Affiliation:
1. I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy
2. Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Italy
3. Department of Medical‐Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy
4. Department of Experimental Medicine, Sapienza University of Rome, Italy
Abstract
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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine
Cited by
110 articles.
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