Daniele Pastori1, Evaristo Ettorre2, Roberto Carnevale3, Cristina Nocella4, Simona Bartimoccia1, Elisabetta Del Sordo1, Vittoria Cammisotto1, Francesco Violi5, Pasquale Pignatelli6. 1. I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy. 2. Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, Division of Gerontology, Sapienza University, Rome, Italy. 3. Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy; Mediterranea Cardiocentro, Napoli, 80122, Italy. 4. IRCCS Neuromed, Pozzilli, 86077, IS, Italy. 5. I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy; Mediterranea Cardiocentro, Napoli, 80122, Italy. 6. I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy; Mediterranea Cardiocentro, Napoli, 80122, Italy. Electronic address: pasquale.pignatelli@uniroma1.it.
Abstract
BACKGROUND AND AIMS: Lipopolysaccharides (LPS) is emerging as a novel risk factor for cardiovascular events (CVEs). Furthermore, in vitro evidence suggested that LPS may elicit proprotein convertase subtilisin/kexin 9 (PCSK9) expression, but their relationship in vivo has not been investigated. METHODS: We conducted a post-hoc analysis of a prospective, single centre cohort study of 907 patients with non-valvular atrial fibrillation (AF). At baseline, PCSK9, LPS and NADPH oxidase (sNox2-dp) were measured. PCSK9 and LPS were correlated with the incidence of CVEs. RESULTS: Median PCSK9 and LPS were 1200 [900-1970] and 49.9 [15.0-108.2] pg/ml, respectively. LPS and PCSK9 were significantly correlated (rS 0.378, p < 0.001). Logistic regression analysis showed that LPS was associated with PCSK9 above the median (odds ratio [OR] 1.727 95% confidence interval [CI] 1.147-2.600 p = 0.009). Other factors associated with PCSK9 above the median were sNox2-dp (OR 1.759 C.I. 95% 1.167-2.650, p = 0.007), use of antiplatelet drugs (OR 0.437 95%CI 0.219-0.871 p = 0.017) and high adherence to Mediterranean diet (OR 0.737 95%CI 0.643-0.845 p = 0.001). Olive oil (OR 0.376 95%CI 0.185-0.763, p = 0.001) and wine (OR 0.460 95%CI 0.289-0.733 p = 0.007) were negatively associated with PCSK9. Patients with concomitant high PCSK9 and LPS (LPS ≥88 pg/ml and PCSK9 ≥1570 pg/ml) had an increased risk of CVEs compared to those with low levels (LPS <24.3 pg/ml and PCSK9 <1000 pg/ml, Log-Rank test, p = 0.022). CONCLUSIONS: This study demonstrated, for the first time in vivo, that circulating levels of PCSK9 and LPS are associated with a mechanism possibly involving NADPH oxidase activation. Patients with concomitant increase of PCSK9 and LPS showed a higher risk of CVEs.
BACKGROUND AND AIMS: Lipopolysaccharides (LPS) is emerging as a novel risk factor for cardiovascular events (CVEs). Furthermore, in vitro evidence suggested that LPS may elicit proprotein convertase subtilisin/kexin 9 (PCSK9) expression, but their relationship in vivo has not been investigated. METHODS: We conducted a post-hoc analysis of a prospective, single centre cohort study of 907 patients with non-valvular atrial fibrillation (AF). At baseline, PCSK9, LPS and NADPH oxidase (sNox2-dp) were measured. PCSK9 and LPS were correlated with the incidence of CVEs. RESULTS: Median PCSK9 and LPS were 1200 [900-1970] and 49.9 [15.0-108.2] pg/ml, respectively. LPS and PCSK9 were significantly correlated (rS 0.378, p < 0.001). Logistic regression analysis showed that LPS was associated with PCSK9 above the median (odds ratio [OR] 1.727 95% confidence interval [CI] 1.147-2.600 p = 0.009). Other factors associated with PCSK9 above the median were sNox2-dp (OR 1.759 C.I. 95% 1.167-2.650, p = 0.007), use of antiplatelet drugs (OR 0.437 95%CI 0.219-0.871 p = 0.017) and high adherence to Mediterranean diet (OR 0.737 95%CI 0.643-0.845 p = 0.001). Olive oil (OR 0.376 95%CI 0.185-0.763, p = 0.001) and wine (OR 0.460 95%CI 0.289-0.733 p = 0.007) were negatively associated with PCSK9. Patients with concomitant high PCSK9 and LPS (LPS ≥88 pg/ml and PCSK9 ≥1570 pg/ml) had an increased risk of CVEs compared to those with low levels (LPS <24.3 pg/ml and PCSK9 <1000 pg/ml, Log-Rank test, p = 0.022). CONCLUSIONS: This study demonstrated, for the first time in vivo, that circulating levels of PCSK9 and LPS are associated with a mechanism possibly involving NADPH oxidase activation. Patients with concomitant increase of PCSK9 and LPS showed a higher risk of CVEs.
Authors: Monika Gawałko; Thomas A Agbaedeng; Arnela Saljic; Dominik N Müller; Nicola Wilck; Renate Schnabel; John Penders; Michiel Rienstra; Isabelle van Gelder; Thomas Jespersen; Ulrich Schotten; Harry J G M Crijns; Jonathan M Kalman; Prashanthan Sanders; Stanley Nattel; Dobromir Dobrev; Dominik Linz Journal: Cardiovasc Res Date: 2022-08-24 Impact factor: 13.081