Hypertension, intracranial arteriosclerosis, and structural brain changes in patients with TIA or ischemic stroke

Hypertension is a major risk factor of structural brain changes, including atrophy and cerebral small vessel disease. Intracranial arteriosclerosis could be an underlying mechanism between hypertension and structural brain changes. This study investigated whether intracranial carotid artery calcification (ICAC), as a proxy for intracranial arteriosclerosis, explains the association between hypertension and structural brain changes in patients with TIA or ischemic stroke. About 968 patients (mean age 62.7 years) with TIA or ischemic stroke from a registry who underwent non-contrast CT (NCCT) and CT-angiography (CTA) were included in this study. Presence and volume (mm3) of ICAC were assessed on CTA. Subtypes of ICAC were assessed on NCCT, where ICAC was categorized into intimal and internal elastic lamina (IEL) type calcification. Structural brain changes, indicated by atrophy, periventricular and deep white matter lesions (WML), and lacunes were assessed on NCCT. Mediation analysis was performed using ICAC, ICAC volume, and ICAC subtypes as mediators. ICAC was prevalent in 67.8% of patients, with 52.6% of them exhibiting intimal calcification, and 26.5% exhibiting IEL calcification. Atrophy, periventricular WML, deep WML, and lacunes were present in 48.1%, 56.4%, 43.0% and 17.1% of patients respectively. The presence of ICAC explained 7.1% of the association of hypertension with periventricular WML, 3.6% with deep WML, and 17.6% with lacunes. Hypertension was associated with increased atrophy through ICAC (OR: 1.02, 95% CI: 1.00-1.05). In subgroup analyses, IEL calcification partly explained the association between hypertension and periventricular WML (16.8%), and atrophy (OR: 1.12, 95% CI: 1.02-1.27). Intimal calcification did not explain any association. ICAC partially explained the association between hypertension and atrophy, periventricular and deep WML, and lacunes. Although intimal calcification was more prevalent in ischemic stroke patients, IEL calcification takes the leading role in explaining the association between hypertension and structural brain changes.