Association Between Blood Free Fatty Acid Concentrations in Midlife and Cerebral Small Vessel Disease

Free fatty acids (FFAs) are a risk factor for recurrent ischemic stroke, primarily via the overproduction of reactive oxygen species. However, the association between FFA concentrations and cerebral small vessel disease (SVD), including lacunes, cerebral microbleeds, and white matter lesions on brain magnetic resonance imaging, remains unclear. This study included 95 patients with acute ischemic stroke (median age: 59 [interquartile range: 49-73] years). The patients were divided into two groups: those aged ≤59 years (midlife patients) and those aged ≥60 years (late-life patients). In the midlife patients, the low serum total FFA concentration was an independent risk factor of lacunes (adjusted odds ratio [aOR]: 0.82, 95% confidence interval [CI]: 0.69-0.96; <i>p</i> = 0.013). Among FFA fractions, low serum free C14:0 (aOR: 0.80, 95% CI: 0.66-0.98; <i>p</i> = 0.028), and free C18:3n-3 (aOR: 0.93, 95% CI: 0.87-0.99; <i>p</i> = 0.015) concentrations were independent risk factors of lacunes in the midlife patients. However, the serum total FFA concentrations did not differ according to the SVD findings in the late-life patients. Therefore, low blood FFA concentrations in midlife can be a novel "nonvascular," nonatheromatous risk factor of SVD, including the presence of lacunes identified on brain magnetic resonance imaging.