ObjectiveMeasuring the body mass index (BMI) or waist circumference (WC) alone is insufficient for assessing possible health risks due to obesity. This study aimed to investigate whether the quotient of WC and BMI can be used as a proxy of the high-risk phenotype of obesity.MethodsData for analysis were derived from the National Health and Nutrition Examination Survey (NHANES 1999-2014). The Waist-BMI Ratio was defined as WC divided by BMI. The associations between Waist-BMI Ratio and mortality were estimated using Cox regression models. Restricted cubic spline and two-piecewise linear regression models were used to identify non-linear relationships. The discriminative abilities of different anthropometric measures were compared using receiver operating characteristic curves (ROC).ResultsThis study is based on data from 35557 adults (51.1% female, mean age 44.9 years). During an average follow-up of 101.8 months, 3680 participants died, including 807 of cardiovascular causes. In fully adjusted models, Waist-BMI Ratio was independently associated with overall (hazard ratio [HR], 1.78; 95% confidence interval [CI], 1.48-2.13) and cardiovascular (HR, 1.77; 95% CI, 1.25-2.52) mortality. Spline analyses revealed that dose-response relationships existed between Waist-BMI Ratio and death. The mortality risk rises dramatically above the cut-off point of the Waist-BMI Ratio (HR, 3.22; 95% CI, 2.43-4.26 for overall mortality and HR, 3.07; 95% CI, 1.71-5.52 for cardiovascular mortality). ROC curve analysis suggested that Waist-BMI Ratio was a better discriminator of mortality (AUC 0.637 for overall and 0.639 for cardiovascular mortality) than BMI, WC, and waist-to-height ratio (Delong’s test all P <0.001).ConclusionsWaist-BMI Ratio was independently associated with overall and cardiovascular mortality in a J-shaped pattern, offering an immense potential risk marker for obesity in the clinical setting.

BackgroundTo investigate the association between insulin resistance (IR), quantified by triglyceride glycemic index (TyG index), cardiovascular mortality (CVM), and all-cause mortality (ACM) in hypertension patients.MethodsWe included 8,554 patients with hypertension aged ≥18 years old from the 1999–2014 National Health and Nutrition Examination Surveys (NHANES). The status of CVM and ACM of participants were followed through December 31, 2015. Cox proportional hazards models and Kaplan-Meier survival curves were used to evaluate the relationship between TyG index, CVM, and ACM.ResultsDuring a median of 82 months follow-up, 1,882 mortality cases had occurred, 434 of which were due to cardiovascular disease. The patients with hypertension with TyG ≥ 10 were older, had a higher chance of being smokers, were obese, had higher blood pressure, and had risk or had cardiovascular disease. In Cox proportional hazards models, compared with the patients with TyG <8, those with TyG ≥ 10 had 56% increased risk for ACM. On the other hand, no significant difference for CVM between the four groups were observed. In the restricted cubic spline regression models, the relationship between TyG index and ACM was non-linear. Subgroup analysis showed non-linear relationship between TyG index and ACM in elderly patients aged ≥60 years. The cut-off value of TyG for ACM was 9.45, and those with higher or lower than 9.45 had more risk of ACM. When TyG index was more than 9.52, the risk for CVM would increase among the whole group. Kaplan-Meier survival curves showed patients with TyG ≥ 10 had higher risk of ACM and CVM (Log rank P < 0.05).ConclusionsWe demonstrated that the association between ACM and TyG index in elderly patients with hypertension aged ≥60 years was non-linear. However, TyG index was only more than 9.52, hence, the risk for CVM would increase among the whole hypertension group.

Purpose: Whether the paradox of high-density lipoprotein cholesterol (HDL-C) and elevated mortality risk extends to hypertensive patients is unclear. We aimed to investigate the association between HDL-C and all-cause and cardiovascular disease mortality in adults with hypertension. Methods: In the National Health and Nutrition Examination Surveys, 11,497 hypertensive participants aged ≥18years old and examined at baseline between 1999 and 2014 were followed up until December 2015. We categorized the HDL-C concentration as ≤30, 31-40, 41-50, 51-60 (reference), 61-70, >70 mg/dL and examined their associations with all-cause and cardiovascular mortality, respectively. Multivariate Cox regression was used to calculated hazard ratio (HR) and 95% confidence interval (CI) for mortality risk. Results: During follow-up (median: 9.2 ± 3.8 years), 3012 deaths and 713 cardiovascular deaths were observed. In the restrictive cubic curves, associations of HDL-C levels and allcause and cardiovascular mortality were detected to be U-shaped. After multivariable adjustment, HRs for all-cause mortality were for the lowest HDL-C concentration (≤30 mg/dL) 1.29 (95% CI, 1.07-1.56) and the highest (>70 mg/dL) 1.20 (1.06-1.37), comparing with the reference group. For cardiovascular mortality, HRs were 1.31 (0.83-1.48) and 1.09 (0.83-1.43), respectively. Similar results were obtained in subgroups stratified by age, gender, race, and taking lipid-lowering drugs. The lowest all-cause mortality risk was observed at HDL-C 66 mg/dL (concentration) and 51-60 mg/dL (range). Conclusion: Both lower and higher HDL-C concentration appeared to be associated with higher mortality in hypertensive population. Further investigation is warranted to clarify the underlying mechanisms.

Multidrug resistance-associated protein 2 (MRP2) plays an important role in bile acid metabolism by transporting toxic organic anion conjugates, including conjugated bilirubin, glutathione, sulfate, and multifarious drugs. MRP2 expression is reduced in cholestatic patients and rodents. However, the molecular mechanism of MRP2 down-regulation remains elusive. In this report, we treated human hepatoma HepG2 cells with interleukin-18 (IL-18) and measured the expression of MRP2, nuclear factor kappa B (NF-κB), farnesoid X receptor (FXR), and the transcription factor Yin Yang 1 (YY1) by quantitative real-time quantitative polymerase chain reaction (PCR) and western blotting. We found that expression of MRP2 was repressed by IL-18 at both the mRNA and protein levels in a dose- and time-dependent manner. Furthermore, the activated NF-κB pathway increased YY1 and reduced FXR. These changes were all attenuated in HepG2 cells with knockdown of the NF-κB subunit, p65. The reduced expression of FXR and MRP2 in HepG2 cells that had been caused by IL-18 treatment was also attenuated by YY1 knockdown. We further observed significantly elevated IL-18, NF-κB, and YY1 expression and decreased FXR and MRP2 expression in bile duct-ligated Sprague Dawley rat livers. Chromatin immunoprecipitation assays also showed that FXR bound to the promoter region in MRP2 was less abundant in liver extracts from bile duct-ligated rats than sham-operated rats. Our findings indicate that IL-18 down-regulates MRP2 expression through the nuclear receptor FXR in HepG2 cells, and may be mediated by NF-κB and YY1.

Background: Traditional anthropometric measures, including body mass index (BMI), are insufficient for evaluating the risk of diabetes. This study aimed to evaluate the performance of new anthropometric measures and a combination of anthropometric measures for identifying diabetes. Methods: A total of 46 979 participants in the National Health and Nutrition Examination Survey program were included in this study. Anthropometric measures, including weight, BMI, waist circumference (WC), waist-to-height ratio (WtHR), conicity index (CI), and A Body Shape Index (ABSI), were calculated. Logistic regression analysis and restricted cubic splines were used to evaluate the association between the anthropometric indices and diabetes. The receiver operating characteristic (ROC) curve analysis was performed to compare the discrimination of different anthropometric measures.Results: All anthropometric measures were positively and independently associated with the risk of diabetes. After adjusting for covariates, the per SD increment in WC, WtHR, and CI increased the risk of diabetes by 81%, 83%, and 81%, respectively. In the ROC analysis, CI showed superior discriminative ability for diabetes (area under the curve 0.714), and its optimum cutoff value was 1.31. Results of the combined use of BMI and other anthropometric measures showed that among participants with BMI <30 kg/m 2 , an elevated level of another metric increased the risk of having diabetes (P < .001). Similarly, at low levels of weight, CI, and ABSI, an elevated BMI increased diabetes risk (P < .001).Conclusions: WtHR and CI had the best ability to identify diabetes when applied to the US noninstitutionalized population. Anthropometric measures containing WC information could improve the discrimination ability.a Xiao-cong Liu and Ying-shan Liu should be considered joint first author.b Jian Kuang and Ying-qing Feng should be considered joint senior author.

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The relationship between fasting blood glucose and first ischemic stroke in older adults was unclear, so we explored this association among older patients with hypertension in China. Methods: We recruited hypertensive participants with 60 or more of age. Fasting blood glucose concentrations were categorized into quartiles. Hazard ratio (HR) and 95% confidence interval (CI) for ischemic stroke were estimated using multivariate Cox regression analysis and subgroup analysis. Results: A total of 3310 (1474 (44.53%) male) patients with mean age of 71.41±7.20 years were included. During the mean follow-up period of 5.5 years, 206 cases of ischemic stroke occurred. After adjusting for potential confounding variables, multivariate adjusted HRs for each standard deviation increment of fasting blood glucose, the risk of ischemic stroke increased by 11% (95% CI: 1.03, 1.21; P= 0.008). In addition, when using the lowest group (Q1) as reference, the multivariate adjusted HRs for first ischemic stroke were 1.76 (95% CI: 1.08, 2.86; P=0.023), 1.73 (95% CI: 1.06, 2.81; P=0.027) and 2.42 (95% CI: 1.49, 3.93; P<0.001) (P for trend<0.001). Subgroup analysis revealed that the association between fasting blood glucose and the risk of ischemic stroke was higher in male (

Background. The association of total choline (TC) intake and its metabolite trimethylamine-N-oxide (TMAO) with hypertension and blood pressure (BP) has not been elucidated. Methods. For the population study, the association of TC intake with hypertension, as well as blood pressure, was determined through logistic along with multiple linear regression analysis from the National Health and Nutrition Examination Survey 2007 to 2018, respectively. For the animal experimental study, spontaneously hypertensive rats (SHRs) were assigned to the water group or water containing 333 mg/L or 1 g/L TMAO group. After 22 weeks treatment of TMAO, blood pressure measurement, echocardiography, and histopathology of the heart and arteries were evaluated. Results. No significant association of TC with hypertension was observed but the trend for ORs of hypertension was decreased with the increased level of TC. Negative association between TC and BP was significant in quintile 4 and quintile 5 range of TC, and the negative trend was significant. The SHR-TMAO groups showed significant higher urine output levels in contrast with the SHR-water group. No difference of diastolic BP was observed, but there was a trend towards lower systolic BP with the increase doses of TMAO in the SHR group. The SHR 1 g/L TMAO rats had a remarkably lower systolic blood pressure than the SHR-water group. Echocardiography showed a diastolic dysfunction alleviating effect in the 1 g/L TMAO group. Conclusion. High TC intake was not linked to elevated risk of hypertension. An inverse relationship of choline intake with systolic BP was observed. The mechanism for the beneficial effect of TC might be associated with the diuretic effect of its metabolite TMAO.