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Gut‐Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet
Open accessAbstract
Background Gut microbiota is emerging as a novel risk factor for atherothrombosis, but the predictive role of gut‐derived lipopolysaccharide ( LPS ) is unknown. We analyzed (1) the association between LPS and major adverse cardiovascular events ( MACE ) in atrial fibrillation ( AF ) and (2) its relationship with adherence to a Mediterranean diet (Med‐diet). Methods and Results This was a prospective single‐center study including 912 AF patients treated with vitamin K antagonists (3716 patient‐years). The primary end point was a composite of MACE . Baseline serum LPS , adherence to Med‐diet (n=704), and urinary excretion of 11‐dehydro‐thromboxane B 2 (TxB 2 , n=852) were investigated. Mean age was 73.5 years; 42.9% were women. A total of 187 MACE (5.0% per year) occurred: 54, 59, and 74 in the first, second, and third tertile of LPS , respectively (log‐rank test P =0.004). Log‐ LPS (hazard ratio 1.194, P =0.009), age (hazard ratio 1.083, P <0.001), and previous cerebrovascular (hazard ratio 1.634, P =0.004) and cardiac events (hazard ratio 1.822, P <0.001) were predictors of MACE . In the whole cohort, AF (versus sinus rhythm) (β 0.087, P =0.014) and low‐density lipoprotein cholesterol (β 0.069, P =0.049) were associated with circulating LPS . Furthermore, Med‐diet score (β −0.137, P <0.001) was predictive of log‐ LPS , with fruits (β −0.083, P =0.030) and legumes (β −0.120, P =0.002) negatively associated with log‐ LPS levels. Log‐ LPS and log‐TxB 2 were highly correlated (r=0.598, P <0.001). Log‐ LPS (β 0.574, P <0.001) and Med‐diet score (β −0.218, P <0.001) were significantly associated with baseline urinary excretion of TxB 2 . Conclusions In this cohort of AF patients, LPS levels were predictive of MACE and negatively affected by high adherence to Med‐diet. LPS may contribute to MACE incidence in AF by increasing platelet activation.
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“In a recent observational study, circulating LPS concentrations were predictive of MACE in a cohort of patients with atrial fibrillation, suggesting that endotoxin translocation impacts CVD complications27.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [27]
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Metadata
- Authors
- Pastori, D., Carnevale, R., Nocella, C., Novo, M., Santulli, M., Cammisotto, V., Menichelli, D., Pignatelli, P., & Violi, F.
- Affiliations
- Sapienza University of Rome (IT)
- Corresponding author
- Violi, Francesco
- ORCID
- Venue
- Journal of the American Heart Association
- Published
- 2017-11-06
- Volume
- 6
- Issue
- 6
- ISSN
- 2047-9980 (ISSN-L)
- PMC
- PMC5669181
- OpenAlex
- W2623414143
- Cited by
- 182
- References
- 45
- Citations by year
- 2026: 22 · 2025: 18 · 2024: 30 · 2023: 28 · 2022: 27 · 2021: 24 · 2020: 12 · 2019: 11 · 2018: 7 · 2017: 3
- FWCI
- 6.97
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Journal of the American Heart Association (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Keywords
- atrial fibrillation, major adverse cardiovascular events, Mediterranean diet adherence, gut microbiota, atherothrombosis, 11-dehydrothromboxane B2, vitamin K antagonists, Fabaceae, fruits, LDL cholesterol, cerebrovascular events, cardiac events, serum biomarkers, risk prediction, vitamin B12 deficiency, folate deficiency, vitamin K deficiency, scurvy, vitamin E deficiency, vitamin A deficiency
- MeSH terms
- Gastrointestinal Microbiome, Aged, Aged, 80 and over, Anticoagulants, Atrial Fibrillation, Bacteria, Cerebrovascular Disorders, Female, Humans, Intestines, Lipopolysaccharides, Male, Patient Compliance, Prospective Studies, Risk Factors, Rome, Time Factors, Vitamin K, Biomarkers, Platelet Activation, Treatment Outcome, Myocardial Ischemia, Diet, Mediterranean, Kaplan-Meier Estimate, Protective Factors
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