Biomaterial Database

Haptoglobin genotype and aneurysmal subarachnoid hemorrhage: Individual patient data analysis. 2019

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

From the Wessex Neurological Centre (B.G., D.O.B., I.G.), University Hospital Southampton NHS Foundation Trust, UK; School of Nursing (D.R., S.A.) and Department of Biostatistics (D.R., T.E.), University of Pittsburgh, PA; Department of Neurology (E.R.B.), Duke University School of Medicine, Durham, NC; NeuroSpring (D.M.B., M.K.B.), Dover, DE; Department of Neurosurgery (S.L.B.), University of Texas Health Science Center at Houston; Department of Anesthesiology, Neurology, Psychiatry, Psychology, Pharmaceutics, and Neuroscience (S.D., J.L.L.), College of Medicine, Center for Translational Research in Neurodegenerative Disease, McKnight Brain Institute, University of Florida, Gainesville; Brain Injury Research Group (J.G.), Division of Cardiovascular Sciences (University of Manchester), Salford Royal NHS Foundation Trust, UK; Clinical Neurosciences, Clinical & Experimental Sciences (P.G., I.G.), Faculty of Medicine, University of Southampton, UK; Department of Neurosurgery (K.I., Y.K.), Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Neurology (J.F.M., M.A.P.), Mayo Clinic, Jacksonville, FL; and Division of Cerebrovascular Neurosurgery (R.J.T.) and Departments of Neurology, Anesthesia/Critical Care Medicine, and Neurosurgery (W.Y., P.A.N.), Johns Hopkins University School of Medicine, Baltimore, MD.

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). 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. 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. This comprehensive IPLD analysis, carefully controlling for covariates, refutes previous studies showing that HP1-1 associates with better outcome after aSAH.

UI	MeSH Term	Description	Entries
D011379	Prognosis	A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.	Prognostic Factor,Prognostic Factors,Factor, Prognostic,Factors, Prognostic,Prognoses
D005838	Genotype	The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.	Genogroup,Genogroups,Genotypes
D006242	Haptoglobins	Plasma glycoproteins that form a stable complex with hemoglobin to aid the recycling of heme iron. They are encoded in man by a gene on the short arm of chromosome 16.	Haptoglobin
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000483	Alleles	Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.	Allelomorphs,Allele,Allelomorph
D013345	Subarachnoid Hemorrhage	Bleeding into the intracranial or spinal SUBARACHNOID SPACE, most resulting from INTRACRANIAL ANEURYSM rupture. It can occur after traumatic injuries (SUBARACHNOID HEMORRHAGE, TRAUMATIC). Clinical features include HEADACHE; NAUSEA; VOMITING, nuchal rigidity, variable neurological deficits and reduced mental status.	Hemorrhage, Subarachnoid,Perinatal Subarachnoid Hemorrhage,Subarachnoid Hemorrhage, Aneurysmal,Subarachnoid Hemorrhage, Spontaneous,SAH (Subarachnoid Hemorrhage),Subarachnoid Hemorrhage, Intracranial,Aneurysmal Subarachnoid Hemorrhage,Aneurysmal Subarachnoid Hemorrhages,Hemorrhage, Aneurysmal Subarachnoid,Hemorrhage, Intracranial Subarachnoid,Hemorrhage, Perinatal Subarachnoid,Hemorrhage, Spontaneous Subarachnoid,Hemorrhages, Aneurysmal Subarachnoid,Hemorrhages, Intracranial Subarachnoid,Hemorrhages, Perinatal Subarachnoid,Hemorrhages, Spontaneous Subarachnoid,Hemorrhages, Subarachnoid,Intracranial Subarachnoid Hemorrhage,Intracranial Subarachnoid Hemorrhages,Perinatal Subarachnoid Hemorrhages,SAHs (Subarachnoid Hemorrhage),Spontaneous Subarachnoid Hemorrhage,Spontaneous Subarachnoid Hemorrhages,Subarachnoid Hemorrhage, Perinatal,Subarachnoid Hemorrhages,Subarachnoid Hemorrhages, Aneurysmal,Subarachnoid Hemorrhages, Intracranial,Subarachnoid Hemorrhages, Perinatal,Subarachnoid Hemorrhages, Spontaneous
D016896	Treatment Outcome	Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.	Rehabilitation Outcome,Treatment Effectiveness,Clinical Effectiveness,Clinical Efficacy,Patient-Relevant Outcome,Treatment Efficacy,Effectiveness, Clinical,Effectiveness, Treatment,Efficacy, Clinical,Efficacy, Treatment,Outcome, Patient-Relevant,Outcome, Rehabilitation,Outcome, Treatment,Outcomes, Patient-Relevant,Patient Relevant Outcome,Patient-Relevant Outcomes