Plasma mid-regional pro-adrenomedullin: A biomarker of the ischemic penumbra in hyperacute stroke |
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| Authors: | Hiroyuki Ishiyama Tomotaka Tanaka Satoshi Saito Teruhide Koyama Akihiro Kitamura Manabu Inoue Naoya Fukushima Yoshiaki Morita Masatoshi Koga Kazunori Toyoda Nagato Kuriyama Makoto Urushitani Masafumi Ihara |
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| Affiliation: | 1. Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan;2. Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan;3. Department of Neurology, Shiga University of Medical Science, Otsu, Japan;4. Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan;5. Department of Radiology, National Cerebral and Cardiovascular Center, Suita, Japan;6. Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan Shizuoka Graduate University of Public Health, Shizuoka, Japan |
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| Abstract: | Reperfusion therapy has improved the outcomes of ischemic stroke but also emphasized the importance of ischemic penumbra. However, blood biomarkers are currently unavailable for this region. Adrenomedullin (ADM) is a neuroprotective peptide, secreted in a compensatory response to brain ischemia. We thus investigated whether an increase in mid-regional pro-ADM (MR-proADM), a stable peptide fragment of the ADM precursor, could act as a biomarker by predicting the ischemic penumbra in hyperacute ischemic stroke (HAIS). We prospectively enrolled consecutive HAIS patients (n = 119; median age, 77 years; male, 59.7%) admitted to our institutes from July 2017 to March 2019 and evaluated plasma MR-proADM levels within 4.5 h of onset. MR-proADM levels in HAIS were compared to healthy controls (n = 1298; median age, 58 years; male, 33.2%) in the Japan Multi-Institutional Collaborative Cohort Study from 2013 to 2017. Furthermore, we evaluated whether MR-proADM levels were associated with the penumbra estimated by clinical-diffusion mismatch (CDM) (National Institute of Health Stroke Scale [NIHSS] ≥8, diffusion ischemic core volume ≤25 ml), or magnetic resonance angiography-diffusion-weighted imaging mismatch (MDM) (NIHSS ≥5, a proximal vessel occlusion with core volume ≤25 ml, or a proximal vessel stenosis/distal vessel occlusion with core volume ≤15 ml). In a case–control study, multivariate logistic analysis showed a significant association between HAIS and MR-proADM ≥0.54 nmol/L (adjusted odds ratio, 7.92 [95% CI, 4.17–15.02], p < 0.001). Though MR-proADM levels in HAIS did not correlate with the ischemic core volume (rs = 0.09, p = 0.348), they were higher in HAIS with CDM (n = 34; 0.81 vs. 0.61 nmol/L, p < 0.001) or MDM (n = 26; 0.83 vs. 0.62 nmol/L, p = 0.002). These differences remained significant after adjusting baseline factors (adjusted odds ratio, 4.06 [95% CI, 1.31–12.55], p = 0.015 and 4.65 [1.35–16.11], p = 0.015, respectively). Plasma MR-proADM is elevated in HAIS, especially in those with a substantial penumbra, suggesting potential as a blood biomarker in this region. |
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| Keywords: | acute ischemic stroke adrenomedullin blood biomarker ischemic penumbra |
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