Serum Alpha-Klotho and Coronary Atherosclerosis: Associations with Coronary CT Angiography Findings and Atherogenic Indices.

Background/Objectives: Alpha-Klotho is a circulating protein with anti-aging and vasculoprotective properties that may play a role in vascular calcification. This study aimed to investigate the association between serum alpha-Klotho levels and coronary atherosclerotic burden assessed by the Agatston score and CAD-RADS grading, as well as cardiometabolic risk indices. Methods: This single-center, prospective, cross-sectional study included 86 patients undergoing coronary computed tomography angiography. Serum alpha-Klotho levels were measured by ELISA. Associations with imaging and metabolic variables were assessed using Spearman correlation and age-adjusted partial correlation analyses. Independent associations were evaluated using multivariable linear regression with HC3-robust standard errors. Binary and ordinal logistic regression models with CAD-RADS as the dependent variable and receiver operating characteristic (ROC) analysis were additionally performed. Results: Serum Klotho levels were negatively correlated with age (ρ = -0.598), Agatston score (ρ = -0.540), and CAD-RADS (ρ = -0.549) (all p < 0.001). Associations with the Agatston score and CAD-RADS remained significant after age adjustment (ρ = -0.348 and -0.352, respectively). AIP also remained independently associated with Klotho after age adjustment (ρ = -0.289, p = 0.007), whereas associations with TyG and METS-IR were attenuated. Multivariable models explained 50-52% of the variance in Klotho. In ordinal logistic regression, Klotho remained independently associated with CAD-RADS severity after adjustment for age, sex, BMI, and AIP (OR = 0.525, p = 0.033). ROC analysis demonstrated moderate discrimination for the presence of coronary atherosclerosis, defined as Agatston score > 0 (equivalently, CAD-RADS > 0 in this cohort) (AUC = 0.754, 95% CI 0.654-0.855); an exploratory, internally derived cutoff of ≤823 pg/mL-not a clinically validated threshold-yielded 72.0% sensitivity and 75.0% specificity (bootstrap-validated optimism-corrected: 69.3% and 72.5%). Conclusions: Lower serum alpha-Klotho levels were independently associated with greater coronary atherosclerotic burden and showed moderate discriminative ability for its presence. These findings are preliminary and support further investigation of alpha-Klotho as a candidate circulating biomarker of coronary atherosclerosis, pending validation in larger, prospective cohorts.