Effect of 5 years of exercise training on the cardiovascular risk profile of older adults: the Generation 100 randomized trial.

AIMS: The aim of this study was to compare the effects of 5 years of supervised exercise training (ExComb), and the differential effects of subgroups of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), with control on the cardiovascular risk profile in older adults. METHODS AND RESULTS: Older adults aged 70-77 years from Trondheim, Norway (n = 1567, 50% women), able to safely perform exercise training were randomized to 5 years of two weekly sessions of HIIT [∼90% of peak heart rate (HR), n = 400] or MICT (∼70% of peak HR, n = 387), together forming ExComb (n = 787), or control (instructed to follow physical activity recommendations, n = 780). The main outcome was a continuous cardiovascular risk score (CCR), individual cardiovascular risk factors, and peak oxygen uptake (VO2peak). CCR was not significantly lower [-0.19, 99% confidence interval (CI) -0.46 to 0.07] and VO2peak was not significantly higher (0.39 mL/kg/min, 99% CI -0.22 to 1.00) for ExComb vs. control. HIIT showed higher VO2peak (0.76 mL/kg/min, 99% CI 0.02-1.51), but not lower CCR (-0.32, 99% CI -0.64 to 0.01) vs. control. MICT did not show significant differences compared to control or HIIT. Individual risk factors mostly did not show significant between-group differences, with some exceptions for HIIT being better than control. There was no significant effect modification by sex. The number of cardiovascular events was similar across groups. The healthy and fit study sample, and contamination and cross-over between intervention groups, challenged the possibility of detecting between-group differences. CONCLUSIONS: Five years of supervised exercise training in older adults had little effect on cardiovascular risk profile and did not reduce cardiovascular events. REGISTRATION: ClinicalTrials.gov: NCT01666340.

The Long-term Effect of Different Exercise Intensities on High-Density Lipoprotein Cholesterol in Older Men and Women Using the Per Protocol Approach: The Generation 100 Study.

OBJECTIVE: To examine whether 5 years of high-intensity interval training (HIIT) increases high-density lipoprotein cholesterol (HDL-C) concentration more than moderate-intensity continuous training (MICT) and control (CON) in older men and women. METHODS: A total of 1567 older adults (790 [50.4%] women) were randomized (2:1:1) to either CON (n=780; asked to follow the national recommendations for physical activity) or 2 weekly sessions of HIIT (10-minute warm-up followed by 4×4-minute intervals at ∼90% of peak heart rate) or MICT (50 minutes of continuous work at ∼70% of peak heart rate). Serum HDL-C concentration was measured by standard procedures at baseline and at 1 year, 3 years, and 5 years. The study took place between August 21, 2012, and June 31, 2018. Linear mixed models were used to determine between-group differences during 5 years using the per protocol approach. RESULTS: Men in HIIT had a smaller reduction in HDL-C (-1.2%) than men in CON (-6.9%) and MICT (-7.8%) after 5 years (P=.01 and P=.03 for CON vs HIIT and MICT vs HIIT, respectively). No effect of exercise intensity on HDL-C was seen in women. Changes in peak oxygen uptake were associated with changes in HDL-C in both men and women, whereas changes in body weight and fat mass were not. CONCLUSION: In men, HIIT seems to be the best strategy to prevent a decline in HDL-C during a 5-year period. No effect of exercise intensity was seen for older women. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01666340.

The relationship between maximum heart rate in a cardiorespiratory fitness test and in a maximum heart rate test.

OBJECTIVES: It is suggested that individuals will not reach their heart rate maximum (HRmax) at an incremental cardiorespiratory fitness (CRF) test and commonly five beats per minute (bpm) are added to the highest heart rate (HR) reached. To our knowledge, there is not sufficient data justifying such estimation. Our aim was to assess whether individuals reached HRmax in an incremental CRF test to exhaustion. DESIGN AND METHODS: Fifty-one males and 57 females (aged 22-70 years) completed both an incremental CRF test (gradual increase in speed and/or inclination until volitional exhaustion) and a test designed to reach HRmax (with repeated work bouts at high intensity before maximal exertion) ≥48h apart. We investigated the relationship between the highest HR in the two tests using hierarchical linear regression analysis, with HRmax from the HRmax test as a dependent variable, and the highest HR reached at the CRF test (HRcrf), whether maximum oxygen uptake was reached on the CRF test, CRF, sex and age as independent variables. RESULTS: HRmax was 2.2 (95% confidence interval, 1.5-2.9) bpm higher in the test designed to reach HRmax than in the CRF test (p<0.001). Only HRcrf significantly predicted HRmax, with no contribution of the other variables in the model. HRmax was predicted from the highest HR reached in an incremental CRF test by multiplying HRcrf with 0.967, and adding 8.197 (HRmax=8.197+[0.967×HRcrf]) beats/min. CONCLUSION: Non-athletes reached close to HRmax in a standard CRF test.

The effect of Mg-Ca-Sr alloy degradation products on human mesenchymal stem cells.

Biodegradable Mg alloys have the potential to replace currently used metallic medical implant devices, likely eliminating toxicity concerns and the need for secondary surgeries, while also providing a potentially stimulating environment for tissue growth. A recently developed Mg-Ca-Sr alloy possesses advantageous characteristics over other Mg alloys, having a good combination of strength and degradation behavior, while also displaying potentially osteogenic properties. To better understand the effect of alloy degradation products on cellular mechanisms, in vitro studies using human bone marrow-derived mesenchymal stem cells were conducted. Ionic products of alloy dissolution were found to be nontoxic but changed the proliferation profile of stem cells. Furthermore, their presence changed the progress of osteogenic development, while concentrations of Mg in particular appeared to induce stem cell differentiation. The work presented herein provides a foundation for future alloy design where structures can be tailored to obtain specific implant performance. These potentially bioactive implants would reduce the risks for patients by shortening their healing time, minimizing discomfort and toxicity concerns, while reducing hospital costs. © 2017 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 697-704, 2018.

Peri-implant tissue response and biodegradation performance of a Mg-1.0Ca-0.5Sr alloy in rat tibia.

Biodegradable magnesium (Mg) alloys combine the advantages of traditional metallic implants and biodegradable polymers, having high strength, low density, and a stiffness ideal for bone fracture fixation. A recently developed Mg-Ca-Sr alloy potentially possesses advantageous characteristics over other Mg alloys, such as slower degradation rates and minimal toxicity. In this study, the biocompatibility of this Mg-Ca-Sr alloy was investigated in a rat pin-placement model. Cylindrical pins were inserted in the proximal tibial metaphyses in pre-drilled holes orthogonal to the tibial axis. Implant and bone morphologies were investigated using µCT at 1, 3, and 6 weeks after implant placement. At the same time points, the surrounding tissue was evaluated using H&E, TRAP and Goldner's trichrome staining. Although gas bubbles were observed around the degrading implant at early time points, the bone remained intact with no evidence of microfracture. Principle findings also include new bone formation in the area of the implant, suggesting that the alloy is a promising candidate for biodegradable orthopedic implants.

The role of surface oxidation on the degradation behavior of biodegradable Mg-RE (Gd, Y, Sc) alloys for resorbable implants.

Biodegradable magnesium (Mg) alloys have the potential to replace currently used implants for fixation, thereby eliminating the need for removal surgeries. To achieve a controllable degradation rate, surface oxidation has been proposed as an avenue to reduce the initial degradation. This study aims to investigate the oxidation behavior of binary Mg-rare earth alloys and the effect on biodegradation. Cast Mg-3X alloys (X=Gd, Y, Sc) were prepared and then oxidized in pure oxygen. The oxidation rate was evaluated using TGA and the oxides were further investigated and characterized using SEM, AES and XPS. The effect of oxidation on the degradation rate was investigated by immersion testing in Hanks' solution. The thermodynamics and oxidation kinetics of the alloys are discussed in regard to the obtained results, and it was concluded that the experimental results are in agreement with thermodynamic predictions.

A study of a biodegradable Mg-3Sc-3Y alloy and the effect of self-passivation on the in vitro degradation.

Magnesium and its alloys have been investigated for their potential application as biodegradable implant materials. Although properties of magnesium such as biocompatibility and susceptibility to dissolution are desirable for biodegradable implant applications, its high degradation rate and low strength pose a significant challenge. A potential way to reduce the initial degradation rate is to form a self-passivating protective layer on the surface of the alloy. Oxides with a low enthalpy of formation result in a strong thermodynamic driving force to produce oxide surfaces that are more stable than the native oxide (MgO), and possibly reduce the initial degradation rate in these alloys. In the present study a ternary Mg-3wt.% Sc-3wt.% Y alloy was investigated and its oxidation behavior studied. The effect of surface passivation on the in vitro degradation rate was studied and the degradation products identified. The results show that the oxide provided an initial degradation barrier and 24h oxidation resulted in a negligible degradation rate for up to 23 days. Furthermore, the degradation products of the alloy showed no significant toxicity to osteoblastic cells, and cell proliferation studies confirmed cell attachment and proliferation on the surface of the oxidized alloy.

Synthesis and characterization of Mg-Ca-Sr alloys for biodegradable orthopedic implant applications.

Magnesium has recently received an increased amount of interest due to its potential use in biodegradable implant applications. The rapid degradation of conventional Mg is, however, a major limitation that needs to be addressed in the design of these materials, along with consideration of toxicity in selection of alloying elements. In this study, five alloys in the Mg-xCa-ySr system (x = 0.5-7.0 wt %; y = 0.5-3.5 wt %) were prepared and characterized for their suitability as degradable orthopedic implant materials. The alloys were characterized using optical microscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, degradation measurements in Hanks' solution at 37°C, compression testing, and in vitro cytotoxicity testing with a mouse osteoblastic cell line. The results indicate that the Mg-1.0Ca-0.5Sr alloy is the most promising alloy for orthopedic implant applications since it showed the lowest degradation rate in Hanks' solution (0.01 mL cm(-2) h(-1)) along with no significant toxicity to MC3T3-E1 osteoblasts and a compressive strength of 274 ± 4 MPa.