Gaastra, Benjamin, 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).
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a two-stage IPLD analysis was conducted, followed by these sensitivity analyses: (1) unadjusted; (2) exclusion of unpublished studies; (3) all permutations of HP genotypes; (4) sliding dichotomy; (5) ordinal regression; (6) one-stage analysis; (7) exclusion of studies not in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Eleven studies (five published, six unpublished), totalling 939 patients, were included.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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