Hypertension Is Associated with White Matter Disruption in Apparently Healthy Middle-Aged Individuals

Abstract

Background and purpose: Traditional cardiovascular risk factors have been associated with white matter disease. Because hypertension results in vascular stiffness and impaired cerebral perfusion, we hypothesized that it would be the most relevant risk factor for microstructural white matter disruption in apparently healthy middle-aged individuals with a family history of early-onset coronary artery disease.

Materials and methods: This was a cross-sectional analysis of participants in the Genetic Study of Atherosclerosis Risk with DTI. Regional fractional anisotropy of 181 segmented brain regions was measured using Eve WM Atlas. Risk factors were examined using univariate analysis for 48 regions representing deep WM structures. Minimal multivariable linear regression models adjusting for age, sex, and race and maximal linear regression models adjusting for cardiovascular risk factors were performed for regions meeting the Bonferroni threshold in the initial analysis.

Results: Included were 116 subjects (mean age, 49 ± 11 years; 57% men) with a moderate load of cardiovascular risk factors. Subjects with hypertension had significantly lower regional fractional anisotropy in the right cingulum and left stria terminalis in the minimal and maximal regression models. Additionally, there was lower regional fractional anisotropy in the left fornix in the maximal model and right sagittal stratum in the minimal model. Systolic blood pressure values were significantly associated with regional fractional anisotropy in the left superior longitudinal fasciculus in the maximal model. There were no significant differences among regional fractional anisotropy values for other cardiovascular risk factors.

Conclusions: In middle-aged apparently healthy individuals with susceptibility to vascular disease, among all known cardiovascular risk factors, hypertension was associated with microstructural WM disruption.

Fig 1.

Bar chart of the regions that showed a significant difference in rFA between subjects with and without hypertension. CGH (R) indicates right cingulum; EC (L), left external capsule; Fx (L), left fornix; Fx (R), right fornix; GCC (L), left genu of the corpus callosum; SS (R), right sagittal stratum; ST (L), left stria terminalis.

Fig 2.

Axial, coronal, and sagittal sections of the FA map, showing areas, in distinct colors, that demonstrate a significant difference of rFA between patients with and without hypertension and areas that show correlation of rFA with systolic blood pressure. Magenta indicates right cingulum; red, left external capsule; orange, left fornix; yellow, right fornix; blue, left genu of the corpus callosum; pink, right sagittal stratum; green, left stria terminalis; white, left superior longitudinal fasciculus.

Fig 3.

Scatterplot showing the relationship of rFA of the left superior longitudinal fasciculus and systolic blood pressure. SLF (L) indicates left superior longitudinal fasciculus.