Low-grade endotoxemia is associated with cardiovascular events in community-acquired pneumonia

Abstract

Community-acquired pneumonia (CAP) is associated with low-grade endotoxemia but its relationship with cardiovascular events (CVE) has not been investigated. We evaluated the incidence of CVE including myocardial infarction, stroke, and cardiovascular death in 523 adult patients hospitalized for CAP. Serum lipopolysaccharide (LPS) and zonulin, a marker of gut permeability, were analyzed in the cohort, that was followed-up during hospitalization and up to 43 months thereafter. During the hospital-stay, 55 patients experienced CVE with a progressive increase from the lowest (0.6%) to highest LPS tertile (23.6%, p<0.001). Logistic regression analyses showed that higher LPS tertile was independently associated with CVE; LPS significantly correlated with age, hs-CRP and zonulin. In a sub-group of 23 CAP patients, blood E. coli DNA was higher in patients compared to 24 controls and correlated with LPS. During the long-term follow-up, 102 new CVE were registered; the highest tertile of LPS levels was associated with incident CVE; Cox regression analysis showed that LPS tertiles, age, history of CHD, and diabetes independently predicted CVE. In CAP low-grade endotoxemia is associated to short- and long-term risk of CVE. Further study is necessary to assess if lowering LPS by non-absorbable antibiotics may result in improved outcomes.