Haptoglobin genotype and aneurysmal subarachnoid hemorrhage: Individual patient data analysis

Ben Gaastra, Dianxu Ren, Sheila Alexander, Ellen R. Bennett, Dawn M. Bielawski, Spiros L. Blackburn, Mark K. Borsody, Sylvain Doré, James Galea, Patrick Garland, Tian He, Koji Iihara, Yoichiro Kawamura, Jenna L. Leclerc, James F. Meschia, Michael A. Pizzi, Rafael J Tamargo, Wuyang Yang, Paul A Nyquist, Diederik O. BultersIan Galea

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: To perform an individual patient-level data (IPLD) analysis and to determine the relationship between haptoglobin (HP) genotype and outcomes after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: The primary outcome was favorable outcome on the modified Rankin Scale or Glasgow Outcome Scale up to 12 months after ictus. The secondary outcomes were occurrence of delayed ischemic neurologic deficit, radiologic infarction, angiographic vasospasm, and transcranial Doppler evidence of vasospasm. World Federation of Neurological Surgeons (WFNS) scale, Fisher grade, age, and aneurysmal treatment modality were covariates for both primary and secondary outcomes. As preplanned, a 2-stage IPLD analysis was conducted, followed by these sensitivity analyses: (1) unadjusted; (2) exclusion of unpublished studies; (3) all permutations of HP genotypes; (4) sliding dichotomy; (5) ordinal regression; (6) 1-stage analysis; (7) exclusion of studies not in Hardy-Weinberg equilibrium (HWE); (8) inclusion of studies without the essential covariates; (9) inclusion of additional covariates; and (10) including only covariates significant in univariate analysis. RESULTS: Eleven studies (5 published, 6 unpublished) totaling 939 patients were included. Overall, the study population was in HWE. Follow-up times were 1, 3, and 6 months for 355, 516, and 438 patients. HP genotype was not associated with any primary or secondary outcome. No trends were observed. When taken through the same analysis, higher age and WFNS scale were associated with an unfavorable outcome as expected. CONCLUSION: This comprehensive IPLD analysis, carefully controlling for covariates, refutes previous studies showing that HP1-1 associates with better outcome after aSAH.

Original languageEnglish (US)
Pages (from-to)e2150-e2164
JournalNeurology
Volume92
Issue number18
DOIs
StatePublished - Apr 30 2019

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Haptoglobins
Subarachnoid Hemorrhage
Genotype
Glasgow Outcome Scale
Neurologic Manifestations
Infarction
Population

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Gaastra, B., Ren, D., Alexander, S., Bennett, E. R., Bielawski, D. M., Blackburn, S. L., ... Galea, I. (2019). Haptoglobin genotype and aneurysmal subarachnoid hemorrhage: Individual patient data analysis. Neurology, 92(18), e2150-e2164. https://doi.org/10.1212/WNL.0000000000007397

Haptoglobin genotype and aneurysmal subarachnoid hemorrhage : Individual patient data analysis. / Gaastra, Ben; Ren, Dianxu; Alexander, Sheila; Bennett, Ellen R.; Bielawski, Dawn M.; Blackburn, Spiros L.; Borsody, Mark K.; Doré, Sylvain; Galea, James; Garland, Patrick; He, Tian; Iihara, Koji; Kawamura, Yoichiro; Leclerc, Jenna L.; Meschia, James F.; Pizzi, Michael A.; Tamargo, Rafael J; Yang, Wuyang; Nyquist, Paul A; Bulters, Diederik O.; Galea, Ian.

In: Neurology, Vol. 92, No. 18, 30.04.2019, p. e2150-e2164.

Research output: Contribution to journalArticle

Gaastra, B, Ren, D, Alexander, S, Bennett, ER, Bielawski, DM, Blackburn, SL, Borsody, MK, Doré, S, Galea, J, Garland, P, He, T, Iihara, K, Kawamura, Y, Leclerc, JL, Meschia, JF, Pizzi, MA, Tamargo, RJ, Yang, W, Nyquist, PA, Bulters, DO & Galea, I 2019, 'Haptoglobin genotype and aneurysmal subarachnoid hemorrhage: Individual patient data analysis', Neurology, vol. 92, no. 18, pp. e2150-e2164. https://doi.org/10.1212/WNL.0000000000007397
Gaastra B, Ren D, Alexander S, Bennett ER, Bielawski DM, Blackburn SL et al. Haptoglobin genotype and aneurysmal subarachnoid hemorrhage: Individual patient data analysis. Neurology. 2019 Apr 30;92(18):e2150-e2164. https://doi.org/10.1212/WNL.0000000000007397
Gaastra, Ben ; Ren, Dianxu ; Alexander, Sheila ; Bennett, Ellen R. ; Bielawski, Dawn M. ; Blackburn, Spiros L. ; Borsody, Mark K. ; Doré, Sylvain ; Galea, James ; Garland, Patrick ; He, Tian ; Iihara, Koji ; Kawamura, Yoichiro ; Leclerc, Jenna L. ; Meschia, James F. ; Pizzi, Michael A. ; Tamargo, Rafael J ; Yang, Wuyang ; Nyquist, Paul A ; Bulters, Diederik O. ; Galea, Ian. / Haptoglobin genotype and aneurysmal subarachnoid hemorrhage : Individual patient data analysis. In: Neurology. 2019 ; Vol. 92, No. 18. pp. e2150-e2164.
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abstract = "OBJECTIVE: To perform an individual patient-level data (IPLD) analysis and to determine the relationship between haptoglobin (HP) genotype and outcomes after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: The primary outcome was favorable outcome on the modified Rankin Scale or Glasgow Outcome Scale up to 12 months after ictus. The secondary outcomes were occurrence of delayed ischemic neurologic deficit, radiologic infarction, angiographic vasospasm, and transcranial Doppler evidence of vasospasm. World Federation of Neurological Surgeons (WFNS) scale, Fisher grade, age, and aneurysmal treatment modality were covariates for both primary and secondary outcomes. As preplanned, a 2-stage IPLD analysis was conducted, followed by these sensitivity analyses: (1) unadjusted; (2) exclusion of unpublished studies; (3) all permutations of HP genotypes; (4) sliding dichotomy; (5) ordinal regression; (6) 1-stage analysis; (7) exclusion of studies not in Hardy-Weinberg equilibrium (HWE); (8) inclusion of studies without the essential covariates; (9) inclusion of additional covariates; and (10) including only covariates significant in univariate analysis. RESULTS: Eleven studies (5 published, 6 unpublished) totaling 939 patients were included. Overall, the study population was in HWE. Follow-up times were 1, 3, and 6 months for 355, 516, and 438 patients. HP genotype was not associated with any primary or secondary outcome. No trends were observed. When taken through the same analysis, higher age and WFNS scale were associated with an unfavorable outcome as expected. CONCLUSION: This comprehensive IPLD analysis, carefully controlling for covariates, refutes previous studies showing that HP1-1 associates with better outcome after aSAH.",
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T1 - Haptoglobin genotype and aneurysmal subarachnoid hemorrhage

T2 - Individual patient data analysis

AU - Gaastra, Ben

AU - Ren, Dianxu

AU - Alexander, Sheila

AU - Bennett, Ellen R.

AU - Bielawski, Dawn M.

AU - Blackburn, Spiros L.

AU - Borsody, Mark K.

AU - Doré, Sylvain

AU - Galea, James

AU - Garland, Patrick

AU - He, Tian

AU - Iihara, Koji

AU - Kawamura, Yoichiro

AU - Leclerc, Jenna L.

AU - Meschia, James F.

AU - Pizzi, Michael A.

AU - Tamargo, Rafael J

AU - Yang, Wuyang

AU - Nyquist, Paul A

AU - Bulters, Diederik O.

AU - Galea, Ian

PY - 2019/4/30

Y1 - 2019/4/30

N2 - OBJECTIVE: To perform an individual patient-level data (IPLD) analysis and to determine the relationship between haptoglobin (HP) genotype and outcomes after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: The primary outcome was favorable outcome on the modified Rankin Scale or Glasgow Outcome Scale up to 12 months after ictus. The secondary outcomes were occurrence of delayed ischemic neurologic deficit, radiologic infarction, angiographic vasospasm, and transcranial Doppler evidence of vasospasm. World Federation of Neurological Surgeons (WFNS) scale, Fisher grade, age, and aneurysmal treatment modality were covariates for both primary and secondary outcomes. As preplanned, a 2-stage IPLD analysis was conducted, followed by these sensitivity analyses: (1) unadjusted; (2) exclusion of unpublished studies; (3) all permutations of HP genotypes; (4) sliding dichotomy; (5) ordinal regression; (6) 1-stage analysis; (7) exclusion of studies not in Hardy-Weinberg equilibrium (HWE); (8) inclusion of studies without the essential covariates; (9) inclusion of additional covariates; and (10) including only covariates significant in univariate analysis. RESULTS: Eleven studies (5 published, 6 unpublished) totaling 939 patients were included. Overall, the study population was in HWE. Follow-up times were 1, 3, and 6 months for 355, 516, and 438 patients. HP genotype was not associated with any primary or secondary outcome. No trends were observed. When taken through the same analysis, higher age and WFNS scale were associated with an unfavorable outcome as expected. CONCLUSION: This comprehensive IPLD analysis, carefully controlling for covariates, refutes previous studies showing that HP1-1 associates with better outcome after aSAH.

AB - OBJECTIVE: To perform an individual patient-level data (IPLD) analysis and to determine the relationship between haptoglobin (HP) genotype and outcomes after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: The primary outcome was favorable outcome on the modified Rankin Scale or Glasgow Outcome Scale up to 12 months after ictus. The secondary outcomes were occurrence of delayed ischemic neurologic deficit, radiologic infarction, angiographic vasospasm, and transcranial Doppler evidence of vasospasm. World Federation of Neurological Surgeons (WFNS) scale, Fisher grade, age, and aneurysmal treatment modality were covariates for both primary and secondary outcomes. As preplanned, a 2-stage IPLD analysis was conducted, followed by these sensitivity analyses: (1) unadjusted; (2) exclusion of unpublished studies; (3) all permutations of HP genotypes; (4) sliding dichotomy; (5) ordinal regression; (6) 1-stage analysis; (7) exclusion of studies not in Hardy-Weinberg equilibrium (HWE); (8) inclusion of studies without the essential covariates; (9) inclusion of additional covariates; and (10) including only covariates significant in univariate analysis. RESULTS: Eleven studies (5 published, 6 unpublished) totaling 939 patients were included. Overall, the study population was in HWE. Follow-up times were 1, 3, and 6 months for 355, 516, and 438 patients. HP genotype was not associated with any primary or secondary outcome. No trends were observed. When taken through the same analysis, higher age and WFNS scale were associated with an unfavorable outcome as expected. CONCLUSION: This comprehensive IPLD analysis, carefully controlling for covariates, refutes previous studies showing that HP1-1 associates with better outcome after aSAH.

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