In this study, we identified a significant association between urinary BPS and increased risk of total CVD, especially in people aged 50–80 years. Furthermore, urinary BPS has significantly associated with an increased risk of stroke.
Although BPA, BPS, and BPF share similar chemical properties, BPS and BPF are not safe alternatives to BPA(Eladak et al. 2015). It has been reported that exposure to high levels of BPS and BPF was significantly associated with obesity(Liu et al. 2019) and abnormal thyroid signaling pathways(Zhang, Ren, et al. 2018). However, there was no study to report the association between BPS and BPF and CVD in human. In this study, we demonstrated differences in the relationship between BPS exposure and the total CVD and its CVD subtypes. Due to the limited use of BPA, BPS is increasingly being used as an alternative to BPA in industrial production(Li et al. 2020). The mechanism of action of BPS is similar to that of BPA and BPF in the body. In contrast, BPS has a similar or even greater biological destructive effect than BPA(Tucker et al. 2018). Prenatal exposure to BPS in mice to was significantly more susceptible to spontaneous epithelial lesions and inflammation, with an incidence greater than observed in vehicle and BPA-exposed animals(Tucker et al. 2018). 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(Russo, Barbato, and Grumetto 2017).
Previous studies have reported that urinary BPA is positively associated with an increased prevalence of total CVD in the U.S. population(Cai et al. 2020; Hu et al. 2019). Another study has shown a positively association between BPA and CVD(Melzer et al. 2010). However, in our study, BPA was not associated with the risk of CVD. Probably due to the stricter regulation of BPA, industry has increased the use of replacement substances(Karrer et al. 2018), leading to lower of BPA exposure.
For BPS and BPF, the association with CVD risk was rarely reported. In this study, we found that BPS increased the risk of CVD, while BPF was not associated with the risk of CVD. In animal studies, exposure to high doses of BPS and BPF has been significantly correlated with abnormal thyroid function(Lee et al. 2019) and obesity(Zhang et al. 2019). In a population study, the higher concentrations of BPS and BPF have been shown to be associated with depressive symptoms(Hao et al. 2021), asthma and hay fever(Mendy et al. 2020).
A very important finding in this study was that BPS exposure was associated an increase of total CVD and stroke risk. Several experiments have reported the effects of BPS. An experiment in mice showed that BPS can decrease left ventricular contractility, increasing phospholamban phosphorylation at serine 16 and decrease threonine 17 phosphorylation, and demonstrates a rapid of BPS to depress heart function(Ferguson, Lorenzen-Schmidt, and Pyle 2019). A study of pregnant mice showed that exposure to BPS reduced recovery from myocardial infarction of adult male progeny(Kasneci et al. 2017). BPS increased the plasma lipid profile of atherogenic proteins, but decrease serum hematological variables and high-density lipoprotein in male rats(Pal et al. 2017). BPS also induced cardiac edema and arrhythmia in zebrafish embryo(Moreman et al. 2017; Mu et al. 2018). However, no correlation between BPS and CVD has been reported in the population.
When stratified by age, we found that exposure to BPS increased the risk of total CVD 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, while the average exposure concentration of BPS in the 50–80 age group was 1.90 ng/ml. It was clear that the older age group had higher exposure levels than the younger age group. BPS dissipated quickly in an oxic soil, with a half-life of 2.8 days(Cao et al. 2020). A study of pharmacokinetics of BPS in humans after single oral administration, seven healthy young adults received BPS 8.75µg/kg orally, and total BPS was observed in serum within 1h after administration and excreted in urine with terminal half-life of 7h(Oh et al. 2018). In another study, six human volunteers administered 0.1mg/kg BPS, Cmax was reached at 0.7h and 1.1h for BPS and its glucuronide, respectively, with plasma elimination half-lives of 7.9h and 9.3h, respectively(Khmiri et al. 2020; Waidyanatha et al. 2020). It may be that the slower metabolic rate of the elderly leads to a higher concentration accumulation of BPS in the 50–80 age group, thus increasing the risk of CVD in the 50–80 age group. Low doses of BPS have been shown to affect cardiac arrhythmias in female rats(Gao et al. 2015). BPS increased the pulse rate of the dorsal vessels in Lumbriculus variegatus(Vought and Wang 2018). Studies have also shown that long-term exposure to BPS can disrupt the body's immune response(Qiu et al. 2018). 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 defense in zebrafish(Qiu et al. 2019). The study found that immune system pathways were also affected by exposure to BPS in zebrafish embryos(Dong et al. 2018).
There are some limitations to our study. First, we used data from a cross-sectional- study precludes 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. Thirdly, the data came from the NHANES, and it can’t represent the whole situation in the world, and it need to be verified in other population.