Tom Wade MD

Today, I review, link to, and excerpt from COREIM‘s Microplastics and Macro CV Health Problems: Beyond Journal Club on APAChE Study with NEJM Group.

All that follows is from the above resource.

Posted: March 5, 2025
By: Dr. Harleen Marwah, Dr. Shreya P. Trivedi, Dr. Phil Landrigan, Dr. Clem Lee and Dr. Greg Katz
Graphic: Dr. Jimin Hwang
Audio: Jerome Reyes

Podcast: Play in new window | Download

Time Stamps Show Notes  Behind The Scenes YouTube Interview Transcript References

Time Stamps

• 02:24 Introduction to Plastic’s Key Players
• 07:59 Bradhill/Observational Work
• 10:33 APAChE Study Deep Dive
• 18:03 Discussion

Show Notes 

Background

• What are plastics?
  • History of plastics
  • What is plastic?
  • Interview with Dr. Landrigan 
• Before the APAChE study, what was the evidence around plastics and human health?
  • First noted in 1970s: cases of liver angiosarcoma in workers at a PVC (polyvinyl chloride) processing plant: 
  • Microplastics have been detected in almost every organ in the body:
    • Lungs
      • 13 human lung tissue samples
      • 39 microplastics were identified in 11/13 samples
    • Liver
      • 17 samples (11 liver, 3 kidney, and 3 spleen) were analyzed across 6 patients with liver cirrhosis and 5 without liver disease.
      • Microplastics detected in ALL patients with cirrhosis
        • Not detected in patients without liver disease!
    • Breast milk
      • Breast milk samples from 34 women were analyzed
      • 26/34 samples detected microplastics
        • Most abundant being polyethylene, polyvinyl chloride, and polypropylene.
          • Notably, no significant relationship between source of plastic exposure and detection of microplastics
    • Brain
    • Placenta
    • Colon
    • Urine and Kidneys
• What is the impact of plastic exposure?
  • • Animal studies: Increased inflammation, oxidative stress, and coagulability
    • In vitro studies: Disrupted cell membranes, influenced gene expression, and a host of other potentially disease-causing mechanisms
  • What about for humans?
    • Cancer mortality in workers at a chemical plant
      • Hepatobiliary cancer mortality was higher among workers exposed to vinyl chloride.
      • Coronary artery disease mortality was higher among long-term workers exposed to carbon disulfide and shift work for 4+ years.
    • Reanalysis of vinyl and polyvinyl workers 
      • Increased mortality rates were observed for all causes of death,
        • Increases in liver cancer among autoclave workers and cardiovascular diseases among PVC baggers.

Bradford Hill Criteria

• The Bradford Hill criteria
  • Principles used to support evidence of a causal relationship between a presumed cause and an observed effect
    • “It is important to note that satisfying these criteria may lend support for causality, but failing to meet some criteria does not necessarily provide evidence against causality, either. Hill’s causal criteria should be viewed as guidelines, not as a “checklist” that must be satisfied for a causal relationship to exist.” (UNC Department of Epidemiology)
  • The 9 criteria
    • Strength (effect size):
      • Larger the association →more likely association is causal.
    • Consistency (reproducibility): 
      • Consistent findings observed by different persons in different places with different samples → strengthens the likelihood of an effect.
    • Specificity:
      • Causation is likely if there is a very specific population at a specific site and disease with no other likely explanation.
    • Temporality:
      • The effect has to occur AFTER the cause
    • Biological gradient (dose–response relationship): 
      • Greater exposure should generally lead to greater incidence of the effect
    • Plausibility:
      • A plausible mechanism between cause and effect is helpful, but may be limited by current knowledge.
    • Coherence:
      • Coherence between epidemiological and laboratory findings increases the likelihood of an effect.
    • Experiment: 
      • Data may be used to support an association.
    • Analogy:
      • Analogous similarities between the observed association and any other associations are helpful.
  • The APAChE study through the lens of the Bradford Hill Criteria
    • Criteria MET in the APAChE study:
      • Consistency (reproducibility)
      • Plausibility
        • In vitro data links microplastics to oxidative stress and inflammation, both of which are part of the pathophysiology of atherosclerosis
      • Coherence
      • Experiment
    • Criteria NOT MET in the APAChE study:
      • Strength (effect size)
      • Specificity
      • Temporality
      • Biological gradient
• APAChE
  • NEJM APAChE (Pollutants in the Atherosclerotic Plaque and Cardiovascular Events) Study
    • Study Objective
      • (1) Are microplastics detectable within atherosclerotic plaque
      • (2) Are the presence of microplastics associated with adverse cardiovascular events
    • Study Methods
      • Design: Prospective, muti-center, observational study.
      • Population:
        • Consecutive patients with asymptomatic extracranial high-grade (> 70%) internal carotid artery stenosis (classified by the North American Symptomatic Carotid Endarterectomy Trial).
      • Procedures:
        • Patients referred for surgery to remove carotid artery blockages were followed
        • Plaques were analyzed and examined for prospective cardiovascular risk
        • Participants were divided into two groups:
          • Plaque with MNPs
          • Plaque without MNPs
      • Primary Outcome:
        • Nonfatal MI
        • Nonfatal stroke
        • Death from any cause
    • Study Results
      • Detectable Microplastics:
        • Polyethylene: 150 patients (58.4%)
        • Polyvinyl chloride: 31 patients (12.1%)
      • Nonfatal MI:
        • 8/107 (7.5%) of patients WITHOUT MNPs
        • 30/150 patients (20%) of patients WITH MNPs
          • Patients with MNPs are More likely to be/have:YoungerMenDiabetes, cardiovascular disease, dyslipidemiaSmoke Less likely to be/have:Hypertensi0n
        • Patients with microplastics in carotid plaque are 4.5-fold more likely to have a negative cardiovascular outcome
          • Higher levels of IL-6 and TNF-alpha in those with microplastics in their carotid plaques
• Discussion
  • Conclusions:
    • • Note: authors from APAChE had a cautious conclusion, clearly stating in their discussion that, “It is important to note that our results do not prove causality.”
    • Uncertainty around causality → Hard to know actionable steps for patients
      • Did microplastics in plaques make patients sicker or are sicker patients more likely to have microplastics in their plaques?
    • What’s next?
      • Wait until the evidence is stronger in terms of causality?
        • There are other things that we know impact disease risk with a higher level of confidence so that we should be wary of the opportunity cost of talking about a speculative risk
      • Precautionary principle is also a reasonable perspective to apply!
        • If there’s a reasonable chance that plastic exposure is harmful, then avoiding it may be an easy win in terms of disease risk
    • Remaining questions:
      • Out of the 11 types of plastics assessed, why were only polyethylene and polyvinyl chloride detected?
        • Why did polyethylene and polyvinyl chloride accumulate preferentially within the plaques in this study?
      • What were the source(s) of exposure for the patients in the study?
        • Does the route of exposure matter: inhalation, topical absorption, or ingestion?
        • How does exposure to pollution and particulate matter influence risk?
        • How does diet or drinking water sources influence outcomes?
      • How much control do we have in mitigating our exposure? How much plastic in our lives comes through our conscious purchasing decisions vs. how much is just present in ambient exposure?
      • What is the cumulative risk of exposure over time and how does that correlate to outcomes?
• “And the fact that the transition will be difficult is not an excuse for perpetuating the current state of affairs.” – Dr. Phil Landrigan
• Other Resources:
  • NEJM Editorial by Dr. Phil Landrigan
  • Dr. Eric Topol Substack Commentary
  • Dr. Greg Katz Substack Commentary

Behind The Scenes YouTube Interview

Subscribe to Core IM’s YouTube Channel for more behind the scenes, whiteboard animations and more!

Mar 1, 2025 #pediatrics #microplastics #residency

Dr. Landrigan is an intellectual leader, researcher, and public health physician with expertise in the pathogenic role of microplastics. In this Behind The Scenes interview with Core IM, he explains the significant and often unappreciated evidence linking microplastics to human disease and empowers viewers with ideas to reduce this in the future. Key Points from the interview:

• Microplastics are ubiquitous in the environment which humans ingest and inhale.
• The Minderoo-Monaco Comission Report documents extensive evidence linking plastic exposure to deleterious health outcomes.
• Observational research studies have linked plastic exposure to increased risk of cardiovascular disease (Marfella et al., NEJM, 2024)
• Individual actions to decrease exposure include buying organic and substituting cloth, glass, or even multi-use plastics for single use ones.
• As global citizens we need to advocate to cap future plastic production
• Plastic production has grown 250 fold over the past 75y and is still increasing
• Healthcare institutions can be a leaders in mitigating consultumption of single use plastics while retaining use of necessary plastic equipment.
• Counseling patients about reducing exposure to and consumption of plastics should become part of routine preventative care.

Interested in learning more about Microplastics and Human Health?: Please check out the full podcast episode at our website: https://www.coreimpodcast.com