Atherosclerosis 233 (2014) 1e2
Contents lists available at ScienceDirect
Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis
Invited commentary
Response to: ‘Reshape of the arterial wall as a slow reacting vascular structure’ Dick H.J. Thijssen a, b, *, Ellen A. Dawson a, Inge van den Munckhof b, Gurpreet K. Birk a, N. Timothy Cable a, Daniel J. Green a, c a b c
Research Institute for Sport and Exercise Science, Liverpool John Moores University, Tom Reilly Building, Byrom Street, Liverpool L3 3AF, United Kingdom Department of Physiology, Radboud University Nijmegen Medical Centre, The Netherlands School of Sport Science, Exercise and Health, The University of Western Australia, Crawley 6009, Western Australia
a r t i c l e i n f o Article history: Received 15 November 2013 Accepted 18 November 2013 Available online 18 December 2013 Keywords: Intima-media thickness Cardiovascular risk Exercise training ultrasound
We sincerely thank Prof. Schmidt-Trucksäss for his constructive comments on our recent paper in Atherosclerosis [1], in which issues were raised related to the rapidity of change in wall thickness (WT). Some years ago, we were similarly ‘surprised’ when we observed a significant increase in carotid and femoral artery WT after only 8 weeks bed rest, and that this increase was (partly) prevented by resistive vibration exercise. [2] We hypothesised that, because of the significant number of smooth muscle cells in the medial-layer, vascular tone may importantly influence measurements of WT. In a subsequent study [3], we confirmed this hypothesis by continuously recording carotid and femoral artery WT in young and older subjects before and after administration of sublingual nitroglycerine. Accordingly, these observations somewhat changed our view that WT is solely a measure of arterial structure. One issue raised by Prof. Schmidt-Trucksäss was the observation of similar changes in femoral and carotid artery WT, despite the remarkable difference in exercise-induced perfusion between both vessels. Whilst the impact of perfusion (or shear stress) on arterial
DOI of original articles: http://dx.doi.org/10.1016/j.atherosclerosis.2013.05.013, http://dx.doi.org/10.1016/j.atherosclerosis.2013.10.037. * Corresponding author. Research Institute for Sport and Exercise Science, Liverpool John Moores University, Tom Reilly Building, Byrom Street, Liverpool L3 3AF, United Kingdom. E-mail address: [email protected] (D.H.J. Thijssen). 0021-9150/$ e see front matter Ó 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.atherosclerosis.2013.11.077
remodeling is well-known, perfusion per se may not be the only stimulus for adaptations in WT. In a recent study, we observed differences between the trained and untrained arms of elite squash players in brachial artery diameter, but not WT [4]. Both arms possessed lower WT than a non-athlete control group. Subsequently, we found a small, but significant decline in brachial artery WT in both arms after 8-weeks bilateral handgrip training, in which we unilaterally abolished exercise-induced perfusion [5]. We interpret these findings as supportive of systemic adaptations in WT during exercise training, with local perfusion playing a more important role in artery diameter change. Prof. Schmidt-Trucksäss also mentions the allocation of subjects to groups, rather than randomization, and the statistical analysis used. Allocation of subjects to the intervention groups did result in unequal distribution of subjects, but was not undertaken on a selective basis. We analysed our data per group, as this provides a direct answer to our primary research question (i.e. ‘does exercise training lead to similar changes in carotid and femoral wall thickness?’). To correct for potential differences in baseline values, we have repeated our data analysis using absolute changes from baseline. These analyses support our primary conclusions, in that a significant change across time was reported for WT and wall:lumen-ratio (P < 0.001 and 0.005, respectively), with no differences between arteries (interaction P-value: 0.14 and 0.07, respectively). Analysis of relative changes from baseline resulted in similar findings. Despite these potential limitations, which we acknowledge, we went to considerable effort to validate and improve the reproducibility of our analysis, which is automated and observed-independent analysis [6,7]. Moreover, data analysis was performed blinded (to subjects and moment of assessment), which supports the robustness of our data set. In summary, we acknowledge that our study was a small hypothesis-raising physiological experiment. We strongly agree with the inference that larger, randomised controlled studies are required for independent verification, an important fundamental tenet in science [8]. Indeed, we hope that eminent researchers in this field, like Prof. Schmidt-Trucksäss, will consider this challenge.
2
D.H.J. Thijssen et al. / Atherosclerosis 233 (2014) 1e2
References [1] Thijssen DH, Dawson EA, van den Munckhof IC, Birk GK, Timothy Cable N, Green DJ. Local and systemic effects of leg cycling training on arterial wall thickness in healthy humans. Atherosclerosis 2013;229:282e6. [2] van Duijnhoven NT, Green DJ, et al. Impact of bed rest on conduit artery remodeling: effect of exercise countermeasures. Hypertension 2010;56:240e6. [3] Thijssen DH, Scholten RR, van den Munckhof IC, Benda N, Green DJ, Hopman MT. Acute change in vascular tone alters intima-media thickness. Hypertension 2011;58:240e6. [4] Rowley NJ, Dawson EA, Birk GK, et al. Exercise and arterial adaptation in humans: uncoupling localized and systemic effects. J Appl Physiol 2011;110:1190e5.
[5] Thijssen DH, Dawson EA, van den Munckhof IC, et al. Exercise-mediated changes in conduit artery wall thickness in humans: role of shear stress. Am J Physiol 2011;301:H241e6. [6] Potter K, Green DJ, Reed CJ, et al. Carotid intima-medial thickness measured on multiple ultrasound frames: evaluation of a DICOM-based software system. Cardiovasc Ultrasound 2007;5:29. [7] Potter K, Reed CJ, Green DJ, Hankey GJ, Arnolda LF. Ultrasound settings significantly alter arterial lumen and wall thickness measurements. Cardiovasc Ultrasound 2008;6:6. [8] Problems with scientific research: How science goes wrong. The Economist; 2013. Oct 19th.
Contents lists available at ScienceDirect
Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis
Invited commentary
Response to: ‘Reshape of the arterial wall as a slow reacting vascular structure’ Dick H.J. Thijssen a, b, *, Ellen A. Dawson a, Inge van den Munckhof b, Gurpreet K. Birk a, N. Timothy Cable a, Daniel J. Green a, c a b c
Research Institute for Sport and Exercise Science, Liverpool John Moores University, Tom Reilly Building, Byrom Street, Liverpool L3 3AF, United Kingdom Department of Physiology, Radboud University Nijmegen Medical Centre, The Netherlands School of Sport Science, Exercise and Health, The University of Western Australia, Crawley 6009, Western Australia
a r t i c l e i n f o Article history: Received 15 November 2013 Accepted 18 November 2013 Available online 18 December 2013 Keywords: Intima-media thickness Cardiovascular risk Exercise training ultrasound
We sincerely thank Prof. Schmidt-Trucksäss for his constructive comments on our recent paper in Atherosclerosis [1], in which issues were raised related to the rapidity of change in wall thickness (WT). Some years ago, we were similarly ‘surprised’ when we observed a significant increase in carotid and femoral artery WT after only 8 weeks bed rest, and that this increase was (partly) prevented by resistive vibration exercise. [2] We hypothesised that, because of the significant number of smooth muscle cells in the medial-layer, vascular tone may importantly influence measurements of WT. In a subsequent study [3], we confirmed this hypothesis by continuously recording carotid and femoral artery WT in young and older subjects before and after administration of sublingual nitroglycerine. Accordingly, these observations somewhat changed our view that WT is solely a measure of arterial structure. One issue raised by Prof. Schmidt-Trucksäss was the observation of similar changes in femoral and carotid artery WT, despite the remarkable difference in exercise-induced perfusion between both vessels. Whilst the impact of perfusion (or shear stress) on arterial
DOI of original articles: http://dx.doi.org/10.1016/j.atherosclerosis.2013.05.013, http://dx.doi.org/10.1016/j.atherosclerosis.2013.10.037. * Corresponding author. Research Institute for Sport and Exercise Science, Liverpool John Moores University, Tom Reilly Building, Byrom Street, Liverpool L3 3AF, United Kingdom. E-mail address: [email protected] (D.H.J. Thijssen). 0021-9150/$ e see front matter Ó 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.atherosclerosis.2013.11.077
remodeling is well-known, perfusion per se may not be the only stimulus for adaptations in WT. In a recent study, we observed differences between the trained and untrained arms of elite squash players in brachial artery diameter, but not WT [4]. Both arms possessed lower WT than a non-athlete control group. Subsequently, we found a small, but significant decline in brachial artery WT in both arms after 8-weeks bilateral handgrip training, in which we unilaterally abolished exercise-induced perfusion [5]. We interpret these findings as supportive of systemic adaptations in WT during exercise training, with local perfusion playing a more important role in artery diameter change. Prof. Schmidt-Trucksäss also mentions the allocation of subjects to groups, rather than randomization, and the statistical analysis used. Allocation of subjects to the intervention groups did result in unequal distribution of subjects, but was not undertaken on a selective basis. We analysed our data per group, as this provides a direct answer to our primary research question (i.e. ‘does exercise training lead to similar changes in carotid and femoral wall thickness?’). To correct for potential differences in baseline values, we have repeated our data analysis using absolute changes from baseline. These analyses support our primary conclusions, in that a significant change across time was reported for WT and wall:lumen-ratio (P < 0.001 and 0.005, respectively), with no differences between arteries (interaction P-value: 0.14 and 0.07, respectively). Analysis of relative changes from baseline resulted in similar findings. Despite these potential limitations, which we acknowledge, we went to considerable effort to validate and improve the reproducibility of our analysis, which is automated and observed-independent analysis [6,7]. Moreover, data analysis was performed blinded (to subjects and moment of assessment), which supports the robustness of our data set. In summary, we acknowledge that our study was a small hypothesis-raising physiological experiment. We strongly agree with the inference that larger, randomised controlled studies are required for independent verification, an important fundamental tenet in science [8]. Indeed, we hope that eminent researchers in this field, like Prof. Schmidt-Trucksäss, will consider this challenge.
2
D.H.J. Thijssen et al. / Atherosclerosis 233 (2014) 1e2
References [1] Thijssen DH, Dawson EA, van den Munckhof IC, Birk GK, Timothy Cable N, Green DJ. Local and systemic effects of leg cycling training on arterial wall thickness in healthy humans. Atherosclerosis 2013;229:282e6. [2] van Duijnhoven NT, Green DJ, et al. Impact of bed rest on conduit artery remodeling: effect of exercise countermeasures. Hypertension 2010;56:240e6. [3] Thijssen DH, Scholten RR, van den Munckhof IC, Benda N, Green DJ, Hopman MT. Acute change in vascular tone alters intima-media thickness. Hypertension 2011;58:240e6. [4] Rowley NJ, Dawson EA, Birk GK, et al. Exercise and arterial adaptation in humans: uncoupling localized and systemic effects. J Appl Physiol 2011;110:1190e5.
[5] Thijssen DH, Dawson EA, van den Munckhof IC, et al. Exercise-mediated changes in conduit artery wall thickness in humans: role of shear stress. Am J Physiol 2011;301:H241e6. [6] Potter K, Green DJ, Reed CJ, et al. Carotid intima-medial thickness measured on multiple ultrasound frames: evaluation of a DICOM-based software system. Cardiovasc Ultrasound 2007;5:29. [7] Potter K, Reed CJ, Green DJ, Hankey GJ, Arnolda LF. Ultrasound settings significantly alter arterial lumen and wall thickness measurements. Cardiovasc Ultrasound 2008;6:6. [8] Problems with scientific research: How science goes wrong. The Economist; 2013. Oct 19th.
