Department of Medicine, Eastern Virginia Medical School, Norfolk, Virginia, USA.
EVMS School of Health Professions, Macon & Joan Brock Virginia Health Sciences, Old Domion University, Norfolk, Virginia, USA.
Br J Clin Pharmacol. 2024 Dec;90(12):3277-3285. doi: 10.1111/bcp.16217. Epub 2024 Aug 20.
The relationship between α-Klotho (αK) and mortality is controversial and has not been examined in a large, diverse cohort. We investigated the association between serum αK protein levels with all-cause and cause-specific mortality in a cohort representative of the US population.
We used National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2016. A nonlinear association between mortality and αK levels as a quadratic variable were examined using Cox proportional hazard models and competing risk models. Multivariable models were adjusted for age, gender, race, hypertension, diabetes, smoking, alcohol use, physical activity, body mass index (BMI), serum cholesterol, estimated glomerular filtration rate, highest educational status attained and family income to poverty threshold ratio.
Of the 13 749 participants, 1569 (11%) died, 7092 (52%) were female, and 5918 (43%) were Caucasian. The mean (SD) of age was 58 (11) years, BMI 29.7 (6.7) kg/m, and αK was 0.85 (0.31) ng/mL. In the adjusted Cox proportional hazards model with quadratic αK, we found a U-shaped relationship between all-cause mortality and αK levels (continuous αK hazard ratio [HR] = 0.56, 95% confidence interval [CI]: 0.37, 0.85; P = .007; squared-αK HR = 1.25, 95% CI: 1.11, 1.41; P < 0.001). A similar U-shaped relationship was noted between αK and cancer mortality in the adjusted Cox proportional hazards model (continuous αK HR = 0.45, 95% CI: 0.19, 1.06; P = 0.07; squared αK HR = 1.32, 95% CI: 1.07, 1.61; P = 0.009). No relationship was present with cardiovascular or other-cause mortality.
In this large diverse cohort, we report a U-shaped relationship between αK with all-cause and cancer mortality. Further research to elucidate the underlying biological mechanism of these relationships is needed.
α-Klotho（αK）与死亡率之间的关系存在争议，并且尚未在大型、多样化的队列中进行研究。我们在代表美国人群的队列中研究了血清αK 蛋白水平与全因和特定原因死亡率之间的关系。
我们使用了 2007 年至 2016 年的国家健康和营养检查调查（NHANES）数据。使用 Cox 比例风险模型和竞争风险模型检查死亡率与αK 水平之间的非线性关系，将αK 水平作为二次变量。多变量模型调整了年龄、性别、种族、高血压、糖尿病、吸烟、饮酒、体力活动、体重指数（BMI）、血清胆固醇、估计肾小球滤过率、最高受教育程度和家庭收入与贫困线的比值。
在 13749 名参与者中，1569 人（11%）死亡，7092 人（52%）为女性，5918 人（43%）为白种人。平均（SD）年龄为 58（11）岁，BMI 为 29.7（6.7）kg/m2，αK 为 0.85（0.31）ng/mL。在调整后的 Cox 比例风险模型中，我们发现全因死亡率与αK 水平之间存在 U 型关系（连续αK 风险比[HR]=0.56，95%置信区间[CI]：0.37，0.85；P=0.007；平方-αK HR=1.25，95%CI：1.11，1.41；P<0.001）。在调整后的 Cox 比例风险模型中，αK 与癌症死亡率之间也存在类似的 U 型关系（连续αK HR=0.45，95%CI：0.19，1.06；P=0.07；平方-αK HR=1.32，95%CI：1.07，1.61；P=0.009）。与心血管或其他原因死亡率无关。
在这个大型、多样化的队列中，我们报告了αK 与全因和癌症死亡率之间的 U 型关系。需要进一步研究来阐明这些关系的潜在生物学机制。
