(CCSP125) SEX DIFFERENCES IN THE RELATIONSHIP BETWEEN THE AGE OF DIAGNOSIS OF HYPERTENSION AND BRAIN STRUCTURE IN MIDLIFE AND OLDER POPULATION: NEW INSIGHTS FROM THE UK BIOBANK

Background: Hypertension is an established leading risk factor for morbidity and mortality from vascular diseases across the lifespan. Early adulthood to midlife high blood pressure has been linked to later reduced brain volume and white matter hyperintensities, both of which are hallmarks of cerebral small vessel disease (CSVD). Independent of blood pressure control, the age of hypertension diagnosis has been identified as a unique contributor to brain structural changes related to cerebral small vessel disease. However, whether the association of age at diagnosis of hypertension with CSVD-related brain atrophy differs between females and males is not fully understood. Therefore, our objective was to assess for sex differences in the association between the age at diagnosis of hypertension and CSVD-related brain structural changes (lower total brain volume and higher volume of white matter hyperintensities).

METHODS AND RESULTS: We used data from the UK Biobank, a prospective cohort study of over 500,000 participants aged 40 to 69 years enrolled between 2006 and 2010. We selected participants with a known age of diagnosis of hypertension who had also obtained a brain MRI between 2014 and 2016 (n = 9,410) and stratified by age of diagnosis of hypertension ( < 35 years, 35-44 years, 45-54 years, 55-64 years, ≥65 years old) and sex. Using propensity score matching a control participant with MRI data but no hypertension was chosen at random. Generalized linear models were used to determine changes in brain structure as a function of age of hypertension diagnosis and sex while controlling for vascular risk factors and demographic covariates.

There was a trend for lower brain volume (adjusted for head size) in males diagnosed with hypertension at a younger age of diagnosis < 35 years,β −23088.6 (95%CI,[−42244.3 to −3932.9]mm3), 35 to 44 years (β −7003.7 [95%CI −15516.5 to 1509]mm3), and 45 to 54 years (β −5260.5 [95%CI −9882.6 to −638.4]mm3) but not in females. The volume of white matter hyperintensities was greater in both males (β 1488.1 (95%CI, [1149.2 to 1827]mm3) and females (1700.1 [1351.9 to 2048.3]mm3) with hypertension compared to without hypertension at all ages; more so in females (p interaction =0.03).

Conclusion: Hypertension diagnosed in early adulthood was associated with smaller brain volumes in males. Even though both males and females with hypertension had a higher volume of white matter hyperintensities, hypertensive females had the highest volume. Therefore, sex-specific analyses are necessary to uncover effect of hypertension related to CSVD in males and females.