Alteration in Carotid Arterial Stiffness During Passive Leg Raising May Reflect Vascular Endothelial Function
Background: Flow-mediated dilation (FMD) is the established parameter of endothelial function but requires skill and specialized equipment. This study aimed to investigate whether changes in carotid artery ultrasound parameters during passive leg raising (PLR) could reflect FMD values.Methods and Re...
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| Published in | Circulation Reports p. CR-25-0047 |
|---|---|
| Main Authors | , , |
| Format | Journal Article |
| Language | English |
| Published |
The Japanese Circulation Society
27.08.2025
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| Subjects | |
| Online Access | Get full text |
| ISSN | 2434-0790 2434-0790 |
| DOI | 10.1253/circrep.CR-25-0047 |
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| Abstract | Background: Flow-mediated dilation (FMD) is the established parameter of endothelial function but requires skill and specialized equipment. This study aimed to investigate whether changes in carotid artery ultrasound parameters during passive leg raising (PLR) could reflect FMD values.Methods and Results: Thirty-six adult males underwent standard FMD measurement. After 15 min of rest, a carotid artery ultrasound was performed to measure the maximal common carotid artery (CCA) diameter and stiffness parameter β. The PLR maneuver was then performed, and the change in these parameters (∆CCAPLRand ∆βPLR) was calculated. There were 6 participants with decreased FMD value (<4%). While the maximal CCA diameter remained unchanged during PLR (P=0.54), the stiffness parameter β significantly decreased during PLR compared with baseline (P=0.014). Among several carotid artery ultrasound parameters, ∆βPLRcorrelated most strongly with FMD (r=−0.70; P<0.001). Receiver operating characteristic analysis showed that ∆βPLRpredicted decreased FMD with an area under the curve of 0.89, sensitivity of 87%, and specificity of 83% at an optimal cut-off of 4.7%.Conclusions: Change in carotid arterial stiffness parameter β during the PLR maneuver correlated with FMD, suggesting it may serve as an alternative indicator for endothelial function. |
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| AbstractList | Background: Flow-mediated dilation (FMD) is the established parameter of endothelial function but requires skill and specialized equipment. This study aimed to investigate whether changes in carotid artery ultrasound parameters during passive leg raising (PLR) could reflect FMD values.Methods and Results: Thirty-six adult males underwent standard FMD measurement. After 15 min of rest, a carotid artery ultrasound was performed to measure the maximal common carotid artery (CCA) diameter and stiffness parameter β. The PLR maneuver was then performed, and the change in these parameters (∆CCAPLRand ∆βPLR) was calculated. There were 6 participants with decreased FMD value (<4%). While the maximal CCA diameter remained unchanged during PLR (P=0.54), the stiffness parameter β significantly decreased during PLR compared with baseline (P=0.014). Among several carotid artery ultrasound parameters, ∆βPLRcorrelated most strongly with FMD (r=−0.70; P<0.001). Receiver operating characteristic analysis showed that ∆βPLRpredicted decreased FMD with an area under the curve of 0.89, sensitivity of 87%, and specificity of 83% at an optimal cut-off of 4.7%.Conclusions: Change in carotid arterial stiffness parameter β during the PLR maneuver correlated with FMD, suggesting it may serve as an alternative indicator for endothelial function. |
| ArticleNumber | CR-25-0047 |
| Author | Kazunori Okada Yasuhiro Hayashi Masahiro Nakabachi |
| Author_xml | – sequence: 1 givenname: Kazunori surname: Okada fullname: Okada, Kazunori – sequence: 2 givenname: Masahiro surname: Nakabachi fullname: Nakabachi, Masahiro – sequence: 3 givenname: Yasuhiro surname: Hayashi fullname: Hayashi, Yasuhiro |
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| Cites_doi | 10.1152/ajpheart.00595.2018 10.1093/eurjcn/zvab102 10.1093/cvr/cvaa085 10.1016/j.atherosclerosis.2010.05.019 10.3390/jcm12082935 10.1016/j.echo.2007.11.011 10.1161/ATVBAHA.123.319932 10.5551/jat.RV22029 10.1161/CIRCHEARTFAILURE.121.008935 10.1016/j.ultrasmedbio.2019.02.014 10.1016/0140-6736(92)93147-F 10.1016/j.jacc.2019.08.012 10.5551/jat.63756 10.1056/NEJM200002173420702 10.1111/anae.12560 10.1253/circj.CJ-23-0890 10.5551/jat.RV17047 10.1161/HYPERTENSIONAHA.117.09612 10.1253/circj.CJ-23-0285 10.1016/j.atherosclerosis.2021.07.009 10.1093/eurheartj/ehz350 10.1253/circj.CJ-22-0810 10.1007/s10396-009-0238-y 10.1016/S0735-1097(01)01746-6 10.5551/jat.31989 10.1186/cc8195 10.1016/S0735-1097(03)00994-X 10.1152/ajpheart.00471.2010 |
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| Copyright | 2025, THE JAPANESE CIRCULATION SOCIETY |
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| References_xml | – reference: 15. Morioka T, Mori K, Emoto M. Is stiffness parameter β useful for the evaluation of atherosclerosis?: Its clinical implications, limitations, and future perspectives. J Atheroscler Thromb 2021; 28: 435–453. – reference: 3. Osawa Y, Arai Y. Preventive effects of physical activity on the development of atherosclerosis: A narrative review. J Atheroscler Thromb 2025; 32: 11–19. – reference: 19. Godfrey GE, Dubrey SW, Handy JM. A prospective observational study of stroke volume responsiveness to a passive leg raise manoeuvre in healthy non-starved volunteers as assessed by transthoracic echocardiography. Anaesthesia 2014; 69: 306–313. – reference: 22. Widlansky ME, Gokce N, Keaney JF Jr, Vita JA. The clinical implications of endothelial dysfunction. J Am Coll Cardiol 2003; 42: 1149–1160. – reference: 4. Fujiyoshi A, Kohsaka S, Hata J, Hara M, Kai H, Masuda D, et al. JCS 2023 guideline on the primary prevention of coronary artery disease. Circ J 2024; 88: 763–842. – reference: 12. Kamran H, Salciccioli L, Namana V, Venkatesan B, Santana C, Stewart M, et al. Passive leg raising induced brachial artery dilation: Is an old technique a simpler method to measure endothelial function? Atherosclerosis 2010; 212: 188–192. – reference: 17. Thijssen DH, Black MA, Pyke KE, Padilla J, Atkinson G, Harris RA, et al. Assessment of flow-mediated dilation in humans: A methodological and physiological guideline. Am J Physiol Heart Circ Physiol 2011; 300: H2–H12. – reference: 27. Asami R, Tanaka T, Shimizu M, Seki Y, Nishiyama T, Sakashita H, et al. Ultrasonic vascular vector flow mapping for 2-D flow estimation. Ultrasound Med Biol 2019; 45: 1663–1674. – reference: 2. Ahmadi A, Argulian E, Leipsic J, Newby DE, Narula J. From subclinical atherosclerosis to plaque progression and acute coronary events: JACC State-of-the-Art Review. J Am Coll Cardiol 2019; 74: 1608–1617. – reference: 18. Stein JH, Korcarz CE, Hurst RT, Lonn E, Kendall CB, Mohler ER, et al. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: A consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Endorsed by the Society for Vascular Medicine. J Am Soc Echocardiogr 2008; 21: 93–111. – reference: 6. Hambrecht R, Wolf A, Gielen S, Linke A, Hofer J, Erbs S, et al. Effect of exercise on coronary endothelial function in patients with coronary artery disease. N Engl J Med 2000; 342: 454–460. – reference: 28. Kamimura T, Aoki S, Nezu T, Eto F, Shiga Y, Nakamori M, et al. Association between carotid wall shear stress-based vascular vector flow mapping and cerebral small vessel disease. J Atheroscler Thromb 2023; 30: 1165–1175. – reference: 16. Petrova M, Gavino A, Li Y, McLachlan CS. Comparison of parameters for assessment of carotid stiffness and their association with carotid atherosclerosis in rural Australian adults: A pilot study. J Clin Med 2023; 12: 2935, doi:10.3390/jcm12082935. – reference: 25. Takei Y, Tomiyama H, Higashi Y, Yamashina A, Chikamori T. Association between endothelial dysfunction and left ventricular diastolic stiffness: Subanalysis of the flow-mediated dilation Japan (FMD-J) study. Circ J 2023; 87: 1203–1211. – reference: 8. Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992; 340: 1111–1115. – reference: 9. Maruhashi T, Soga J, Fujimura N, Idei N, Mikami S, Iwamoto Y, et al. Endothelial function is impaired in patients receiving antihypertensive drug treatment regardless of blood pressure level: FMD-J study (flow-mediated dilation Japan). Hypertension 2017; 70: 790–797. – reference: 23. Dikalov S, Itani H, Richmond B, Vergeade A, Rahman SMJ, Boutaud O, et al. Tobacco smoking induces cardiovascular mitochondrial oxidative stress, promotes endothelial dysfunction, and enhances hypertension. Am J Physiol Heart Circ Physiol 2019; 316: H639–H646. – reference: 20. Biais M, Vidil L, Sarrabay P, Cottenceau V, Revel P, Sztark F. Changes in stroke volume induced by passive leg raising in spontaneously breathing patients: Comparison between echocardiography and Vigileo/FloTrac device. Crit Care 2009; 13: R195, doi:10.1186/cc8195. – reference: 10. Thijssen DHJ, Bruno RM, van Mil ACCM, Holder SM, Faita F, Greyling A, et al. Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans. Eur Heart J 2019; 40: 2534–2547. – reference: 11. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: A report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 2002; 39: 257–265. – reference: 1. Kawai K, Finn AV, Virmani R. Subclinical atherosclerosis collaborative. Arterioscler Thromb Vasc Biol 2024; 44: 12–23. – reference: 24. Saz-Lara A, Martínez-Vizcaíno V, Sequí-Domínguez I, Álvarez-Bueno C, Notario-Pacheco B, Cavero-Redondo I. The effect of smoking and smoking cessation on arterial stiffness: A systematic review and meta-analysis. Eur J Cardiovasc Nurs 2022; 21: 297–306. – reference: 13. Terminology and Diagnostic Criteria Committee, Japan Society of Ultrasonics in Medicine. Standard method for ultrasound evaluation of carotid artery lesions. J Med Ultrason 2009; 36: 219–226. – reference: 21. van de Bovenkamp AA, Wijkstra N, Oosterveer FPT, Vonk Noordegraaf A, Bogaard HJ, van Rossum AC, et al. The value of passive leg raise during right heart catheterization in diagnosing heart failure with preserved ejection fraction. Circ Heart Fail 2022; 15: e008935, doi:10.1161/CIRCHEARTFAILURE.121.008935. – reference: 14. Nezu T, Hosomi N, Aoki S, Matsumoto M. Carotid intima-media thickness for atherosclerosis. J Atheroscler Thromb 2016; 23: 18–31. – reference: 7. Silva JKTNF, Menêses AL, Parmenter BJ, Ritti-Dias RM, Farah BQ. Effects of resistance training on endothelial function: A systematic review and meta-analysis. Atherosclerosis 2021; 333: 91–99. – reference: 26. Tsukada YT, Aoki-Kamiya C, Mizuno A, Nakayama A, Ide T, Aoyama R, et al. JCS/JCC/JACR/JATS 2024 guideline on cardiovascular practice with consideration for diversity, equity, and inclusion. Circ J 2025; 89: 658–739. – reference: 5. Alexander Y, Osto E, Schmidt-Trucksäss A, Shechter M, Trifunovic D, Duncker DJ, et al. Endothelial function in cardiovascular medicine: A consensus paper of the European Society of Cardiology Working Groups on Atherosclerosis and Vascular Biology, Aorta and Peripheral Vascular Diseases, Coronary Pathophysiology and Microcirculation, and Thrombosis. 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