Association of endotoxemia with carotid atherosclerosis and cardiovascular disease
Open accessAbstract
Objectives Focus of the current study was on the significance of bacterial endotoxin, which shows a variety of pro-atherogenic properties and may occur at high concentration in the circulation of infected subjects.Background The possibility of an infectious risk factor in atherogenesis and cardiovascular disease has stimulated research interest, but the nature of such process remains obscure.Methods We measured plasma endotoxin levels (LAL assay) in a random population of 516 men and women 50 to 79 years old at the 1990 baseline evaluation (Bruneck Study). End points of this prospective survey were incident (early) atherosclerosis in the carotid arteries as assessed with high-resolution Duplex ultrasound (five-year follow-up rate, 98%) and incident cardiovascular disease (follow-up rate, 100%).Results Median endotoxin concentration amounted to 14.3 pg/ml (range, 6.0 to 209.2 pg/ml). Subjects with levels beyond 50 pg/ml (90th percentile) faced a threefold risk of incident atherosclerosis (odds ratio [95% confidence interval] 2.9 [1.4-6.3]; p < 0.01). The risk associated with high endotoxin was most pronounced in subjects with chronic infections and in current and ex-smokers. Notably, smokers with low endotoxin levels and nonsmokers did not differ in their atherosclerosis risk, whereas smokers with high levels almost invariably developed new lesions. All findings emerged as independent of vascular risk factors. Similar results were obtained for incident cardiovascular disease.Conclusions The current study yields first epidemiologic evidence that endotoxemia constitutes a strong risk factor of early atherogenesis in subjects with chronic or recurrent bacterial infections and a link in the association between cigarette smoking and atherosclerotic disease.
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Blood plasma endotoxin levels are normally low in healthy humans.
“Blood plasma levels of endotoxin are normally low”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [8]
Endotoxin is present in plasma of all healthy humans at very variable levels between 0.01 and 0.5 EU/ml (mean 0.1 ± 0.2 EU/ml), equivalent to about 1 and 50 pg/ml.
“Endotoxin is present in plasma of all healthy humans at very variable levels between 0.01 and 0.5 EU/ml (mean 0.1 ± 0.2 EU/ml), equivalent to about 1 and 50 pg/ml [7, 8].”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [8]
Subclinical endotoxemia is a strong risk factor for carotid atherosclerosis, and weekly injection of lipopolysaccharide worsens formation of atherosclerosis in animal models.
“A clinical study revealed that subclinical endotoxemia is a strong risk factor for carotid atherosclerosis and that weekly injection of lipopolysaccharide worsens the formation of atherosclerosis in animal models.”
From <i>Akkermansia Muciniphila</i> Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in <i>Apoe</i> <sup>−/−</sup> Mice (2016) · cites this paper as [41]
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- Authors
- Wiedermann, C. J., Kiechl, S., Dunzendorfer, S., Schratzberger, P., Egger, G., Oberhollenzer, F., & Willeit, J.
- Affiliations
- Innsbruck Medical University (AT)
- Krankenhaus Bruneck (IT)
- Corresponding author
- Wiedermann, Christian J
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 1999-12
- Volume
- 34
- Issue
- 7
- Pages
- 1975-1981
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W1535151445
- Cited by
- 505
- References
- 52
- Citations by year
- 2026: 13 · 2025: 16 · 2024: 22 · 2023: 24 · 2022: 26 · 2021: 33 · 2020: 22 · 2019: 19 · 2018: 15 · 2017: 26 · 2016: 20 · 2015: 28 · 2014: 19 · 2013: 31 · 2012: 23
- FWCI
- 3.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Keywords
- endotoxemia, bacterial endotoxin, carotid atherosclerosis, cardiovascular disease, atherogenesis, chronic bacterial infection, cigarette smoking, infection risk factors, Bruneck Study
- MeSH terms
- Aged, Bacterial Infections, Blood Flow Velocity, Cardiovascular Diseases, Carotid Artery Diseases, Carotid Artery, Internal, Chronic Disease, Endotoxins, Female, Humans, Italy, Limulus Test, Male, Middle Aged, Prospective Studies, Surveys and Questionnaires, Risk Factors, Incidence, Prevalence, Survival Rate, Odds Ratio, Ultrasonography, Doppler, Duplex, Endotoxemia
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