Tang Jiao, Xu Zhehao, Ren Li, Xu Jiahua, Chen Xin, Jin Yian, Liang Ruiyun, Zhang Huanji
Department of Cardiovascular Medicine, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
Department of General Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Lipids Health Dis. 2024 Dec 18;23(1):408. doi: 10.1186/s12944-024-02400-w.
Cardiovascular-kidney-metabolic (CKM) syndrome is characterized as a systemic disease resulting from the pathophysiological interplay among metabolic risk factors, chronic kidney disease (CKD), and cardiovascular disease (CVD). The Klotho protein may serve as a novel biomarker. However, the utility of serum Klotho levels as an indicator of severity and mortality risk in CKM syndrome remains uncertain.
This study involved 9,871 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2016. Serum Klotho levels were measured using an enzyme-linked immunosorbent assay kit. The optimal cutoff value was established through the maximum Youden's index. Multivariable weighted regression models were employed to calculate the odds ratio and hazard ratio, along with the 95% confidence interval, to evaluate the association between serum Klotho levels and the severity of CKM syndrome, as well as all-cause and cardiovascular mortality. Additionally, the receiver operating characteristic curve and restricted cubic spline curves were utilized to assess predictive efficacy and to explore nonlinear relationships.
After adjusting for potential confounding factors, a non-linear relationship was seen between the Klotho protein, and CKM syndrome. In the multivariable, piecewise logistic regression, when the Serum klotho was less than 801, the risk of CKM syndrome decreased with the increase in Serum klotho (OR = 0.82, 95%CI 0.70, 0.96; p < 0.001). Furthermore, we observed the association when the Serum klotho was greater than 801 (OR = 0.94, 95%CI 0.89, 0.99; p = 0.035). The relationship between serum Klotho levels and all-cause mortality was U-shaped, while the relationship with cardiovascular mortality was L-shaped. Specifically, low serum Klotho levels were associated with an increase in all-cause mortality by 21% and cardiovascular mortality by 76% among patients with CKM syndrome. Furthermore, serum Klotho levels demonstrated excellent predictive efficacy for both the severity and mortality associated with CKM syndrome.
This study indicates that low serum Klotho levels serve as reliable indicators of both the severity of CKM syndrome and the associated risk of mortality.
心血管 - 肾脏 - 代谢（CKM）综合征是一种由代谢危险因素、慢性肾脏病（CKD）和心血管疾病（CVD）之间的病理生理相互作用导致的全身性疾病。Klotho蛋白可能是一种新型生物标志物。然而，血清Klotho水平作为CKM综合征严重程度和死亡风险指标的效用仍不确定。
本研究纳入了9871名来自2007年至2016年期间进行的美国国家健康与营养检查调查（NHANES）的参与者。使用酶联免疫吸附测定试剂盒测量血清Klotho水平。通过最大约登指数确定最佳截断值。采用多变量加权回归模型计算比值比和风险比以及95%置信区间，以评估血清Klotho水平与CKM综合征严重程度以及全因和心血管死亡率之间的关联。此外，利用受试者工作特征曲线和受限立方样条曲线评估预测效能并探索非线性关系。
在调整潜在混杂因素后，发现Klotho蛋白与CKM综合征之间存在非线性关系。在多变量分段逻辑回归中，当血清Klotho低于801时，CKM综合征风险随血清Klotho升高而降低（比值比 = 0.82，95%置信区间0.70，0.96；p < 0.001）。此外，当血清Klotho大于801时我们也观察到了这种关联（比值比 = 0.94，95%置信区间0.89，0.99；p = 0.035）。血清Klotho水平与全因死亡率之间的关系呈U形，而与心血管死亡率之间的关系呈L形。具体而言，在CKM综合征患者中，低血清Klotho水平与全因死亡率增加21%以及心血管死亡率增加76%相关。此外，血清Klotho水平对CKM综合征相关的严重程度和死亡率均显示出良好的预测效能。
本研究表明，低血清Klotho水平是CKM综合征严重程度和相关死亡风险的可靠指标。
