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Resistance training as a medicine to improve endothelial function

Resistance training as a medicine to improve endothelial function Arno Schmidt-Trucksäss arno.schmidt-trucksaess@unibas.ch Editorial on “Resistance training as a medicine to improve endothelial function” see Ref(1). Department of Sport, Exercise and Health, Division Sports and Exercise Medicine, University of Basel, Switzerland Abstract The idea that resistance training is not exclusively detrimental to the arterial endothelium is slowly gaining acceptance [[2],[3]]. Up to now, it has been predominantly assumed that endurance training is more or less exclusively suitable for increasing blood flow in the arteries to a clinically relevant degree. However, recently resistance training has also been given greater importance in protecting arterial endothelial function [[4]]. In the study by Farah et al. in this issue of Atherosclerosis [[1]], it is shown that both dynamic resistance training and isometric hand grip training contribute to improved endothelial function measured as flow-mediated dilatation of the brachial artery. Surprisingly, this applies equally to healthy individuals as well as to patients with cardiovascular and metabolic diseases. The intervention studies based on resistance training included in the systematic review and meta-analysis by Farah et al. [[1]] that had a positive effect on endothelial function were predominantly performed at a load intensity between 50 and 70% of the one repetition maximum with 8–12 repetitions in 2–3 series involving large muscle groups. Isometric training consisted of hand grip training at 30% maximum strength with mostly sustained single contractions of 2 min duration but also single contractions in intervals of seconds over 20 min. The fact that these two forms of resistance training lead to similar improvements in flow-mediated dilatation of the brachial artery, although they are completely different in nature, could be due to the anatomical localisation of the artery. Both resistance training of large muscle groups and hand grip training involve the local musculature of the arm, respectively the artery where the FMD is measured. This leaves entirely open whether the effect on arterial function is a local or a systemic effect. Farah et al. [[1]] wisely refrain from making assumptions, especially since it is outside the focus of the systematic review with meta-analysis to address the underlying physiological mechanisms. Since the first studies around the year 2000, there has been a considerable need for research in this area, whereby increased attention should be paid to the interplay of vasodilating (NO-mediated, anti-inflammatory, anti-oxidative etc) and vasoconstrictor mechanisms (endothelin-1, sympathoadrenergic etc) [[4]]. More specifically related to the type of resistance training, however, it should be clarified how low compared to high intensity resistance training affects the volume of local and systemic blood flow, taking into account antegrade and retrograde blood flow; recent research [[5]] suggested its great importance of retrograde flow for the development of endothelial dysfunction. It is also a surprising result of the systematic review of Farah et al. [[1]] that the improvement in FMD is comparable in healthy individuals and patients with cardiovascular and metabolic disease. Should this indicate an isolated positive effect of local blood flow that is independent of existing disease and arteriosclerotic risk factor burden? Or do the results lie in a similar range, rather by chance, considering different measurement methods of the FMD in terms of duration of ischemia (5 or 6 min) and measurement after release of ischemia (between 1 and 3 min), localisation of the cuff (mostly distal to the measurement site of the brachial artery, but also proximal), or use of different analyzing software? To achieve more robust results in the future, Farah et al. [[1]] recommend to conduct studies using uniform methodological standards as proposed for FMD [[6]]. In addition, the sample size for the primary endpoint should be predefined, and studies should be conducted as multicentre studies if possible to achieve the highest quality standards. This would be the logical consequence if exercise was understood as a drug with comparable clinical value of a pharmacological therapy. The systematic review with meta-analysis by Farah et al. [[1]] provides evidence that resistance training can also have positive effects on endothelial function, but it also shows how much is still unclear. To date, there are no solid intervention studies on the effect of physical training on low flow-mediated constriction and on the combination of low flow-mediated constriction and FMD, the vasoactive range [[7]]. Likewise, studies that include other vascular beds as well as microvascular vessels are largely lacking. To conclude, there are several research gaps and standardisation of future intervention studies is urgently needed so that resistance training can be appropriately used and prescribed as medicine to treat the endothelium. The systematic review by Farah et al. [[1]] contributes significantly to achieve these goals.

Resistance training as a medicine to improve endothelial function Arno Schmidt-Trucksäss arno.schmidt-trucksaess@unibas.ch Editorial on “Resistance training as a medicine to improve endothelial function” see Ref(1). Department of Sport, Exercise and Health, Division Sports and Exercise Medicine, University of Basel, Switzerland Abstract The idea that resistance training is not exclusively detrimental to the arterial endothelium is slowly gaining acceptance [[2],[3]]. Up to now, it has been predominantly assumed that endurance training is more or less exclusively suitable for increasing blood flow in the arteries to a clinically relevant degree. However, recently resistance training has also been given greater importance in protecting arterial endothelial function [[4]]. In the study by Farah et al. in this issue of Atherosclerosis [[1]], it is shown that both dynamic resistance training and isometric hand grip training contribute to improved endothelial function measured as flow-mediated dilatation of the brachial artery. Surprisingly, this applies equally to healthy individuals as well as to patients with cardiovascular and metabolic diseases. The intervention studies based on resistance training included in the systematic review and meta-analysis by Farah et al. [[1]] that had a positive effect on endothelial function were predominantly performed at a load intensity between 50 and 70% of the one repetition maximum with 8–12 repetitions in 2–3 series involving large muscle groups. Isometric training consisted of hand grip training at 30% maximum strength with mostly sustained single contractions of 2 min duration but also single contractions in intervals of seconds over 20 min. The fact that these two forms of resistance training lead to similar improvements in flow-mediated dilatation of the brachial artery, although they are completely different in nature, could be due to the anatomical localisation of the artery. Both resistance training of large muscle groups and hand grip training involve the local musculature of the arm, respectively the artery where the FMD is measured. This leaves entirely open whether the effect on arterial function is a local or a systemic effect. Farah et al. [[1]] wisely refrain from making assumptions, especially since it is outside the focus of the systematic review with meta-analysis to address the underlying physiological mechanisms. Since the first studies around the year 2000, there has been a considerable need for research in this area, whereby increased attention should be paid to the interplay of vasodilating (NO-mediated, anti-inflammatory, anti-oxidative etc) and vasoconstrictor mechanisms (endothelin-1, sympathoadrenergic etc) [[4]]. More specifically related to the type of resistance training, however, it should be clarified how low compared to high intensity resistance training affects the volume of local and systemic blood flow, taking into account antegrade and retrograde blood flow; recent research [[5]] suggested its great importance of retrograde flow for the development of endothelial dysfunction. It is also a surprising result of the systematic review of Farah et al. [[1]] that the improvement in FMD is comparable in healthy individuals and patients with cardiovascular and metabolic disease. Should this indicate an isolated positive effect of local blood flow that is independent of existing disease and arteriosclerotic risk factor burden? Or do the results lie in a similar range, rather by chance, considering different measurement methods of the FMD in terms of duration of ischemia (5 or 6 min) and measurement after release of ischemia (between 1 and 3 min), localisation of the cuff (mostly distal to the measurement site of the brachial artery, but also proximal), or use of different analyzing software? To achieve more robust results in the future, Farah et al. [[1]] recommend to conduct studies using uniform methodological standards as proposed for FMD [[6]]. In addition, the sample size for the primary endpoint should be predefined, and studies should be conducted as multicentre studies if possible to achieve the highest quality standards. This would be the logical consequence if exercise was understood as a drug with comparable clinical value of a pharmacological therapy. The systematic review with meta-analysis by Farah et al. [[1]] provides evidence that resistance training can also have positive effects on endothelial function, but it also shows how much is still unclear. To date, there are no solid intervention studies on the effect of physical training on low flow-mediated constriction and on the combination of low flow-mediated constriction and FMD, the vasoactive range [[7]]. Likewise, studies that include other vascular beds as well as microvascular vessels are largely lacking. To conclude, there are several research gaps and standardisation of future intervention studies is urgently needed so that resistance training can be appropriately used and prescribed as medicine to treat the endothelium. The systematic review by Farah et al. [[1]] contributes significantly to achieve these goals. References Silva JK TNF, Menêses AL, Parmenter BJ et al., Effects of Resistance Training on Endothelial Function: A Systematic Review and Meta-Analysis, Atherosclerosis in press, doi: 10.1016/j.atherosclerosis.2021.07.009.

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