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Background: The cardio-ankle vascular index (CAVI) is a surrogate marker of arteriosclerosis in patients with acute ischemic stroke that is independent of blood pressure. Brain white matter lesions (WMLs) on magnetic resonance imaging (MRI) is the core marker of cerebral small vessel diseases, including lacunar infarction or microbleeds. However, whether WMLs are associated with CAVI is still unclear. This study was conducted to clarify whether the WMLs detected during medical checkup in subjects without cardio-cerebrovascular diseases were associated with the CAVI or vascular risk factors.Methods: CAVI and vascular risk factors were assessed in 280 subjects (mean age, 52.6 years) who underwent brain MRI. Arterial stiffness was evaluated using CAVI. The patients were divided into two groups according to the presence or absence of WMLs. Clinical characteristics were compared between the two groups. WML was defined as a cap or pencil-thin lining of periventricular hyperintensity and/or punctate focus of a deep white-matter hyperintense lesion according to the Fazekas grades on fluid-attenuated inversion recovery (FLAIR).Results: CAVI was significantly higher in the subjects with than in those without WMLs (8.17 vs 7.22, p < 0.001). In the multivariable analyses, CAVI, particularly a 1-point increase in CAVI (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.68-3.03), was independently associated with the presence of WMLs. Hypertension (HT) was also independently associated with the presence of WMLs (OR, 2.01; 95% CI, 1.15-3.52). The effects of the four combinations of low/high levels of CAVI and the subjects with or without HT on the presence of WMLs were also analyzed. After adjustment for age, sex, and diabetes mellitus, the subjects with a higher CAVI (median, ≥7.4) and HT had greater odds that they may have WMLs (OR, 3.44; 95% CI, 1.04-11.4) than the subjects with lower CAVI and without HT. By contrast, the OR was not significant in the combinations of lower CAVI and HT, and higher CAVI and without HT.Conclusions: Both increased CAVI and HT were independently associated with the presence of WML even in its early stage. Nevertheless, the presence of a WML could be predicted more reliably by considering these two factors together rather than either alone.