The association of Serum Klotho with the prevalence of cardiovascular disease and prognosis in general population: results from the National Health and Nutrition Examination Survey 2007-2016.

Background: Previous studies have extensively investigated traditional predictors of cardiovascular disease (CVD) development, 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 population 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 regression analysis was used to analyze the association between Klotho and the prevalence of primary outcome, and the restricted cubic 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% ( = 1201), of which 4.7% ( = 574) were CAD, 3.7% ( = 454) were congestive heart failure, and 4.1% ( = 497) were stroke. Binary logistics regression analysis showed that higher Klotho quartiles were associated with the decreased prevalence of CVD [Quartile 4 . Quartile 1: odds ratio (OR) (95% CI): 0.77 (0.64-0.93), = 0.006] and congestive heart failure [Quartile 4 . Quartile 1: 0.75 (0.56-0.99), = 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 = 0.838), congestive heart failure (nonlinear = 0.110) and stroke (nonlinear = 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 decreased, 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 association between Klotho and mortality.

Conclusion: High Klotho level was associated with low prevalence of CVD and low risk of mortality in general population.