Modulatory Effects of Hypertension on Aging-Related White Matter Hyperintensities: A Comparative Study Among Stroke Patients and Stroke-Free Community-Based Cohort

The increased vulnerability of the aging human brain to hypertension-induced neurovascular impairments, including cerebral small vessel diseases (SVD), marked by MRI-visible white matter hyperintensities (WMH), is well recognized. We examined WMH burdens between stroke patients and stroke-free participants across three age groups and explored patterns of modifiable risk factors, specifically the modulating effects of hypertension on WMH burden, providing insights for potential therapeutic interventions. This study comprised one hospital-based cohort of 254 stroke patients and another community-based cohort of 254 stroke-free normative participants. Clinical variables were obtained consecutively, and MRI neuroimaging classified WMH as absent, mild, moderate, or severe. A step-by-step statistical analysis was performed to explore the said gaps. There were 508 participants (mean age 63.5 ± 8.9 years) with 285 males. A similar prevalence but different WMH burden was recorded between stroke and normative cohorts across different age groups. The modulating effect of hypertension on WMH severity varied across age groups and is greater in middle-aged adults; intriguingly, this effect diminished in elderly adults (b = -0.882, 95%CI [-1.591, -0.172], t = -2.442, p = 0.015). It was shown that, in a non-uniform fashion across different age groups, hypertension is a culprit risk factor for exacerbating WMH severity, and middle-aged adults are the most vulnerable. While the elevation of systolic blood pressure predisposes adults to brain white matter deterioration, the decline in diastolic blood pressure suggests a protective role. Recognizing hypertension as a modifiable risk factor and understanding the aging-related changes in blood pressure patterns open avenues for developing age-specific strategies for the mitigation and management of WMH progression.

Keywords: aging; cerebral small vessel diseases; hypertension; modulation; stroke; white matter hyperintensities.