Serum levels of non-persistent environmental pollutants and risk of incident hypertension in a sub-cohort from the EPIC study

Highlights

• Concentrations of 7 npEPs were quantified in serum from 670 adults.

• Detection rates ranged from 19.6% (BP) to 88.5% (MP).

• PP concentrations were positively associated with AHT risk.

• No associations were found for the rest of pollutants.

Abstract

Background

The prevalence of arterial hypertension (AHT), a well-known risk factor for cardiovascular disease, has considerably increased over last decades. Non-persistent environmental pollutants (npEPs) are a group of ubiquitous chemicals, widely used in consumer products such as food packaging and cosmetics, which have been identified as endocrine disrupting chemicals and obesogens. The aim of this study was to assess the potential associations of serum levels of three groups of npEPs with the risk of incident AHT.

Methods

Cohort study within a sub-cohort of Granada EPIC-Spain center (n = 670). We quantified serum concentrations of three groups of npEPs, i.e., bisphenol A (BPA), four parabens: methylparaben (MP), ethylparaben (EP), propylparaben (PP) and butylparaben (BP), and two benzophenones: benzophenone 1 (BP1), benzophenone 3 (BP3), in samples collected at recruitment. Statistical analyses were performed by means of Cox Proportional Hazard Models.

Results

Median follow-up time was 23 years. BPA and MP were found in >80% of the study population. Individuals within the 4th PP quartile (0.53–9.24 ng/ml) showed a statistically significant increased risk of AHT (HR = 1.40, p = 0.015). No associations were found for the rest of pollutants.

Conclusions

Overall, we evidenced no associations of most npEPs with AHT risk, with the exception of an increased risk in the highest PP percentiles. Considering the limitations of using one spot serum sample for exposure characterization, further research on the potential contribution of npEPs on the development of AHT risk is warranted.

Introduction

The global prevalence of Arterial hypertension (AHT) has markedly increased over last decades, reaching 40% of adults >25 years old in 2010 (Mills et al., 2016; WHO, 2013). The worldwide age-standardized prevalence of raised blood pressure (systolic blood pressure [SBP] ≥140 mm Hg or diastolic blood pressure [DBP] ≥90 mm Hg) in adults was estimated as ≥ 20% in 2015 (Stanaway et al., 2018; Zhou et al., 2017). In addition, SBP >115 mm Hg has been considered as the leading risk factor for the global burden of disease in 2017 (Stanaway et al., 2018).

External and potentially-modifiable risk factors affecting the development of AHT include unhealthy diet (e.g. high salt intake), lack of physical activity, obesity, smoking, and exposure to persistent stress (WHO, 2013). Among environmental aspects, the role of chronic exposure to low doses of ubiquitous environmental pollutants is of increasing concern (Ahmadkhaniha et al., 2014; Amin et al., 2019; Duan et al., 2018; Gong et al., 2013; Grice et al., 2017; Hwang et al., 2018; Ngwa et al., 2015; Provvisiero et al., 2016; Ruzzin et al., 2010; Silver et al., 2011; Yang et al., 2017). Specifically, there is a group of widely-used chemicals, known as non-persistent environmental pollutants (npEPs) (Artacho-Cordón et al., 2018). Among them, Bisphenol A (BPA) is an industrial chemical originally developed as a synthetic oestrogen, widely used in the manufacture of polymers and epoxy resins, as well as in polycarbonate and polysulfone plastics. BPA is one of the highest volume chemicals produced worldwide (Mcgroup, 2013) and, consequently, the general population is frequently and inadvertently exposed to this chemical (Geens et al., 2012; vom Saal and Hughes, 2005). In this regard, it has been estimated that >90% of the general population in the US, Europe and Asia present detectable values of BPA (Hormann et al., 2014; Liao and Kannan, 2012; Vandenberg et al, 2009, 2010). Diet is considered the main exposure route to BPA in the general population, since it is frequently present in food packaging, e.g., tins, cans, or plastic boxing, from which BPA can migrate to the food under certain environmental conditions (Brotons et al., 1995; Ćwiek-Ludwicka, 2015; Geens et al., 2012; Grumetto et al., 2008; Hahladakis et al., 2018; Huang et al., 2017; López-Cervantes and Paseiro-Losada, 2003).

On the other hand, parabens (PBs) are widely used as antimicrobial preservatives in cosmetics, pharmaceuticals, food and beverages (Cosmetic Ingredient Review, 2008) and Benzophenones (BPs) are synthetic chemicals frequently used in personal care products UV filters (Louis et al., 2014). BPs have been detected in urine and some other biological matrices, such as placenta (Vela-Soria et al., 2011), human breast milk (Schlumpf et al., 2008) and menstrual blood (Jiménez-Díaz et al., 2016).

In general, npEPs are rapidly eliminated from humans. Indeed, BPA is readily glucuro-conjugated or sulfo-conjugated in the liver, and finally excreted in urine, once absorbed in the intestine (half-life in humans: 7–8 h) (vom Saal and Hughes, 2005). In the same way, PBs and BPs are also rapidly metabolized and excreted from the body, mainly during the first 24 h after exposure (Błędzka et al., 2014; Soni et al., 2005; Watanabe et al., 2015).

These npEPs are considered potential metabolic and endocrine disruptors, since they can induce metabolic syndrome–related conditions (Casals-Casas and Desvergne, 2011; Heindel et al., 2015). In this regard, these pollutants can act as obesogens, which are functionally defined as chemicals that promote obesity and, thus, obesity-related diseases, including insulin resistance, cardiovascular disease or even cancer (Hwang et al., 2018; Shankar and Teppala, 2012; Trasande et al., 2012) in humans or animals (Grü;n and Blumberg, 2006). Suspected biological mechanisms include thyroid dysfunction (Streeten et al., 1988), weight gain (Juhaeri et al., 2002), insulin resistance (Sowers, 2004), hyperlipidaemia (Laaksonen et al., 2008), oxidative stress (Rodrigo et al., 2007), and higher systemic inflammation (Lakoski et al., 2006). However, the implications of npEP exposure and AHT to the general population are still controversial due to the lack of homogeneous results (Bae et al., 2012; Bae and Hong, 2015; Gao and Wang, 2014; Shankar et al., 2012; Shankar and Teppala, 2012; Shiue, 2014a, 2014b).

The present study, which is framed within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, aims to assess longitudinal associations of serum concentrations of selected npEPs at recruitment with the risk of incident AHT.