Gut‐Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet

BackgroundGut 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 relationshi...

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Main Authors: Daniele Pastori, Roberto Carnevale, Cristina Nocella, Marta Novo, Maria Santulli, Vittoria Cammisotto, Danilo Menichelli, Pasquale Pignatelli, Francesco Violi
Format: Article
Language:English
Published: Wiley 2017-11-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Subjects:
Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.117.005784
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author Daniele Pastori
Roberto Carnevale
Cristina Nocella
Marta Novo
Maria Santulli
Vittoria Cammisotto
Danilo Menichelli
Pasquale Pignatelli
Francesco Violi
author_facet Daniele Pastori
Roberto Carnevale
Cristina Nocella
Marta Novo
Maria Santulli
Vittoria Cammisotto
Danilo Menichelli
Pasquale Pignatelli
Francesco Violi
author_sort Daniele Pastori
collection DOAJ
description BackgroundGut 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 ResultsThis 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 B2 (TxB2, 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‐TxB2 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 TxB2. ConclusionsIn 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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spelling doaj.art-de91d3f13b48449db7c276ceea72a9fd2022-12-21T23:12:05ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802017-11-016610.1161/JAHA.117.005784Gut‐Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean DietDaniele Pastori0Roberto Carnevale1Cristina Nocella2Marta Novo3Maria Santulli4Vittoria Cammisotto5Danilo Menichelli6Pasquale Pignatelli7Francesco Violi8I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, ItalyI Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, ItalyI Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, ItalyI Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, ItalyI Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, ItalyI Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, ItalyI Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, ItalyI Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, ItalyI Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, ItalyBackgroundGut 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 ResultsThis 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 B2 (TxB2, 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‐TxB2 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 TxB2. ConclusionsIn 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.https://www.ahajournals.org/doi/10.1161/JAHA.117.005784atrial fibrillationcardiovascular eventslipopolysaccharideMediterranean dietthromboxane
spellingShingle Daniele Pastori
Roberto Carnevale
Cristina Nocella
Marta Novo
Maria Santulli
Vittoria Cammisotto
Danilo Menichelli
Pasquale Pignatelli
Francesco Violi
Gut‐Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
atrial fibrillation
cardiovascular events
lipopolysaccharide
Mediterranean diet
thromboxane
title Gut‐Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet
title_full Gut‐Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet
title_fullStr Gut‐Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet
title_full_unstemmed Gut‐Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet
title_short Gut‐Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet
title_sort gut derived serum lipopolysaccharide is associated with enhanced risk of major adverse cardiovascular events in atrial fibrillation effect of adherence to mediterranean diet
topic atrial fibrillation
cardiovascular events
lipopolysaccharide
Mediterranean diet
thromboxane
url https://www.ahajournals.org/doi/10.1161/JAHA.117.005784
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