Microplastics and Nanoplastics in Atheromas and Cardiovascular Events

Abstract

Background: Microplastics and nanoplastics (MNPs) are emerging as a potential risk factor for cardiovascular disease in preclinical studies. Direct evidence that this risk extends to humans is lacking.

Methods: We conducted a prospective, multicenter, observational study involving patients who were undergoing carotid endarterectomy for asymptomatic carotid artery disease. The excised carotid plaque specimens were analyzed for the presence of MNPs with the use of pyrolysis-gas chromatography-mass spectrometry, stable isotope analysis, and electron microscopy. Inflammatory biomarkers were assessed with enzyme-linked immunosorbent assay and immunohistochemical assay. The primary end point was a composite of myocardial infarction, stroke, or death from any cause among patients who had evidence of MNPs in plaque as compared with patients with plaque that showed no evidence of MNPs.

Results: A total of 304 patients were enrolled in the study, and 257 completed a mean (±SD) follow-up of 33.7±6.9 months. Polyethylene was detected in carotid artery plaque of 150 patients (58.4%), with a mean level of 21.7±24.5 μg per milligram of plaque; 31 patients (12.1%) also had measurable amounts of polyvinyl chloride, with a mean level of 5.2±2.4 μg per milligram of plaque. Electron microscopy revealed visible, jagged-edged foreign particles among plaque macrophages and scattered in the external debris. Radiographic examination showed that some of these particles included chlorine. Patients in whom MNPs were detected within the atheroma were at higher risk for a primary end-point event than those in whom these substances were not detected (hazard ratio, 4.53; 95% confidence interval, 2.00 to 10.27; P<0.001).

Conclusions: In this study, patients with carotid artery plaque in which MNPs were detected had a higher risk of a composite of myocardial infarction, stroke, or death from any cause at 34 months of follow-up than those in whom MNPs were not detected. (Funded by Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale and others; ClinicalTrials.gov number, NCT05900947.).

Figure 1.. MNPs in Carotid Artery Plaque.

Enrolled patients were screened for the presence of microplastics and nanoplastics (MNPs) in carotid artery plaque excised during endarterectomy (Panel A). Median and individual levels of polyethylene and polyvinyl chloride in excised carotid artery plaque that contained evidence of these compounds are shown in micrograms per milligram of atherosclerotic plaque (Panel B).

Figure 2.. Electron Microscopy Analysis of Atheromatous Plaque.

Panel A shows transmission electron microscopy images of particles of high internal electron transparency contoured by a very thin electron opaque line. These particles do not resemble usual organic material owing to their particularly irregular shape. These particles (arrows) were detected inside living macrophages and outside in the amorphous material of the plaque (arrows). Panel B shows images of the same specimen obtained with scanning electron microscopy using back-scattered electrons, which showed macrophages dispersed in the amorphous plaque material (arrows) and small particles of low-reflecting material contoured by a thin line of high-reflecting material identified in the plaque (red boxes).

Figure 3.. Inflammatory Markers in Plaque Samples.

Panels A through D show the abundance of interleukin-18, interleukin-1β, tumor necrosis factor α (TNF-α), and interleukin-6, respectively, assessed by means of enzyme-linked immunosorbent assay. Panels E, F, and G show the abundance of collagen, CD3, and CD68, respectively, measured by immunohistochemical assay in the group of patients with evidence of MNPs within the plaque and the group with no evidence of MNPs. Medians and individual values are shown.

Figure 4.. Associations between the Presence of MNPs and Cardiovascular Events.

Shown is the cumulative incidence curve of the composite outcome — nonfatal stroke, nonfatal myocardial infarction, or death from any cause. The results were estimated with the use of Cox regression analysis with adjustment for age, sex, body-mass index, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, creatinine, diabetes, hypertension, and previous cardiovascular events in the group of patients with evidence of MNPs in plaque and the group of patients with no evidence of MNPs in plaque. The inset shows the same data on an expanded y axis.