Research Highlights the Sex and Gender Disparities in Acute Ischemic Stroke

R&E Foundation grant used high spatial resolution vessel wall MR imaging to determine intracranial plaque burden

BY JENNIFER ALLYN June 13, 2024

Song

Hypertension affects approximately 1.39 billion adults globally. It is associated with the development of intracranial atherosclerosis (ICAS), which in turn is one of the leading causes of acute ischemic stroke (AIS).

For women, AIS risk increases as they age and results in more debilitating outcomes. These findings may be attributable to both sex‐specific survival bias and a more rapid age‐related increase in blood pressure experienced by women. How and if these differences in prevalence rates of hypertension by gender impact ICAS burden and AIS risk remain unknown.

In her 2019 Bayer HealthCare/RSNA Research Scholar Grant, “Sex‐differences in Intracranial Arterial Wall Changes Using 3T and 7T Multicontrast Vessel Wall Imaging,” Jae W. Song, MD, MS, assistant professor of radiology at the Hospital of the University of Pennsylvania, and colleagues used 3T multicontrast vessel wall MRI to identify gender-differences in intracranial vessel wall lesion burden in hypertensive patients who suffered a stroke. “This advanced high spatial-resolution vessel wall imaging technique allows accurate detection of intracranial plaque because it enables us to image stages of plaque development that may not yet cause luminal stenosis,” Dr. Song said.

“The long-term aim is to investigate how women’s reproductive stages, such as pre-, peri- and post-menopausal stages, influence risk factors, ICAS and stroke outcomes. By recognizing gender disparities in stroke outcomes and the unique physiology of a woman’s life, the overarching objective of this investigation was to establish evidence and support toward establishing gender-specific screening and therapy guidelines.”

JAE W. SONG, MD, MS

Women and Men May Need Different Approaches to Treating Hypertension

Dr. Song and her team designed a retrospective multicenter study identifying patients with AIS whose diagnosis was confirmed by diffusion weighted imaging. All patients were imaged with intracranial vessel wall MR imaging within eight weeks of the event to determine the intracranial plaque burden by counting the total number of discrete plaques in the proximal intracranial arteries.

A comparison of men versus women in this cohort showed that men had a higher total plaque burden than women. When accounting for patients on anti-hypertensive medications, women showed a greater magnitude in the reduction of proximal plaque burden than men, suggesting a difference in treatment response among women and men.

“The lifetime risk of stroke is higher for women than men given their longer life expectancy, biologic sex and differences in risk factor profile. As women age, they have a higher disease burden of cardiovascular risk factors, including atrial fibrillation, diabetes, worsening lipid profiles, and higher prevalence of hypertension compared to men,” Dr. Song said. “Furthermore, women carry sex-specific risk factors that contribute to the risk and severity of AIS, including the age of menarche, menopause, pregnancy and its complications.”

These results raised several intriguing questions for the researchers, including: do men and women respond to anti-hypertensive treatment differently and should there be different hypertensive treatment guidelines for women given the steep increase in incidence of hypertension in postmenopausal women?

“Evidence shows sex-differences in the strength of association of stroke risk factors, clinical presentation, assessment, response to treatment and outcomes. Therefore, a comprehensive but personalized approach to care for patients is essential and includes consideration of sex and gender disparities,” Dr. Song said. “A prospective, longitudinal study with a larger sample size and details of hypertension medication dose/types, medication compliance, menopausal state and hormone levels would enable us to gain better insight into sex-differences in stroke related to intracranial atherosclerosis. This may also have implications in the development or progression of vascular dementia. As women are historically under-represented in major clinical trials, strategies to ensure adequate representation of women are also needed.”

Dr. Song and her team published the results of their study in the Journal of the American Heart Association in 2022.

Research Pivot Due to Pandemic

Dr. Song and her team were hampered in their research by the COVID-19 pandemic but were able to continue their research with some adaptations.

“During the COVID-19 pandemic, resources, personnel and time were reallocated. Despite the restrictions with the inability to conduct onsite recruitment and research, I adapted and redirected my resources and time to other opportunities,” Dr. Song said. “For example, I found ways to work remotely with my mentees and collaborators during the pandemic. We published four systematic reviews/meta-analyses and two original manuscripts analyzing retrospective imaging data. This work strengthened foundational knowledge, generated preliminary data and strengthened collaborative relationships.”

Despite the slight schedule delays due to the pandemic, the Bayer HealthCare/RSNA Research Scholar Grant was invaluable to help Dr. Song protect her research time.

“The R&E grant gave me time to gather preliminary data, learn research methodology and gain experience in manuscript and grant writing. It was a critical source of early support in my career and provided me with a springboard upon which I could begin my physician-scientist career,” Dr. Song said. “I am sincerely grateful to the R&E Foundation and my mentors. I feel privileged to be part of a cohort of R&E Foundation grant awardees.”