Development and validation of a diagnostic nomogram in pulmonary hypertension due to left heart disease.

BACKGROUND: Pulmonary hypertension (pH) due to left heart disease (pH-LHD) is the most common form of pH in clinical practice. OBJECTIVES: The purpose of the study is to develop a diagnostic nomogram predictive model combining conventional noninvasive examination and detection indicators. METHODS: Our study retrospectively included 361 patients with left heart disease (LHD) who underwent right heart catheterization between 2013 and 2020. All patients were randomly divided into a training cohort (253, 70 %) and a validation cohort (108, 30 %). pH was defined as resting mean pulmonary arterial pressure (mPAP) ≥25 mmHg measured by RHC examination. Data dimension reduction and feature selection were used by Lasso regression model. The nomogram was constructed based on multivariable logistic regression. RESULTS: A total of 175 patients with LHD were diagnosed with pH during their hospitalization, representing 48.5 % of the cohort. The mean age of the overall group was 55.6 years, with 76.7 % being male patients. Excessive resting heart rate, elevated New York Heart Association functional class, increased red blood cell distribution width, right ventricular end-diastolic diameter, and pulmonary artery systolic pressure measured by echocardiography were independently associated with the prevalence of pH-LHD. The inclusion of these 5 variables in the nomogram showed good discrimination (AUC = 0.866 [95 % CI, 0.820-0.911]) and optimal calibration (Hosmer-Lemeshow test, P = 0.791) for the validation cohort. CONCLUSIONS: The noninvasive nomogram of pH-LHD developed in this study has excellent diagnostic value and clinical applicability, and can more accurately evaluate the presence risk of pH in patients with LHD.

Comparison of arterial stiffness indices measured by pulse wave velocity and pulse wave analysis for predicting cardiovascular and all-cause mortality in a Chinese population.

Arterial stiffness measured by pulse wave velocity and pulse wave analysis has been widely studied in different populations in terms of its correlation with cardiovascular events and all-cause mortality. It remains unknown which arterial stiffness index is better for risk stratification in the general population. We included 4129 participants from Gaoyou County, Jiangsu Province, China, with a median follow-up of 11 years. The primary endpoint was cardiovascular mortality, and the secondary endpoint was all-cause mortality. Harrell's C-index, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) based on the Cox proportional hazards regression model were evaluated to assess predictive discrimination and accuracy. The associations between the 4 indices and cardiovascular mortality remained significant after adjusting for the Framingham Risk Score (FRS) and/or associated risk factors. Considering reclassification based on the newly integrated models (FRS model combined with the 4 indices), NRI for cardiovascular mortality showed that haPWV and baPWV had more significant improvement in reclassification compared with C1 and C2 [NRI with 95% CI: haPWV 0.410 (0.293, 0.523); baPWV 0.447 (0.330, 0.553); C1 0.312 (0.182, 0.454); C2 0.328 (0.159, 0.463); all P < 0.05]. This study showed that pulse wave velocity (haPWV and baPWV) provides better discrimination of long-term risk than arterial elasticity indices (C1 and C2) in the general population.

Correlation of ventricle epicardial fat volume and triglyceride-glucose index in patients with chronic heart failure.

To explore the association of ventricle epicardial fat volume (EFV) calculated by cardiac magnetic resonance (CMR) and the insulin resistance indicator of triglyceride-glucose (TyG) index in patients with chronic HF (CHF), this retrospective cohort study included adult CHF patients with confirmed diagnosis of heart failure from January 2018 to December 2020. All patients underwent 3.0T CMR, and EFV were measured under short-axis cine. Spearman correlation, multivariate linear regression, and restricted cubic spline (RCS) regression were used to analyze their association. There were 516 patients with CHF, of whom 69.8% were male. Median EFV was 57.14mL and mean TyG index was 8.48. Spearman correlation analysis showed that TyG index was significantly correlated with the EFV in CHF patients (r = 0.247, P < 0.001). Further analysis showed that TyG index levels were significantly associated with EFV as both continuous variables (Unstandardized ß = 6.556, P < 0.001) and across the increasing quartiles (ß = 7.50, 95% CI [1.41, 13.59], P < 0.05). RCS demonstrated there were a positive trend and linear association between EFV and TyG index in CHF patients (P for nonliearity = 0.941). In patients with CHF, the TyG index was positively and linearly associated with the EFV, which supports the metabolic roles of epicardial adipose tissue regarding insulin resistance.

Low lean mass with obesity in older adults with hypertension: prevalence and association with mortality rate.

BACKGROUND: The influence of sarcopenic obesity (SO) on overall survival in older adults with hypertension has not been addressed. The aim of this study was to investigate the prevalence and mortality predictive value of various body composition phenotypes, focusing mainly on SO, in older adults with hypertension. METHODS: We included 1105 hypertensive patients aged ≥ 60 years from the National Health and Nutrition Examination Survey 1999-2004. Sarcopenia was broadly defined based on low lean mass (LLM; as measured by dual-energy X-ray absorptiometry), and was defined using appendicular lean mass (ALM) divided by height squared (ALM/height2), weight (ALM/weight), and body mass index (BMI; ALM/BMI), respectively. Obesity was defined as BMI ≥ 30 kg/m2, body fat percentage ≥ 30/42%, or waist circumference ≥ 102/88 cm. The prevalence of LLM with obesity was estimated according to each ALM index (ALMI). Multivariable Cox regression analysis and sensitivity analysis were used to examine the association between various body composition phenotypes and all-cause mortality. RESULTS: In older adults with hypertension, the prevalence of LLM with obesity by the ALM/height2 index (9.8%) was lower relative to the ALM/weight (11.7%) and ALM/BMI indexes (19.6%). After a median follow-up of 15.4 years, 642 deaths occurred. In the fully adjusted models, LLM with obesity was significantly associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.14-2.49, P = 0.008; HR 1.48, 95% CI 1.04-2.10, P = 0.028; HR 1.30, 95% CI 1.02-1.66, P = 0.037; respectively) compared with the normal body phenotype, with no statistical differences found in individuals with LLM or obesity alone. Sensitivity analysis confirmed the robustness of the results. CONCLUSIONS: The prevalence of LLM with obesity markedly differed in older adults with hypertension according to the 3 different ALMIs, varying from 9.8%, 11.7%, to 19.6%. Patients with both LLM and obesity had a higher risk of all-cause mortality. Further large, prospective, cohort studies are warranted to validate these findings and uncover underlying mechanisms.

Negative association between triglyceride glucose index and BMI-adjusted skeletal muscle mass index in hypertensive adults.

BACKGROUND: The triglyceride glucose (TyG) index, an indicator of insulin resistance, is often associated with adverse outcomes in various cardiovascular diseases, while hypertension is associated with an increased risk of cardiovascular diseases. As the loss of muscle mass in people with hypertension is poorly understood, the current study aimed to explore the relationship between TyG index and muscle mass in hypertensive population. METHODS: We analyzed data from hypertensive adult participants in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. The TyG index and body mass index (BMI)-adjusted skeletal muscle mass index (SMI) were calculated and the relationship between the two was evaluated using multivariable linear regression and restricted cubic spline (RCS) regression models. RESULTS: A total of 1633 participants in the dataset were included for the final analysis. In the multivariable regression analysis, the adjusted ß of SMI with a 95% confidence interval (CI) for the highest TyG index quartile was - 5.27 (- 9.79 to - 0.75), compared with the lowest quartile. A negative linear relationship between TyG index and SMI was plotted by RCS regression (nonlinear P = 0.128). Stratified models of non-smoking women of different ages also demonstrated that SMI decreased as TyG index increased (all P for trend < 0.05). CONCLUSION: This linear and negative correlation between TyG index and SMI in hypertensive patients suggests that insulin resistance adversely affects muscle mass.

Prognostic value of ventricle epicardial fat volume by cardiovascular magnetic resonance in chronic heart failure.

The purpose of this study is to explore the prognostic values of ventricle epicardial fat volume (EFV) calculated by cardiac magnetic resonance in patients with chronic heart failure (CHF). A total of 516 patients with CHF (left ventricular ejection fraction ≤ 50%) were recruited, and 136 (26.4%) of whom experienced major adverse cardiovascular events (MACE) within median follow-up of 24 months. The target marker-EFV was found to be associated with MACE in both univariate and multivariable analysis adjusted for various clinical variables (p < 0.01), regardless as a continuous variable and categorized by X-tile program. EFV also showed promising predictive ability, with an area under the curve of 0.612, 0.618, and 0.687 for the prediction of 1-year, 2-year, and 3-year MACE, respectively. In conclusion, EFV could be a useful prognostic marker for CHF patients, helping to identify individuals at greater risk of MACE.

The role of the angiography-derived index of microcirculatory resistance in the prognosis of patients with dilated cardiomyopathy.

Background: The coronary angiography-derived index of microcirculatory resistance (caIMR) is a novel noninvasive method to assess coronary microvascular dysfunction (CMD). However, the association between caIMR and the prognosis of patients with dilated cardiomyopathy (DCM) is unclear. We aimed to explore the role of the caIMR in evaluating the outcome of patients with DCM. Methods: We consecutively and retrospectively enrolled patients with DCM in the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China, from January 2013 to January 2018. The caIMR was calculated for eligible patients. The primary end point in this study was composite events, including rehospitalization related to heart failure (HF), device implantation, heart transplantation, or cardiac death. Patients were categorized into groups based on whether they had composite events (the events and no-events groups), and differences in the baseline and end points between these two groups were analyzed. Results: A total of 95 eligible patients with DCM were enrolled in the study, 36 of whom had end point events. The best cutoff values of the caIMR for the left anterior descending (LAD) artery, left circumflex (LCX) artery, and right coronary artery (RCA) were >29.8 with an area under the curve (AUC) of 0.828, >25.5 with an AUC of 0.720, and >29.7 with an AUC of 0.717, respectively (all P values <0.001). Patients were then classified into the higher caIMR group and the lower caIMR group based on the cutoff value. Kaplan-Meier analyses showed that patients with a higher caIMR had increased cumulative risks of end point events regardless of the cutoff values for the LAD, LCX, and RCA (all log-rank P values <0.001). After adjustment for confounders, Cox regression analyses indicated that LAD-caIMR was an independent risk factor for end point events in patients with DCM [hazard ratio (HR) =1.11; 95% CI: 1.06-1.16]. Conclusions: A higher caIMR was significantly associated with the poor prognosis of patients with DCM.

Construction of a web-based dynamic nomogram for predicting the prognosis in acute heart failure.

AIMS: The early identification and appropriate management may provide clinically meaningful and substained benefits in patients with acute heart failure (AHF). This study aimed to develop an integrative nomogram with myocardial perfusion imaging (MPI) for predicting the risk of all-cause mortality in AHF patients. METHODS AND RESULTS: Prospective study of 147 patients with AHF who received gated MPI (59.0 [47.5, 68.0] years; 78.2% males) were enrolled and followed for the primary endpoint of all-cause mortality. We analysed the demographic information, laboratory tests, electrocardiogram, and transthoracic echocardiogram by the least absolute shrinkage and selection operator (LASSO) regression for selection of key features. A multivariate stepwise Cox analysis was performed to identify independent risk factors and construct a nomogram. The predictive values of the constructed model were compared by Kaplan-Meier curve, area under the curves (AUCs), calibration plots, continuous net reclassification improvement, integrated discrimination improvement, and decision curve analysis. The 1, 3, and 5 year cumulative rates of death were 10%, 22%, and 29%, respectively. Diastolic blood pressure [hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.93-0.99; P = 0.017], valvular heart disease (HR 3.05, 95% CI 1.36-6.83; P = 0.007), cardiac resynchronization therapy (HR 0.37, 95% CI 0.17-0.82; P = 0.014), N-terminal pro-B-type natriuretic peptide (per 100 pg/mL; HR 1.02, 95% CI 1.01-1.03; P < 0.001), and rest scar burden (HR 1.03, 95% CI 1.01-1.06; P = 0.008) were independent risk factors for patients with AHF. The cross-validated AUCs (95% CI) of nomogram constructed by diastolic blood pressure, valvular heart disease, cardiac resynchronization therapy, N-terminal pro-B-type natriuretic peptide, and rest scar burden were 0.88 (0.73-1.00), 0.83 (0.70-0.97), and 0.79 (0.62-0.95) at 1, 3, and 5 years, respectively. Continuous net reclassification improvement and integrated discrimination improvement were also observed, and the decision curve analysis identified the greater net benefit of the nomogram across a wide range of threshold probabilities (0-100% at 1 and 3 years; 0-61% and 62-100% at 5 years) compared with dismissing the included factors or using either factor alone. CONCLUSIONS: A predictive nomogram for the risk of all-cause mortality in patients with AHF was developed and validated in this study. The nomogram incorporated the rest scar burden by MPI is highly predictive, and may help to better stratify clinical risk and guide treatment decisions in patients with AHF.

Associations of Serum Carotenoids With Risk of All-Cause and Cardiovascular Mortality in Hypertensive Adults.

Background Systemic oxidative stress is involved in the development of hypertension, whereas carotenoids are a group of natural antioxidants. Our study aims to evaluate the relationships between the serum concentrations of major carotenoids and mortality in hypertensive adults. Methods and Results Data on 5 serum carotenoids from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 2001-2006 were included. Outcome measures (all-cause and cardiovascular mortality) were identified from the National Death Index through December 31, 2019. Multiple Cox proportional hazards regression and restricted cubic spline analyses were performed to determine the association between carotenoid levels and outcomes. A total of 8390 hypertensive adults were included in the analysis. At a median follow-up duration of 16.6 years, all-cause and cardiovascular mortality occurred in 4005 (47.74%) and 1205 (14.36%) participants, respectively. Compared with the lowest quartiles, the highest quartiles of 5 major serum carotenoids were associated with lower risk of all-cause mortality, with multivariable-adjusted hazard ratios (HRs) of 0.63 (95% CI, 0.56-0.71) for α-carotene, 0.70 (95% CI, 0.61-0.80); for ß-carotene, 0.67 (95% CI, 0.58-0.76); for ß-cryptoxanthin, 0.74 (95% CI, 0.64-0.86) for lycopene; and 0.72 (95% CI, 0.63-0.83) for lutein/zeaxanthin. For cause-specific mortality, this association with the fourth quartile of serum carotenoids was evident for a reduced rate of cardiovascular mortality, with a 32% reduction for α-carotene (HR, 0.68 [95% CI, 0.55-0.86]), a 29% reduction for ß-cryptoxanthin (HR, 0.71 [95% CI, 0.56-0.89]), and a 26% reduction for lycopene (HR, 0.74 [95% CI, 0.59-0.94]), but not for ß-carotene and lutein/zeaxanthin. In addition, we found that serum α-carotene, ß-carotene, ß-cryptoxanthin, and lutein/zeaxanthin levels were nonlinearly related to all-cause mortality with inflection points of 2.43, 8.49, 5.12, and 14.17 µg/dL, respectively. Serum α-carotene, ß-cryptoxanthin, and lutein/zeaxanthin concentrations showed nonlinear associations with cardiovascular mortality with inflection points of 2.31, 5.26, and 15.40 µg/dL, respectively. Conclusions Findings suggest that higher serum carotenoid concentrations were associated with lower risks of all-cause and cardiovascular mortality in hypertensive adults.

Nonlinear associations of serum cobalamin with risk of all-cause and cardiovascular mortality in hypertensive adults.

Our study aims to evaluate the associations between the serum cobalamin (vitamin B12) and related biomarkers with mortality in hypertensive adults. Data on serum cobalamin from the National Health and Nutrition Examination Survey (NHANES) 1999-2006 and 2011-2014 were included. Mortality status was linked to National Death Index mortality data through 31 December, 2019. Cox regression and restricted cubic spline (RCS) analyses were used to determine the hazard ratios (HRs) and 95% CIs for mortality risk. A total of 9934 hypertensive adults were included in the analysis (mean age, 58.1 ± 17.5 years; 4899 [49.3%] men). At 11.0 years of mean follow-up, 935 cardiovascular deaths and 3096 all-cause deaths were identified. Compared to the third quartiles, the first and fourth quartiles of serum cobalamin were associated with risk of cardiovascular mortality, with multivariable-adjusted HRs of 1.26 (1.05-1.53) and 1.40 (1.17-1.68). Similar results were observed in the relationship between serum cobalamin and all-cause mortality. These results were supported by the RCS analysis. The inflection points for the nonlinear associations of serum cobalamin with cardiovascular and all-cause mortality were 649.9 pg/mL and 577.2 pg/mL, respectively. In addition, compared with the second quartile of circulating methylmalonic acid (MMA, a cobalamin-deficiency marker), this association with the fourth quartile was evident for an increased rate of cardiovascular and all-cause mortality, with 111% (HR = 2.11, 1.71-2.61) and 73% (HR = 1.73, 1.55-1.93) increase. Findings suggest that both lower and higher serum cobalamin concentrations were associated with a higher risk of cardiovascular and all-cause mortality in hypertensive adults. This study was a prospective cohort study that included serum cobalamin data from 9934 hypertensive adults from the NHANES from 1999-2006 and 20011-2014. Findings suggested that both lower and higher serum cobalamin concentrations were associated with a higher risk of cardiovascular and all-cause mortality in hypertensive adults.

Urinary phenols and parabens metabolites associated with cardiovascular disease among adults in the United States.

The field of environmental health has begun to examine the effects of higher-order chemical combinations. The current literature lacks studies exploring associations between multiple organic chemical mixtures and cardiometabolic diseases (CVDs). This study aimed to evaluate associations between urinary phenols, parabens metabolites, and total and individual CVDs among a nationally representative sample of adults in the US. This cross-sectional study analyzed 7 urinary chemicals detected among the general population from the 2005-2016 National Health and Nutrition Examination Survey (NHANES, n=10,428). Multivariate logistic regression and weighted quantile sum (WQS) regression were applied to examine relationships between phenols and parabens metabolites, alone and in combination, and total and individual CVDs prevalence. Compared with the lowest quartile, URBPA (OR: 1.52; 95% CI: 1.20-1.91; P=0.001) levels in the highest quartile were independently associated with increased total CVD. The WQS index of phenols and parabens mixtures were independently correlated with total CVD (adjusted odds ratios [OR]: 1.16; 95% confidence interval [CI]:1.06-1.28; P=0.002), angina (adjusted OR: 1.30; 95% CI: 1.07-1.59; P=0.009), and heart attack (adjusted OR: 1.30; 95% CI: 1.12-1.51, P<0.001). Urinary bisphenol A (URBPA, weight=0.636) was the most heavily weighted component in the total CVD model. Restricted cubic spline regression demonstrated positive correlations and nonlinear associations between URBPA and both total CVD (P for nonlinearity=0.032) and individual CVD (heart attack; P for nonlinearity=0.031). Our findings suggested that high combined levels of phenols, and parabens are associated with an increased CVD risk, with URBPA contributing the highest risk.

Associations of Inflammation with Risk of Cardiovascular and All-Cause Mortality in Adults with Hypertension: An Inflammatory Prognostic Scoring System.

Background: Inflammation is one of the major pathways in the progression of hypertension (HTN), and the related inflammatory markers have demonstrated certain predictive values. The current study aimed to integrate these markers to construct an inflammatory prognostic scoring (IPS) system and to assess the prognostic values of IPS in patients with HTN. Methods: A total of 9846 adult participants with HTN from NHANES 1999-2010 were enrolled and followed up. Demographic characteristics and the related laboratory results for the 12 inflammatory markers were collected. LASSO-COX regression, Kaplan-Meier, restricted cubic spline COX regression (RCS), receiver operator characteristic curve (ROC), and random survival forests (RSF) analysis were applied to explore the values of individual and IPS parameters. Results: At the census date of follow-up, 2387 (24.2%) were identified as all-cause deaths and 484 (4.9%) as cardiovascular deaths. All inflammatory markers showed certain prognostic values. Then, based on the LAASO analysis, LDH, ALP, LYM, NLR, MLR, SIRI, and RDW were included in the construction of the IPS system. The higher IPS had significantly worse long-term prognosis in Kaplan-Meier analysis (p log-rank <0.001). Also, IPS remained an independent prognosticator compared to the lowest quartile (All p for trend <0.001), and the ROC showed satisfactory values in the long-term prognosis of both cardiovascular and all-cause mortality. RCS further showed a linear association of IPS with cardiovascular mortality and all-cause mortality (p for non-linearity >0.05). Two different algorithms of RSF, variable importance and minimal depth, to evaluate the prognostic importance showed that IPS was the best in survival prediction. Conclusion: Our results highlight that a higher IPS (system integrating the inflammatory markers) was associated with the increased risk of cardiovascular and all-cause mortality in patients with HTN, suggesting that IPS is a useful method for risk stratification in HTN.

Inverse association of serum carotenoid levels with prevalence of hypertension in the general adult population.

Carotenoid levels are inversely associated with blood pressure (BP). This study focused on the effects of individual and combined serum carotenoids on BP and hypertension, which have not been established to date. Data from National Health and Nutrition Examination Survey (NHANES) 2001-2006 were analyzed in this cross-sectional study. Multivariate logistic, linear, and weighted quantile sum (WQS) regression analyses were applied to explore the associations of six serum carotenoids (α-carotene, ß-cryptoxanthin, lutein/zeaxanthin, trans-lycopene, trans-ß-carotene, and cis-ß-carotene), individually and in combination, with BP/hypertension. The linearity of correlations was further assessed using restricted cubic spline (RCS) regression. A total of 11,336 adults were included for analysis. Data from multivariate models showed that all six carotenoids were independently and negatively associated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP; all p < 0.05). Compared to the first quartile, the fourth quartile of α-carotene (odds ratio [OR] = 0.64 [0.52-0.77]), ß-cryptoxanthin (OR = 0.74 [0.60-0.90]), trans-ß-carotene (OR = 0.50 [0.40-0.61]), and cis-ß-carotene (OR = 0.47 [0.35-0.64]) were significantly and inversely related to hypertension (all p < 0.05). Moreover, WQS analysis revealed that the combination of all six serum carotenoids was negatively associated with BP and hypertension (all P<0.001), among which trans-ß-carotene was the most significant contributor to the protective effect against hypertension (weight, 59.50%). Dose-response analyses demonstrated a linear inverse association of all carotenoids with hypertension (p for non-linearity > 0.05). Our collective findings indicate that higher levels of all six mixed serum carotenoids are correlated with decreased prevalence of hypertension, among which ß-carotene exerts the most significant effect, which may provide a basis and direction for further studies.

Long-term prognostic value of inflammatory biomarkers for patients with acute heart failure: Construction of an inflammatory prognostic scoring system.

Objective: Systemic inflammation is associated with a poor prognosis in acute heart failure (AHF). This study was to assess the long-term prognostic value of combining the accessible inflammatory markers in relation to all-cause mortality in patients with AHF. Methods: Consecutive patients with AHF who were hospitalized between March 2012 and April 2016 at the Department of Cardiology of the First Affiliated Hospital of Nanjing Medical University were enrolled in this prospective study. The LASSO regression model was used to select the most valuable inflammatory biomarkers to develop an inflammatory prognostic scoring (IPS) system. Kaplan-Meier method, multivariate COX regression and time-dependent ROC analysis were used to assess the relationship between inflammatory markers and AHF prognosis. A randomized survival forest model was used to estimate the relative importance of each inflammatory marker in the prognostic risks of AHF. Results: A total of 538 patients with AHF were included in the analysis (mean age, 61.1 ± 16.0 years; 357 [66.4%] men). During a median follow-up of 34 months, there were 227 all-cause deaths (42.2%). C-reactive protein (CRP), red blood cell distribution width (RDW) and neutrophil-to-lymphocyte ratio (NLR) were incorporated into the IPS system (IPS = 0.301×CRP + 0.263×RDW + 0.091×NLR). A higher IPS meant a significantly worse long-term prognosis in Kaplan-Meier analysis, with 0.301 points as the optimal cut-off value (P log-rank <0.001). IPS remained an independent prognostic factor associated with an increased risk of all-cause mortality among patients with AHF in multivariate Cox regression models with a full adjustment of the other significant covariables. Random forest variable importance and minimal depth analysis further validated that the IPS system was the most predictive for all-cause mortality in patients with AHF. Conclusions: Inflammatory biomarkers were associated with the risk of all-cause mortality in patients with AHF, while IPS significantly improved the predictive power of the model and could be used as a practical tool for individualized risk stratification of patients with AHF.

Inverse association between blood ethylene oxide levels and obesity in the general population: NHANES 2013-2016.

Background: Ethylene oxide (EO) has been shown to associate with increased cardiovascular risk. This study aimed to explore the relationship and its meditating factors between EO exposure and the major cardiovascular risk factor of obesity among the general adult population. Methods: Cross-sectional data of 3,220 participants from National Health and Nutritional Examination Survey (NHANES) 2013-2016 were enrolled. Obesity was defined as body mass index (BMI) ≥30 kg/m2, and abdominal obesity was defined as waist circumference (WC) ≥102 cm in men and ≥88 cm in women. The association among hemoglobin adduct of EO (HbEO), inflammatory biomarkers, and obesity was evaluated using restricted cubic splines and the multivariable linear regression model. Mediation analysis was used to further assess their association. Results: The increased quartiles of HbEO were inversely associated with BMI and WC [Q1 vs. Q4, BMI: ß = -2.98 (-3.74, -2.22), WC: ß = -6.50 (-8.60, -4.39); all p for trend < 0.05], and were inversely associated with obesity after full adjustment [obesity: OR = 0.43 (0.31, 0.58), abdominal obesity: OR = 0.42 (0.27, 0.65); all p for trend < 0.05]. The levels of alkaline phosphatase, white blood cells, lymphocytes, and neutrophils were also positively associated with BMI and WC (all p < 0.05). Mediation analysis showed that exposure of EO not only had a negative direct effect on BMI and WC, but also generated an inverse indirect effect. Conclusions: Current findings showed an inverse association between HbEO and obesity, and suggested that systemic inflammation may not be their only mediator. Additional research is required to explore the underlying link of EO and system metabolism.

Effect of blood pressure on the mortality of the elderly population with (pre)frailty: Results from NHANES 1999-2004.

Backgrounds: The optimal blood pressure of elderly people with frailty or prefrailty is still unclear. We aimed to explore the relationship between blood pressure and mortality in the elderly with (pre)frailty. Methods: A total of 528 participants aged 60 years and older were exacted for analyses of the association between blood pressure and mortality from the database of the National Health and Nutrition Examination Survey (NHANES) (1999-2004). Kaplan-Meier curves and log-rank tests were used to investigate the differences in survival between groups. Multivariable Cox regression and restricted cubic spline (RCS) analyses were applied to explore the relationship between blood pressure and mortality. Results: During the median follow-up time of 116.5 [interquartile range (IQR) of 60-186] months, 363 all-cause deaths and 122 cardiac deaths were documented. For all-cause mortality, more participants died with systolic blood pressure (SBP) < 110 mmHg and SBP ≥ 170 mmHg (log-rank p = 0.004). After adjusting for confounders, SBP < 110 mmHg [hazard ratio (HR) 1.52, 95% CI: 0.96-2.41] and SBP ≥ 170 mmHg (HR 1.53, 95% CI: 1.09-2.15) had higher risks of all-cause mortality compared with SBP within 130-150 mmHg. There were no significant differences in all-cause mortality among DBP categories. A J-curve association was identified between the SBP and hazard ratio for all-cause mortality (p for non-linear = 0.028), with 138.6 mmHg as the lowest hazard ratio of all-cause mortality; each 10 mmHg of SBP rise was associated with a 9% increased risk in all-cause mortality (HR 1.09, 95% CI 1.00-1.18). Additionally, a non-linear relationship was determined between SBP and the hazard ratio for cardiac deaths (p for non-linear = 0.030), with 140.1 mmHg as the lowest hazard ratio of cardiac deaths. When SBP was higher than 140.1 mmHg, each 10 mmHg rise in SBP was associated with a 17% increased risk of cardiac deaths (HR 1.17, 95% CI: 1.02-1.34). Conclusion: Both lower and higher SBP levels are associated with higher risks of all-cause mortality in older individuals with (pre)frailty. There are J-shaped associations between SBP and mortality, with the optimal SBP being approximately 140 mmHg for this population specifically.

Association of remnant cholesterol and non-high density lipoprotein cholesterol with risk of cardiovascular mortality among US general population.

Background: There are strong association between remnant cholesterol (RC)/non-high density lipoprotein cholesterol (NHDL-C) and increase cardiovascular (CV) risk. The aim of present study was to investigate the association between target lipid parameters (RC and NHDL-C) and the risk of CV mortality in general population. Methods: Data set from an open database-National Health and Nutrition Examination Surveys (NHANES) 2003-2014 were extracted (n = 14992). Kaplan-Meier, multivariable COX regression, and restricted cubic spline (RCS) parameters. Results: Compared to the lowest quartile, RC (adjusted hazard ratio [HR] = 1.63 95%CI 1.05-2.52, P for trend = 0.037) and triglycerides (TG: Model 3: HR = 1.69 95%CI 1.10-2.60, P for trend = 0.049) in the highest quartile were independently associated with the increased cardiovascular mortality, while NHDL-C and apolipoprotein B (ApoB) in adjusted models did not show association (P for trend >0.05). In addition, RCS regression demonstrated that RC (P for nonlinearity = 0.011) and TG (P for nonlinearity = 0.010) levels had a similar J-shape association with CV mortality. Threshold effect analysis showed that when RC ≤ 29.3 mg/dL, the level of RC and CV mortality risk were positively correlated. Conclusions: Our findings suggest high RC levels are associated with an increased risk of CV mortality, which support that the integration of TG-rich lipoproteins parameters in risk assessment might optimize the identification and management of selected population.

Identification of Immune-Related Genes in Patients with Acute Myocardial Infarction Using Machine Learning Methods.

Objective: This study aimed to analyze immune-related genes and immune cell components in the peripheral blood of patients with acute myocardial infarction (AMI). Methods: Six datasets were obtained from the GEO repository comprising 88 healthy samples and 215 AMI samples. We performed the weighted gene co-expression analysis (WGCNA) and five machine learning (ML) methods to identify immune-related genes and construct diagnostic models. CIBERSORT algorithm was adopted for the assessment of the degree of immune infiltration. Finally, RT-PCR, immunofluorescence double and immunohistochemistry were conducted to analyze the expression level of the identification of featured immune-related genes and localization relationship in heart tissue of AMI mouse model. Results: A total of 496 immune-related DEGs were obtained between AMI and normal samples. WGCNA finally determined the co-expression modules that showed the most significantly positively associated with AMI (r=0.41; P<0.001). Among the five ML models, XGBoost had the highest AUC (0.849) and accuracy (0.812) to discriminate patients with AMI from normal in the validation sets. Furthermore, we found that the proportion of chemokine receptor (CCR), macrophages, neutrophils, and Treg cells in the AMI groups was significantly higher than that in the normal groups. In vitro RT-PCR verification revealed that SOCS3, MMP9, and AQP9 expression increased significantly in the AMI mouse model. Among the 22 immune cells, AQP9, MMP9, and SOCS3 displayed the strongest positive correlation with neutrophils. In MI-mice, MPO stained strongly along the lateral cardiomyocytes, whereas it was weaker in sham mice. Combined immunofluorescence was observed in same parts of the cytoplasm of cardiomyocytes in myocardial infarction area, indicating co-localization of MPO with MMP9 and SOCS3 in these areas, respectively. Conclusion: Immune-related genes and immune cells are intimately related to AMI. Constructing different ML models based on these biomarkers could be a valuable approach to diagnosing AMI in clinical practice.

The role of doped-Mn on enhancing arsenic removal by MgAl-LDHs.

To meet the challenges posed by global arsenic water contamination, the MgAlMn-LDHs with extraordinary efficiency of arsenate removal was developed. In order to clarify the enhancement effect of the doped-Mn on the arsenate removal performance of the LDHs, the cluster models of the MgAlMn-LDHs and MgAl-LDHs were established and calculated by using density functional theory (DFT). The results shown that the doped-Mn can significantly change the electronic structure of the LDHs and improve its chemical activity. Compared with the MgAl-LDHs that without the doped-Mn, the HOMO-LUMO gap was smaller after doping. In addition, the -OH and Al on the laminates were also activated to improve the adsorption property of the LDHs. Besides, the doped-Mn existed as a novel active site. On the other hand, the MgAlMn-LDHs with the doped-Mn, the increased of the binding energy, as well as the decreased of the ion exchange energy of interlayer Cl-, making the ability to arsenate removal had been considerably elevated than the MgAl-LDHs. Furthermore, there is an obvious coordination covalent bond between arsenate and the laminates of the MgAlMn-LDHs that with the doped-Mn.

Renal Function Mediates the Association Between Klotho and Congestive Heart Failure Among Middle-Aged and Older Individuals.

Objective: Using a newly released National Health and Nutrition Examination Survey (NHANES) data of serum Klotho, this study aimed to explore the relationship between Klotho and specific cardiovascular diseases (CVD), as well as the mediation effect of renal function, among middle-aged and older individuals within the general population. Methods: This nationally representative cross-sectional study analyzed data from the 2007-2016 NHANES. A total of 13,765 participants, who aged 40 years or older, from the general population were examined. Klotho were divided into four groups based on median and interquartile range. The associations among Klotho (exposure), congestive heart failure (CHF; outcome), and renal function markers [estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), uric acid (UA), and urine albumin-to-creatinine ratio (UACR); mediators] were investigated using mediation analysis. Results: In comparison to the lowest quartile, Klotho in the highest quartile was independently associated with the prevalence of CHF (OR 0.59; 95% CI 0.46-0.77, p for trend = 0.001), but not with other individual CVDs. Klotho had a significant direct effect on the prevalence of CHF (all p < 0.001), while eGFR, BUN, UA, and UACR partly mediated the indirect effect of Klotho on the prevalence of CHF (all p < 0.05), explaining 19.51, 6.98, 13.93, and 0.71% of the association between Klotho and CHF, respectively. Additionally, restricted cubic spline regression demonstrated a linear association and negative correlation between Klotho level and CHF. Conclusion: These findings suggest that Klotho is closely linked to CHF and renal function may be a key mediator of this association.