A systematic review and meta-analysis of literature on the association between environmental endocrine disrupting chemicals (EDCs) and cardiovascular diseases was published on April 9, 2020, in the peer-reviewed journal Environmental Research. Xiangjun Fu and colleagues from the School of Public Health, Zunyi Medical University, Guizhou, PR China, analyzed 29 eligible studies with “a total sample size of 88,891” and found significant cardiovascular disease (CVD) associations for several groups of examined substances. Among others, exposure to phthalates and bisphenol A (BPA, CAS 80-05-07) was found to be positively associated with CVD risk (odds ratio (OR) of 1.11 with 95% CI 1.06-1.17 for phthalates and OR of 1.19 with 95% CI 1.03-1.37 for BPA). The authors concluded that “long-term exposure [to EDCs] can influence cardiovascular health in humans.”

An article published on October 14, 2020, in the peer-reviewed journal Science of the Total Environment, reported on the epidemiological analysis of a potential association between bisphenol A and cardiovascular disease. Shinje Moon and colleagues from the Departments of Internal Medicine in Colleges of Medicine from Hallym University and Hanyang University, both Seoul, Republic of Korea, first examined the data collected during 2003-2016 within the US National Health and Nutrition Examination Survey (NHANES). They collected records of BPA concentrations in the urine, adjusted them for creatinine (Cr, ng/mg) and normalized using natural logarithmic transformation. In this way obtained ln-BPA/Cr values were then used as a predictor in a multivariate logistic regression analysis performed to estimate the odds ratio (OR) and 95% confidence interval (CI) for CVD. This analysis of NHANES data, performed with 11,857 adults, showed that “after adjusting for age, sex, race/ethnicity, body mass index (BMI), cigarette smoking, diabetes status, hypertension, and dyslipidemia, OR between ln-BPA/Cr and CVD was 1.13 (95% CI: 1.02-1.24).” The OR continued to be significant (1.18; 95% CI: 1.04-1.33) even after propensity-score-matching with some of the potential confounding factors, and “a restricted cubic spline plot of this relationship revealed a dose-dependent increase in OR.” In addition, the authors performed “a Mantel-Haenszel meta-analysis with [additional] five eligible studies and NHANES 2003-2016 data,” including 22,878 human subjects in total. In this analysis, similar to the NHANES-only study, “after adjusting for age, sex, and various cardiometabolic risk factors, OR was 1.13 (95% CI, 1.03-1.23).” They concluded that their work “provides additional epidemiological evidence supporting an association between BPA and CVD.”

In contrast to the above-discussed study, no association was found between the frequency of BPA detection in serum (at values >0.2 ng/ml) and risk of ischemic heart disease. This study, described in an article published on July 20, 2020, in the peer-reviewed journal Chemosphere, by Elena Salamanca-Fernandez and colleagues from the Andalusian School of Public Health (EASP), Granada, Spain, involved 4,636 participants followed for 16 years within the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC). BPA levels were measured in serum samples collected upon participant recruitment, and “follow-up was performed by linking with national and regional databases and reviewing patients’ clinical records.” The authors “evidenced a similar percentage of detection of BPA among cases [(946 subjects who developed ischemic heart disease)] and sub-cohort participants [(3,690 subjects)]” from the followed population, and thus found “no clear association” with risk of ischemic heart disease. However, it was acknowledged that “further investigation is needed,” which should be focused, for example, not only on a one-time detection frequency per se, which was very high in both case and control populations, but also on differentiating between high and low exposure levels.

A review by Zena Wehbe and colleagues from the Department of Biology, American University of Beirut, Lebanon, published on February 29, 2020, in the peer-reviewed journal Current Hypertension Reports, provides a “critical summary of existing findings on BPA and hypertension, with particular attention to genomic, non-genomic, molecular, and cellular mechanisms of action.” The authors suggested that BPA can disrupt cardiovascular health due to its interaction with both cytosolic and membrane-located estrogen receptors, particularly because “estrogen plays an important role in cardiovascular physiology.” They concluded that “existing literature, though limited, established BPA as a source of disruption in cardiovascular health, particularly hypertension,” and noted that “effects of BPA are largely dependent on the dose, patient gender, tissue, and developmental stage of the exposed tissue/organ.”

An article published on June 12, 2020, in the peer-reviewed journal Environmental Pollution, focused on the associations between maternal BPA exposure during pregnancy and cardio-metabolic risk factors in children at 2 years of age. This prospective cohort study was carried out with 2018 pregnant women enrolled during 2012-2013. Urinary BPA concentrations were measured in both pregnant mothers (detected in 98.2%) and children during their 2nd year check-up (detected in 99.4%). The examined cardio-metabolic risk factors included anthropometric measurements of child adiposity, random morning plasma glucose, serum insulin and lipids, as well as systolic and diastolic blood pressure. Higher blood pressure was found in girls prenatally exposed to higher BPA concentrations, but not in boys. However, in boys, higher plasma glucose concentrations were found in some cases. None of the other examined cardio-metabolic risk factors were associated with prenatal BPA exposure. BPA exposure in children also showed no association with any of the examined parameters. The authors concluded that “BPA exposure during prenatal period,” which is a “susceptible time for for fetal development,” may be associated “in a sex-specific manner” with increased blood pressure and glucose levels in young children. However, “further independent cohort studies are needed to confirm these findings.”

In an article published on July 21, 2020, in the peer-reviewed journal Birth Defects Research, Manelle Ramadan and colleagues from Children’s National Hospital, Washington DC, US, presented a review of the “literature on environmental and clinical exposures to bisphenols and phthalates.” A particular focus was on BPA and di-2-ethyl hexyl phthalate (DEHP, CAS 117-81-7), with the aim to “highlight experimental work that suggests that these chemicals may exert a negative influence on cardiovascular health, and emphasize areas of concern that related to vulnerable pediatric groups.” The authors emphasized that associations between EDC exposure and cardiovascular health outcomes are “particularly worrisome for sensitive populations, including fetal, infant and pediatric groups—with underdeveloped metabolic capabilities and developing organ systems.” They further discussed “gaps in our current knowledge” and future research necessary “to resolve the relationship between chemical exposures and the impact on pediatric cardiovascular physiology.” The authors underscored the importance of collaborative work “between investigators with expertise in epidemiology, clinical, and basic science to fully address cardiovascular health concerns related to ‘plastic’ exposure.” They further highlighted the need for more studies focused on mixture effects as well as on the cardiac safety profiles of BPA and DEHP alternatives.

Similar conclusions were reached in another review focused on the mechanisms of cardiovascular toxicity of BPA and one of its alternatives, bisphenol S (BPS, CAS 80-09-1), published on March 18, 2020, in the peer-reviewed journal Science of the Total Environment. Yin-Feng Zhang and colleagues from Qingdao University and Ningxia Medical University, both in China, compiled “striking evidence of the correlation between BPA exposure and various CVDs” and observed that “a nonmonotonic dose-response curve (NMDRC) was common in studies of the CV effects of BPA in vivo.” Therefore, they suggest that “the CV impairment induced by low doses of BPA should be highlighted, especially during developmental exposure or during co-exposure with other risk factors.” Emerging evidence for BPS also shows its potential involvement in CVD. Therefore, the authors called for “immediate epidemiological investigations and animal studies to reveal the relationships of BPS and other BPA alternative with human CVDs.” Overall, studies on bisphenols and CVD “should be strengthened, especially with respect to the mechanisms, prevention and treatment.”

References

Moon, S., et al. (2020). “Effects of Bisphenol A on cardiovascular disease: An epidemiological study using National Health and Nutrition Examination Survey 2003-2016 and meta-analysis.Science of the Total Environment DOI 10.1016/j.scitotenv.2020.142941 (published October 14, 2020).

Fu, X., et al. (2020) “The association between environmental endocrine disruptors and cardiovascular diseases: A systematic review and meta-analysis.Environmental Research 187: 109464.

Ouyang, F., et al. (2020) “Maternal prenatal urinary bisphenol A level and child cardio-metabolic risk factors: A prospective cohort study.Environmental Pollution 265: 115008.

Ramadan, M., et al. (2020). “Bisphenols and phthalates: Plastic chemical exposures can contribute to adverse cardiovascular health outcomes.Birth Defects Research 112: 1362-1385.

Salamanca-Fernandez, E., et al. (2020). “Bisphenol A exposure and risk of ischemic heart disease in the Spanish European Prospective Investigation into cancer and nutrition study.Chemosphere 261: 127697.

Wehbe, Z., et al. (2020). “Estrogen and bisphenol A in hypertension.Current Hypertension Reports 22: 23.

Zhang, Y.-F., et al. (2020). “Cardiovascular toxicity and mechanism of bisphenol A and emerging risk of bisphenol S.Science of the Total Environment 723: 137952.

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