New review unravels role of phthalates in heart disease

Phthalates are essential elements in the plastics industry and, as a result, are often found as contaminants throughout the environment. In the environment, phthalates can disrupt endocrine functions by being easily absorbed by humans and binding to molecules that interfere with hormone imbalance. Thus, phthalate exposure can lead to a variety of diseases, particularly cardiovascular diseases (CVDs), at all ages.

In a recent review published in Hazardous Material Diaryresearchers review existing data on the impact of phthalate exposure on cardiovascular health.

To study: Exposure to phthalates leads to a growing concern for cardiovascular health. Image credit: Fer Gregory / Shutterstock.com

About the review

Databases such as Web of Science, Scopus, and PubMed were searched for relevant records published between 2015 and April 2022. Only experimental or epidemiological studies in humans that included men and women and assessed the impact of phthalate exposure on risk of CVD among individuals of all ages were included. Non-human studies, duplicate records, inaccessible records, and studies published in languages ​​other than English were excluded.

What are phthalates?

Phthalates are chemicals categorized by the US Environmental Protection Agency (EPA) as priority environmental pollutants.

High molecular weight phthalates are used to improve the elasticity and flexibility of polymers such as polyvinyl chloride (PVC) in various industrial and household products such as furniture, tiles, adhesives, paints, waterproofs, shower curtains, upholstery from automobiles, shoes, dust, food packaging, medical devices, diapers and toys. Low molecular weight phthalates are used as additives and solvents in paints, sinks and personal care products such as cosmetics.

Phthalates are able to leach into the environment as they do not covalently bond to polymers. Phthalates have been identified in water, air, food, consumer products and biological fluids such as blood, urine, amniotic fluid, saliva and human milk.

Inhalation, ingestion and skin absorption are the main routes of exposure. However, prenatal and intravenous exposure during medical interventions is also of concern.

Effects of phthalate exposure on cardiovascular health

Exposure to certain phthalates, including monomethyl phthalate (MMP) and monobenzyl phthalate (MBzP), can promote atherosclerosis by facilitating carotid artery plaque formation and altering carotid intima-media thickness (CIMT).

Exposure to bis(2-ethylhexyl)phthalate (DEHP) promotes endothelial cell apoptosis, alters deoxyribonucleic acid (DNA) methylation, and facilitates atherosclerosis due to its pro-atherogenic and pro-senescence activities, with inhibition of cholesterol efflux per altered microRNA 200 c (miR200c) -5p-ATP-binding cassette subfamily A activity member 1 (ABCA1). DEHP also increases the expression of plasminogen activator type 1 inhibitor and has procoagulant effects.

Phthalates such as DEHP and metabolites of di-n-butyl phthalate (DBP), including mono-2-ethylhexyl phthalate (MEHP), monobutyl phthalate (MBP) and mono-isobutyl phthalate (MiBP) may increase levels of atherothrombotic markers, such as fibrinogen, plasma D-dimer and high-sensitivity C-reactive protein among patients with coronary artery disease (CAD).

Phthalates, such as MEP, alter blood pressure by potentiating peroxisome proliferator-activated receptor gamma (PPARγ) activity and inhibiting the renin-angiotensin-aldosterone system (RAAS). Interestingly, maternal exposure to phthalates lowers blood pressure (BP) in offspring, while direct exposure to phthalates among children increases BP. In addition, exposure to MEP increases the risk of preeclampsia due to increased levels of soluble fms-like tyrosine kinase 1 and placental growth factor (sFlt-1/PlGF), increased oxidative stress, and production of inflammatory cytokines.

DEHP alters cardiac electrical conduction by decreasing the expression of genes associated with the electrical activity of cardiac cells and calcium transport, including connexin 43, calponin, and calsequestrin, and by reducing calcium levels in the sarcoplasmic reticulum.

Exposure to phthalates, particularly DEHP, may impair the recovery of patients undergoing cardiac surgery due to decreased cell viability and mitochondrial membrane potential, increased leakage of lactate dehydrogenase (LDH) and production of reactive oxygen species (ROS ), promoting apoptosis in cardiomyocytes.

Exposure to certain phthalates, especially MBP, can lead to stroke due to interruptions in the glycolytic pathway and inhibition of proteins associated with DNA transcription and ribonucleic acid (RNA) biogenesis. Furthermore, phthalates increase cardiometabolic risks such as diabetes by increasing gestational weight gain, impairing glucose tolerance, increasing insulin resistance, and altering pyrimidine, amino acid, and galactose metabolism.

Phthalate exposure can also cause obesity due to increased levels of triglycerides and total cholesterol. Furthermore, phthalates disrupt hormonal balance due to their antiandrogenic, estrogenic, and antithyroid effects.

Conclusions

Based on the review findings, CVDs can develop among individuals of all ages and genders who are frequently exposed to phthalates.

Consumption of phthalates can be reduced by minimizing intake of canned and packaged foods and using stainless steel, porcelain, glass or eco-friendly “green” products instead of plastics. The general public should also be educated about the harmful effects of phthalates and their presence in various everyday products and the environment.