Common and distinct risk profiles of asymptomatic extra- and intracranial atherosclerosis in the Nagahama cohort

Background and Purpose Atherosclerotic burden increases the risk of both extracranial internal carotid artery stenosis (ICS) and intracranial large artery disease (ICAD). However, the differences in risk profiles have not been thoroughly investigated. Methods Participants were recruited from the Nagahama study cohort in Japan. Individuals over 60 years old who underwent 1.5-T head and neck magnetic resonance angiography (MRA) between July 2013 and February 2017 were included. ICAD was defined as WASID ≥ 50%, and ICS was defined as NSCET ≥ 30%. The prevalence and association of risk factors, including proatherogenic and proinflammatory factors, and the p.R4810K variant in the RNF213 gene, were investigated. Multivariable logistic regression analyses were performed. Results A total of 3089 individuals participated in the study, with a mean age of 68.1 ± 5.3 years, and 36.0% were males. Among them, 52 (1.7%) had ICS, 119 (3.8%) had ICAD, and 15 (0.49%) had both conditions. Alopecia areata was an independent predictor for both ICS (Odds ratio [OR] 3.5; 95% CI 1.3-8.3) and ICAD (OR 2.1; 95% CI 1.0-3.9). Diabetes (OR 3.7; 95% CI 2.0-7.0) and older age (OR 2.4; 95% CI 1.2-4.5) were associated only with ICS, while the RNF213 variant was associated with only ICAD (OR 5.7; 95% CI 1.6-16.0). ICS and ICAD were also independently associated with each other. Conclusions In this MRA-based large scale study, alopecia areata, known as a systemic inflammatory disease, was shown to be a common risk factor for ICS and ICAD. While conventional atherosclerotic factors were associated with ICS, non-atherosclerotic factors appear to contribute to ICAD in Japan.