Circulating Amino Acids Independently Predict Longitudinal Progression of Cardio-Ankle Vascular Index in Japanese Older Adults: The Kyotango Longevity Cohort Study.

Background: Arterial stiffness is an established predictor of cardiovascular morbidity and mortality. Circulating amino acids have emerged as metabolic markers linked to cardiovascular risk, but longitudinal evidence in community-dwelling Japanese older adults remains limited. Therefore, we investigated whether baseline amino acid profiles predict progression of arterial stiffness, as assessed by the cardio-ankle vascular index (CAVI), in this population. Methods and Results: This prospective analysis of the Kyotango Longevity Cohort Study included 592 participants aged ≥65 years with repeated CAVI measurements (mean follow-up 3.2±0.5 years). Fasting blood samples were analyzed for 23 amino acids with sufficient data availability at baseline. Primary screening analyses adjusted for age, sex, and baseline CAVI identified glutamic acid, isoleucine, and leucine as significantly associated with greater CAVI increase (q<0.10). After multivariable adjustment for cardiovascular risk factors, these associations remained significant. No significant interactions were observed between the identified amino acids and markers of inflammation (interleukin 6 and high-sensitivity C-reactive protein), oxidative stress (8-hydroxy-2'-deoxyguanosine), or physical function (grip strength). Branched-chain amino acids and Fischer ratio were also independently associated with CAVI progression. Conclusions: Circulating amino acid profiles, particularly glutamic acid, leucine, and isoleucine, together with branched-chain amino acid-derived indices, independently predict longitudinal progression of arterial stiffness as assessed by CAVI in Japanese older adults.