The association of Serum Klotho with the prevalence of car-diovascular disease and prognosis in general population:re-sults from the National Health and Nutrition Examination Su-rvey 2007-2016

Yi-Ting CAI; Shu-Ying QI; Shu-Yuan QI; Rong XU; Hong-Yan ZHU; Guang-Yao ZHAI

doi:10.26599/1671-5411.2024.11.008

摘要：Background Previous studies have extensively investigated traditional predictors of cardiovascular disease(CVD)develop-ment,progression,and prognosis.However,the influence of novel indicators such as Klotho,on CVD prevalence and prognosis in the general population remains unclear. Method This was an observational study that utilized cross-sectional and longitudinal methods to examine the general popula-tion in the National Health and Nutrition Examination Survey(NHANES)2007-2016.The participants were divided into four groups according to the Klotho quartiles.Primary outcome was CVD[coronary artery disease(CAD),congestive heart failure,and stroke],secondary outcomes were all-cause mortality and cardiovascular mortality.Survey-weighted binary logistic regres-sion analysis was used to analyze the association between Klotho and the prevalence of primary outcome,and the restricted cu-bic spline(RCS)curve was used to further analyze the nonlinear relationship.Subgroup analyses were conducted to investigate the association between Klotho values and CVD prevalence using survey-weighted binary logistic regression.The incidence of the secondary outcomes among four groups was assessed through Kaplan-Meier survival analysis.Additionally,the relationship between Klotho values and secondary endpoints was explored using survey-weighted Cox proportional hazards regression across various patient subpopulations. Results A total of 12,146 participants(56.8±10.7 years,48.5％male)were included in our study.The total incidence of CVD was 9.9％(n=1201),of which 4.7％(n=574)were CAD,3.7％(n=454)were congestive heart failure,and 4.1％(n=497)were stro-ke.Binary logistics regression analysis showed that higher Klotho quartiles were associated with the decreased prevalence of CVD[Quartile 4 vs.Quartile 1:odds ratio(OR)(95％CI):0.77(0.64-0.93),P=0.006]and congestive heart failure[Quartile 4 vs.Quartile 1∶0.75(0.56-0.99),P=0.048],However,no significant associations were found between Klotho levels and the outcomes of CAD or stroke.RCS curve illustrated a high Klotho value was negatively correlated with the prevalence of CVD(nonlinear P=0.838),congestive heart failure(nonlinear P=0.110)and stroke(nonlinear P=0.972).No significant interactions were observed in any subgroups regarding the associations between Klotho and prevalence of CVD.After a median follow-up period of 93 months(range:from 1 to 160 months),there were 1228 cases(10.1％)of all-cause mortality in the general population,including 296 cases(2.4％)of cardiovascular mortality.The Kaplan-Meier curves indicated that lower Klotho levels were associated with a significant increase in all-cause mortality across the general population,CVD population,and non-CVD population.As Klotho levels de-creased,there was also a notable rise in cardiovascular mortality in both the general population and the CVD population.In the overall population,Cox regression analyses demonstrated that higher Klotho values were associated with a decreased risk of both all-cause and cardiovascular mortality.And no significant interaction was observed in the CVD subgroup regarding the as-sociation between Klotho and mortality. Conclusion High Klotho level was associated with low prevalence of CVD and low risk of mortality in general population.