Pastori Daniele, Carnevale Roberto, Nocella Cristina, Novo Marta, Santulli Maria, Cammisotto Vittoria, Menichelli Danilo, Pignatelli Pasquale, Violi Francesco
I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Italy.
J Am Heart Assoc. 2017 Jun 5;6(6):e005784. doi: 10.1161/JAHA.117.005784.
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).
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 (TxB, 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 =0.004). Log-LPS (hazard ratio 1.194, =0.009), age (hazard ratio 1.083, <0.001), and previous cerebrovascular (hazard ratio 1.634, =0.004) and cardiac events (hazard ratio 1.822, <0.001) were predictors of MACE. In the whole cohort, AF (versus sinus rhythm) (β 0.087, =0.014) and low-density lipoprotein cholesterol (β 0.069, =0.049) were associated with circulating LPS. Furthermore, Med-diet score (β -0.137, <0.001) was predictive of log-LPS, with fruits (β -0.083, =0.030) and legumes (β -0.120, =0.002) negatively associated with log-LPS levels. Log-LPS and log-TxB were highly correlated (r=0.598, <0.001). Log-LPS (β 0.574, <0.001) and Med-diet score (β -0.218, <0.001) were significantly associated with baseline urinary excretion of TxB.
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.
肠道微生物群正成为动脉粥样硬化血栓形成的一个新的危险因素，但肠道来源的脂多糖（LPS）的预测作用尚不清楚。我们分析了（1）LPS与房颤（AF）患者主要不良心血管事件（MACE）之间的关联，以及（2）其与坚持地中海饮食（Med-diet）的关系。
这是一项前瞻性单中心研究，纳入了912例接受维生素K拮抗剂治疗的AF患者（3716患者-年）。主要终点是MACE的复合终点。研究了基线血清LPS、对Med-diet的依从性（n = 704）以及11-脱氢血栓素B（TxB，n = 852）的尿排泄情况。平均年龄为73.5岁；42.9%为女性。共发生187例MACE（每年5.0%）：LPS三分位数的第一、第二和第三组分别为54例、59例和74例（对数秩检验=0.004）。Log-LPS（风险比1.194，P = 0.009）、年龄（风险比1.083，P < 0.001）以及既往脑血管事件（风险比1.634，P = 0.004）和心脏事件（风险比1.822，P < 0.001）是MACE的预测因素。在整个队列中，AF（与窦性心律相比）（β 0.087，P = 0.014）和低密度脂蛋白胆固醇（β 0.069，P = 0.049）与循环LPS相关。此外，Med-diet评分（β -0.137，P < 0.001）可预测Log-LPS，水果（β -0.083，P = 0.030）和豆类（β -0.120，P = 0.002）与Log-LPS水平呈负相关。Log-LPS和Log-TxB高度相关（r = 0.598，P < 0.001）。Log-LPS（β 0.574，P < 0.001）和Med-diet评分（β -0.218，P < 0.001）与TxB的基线尿排泄显著相关。
在这个AF患者队列中，LPS水平可预测MACE，并受到对Med-diet高依从性的负面影响。LPS可能通过增加血小板活化促进AF患者MACE的发生。
