Sex Differences in Frequency, Severity, and Distribution of Cerebral Microbleeds.
Fandler-Höfler S., Eppinger S., Ambler G., Nash P., Kneihsl M., Lee K-J., Lim J-S., Shiozawa M., Koga M., Li L., Lovelock C., Chabriat H., Hennerici M., Wong YK., Mak HKF., Prats-Sanchez L., Martínez-Domeño A., Inamura S., Yoshifuji K., Arsava EM., Horstmann S., Purrucker J., Lam BYK., Wong A., Kim YD., Song T-J., Lemmens R., Uysal E., Tanriverdi Z., Bornstein NM., Ben Assayag E., Hallevi H., Molad J., Nishihara M., Tanaka J., Coutts SB., Polymeris A., Wagner B., Seiffge DJ., Lyrer P., Kappelle LJ., Salman RA-S., Hernandez MV., Jäger HR., Lip GYH., Fischer U., El-Koussy M., Mas J-L., Legrand L., Karayiannis C., Phan T., Gunkel S., Christ N., Abrigo J., Chu W., Leung T., Chappell F., Makin S., Hayden D., Williams DJ., Mess WH., Kooi ME., Barbato C., Browning S., Tuladhar AM., Maaijwee N., Guevarra AC., Mendyk A-M., Delmaire C., Köhler S., van Oostenbrugge R., Zhou Y., Xu C., Hilal S., Robert C., Chen C., Lou M., Staals J., Bordet R., Kandiah N., de Leeuw F-E., Simister R., Bos D., Kelly PJ., Wardlaw J., Soo Y., Fluri F., Srikanth V., Calvet D., Jung S., Kwa VIH., Engelter ST., Peters N., Smith EE., Hara H., Yakushiji Y., Orken DN., Thijs V., Heo JH., Mok V., Veltkamp R., Ay H., Imaizumi T., Lau KK., Jouvent E., Rothwell PM., Toyoda K., Bae H-J., Marti-Fabregas J., Wilson D., Best J., Fazekas F., Enzinger C., Werring DJ., Gattringer T., Microbleeds International Collaborative Network None.
IMPORTANCE: Cerebral small vessel disease (SVD) is associated with various cerebrovascular outcomes, but data on sex differences in SVD are scarce. OBJECTIVE: To investigate whether the frequency, severity, and distribution of cerebral microbleeds (CMB), other SVD markers on magnetic resonance imaging (MRI), and outcomes differ by sex. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used pooled individual patient data from the Microbleeds International Collaborative Network, including patients from 38 prospective cohort studies in 18 countries between 2000 and 2018, with clinical follow-up of at least 3 months (up to 5 years). Participants included patients with acute ischemic stroke or transient ischemic attack with available brain MRI. Data were analyzed from April to December 2023. MAIN OUTCOMES AND MEASURES: Outcomes of interest were presence of CMB, lacunes, and severe white matter hyperintensities determined on MRI. Additionally, mortality, recurrent ischemic stroke, and intracranial hemorrhage during follow-up were assessed. Multivariable random-effects logistic regression models, Cox regression, and competing risk regression models were used to investigate sex differences in individual SVD markers, risk of recurrent cerebrovascular events, and death. RESULTS: A total of 20 314 patients (mean [SD] age, 70.1 [12.7] years; 11 721 [57.7%] male) were included, of whom 5649 (27.8%) had CMB. CMB were more frequent in male patients, and this was consistent throughout different age groups, locations, and in multivariable models (female vs male adjusted odds ratio [aOR], 0.86; 95% CI, 0.80-0.92; P