Age affects the association of red blood cell indices with efficacy of remote ischemic conditioning in patients with acute moderate ischemic stroke.
Acute ischemic stroke
Red cell indices
Remote ischemic conditioning
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
29 Sep 2024
29 Sep 2024
Historique:
received:
02
07
2024
accepted:
25
09
2024
medline:
30
9
2024
pubmed:
30
9
2024
entrez:
29
9
2024
Statut:
epublish
Résumé
We conducted a post hoc analysis of Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke (RICAMIS) to investigate whether red blood cell (RBC) indices are associated with efficacy of remote ischemic conditioning (RIC), and whether the association is affected by age. In this post hoc analysis, patients with RBC indices at admission were enrolled. RBC indices including RBC count, hematocrit (HCT), mean corpuscular volume (MCV), hemoglobin (HB), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were analyzed. According to the median of these RBC indices, eligible patients were divided into high and low groups, which were further subdivided into RIC and control subgroups. Primary endpoint was excellent functional outcome defined as a modified Rankin Scale score of 0-1 at 90 days, which was used to evaluate RIC efficacy. RIC efficacy as well as effect of age on RIC efficacy were analyzed across the high and low groups of different RBC indices, and the interaction effects of RBC indices on RIC efficacy were evaluated. A total of 1640 patients were enrolled in the final analysis. In overall patients, no significant interaction effects of RIC intervention by all RBC indices were found, although there was a trend in interaction effect of RIC intervention by MCH (p = 0.116). However, we found an effect of age on the association of MCH with RIC efficacy. In patients over 60 years old, MCH significantly affected RIC efficacy (p = 0.006) and RIC significantly produced a higher proportion of primary outcome in high MCH (72.6% vs. 59.1%, P < 0.001) vs. low MCH group (61.2% vs. 62%, P = 0.829), which was not identified in patients under 60 years old. Furthermore, RIC efficacy decreased with increasing age in patients with low MCH with significant interaction effect (p = 0.012), while RIC efficacy increased with increasing age in patients with high MCH although no significant interaction (p = 0.126). No significant interaction effects of RIC intervention by RBC count, HCT, MCV, HB, and MCHC were found regardless of age. This secondary analysis of RICAMIS suggested that RIC exhibited more obvious benefit in AIS patients over 60 years old with high MCH compared with those with low MCH group, but RBC count, HCT, MCV, HB, and MCHC were not associated with the efficacy of RIC treatment regardless of age.
Identifiants
pubmed: 39343777
doi: 10.1038/s41598-024-74293-9
pii: 10.1038/s41598-024-74293-9
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
22561Subventions
Organisme : the Science and Technology Project Plan of Liaoning Province
ID : 2022JH2/101500020
Informations de copyright
© 2024. The Author(s).
Références
Powers, W. J. et al. 2018 guidelines for the early management of patients with Acute ischemic stroke: a Guideline for Healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 49 (3), e46–e110 (2018).
pubmed: 29367334
doi: 10.1161/STR.0000000000000158
Liu, L. et al. Chinese Stroke Association guidelines for clinical management of cerebrovascular disorders: executive summary and 2019 update of clinical management of ischaemic cerebrovascular diseases. Stroke Vasc Neurol.5 (2), 159–176 (2020).
pubmed: 32561535
pmcid: 7337371
doi: 10.1136/svn-2020-000378
O’Collins, V. E. et al. 1,026 experimental treatments in acute stroke. Ann. Neurol.59 (3), 467–477 (2006).
pubmed: 16453316
doi: 10.1002/ana.20741
Lu, M., Wang, Y., Ren, H., Yin, X. & Li, H. Research progress on the mechanism of action and clinical application of remote ischemic post-conditioning for acute ischemic stroke. Clin. Neurol. Neurosurg.244, 108397 (2024).
pubmed: 38968813
doi: 10.1016/j.clineuro.2024.108397
Kan, X. et al. Efficacy and safety of remote ischemic conditioning for acute ischemic stroke: a comprehensive meta-analysis from randomized controlled trials. CNS Neurosci. Ther.29 (9), 2445–2456 (2023).
pubmed: 37183341
pmcid: 10401132
doi: 10.1111/cns.14240
Zhou, D. et al. Remote ischemic conditioning: a promising therapeutic intervention for multi-organ protection. Aging (Albany NY). 10 (8), 1825–1855 (2018).
pubmed: 30115811
doi: 10.18632/aging.101527
Keevil, H., Phillips, B. E. & England, T. J. Remote ischemic conditioning for stroke: a critical systematic review. Int. J. Stroke. 19 (3), 271–279 (2024).
pubmed: 37466245
doi: 10.1177/17474930231191082
Kleinbongard, P., Skyschally, A. & Heusch, G. Erratum to: Cardioprotection by remote ischemic conditioning and its signal transduction. Pflugers Arch.469 (5–6), 843 (2017).
pubmed: 28154919
doi: 10.1007/s00424-017-1936-8
Baranova, K., Nalivaeva, N. & Rybnikova, E. Neuroadaptive biochemical mechanisms of remote ischemic conditioning. Int. J. Mol. Sci.24 (23), 17032 (2023).
pubmed: 38069355
pmcid: 10707673
doi: 10.3390/ijms242317032
Comità, S., Rubeo, C., Giordano, M., Penna, C. & Pagliaro, P. Pathways for Cardioprotection in Perspective: Focus on Remote Conditioning and Extracellular vesicles. Biology (Basel). 12(2): 308. (2023).
Lieder, H. R. et al. Vago-Splenic Axis in Signal Transduction of Remote Ischemic Preconditioning in pigs and rats. Circ. Res.123 (10), 1152–1163 (2018).
pubmed: 30359199
pmcid: 7304918
doi: 10.1161/CIRCRESAHA.118.313859
Lieder, H. R. et al. Vago-splenic signal transduction of cardioprotection in humans. Eur. Heart J.45 (34), 3164–3177 (2024).
pubmed: 38842545
doi: 10.1093/eurheartj/ehae250
Hildebrandt, H. A. et al. Kinetics and Signal Activation Properties of circulating factor(s) from healthy volunteers undergoing remote ischemic pre-conditioning. JACC Basic. Transl Sci.1 (1–2), 3–13 (2016).
pubmed: 27642642
pmcid: 5012372
doi: 10.1016/j.jacbts.2016.01.007
Lieder, H. R. et al. Platelet-mediated transfer of Cardioprotection by Remote Ischemic Conditioning and its abrogation by Aspirin but not by Ticagrelor. Cardiovasc. Drugs Ther.37 (5), 865–876 (2023).
pubmed: 35595877
doi: 10.1007/s10557-022-07345-9
Hess, D. C. et al. Remote ischaemic conditioning-a new paradigm of self-protection in the brain. Nat. Rev. Neurol.11 (12), 698–710 (2015).
pubmed: 26585977
doi: 10.1038/nrneurol.2015.223
Weir, P., Maguire, R., O’Sullivan, S. E. & England, T. J. A meta-analysis of remote ischaemic conditioning in experimental stroke. J. Cereb. Blood Flow. Metab.41 (1), 3–13 (2021).
pubmed: 32538284
doi: 10.1177/0271678X20924077
Dammavalam, V. et al. Neuroprotection during Thrombectomy for Acute ischemic stroke: a review of future therapies. Int. J. Mol. Sci.25 (2), 891 (2024).
pubmed: 38255965
pmcid: 10815099
doi: 10.3390/ijms25020891
Zhao, W., Hausenloy, D. J., Hess, D. C., Yellon, D. M. & Ji, X. Remote ischemic conditioning: challenges and opportunities. Stroke. 54 (8), 2204–2207 (2023).
pubmed: 37417240
doi: 10.1161/STROKEAHA.123.043279
Chen, H. S. et al. Effect of remote ischemic conditioning vs Usual Care on neurologic function in patients with Acute Moderate Ischemic Stroke: the RICAMIS Randomized Clinical Trial. JAMA. 328 (7), 627–636 (2022).
pubmed: 35972485
pmcid: 9382441
doi: 10.1001/jama.2022.13123
Blauenfeldt, R. A. et al. Remote ischemic conditioning for Acute Stroke: the RESIST Randomized Clinical Trial. JAMA. 330 (13), 1236–1246 (2023).
pubmed: 37787796
pmcid: 10548297
doi: 10.1001/jama.2023.16893
Končekova, J., Kotorova, K., Gottlieb, M., Bona, M. & Bonova, P. Remote ischaemic preconditioning accelerates brain to blood glutamate efflux via EAATs-mediated transport. Neurochem Res.48 (12), 3560–3570 (2023).
pubmed: 37528283
pmcid: 10584753
doi: 10.1007/s11064-023-04002-x
Jachova, J., Gottlieb, M., Nemethova, M., Bona, M. & Bonova, P. Brain to blood efflux as a mechanism underlying the neuroprotection mediated by rapid remote preconditioning in brain ischemia. Mol. Biol. Rep.47 (7), 5385–5395 (2020).
pubmed: 32627140
doi: 10.1007/s11033-020-05626-w
Bonova, P. et al. Accelerated capacity of glutamate uptake via blood elements as a possible tool of rapid remote conditioning mediated tissue protection. Neurochem Int.142, 104927 (2021).
pubmed: 33259861
doi: 10.1016/j.neuint.2020.104927
Wang, L. et al. Remote ischemic conditioning enhances oxygen supply to ischemic brain tissue in a mouse model of stroke: role of elevated 2,3-biphosphoglycerate in erythrocytes. J. Cereb. Blood Flow. Metab.41 (6), 1277–1290 (2021).
pubmed: 32933360
doi: 10.1177/0271678X20952264
Bonova, P. et al. Rapid remote conditioning mediates modulation of blood cell paracrine activity and leads to the production of a secretome with neuroprotective features. J. Neurochem. 154 (1), 99–111 (2020).
pubmed: 31600838
doi: 10.1111/jnc.14889
Gu, T. et al. The role of plasma Extracellular vesicles in Remote Ischemic Conditioning and Exercise-Induced ischemic tolerance. Int. J. Mol. Sci.23 (6), 3334 (2022).
pubmed: 35328755
pmcid: 8951333
doi: 10.3390/ijms23063334
Ramos-Zaldívar, H. M. et al. Extracellular vesicles through the blood-brain barrier: a review. Fluids Barriers CNS. 19 (1), 60 (2022).
pubmed: 35879759
pmcid: 9310691
doi: 10.1186/s12987-022-00359-3
Cui, Y., Yuan, Z. M., Liu, Q. Y., Wang, Y. J. & Chen, H. S. Remote ischemic conditioning and outcomes in Acute Ischemic Stroke with Versus without large artery atherosclerosis. Stroke. 54 (12), 3165–3168 (2023).
pubmed: 37850359
doi: 10.1161/STROKEAHA.123.045040
Kim, T. H. & Vemuganti, R. Effect of sex and age interactions on functional outcome after stroke. CNS Neurosci. Ther.21 (4), 327–336 (2015).
pubmed: 25404174
doi: 10.1111/cns.12346
Weimar, C. et al. Age and National Institutes of Health Stroke Scale score within 6 hours after onset are accurate predictors of outcome after cerebral ischemia: development and external validation of prognostic models. Stroke. 35 (1), 158–162 (2004).
pubmed: 14684776
doi: 10.1161/01.STR.0000106761.94985.8B
Beuker, C. et al. Association of age with 1-year outcome in patients with acute ischaemic stroke treated with thrombectomy: real-world analysis in 18 506 patients. J. Neurol. Neurosurg. Psychiatry. 94 (8), 631–637 (2023).
pubmed: 37001983
doi: 10.1136/jnnp-2022-330506
Bizjak, D. A. et al. Does endurance training improve red blood cell aging and hemorheology in moderate-trained healthy individuals. J. Sport Health Sci.9 (6), 595–603 (2020).
pubmed: 33308809
doi: 10.1016/j.jshs.2019.02.002
Bettiol, A. et al. Erythrocyte oxidative stress and thrombosis. Expert Rev. Mol. Med.24, e31 (2022).
pubmed: 36017709
pmcid: 9884766
doi: 10.1017/erm.2022.25
Papadopoulos, C. et al. Unexplored roles of erythrocytes in Atherothrombotic Stroke. Neurol. Int.15 (1), 124–139 (2023).
pubmed: 36810466
pmcid: 9944955
doi: 10.3390/neurolint15010011
Shams Vahdati, S., Ala, A., Vahed, N., Mohammadi, S. & Ameli, H. Complete blood count parameters as prognostic factor of stroke: a systematic review. Basic. Clin. Neurosci.13 (6), 745–754 (2022).
pubmed: 37323954
pmcid: 10262284
doi: 10.32598/bcn.2021.2168.2
Zhang, R. et al. Hemoglobin concentration and clinical outcomes after Acute ischemic stroke or transient ischemic attack. J. Am. Heart Assoc.10 (23), e022547 (2021).
pubmed: 34845923
pmcid: 9075388
doi: 10.1161/JAHA.121.022547
Wu, T. H. et al. Gradient relationship between increased Mean Corpuscular volume and Mortality Associated with cerebral ischemic stroke and ischemic heart disease: a longitudinal study on 66,294 Taiwanese. Sci. Rep.8 (1), 16517 (2018).
pubmed: 30409990
pmcid: 6224537
doi: 10.1038/s41598-018-34403-w
Grau, M. et al. Effects of recurring IPC vs. rIPC maneuvers on Exercise Performance, Pulse Wave Velocity, and Red Blood Cell Deformability: special consideration of Reflow varieties. Biology (Basel). 11 (2), 163 (2022).
pubmed: 35205030
Tomschi, F., Niemann, D., Bloch, W., Predel, H. G. & Grau, M. Ischemic preconditioning enhances performance and erythrocyte deformability of responders. Int. J. Sports Med.39 (8), 596–603 (2018).
pubmed: 29883988
doi: 10.1055/a-0631-2887
Hess, D. C. et al. Conditioning medicine for ischemic and hemorrhagic stroke. Cond Med.4 (3), 124–129 (2021).
pubmed: 34414362
pmcid: 8372992
Abel, F. et al. Extracellular vesicles isolated from patients undergoing remote ischemic preconditioning decrease hypoxia-evoked apoptosis of cardiomyoblasts after isoflurane but not propofol exposure. PLoS One. 15 (2), e0228948 (2020).
pubmed: 32059016
pmcid: 7021285
doi: 10.1371/journal.pone.0228948
Frey, U. H. et al. Remote ischaemic preconditioning increases serum extracellular vesicle concentrations with altered micro-RNA signature in CABG patients. Acta Anaesthesiol. Scand.63 (4), 483–492 (2019).
pubmed: 30548252
doi: 10.1111/aas.13296
LoBue, A. et al. Red blood cell endothelial nitric oxide synthase: a major player in regulating cardiovascular health. Br. J. Pharmacol. (2023).
Kleinbongard, P. et al. Red blood cells express a functional endothelial nitric oxide synthase. Blood. 107 (7), 2943–2951 (2006).
pubmed: 16368881
doi: 10.1182/blood-2005-10-3992
Murillo, D., Kamga, C., Mo, L. & Shiva, S. Nitrite as a mediator of ischemic preconditioning and cytoprotection. Nitric Oxide. 25 (2), 70–80 (2011).
pubmed: 21277988
pmcid: 3118399
doi: 10.1016/j.niox.2011.01.003
Kimura, H., Hamasaki, N., Yamamoto, M. & Tomonaga, M. Circulation of red blood cells having high levels of 2,3-bisphosphoglycerate protects rat brain from ischemic metabolic changes during hemodilution. Stroke. 26 (8), 1431–1436 (1995). discussion 1436–1437.
pubmed: 7631349
doi: 10.1161/01.STR.26.8.1431
Ninness, J. R., Kimber, R. W. & McDonald, J. W. Erythrocyte 2,3-DPG, ATP and oxygen affinity in hemodialysis patients. Can. Med. Assoc. J.111 (7), 661–665 (1974).
pubmed: 4413276
pmcid: 1947864
Sun, C. W. et al. Hemoglobin β93 cysteine is not required for export of nitric oxide Bioactivity from the Red Blood Cell. Circulation. 139 (23), 2654–2663 (2019).
pubmed: 30905171
pmcid: 6546526
doi: 10.1161/CIRCULATIONAHA.118.039284
Bonova, P. et al. Identification of proteins responsible for the neuroprotective effect of the Secretome Derived from Blood cells of remote ischaemic conditioned rats. Biomolecules. 12 (10), 1423 (2022).
pubmed: 36291633
pmcid: 9599669
doi: 10.3390/biom12101423
Kleinbongard, P. et al. Confounders of Cardioprotection by remote ischemic preconditioning in patients undergoing coronary artery bypass grafting. Cardiology. 133 (2), 128–133 (2016).
pubmed: 26536214
doi: 10.1159/000441216
Kleinbongard, P., Bøtker, H. E., Ovize, M., Hausenloy, D. J. & Heusch, G. Co-morbidities and co-medications as confounders of cardioprotection-does it matter in the clinical setting. Br. J. Pharmacol.177 (23), 5252–5269 (2020).
pubmed: 31430831
pmcid: 7680006
doi: 10.1111/bph.14839
Racine, M. L. & Dinenno, F. A. Reduced deformability contributes to impaired deoxygenation-induced ATP release from red blood cells of older adult humans. J. Physiol.597 (17), 4503–4519 (2019).
pubmed: 31310005
doi: 10.1113/JP278338
Spinelli, S. et al. Aging Injury impairs Structural properties and Cell Signaling in Human Red Blood cells; Açaì Berry is a Keystone. Antioxidants (Basel). 12(4). (2023).
Mairbäurl, H. Red blood cells in sports: effects of exercise and training on oxygen supply by red blood cells. Front. Physiol.4, 332 (2013).
pubmed: 24273518
pmcid: 3824146
doi: 10.3389/fphys.2013.00332
Zhao, W., Li, S., Ren, C., Meng, R. & Ji, X. Chronic remote ischemic conditioning may mimic regular Exercise:perspective from Clinical studies. Aging Dis.9 (1), 165–171 (2018).
pubmed: 29392091
pmcid: 5772854
doi: 10.14336/AD.2017.1015
Wang, Q., Li, W. N., Otkur, W., Cui, Y. & Chen, H. S. Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic Immune inflammation index and efficacy of remote ischemic conditioning in Acute ischemic stroke: a Post Hoc exploratory analysis of the RICAMIS Study. J. Inflamm. Res.17, 5543–5553 (2024).
pubmed: 39185106
pmcid: 11344552
doi: 10.2147/JIR.S460928
Zhang, Y. N. et al. Diabetes, fasting blood glucose and the efficacy of remote ischaemic conditioning: a secondary analysis of the RICAMIS trial. Diabetes Obes. Metab.25 (9), 2689–2696 (2023).
pubmed: 37288603
doi: 10.1111/dom.15156
Agrawal, R. et al. Assessment of red blood cell deformability in type 2 diabetes mellitus and diabetic retinopathy by dual optical tweezers stretching technique. Sci. Rep.6, 15873 (2016).
pubmed: 26976672
pmcid: 4792142
doi: 10.1038/srep15873