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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.

journal of the american heart association

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