Kimberley L.Way *,Angelo Sabag ,Angela S.Lee ,Stephen M.Twigg ,Nathan A.Johnson

a School of Exercise and Nutrition Sciences,Faculty of Health,Deakin University,Burwood,VIC 3125,Australia

b Exercise Physiology and Cardiovascular Health Lab,University of Ottawa Heart Institute,Ottawa,ON K1Y 4W7,Canada

c NICM Health Research Institute,Western Sydney University,Westmead,NSW 2145,Australia

d Central Clinical School,Faculty of Medicine and Health,University of Sydney,Camperdown,NSW 2050,Australia

e Department of Endocrinology,Diabetes Centre,Royal Prince Alfred Hospital,Sydney,NSW 2050,Australia

f Discipline of Exercise and Sports Science,Faculty of Medicine and Health,University of Sydney,Lidcombe,NSW 2141,Australia

g Boden Collaboration for Obesity,Nutrition,Exercise and Eating Disorders,University of Sydney,Camperdown,NSW 2006,Australia

Dear editor,

We thank Lopes et al.1for their interest in our study and for writing an insightful commentary based on our findings,which were recently published in the Journal of Sport and Health Science,2and for their work.3As noted by the authors,there is consistency in several key findings between our laboratories,and this should serve as a basis for future investigation in this area.We agree that there has been little work examining the effect of high-intensity interval exercise(HIIE) on central arterial stiffness,wave ref lections,and hemodynamic responses.However,research is particularly lacking in adults with metabolic diseases,a population with a signif icantly increased risk of developing cardiovascular disease and cardiovascular mortality.To further the important discussion Lopes et al.1have raised in their commentary,our response focuses on raising additional points concerning the responses in central arterial stiffness,wave ref lections,and hemodynamics observed following HIIE in adults with metabolic diseases.With this,we hope to shed light on the importance of research in HIIE for this population and their arterial health.

Previous work examining the effect of aerobic exercise in both acute and chronic exercise settings on such arterial health outcomes has been conducted predominately in young,healthy adults.4As highlighted in the commentary by Lopes et al.,1a transient reduction in wave ref lections (as measured by augmentation index at a heart rate of 75 beats/min (AIx＠75))may be intensity dependent,given the findings from each of our respective studies in adults with diabetes2or obesity.3Both studies observed a signif icant transient reduction in AIx＠75 following a single bout of HIIE;this did not occur after a single bout of moderate-intensity continuous exercise(MICE) or control.Although Lopes et al.1highlighted that AIx represents the capacity of the peripheral vessels to dampen the propagation of the forward wave throughout the arterial tree,a recent study has found that AIx also represents cardiac mechanics.5Using cardiac computational modeling,Heusinkveld et al.5showed that reduced left ventricular shortening velocity was associated with a signif icantly earlier arrival of wave ref lections,which,in turn,increased AIx.This suggests that HIIE may play a role in transiently increasing the left ventricular shortening velocity and improving cardiac mechanics in adults with diabetes or obesity.Additionally,the improvements observed in AIx could also be explained by the biochemical benef its associated with a bout of aerobic exercise,such as increased nitric oxide bioavailability.6It is now established that chronic hyperglycemia7and increased ectopic fat8can contribute to cardiac remodeling and alter cardiac structure and function.8For instance,left ventricular hypertrophy,8,9worse left ventricular systolic8and diastolic function,9and reduced ejection fraction9have been observed in people with diabetes or obesity.Such cardiac remodeling can increase the risk of developing heart failure or cardiomyopathies.Much like improving insulin sensitivity through repeated bouts of exercise,it appears that AIx could be managed through bouts of HIIE.In contrast to the findings from the Lopes’ group,10we recently showed in adults with obesity and diabetes that 12 weeks of low-volume HIIE (1×90% peak volume of oxygen for 4 min,3 times per week)did not reduce AIx.11Although it appears that chronic aerobic exercise appears to decrease AIx in healthy individuals,the effect in people with metabolic diseases remains unclear.

An acute bout of exercise may not improve central arterial stiffness(as measured via carotid-femoral pulse wave velocity(PWV)),but systematic reviews and meta-analyses show that chronic,regular aerobic training may be required to reduce central arterial stiffness in healthy adults12and in those with cardiovascular diseases.13As highlighted in the commentary by Lopes et al.,1it is unlikely that acute exercise provides a suff icient stimulus to promote structural changes in the arteries.However,the effect of chronic,regular HIIE appears to have inconsistent findings.Similar to the Lopes’et al.group,10we found a signif icant reduction in PWV (albeit small) after our 12 weeks of low-volume HIIE intervention in adults with type 2 diabetes and obesity.11However,we did not observe a reduction in PWV following MICE.11Yet another study conducted by our group found no reduction in PWV following 12 weeks of HIIE in adults with type 1 diabetes (4×4 min at 85%－95%peak heart rate(HRpeak)interspersed with 3 min of active recovery at 50%－70%HRpeak,3 times per week).14This result was surprising,given that we did not find a signif icant difference in transient responses between adults with type 1 or type 2 diabetes in central arterial stiffness,wave ref lections,or hemodynamics following a bout of HIIE.2Similarly,Holloway et al.15found that 6 weeks of HIIE in young,healthy adults resulted in no change in PWV.It should be noted that the work-to-rest ratio employed in the Holloway study15was 1:2;whereas the work of our laboratory and the Lopes’group10was based on higher work-to-rest ratios.Given the accelerated cardiovascular pathology observed in metabolic diseases,a more aggressive exercise prescription may be required to provide an adequate stimulus to elicit chronic arterial structural changes.Further research needs to be conducted to determine the effect and underlying mechanisms of HIIE as a potential therapy for improving central arterial stiffness in metabolic diseases.

Sex differences should be more thoroughly evaluated when examining the effect of HIIE on central arterial stiffness,wave ref lections,and hemodynamic responses.Important points have been raised in the commentary by Lopes et al.1including that females appear to experience a greater reduction in AIx than males following HIIE.We agree,and we recognize that not performing a sex analysis may have attenuated the results observed in AIx in our study.A metaanalysis of 37 prospective trials showed that diabetes led to a profoundly (50%) greater relative risk of fatal coronary heart disease in females when compared to males.16The greater cardiovascular burden experienced by females should be accounted for in future studies using larger sample sizes to examine sex differences.

Early evidence suggests that HIIE is effective in eliciting a transient reduction in AIx in individuals with metabolic conditions (such as diabetes and/or obesity),which is not observed with MICE.This suggests that there may be transient improvements in cardiac and vascular function,which play a crucial role in the management of arterial health,similar to the changes observed in insulin sensitivity with acute exercise.Given the cardiovascular burden experienced by individuals with metabolic diseases,it is important that further research be conducted to elucidate the role of exercise intensity,sex,and disease status on acute and chronic exercise-related adaptions to arterial structure and health.

Authors’contributions

KLW conceived the letter of response and drafted the manuscript;AS,ASL,SMT,and NAJ provided critical input for the manuscript.All authors have read and approved the final version of the manuscript,and agree with the order of presentation of the authors.

Competing interests

The authors declare that they have no competing interests.