Skip to main content

The bisphenol F and bisphenol S and cardiovascular disease: results from NHANES 2013–2016

Abstract

Background

Bisphenol F (BPF) and bisphenol S (BPS) have replaced bisphenol A (BPA) in the manufacturing of products containing polycarbonates and epoxy resins; however, the effects of these substitutes on the risk of cardiovascular disease (CVD), including congestive heart failure, coronary heart disease, angina pectoris, heart attack, and stroke, have not been assessed.

Objective

To examine the association of urinary BPS and BPF with CVD risk in a U.S. representative U.S. population.

Methods

Cross-sectional data from 1267 participants aged 20–80 years from the 2013–2016 National Health and Nutrition Examination Survey (NHANES) were analyzed. Survey-weighted multiple logistic regression was used to assess the association between BPA, BPF, BPS and CVD. The Bayesian kernel machine regression (BKMR) model was applied to assess the mixture effect.

Results

A total of 138 patients with CVD were identified. After adjusting for potential confounding factors, the T3 tertile concentration of BPS increased the risk of total CVD (OR: 1.99, 95% CI 1.16–3.40). When stratified by age, we found that BPS increased the risk of CVD in the 50–80 age group (OR: 1.40, 95% CI 1.05–1.87). BPS was positively associated with the risk of coronary heart disease, and the T3 tertile concentration of BPS increased the coronary heart disease risk by 2.22 times (95% CI 1.04–4.74). No significant association was observed between BPF and CVD. Although the BKMR model did not identify the mixed exposure effect of BPS, the risk of CVD increased with increasing compound concentration.

Conclusion

Our results suggest that BPS may increase the risk of total CVD and coronary heart disease in the US population, and prospective studies are needed to confirm the results.

Introduction

Bisphenol is a chemical epoxy resin compound containing two hydroxyl phenyl groups [27, 45]. Bisphenol, as an endocrine disruptor, has adverse effects at very low doses [45]. Bisphenol A (BPA) has long been used in plastics [5, 8]. Higher concentrations of BPA have been associated with CVD [4], obesity [41], diabetes [44], and hypertension [6], and brain [39], reproductive system damage[33]. However, due to these adverse effects, some countries have started to ban or restrict the use of BPA in consumer products.

Bisphenol S (BPS) and bisphenol F (BPF) are two substitutes for BPA [37]. BPF and BPS can be found in food packaging items, beverage containers, paper products [27], personal care products (e.g., body wash, hair care products, makeup, lotions, toothpaste) [24], food (e.g., dairy products, meat and meat products, vegetables, canned foods, cereals) [23], and baby bottles [42]. Recently, health concerns have been raised about these substitutes as well. Higher concentrations of BPS and BPF were associated with depressive symptoms [12], asthma, and hay fever [27]. Due to endocrine-disrupting effects similar to BPA [10, 20, 37], we hypothesized that exposure to BPS or BPF is associated with an increased risk of CVD in humans [10].

Cardiovascular disease (CVD) is recognized as the leading cause of death, with an estimated annual mortality of 17.9 million worldwide and more than 800,000 deaths occurring in the USA (AHA report 2020) [47]. Approximately 80% of CVD deaths are attributable to heart attacks and strokes, and one-third occur in people < 70 years [47]. Atherosclerosis is the most common form of vascular disease and constitutes the major cause of death, causing 17.5 million CVD deaths annually (31% of the global mortality) [43]. Although traditional risk factors for CVD, such as family history, diabetes, hypertension, dyslipidemia, and obesity, have been identified, nearly 20% of CVD patients do not have any of these risk factors [19, 51, 52]. Environmental factors, including nonylphenol (NP), bisphenol A (BPA), polychlorinated biphenyl (PCB), organo-chlorine pesticide (OCP), and phthalate (PAE) [10], exert additional synergistic or additive effects on these traditional risk factors, further increasing the risk of CVD [2, 17, 50].

Using the National Health and Nutrition Examination Survey (NHANES), we performed a cross-sectional analysis using a representative U.S. adult population to examine the association between BPS and BPF exposure and CVD, including congestive heart failure, coronary heart disease, angina pectoris, heart attack, and stroke.

Materials and methods

Study population

Our study is based on data from the National Health and Nutrition Examination Survey (NHANES) 2013–2016. Detailed descriptions of the NHANES study design and methods are available elsewhere (National Center for Health Statistics, NCHS). “The NHANES is a program of studies designed to assess the health and nutritional status of adults and children in the United States” (https://www.cdc.gov/nchs/nhanes/about_nhanes.htm). The survey is unique in its combination of interviews, physical examinations, and laboratory tests designed with multilevel probability sampling. All participants provided informed consent when they were recruited to participate in the study [4]. The National Center for Health Statistics Research Ethics Review Board approved the implementation of the protocol for the NHANES [4]. From 2013 to 2016, a total of 1,267 NHANES participants with available bisphenol and CVD data were included in the final analysis. The whole data integration process is shown in the figure below (Fig. 1).

Fig. 1
figure 1

Eligible participants and those included in the analyses of the associations between bisphenols and the risk of CVD in adults

CVD

CVD was determined by a combination of a self-reported physician diagnosis and the completion of a standardized medical condition questionnaire. The participants were asked five separate questions: "Has a physician or other health care professional ever told you that you have had congestive heart failure/ coronary heart disease/ angina pectoris/ heart attack/ stroke?" If the participant answered "yes" to any of the five separate questions above, the participant was determined to be a patient with CVD (https://wwwn.cdc.gov/Nchs/Nhanes/2015-2016/MCQ_I.htm). We excluded all participants who said they did not know and those who refused to answer.

Bisphenol exposure

As part of the NHANES ongoing biological surveillance program, in one third of NHANES participants, BPS and BPF were measured using online solid-phase extraction high-performance liquid chromatography with atmospheric pressure chemical ionization–mass spectrometry (https://wwwn.cdc.gov/nchs/data/nhanes/2015-2016/manuals/2016_MEC_Laboratory_Procedures_Manual.pdf). The lower limits of detection of BPS, BPF and BPA were 0.1, 0.2 and 0.2 ng/mL, respectively. The NHANES quality assurance and quality control (QA/QC) protocols meet the 1988 Clinical Laboratory Improvement Act mandates.

(https://wwwn.cdc.gov/nchs/data/nhanes/2015-2016/manuals/2016_MEC_Laboratory_Procedures_Manual.pdf).

Covariates

From demographics and questionnaire data, we selected the following as potential confounding variables in our analysis: age, sex, race/ethnicity, education level, the family poverty-income ratio (PIR), smoking status, alcohol drinking status, physical activity, blood pressure, and diabetes. Data on energy intake were acquired from the dietary intake data collected in two 24 dietary recall interviews. Based on the body measurement examination data and questionnaire data, we obtained body mass index (BMI, kg/m2) and blood pressure data. Based on measurements in the laboratory data, we obtained urine creatinine data, and low-density lipoprotein (LDL) data. The PIR, as a proxy for socioeconomic status, was estimated using guidelines and adjustment for family size, year and state [27]. Urinary creatinine is used to describe the degree of urine dilution [27]. Urine creatinine analysis was performed on a Roche Mod P using an enzymatic (creatinase) method [14].

Statistical analysis

The survey procedure using the NHANES database was adapted to the complex survey design and included appropriate sample weights for this random subsample to obtain accurate estimates representing the civilian population of the United States (https://www.cdc.gov/nchs/data/nhanes/nhanes_13_14/NHANES_Overview_Brochure.pdf). Categorical variables are presented as frequency and percentage, while continuous variables are presented as the mean and standard deviation (SD). Categorical variables and continuous variables were compared using the χ2 test and the t test, respectively. The association between bisphenols and the risk of CVD was analysed by survey-weighted multiple logistic regression analysis, and three separate models were constructed for each bisphenol that was available in the NHANES database. The adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for CVD by the tertiles of each bisphenol were calculated. Subgroup analyses were performed to investigate the association between the bisphenols and CVD subtypes (congestive heart failure, coronary heart disease, angina pectoris, heart attack, and stroke). All variables were checked for normality of distribution, and log transformations were applied on the independent variable. The levels of BPS, BPF and BPA were divided into tertiles (T1, T2, and T3) and we described them in the statistics. The restricted cubic spline (RCS) model was used to further investigate the nonlinear relationship between the bisphenols and the risk of CVD. The BKMR model estimates the multivariable exposure–response function in a flexible way that allows for nonlinearity, while adjusting for covariates including potential confounding factors, and then simultaneously conducting variable selection on the groups of correlated exposures as well as on the individual exposures within each group to address the multicollinearity problem [3]. We stratified and interacted the associations of age, gender, smoking status, alcohol drinking status, blood pressure, BMI, PIR and physical activity for their association with the risk of CVD. We further used the BKMR model to explore the relationships between a mixture of BPS, BPF, and BPA exposures and the risk of CVD. We used STATA to perform a stratified analysis and interaction on the data. All data analyses were performed in STATA (version 16.0 SP) and R (version 4.0.5) software.

Results

Cohort characteristics

A total of 1267 participants were finally included in our study, of whom 138 (10.90%) had CVD. The CVD subtypes was 2.76%, 4.19%, 2.05%, 4.66%, and 3.79% for congestive heart failure, coronary heart disease, angina pectoris, heart attack, and stroke, respectively. The average ages of the non-CVD and CVD patients were 47.78 ± 16.98 and 65.83 ± 11.17 years, respectively. In the overall study population, there were more non-Hispanic whites (47.10%) and non-Hispanic blacks (26.09%) among CVD group than the health group. There were significant differences in age, physical activity, smoking status, cancer, diabetes, and blood pressure (all P < 0.05) between the non-CVD and CVD patients (Table 1).

Table 1 Participant characteristics (N = 1267) in NHANES 2013–2016

Association between bisphenols exposure and the risk of total CVD

The T3 tertile of BPS increased the risk of total CVD by 1.99 times (95% CI 1.16–3.40) compared to the T1 tertile after adjusting for covariates, with a P for trend was of 0.011. An association between BPF, BPA and the risk of total CVD (Table 2) was not identified. When stratified by age, we found that the T3 tertile of BPS increased the risk of CVD by 1.40 times (95% CI 1.05–1.87), with a P for trend of 0.021 in the 50–80 age group, and we did not find this association in the 20–49 age group (Fig. 2).

Table 2 Associations of Bisphenols with total CVD risk in US adults 2013–2016
Fig. 2
figure 2

Forest Plot of the Primary Outcome According to Subgroups. The P value is the trend of stratified analysis. P-i. is the p value the interaction between BPS and the subgroup. Adjusted for sex, age, race, education level, PIR, physical activity, alcohol drinking status, smoking status, BMI, blood pressure, diabetes, LDL-C level, energy intake, and urine creatinine concentration

We further performed the analysis stratified, we found that BPS increased the risk of CVD in the 50–80 year subgroup of age, overweight/obesity subgroup of BMI, PIR < 2.5 subgroup of PIR, never/moderate subgroup of physical activity, and former/active smoker subgroup of smoking status (Fig. 2). We found no association between the interaction and the risk of CVD (Fig. 2). The RCS model showed that there was a linear relationship between BPS and the risk of CVD (P for nonlinear association = 0.9268) in all participants (Additional file 1: Fig. S1A). The RCS model showed that there was a linear relationship between BPF and the risk of CVD (P for nonlinear association = 0.0878) in all participants (Additional file 1: Fig. S1B).

The mixed-effects between bisphenols and the risk of CVD using the BKMR model

The BKMR model did not identify a mixture exposure effect of BPS, BPF and BPA (Fig. 3).

Fig. 3
figure 3

BKMR model was used to assess the mixture effects between bisphenols and the risk of CVD. A Combined effects of the bisphenols mixture on CVD risk estimated by the BKMR model, adjusting for sex, age, race, education level, PIR, physical activity, alcohol drinking status, smoking status, BMI, blood pressure, diabetes, LDL-C, energy, and urine creatinine. B Univariate exposure–response functions and 95% confidence interval for each bisphenol with the other two bisphenols fixed at the median

The associations between bisphenols and subgroup CVD risk

We found that BPS was positively associated with the risk of coronary heart disease, and the T3 tertile of BPS increased the risk of coronary heart disease by 2.22 times (95% CI 1.04–4.74) after adjusting for all the covariates, with a P for trend of 0.036 (Table 3). We did not observe an association between the bisphenols and coronary heart disease, angina pectoris, heart attack or stroke.

Table 3 Associations of Bisphenols with CVD subgroup risk

Discussion

In this study, we identified a significant association between urinary BPS and an increased risk of total CVD, especially in people aged 50–80 years. Furthermore, urinary BPS was significantly associated with an increased risk of coronary heart disease.

Although BPA, BPS, and BPF share similar chemical properties, BPS and BPF are not safe alternatives for BPA [8]. One study tested the effects of BPS, BPF and BPA on testosterone secretion, and showed that BPS inhibited testosterone even more than BPA did [8]. Compared with BPA and BPF, BPS exposure significantly affected liver lipid and glucose metabolism [28]. It has been reported that exposure to high levels of BPS and BPF is significantly associated with obesity [25] and abnormal thyroid signalling pathways [21, 51, 52]. However, no study has reported the association between BPS and BPF and CVD in humans. In this study, we demonstrated differences in the relationship between BPS exposure and total CVD and CVD subtypes. Due to the limited use of BPA, BPS is increasingly being used as an alternative to BPA in industrial production [22]. The mechanism of action of BPS in the body is similar to that of BPA and BPF, and they have similar chemical structures [1, 34, 36]. In contrast, BPS has a similar or an even greater destructive biological effect than BPA [46]. Mice that were prenatally exposed to BPS to were significantly more susceptible to spontaneous epithelial lesions and inflammation, with an incidence greater than that observed in vehicle and BPA-exposed animals [46]. It has been proposed that humans are becoming widely exposed to BPS, and dietary intake, inhalation, and skin contact are believed to be the main sources of human exposure to BPS [38].

Previous studies have reported that urinary BPA is positively associated with an increased prevalence of total CVD in the U.S. population [4, 13]. Another study has shown a positive association between BPA and CVD [26]. However, in our study, BPA was not associated with the risk of CVD. Most likely due to the stricter regulation of BPA, industries have increased the use of replacement substances [15], leading to lower BPA exposure. However, for BPS and BPF, the association with CVD risk has rarely been reported.

A very important finding in this study was that BPS exposure was associated with an increase in total CVD and coronary heart disease risk. Several animal experiments have reported the effects of BPS. BPS can decrease left ventricular contractility and rapidly depresses heart function by increasing phospholamban phosphorylation of serine 16 and decreasing threonine 17 phosphorylation in mice [9]. A study of pregnant mice showed that exposure to BPS reduced the recovery of adult male progeny from myocardial infarction [16]. BPS also increased the plasma lipid profiles of atherogenic proteins, but decreased serum hematological variables and high-density lipoprotein in male rats [32]. BPS induced cardiac oedema and arrhythmia in zebrafish embryos [29, 30]. Low doses of BPS have been shown to cause cardiac arrhythmias in female rats [11]. BPS increased the pulse rate of the dorsal vessels in Lumbriculus variegatus [48].These animal studies have shown that BPS is harmful to cardiovascular health.

When stratified by age, we found that exposure to BPS increased the risk of total CVD in participants between 50 and 80 years of age. BPS exposure increased the risk of total CVD in the older age group, possibly due to longer exposure and higher exposure levels than the younger age group.

Based on the data of the population included in our study, the average exposure concentration of BPS in the 20–49 age group was 1.26 ng/ml (95% CI 0.61,4.97, P = 0.286), while the average exposure concentration of BPS in the 50–80 age group was 1.90 ng/ml (95% CI 1.05,1.87, P = 0.021). It was clear that the older age group had higher exposure levels than the younger age group. In a study of the pharmacokinetics of BPS in humans after a single oral administration, seven healthy young adults received 8.75 μg/kg of BPS orally, and the total BPS was observed in serum within 1 h after administration and excreted in urine with a terminal half-life of 7 h [31]. In another study, six human volunteers were administered 0.1 mg/kg of BPS, and reached Cmax at 0.7 and 1.1 h for BPS and its glucuronide, respectively, with plasma elimination half-lives of 7.9 and 9.3 h, respectively [18, 49]. It might be that the metabolism of BPS slows down in the body with the decreasing of the metabolic rate, renal excretory [40] and immune functions in the elderly population, leading to a relatively higher concentration of BPS accumulation in the age group of 50–80 years, thus increasing their risk of CVD. Studies have also shown that long-term exposure to BPS can disrupt the body's immune response [34, 36]. These factors may account for the increased risk of CVD in the 50–80 age group. Further studies have shown that exposure to BPS in zebrafish can alter the immune function of offspring, increase lysozyme activity, change oxidative stress and inflammatory cytokines, and lead to decreased immune defenced in zebrafish [35]. The study found that immune system pathways were also affected by exposure to BPS in zebrafish embryos [7].

Our study has the following advantages. First, the toxicity of bisphenols has long been reported, but the possible health-damaging effects of low-concentration BPS and BPF in the human body have not been reported. For the first time, we found through large sample populational data that BPS may be related to CVD and may be positively related to CHD. There are some limitations to our study. We used data from a cross-sectional study to preclude the inference of the cause–effect relationship. The data we used to define CVD were self-reported by participants, and the accuracy of the data may be biased. In addition, one limitation in our study was that there was only on bisphenol measurement duo to the short biological half-life.

Conclusion

We found that BPS level are significantly associated with the risks of total CVD and coronary heart disease in the U.S population from a cross-sectional study, and the prospective studies are needed to explore on the mechanisms of BPS and BPF on CVD.

Availability of data and materials

The data used in this study can be downloaded for free in NHANES.

References

  1. Audebert M, Dolo L, Perdu E, Cravedi JP, Zalko D (2011) Use of the γH2AX assay for assessing the genotoxicity of bisphenol A and bisphenol F in human cell lines. Arch Toxicol 85:1463–1473

    CAS  Google Scholar 

  2. Bhatnagar A (2017) Environmental determinants of cardiovascular disease. Circ Res 121:162–180

    CAS  Google Scholar 

  3. Bobb JF, Claus Henn B, Valeri L, Coull BA (2018) Statistical software for analyzing the health effects of multiple concurrent exposures via Bayesian kernel machine regression. Environ Health 17:67

    Google Scholar 

  4. Cai S, Rao X, Ye J, Ling Y, Mi S, Chen H, Fan C, Li Y (2020) Relationship between urinary bisphenol a levels and cardiovascular diseases in the U.S. adult population, 2003–2014. Ecotoxicol Environ Saf 192:110300

    CAS  Google Scholar 

  5. Casey MF, Neidell M (2013) Disconcordance in statistical models of bisphenol A and chronic disease outcomes in NHANES 2003–08. PLoS ONE 8:e79944

    CAS  Google Scholar 

  6. Commodore-Mensah Y, Selvin E, Aboagye J, Turkson-Ocran RA, Li X, Himmelfarb CD, Ahima RS, Cooper LA (2018) Hypertension, overweight/obesity, and diabetes among immigrants in the United States: an analysis of the 2010–2016 National Health Interview Survey. BMC Public Health 18:773

    Google Scholar 

  7. Dong X, Zhang Z, Meng S, Pan C, Yang M, Wu X, Yang L, Xu H (2018) Parental exposure to bisphenol A and its analogs influences zebrafish offspring immunity. Sci Total Environ 610–611:291–297

    Google Scholar 

  8. Eladak S, Grisin T, Moison D, Guerquin MJ, N’Tumba-Byn T, Pozzi-Gaudin S, Benachi A, Livera G, Rouiller-Fabre V, Habert R (2015) A new chapter in the bisphenol A story: bisphenol S and bisphenol F are not safe alternatives to this compound. Fertil Steril 103:11–21

    CAS  Google Scholar 

  9. Ferguson M, Lorenzen-Schmidt I, Pyle WG (2019) Bisphenol S rapidly depresses heart function through estrogen receptor-β and decreases phospholamban phosphorylation in a sex-dependent manner. Sci Rep 9:15948

    Google Scholar 

  10. Fu X, Xu J, Zhang R, Yu J (2020) The association between environmental endocrine disruptors and cardiovascular diseases: a systematic review and meta-analysis. Environ Res 187:109464

    CAS  Google Scholar 

  11. Gao X, Ma J, Chen Y, Wang HS (2015) Rapid responses and mechanism of action for low-dose bisphenol S on ex vivo rat hearts and isolated myocytes: evidence of female-specific proarrhythmic effects. Environ Health Perspect 123:571–578

    Google Scholar 

  12. Hao K, Luo J, Sun J, Ge H, Wang Z (2021) Associations of urinary bisphenol A and its alternatives bisphenol S and F concentrations with depressive symptoms among adults. Chemosphere 279:130573

    CAS  Google Scholar 

  13. Hu C, Schöttker B, Venisse N, Limousi F, Saulnier PJ, Albouy-Llaty M, Dupuis A, Brenner H, Migeot V, Hadjadj S (2019) Bisphenol A, chlorinated derivatives of bisphenol A and occurrence of myocardial infarction in patients with type 2 diabetes: nested case-control studies in two European Cohorts. Environ Sci Technol 53:9876–9883

    CAS  Google Scholar 

  14. Jain RB (2017) Trends in the levels of urine and serum creatinine: data from NHANES 2001–2014. Environ Sci Pollut Res Int 24:10197–10204

    Google Scholar 

  15. Karrer C, Roiss T, von Goetz N, Gramec Skledar D, Peterlin Mašič L, Hungerbühler K (2018) Physiologically Based Pharmacokinetic (PBPK) Modeling of the Bisphenols BPA, BPS, BPF, and BPAF with New Experimental Metabolic Parameters: Comparing the Pharmacokinetic Behavior of BPA with Its Substitutes. Environ Health Perspect 126:077002

    Google Scholar 

  16. Kasneci A, Lee JS, Yun TJ, Shang J, Lampen S, Gomolin T, Cheong CC, Chalifour LE (2017) From the cover: lifelong exposure of C57bl/6n male mice to bisphenol A or bisphenol S reduces recovery from a myocardial infarction. Toxicol Sci 159:189–202

    CAS  Google Scholar 

  17. Kaufman JD, Adar SD, Barr RG, Budoff M, Burke GL, Curl CL, Daviglus ML, Diez Roux AV, Gassett AJ, Jacobs DR Jr, Kronmal R, Larson TV, Navas-Acien A, Olives C, Sampson PD, Sheppard L, Siscovick DS, Stein JH, Szpiro AA, Watson KE (2016) Association between air pollution and coronary artery calcification within six metropolitan areas in the USA (the Multi-Ethnic Study of Atherosclerosis and Air Pollution): a longitudinal cohort study. Lancet 388:696–704

    CAS  Google Scholar 

  18. Khmiri I, Côté J, Mantha M, Khemiri R, Lacroix M, Gely C, Toutain PL, Picard-Hagen N, Gayrard V, Bouchard M (2020) Toxicokinetics of bisphenol-S and its glucuronide in plasma and urine following oral and dermal exposure in volunteers for the interpretation of biomonitoring data. Environ Int 138:105644

    CAS  Google Scholar 

  19. Khot UN, Khot MB, Bajzer CT, Sapp SK, Ohman EM, Brener SJ, Ellis SG, Lincoff AM, Topol EJ (2003) Prevalence of conventional risk factors in patients with coronary heart disease. JAMA 290:898–904

    Google Scholar 

  20. Kuruto-Niwa R, Nozawa R, Miyakoshi T, Shiozawa T, Terao Y (2005) Estrogenic activity of alkylphenols, bisphenol S, and their chlorinated derivatives using a GFP expression system. Environ Toxicol Pharmacol 19:121–130

    CAS  Google Scholar 

  21. Lee S, Kim C, Shin H, Kho Y, Choi K (2019) Comparison of thyroid hormone disruption potentials by bisphenols A S, F, and Z in embryo-larval zebrafish. Chemosphere 221:115–123

    CAS  Google Scholar 

  22. Li A, Zhuang T, Shi W, Liang Y, Liao C, Song M, Jiang G (2020) Serum concentration of bisphenol analogues in pregnant women in China. Sci Total Environ 707:136100

    CAS  Google Scholar 

  23. Liao C, Kannan K (2013) Concentrations and profiles of bisphenol A and other bisphenol analogues in foodstuffs from the United States and their implications for human exposure. J Agric Food Chem 61:4655–4662

    CAS  Google Scholar 

  24. Liao C, Kannan K (2014) A survey of alkylphenols, bisphenols, and triclosan in personal care products from China and the United States. Arch Environ Contam Toxicol 67:50–59

    CAS  Google Scholar 

  25. Liu B, Lehmler HJ, Sun Y, Xu G, Sun Q, Snetselaar LG, Wallace RB, Bao W (2019) Association of bisphenol A and its substitutes bisphenol F and bisphenol S, with obesity in United States Children and Adolescents. Diabetes Metab J 43:59–75

    Google Scholar 

  26. Melzer D, Rice NE, Lewis C, Henley WE, Galloway TS (2010) Association of urinary bisphenol a concentration with heart disease: evidence from NHANES 2003/06. PLoS ONE 5:e8673

    Google Scholar 

  27. Mendy A, Salo PM, Wilkerson J, Feinstein L, Ferguson KK, Fessler MB, Thorne PS, Zeldin DC (2020) Association of urinary levels of bisphenols F and S used as bisphenol A substitutes with asthma and hay fever outcomes. Environ Res 183:108944

    CAS  Google Scholar 

  28. Meng Z, Wang D, Yan S, Li R, Yan J, Teng M, Zhou Z, Zhu W (2018) Effects of perinatal exposure to BPA and its alternatives (BPS, BPF and BPAF) on hepatic lipid and glucose homeostasis in female mice adolescent offspring. Chemosphere 212:297–306

    CAS  Google Scholar 

  29. Moreman J, Lee O, Trznadel M, David A, Kudoh T, Tyler CR (2017) Acute toxicity, teratogenic, and estrogenic effects of bisphenol A and its alternative replacements bisphenol S, Bisphenol F, and bisphenol AF in zebrafish embryo-larvae. Environ Sci Technol 51:12796–12805

    CAS  Google Scholar 

  30. Mu X, Huang Y, Li X, Lei Y, Teng M, Li X, Wang C, Li Y (2018) Developmental effects and estrogenicity of Bisphenol A alternatives in a zebrafish embryo model. Environ Sci Technol 52:3222–3231

    CAS  Google Scholar 

  31. Oh J, Choi JW, Ahn YA, Kim S (2018) Pharmacokinetics of bisphenol S in humans after single oral administration. Environ Int 112:127–133

    CAS  Google Scholar 

  32. Pal S, Sarkar K, Nath PP, Mondal M, Khatun A, Paul G (2017) Bisphenol S impairs blood functions and induces cardiovascular risks in rats. Toxicol Rep 4:560–565

    CAS  Google Scholar 

  33. Pivonello C, Muscogiuri G, Nardone A, Garifalos F, Provvisiero DP, Verde N, de Angelis C, Conforti A, Piscopo M, Auriemma RS, Colao A, Pivonello R (2020) Bisphenol A: an emerging threat to female fertility. Reprod Biol Endocrinol 18:22

    CAS  Google Scholar 

  34. Qiu W, Shao H, Lei P, Zheng C, Qiu C, Yang M, Zheng Y (2018) Immunotoxicity of bisphenol S and F are similar to that of bisphenol A during zebrafish early development. Chemosphere 194:1–8

    CAS  Google Scholar 

  35. Qiu W, Yang M, Liu J, Xu H, Luo S, Wong M, Zheng C (2019) Bisphenol S-induced chronic inflammatory stress in liver via peroxisome proliferator-activated receptor γ using fish in vivo and in vitro models. Environ Pollut 246:963–971

    CAS  Google Scholar 

  36. Qiu W, Yang M, Liu S, Lei P, Hu L, Chen B, Wu M, Wang KJ (2018) Toxic effects of bisphenol S showing immunomodulation in fish macrophages. Environ Sci Technol 52:831–838

    CAS  Google Scholar 

  37. Rochester JR, Bolden AL (2015) Bisphenol S and F: a systematic review and comparison of the hormonal activity of bisphenol a substitutes. Environ Health Perspect 123:643–650

    CAS  Google Scholar 

  38. Russo G, Barbato F, Grumetto L (2017) Monitoring of bisphenol A and bisphenol S in thermal paper receipts from the Italian market and estimated transdermal human intake: a pilot study. Sci Total Environ 599–600:68–75

    Google Scholar 

  39. Santoro A, Chianese R, Troisi J, Richards S, Nori SL, Fasano S, Guida M, Plunk E, Viggiano A, Pierantoni R, Meccariello R (2019) Neuro-toxic and Reproductive Effects of BPA. Curr Neuropharmacol 17:1109–1132

    CAS  Google Scholar 

  40. Scrutinio D, Passantino A, Santoro D, Cacciapaglia E, Farinola G (2009) Prognostic value of formulas estimating excretory renal function in the elderly with systolic heart failure. Age Ageing 38:296–301

    Google Scholar 

  41. Shankar A, Teppala S, Sabanayagam C (2012) Urinary bisphenol a levels and measures of obesity: results from the national health and nutrition examination survey 2003–2008. ISRN Endocrinol 2012:965243

    Google Scholar 

  42. Simoneau C, Valzacchi S, Morkunas V, Van den Eede L (2011) Comparison of migration from polyethersulphone and polycarbonate baby bottles. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 28:1763–1768

    CAS  Google Scholar 

  43. Stefanadis C, Antoniou CK, Tsiachris D, Pietri P (2017) Coronary atherosclerotic vulnerable plaque: current perspectives. J Am Heart Assoc. https://doi.org/10.1161/JAHA.117.005543

    Article  Google Scholar 

  44. Stojanoska MM, Milosevic N, Milic N, Abenavoli L (2017) The influence of phthalates and bisphenol A on the obesity development and glucose metabolism disorders. Endocrine 55:666–681

    CAS  Google Scholar 

  45. Thoene M, Rytel L, Nowicka N, Wojtkiewicz J (2018) The state of bisphenol research in the lesser developed countries of the EU: a mini-review. Toxicol Res (Camb) 7:371–380

    CAS  Google Scholar 

  46. Tucker DK, Hayes Bouknight S, Brar SS, Kissling GE, Fenton SE (2018) Evaluation of prenatal exposure to bisphenol analogues on development and long-term health of the mammary gland in female mice. Environ Health Perspect 126:087003

    Google Scholar 

  47. Virani SS, Alonso A, Aparicio HJ, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Cheng S, Delling FN, Elkind MSV, Evenson KR, Ferguson JF, Gupta DK, Khan SS, Kissela BM, Knutson KL, Lee CD, Lewis TT, Liu J, Loop MS, Lutsey PL, Ma J, Mackey J, Martin SS, Matchar DB, Mussolino ME, Navaneethan SD, Perak AM, Roth GA, Samad Z, Satou GM, Schroeder EB, Shah SH, Shay CM, Stokes A, VanWagner LB, Wang NY, Tsao CW (2021) Heart disease and stroke statistics-2021 update: a report from the American Heart Association. Circulation 143:e254–e743

    Google Scholar 

  48. Vought V, Wang HS (2018) Impact of common environmental chemicals bisphenol A and bisphenol S on the physiology of Lumbriculus variegatus. Environ Toxicol Pharmacol 60:225–229

    CAS  Google Scholar 

  49. Waidyanatha S, Black SR, Silinski M, Sutherland V, Fletcher BL, Fernando RA, Fennell TR (2020) Comparative toxicokinetics of bisphenol S in rats and mice following gavage administration. Toxicol Appl Pharmacol 406:115207

    CAS  Google Scholar 

  50. Xu C, Liang J, Xu S, Liu Q, Xu J, Gu A (2020) Increased serum levels of aldehydes are associated with cardiovascular disease and cardiovascular risk factors in adults. J Hazard Mater 400:123134

    CAS  Google Scholar 

  51. Zhang YF, Ren XM, Li YY, Yao XF, Li CH, Qin ZF, Guo LH (2018) Bisphenol A alternatives bisphenol S and bisphenol F interfere with thyroid hormone signaling pathway in vitro and in vivo. Environ Pollut 237:1072–1079

    CAS  Google Scholar 

  52. Zhang Y, Huang M, Zhuang P, Jiao J, Chen X, Wang J, Wu Y (2018) Exposure to acrylamide and the risk of cardiovascular diseases in the National Health and Nutrition Examination Survey 2003–2006. Environ Int 117:154–163

    CAS  Google Scholar 

Download references

Acknowledgements

This study analyzed using the data provided by the National Health and Nutrition Examination Survey 2013–2016. Data from this survey will be used in epidemiological studies and health sciences research, which help develop sound public health policy, direct and design health programs and services, and expand the health knowledge for the Nation.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

Authors

Contributions

RW: conceptualization, methodology, software, validation, and writing—original draft. QF: writing—review, software, and validation. SL and XW: software and data curation. HL and YW and LW: investigation and resources. GH and GC and CJ: validation, supervision, writing—review and editing, and project administration. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Guang Hao, Guangwen Cao or Chunxia Jing.

Ethics declarations

Ethics approval and consent to participate

The NHANES agreement has been reviewed and approved by the NCHS Research Ethics Committee. All participants provided written informed consent before participating.

Consent for publication

All participants provided written informed consent prior to participation.

Competing interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1: Fig S1.

The restricted cubic spline model was used to analyze the relationship between Bisphenols and the risk of CVD. A BPS; B BPF; C BPA. The analysis adjusted for gender, age, race, education level, PIR, physical activity, alcohol drinking status, smoking status, BMI, blood pressure, cancer, diabetes, LDL-C, energy, urine creatinine.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, R., Fei, Q., Liu, S. et al. The bisphenol F and bisphenol S and cardiovascular disease: results from NHANES 2013–2016. Environ Sci Eur 34, 4 (2022). https://doi.org/10.1186/s12302-021-00586-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12302-021-00586-9

Keywords