Critical Closing Pressure Mediates the Association of Intracranial Artery Calcification with White Matter Hyperintensities

INTRODUCTION: This study sought to investigate the severity of intracranial artery calcification (IAC) in relation to white matter hyperintensities (WMHs), and whether the association was mediated by cerebral autoregulation (CA). METHODS: A total of 144 patients with cerebral small vessel disease were included in this study. The severity of WMH was assessed using Fazekas scores in FLAIR-magnetic resonance imaging images. On non-contrast head computed tomography images, the severity of IAC was measured by IAC scores and further classified as intimal or medial calcification. As proxy of CA, critical closing pressure (CrCP) was determined by analyzing blood pressure-flow velocity relationships in the middle cerebral artery. Mediation analyses were conducted examine the proportion of mediation of CrCP on the association between IAC and WMH. RESULTS: IAC scores were found to be associated with WMH scores (β 0.364; 95% confidence interval [CI], 0.133-0.409; p < 0.001). After multivariable adjustment, a statistically significant association was observed between IAC scores and higher CrCP values (β, 0.329; 95% CI, 0.129-0.528; p = 0.001). Mediation analyses revealed that CrCP partially mediated (10.3%) the association between higher IAC scores and increased WMH severity. The proportion of mediation was driven by a medial calcification pattern (13.9%). CONCLUSION: This hospital-based study demonstrated the association between higher IAC scores and the severity of WMH in patients with cerebral small vessel disease, which can be partially mediated by CA as indicated by CrCP, especially for the patients with predominantly medial calcification.