Limited information is available regarding the linkage between hypertension (HTN) and ischemic stroke based on sex.¹ Recently, at the International Stroke Conference 2022, Dr. Tracey E. Madsen, MD, Associate Director, Division of Sex and Gender, Co-Director at RIH and TMH Stroke Centers, from the United States (US), presented the implications of stroke risk factors in both sexes.¹ The incidence of stroke is primarily attributed to HTN, which is among the various modifiable risk factors.¹ The Greater Cincinnati Northern Kentucky Stroke study showed that the incidence of stroke in both male and female rose significantly with age, predominantly in the older age groups (65-84 years and >85 years), when compared with the younger age groups (20-44 years and 45-64 years).¹ Data showed that women had a lower stroke risk when compared with men in the age groups of 45-65 years and 65-84 years.¹

Figures showed that in the US, about 47.3% of adults were diagnosed with Stage 1 HTN [systolic blood pressure (SBP) level of 130mmHg/diastolic blood pressure (DBP) level of 80mmHg]; when compared with the white adults, while a greater percentage of black adults experienced a higher rate of HTN [41.5% vs. 48.2%, respectively; multivariable-adjusted prevalence ratio=0.88; 95% CI: 0.81-0.96].¹ Among the participants with HTN, the percentage of adults with controlled blood pressure (BP) (SBP level of <140mmHg and DBP level of <90mmHg) increased from 31.8 % (95% CI: 26.9%-36.7%) to 53.8% (95% CI: 48.7%-59.0%) between 1999-2013, and decreased to 43.7% (95% CI: 40.2%-47.2%) in 2017-2018.¹ Among the participants who took antihypertensive medication, the percentage of adults with controlled BP increased from 53.4% to 68.3% from 1999 to 2013, and decreased to 64.8% in 2018.¹

Scientists revealed that by midlife, BP levels in women rise and catch up to that of the men’s levels.¹ When compared with men, women in their 20’s tend to exhibit increased rates of BP elevation with aging.¹ Moreover, all BP components such as SBP, pulse pressure (PP),  mean arterial pressure (MAP), and DBP were found to be increased in women as opposed to men, with SBP and PP the highest, thereby, suggesting that women experience a different trajectory of BP.¹ The Northern Manhattan Study revealed that the population attributable risk for stroke due to HTN accounted for 30%.¹ Likewise, the Global Burden of Disease 2019 study also showed that among all other stroke risk factors, high SBP accounted for the largest proportion of disability-adjusted life years for ischemic stroke, intracerebral hemorrhage and subarachnoid hemorrhage.¹

The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study (N=26,461) included participants >45 years old (with 40% black individuals), whose BP levels were stratified as normotensive (<120mmHg), prehypertension (120-129mmHg), stage 1 (130-139mmHg), and stage 2 (>140mmHg) blood pressure strata.¹ Dr. Madsen mentioned that the association of stroke changed drastically in women, whereas the effect sizes for women were greater than men.¹ The overall pooled effect estimate for women was 1.25 (95% CI: 1.16-1.34) and 1.14 (95% CI: 1.05-1.23; p=0.09) for men. The pooled effect estimates of the average increase in stroke risk per increase in the number of medications were similar by sex (1.23, 95% CI: 1.14-1.33 for women; 1.21, 95% CI: 1.12-1.31 for men; p=0.79).¹

Dr. Madsen explained some of the ongoing hypothesis for sex-specific differences in the BP trajectories over the lifespan, including sex hormones, sexually dimorphic processes like insulin resistance, long-term effects of reproductive risk factors such as preeclampsia, and sex-specific genetic risks.¹ She added that the loss of estrogen and other female-specific sex hormones affected a variety of processes through the menopausal transition and after menopause; such as salt sensitivity, renin-angiotensin system, vascular aging, and arterial stiffness.¹ A study which identified sexually dimorphic metabolic profiles in arterial HTN showed that men displayed metabolic footprints on histidine, whereas women displayed metabolic footprints on arginine and nitric oxide pathway which was related to insulin resistance (also a sexually dimorphic pathway).¹

Last but not least, Dr. Madsen suggested several strategies to improve BP control, including earlier and broader screening for women with the use of different methods, such as home screening and ambulatory BP measurement.¹ She added that due to the stronger association between Stage 1 and 2 HTN and ischemic stroke in women than men, the use of sex-specific stroke prediction tools should be considered.¹ Moreover, she suggested that more women should be enrolled in prevention trials for improved benefits.¹ She also recommended improved guideline adherence with special emphasis to improve HTN screening at younger ages and involve those high-risk groups, such as Black and Hispanic women.¹ To conclude, Dr. Madsen said in the future, more studies pertaining to sex-specific approaches and secondary stroke prevention should be conducted, while increased attention should be focused on interventions that are effective for diverse populations.¹