Personalized Activity Intelligence (PAI) for prevention of cardiovascular disease and promotion of physical activity

Purpose To derive and validate a single metric of activity tracking that associates with lower risk of cardiovascular disease mortality. Methods We derived an algorithm, Personalized Activity Intelligence (PAI), using the HUNT Fitness Study (n\ua0= 4631), and validated it in the general HUNT population (n\ua0= 39,298) aged 20-74 years. The PAI was divided into three sex-specific groups (≤50, 51-99, and ≥100), and the inactive group (0 PAI) was used as the referent. Hazard ratios for all-cause and cardiovascular disease mortality were estimated using Cox proportional hazard regressions. Results After >1 million person-years of observations during a mean follow-up time of 26.2 (SD 5.9) years, there were 10,062 deaths, including 3867 deaths (2207 men and 1660 women) from cardiovascular disease. Men and women with a PAI level ≥100 had 17% (95% confidence interval [CI], 7%-27%) and 23% (95% CI, 4%-38%) reduced risk of cardiovascular disease mortality, respectively, compared with the inactive groups. Obtaining ≥100 PAI was associated with significantly lower risk for cardiovascular disease mortality in all prespecified age groups, and in participants with known cardiovascular disease risk factors (all P-trend

Inherited physical capacity: Widening divergence from young to adult to old

Cardiorespiratory performance segregates into rat strains of inherited low- and high-capacity runners (LCRs and HCRs); during adulthood, this segregation remains stable, but widens in senescence and is followed by segregated function, health, and mortality. However, this segregation has not been investigated prior to adulthood. We, therefore, assessed cardiorespiratory performance and cardiac cell (cardiomyocyte) structure–function in 1- and 4-month-old LCRs and HCRs. Maximal oxygen uptake was 23% less in LCRs at 1-month compared to HCRs at 1-month, and 72% less at 4 months. Cardiomyocyte contractility was 37−56% decreased, and Ca2+ release was 34−62% decreased, in 1- and 4-month LCRs versus HCRs. This occurred because HCRs had improved contractility and Ca2+ release during maturation, whereas LCRs did not. In quiescent cardiomyocytes, LCRs displayed 180% and 297% more Ca2+ sparks and 91% and 38% more Ca2+ waves at 1 and 4 months versus HCRs. Cell sizes were not different between LCRs and HCRs, but LCRs showed reduced transverse-tubules versus HCRs, though no discrepant transverse-tubule generation occurred during maturation. In conclusion, LCRs show reduced scores for aerobic capacity and cardiomyocyte structure–function compared to HCRs and there is a widening divergence between LCRs and HCRs during juvenile to near-adult maturation

Even low level of physical activity is associated with reduced mortality among people with metabolic syndrome, a population based study (the HUNT 2 study, Norway)

<p>Abstract</p> <p>Background</p> <p>Low levels of physical activity may increase the risk of developing metabolic syndrome, a cluster of metabolic factors that are associated with the risk of premature death. It has been suggested that physical activity may reduce the impact of factors associated with metabolic syndrome, but it is not known whether physical activity may reduce mortality in people with metabolic syndrome.</p> <p>Methods</p> <p>In a prospective study of 50,339 people, 13,449 had metabolic syndrome at baseline and were followed up for ten years to assess cause-specific mortality. The population was divided into two age groups: those younger than 65 years of age and those older than age 65. Information on their physical activity levels was collected at baseline.</p> <p>Results</p> <p>Metabolic syndrome was associated with higher mortality from all causes (hazard ratio (HR) 1.35, 95% confidence interval (95% CI) 1.20 to 1.52) and from cardiovascular causes (HR 1.78, 95% CI 1.39 to 2.29) in people younger than 65 years old than among other populations. In older people, there was no overall association of metabolic syndrome with mortality. People with metabolic syndrome who reported high levels of physical activity at baseline were at a reduced risk of death from all causes compared to those who reported no physical activity, both in the younger age group (HR 0.52, 95% CI 0.37 to 0.73) and in the older age group (HR 0.59, 95% CI 0.47 to 0.74).</p> <p>Conclusion</p> <p>Among people with metabolic syndrome, physical activity was associated with reduced mortality from all causes and from cardiovascular causes. Compared to inactivity, even low levels of physical activity were associated with reduced mortality.</p

Chronic CaMKII inhibition blunts the cardiac contractile response to exercise training

Activation of the multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays a critical role modulating cardiac function in both health and disease. Here, we determined the effect of chronic CaMKII inhibition during an exercise training program in healthy mice. CaMKII was inhibited by KN-93 injections. Mice were randomized to the following groups: sham sedentary, sham exercise, KN-93 sedentary, and KN-93 exercise. Cardiorespiratory function was evaluated by ergospirometry during treadmill running, echocardiography, and cardiomyocyte fractional shortening and calcium handling. The results revealed that KN-93 alone had no effect on exercise capacity or fractional shortening. In sham animals, exercise training increased maximal oxygen uptake by 8% (p < 0.05) compared to a 22% (p < 0.05) increase after exercise in KN-93 treated mice (group difference p < 0.01). In contrast, in vivo fractional shortening evaluated by echocardiography improved after exercise in sham animals only: from 25 to 32% (p < 0.02). In inactive mice, KN-93 reduced rates of diastolic cardiomyocyte re-lengthening (by 25%, p < 0.05) as well as Ca2+ transient decay (by 16%, p < 0.05), whereas no such effect was observed after exercise training. KN-93 blunted exercise training response on cardiomyocyte fractional shortening (63% sham vs. 18% KN-93; p < 0.01 and p < 0.05, respectively). These effects could not be solely explained by the Ca2+ transient amplitude, as KN-93 reduced it by 20% (p < 0.05) and response to exercise training was equal (64% sham and 47% KN-93; both p < 0.01). We concluded that chronic CaMKII inhibition increased time to 50% re-lengthening which were recovered by exercise training, but paradoxically led to a greater increase in maximal oxygen uptake compared to sham mice. Thus, the effect of chronic CaMKII inhibition is multifaceted and of a complex nature

Exercise training prevents oxidative stress and ubiquitin-proteasome system overactivity and reverse skeletal muscle atrophy in heart failure

Background: Heart failure (HF) is known to lead to skeletal muscle atrophy and dysfunction. However, intracellular mechanisms underlying HF-induced myopathy are not fully understood. We hypothesized that HF would increase oxidative stress and ubiquitin-proteasome system (UPS) activation in skeletal muscle of sympathetic hyperactivity mouse model. We also tested the hypothesis that aerobic exercise training (AET) would reestablish UPS activation in mice and human HF. Methods/Principal Findings: Time-course evaluation of plantaris muscle cross-sectional area, lipid hydroperoxidation, protein carbonylation and chymotrypsin-like proteasome activity was performed in a mouse model of sympathetic hyperactivity-induced HF. At the 7th month of age, HF mice displayed skeletal muscle atrophy, increased oxidative stress and UPS overactivation. Moderate-intensity AET restored lipid hydroperoxides and carbonylated protein levels paralleled by reduced E3 ligases mRNA levels, and reestablished chymotrypsin-like proteasome activity and plantaris trophicity. In human HF (patients randomized to sedentary or moderate-intensity AET protocol), skeletal muscle chymotrypsin-like proteasome activity was also increased and AET restored it to healthy control subjects' levels. Conclusions: Collectively, our data provide evidence that AET effectively counteracts redox imbalance and UPS overactivation, preventing skeletal myopathy and exercise intolerance in sympathetic hyperactivity-induced HF in mice. Of particular interest, AET attenuates skeletal muscle proteasome activity paralleled by improved aerobic capacity in HF patients, which is not achieved by drug treatment itself. Altogether these findings strengthen the clinical relevance of AET in the treatment of HF.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2006/61523-7, 2006/58460-4]Conselho Nacional de Pesquisa e Desenvolvimento (CNPq) [473251/2009-4, 301519/2008-0, 301867/2010-0]Conselho Nacional de Pesquisa e Desenvolvimento (CNPq

A Multi-Center Comparison of VO2peak Trainability Between Interval Training and Moderate Intensity Continuous Training

There is heterogeneity in the observed VO2peak response to similar exercise training, and different exercise approaches produce variable degrees of exercise response (trainability). The aim of this study was to combine data from different laboratories to compare VO2peak trainability between various volumes of interval training and Moderate Intensity Continuous Training (MICT). For interval training, volumes were classified by the duration of total interval time. High-volume High Intensity Interval Training (HIIT) included studies that had participants complete more than 15 min of high intensity efforts per session. Low-volume HIIT/Sprint Interval Training (SIT) included studies using less than 15 min of high intensity efforts per session. In total, 677 participants across 18 aerobic exercise training interventions from eight different universities in five countries were included in the analysis. Participants had completed 3 weeks or more of either high-volume HIIT (n = 299), low-volume HIIT/SIT (n = 116), or MICT (n = 262) and were predominately men (n = 495) with a mix of healthy, elderly and clinical populations. Each training intervention improved mean VO2peak at the group level (P \u3c 0.001). After adjusting for covariates, high-volume HIIT had a significantly greater (P \u3c 0.05) absolute VO2peak increase (0.29 L/min) compared to MICT (0.20 L/min) and low-volume HIIT/SIT (0.18 L/min). Adjusted relative VO2peak increase was also significantly greater (P \u3c 0.01) in high-volume HIIT (3.3 ml/kg/min) than MICT (2.4 ml/kg/min) and insignificantly greater (P = 0.09) than low-volume HIIT/SIT (2.5 mL/kg/min). Based on a high threshold for a likely response (technical error of measurement plus the minimal clinically important difference), high-volume HIIT had significantly more (P \u3c 0.01) likely responders (31%) compared to low-volume HIIT/SIT (16%) and MICT (21%). Covariates such as age, sex, the individual study, population group, sessions per week, study duration and the average between pre and post VO2peak explained only 17.3% of the variance in VO2peak trainability. In conclusion, high-volume HIIT had more likely responders to improvements in VO2peak compared to low-volume HIIT/SIT and MICT

Exercise Training Reverses Extrapulmonary Impairments in Smoke-exposed Mice

Purpose: Cigarette smoking is the main risk factor for chronic obstructive pulmonary disease and emphysema. However, evidence on the extrapulmonary effects of smoke exposure that precede lung impairments remains unclear at present, as are data on nonpharmacological treatments such as exercise training. Methods: Three groups of mice, including control (n = 10), smoking (n = 10), and smoking with 6 wk of high-intensity interval treadmill running (n = 11), were exposed to 20 wk of fresh air or whole-body cigarette smoke. Exercise capacity (peak oxygen uptake) and lung destruction (histology) were subsequently measured, whereas the heart, peripheral endothelium (aorta), and respiratory (diaphragm) and limb (extensor digitorum longus and soleus) skeletal muscles were assessed for in vivo and in vitro function, in situ mitochondrial respiration, and molecular alterations. Results: Smoking reduced body weight by 26% (P 0.05). Smoking impaired exercise capacity by 15% while inducing right ventricular dysfunction by ~20%, endothelial dysfunction by ~20%, and diaphragm muscle weakness by ~15% (all P < 0.05), but these were either attenuated or reversed by exercise training (P < 0.05). Compared with controls, smoking mice had normal limb muscle and mitochondrial function (cardiac and skeletal muscle fibers); however, diaphragm measures of oxidative stress and protein degradation were increased by 111% and 65%, respectively (P < 0.05), but these were attenuated by exercise training (P < 0.05). Conclusions: Prolonged cigarette smoking reduced exercise capacity concomitant with functional impairments to the heart, peripheral endothelium, and respiratory muscle that preceded the development of overt emphysema. However, high-intensity exercise training was able to reverse these smoke-induced extrapulmonary impairments

Interval training

No abstract available