Saana Pihlasviita, Olli S Mattila, Tiina Nukarinen, Markku Kuisma, Heini Harve-Rytsälä, Juhani Ritvonen, Gerli Sibolt, Sami Curtze, Daniel Strbian, Mikko Pystynen, Turgut Tatlisumak, Perttu J Lindsberg
{"title":"血浆对称二甲基精氨酸是严重急性缺血性中风的代谢物生物标志物。","authors":"Saana Pihlasviita, Olli S Mattila, Tiina Nukarinen, Markku Kuisma, Heini Harve-Rytsälä, Juhani Ritvonen, Gerli Sibolt, Sami Curtze, Daniel Strbian, Mikko Pystynen, Turgut Tatlisumak, Perttu J Lindsberg","doi":"10.3389/fneur.2024.1472424","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>After severe ischemic stroke (IS), circulating levels of symmetric dimethylarginine (SDMA) increase. We investigated the early dynamics of SDMA in stroke to potentially aid with prehospital identification of severe IS from hemorrhagic stroke (HS).</p><p><strong>Methods: </strong>We performed targeted mass spectrometry (MS) measurements of SDMA in two sequential acute plasma samples (early and secondary) of 50 IS patients with LVO and 49 HS patients. Secondary samples of 227 IS and 84 HS patients with moderate to severe symptoms (NIHSS ≥ 7) subsequently underwent ELISA validation.</p><p><strong>Results: </strong>The median (IQR) last-known-well (LKW) to sampling times were 43 min (35-67) for early samples in the MS analysis, and 83 min (65-113) for secondary samples in MS and ELISA analyses. No inter-group differences existed in early samples, but IS patients had significantly higher mean (IQR) SDMA levels in secondary samples in both analyses: 5.8 (5.3-6.9) vs. 5.1 (4.2-5.8) A.U. for HS, <i>p</i> < 0.001, with MS; and 0.82 (0.72-1.01) vs. 0.71 (0.58-0.85) nmol/mL for HS, <i>p</i> < 0.001, with ELISA. For IS patients, higher SDMA levels were associated with cardioembolic stroke: 0.84 (0.73-1.09) vs. 0.79 (0.71-0.91) nmol/mL for other etiologies, <i>p</i> = 0.042, and poor outcome: modified Rankin Scale (mRS) 4-6; 0.90 (0.73-1.06) vs. 0.80 (0.72-0.97) nmol/mL for mRS 0-3 (<i>p</i> = 0.045).</p><p><strong>Conclusion: </strong>In a large clinical cohort of stroke patients with moderate to severe symptoms, our data suggest that SDMA can assist in differentiation of IS and HS patients already 1 h and a half after symptom onset. 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No inter-group differences existed in early samples, but IS patients had significantly higher mean (IQR) SDMA levels in secondary samples in both analyses: 5.8 (5.3-6.9) vs. 5.1 (4.2-5.8) A.U. for HS, <i>p</i> < 0.001, with MS; and 0.82 (0.72-1.01) vs. 0.71 (0.58-0.85) nmol/mL for HS, <i>p</i> < 0.001, with ELISA. For IS patients, higher SDMA levels were associated with cardioembolic stroke: 0.84 (0.73-1.09) vs. 0.79 (0.71-0.91) nmol/mL for other etiologies, <i>p</i> = 0.042, and poor outcome: modified Rankin Scale (mRS) 4-6; 0.90 (0.73-1.06) vs. 0.80 (0.72-0.97) nmol/mL for mRS 0-3 (<i>p</i> = 0.045).</p><p><strong>Conclusion: </strong>In a large clinical cohort of stroke patients with moderate to severe symptoms, our data suggest that SDMA can assist in differentiation of IS and HS patients already 1 h and a half after symptom onset. 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引用次数: 0
摘要
导言：严重缺血性卒中（IS）后，循环中的对称二甲基精氨酸（SDMA）水平升高。我们研究了 SDMA 在脑卒中早期的动态变化，以帮助院前识别严重缺血性脑卒中（IS）和出血性脑卒中（HS）：方法：我们对 50 名患有 LVO 的 IS 患者和 49 名 HS 患者的两份连续急性血浆样本（早期样本和二次样本）中的 SDMA 进行了靶向质谱（MS）测量。随后，对227例IS和84例HS中重度症状（NIHSS≥7）患者的二次样本进行了ELISA验证：在 MS 分析中，早期样本从最后已知孔（LKW）到采样的中位（IQR）时间为 43 分钟（35-67），在 MS 和 ELISA 分析中，二次样本的中位（IQR）时间为 83 分钟（65-113）。在早期样本中不存在组间差异，但在两次分析中，IS 患者二次样本中的 SDMA 平均水平（IQR）明显更高：MS患者为5.8 (5.3-6.9) A.U. vs. HS患者为5.1 (4.2-5.8) A.U.，P < 0.001；ELISA患者为0.82 (0.72-1.01) nmol/mL vs. HS患者为0.71 (0.58-0.85) nmol/mL，P < 0.001。对于 IS 患者，较高的 SDMA 水平与心肌栓塞性中风相关：其他病因：0.84 (0.73-1.09) nmol/mL vs. 0.79 (0.71-0.91) nmol/mL，p = 0.042；预后差：改良Rankin量表（mRS）4-6；0.90 (0.73-1.06) nmol/mL vs. 0.80 (0.72-0.97) nmol/mL，mRS 0-3（p = 0.045）：我们的数据表明，在症状出现 1 小时半后，SDMA 就能帮助区分 IS 和 HS 患者。SDMA 未来可能被证明具有诊断中风生物标志物的价值。
Plasma symmetric dimethylarginine as a metabolite biomarker of severe acute ischemic stroke.
Introduction: After severe ischemic stroke (IS), circulating levels of symmetric dimethylarginine (SDMA) increase. We investigated the early dynamics of SDMA in stroke to potentially aid with prehospital identification of severe IS from hemorrhagic stroke (HS).
Methods: We performed targeted mass spectrometry (MS) measurements of SDMA in two sequential acute plasma samples (early and secondary) of 50 IS patients with LVO and 49 HS patients. Secondary samples of 227 IS and 84 HS patients with moderate to severe symptoms (NIHSS ≥ 7) subsequently underwent ELISA validation.
Results: The median (IQR) last-known-well (LKW) to sampling times were 43 min (35-67) for early samples in the MS analysis, and 83 min (65-113) for secondary samples in MS and ELISA analyses. No inter-group differences existed in early samples, but IS patients had significantly higher mean (IQR) SDMA levels in secondary samples in both analyses: 5.8 (5.3-6.9) vs. 5.1 (4.2-5.8) A.U. for HS, p < 0.001, with MS; and 0.82 (0.72-1.01) vs. 0.71 (0.58-0.85) nmol/mL for HS, p < 0.001, with ELISA. For IS patients, higher SDMA levels were associated with cardioembolic stroke: 0.84 (0.73-1.09) vs. 0.79 (0.71-0.91) nmol/mL for other etiologies, p = 0.042, and poor outcome: modified Rankin Scale (mRS) 4-6; 0.90 (0.73-1.06) vs. 0.80 (0.72-0.97) nmol/mL for mRS 0-3 (p = 0.045).
Conclusion: In a large clinical cohort of stroke patients with moderate to severe symptoms, our data suggest that SDMA can assist in differentiation of IS and HS patients already 1 h and a half after symptom onset. SDMA may prove to have future value in a diagnostic stroke biomarker panel.
期刊介绍：
The section Stroke aims to quickly and accurately publish important experimental, translational and clinical studies, and reviews that contribute to the knowledge of stroke, its causes, manifestations, diagnosis, and management.
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