plastics: too many and too bad for our bodies
A recent Italian study found that microplastics detected in carotid artery plaques were associated with an increased risk of subsequent cardiovascular events (see cardiovasc plastics increase NEJM2024 in dropbox, or DOI: 10.1056/NEJMoa2309822)
Details:
-- 257 patients who had asymptomatic carotid artery disease were enrolled in this prospective, multicenter, observational study; these patients underwent carotid endarterectomy (all patients had >70% carotid artery stenosis) with specimens analyzed for the present of microplastics and nanoplastics (MNPs), from 2019-2020
-- mean age 72, males 75%, BMI 28rom 1019-2020
-- hypertension 73%, blood pressure 126/77, 20% smokers, heart rate 83, diabetes 34%, cardiovascular disease 42%, dyslipidemia 47%, total cholesterol 148/HDL 42/LDL 75/triglycerides 180
-- medications: beta blockers 41%, ACE inhibitors 65%, ARBs 26%, calcium blockers 10%, diuretics 17%, antiplatelet drugs 97%, statins 95%, ezetimibe 18%
-- median carotid stenosis: 77%
-- those with MNPs present tended to be somewhat younger (71 versus 73 years old), more often male, more often had the comorbidities of hypertension, smoking, increased heart rate, diabetes, cardiovascular disease, LDL cholesterol (77 versus 74 mg/dL), and be on calcium blockers (though less likely to be on diuretics or ARBs)
-- primary endpoint: composite of myocardial infarction, stroke, or death from any cause, comparing those with, versus patients without, carotid artery plaque MNPs
-- the analysis below was adjusted for age, sex, BMI, total cholesterol, HDL, LDL, triglycerides, creatinine, diabetes, hypertension, and prior cardiovascular events
-- inflammatory biomarkers were also assessed, including IL-18, IL-1b,TNF-a, and IL-6
-- Follow-up 34 months
Results:
-- no apparent difference in the incidence of MNPs by the geographic area where they lived
-- MNPs detected in the coronary artery plaques:
-- polyethylene: found in 150 patients (58.4%), mean level 21.7 +/- 24.5 µg per mg of plaque
-- in those having polyethylene, polyvinylchloride was also present in 31 patients (12.1% of the total): mean level 5.2 +/- 2.4 µg per mg of plaque
-- electron microscopy: visible, jagged-edged foreign particles were found among plaque macrophages, almost all smaller than 1µm (probably nanometers in size)
-- some of these particles included higher levels of chlorine (eg, from polyvinylchloride), and lower levels of carbon and oxygen
-- isotopic assessment of carbon (carbon-13 versus carbon-12) in the plaques suggested contamination with petroleum-derived material, since these plastics detected had lower carbon-13 levels than is found in human tissue
--inflammatory markers:
-- MNPs present vs absent: significant increases in interleukin-18, interleukin-1beta, interleukin-6, and TNF-alpha
-- Cardiovascular events:
-- MNPs present: 30 of 150 patients (20%), 6.1 events per 100 person person-years
-- MNPs absent: 8 of 107 patients (7.5%), 2.2 events per 100 person-years
-- 4-5x the event rate, HR 4.53 (2.00-10.27), p<0.001
-- when the levels of MNPs were evaluated as a continuous variable, there was a dose-dependent relationship (the higher the level of MNPs, the more cardiovascular events)
of note, these curves are splaying apart, suggesting that longer follow-up would yield even worse outcomes for those with MNPs!!!
Commentary:
-- as we all know, plastics are omnipresent in our world, and the production of plastics is increasing, expected to continue increasing until 2050 (https://www.science.org/doi/10.1126/sciadv.1700782)
-- other studies have found that 25% of the whole blood samples from healthy volunteers had a maximum polyethylene concentration of 7.1 µg per mL
-- human studies have detected MNPs in the placenta, lungs, liver, breast milk, urine and blood; polyethylene and polyvinylchloride were the most abundant MNPs found
-- and these little plastic particles find many ways to enter our bodies: ingestion of contaminated foods (including bottled water: https://www.cnn.com/2024/01/
-- MNPs promote oxidative stress, inflammation and apoptosis of vascular cells, including endothelial cells, leading to endothelial dysfunction, myocardial fibrosis, and impaired cardiac function in animals
-- MNPs have been shown to induce pro-inflammatory pathways
-- this study found that MNPs are in fact incorporated in human atherosclerotic plaque, and when found, are associated with inflammatory cytokines as well as a really large increase in adverse cardiovascular effects (the composite of MI, stroke or death from any cause); this increase in adverse events had an increasing trajectory over the short period of this study (34 months). What would be the longer-term risks??? very concerning since MNPs are found in the placenta/breast milk, and in younger adults
-- in particular, this study found that the “large majority” of MNPs were below the 200nm or 10 µm in diameter that penetrate blood vessels and are absorbed into the blood, and do penetrate the gut and other barriers
-- the findings in this study are not at all surprising. It is clear that chronic inflammation is associated with increased cardiovascular risk, including by many diseases that are associated with increased inflammatory responses (rheumatoid arthritis, psoriasis, lupus, diabetes, depression….) as well as many exposures (air pollution, psychological stress, etc): see https://gmodestmedblogs.
-- this study found increased levels of the inflammatory cytokines IL-18, IL-1b,TNF-a, and IL-6 in patients with MNPs in their carotid samples
-- observational occupational health studies have found that plastic-related pollution (including polyvinylchloride) is associated with increased cardiovascular risk (it is hard to disassociate this exposure to the many other pollutants that the workers faced, though animal studies do confirm the association with plastic as likely causal)
-- of note, polyethylene and polyvinylchloride are used in the production of food and cosmetics containers and water pipes, leading to their detection in drinking water, as well as many foods, cosmetic products, and the air
--the WHO notes that MNPs larger than 150 µm or 10 µm in diameter do not penetrate blood vessels/are absorbed into the blood
-- this study found that the vast majority of MNPs detected were less than 200 nm, the suggested threshold for the gut and other barriers, and actually were visible in the study and the extracellular space as scattered debris
-- some other human studies have found that MNPs of up to 30 µm have been found in liver samples, up to 10 µm in placenta samples, up to 88 µm in lung samples, up to 12-15 µm in breast milk and urine, and more than 700 nm in whole blood, per the review in this article
-- the major concern, of course, is the huge amount of plastics in the environment and expected to be increasingly so over time; their wide dispersal in our food supply (even fruits and vegetables: https://www.sciencedirect.
Limitations:
-- these results from the study are associations and cannot be considered causal, since this was an observational study and not a randomized controlled trial (the latter being impossible to do), since there may well be unmeasured confounding variables
-- for example, though they did find no difference in their results depending on where patients live, we have no specifics about these areas or if they have anything in common with many other areas in the world, all limiting the generalizability of the results to elsewhere
-- there were no important granular data for many of the baseline characteristics: how severe was the diabetes, or hypertension, or smoking?
-- there was no information about the array of other things that raise systemic inflammation and the associated increase in bad cardiovascular outcomes: psychological stress, depression, visceral obesity (vs just the BMI), HIV, rhematioid arthritis/psoriasis/lupus, chronic kidney disease (which progresses with inflammation and oxidative stress). This makes it hard to know what the specific role of MNPs has in increasing cardiovascular outcomes
-- this study only involved asymptomatic patients undergoing carotid endarterectomy and may not be generalizable to the population overall
so,
-- unfortunately, this article adds to the variety of quite bad news about our future, with the common thread that our political systems seem to value short-term benefits over long-term consequences: climate change, loss of biological diversity, overuse of items that cause pollution (fossil fuels, chemicals/fertilizers that invade our water supply), destruction of wetlands, etc , etc
-- and, there is a real issue in how we evaluate in a systematic way the many new products that are released into the environment: thousands of new chemicals are developed every year (a report in 2017 suggested that “new chemical compounds are produced at a rate of 10 million per year, which translates into 1,000 new ones synthesized every hour” (https://www.smithsonianmag.
-- it is clear that the only real solution is a huge, concerted, global effort to redirect our current path...
geoff
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