In a prospective observational study, patients with microplastics and nanoplastics (MNPs) in a carotid plaque had a higher risk of MI, stroke, or all-cause mortality compared with those with no MNPs. It should be noted this is no proof of causality.

This summary is based on the publication of Marfella R, Prattichizzo F, Sardu C, et al. - Microplastics and Nanoplastics in Atheromas and Cardiovascular Events. N Engl J Med. 2024 Mar 7;390(10):900-910. doi: 10.1056/NEJMoa2309822

Introduction and methods

Background

Recent preclinical studies (in human cells or tissues and animal models) have suggested microplastics and nanoplastics (MNPs) are a potential risk factor for CVD [1]. However, evidence of MNP infiltration into vascular lesions in humans is lacking, and an association between the burden of MNPs and CVD has not been established.

Aim of the study

The study aim was to investigate the presence of MNPs in atherosclerotic plaques excised from human carotid arteries and whether their presence is associated with CV events.

Methods

In this prospective observational study, 304 consecutive patients undergoing carotid endarterectomy for asymptomatic extracranial high-grade (>70%) internal carotid artery stenosis were included at 3 Italian hospitals from August 2019 through July 2020. The presence of 11 MNPs (microplastics are particles <5 mm and nanoplastics are particles <1000 nm) was measured in excised carotid artery plaque specimens using pyrolysis–gas chromatography–mass spectrometry, electron microscopy, and stable isotope analysis. Presence of inflammatory biomarkers (IL-18, IL-1β, IL-6, TNF-α ) were assessed with ELISA, whereas collagen content and CD3 and CD68 levels were examined using immunohistochemical assay. Mean ± SD follow-up time was 33.7 ± 6.9 months.

Outcomes

The primary endpoint was a composite outcome of nonfatal MI, nonfatal stroke, or all-cause mortality. Secondary endpoints included levels of inflammatory biomarkers, collagen, CD3, and CD68 in plaque samples.

Main results

Presence of microplastics and nanoplastics

• Of the 257 patients who completed the follow-up, 150 (58.4%) had a detectable amount of polyethylene in the excised carotid plaque (mean: 21.7 ± 24.5 μg/mg), of whom 31 (12.1%) also had a measurable amount of polyvinyl chloride (mean: 5.2 ± 2.4 μg/mg).
• With transmission electron microscopic analysis of 10 randomly selected samples that were positive for both polyethylene and polyvinyl chloride, particles with jagged edges that were probably of foreign origin were identified inside foamy macrophages present in the atheromatous plaque and in the amorphous material of the plaque. Almost all these particles were <1 μm (probably nanometers) in size.
• Scanning electron microscopy showed that some of these particles included chlorine.
• Linear regression analysis demonstrated a correlation between the amount of polyethylene and the expression levels of inflammatory biomarkers, collagen, and CD3 and CD68 (the latter being markers of lymphocyte and macrophage infiltration, respectively).

Association of microplastics and nanoplastics with CV events

• The incidence rate of the primary endpoint (i.e., nonfatal MI, nonfatal stroke, or all-cause mortality) was 20.0% (30/150) in the group of patients with evidence of MNPs (6.1 events per 100 patient-years) and 7.5% (8/107) in those with no evidence of MNPs (2.2 events per 100 patient-years). The HR adjusted for CVD risk factors at 34 months of follow-up was 4.53 (95%CI: 2.00–10.27; P<0.001).
• When MNP levels were analyzed as a continuous variable, there was an association with the primary endpoint.

Conclusion

This Italian, prospective, observational study among patients with asymptomatic carotid artery disease undergoing carotid endarterectomy demonstrated that nearly 60% had a detectable amount of polyethylene in the excised carotid plaque and 12% also had a measurable amount of polyvinyl chloride. Patients with evidence of MNPs had a higher risk of MI, stroke, or all-cause mortality at 34-month follow-up compared with those in whom no MNPs were detected. The author stress that their results are no proof of causality: “The association between the presence of MNPs within plaque[s] and the incidence of a composite of cardiovascular disease or death outcomes may also entail the risk from exposure to other residual, unmeasured confounding variables, such as unknown exposures during the life course of the patient or, more broadly, the health status and behaviors of the patients.” They also point out that “[d]espite the preventive measures adopted, laboratory contamination cannot be firmly ruled out.”

Reference

1. Zhu X, Wang C, Duan X, Liang B, Genbo Xu E, Huang Z. Micro- and nanoplastics: a new cardiovascular risk factor? Environ Int 2023; 171: 107662.

Find this article online at N Engl J Med.