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Background The association between 25-hydroxyvitamin D and mortality remains controversial. Klotho, a biomarker of vitamin D activation and metabolism, may play a key role in this association. However, it is unclear whether the association between vitamin D deficiency and mortality risk is modified by klotho levels. Therefore, this study investigated the joint association of serum 25-hydroxyvitamin D [25(OH)D] and klotho with mortality risk in American community-dwelling adults. Methods A total of 9870 adults from the National Health and Nutrition Examination Survey (2007-2016) were included in our study. Mortality data were ascertained by linking participants to National Death Index records. Cox proportional hazards models were used to assess the association among serum 25(OH)D, serum klotho, and all-cause and cardiovascular disease (CVD) mortality. Results We found a significant interaction between klotho and serum 25(OH)D in all-cause mortality (P =.028). With klotho > 848.4 pg/mL (risk threshold on mortality), no significant all-cause and CVD mortality risk was observed at any level of serum 25(OH)D. However, with klotho < 848.4 pg/mL, a significant all-cause and CVD mortality risk was observed with serum 25(OH)D < 50 nmol/L [hazards ratio (HR), 1.36; 95% confidence interval (CI), 1.10-1.69; HR, 1.78; 95% CI, 1.16-3.45) and serum 25(OH)D of continuous variable (HR, 0.98; 95% CI,.97-.99; HR, 0.98; 95% CI,.98-.99). In addition, vitamin D metabolism disruption accessed by the combination of decreasing serum 25(OH)D (<50 nmol/L) and klotho (<848.4 pg/mL) was associated with significant all-cause mortality (HR, 1.48; 95% CI, 1.11-1.96) and CVD mortality (HR, 2.36; 95% CI, 1.48-3.75). Conclusions Vitamin D-associated mortality risk is observed only with concurrently decreasing klotho, indicating that vitamin D metabolism dysfunction increases the risk of mortality. Klotho levels could help predict long-term mortality outcomes and thus may be useful concurrently for guiding vitamin D supplementation therapy decision-making in populations with vitamin D deficiency. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the associations between the triglyceride-glucose (TyG) index in young adulthood with incident cardiovascular disease (CVD) and mortality. Methods: We included 4,754 participants from the Coronary Artery Risk Development in Young Adults study at baseline. The TyG index was calculated as ln (fasting TG [mg/dl] × fasting glucose [mg/dl]/2), and the TyG index trajectories were identified by using the latent class growth mixture model. We evaluated the association between the baseline and trajectories of the TyG index with incident CVD events and all-cause mortality using Cox proportional hazards regression analysis. The added value of the TyG index included in pooled cohort equations for CVD prediction was also analyzed. Results: Among 4754 participants (mean age 24.72 years, 45.8% male, 51.2% black), there were 158 incident CVD events and 246 all-cause mortality during a median 25 years follow-up. After adjusting for multiple confounding variables, each one-unit increase in the TyG index was associated with a 96% higher CVD risk (hazard ratio [HR] 1.96, 95% confidence interval [CI] 1.44–2.66) and a 85% higher all-cause mortality risk (HR 1.85, 95% CI 1.45–2.36). Three distinct trajectories of the TyG index along the follow-up duration were identified: low (44.0%), moderate (45.5%), and high (10.5%). Compared with those participants in the low TyG index trajectory group, those in the high TyG index trajectory group had a greater risk of CVD events (HR 2.35, 95% CI 1.34–4.12) and all-cause mortality (HR 3.04, 95% CI 1.83–5.07). The addition of baseline TyG index to pooled cohort equations for CVD improved the C-statistics (P < 0.001), integrated discrimination improvement value (P < 0.001), and category-free net reclassification improvement value (P = 0.003). Conclusions: Higher baseline TyG index levels and higher long-term trajectory of TyG index during young adulthood were significantly associated with an increased risk of incident CVD events and all-cause mortality in later life. [ABSTRACT FROM AUTHOR]