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.