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Haptoglobin genotype and aneurysmal subarachnoid haemorrhage: individual patient data analysis

Haptoglobin genotype and aneurysmal subarachnoid haemorrhage: individual patient data analysis
Haptoglobin genotype and aneurysmal subarachnoid haemorrhage: individual patient data analysis
Objective:
To perform an individual patient level data (IPLD) analysis and determine the relationship between haptoglobin (HP) genotype and outcomes after aneurysmal subarachnoid haemorrhage (aSAH).

Methods:
The primary outcome was favourable outcome on the modified Rankin Scale or Glasgow Outcome Score up to 12 months post-ictus. The secondary outcomes were occurrence of delayed ischemic neurological deficit, radiological infarction, angiographic vasospasm and transcranial Doppler evidence of vasospasm. World Federation of Neurological Surgeons scale, Fisher grade, age and aneurysmal treatment modality were covariates for both primary and secondary outcomes. As pre-planned, a two-stage IPLD analysis was conducted, followed by these sensitivity analyses: (1) unadjusted; (2) exclusion of unpublished studies; (3) all permutations of HP genotypes; (4) sliding dichotomy; (5) ordinal regression; (6) one-stage analysis; (7) exclusion of studies not in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; (10) only including covariates significant in univariate analysis.

Results:
Eleven studies (five published, six unpublished), totalling 939 patients, were included.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 were associated with an unfavourable 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.
0028-3878
e2150-e2164
Gaastra, Ben
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Ren, Dianxu
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Alexander, Sheila
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Bennett, Ellen R.
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Bielawski, Dawn M.
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Blackburn, Spiros L.
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Borsody, Mark K.
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Doré, Sylvain
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Galea, James
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Garland, Patrick
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He, Tian
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Iihara, Koji
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Kawamura, Yoichiro
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Leclerc, Jenna L.
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Meschia, James F.
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Pizzi, Michael A.
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Tamargo, Rafael J.
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Yang, Wuyang
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Nyquist, Paul A.
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Bulters, Diederik O.
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Galea, Ian
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Gaastra, Ben
c6a69fe5-84a6-4a41-990c-8999afb00822
Ren, Dianxu
6786b499-ff89-479d-a3a8-38fba114188a
Alexander, Sheila
47c15a44-3ab4-431a-9b9c-71a36feec7fc
Bennett, Ellen R.
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Bielawski, Dawn M.
52e0ab22-8086-4aca-9393-568183b6ff21
Blackburn, Spiros L.
dbf01e31-f361-458f-bca7-9bc11b8a19a0
Borsody, Mark K.
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Doré, Sylvain
35207796-1991-4247-bd28-e73a3b6de60a
Galea, James
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Garland, Patrick
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He, Tian
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Iihara, Koji
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Kawamura, Yoichiro
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Leclerc, Jenna L.
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Meschia, James F.
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Pizzi, Michael A.
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Tamargo, Rafael J.
47533618-0e96-4b7c-aee2-ecf0e6cc8188
Yang, Wuyang
d838fd62-a4cd-47d5-ad68-695d87bf2f29
Nyquist, Paul A.
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Bulters, Diederik O.
f2080cef-122a-486d-925d-455316b8cd41
Galea, Ian
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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. and Galea, Ian (2019) Haptoglobin genotype and aneurysmal subarachnoid haemorrhage: individual patient data analysis. Neurology, 92 (18), e2150-e2164. (doi:10.1212/WNL.0000000000007397).

Record type: Article

Abstract

Objective:
To perform an individual patient level data (IPLD) analysis and determine the relationship between haptoglobin (HP) genotype and outcomes after aneurysmal subarachnoid haemorrhage (aSAH).

Methods:
The primary outcome was favourable outcome on the modified Rankin Scale or Glasgow Outcome Score up to 12 months post-ictus. The secondary outcomes were occurrence of delayed ischemic neurological deficit, radiological infarction, angiographic vasospasm and transcranial Doppler evidence of vasospasm. World Federation of Neurological Surgeons scale, Fisher grade, age and aneurysmal treatment modality were covariates for both primary and secondary outcomes. As pre-planned, a two-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) one-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; (10) only including covariates significant in univariate analysis.

Results:
Eleven studies (five published, six unpublished), totalling 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 were associated with an unfavourable 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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More information

Accepted/In Press date: 4 February 2019
e-pub ahead of print date: 5 April 2019
Published date: 30 April 2019

Identifiers

Local EPrints ID: 428569
URI: http://eprints.soton.ac.uk/id/eprint/428569
ISSN: 0028-3878
PURE UUID: 9195d188-c37f-4a87-b41d-e1a44f311f1f
ORCID for Ian Galea: ORCID iD orcid.org/0000-0002-1268-5102

Catalogue record

Date deposited: 01 Mar 2019 17:30
Last modified: 26 Nov 2021 02:47

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Contributors

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

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