Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).

In highly trained soccer players, additional speed endurance training is associated with an improved ability to perform repeated high-intensity work. To what extent the training-induced changes in V˙O2 kinetics and mechanical efficiency in type I fibers caused the improvement in performance warrants further investigation.

Purpose: Accumulated time at a high percentage of peak oxygen consumption (VO2peak) is important for improving performance in endurance athletes. The present study compared the acute effect of a roller-ski skating session containing work intervals with a fast start followed by decreasing speed (DEC) with a traditional session where the work intervals had a constant speed (similar to the mean speed of DEC; TRAD) on physiological responses, rating of perceived exertion, and leg press peak power. Methods: A total of 11 well-trained cross-country skiers performed DEC and TRAD in a randomized order (5 × 5-min work intervals, 3-min relief). Each 5-minute work interval in the DEC protocol started with 1.5 minutes at 100% of maximal aerobic speed followed by 3.5 minutes at 85% of maximal aerobic speed, whereas the TRAD protocol had a constant speed at 90% of maximal aerobic speed. Results: DEC induced a higher VO2 than TRAD, measured as both peak and average of all work intervals during the session (98.2% [2.1%] vs 95.4% [3.1%] VO2peak, respectively, and 87.6% [1.9%] vs 86.1% [3.2%] VO2peak, respectively) with a lower mean rating of perceived exertion after DEC than TRAD (16.1 [1.0] vs 16.5 [0.7], respectively) (all P < .05). There were no differences between sessions for mean heart rate, blood lactate concentration, or leg press peak power. Conclusion: DEC induced a higher mean VO2 and a lower rating of perceived exertion than TRAD, despite similar mean speed, indicating that DEC can be a good strategy for interval sessions aiming to accumulate more time at a high percentage of VO2peak.

Aim & Methods: Extreme endurance exercise provides a valuable research model for understanding the adaptive metabolic response of older and younger individuals to intense physical activity. Here, we compare a wide range of metabolic and physiologic parameters in two cohorts of seven trained men, age 30 ± 5 years or age 65 ± 6 years, before and after the participants travelled ≈3000 km by bicycle over 15 days. Results: Over the 15-day exercise intervention, participants lost 2-3 kg fat mass with no significant change in body weight. VȮ 2 max did not change in younger cyclists, but decreased (p = 0.06) in the older cohort. The resting plasma FFA concentration decreased markedly in both groups, and plasma glucose increased See related editorial: Henriksson J. 2022. Extreme duration endurance exercise affects old and younger men differently-Older individuals experience a negative adaptive response affecting cardiovascular function. Acta Physiol (Oxf). e13843.

Peak fat oxidation rate (PFO) and the intensity that elicits PFO (Fat max ) are commonly determined by a validated graded exercise test (GE) on a cycling ergometer with indirect calorimetry. However, for upper body exercise fat oxidation rates are not well elucidated and no protocol has been validated. Thus, our aim was to test validity and inter-method reliability for determination of PFO and Fat max in trained men using a GE protocol applying double poling on a ski-ergometer. PFO and Fat max were assessed during two identical GE tests (GE1 and GE2) and validated against separated short continuous exercise bouts (SCE) at 35%, 50%, and 65% of VȮ 2peak on the ski-ergometer in 10 endurance-trained men (VȮ 2peak : 65.1 ± 1.0 mL·min −1 ·kg −1 , mean ± SEM). Between GE tests no differences were found in PFO (GE1:0.42 ± 0.03; GE2: 0.45 ± 0.03 g·min −1 , P = .256) or Fat max (GE1: 41 ± 2%; GE2: 43 ± 3% of VȮ 2peak , P = .457) and the intra-individual coefficient of variation (CV) was 8 ± 2% and 11 ± 2% for PFO and Fat max , respectively. Between GE and SCE tests, PFO (GE avg : 0.44 ± 0.03; SCE; 0.47 ± 0.06 g·min −1 , P = .510) was not different, whereas a difference in Fat max (GE avg : 42 ± 2%; SCE: 52 ± 4% of VȮ 2peak , P = .030) was observed with a CV of 17 ± 4% and 15 ± 4% for PFO and Fat max , respectively. In conclusion, GE has a high day-to-day reliability in determination of PFO and Fat max in trained men, whereas it is unclear if PFO and Fat max determined by GE reflect continuous exercise in general. K E Y W O R D Sexercise testing, Fat max , lipid metabolism, peak fat oxidation, test reliability, test validity, upper body exercise 1678 |

The peak fat oxidation rate (PFO) and the exercise intensity that elicits PFO (Fat max) are associated with endurance performance during exercise primarily involving lower body musculature, but it remains elusive whether these associations are present during predominant upper body exercise. The aim was to investigate the relationship between PFO and Fat max determined during a graded exercise test on a ski-ergometer using double-poling (GET-DP) and performance in the long-distance crosscountry skiing race, Vasaloppet. Forty-three healthy men completed GET-DP and Vasaloppet and were divided into two subgroups: recreational (RS, n = 35) and elite (ES, n = 8) skiers. Additionally, RS completed a cycle-ergometer GET (GET-Cycling) to elucidate whether the potential relationships were specific to exercise modality. PFO (r 2 = .10, P = .044) and Fat max (r 2 = .26, P < .001) were correlated with performance; however, V O 2peak was the only independent predictor of performance (adj. R 2 = .36) across all participants. In ES, Fat max was the only variable associated with performance (r 2 = .54, P = .038). Within RS, DP V O 2peak (r 2 = .11, P = .047) and ski-specific training background (r 2 = .30, P = .001) were associated with performance. Between the two GETs, Fat max (r 2 = .20, P = .006) but not PFO (r 2 = .07, P = .135) was correlated. Independent of exercise mode, neither PFO nor Fat max were associated with performance in RS (P > .05). These findings suggest that prolonged endurance performance is related to PFO and Fat max but foremost to V O 2peak during predominant upper body exercise. Interestingly, Fat max may be an important determinant of performance among ES. Among RS, DP V O 2peak , and skiing experience appeared as performance predictors. Additionally, whole-body fat oxidation seemed specifically coupled to exercise modality. K E Y W O R D S crosscountry skiing, double-poling, peak fat oxidation, prolonged endurance performance | 2045 RØMER Et al. Note: Data are presented as mean ± 95% CI and range. Abbreviations: BMI, body mass index; FFM, fat-free mass; UBMM, upper body muscle mass (arm + torso). a n = 42 and n = 7 for all participants and ES, respectively.

It has recently been established that myosin, the molecular motor protein, is able to exist in two conformations in relaxed skeletal muscle. These conformations are known as the super-relaxed (SRX) and disordered-relaxed (DRX) states and are finely balanced to optimize ATP consumption and skeletal muscle metabolism. Indeed, SRX myosins are thought to have a 5- to 10-fold reduction in ATP turnover compared with DRX myosins. Here, we investigated whether chronic physical activity in humans would be associated with changes in the proportions of SRX and DRX skeletal myosins. For that, we isolated muscle fibers from young men of various physical activity levels (sedentary, moderately physically active, endurance-trained, and strength-trained athletes) and ran a loaded Mant-ATP chase protocol. We observed that in moderately physically active individuals, the amount of myosin molecules in the SRX state in type II muscle fibers was significantly greater than in age-matched sedentary individuals. In parallel, we did not find any difference in the proportions of SRX and DRX myosins in myofibers between highly endurance- and strength-trained athletes. We did however observe changes in their ATP turnover time. Altogether, these results indicate that physical activity level and training type can influence the resting skeletal muscle myosin dynamics. Our findings also emphasize that environmental stimuli such as exercise have the potential to rewire the molecular metabolism of human skeletal muscle through myosin.

Background and Aims Low-dose colchicine reduces cardiovascular risk in patients with coronary artery disease (CAD), but absolute benefits may vary between individuals. This study aimed to assess the range of absolute benefit from low-dose colchicine according to individual patient risk profile. Methods The ESC guideline-recommended SMART-REACH model was combined with the relative treatment effect of low-dose colchicine, and applied to CAD patients from the LoDoCo2 trial and UCC-SMART cohort (n = 10,830). Individual treatment benefit was expressed as 10-year absolute risk reductions (ARRs) for myocardial infarction, stroke, or cardiovascular death (MACE), and MACE-free life-years gained. Predictions were also performed for MACE plus coronary revascularization (MACE+), using a new lifetime model derived in the REACH registry. Colchicine was compared to other ESC guideline-recommended intensified (step 2) prevention strategies, i.e. low density lipoprotein-cholesterol (LDL-c) reduction to 1.4 mmol/L, and systolic blood pressure (SBP) reduction to 130 mmHg. Generalizability to other populations was assessed in CAD patients from REACH North America and Western Europe (n = 25,812). Results Median 10-year ARR from low-dose colchicine was 4.6% (interquartile range [IQR] 3.6–6.0%) for MACE, and 8.6% (IQR 7.6–9.8%) for MACE + . Lifetime benefit was 2.0 (IQR 1.6–2.5) MACE-free years, and 3.4 (IQR 2.6–4.2) MACE + -free life-years gained. For LDL-c and SBP reduction respectively, median 10-year ARR for MACE was 3.0% (IQR 1.5-5.1%) and 1.7% (IQR 0.0-5.7%), and lifetime benefit was 1.2 (IQR 0.6-2.1) and 0.7 (IQR 0.0-2.3) MACE-free life-years gained. Similar results were obtained for MACE+, and in American and European patients from REACH. Conclusions The absolute benefits of low-dose colchicine vary between individual patients with chronic CAD. They may be expected to be of at least similar magnitude to those of intensified LDL-c and SBP reduction in a majority of patients already on conventional lipid-lowering and blood pressure-lowering therapy.