The inverse and independent association between cardiorespiratory fitness (CRF) and arterial thrombotic disease is well established. However, the potential association between CRF and venous thromboembolism (VTE) is not well known. We aimed to assess the prospective association of CRF with the risk of VTE. Design. Cardiorespiratory fitness, as measured by maximal oxygen uptake (VO2max), was assessed using a respiratory gas exchange analyser in 2,249 men aged 42-61 years without a history of VTE at baseline in the Kuopio Ischemic Heart Disease prospective cohort. Cox-regression models were used to calculate hazard ratios (HR) with 95% confidence interval (CI) for VTE. We corrected for within-person variability in CRF levels using data from repeat measurements taken several years apart. Results. There were 144 (6.4%) incident VTE events recorded during a median follow-up of 25.2 years. The age-adjusted regression dilution ratio of CRF was 0.58 (95% CI: 0.53-0.64). The risk of VTE did not significantly decrease per 1 standard deviation increase in CRF in age-adjusted analysis (HR 0.90; 95% CI 0.75-1.08). The association remained consistent in analyses adjusted for several established and emerging risk factors (HR 0.90; 95% CI 0.73-1.12). The corresponding adjusted HRs were 0.80 (95% CI: 0.52-1.23) and 0.82 (95% CI: 0.51-1.32) respectively, when comparing the extreme tertiles of CRF levels. Conclusions. In a middle-aged Caucasian male population, CRF was not associated with future risk of VTE. Further studies are required to confirm and to generalize these findings, particulary in women and other age groups.

Evidence for the role of isometric exercise training in reducing blood pressure: potential mechanisms and future directions.

Hypertension, or the chronic elevation in resting arterial blood pressure (BP), is a significant risk factor for cardiovascular disease and estimated to affect ~1 billion adults worldwide. The goals of treatment are to lower BP through lifestyle modifications (smoking cessation, weight loss, exercise training, healthy eating and reduced sodium intake), and if not solely effective, the addition of antihypertensive medications. In particular, increased physical exercise and decreased sedentarism are important strategies in the prevention and management of hypertension. Current guidelines recommend both aerobic and dynamic resistance exercise training modalities to reduce BP. Mounting prospective evidence suggests that isometric exercise training in normotensive and hypertensive (medicated and non-medicated) cohorts of young and old participants may produce similar, if not greater, reductions in BP, with meta-analyses reporting mean reductions of between 10 and 13 mmHg systolic, and 6 and 8 mmHg diastolic. Isometric exercise training protocols typically consist of four sets of 2-min handgrip or leg contractions sustained at 20-50 % of maximal voluntary contraction, with each set separated by a rest period of 1-4 min. Training is usually completed three to five times per week for 4-10 weeks. Although the mechanisms responsible for these adaptations remain to be fully clarified, improvements in conduit and resistance vessel endothelium-dependent dilation, oxidative stress, and autonomic regulation of heart rate and BP have been reported. The clinical significance of isometric exercise training, as a time-efficient and effective training modality to reduce BP, warrants further study. This evidence-based review aims to summarize the current state of knowledge regarding the effects of isometric exercise training on resting BP.

Effect of ipratropium bromide on EIB in children depends on vagal activity.

PURPOSE: Ipratropium bromide (IB) has been used to prevent exercise-induced bronchoconstriction (EIB), but its effect varies among individuals. We hypothesized that such variability may reflect individual differences in vagal activity (VA), and therefore determined whether a correlation exists between VA and the effect of IB on EIB in 13.0 (+/-0.8)-yr-old children with asthma and documented EIB. METHODS: Subjects served as their own control and were tested on three occasions in an ambient temperature of 5 degrees C. Visit I included no treatment. In visits II and III (counterbalanced sequence) subjects inhaled either 500 microg IB or 0.9% NaCl as a placebo, 45 min before exercise provocation. Investigators and the subjects were blinded to the inhaled substance. VA was assessed by a 4-s exercise test (3). The ratio of resting ECG R-R-interval at full inspiration to the lowest R-R interval during 4-s cycling was taken as an index of VA. Eight-minute cycling at constant work rate (HR=173+/-4 bpm) at 5 degrees C was used to provoke EIB. A two-factor (treatment x time) repeated-measures ANOVA was used. RESULTS: The exercise-induced drop in FEV1 was similar in the three sessions. However, because the IB caused a 15.7+/-4.1 increase in FEV1 preexercise, the postexercise values after a placebo or no treatment were consistently lower than after IB. The beneficial response to IB, compared with no treatment and with placebo, was positively correlated to VA (for FEV1: r=0.91, P=0.002; and r=0.90, P=0.002, respectively). CONCLUSION: We suggest that the therapeutic effect of IB on exercise-induced asthma may be related to vagal activity.

Efeitos do treinamento físico contra resistência sobre a composiçäo corporal e a potência muscular em adultos deficientes de hormônio do crescimento / Effects of physical training against resistance over the corporal composition and the muscular potency in deficient adults of growth hormone

A síndrome de deficiência do hormônio de crescimento (GH) no adulto está bem esclarecida, assim como os benefícios da terapia de reposiçäo com o GH recombinante. Dentre as alteraçöes observadas nesses pacientes, as da composiçäo corporal estäo entre as mais estudadas, sendo caracterizadas por um aumento da gordura corporal total com predomínio de gordura no tronco, diminuiçäo da massa magra, da força muscular e da água corporal total. Todas säo quase completamente revertidas após tratamento de reposiçäo com GH. Estudamos a composiçäo corporal e potência muscular de 11 pacientes com deficiência de GH, antes e após serem submetidos a um programa de treinamento com exercícios contra resistência por 12 semanas, sem reposiçäo com o GH. Avaliamos a composiçäo corporal através de medidas de circunferências, dobras cutâneas, peso, altura, cálculo do índice de massa corporal e relaçäo cintura-quadril. A potência muscular localizada foi avaliada em vários grupos musculares através de cinco exercícios numa unidade de exercícios musculares localizados, onde foi acoplado um tensiômetro. Após análise dos resultados, observamos que näo houve mudança na composiçäo corporal destes pacientes, em relaçäo ao índice de massa corporal, relaçäo cintura-quadril e peso. Quando estudamos separadamente a soma das dobras cutâneas centrais e periféricas, houve diminuiçäo no volume da soma das dobras centrais. Em relaçäo à força e potência muscular, näo houve ganho de força de preensäo manual medida através do dinamômetro (p>0,05), já a potência mostrou um aumento significativo após treinamento (p<0,01). Concluímos que esses pacientes, se submetidos a um programa de treinamento de exercícios contra resistência realizado em casa, ganham potência muscular e que esta forma de exercício é uma alternativa terapêutica para que possam melhorar sua qualidade de vida, quando näo for possível a utilizaçäo do GH.