RESUMO
AIMS: 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. METHODS: 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. RESULTS: 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/m2, 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. CONCLUSIONS: 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.
RESUMO
BACKGROUND: Evidence from animal models suggests a role for the organic ultraviolet filter benzophenone-3's (BP-3) on white blood cells (WBCs). However, BP-3's effect on WBCs in humans is unknown. MATERIALS AND METHODS: We used National Health and Nutrition Examination Survey data from 2003 to 2016. We included participants >6 years with data on urinary BP-3, urinary creatinine, and WBC count. Quintiles of urinary creatinine-normalized BP-3 (CnBP-3) levels were used in linear regression models adjusting for age, gender, race, body mass index (BMI), smoking status, education level, family income to poverty threshold ratio, survey cycle, and season. RESULTS: Of the 16 959 participants, 8564 (50.5%) were females, 6602 (38.9%) were White, and 3870 (22.8%) were Black. The mean (standard deviation) age was 37.6 (22.7) years, BMI was 26.8 (7.40) kg/m2, WBC count was 7.22 (2.53) × 109/L, neutrophil count was 4.15 (1.86) × 109/L, and lymphocyte count was 2.25 (1.33) × 109/L and median (interquartile range) of CnBP-3 was 12.1 (44.9) µg/gm. The highest quintile of CnBP-3 was associated with significantly lower WBC and neutrophil counts compared to the lowest quintile of CnBP-3 (Δ quintiles = -137 × 106/L, 95% CI: -249 to -24, p = 0.02 and = -177 × 106/L, 95% CI: -323 to -30, p = 0.02, respectively). In contrast, we did not observe a difference in lymphocyte count between the lowest and highest quintiles of CnBP-3 in unadjusted or adjusted analyses. CONCLUSION: We found an inverse relationship between BP-3 levels and WBC and neutrophil counts, and not with lymphocyte count. Further research is needed to confirm our findings.