Anti-aging protein α-Klotho is potential for reducing comorbidity risk of cardiometabolic diseases in vulnerable populations and enhancing long-term prognosis.

Additionally, the pathways ‘α-Klotho → obesity → T2DM → CVD’ ( p = 0.064) and ‘α-Klotho → obesity → CKD → CVD’ ( p = 0.061) showed borderline significance, implying a potential but less pronounced mediation effect.

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Among the population with cardiometabolic comorbidities, Klotho showed an approximately L-shaped dose-response relationship, with an overall trend towards a predominantly negative association with the risk of all-cause mortality.

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In the fully adjusted model, the odds ratio (OR) was 0.56, indicating that with each unit increase in log10(α-Klotho), there was a decreasing trend in the number of metabolic comorbidities accompanying CVD, with a magnitude of 0.56 times.

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