Association of α-klotho concentrations with cardiovascular and all-cause mortality in American adults with depression: a national prospective cohort study

This study examines α-klotho levels in depressed American adults and their association with cardiovascular disease and all-cause mortality, utilizing data from the National Health and Nutrition Examination Survey (2007–2016) and mortality details from the National Death Index up to December 31, 2019. Including 3329 participants with depression, findings revealed 485 all-cause and 113 cardiovascular deaths. To investigate the nonlinear association between α-klotho and mortality, the Cox proportional hazards regression model, restricted cubic splines, and two-piecewise Cox proportional hazards model were developed. Analyzes indicated an “L-shaped” relationship between ln-transformed α-klotho levels and all-cause mortality, with a significant threshold effect at 6.53 ln(pg/ml). Below this threshold, ln-transformed α-klotho levels were inversely related to all-cause mortality (adjusted HR 0.33, 95%CI = 0.19–0.56), with no significant association above it (adjusted HR 1.41, 95%CI = 0.84–2.36). Cardiovascular mortality showed no link to α-klotho levels. Subgroup analysis shown that, the association between ln-transformed α-klotho concentration and all-cause mortality was consistent in subgroups according to gender, age, BMI, race, and depression(adjusted P > 0.05). The study uncovers a non-linear “L-shaped” association between ln-transformed α-klotho levels and all-cause mortality in depressed individuals, suggesting α-klotho assessment as a tool for identifying high-risk patients and guiding preventive strategies to enhance survival.