Abstract

Background and objective: Small, single-center studies point to biological and clinical differences in women and men who sustain a spontaneous, non-traumatic intracerebral hemorrhage (ICH). Leveraging data from four landmark studies of ICH, we investigated the impact of sex on risk factors, location, severity and outcome of ICH. Design: Individual patient data meta-analysis of four studies of ICH, including three randomized clinical trials and one multi-ethnic observational study. Setting: Academic medical centers in the United States. Patients: Patients with neuroimaging confirmed ICH. Measurements: We conducted an individual patient data meta-analysis of four landmark studies of ICH: ERICH, ATACH-II, FAST and MISTIE-III. We evaluated whether sex was associated with specific risk factor profiles, hemorrhage location (deep or lobar), neuroimaging severity (hematoma volume and expansion), and poor 90-day functional outcomes (defined as a modified Rankin scale 4 to 6). Main Results: A total of 4,812 ICH patients were evaluated (mean age 62, 60% males). Men with ICH were younger, more likely to be smokers and diabetics, and less likely to be on anticoagulants (all p<0.05). In multivariable analyses, male sex was associated with non-lobar location (odds ratio [OR], 1.69; 95% CI, 1.42-2.01; p<0.001), larger hemorrhages (beta, 0.21; 95% CI, 0.14-0.28; p<0.001) and a higher risk of hematoma expansion (OR, 1.31; 95% CI, 1.10-1.56; p=0.003). Despite the larger hemorrhage volume and higher risk of expansion, male sex was associated with a 22% lower risk of poor outcomes (OR, 0.78; 95% CI, 0.67-0.91; p=0.001). Conclusions: Men with ICH are more likely to have vascular risk factors, have larger hemorrhage volumes, and have higher risk of hemorrhage expansion. They are also more likely to have a good outcome at 90 days compared to women.

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