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

Abstract

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.

Metabolic Endotoxemia: A Potential Underlying Mechanism of the Relationship between Dietary Fat Intake and Risk for Cognitive Impairments in Humans?

“…In this latter study [54], higher consumption of fish and healthy snacks (including fruits and berries, fresh vegetables, soft drinks, yoghurt and low-fat cheese) and higher adherence to a modern diet (composed of fresh vegetables, pasta and rice, poultry, meat dishes and fried or grilled foods) were all significantly associated with lower fasting LPS levels in serum [54]. Finally, among elderly patients with nonvalvular atrial fibrillation, higher adherence to a Mediterranean-type diet was inversely correlated with fasting circulating LPS levels [55]. Interestingly, among Mediterranean diet food components, higher intake of fruits and legumes showed a major association with lower levels of LPS.…”

Low-Dose Dexmedetomidine Accelerates Gastrointestinal Function Recovery in Patients Undergoing Lumbar Spinal Fusion

“…LPS is a product of gut microbiota, and about 100 trillion gut bacteria contribute to an enteric reservoir greater than 1 g of LPS (Pastori et al, 2017). In some clinical settings, such as intestinal ischemia, surgical stress or intestinal mucosa injury, LPS may enter the systemic circulation as a consequence of increased gut permeability.…”

Mediterranean diet and health status: Active ingredients and pharmacological mechanisms

“…The microbiome of the human gut is regarded to be a crucial link between nutritional habits and our health (De Angelis et al, ). A number of favourable effects of the MedDiet on the microbiota were reported (De Filippis et al, ; Pastori et al, ). Specific ingredients such as proteins and fibre affect the composition of the microbiome, including synthesis and release of metabolites modulating the immune system and inflammation (Clemente, Ursell, Parfrey, & Knight, ; Richards, Yap, McLeod, Mackay, & Mariño, ).…”