Metabolic Syndrome and Efficacy of Remote Ischemic Postconditioning in Acute Moderate Ischemic Stroke: A Post Hoc Analysis of the RICAMIS Trial

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Metabolic Syndrome and Efficacy of Remote Ischemic Postconditioning in Acute Moderate Ischemic Stroke: A Post Hoc Analysis of the RICAMIS Trial

Yi‐Na Zhang, MD https://orcid.org/0000-0003-0921-0058, Qiong Wu, MD, Yu Cui, PhD https://orcid.org/0000-0002-4925-1500, Nan‐Nan Zhang, MM https://orcid.org/0009-0000-4414-2906, and Hui‐Sheng Chen, MD https://orcid.org/0000-0002-7486-1992 chszh@aliyun.comAuthor Info & Affiliations

Journal of the American Heart Association

New online

https://doi.org/10.1161/JAHA.124.037859

• Abstract
• Nonstandard Abbreviations and Acronyms
• Clinical Perspective
• METHODS
• RESULTS
• DISCUSSION
• CONCLUSIONS
• Sources of Funding
• Acknowledgments
• Footnotes
• Supplemental Material
• References
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Abstract

Background

Metabolic syndrome (METS) is associated with poor outcomes after acute ischemic stroke. This study aimed to investigate the relationship between METS and efficacy of remote ischemic postconditioning (RIPostC) in acute moderate ischemic stroke using the database of the RICAMIS (Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke) trial.

Methods and Results

In the RICAMIS trial, eligible participants were patients with acute moderate ischemic stroke within 48 hours of onset who did not receive reperfusion treatment. A total of 1482 patients were enrolled in this secondary analysis, including the METS (602) and non‐METS (880) group according to the METS definitions of the Chinese Diabetes Society, which was further subdivided into RIPostC and control subgroups. The primary outcome was excellent functional outcome, defined as a modified Rankin Scale score of 0 to 1 at 90 days. The differences in clinical outcomes between the RIPostC subgroup and control subgroup were compared in patients with METS or non‐METS, respectively, and the interaction effects of RIPostC treatment assignment with METS status were evaluated. The baseline characteristics between RIPostC and control subgroups across patients with METS and non‐METS were well balanced, except the difference in Trial of Org 10 172 in Acute Stroke Treatment stroke mechanism in the METS group. Compared with control, RIPostC was associated with high probability of excellent functional outcome in patients with METS (68.8% versus 56.1%; odds ratio [OR], 1.751 [95% CI, 1.248–2.456]; P=0.001), but not in patients without METS (66.6% versus 64.6%; OR, 1.103 [95% CI, 0.833–1.461]; P=0.494). Notably, a significant interaction effect between treatments (RIPostC or control) by different METS status on excellent functional outcome was observed (P=0.039).

Conclusions

The secondary analysis suggests for the first time that RIPostC may provide greater benefit in patients with acute ischemic stroke with METS versus non‐METS.

Nonstandard Abbreviations and Acronyms

AIS

acute ischemic stroke

LAA

large artery atherosclerosis

METS

metabolic syndrome

NIHSS

National Institutes of Health Stroke Scale

RICAMIS

Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke

RIPostC

remote ischemic postconditioning

TOAST

Trial of Org 10172 in Acute Stroke Treatment

Clinical Perspective

What Is New?

•

This is the first report of patients with acute moderate ischemic stroke, within 48 hours of onset, who did not receive reperfusion treatment and in whom remote ischemic postconditioning treatment produced greater probability of excellent clinical outcome in patients with metabolic syndrome compared with patients without metabolic syndrome.

What Are the Clinical Implications?

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Patients with acute moderate ischemic stroke with metabolic syndrome may get more benefit from remote ischemic postconditioning, which needs to be validated in future trials.(Why?)

Remote ischemic postconditioning (RIPostC), a noninvasive and nonpharmacological procedure performed by intermittently blocking the blood flow of both upper limbs, has been found to be potentially beneficial in acute ischemic stroke (AIS).^{1, 2} The recent RICAMIS (Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke) trial has demonstrated that RIPostC can improve 3‐month functional outcomes in patients with moderate AIS,³ although this finding was not confirmed by the RESIST (Remote Ischemic Conditioning in Patients With Acute Stroke) study.⁴ It is an important clinical concern to identify a suitable population who can benefit from RIPostC.

Metabolic syndrome (METS) represents a clustering of metabolic abnormalities, including 4 core components: dyslipidemia, elevated blood pressure, abnormal blood glucose, and obesity.⁵ Several studies have suggested that METS is associated with poor clinical outcome^{6, 7} and weakens the benefit of recanalization therapy in AIS.^{7, 8} The underlying mechanisms may involve impaired endogenous fibrinolytic capacity, endothelial dysfunction, inflammatory response, and hampered angiogenesis induced by METS.^{9, 10} Furthermore, neuroprotective mechanisms of RIPostC include modulation of microcirculation, endothelial function, oxidative stress, inflammation, neurogenesis, apoptosis, and autophagy.¹¹ Given the overlap of neuroprotective effects of RIPostC with the mechanisms underlying METS‐mediated damage on stroke, we hypothesize that METS may affect the efficacy of RIPostC in AIS. Therefore, this study was designed to investigate the association of METS with the efficacy of RIPostC in the RICAMIS trial.

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