Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, P.R. China.
NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, Guangdong 510080, P. R. China.
J Clin Endocrinol Metab. 2024 Jan 18;109(2):581-591. doi: 10.1210/clinem/dgad480.
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.
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.
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).
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.
25-羟维生素 D 与死亡率之间的关联仍存在争议。Klotho 是维生素 D 激活和代谢的生物标志物，它可能在这种关联中发挥关键作用。然而，维生素 D 缺乏与死亡风险之间的关联是否受 Klotho 水平的影响尚不清楚。因此，本研究旨在调查血清 25-羟维生素 D [25(OH)D]和 Klotho 与美国社区居住的成年人死亡风险之间的联合关联。
共有 9870 名来自国家健康和营养检查调查（2007-2016 年）的成年人纳入本研究。通过将参与者与国家死亡指数记录相关联来确定死亡率数据。使用 Cox 比例风险模型评估血清 25(OH)D、血清 Klotho 与全因和心血管疾病 (CVD) 死亡率之间的关系。
我们发现 Klotho 与全因死亡率之间存在显著的交互作用（P =.028）。Klotho > 848.4 pg/mL（死亡率风险阈值）时，无论血清 25(OH)D 水平如何，均未观察到全因和 CVD 死亡的显著风险。然而，Klotho < 848.4 pg/mL 时，血清 25(OH)D < 50 nmol/L 时观察到全因和 CVD 死亡率的显著风险[风险比 (HR)，1.36；95%置信区间 (CI)，1.10-1.69；HR，1.78；95%CI，1.16-3.45]和血清 25(OH)D 连续变量（HR，0.98；95%CI，0.97-.99；HR，0.98；95%CI，0.98-.99）。此外，通过血清 25(OH)D 降低（<50 nmol/L）和 Klotho 降低（<848.4 pg/mL）相结合来评估维生素 D 代谢紊乱与全因死亡率（HR，1.48；95%CI，1.11-1.96）和 CVD 死亡率（HR，2.36；95%CI，1.48-3.75）显著相关。
只有 Klotho 同时降低时才观察到与维生素 D 相关的死亡风险，这表明维生素 D 代谢功能障碍增加了死亡风险。Klotho 水平可帮助预测长期死亡率结果，因此对于指导维生素 D 缺乏人群的维生素 D 补充治疗决策可能有用。
