Microplastics and Nanoplastics in Atheroma and Cardiovascular Events

BLUF (Bottom Line Up Front):

In a recent study by Marfella et al. in The New England Journal of Medicine on microplastics and nanoplastics (MNPs) within atherosclerotic plaques found a significant association with increased risk of cardiovascular events. This research has not only characterized MNPs as an environmental hazard but now highlights them as a significant health risk. The message is clear to limit exposure to these particles. However, it's vital to adopt a sensible approach, avoiding alarmist reactions. Exposure to MNPs is inevitable in our current environment, but steps can be taken to mitigate this exposure and, in turn, reduce health risks. Importantly, the focus should also remain on broader cardiovascular health strategies. Ensuring minimal plaque development is critical, without plaque, the risk of Atherosclerotic cardiovascular diseases (ASCVD) diminishes significantly. Maintaining a healthy lifestyle, including regular exercise,

controlling blood pressure, avoiding smoking, and managing lipid profiles, is paramount.  Together, these strategies offer a balanced approach to reducing not just MNPs exposure but also the overall risk of developing ASCVD, highlighting a comprehensive path forward in safeguarding our health against emerging environmental and health challenges.

Introduction:

MNP are fragments of plastic materials measuring less than 5mm for microplastics and less than 100nm for nanoplastics, have emerged as pervasive environmental pollutants. These tiny particles originate from the breakdown of larger plastic debris, a consequence of physical, chemical, and biological degradation processes. Common sources include packaging materials, textiles, tyres, and personal care products that shed microbeads. Additionally, industrial processes and waste management practices contribute to their dissemination into the environment.

MNPs have been detected across diverse ecosystems, from the most remote areas to densely populated urban centers. They are found in marine waters, freshwater systems, soils, air, and even Arctic ice, illustrating their extensive dispersion facilitated by water currents, wind, and animal vectors. The abundance of MNPs in the environment has been steadily increasing, echoing the global increase in plastic production, which exceeds 300 million tonnes annually. Their global presence is primarily attributed to the durability of plastics, which can persist in the environment for hundreds to thousands of years, coupled with inadequate waste management and recycling practices worldwide.

This spread of MNPs in the environment poses significant ecological problems. They have been found inside a vast array of organisms, including fish, birds, and mammals, often causing physical harm, chemical exposure, and even mortality. Microplastics can absorb and concentrate environmental pollutants, acting as vectors for transporting toxic substances into food webs. Their presence in the environment also affects biodiversity, habitat functionality, and the health of ecosystems.

The recognition of MNPs as an environmental issue has been established for some time; however, their identification as a potential health problem is more recent. Research indicates that humans are exposed to MNPs through various pathways, including consumption of contaminated food and water, inhalation of air particles, and through the skin. Emerging evidence links MNPs to inflammatory responses, oxidative stress, and genotoxicity in human cells and model organisms, raising concerns about their potential role in the development of various diseases, including cardiovascular diseases, as highlighted in recent studies.

The convergence of environmental science and public health research on MNPs highlights the urgency of addressing plastic pollution not only to protect ecosystems but also to safeguard human health. As the body of evidence grows, it becomes increasingly clear that the issue of MNPs requires concerted global action, spanning from reducing plastic production and improving waste management to conducting comprehensive health impact assessments.

In a recent publication in The New England Journal of Medicine, Marfella et al. (2024) provided compelling evidence that MNPs present in atherosclerotic plaques are significantly associated with an increased risk of cardiovascular events,highlighting the relationship between environmental pollution and human health.

Paper Overview

The primary purpose of the study was to investigate the potential association between the presence of microplastics and MNPs within atherosclerotic plaque and the incidence of cardiovascular events in humans. This research appears against a backdrop of increasing preclinical evidence suggesting that MNPs could represent a novel risk factor for cardiovascular diseases. The hypothesis suggests that MNPs, once integrated into human tissues, particularly within arterial plaque, might contribute to or exacerbate cardiovascular pathologies, leading to an increased risk of events such as myocardial infarction, stroke, or death.

This hypothesis was based on the known mechanisms by which MNPs have been suggested to impact vascular health, including inducing oxidative stress, inflammation, and apoptosis in endothelial and other vascular cells. The researchers aimed to extend these observations from preclinical models to a human population, thereby addressing a significant gap in our understanding of the implications of environmental pollution on cardiovascular health. By focusing on patients undergoing carotid endarterectomy (a procedure to remove atherosclerotic plaque from the carotid artery) the study provided a direct assessment of the presence of MNPs in vascular lesions and their potential contribution to cardiovascular risk.

What Did They Test

The study specifically investigated the presence and concentration of MNPs in atherosclerotic plaque specimens excised from patients undergoing carotid endarterectomy for asymptomatic carotid artery disease.

The aim was to detect and quantify MNPs within the excised atherosclerotic plaque. The study focused on identifying the types of plastics present in the plaques, with a  particular emphasis on polyethylene and polyvinyl chloride, which were the main MNPs of interest based on their prevalence and potential health impacts.

As well as just identifying the presence of MNPs, the study wanted to see if these findings correlated with cardiovascular outcomes. The primary endpoint was a composite of myocardial infarction, stroke, or death from any cause, comparing patients with MNPs detected in their plaque to those without.

To further understand the potential mechanisms behind the observed associations, the study also evaluated the levels of various inflammatory biomarkers in the plaques, such as interleukins and tumor necrosis factor-alpha, through enzyme-linked immunosorbent assay (ELISA) and immunohistochemical assays.

By examining these components, the study aimed to establish a direct link between

environmental pollution, specifically the presence of MNPs in vascular tissues, and the risk of cardiovascular events, thereby contributing to our understanding of how synthetic pollutants may impact human health.

Findings

MNPs were detected in the carotid artery plaque of a significant proportion of the patient population. Specifically, polyethylene was found in 58.4% of patients (150 out of 257), with a mean level of 21.7±24.5 μg/mg of plaque. Polyvinyl chloride was also detected in 12.1% of patients (31 out of 257), with a mean level of 5.2±2.4 μg/mg of plaque. This confirms the presence of these particles within atherosclerotic lesions.

Patients with MNPs detected within their atherosclerotic plaque exhibited a significantly higher risk of experiencing a myocardial infarction, stroke, or death from any cause, compared to those without MNPs. The study reported a hazard ratio of 4.53 (95% confidence interval, 2.00 to 10.27; P<0.001), indicating a statistically significant more than fourfold increase in risk.

The study also explored the relationship between the presence of MNPs and levels of inflammatory biomarkers within the plaque. Patients with MNPs in their plaque showed elevated levels of inflammatory markers, suggesting a potential mechanism through which MNPs could contribute to cardiovascular risk.

These findings highlight the potential of MNPs as a novel risk factor for cardiovascular disease, linking environmental pollution more closely with human health outcomes as well as a step forward in understanding the broader implications of plastic pollution, especially concerning heart health and the potential for MNPs to drive inflammatory processes within vascular lesions.

What do these findings mean?

The detection of MNPs in carotid artery plaques and their association with increased cardiovascular events introduce MNPs as a new environmental risk factor for cardiovascular disease. This expands our understanding of heart disease aetiology to include environmental pollutants not previously considered in this context.

The correlation between MNPs presence and elevated inflammatory biomarkers within the plaque suggests a potential mechanism of action. MNPs may contribute to cardiovascular risk through promoting inflammation within vascular lesions, a known pathogenic pathway in atherosclerosis development and progression. This insight is crucial for developing targeted interventions to mitigate the risk associated with MNPs.

These findings signal significant public health and environmental concerns, highlighting the need for strategies to reduce MNP pollution. Given the widespread use and persistence of plastics in the environment, this research underscores the importance of re-evaluating waste management practices and reducing plastic use to mitigate cardiovascular health risks.

The study highlights the necessity for further research to explore the prevalence of MNPs across more diverse populations and settings, their precise mechanisms of contributing to cardiovascular pathology, and effective interventions to minimize exposure and associated health risks.

How does this affect you?

The findings have several implications for lifestyle changes aimed at reducing exposure to these pollutants and mitigating their potential health risks. Here are practical recommendations for individuals seeking to minimize their MNP exposure and, by extension, potentially reduce their cardiovascular risk:

Reduce Plastic Use: Choose alternatives to single-use plastics in daily life. Use reusable bags, bottles, and containers made from safer, sustainable materials like glass, stainless steel, or bamboo. Reducing reliance on plastic products can decrease the overall production and eventual breakdown into MNPs. Many canned foods use cans lined with plastic containing bisphenol A (BPA). Seeking out BPA-free cans can reduce your exposure not only to BPA but also to the microplastics that may derive from these plastic linings.

Refrain from Heating Foods in Plastic Containers: When heating food, choose glass or ceramic containers instead of plastic. Heating plastic can lead to the leaching of chemicals and potentially MNPs into the food, increasing your exposure. Glass and ceramic are safer alternatives that do not pose this risk.

Choose Natural Fibers: Wear clothing made from natural fibers such as cotton, wool, silk, or hemp instead of synthetic fibers, which shed plastic microfibers into the environment, especially during washing. Also, use natural fiber cleaning utensils such as sponges and brushes.

Be Mindful of Cosmetics and Personal Care Products: Avoid cosmetics, toothpastes, and skincare products containing microbeads or polyethylene. Look for products with natural ingredients or those labeled as "microplastic-free."

Proper Plastic Disposal and Recycling: Dispose of plastic waste properly and participate in recycling programs. Proper waste management reduces the likelihood of plastics breaking down into MNPs in the environment.

Support and Advocate for Environmental Policies: Support policies and initiatives aimed at reducing plastic pollution, increasing recycling efforts, and developing biodegradable alternatives to conventional plastics. Participate in or organize local clean-up efforts to reduce plastic waste in your community, including beaches, rivers, and urban areas.

Summary:

This study shows a correlation that individuals with microplastics and nanoplastics (MNPs) detected in carotid plaques have a significantly higher incidence of myocardial infarction (MI), stroke, or death from any cause compared to those without MNPs in their atheroma. This finding draws attention to the potential cardiovascular (CV) effects of MNPs, supported by mechanistic data from preclinical models suggesting both the direct translocation of MNPs into circulation and indirect mechanisms. However, the study also acknowledges the complexity of this association, noting the potential for other residual, unmeasured confounding variables, such as unknown exposures throughout a patient's life or broader aspects of health status and behaviours that may influence these outcomes. This underscores the necessity for further prospective studies to clarify these relationships.

Incorporating lifestyle changes to reduce MNP pollution can lower the risk of adverse health outcomes, highlighting the role of individual actions and the need for collective efforts and systemic changes to tackle the root causes of plastic pollution and its health impacts. The recognition of MNPs as a health risk, in addition to being an environmental hazard, necessitates a pragmatic approach to mitigate exposure while acknowledging the inevitability of encountering these particles. Importantly, the strategy to prevent atherosclerotic cardiovascular diseases (ASCVD) extends beyond merely reducing MNP exposure. The absence or minimisation of arterial plaque is key to reducing ASCVD risk.

Therefore, maintaining a healthy lifestyle, including regular physical activity, blood pressure control, smoking cessation, and lipid profile management, is essential. These proactive health measures, alongside efforts to decrease exposure to MNPs, provide a comprehensive defence against the risks posed by both environmental pollutants and traditional cardiovascular risk factors.

Marfella R, Prattichizzo F, Sardu C, Fulgenzi G, Graciotti L, Spadoni T, D'Onofrio N, Scisciola L, La Grotta R, Frigé C, Pellegrini V, Municinò M, Siniscalchi M, Spinetti F, Vigliotti G, Vecchione C, Carrizzo A, Accarino G, Squillante A, Spaziano G, Mirra D, Esposito R, Altieri S, Falco G, Fenti A, Galoppo S, Canzano S, Sasso FC, Matacchione G, Olivieri F, Ferraraccio F, Panarese I, Paolisso P, Barbato E, Lubritto C, Balestrieri ML, Mauro C, Caballero AE, Rajagopalan S, Ceriello A, D'Agostino B, Iovino P, Paolisso G. Microplastics and Nanoplastics in Atheromas and Cardiovascular Events. N Engl J Med. 2024 Mar 7;390(10):900-910. doi: 10.1056/NEJMoa2309822. PMID: 38446676.

By Dr Andrew Crockett