7602fffe57df38f7dc0d430ec913e708 237367.pdf b98486f5aaaaf6c290955a6982be2ef23cce58fd 237367.pdf 10a2c1e33c203f36989ef3a9e4738b136263d027825cc42486e435cf78e556bf 237367.pdf Title: Blood Biomarkers to Predict Long-Term Mortality after Ischemic Stroke Subject: Stroke is a major cause of disability and death globally, and prediction of mortality represents a crucial challenge. We aimed to identify blood biomarkers measured during acute ischemic stroke that could predict long-term mortality. Nine hundred and forty-one ischemic stroke patients were prospectively recruited in the Stroke-Chip study. Post-stroke mortality was evaluated during a median 4.8-year follow-up. A 14-biomarker panel was analyzed by immunoassays in blood samples obtained at hospital admission. Biomarkers were normalized and standardized using Z-scores. Multiple Cox regression models were used to identify clinical variables and biomarkers independently associated with long-term mortality and mortality due to stroke. In the multivariate analysis, the independent predictors of long-term mortality were age, female sex, hypertension, glycemia, and baseline National Institutes of Health Stroke Scale (NIHSS) score. Independent blood biomarkers predictive of long-term mortality were endostatin > quartile 2, tumor necrosis factor receptor-1 (TNF-R1) > quartile 2, and interleukin (IL)-6 > quartile 2. The risk of mortality when these three biomarkers were combined increased up to 69%. The addition of the biomarkers to clinical predictors improved the discrimination (integrative discriminative improvement (IDI) 0.022 (0.007–0.048), p < 0.001). Moreover, endostatin > quartile 3 was an independent predictor of mortality due to stroke. Altogether, endostatin, TNF-R1, and IL-6 circulating levels may aid in long-term mortality prediction after stroke. Keywords: ischemic stroke; biomarker; mortality; endostatin; IL-6; TNF-R1 Author: Laura Ramiro, Laura Abraira, Manuel Quintana, Paula García-Rodríguez, Estevo Santamarina, Jose Álvarez-Sabín, Josep Zaragoza, María Hernández-Pérez, Xavier Ustrell, Blanca Lara, Mikel Terceño, Alejandro Bustamante and Joan Montaner Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sat Feb 20 03:26:29 2021 CET ModDate: Sat Feb 20 03:34:54 2021 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 11 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1260289 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- SDGJWK+VnURWPalladioL Type 1 Custom yes yes no 10 0 RMFJRF+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 HMDCEO+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 IAEAXI+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 ILUGHX+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 PJCGLK+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 37 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 59 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 63 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 67 0 UWJUYN+CMSY10 Type 1 Builtin yes yes no 79 0 ZXDKIP+EURM10 Type 1 Builtin yes yes no 83 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes no 93 0 PFDHIG+Calibri,Bold CID TrueType Identity-H yes yes yes 107 0 PFDDPE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 113 0 PFDDPG+PalatinoLinotype TrueType WinAnsi yes yes no 116 0 PFDDPI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 119 0 PFDFNO+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 122 0 PFDHHF+Calibri CID TrueType Identity-H yes yes yes 125 0 PFDDPE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 141 0 PFDDPF+PalatinoLinotype CID TrueType Identity-H yes yes yes 144 0 PFDDPG+PalatinoLinotype TrueType WinAnsi yes yes no 150 0 PFDDPI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 153 0 PFDDPE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 165 0 PFDDPF+PalatinoLinotype CID TrueType Identity-H yes yes yes 168 0 PFDDPG+PalatinoLinotype TrueType WinAnsi yes yes no 174 0 PFDDPI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 177 0 PFDDPE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 195 0 PFDDPF+PalatinoLinotype CID TrueType Identity-H yes yes yes 198 0 PFDDPG+PalatinoLinotype TrueType WinAnsi yes yes no 204 0 PFDDPI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 207 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2021-03-11 02:32:33 CET RepresentationInformation: 237367.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2021-03-10 09:40:14 CET Size: 1260289 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 346 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Children: Item: Title: Study Design Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Blood Sample Collection and Biomarker Measurement Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Clinical Assessment Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Children: Item: Title: Demographics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Clinical Characteristics and Mortality Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Blood Biomarkers and Mortality Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Mortality Due to Stroke Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Info: Title: Blood Biomarkers to Predict Long-Term Mortality after Ischemic Stroke Author: Laura Ramiro, Laura Abraira, Manuel Quintana, Paula García-Rodríguez, Estevo Santamarina, Jose Álvarez-Sabín, Josep Zaragoza, María Hernández-Pérez, Xavier Ustrell, Blanca Lara, Mikel Terceño, Alejandro Bustamante and Joan Montaner Subject: Stroke is a major cause of disability and death globally, and prediction of mortality represents a crucial challenge. We aimed to identify blood biomarkers measured during acute ischemic stroke that could predict long-term mortality. Nine hundred and forty-one ischemic stroke patients were prospectively recruited in the Stroke-Chip study. Post-stroke mortality was evaluated during a median 4.8-year follow-up. A 14-biomarker panel was analyzed by immunoassays in blood samples obtained at hospital admission. Biomarkers were normalized and standardized using Z-scores. Multiple Cox regression models were used to identify clinical variables and biomarkers independently associated with long-term mortality and mortality due to stroke. In the multivariate analysis, the independent predictors of long-term mortality were age, female sex, hypertension, glycemia, and baseline National Institutes of Health Stroke Scale (NIHSS) score. Independent blood biomarkers predictive of long-term mortality were endostatin > quartile 2, tumor necrosis factor receptor-1 (TNF-R1) > quartile 2, and interleukin (IL)-6 > quartile 2. The risk of mortality when these three biomarkers were combined increased up to 69%. The addition of the biomarkers to clinical predictors improved the discrimination (integrative discriminative improvement (IDI) 0.022 (0.007 0.048), p < 0.001). Moreover, endostatin > quartile 3 was an independent predictor of mortality due to stroke. Altogether, endostatin, TNF-R1, and IL-6 circulating levels may aid in long-term mortality prediction after stroke. Keywords: ischemic stroke; biomarker; mortality; endostatin; IL-6; TNF-R1 Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sat Feb 20 03:26:29 CET 2021 ModDate: Sat Feb 20 03:34:54 CET 2021 ID: 0x31cfcf5f9af888f5c5615edaf362c5b5, 0x31cfcf5f9af888f5c5615edaf362c5b5 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: ZXDKIP+EURM10 FontSubset: true FirstChar: 11 LastChar: 22 FontDescriptor: FontName: ZXDKIP+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: HMDCEO+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 241 FontDescriptor: FontName: HMDCEO+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: IAEAXI+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: IAEAXI+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: SDGJWK+VnURWPalladioL FontSubset: true FirstChar: 129 LastChar: 243 FontDescriptor: FontName: SDGJWK+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: ILUGHX+VnURWPalladioL-Bold FontSubset: true FirstChar: 129 LastChar: 189 FontDescriptor: FontName: ILUGHX+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: QLBIEB+URWPalladioL-BoldItal FontSubset: true FirstChar: 110 LastChar: 112 FontDescriptor: FontName: QLBIEB+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: RMFJRF+URWPalladioL-Ital FontSubset: true FirstChar: 3 LastChar: 121 FontDescriptor: FontName: RMFJRF+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: UWJUYN+CMSY10 FontSubset: true FirstChar: 0 LastChar: 21 FontDescriptor: FontName: UWJUYN+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 35, 759, 96, 795 Annotation: Subtype: Link Rect: 515, 759, 560, 795 Annotation: Subtype: Link Rect: 104, 662, 115, 675 Annotation: Subtype: Link Rect: 194, 662, 205, 675 Annotation: Subtype: Link Rect: 303, 662, 314, 675 Annotation: Subtype: Link Rect: 433, 662, 444, 675 Annotation: Subtype: Link Rect: 116, 346, 154, 355 Annotation: Subtype: Link Rect: 35, 334, 127, 343 Annotation: Subtype: Link Rect: 35, 162, 97, 184 Annotation: Subtype: Link Rect: 153, 89, 154, 98 Annotation: Subtype: Link Rect: 35, 77, 147, 86 Annotation: Subtype: Link Rect: 453, 68, 460, 76 ActionDest: 214 Annotation: Subtype: Link Rect: 97, 17, 232, 28 Annotation: Subtype: Link Rect: 423, 17, 558, 28 Annotation: Subtype: Link Rect: 35, 446, 87, 465 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 431, 674, 438, 683 ActionDest: 214 Annotation: Subtype: Link Rect: 441, 674, 448, 683 ActionDest: 214 Annotation: Subtype: Link Rect: 509, 649, 516, 658 ActionDest: 214 Annotation: Subtype: Link Rect: 520, 649, 526, 658 ActionDest: 214 Annotation: Subtype: Link Rect: 399, 598, 406, 608 ActionDest: 214 Annotation: Subtype: Link Rect: 409, 599, 421, 608 ActionDest: 214 Annotation: Subtype: Link Rect: 247, 459, 259, 468 ActionDest: 214 Annotation: Subtype: Link Rect: 515, 384, 527, 393 ActionDest: 214 Annotation: Subtype: Link Rect: 308, 120, 320, 129 ActionDest: 214 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 250, 596, 262, 605 ActionDest: 214 Annotation: Subtype: Link Rect: 419, 546, 431, 555 ActionDest: 214 Annotation: Subtype: Link Rect: 531, 534, 543, 543 ActionDest: 214 Annotation: Subtype: Link Rect: 481, 168, 493, 177 ActionDest: 214 Annotation: Subtype: Link Rect: 192, 128, 199, 140 ActionDest: 90 Annotation: Subtype: Link Rect: 195, 78, 202, 90 ActionDest: 90 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 191, 194, 198, 206 ActionDest: 90 Annotation: Subtype: Link Rect: 327, 157, 335, 169 ActionDest: 97 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 344, 463, 351, 475 ActionDest: 97 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 199, 720, 206, 732 ActionDest: 131 Annotation: Subtype: Link Rect: 244, 682, 251, 694 ActionDest: 131 Annotation: Subtype: Link Rect: 193, 62, 200, 74 ActionDest: 90 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 312, 594, 319, 606 ActionDest: 182 Annotation: Subtype: Link Rect: 450, 205, 457, 217 ActionDest: 185 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 492, 381, 504, 390 ActionDest: 214 Annotation: Subtype: Link Rect: 508, 381, 519, 390 ActionDest: 217 Annotation: Subtype: Link Rect: 450, 293, 457, 303 ActionDest: 214 Annotation: Subtype: Link Rect: 457, 293, 469, 303 ActionDest: 217 Annotation: Subtype: Link Rect: 257, 181, 268, 190 ActionDest: 217 Annotation: Subtype: Link Rect: 311, 168, 323, 177 ActionDest: 217 Annotation: Subtype: Link Rect: 479, 143, 491, 152 ActionDest: 217 Annotation: Subtype: Link Rect: 493, 143, 505, 152 ActionDest: 217 Annotation: Subtype: Link Rect: 190, 118, 202, 127 ActionDest: 217 Annotation: Subtype: Link Rect: 261, 118, 273, 127 ActionDest: 217 Annotation: Subtype: Link Rect: 465, 67, 477, 77 ActionDest: 217 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 450, 735, 462, 744 ActionDest: 217 Annotation: Subtype: Link Rect: 469, 710, 481, 719 ActionDest: 217 Annotation: Subtype: Link Rect: 531, 697, 543, 706 ActionDest: 217 Annotation: Subtype: Link Rect: 544, 697, 556, 706 ActionDest: 217 Annotation: Subtype: Link Rect: 544, 622, 556, 631 ActionDest: 217 Annotation: Subtype: Link Rect: 439, 584, 451, 593 ActionDest: 217 Annotation: Subtype: Link Rect: 214, 546, 226, 556 ActionDest: 217 Annotation: Subtype: Link Rect: 388, 296, 400, 304 ActionDest: 217 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 82, 468, 119, 478 Annotation: Subtype: Link Rect: 519, 455, 557, 466 Annotation: Subtype: Link Rect: 269, 432, 306, 443 Annotation: Subtype: Link Rect: 313, 432, 349, 443 Annotation: Subtype: Link Rect: 425, 409, 462, 420 Annotation: Subtype: Link Rect: 465, 386, 503, 397 Annotation: Subtype: Link Rect: 509, 386, 545, 397 Annotation: Subtype: Link Rect: 189, 363, 227, 374 Annotation: Subtype: Link Rect: 224, 340, 261, 351 Annotation: Subtype: Link Rect: 267, 340, 303, 351 Annotation: Subtype: Link Rect: 241, 306, 278, 317 Annotation: Subtype: Link Rect: 107, 284, 144, 294 Annotation: Subtype: Link Rect: 82, 261, 119, 271 Annotation: Subtype: Link Rect: 126, 261, 162, 271 Annotation: Subtype: Link Rect: 95, 226, 133, 236 Annotation: Subtype: Link Rect: 459, 202, 497, 213 Annotation: Subtype: Link Rect: 59, 169, 97, 179 Annotation: Subtype: Link Rect: 103, 169, 139, 179 Annotation: Subtype: Link Rect: 122, 123, 159, 133 Annotation: Subtype: Link Rect: 166, 123, 202, 133 Annotation: Subtype: Link Rect: 185, 100, 223, 110 Annotation: Subtype: Link Rect: 320, 76, 357, 87 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 340, 721, 377, 732 Annotation: Subtype: Link Rect: 383, 721, 419, 732 Annotation: Subtype: Link Rect: 158, 699, 195, 709 Annotation: Subtype: Link Rect: 201, 699, 237, 709 Annotation: Subtype: Link Rect: 399, 675, 437, 686 Annotation: Subtype: Link Rect: 345, 652, 383, 663 Annotation: Subtype: Link Rect: 310, 617, 348, 628 Annotation: Subtype: Link Rect: 161, 583, 199, 594 Annotation: Subtype: Link Rect: 205, 583, 241, 594 Annotation: Subtype: Link Rect: 241, 549, 279, 559 Annotation: Subtype: Link Rect: 277, 526, 315, 536 Annotation: Subtype: Link Rect: 321, 526, 357, 536 Annotation: Subtype: Link Rect: 174, 491, 211, 502 Annotation: Subtype: Link Rect: 478, 468, 515, 479 Annotation: Subtype: Link Rect: 521, 468, 557, 479 Annotation: Subtype: Link Rect: 478, 445, 515, 456 Annotation: Subtype: Link Rect: 521, 445, 557, 456 Annotation: Subtype: Link Rect: 501, 433, 539, 444 Annotation: Subtype: Link Rect: 285, 410, 323, 421 Annotation: Subtype: Link Rect: 313, 387, 350, 398 Annotation: Subtype: Link Rect: 357, 387, 393, 398 Annotation: Subtype: Link Rect: 352, 364, 389, 375 Annotation: Subtype: Link Rect: 395, 364, 431, 375 Annotation: Subtype: Link Rect: 415, 341, 453, 352 Annotation: Subtype: Link Rect: 168, 308, 206, 318 Annotation: Subtype: Link Rect: 212, 308, 248, 318 Annotation: Subtype: Link Rect: 282, 285, 319, 295 Annotation: Subtype: Link Rect: 325, 285, 361, 295 Checksum: e12702fa Type: CRC32 Checksum: 7602fffe57df38f7dc0d430ec913e708 Type: MD5 Checksum: b98486f5aaaaf6c290955a6982be2ef23cce58fd Type: SHA-1