Estimating human pharmacokinetic parameters forelectronic nicotine delivery system products from chemical analyses of their aerosols.

The ability of Electronic Nicotine Delivery Systems (ENDS) to deliver nicotine is central to their function to substitute for cigarettes, allowing people who smoke to switch away from smoking, thus reducing their exposure to harmful chemicals in cigarette smoke. The nicotine concentration in ENDS e-liquid has proved to be a poor predictor of nicotine uptake in users. Using meta-analytic methods to analyze 12 pharmacokinetic studies of nicotine-salt closed-system ENDS, this paper examines whether the mass of nicotine/puff of aerosol can predict Cmax in pharmacokinetic studies. Cmax values were available for 38 products, in 58 use conditions (including both controlled [3 s] and ad libitum puffing), comprising 1769 participant observations. Nicotine/puff data reflected chemical analyses of aerosol obtained under nonintense (3 s) or intense (6 s) machine puffing. Meta-regression analyses (weighted by reliability of Cmax estimate) assessed the relationship of nicotine/puff to Cmax. In some models, empirical data were used to impute the variation in Cmax or the nicotine/puff value under intense puffing. In simple linear models, Cmax was significantly associated with nicotine/puff under all combinations of intense/nonintense and controlled/ad-libitum conditions, with R2 values of 0.71-0.77. More complex models based on quadratic effects or log[nicotine/puff] did not generally improve upon more parsimonious linear models. Application of the model illustrates the divergence between nicotine concentration in e-liquids and expected Cmax when other ENDS parameters vary. The meta-analytic model may have utility in settings where clinical pharmacokinetic data are not available, including product development.

Identifying optimal candidates for primary tumor surgery in patients with metastatic head and neck cancer.

Background: Primary tumor surgery (PTS) may enhance survival among part of patients with metastatic head and neck cancer (mHNC). Herein, a predictive model was needed to construct to identify who can gain benefit remarkably from tumor resection. Methods: Data of patients with mHNC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The best cut-off value of age were analyzed using the X-tile software. One-to-one PSM, Kaplan-Meier method, and log-rank test were performed for survival analysis.The independent factors determined using the multivariate Cox proportional hazard regression were used to construct the nomogram. Results: A total of 1,614 patients diagnosed with mHNC were included; among them, 356 (22.0%) underwent a surgical procedure for the excision of the primary tumor. cancer-specific survival (CSS) was remarkably prolonged in the PTS group relative to the non-PTS group following PSM [Median:19 months vs. 9 months; hazard ratio (HR) 0.52, P < 0.001]. Patients with mHNC who were younger than 52 years old, had well-differentiated tumors, had T1 and N0 stages, and were married at the time of the study may have significantly benefited from PTS. In addition, we constructed a nomogram based on the factors that independently affect the CSS in multivariate Cox analysis. The nomogram showed excellent discrimination in both the training and validation sets (AUC: 0.732 and 0.738, respectively). Conclusion: A practical predictive model was constructed to determine the appropriate patients with mHNC, who would benefit from surgical resection.

Comparing Adult Smokers Who Switched to JUUL versus Continuing Smokers: Biomarkers of Exposure and of Potential Harm and Respiratory Symptoms.

OBJECTIVES: Real-world evidence on exposure to harmful and potentially harmful constituents (HPHCs) and on biological effects in cigarette smokers who switch to electronic nicotine delivery systems (ENDS) can inform the health effects of switching. AIMS AND METHODS: This cross-sectional, observational study assessed adults who had smoked ≥10 cigarettes/day for ≥10 years, comparing 124 continuing cigarette smokers (Smokers) to 140 former smokers who switched to JUUL-brand ENDS exclusively for ≥6 months (Switchers). Assessments included biomarkers of exposure (BOEs) to select HPHCs, biomarkers of potential harm (BOPHs) related to smoking-related diseases, psychometric assessments of dependence on cigarettes and ENDS, respectively, and respiratory symptoms. Planned analyses compared geometric means, adjusted for demographic covariates; further analyses adjusted for additional lifestyle and smoking history covariates. RESULTS: Nicotine levels were significantly higher in Switchers (median time switched = 3 years), who were unusually heavy users of JUUL. All other BOEs, including NNAL and HPMA3 (primary endpoints), were significantly lower in Switchers than Smokers. Most BOPHs (sICAM-1 [primary], and eg, white blood cell count, MCP1, HbA1c) were significantly lower in Switchers than Smokers; HDL was significantly higher. Switchers reported significantly lower dependence on JUUL than Smokers did on cigarettes, and respiratory symptom scores were significantly lower among Switchers than Smokers. CONCLUSIONS: Compared to continuing smokers, smokers who switched to JUUL had substantially lower exposures to multiple HPHCs, favorable differences in markers of inflammation, endothelial function, oxidative stress, and cardiovascular risk, and fewer respiratory symptoms. These findings suggest that switching from cigarettes to JUUL likely reduces smokers' health risks. IMPLICATIONS: Short-term confinement studies and randomized clinical trials demonstrate that adult smokers who switch completely to ENDS experience substantial reductions in exposure to many smoking-related toxicants. This study extends those findings to longer periods of switching to JUUL-brand ENDS (almost 3 years on average) under naturalistic use conditions in real-world settings and also found that switching to JUUL resulted in favorable differences in BOPHs more proximally related to smoking-induced disease, as well as in respiratory symptoms. Smokers who switch to ENDS reduce their exposure to toxicants, likely reducing their disease risk.

Family function and emotional behavior problems in Chinese children and adolescents: A moderated mediation model.

BACKGROUND: Studies have shown that family function is associated with emotional behavior problems. However, the underlying relationship mechanisms between family function and emotional behavior problems in children and adolescents is not fully understood. Therefore, the purpose of this study is to explore the mediating effect of resilience and the moderating effect of sleep quality using a moderated mediation model. METHODS: 6363 children and adolescents in grades four to nine were surveyed in some areas of Anhui Province, China. Family function, resilience, sleep quality, and emotional behavior problems were measured through a self-administered questionnaire. All data analysis was by performed by SPSS 23.0. RESULTS: The results showed that family function was negatively associated with emotional behavior problems (r = -0.307, p < 0.01). Resilience partially mediated the relationship between family function and emotional behavior problems (indirect effect = -0.108, accounted for 38.4 %). Sleep quality moderated the relationship between family function and resilience (ß = -0.039, P < 0.001). CONCLUSION: Resilience and sleep quality respectively played a mediating and moderating effect in the relationship between family function and emotional behavior problems. These findings suggest that we should pay attention to the family function of children and adolescents in time, improve their resilience and sleep quality, so as to effectively reduce the occurrence of emotional behavior problems.

Association between sleep change patterns and mental health among preschoolers: The mediating role of resilience.

Sleep disturbance has been recognized as an important factor influencing mental health problems in preschool children. However, no longitudinal studies have investigated the association between sleep change patterns and mental health in preschoolers or the mediating role of resilience. Here, data were collected from 1595 preschool children in 26 kindergartens in four counties in Anhui Province, China, who were followed up (T2) 1 year apart based on baseline surveys (T1). The primary caregivers of the children were asked to complete a structured questionnaire through face-to-face interviews or by completing it themselves. Pearson's correlation and linear regression were used to analyze the relationships among sleep patterns, mental health, and resilience in preschoolers. A structural equation model was used for the mediation analysis. Four patterns of sleep change were identified: persistent-low pattern (1.7%), decreasing pattern (9.8%), increasing pattern (7.3%), and persistent-high pattern (81.3%). Compared to the persistent-low pattern, the increasing pattern and persistent-high pattern were associated with emotional behavioral problems (EBPs) and anxiety. Resilience played a fully mediating role in the relationship between increasing pattern, persistent-high pattern, and EBPs. Resilience partially mediated the effects of increasing and persistent-high pattern on anxiety. More attention should be paid to sleep problems in children with increasing and persistent-high sleep patterns. Resilience is important for understanding the mechanism underlying the correlation between sleep patterns, EBPs, and anxiety. Considering the EBPs and anxiety of preschool children, early intervention for resilience should be considered.

Adverse childhood experiences of emotional and physical abuse and emotional and behavioral problems: the mediating effects of family function and resilience.

Adverse childhood experiences are a widespread phenomenon that can have a variety of negative effects on children. Emotional and behavioral problems (EBP) in children have been gaining interest in recent years. Therefore, this study aims to explore the association between emotional and physical abuse (EPA) and preschool children's EBP, as well as to assess the mediating effects of family function and resilience in this association. A cross-sectional study was conducted, and we recruited 3,636 participants from 26 kindergartens in three cities. Correlation analysis and regression analysis were used to test the relationships between EPA, mediators (family function and resilience), and EBP. Structural equation modeling was used to perform the mediation analyses. The results of this study showed that EPA predicted EBP in preschool children, family function, and resilience independently and in combination to mediate the relationship. Therefore, improving family function and increasing children's level of resilience are beneficial methods for the prevention and intervention of EBP in preschool children who experience EPA, but most fundamentally to avoid or reduce the occurrence of abuse. Further longitudinal studies are needed to confirm our findings and explore possible mediating mechanisms.

A distributed lag non-linear time-series study of ambient temperature and healthcare-associated infections in Hefei, China.

Little is known about the effects of temperature on healthcare-associated infections (HAIs). A distributed lag non-linear model was used to estimate the association between ambient temperature and HAIs in Hefei, China. In total, 9,592 HAIs were included. The effect of low temperature (-0.1°C, 2.5th percentile) was significant on the current day (RR = 1.108, 95%CI:1.003-1.222), and then appeared on the 4th day (RR = 1.045, 95%CI:1.007-1.084) and the 5th day (RR = 1.033, 95%CI:1.006-1.061). The cumulative lag effects of low temperature lasted from the 5th to 10th days (RR = 1.123-1.143), and a long-term cumulative lag effect was observed on the 14th day (RR = 1.157, 95%CI:1.001-1.338). The lag effect of high temperature (31.0°C, 97.5th percentile) was not statistically significant. However, the effects of temperatures on HAIs were not significant among gender or age subgroups. This study suggests that the low temperatures have acute and lag effects on HAIs in Hefei, China.

Short-term exposure to ambient ozone and cardiovascular mortality in China: a systematic review and meta-analysis.

Air pollution is a major public health concern in China. Notwithstanding this, there is limited evidence regarding the impact of short-term exposure to ambient ozone on cardiovascular mortality in the Chinese population. Therefore, we conducted this meta-analysis to address this important question. The random-effects model was applied to pool the results from individual studies. Finally, 32 effect estimates extracted from 19 studies were pooled in this meta-analysis. The pooled relative risk for cardiovascular mortality for each 10 µg/m3 increment in ozone concentration was 1.0068 (95% CI: 1.0049, 1.0086). Ths significant positive association between ozone exposure and cardiovascular mortality was also observed in different two-pollutant models. This meta-analysis revealed that exposure to ozone was associated with an increased risk of cardiovascular mortality in China, and more efforts on controlling the population from ozone are needed to improve cardiovascular health of Chinese population.

Exploratory analysis of the association between organophosphate ester mixtures with high blood pressure of children and adolescents aged 8-17 years: cross-sectional findings from the National Health and Nutrition Examination Survey.

Epidemiological studies on the effect of organophosphate esters (OPEs) on high blood pressure (BP) among children and adolescents are scant. Therefore, the main objective of the present study was to explore the effect of exposure to OPEs on high BP among children and adolescents. A total of 1340 participants were included in the current analyses. Multivariable logistic regression models were implemented to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to examine the association between OPE metabolites and high BP. We also assessed the modified effect of sex, age, and overweight/obesity on this association. Furthermore, quantile g-computation (Qgcomp) and Bayesian kernel machine regression (BKMR) were exhibited to analyze the association between multiple OPE metabolite mixtures and high BP. After adjusting for covariates, the highest (vs. lowest) tertiles of bis (1-choloro-2-propyl) phosphate (BCPP), bis-2-chloroethyl phosphate (BCEP), and di-n-butyl phosphate (DBUP) were associated with 1.23 (95% CI: 0.83, 1.83), 1.27 (95% CI: 0.85, 1.92), and 1.01 (95% CI: 0.67, 1.53) odds ratios for high BP, respectively. In the Qgcomp, a quartile increase in OPE metabolite mixtures was weakly associated with an elevated risk of high BP (adjusted OR: 1.06, 95CI%: 0.81, 1.37). The results from BKMR showed a positive trend of association between OPE metabolite mixture on the risk of high BP. In conclusion, our study demonstrated that higher levels of BCPP, BCEP, and DBUP were weakly associated with high BP among US children and adolescents. Moderate evidence suggested OPE metabolite mixtures had positive joint effects on high BP. Consequently, longitudinal studies with repeated measurements are warranted to examine the relationships between multiple OPE metabolites and high blood pressure among children and adolescents.

Impact of prior cancer history on survival of patients with hypopharyngeal cancer.

BACKGROUND: The impact of prior cancer history on survival of hypopharyngeal cancer patients remains unknown. The present study assessed the impact of prior cancer history on survival of patients with hypopharyngeal cancer. METHODS: Patients with primary hypopharyngeal cancer diagnosed between 2004 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was conducted to balance baseline characteristics. One-to-one PSM, Kaplan-Meier method, and log-rank test were performed for survival analysis. RESULTS: We included 5017 patients with hypopharyngeal cancer. Prior cancer history had no significant impact on overall survival of hypopharyngeal cancer patients in comparison with those without prior cancer history (p = 0.845, after PSM). Subgroup analysis showed that prior cancer history had no significant effect on overall survival of hypopharyngeal cancer patients. CONCLUSION: More hypopharyngeal cancer patients with prior cancer history should be considered for clinical trials. However, further prospective studies are needed.

Association between household air pollution and all-cause and cause-specific mortality: a systematic review and meta-analysis.

Recently, a growing number of epidemiological studies have examined the relationship between household air pollution (HAP) and all-cause and cause-specific mortality. While the results were not entirely consistent, the current study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) protocol to conduct a comprehensive review and meta-analysis. Data sources were PubMed, Web of Science, Embase, and Cochrane Library for studies published up to 12 May 2022. The pooled relative risks (RRs) with 95% confidence intervals (CI) were used to estimate the effect of household air pollution on all-cause and cause-special mortality. Then I square value (I2) was used to assess heterogeneity, and random-effects model was used as the pooling method. Seventeen studies were included in the quantitative analysis. Our results showed a significant association between household air pollution and increased risks of all-cause mortality (RR = 1.12, 95% CI = 1.06-1.19) and cardiovascular disease mortality (RR = 1.13, 95% CI = 1.04-1.24). Similarly, the associations between household air pollution and mortality from other specific causes (respiratory, ischemic heart disease, stroke, and total cancer) were positive, although they were not statistically significant. The study suggests that exposure to household air pollution increases the risk of all-cause mortality and cardiovascular disease mortality. In addition, our results found a trend of increased mortality from the respiratory system, ischemic heart disease, stroke, and total cancer, with household air pollution.

Exploratory analysis of the association between pyrethroid exposure and rheumatoid arthritis among US adults: 2007-2014 data analysis from the National Health and Nutrition Examination Survey (NHANES).

Previous studies indicate that pesticide use may play an important role in the occurrence and development of rheumatoid arthritis (RA); however, little is known about the effect of specific pesticides on RA. The objective of this study was to evaluate whether pyrethroid exposure was linked to RA in adults. Data were originated from the 2007-2014 National Health and Nutrition Examination Survey (NHANES). The levels of pyrethroid exposure were assessed by 3-phenoxybenzoic acid (3-PBA) concentrations in urine samples. We built multivariate logistic regression models to assess associations between pyrethroid exposure and RA among US adults. A restricted cubic spline plot (three knots) was applied to test whether there was a nonlinear relationship between exposure to pyrethroid pesticides and the prevalence of RA. Finally, 4384 subjects were included in our analysis with 278 RA patients. In crude model, higher level of 3-PBA (creatinine-adjusted) was positively associated with RA (OR: 1.51, 95% CI: 1.07, 2.15). After adjustment for sex, race/ethnicity, education, body mass index, family poverty income, level of education, marital status, smoking status, alcohol usage, physical activity, hypertension, and urinary creatinine, the highest (vs lowest) quartile of 3-PBA was associated with an increased prevalence of RA (OR: 1.23, 95% CI: 0.86, 1.79). Significantly positive associations between 3-PBA concentration and RA were observed in the population aged between 40 and 59 years and with lower level of education. The restricted cubic spline plot presented an increase in trend and indicated that pyrethroid exposure was linearly associated with occurrence of RA (p for nonlinearity = 0.728). In conclusion, our study indicated that pyrethroid pesticide exposure was associated with an increased risk of RA. Higher levels of pyrethroid exposure were linearly associated with increased prevalence of RA in adults. Certainly, our findings are in great need of further corroboration by prospective studies with strict design.

Association between the history of abortion and gestational diabetes mellitus: A meta-analysis.

PURPOSE: Gestational diabetes mellitus (GDM) is a common metabolic disease in pregnant women. The purpose of this study was to determine whether a history of abortion increases the risk of GDM by meta-analysis. METHODS: A comprehensive literature search was conducted in nine databases of studies on the association between abortion history and GDM up to April 12, 2022. Fixed- or random-effects models were used to estimate the pooled odds ratio (OR) and 95% CI. The I square value (I2) was used to assess heterogeneity. Possible sources of heterogeneity were explored by conducting subgroup analysis and meta-regression. A sensitivity analysis was also performed for this meta-analysis. Publication bias was assessed by funnel plots and Egger's tests. RESULTS: Thirty-one studies enrolling 311,900 subjects were included in this meta-analysis. The risk of GDM was higher in women who experienced abortion than in those who did not (OR = 1.41 95% CI: 1.28-1.55, I2 = 66.8%). The risk of GDM increased with an increasing number of abortions (1 time: OR = 1.67, 95% CI = 1.26-2.22; 2 times: OR = 2.10, 95% CI = 1.26-3.49; ≥3 times: OR = 2.49, 95% CI = 1.24-5.01). Both spontaneous abortion (OR = 1.52, 95% CI = 1.30-1.78) and induced abortion (OR = 1.07, 95% CI = 1.03-1.11) were associated with an increased risk of GDM. CONCLUSIONS: A history of abortion was associated with an increased risk of GDM in pregnant women, which may be a risk factor for predicting GDM.

Combined effects of multiple metals on hearing loss: A Bayesian kernel machine regression approach.

BACKGROUND: Exposure to heavy elements is considered one of the risks of hearing loss. The combined effect of multiple metals on different hearing losses has not been extensively studied. METHODS: This study deals with the association between different metals (Ba, Cd, Co, Cs, Mo, Pb, Mn, Sn, Sb, Tl, W) and hearing loss in the 2013-2018 National Health and Nutrition Examination Survey (NHANES). Associations were estimated by a generalized linear regression model (GLM) adjusting for age, gender, race/ethnicity, educational level, marital status, drinking status, hypertension, diabetes, smoking status, noise exposure, body mass index, and income-poverty ratio. The joint effects of mixed exposure were assessed by weighted quantile sum (WQS) model and Bayesian kernel machine regression (BKMR). The effect of multiple metals on speech-frequency hearing loss (SFHL) and high-frequency hearing loss (HFHL) was further calculated. The odds ratio (OR) indicates the risk of every metal exposure. RESULTS: A total of 2205 adult participants were enrolled from NHANES. Cd, Pb, Sb and Sn had significant effects on total hearing loss. The WQS model found that mixed exposure to heavy elements was significantly positively associated with total hearing loss (OR: 1.136; 95% CI: 1.031, 1.253) after adjusting for various covariates. The ORs of mixed exposure in the SFHL and HFHL groups were 1.066 (95% CI: 0.994, 1.143) and 1.102 (95% CI: 1.013, 1.199), respectively. BKMR found a significant positive association between multiple metals and hearing loss. The results showed that there may be potential interactions between Cd, Pb and other metals. CONCLUSIONS: Multiple metals have joint effects on hearing loss in the United States. The findings provide practitioners with important scientific evidence for possible interventions.

Famine exposure in adolescence is associated with a higher risk of overweight/obesity and abdominal obesity in adulthood: A meta-analysis.

Some studies have shown that famine exposure during adolescence can increase cardiovascular disease and diabetes susceptibility in later life. The association between famine exposure in adolescence and overweight/obesity and abdominal obesity in adulthood has been inconsistent. Based on previous studies, we hypothesized that famine exposure in adolescence increases the risk of overweight/obesity and abdominal obesity in adulthood. Eight databases, including PubMed, Embase, Cochrane Library, and Web of Science, were searched from their inception until November 2021. We initially identified 3982 records and finally included 7 articles after screening. The included articles were of moderate to high quality, containing 16 estimates of overweight/obesity and 3 estimates of abdominal obesity. Pooled odds ratios (ORs) with 95% CIs were used to estimate the association between them. The random effects model was adopted as the pooling method. There was a significant association between famine exposure in adolescence and overweight/obesity in adulthood (OR, 1.17; 95% CI, 1.02-1.33). Adolescents exposed to famine had a greater risk of abdominal obesity in adulthood than their unexposed counterparts (OR, 1.35; 95% CI, 1.03-1.76). These results were more pronounced in females than in males. In summary, our meta-analysis indicates that famine exposure during adolescence increases the risk of overweight/obesity and abdominal obesity in adulthood. This suggests that we need to pay timely attention to the nutritional status of adolescents to prevent adverse health consequences of malnutrition. More high-quality studies are needed to confirm these conclusions, given the limitations of this study.

Association between solid fuel combustion and diabetes mellitus: a systematic review and meta-analysis.

In recent years, many epidemiological studies have investigated the relationship between solid fuel combustion and diabetes mellitus (DM). This meta-analysis was performed to explore the potential association between solid fuel combustion and DM. A comprehensive literature search was conducted to identify all relevant studies published prior to January 14, 2022. The pooled odds ratios (OR) with 95% confidence intervals (CI) were used to estimate the effect of solid fuel combustion on DM. The I square value (I2) was used to assess heterogeneity. Due to the heterogeneity of the studies (I2 = 66.70%), a random-effect model was used as the pooling method. A total of 9 articles (10 available datasets) were used for this systematic review and meta-analysis, involving 45,620 study subjects. The results of the meta-analysis showed a statistically positive relationship between household solid fuel combustion and the risk of DM (OR = 1.46, 95% CI = 1.09-1.97). Subgroup analysis based on fuel type revealed a statistically significant association in the mixed solid fuel group (OR = 2.03, 95% CI = 1.59-2.59), but not in the single biomass group (OR = 1.04, 95% CI = 0.73-1.49). This meta-analysis suggests that solid fuel combustion may be associated with an increased risk of DM.

Computational modeling method to estimate secondhand exposure potential from exhalations during e-vapor product use under various real-world scenarios.

Potential secondhand exposure of exhaled constituents from e-vapor product (EVP) use is a public health concern. We present a computational modeling method to predict air levels of exhaled constituents from EVP use. We measured select constituent levels in exhaled breath from adult e-vapor product users, then used a validated computational model to predict constituent levels under three scenarios (car, office, and restaurant) to estimate likely secondhand exposure to non-users. The model was based on physical/thermodynamic interactions between air, vapor, and particulate phase of the aerosol. Input variables included space setting, ventilation rate, total aerosol amount exhaled, and aerosol composition. Exhaled breath samples were analyzed after the use of four different e-liquids in a cartridge-based EVP. Nicotine, propylene glycol, glycerin, menthol, formaldehyde, acetaldehyde, and acrolein levels were measured and reported based on a linear mixed model for analysis of covariance. The ranges of nicotine, propylene glycol, glycerin, and formaldehyde in exhaled breath were 89.44-195.70 µg, 1199.7-3354.5 µg, 5366.8-6484.7 µg, and 0.25-0.34 µg, respectively. Acetaldehyde and acrolein were below detectable limits; thus, no estimated exposure to non-EVP users is reported. The model predicted that nicotine and formaldehyde exposure to non-users was substantially lower during EVPs use compared to cigarettes. The model also predicted that exposure to propylene glycol, glycerin, nicotine and formaldehyde among non-users was below permissible exposure limits.

Combined exposure to multiple metals on cardiovascular disease in NHANES under five statistical models.

BACKGROUND: It is well-documented that heavy metals are associated with cardiovascular disease (CVD). However, there is few studies exploring effect of metal mixture on CVD. Therefore, the primary objective of present study was to investigate the joint effect of heavy metals on CVD and to identify the most influential metals in the mixture. METHODS: Original data for study subjects were obtained from the National Health and Nutrition Examination Survey. In this study, adults with complete data on 12 kinds of urinary metals (antimony, arsenic, barium, cadmium, cobalt, cesium, molybdenum, mercury, lead, thallium, tungsten, and uranium), cardiovascular disease, and core covariates were enrolled. We applied five different statistical strategies to examine the CVD risk with metal exposure, including multivariate logistic regression, adaptive elastic net combined with Environmental Risk Score, Quantile g-computation, Weighted Quantile Sum regression, and Bayesian kernel machine regression. RESULTS: Higher levels of cadmium, tungsten, cobalt, and antimony were significantly associated with Increased risk of CVD when covariates were adjusted for multivariate logistic regression. The results from multi-pollutant strategies all indicated that metal mixture was positively associated with the risk of CVD. Based on the results of multiple statistical strategies, it was determined that cadmium, tungsten, cobalt, and antimony exhibited the strongest positive correlations, whereas barium, lead, molybdenum, and thallium were most associated with negative correlations. CONCLUSION: Overall, our study demonstrates that exposure to heavy metal mixture is linked to a higher risk of CVD. Meanwhile, this association may be driven primarily by cadmium, tungsten, cobalt, and antimony. Further prospective studies are warranted to validate or refute our primary findings as well as to identify other important heavy metals linked with CVD.