Circulating Lipopolysaccharides and Impaired Antioxidant Status in Patients With Atrial Fibrillation. Data From the ATHERO-AF Study

Objectives: Atrial fibrillation (AF) is characterized by an oxidative imbalance, which is associated with an increased risk of cardiovascular events (CVEs). It is unclear whether low grade endotoxemia may contribute to the impaired antioxidant status in AF patients. We investigated the relationship between circulating lipopolysaccharides (LPS) and antioxidant status in AF patients.Patients and Methods:Post-hoc analysis from the ongoing prospective observational cohort ATHERO-AF study including 907 patients. Antioxidant status was evaluated by the activity of glutathione peroxidase 3 (GPx3) and superoxide dismutase (SOD). Patients were divided into two groups to evaluate the risk of CVEs: (1) LPS below median and GPx3 above median (n = 254); (2) LPS above median and GPx3 below median (n = 263).Results: The mean age was 73.5 ± 8.3 years, and 43.1% were women. Median LPS and GPx3 were 50.0 pg/ml [interquartile range (IQR) 15–108] and 20.0 U/ml (IQR 10.0–34.0), respectively. Patients of Groups 2 were older, with a higher prevalence of heart failure. LPS above the median was associated with reduced GPx3 [Odds Ratio for LPS 1.752, 95% Confidence Interval (CI) 1.344–2.285, p < 0.001] and SOD (OR 0.525, 95%CI 0.403–0.683) activity after adjustment for CHA2DS2VASc score. In a mean follow-up of 54.0 ± 36.8 months, 118 CVEs occurred, 42 in Group 1 and 76 in Group 2 (Log-Rank test p = 0.001). At multivariable Cox regression analysis, Group 2 was associated with a higher risk of CVEs [Hazard Ratio (HR) 1.644, 95%CI 1.117–2,421, p = 0.012], along with age ≥ 75 years (HR 2.035, 95%CI 1.394–2.972, p < 0.001), diabetes (HR 1.927, 95%CI 1.280–2.900, p = 0.002), and previous cerebrovascular disease (HR 1.895, 95%CI 1.251–2.870, p = 0.003) and previous cardiovascular disease (HR 1.708, 95%CI 1.149–2.538, p = 0.008).Conclusions: Our study indicates that circulating LPS may contribute to impaired antioxidant status in patients with AF. Patients with coincidentally high LPS and reduced GPx3 activity showed the highest risk of CVEs.

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Effects of the ANXA6 polymorphisms on glioma risk and patients prognosis

10.21203/rs.2.16678/v1 ◽

2019 ◽

Author(s):

Tuo Wang ◽

Yao Sun ◽

Zichao Xiong ◽

Jiamin Wu ◽

Xiaoying Ding ◽

...

Keyword(s):

Regression Analysis ◽

Cox Regression ◽

Rank Test ◽

Low Grade ◽

Nucleotide Polymorphisms ◽

Glioma Patient ◽

Chinese Han ◽

Cox Regression Analysis ◽

Increased Risk ◽

Glioma Risk

Abstract BACKGROUND Glioma is the most frequent malignant primary brain tumor, and the outcomes for patients with glioma remain poor. The purpose of this study is to explore the association between ANXA6 polymorphisms and glioma risk as well as the prognosis of glioma patients in the Chinese Han population.METHODS We selected nine single-nucleotide polymorphisms (SNPs) in ANXA6 which were genotyped by Agena MassARRAY from 593 glioma patients and 589 healthy controls. The odds ratio (OR) and 95% confidence interval (CI) were calculated by logistic regression analysis to evaluate the association SNPs with glioma risk. The association between polymorphisms and survival of glioma patient were evaluated using the log-rank test, Kaplan-Meier and Cox regression analysis. RESULTS: Overall analysis found that rs3762993 was significantly associated with an increased glioma risk. Stratification analysis found that rs11960458 was strongly associated with an increased risk of glioma in age >41; rs3762993 was also found to be associated an increased with glioma risk in age >41, ≤41, male and low-grade glioma; but rs4958892 was associated with a decreased risk of glioma in age>41 and male. Interestingly, rs11960458 and rs888988 were correlated with poor prognosis of glioma patient. Furthermore, age, extent of resection and chemotherapy were found to be key prognostic factors in survival of glioma patients.CONCLUSIONS In conclusion, our results indicated that ANXA6 polymorphisms were associated with glioma susceptibility and prognosis. Further studies are required to confirm the results and elucidate the mechanisms of the ANXA6 polymorphisms affect the glioma risk and prognosis.

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684 Cardiac troponins and adverse outcomes in European patients with atrial fibrillation: a report from the ESC-EHRA EORP atrial fibrillation general long-term registry

European Heart Journal Supplements ◽

10.1093/eurheartj/suab127.052 ◽

2021 ◽

Vol 23 (Supplement_G) ◽

Author(s):

Marrco Vitolo ◽

Vincenzo Livio Malavasi ◽

Marco Proietti ◽

Igor Diemberger ◽

Laurent Fauchier ◽

...

Keyword(s):

Atrial Fibrillation ◽

Regression Analysis ◽

Cox Regression ◽

Adverse Outcomes ◽

Cox Regression Analysis ◽

Coronary Syndrome ◽

Increased Risk ◽

History Of ◽

Cardiac Troponins

Abstract Aims Cardiac troponins (cTn) have been reported to be predictors for adverse outcomes in atrial fibrillation (AF), patients, but their actual use is still unclear. To assess the factors associated with cTn testing in routine clinical practice and to evaluate the association of elevated levels of cTn with adverse outcomes in a large contemporary cohort of European AF patients. Methods and results Patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry were stratified into three groups according to cTn levels as (i) cTn not tested, (ii) cTn in range (≤99th percentile), and (iii) cTn elevated (>99th percentile). The composite outcome of any thromboembolism/any acute coronary syndrome (ACS)/cardiovascular (CV) death, defined as major adverse cardiovascular events (MACE) and all-cause death were the main endpoints. 10 445 (94.1%) AF patients were included in this analysis [median age 71 years, interquartile range (IQR): 63–77; males 59.7%]. cTn were tested in 2834 (27.1%). Overall, cTn was elevated in 904 (8.7%) and in-range in 1930 (18.5%) patients. Patients in whom cTn was tested tended to be younger (P < 0.001) and more frequently presenting with first detected AF and atypical AF-related symptoms (i.e. chest pain, dyspnoea, or syncope) (P < 0.001). On multivariable logistic regression analysis, female sex, in-hospital enrollment, first-detected AF, CV risk factors, history of coronary artery disease (CAD), and atypical AF symptoms were independently associated with cTn testing. After a median follow-up of 730 days (IQR: 692–749), 957 (9.7%) composite endpoints occurred while all-cause death was 9.5%. Kaplan–Meier analysis showed a higher cumulative risk for both outcomes in patients with elevated cTn levels (Figure) (Log Rank tests, P < 0.001). On adjusted Cox regression analysis, elevated levels of cTn were independently associated with a higher risk for MACE [hazard ratio (HR): 1.74, 95% confidence interval (CI): 1.40–2.16] and all-cause death (HR 1.45, 95% CI: 1.21–1.74). Elevated levels of cTn were independently associated with a higher occurrence of MACE, all-cause death, any ACS, CV death and hospital readmission even after the exclusion of patients with history of CAD, diagnosis of ACS at discharge, those who underwent coronary revascularization during the admission and/or who were treated with oral anticoagulants plus antiplatelet therapy. Conclusions Elevated cTn levels were independently associated with an increased risk of all-cause mortality and adverse CV events, even after exclusion of CAD patients. Clinical factors that might enhance the need to rule out CAD were associated with cTn testing.

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Association Between Gout and Injury Risk: A National Retrospective Cohort Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17103679 ◽

2020 ◽

Vol 17 (10) ◽

pp. 3679

Author(s):

Shih-Hsiang Ou ◽

Chu-Lin Chou ◽

Chia-Wei Lin ◽

Wu-Chien Chien ◽

Te-Chao Fang ◽

...

Keyword(s):

Retrospective Cohort ◽

Injury Risk ◽

Cox Regression ◽

Drug Intervention ◽

Cox Regression Analysis ◽

Analysis Group ◽

Risk Of Injury ◽

Increased Risk ◽

Insurance Database

The association between gout and injury remains unclear. This study aimed to investigate the injury risk in patients with gout. Using the Longitudinal Health Insurance Database (LHID) from 2000 to 2010 in Taiwan, patients with gout (group CFG) and those without gout (group C) were enrolled for further analysis. The CFG group was separated into two subgroups (with and without medication) to determine whether the risk of injury was reduced with drug intervention. The follow-up period was defined as the time from the initial diagnosis of gout to the date of injury. A total of 257,442 individuals were enrolled in this study, with 85,814 people in group CFG and 171,628 people in group C. Using Cox regression analysis, group CFG showed a significant increase in the risk of injury. Traffic injuries, poisoning, falls, crushing/cutting/piercing injury, and suicides were prominent among these injuries. Furthermore, when urate-lowing drugs were used to treat the CFG group, there were no significant differences in the occurrence of injury. Patients with gout had an increased risk of injury overall, and drug intervention did not lower the risk of injury in these patients.

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Increased risk of Parkinson’s disease among patients with age-related macular degeneration

BMC Ophthalmology ◽

10.1186/s12886-021-02196-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Po-Yu Jay Chen ◽

Lei Wan ◽

Jung-Nien Lai ◽

Chih Sheng Chen ◽

Jamie Jiin-Yi Chen ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Macular Degeneration ◽

Cox Regression ◽

Age Related Macular Degeneration ◽

Rank Test ◽

Cox Regression Analysis ◽

Age Related ◽

Increased Risk

Abstract Background This study aimed to investigate the risk of Parkinson’s disease (PD) among patients with age-related macular degeneration (AMD) and its association with confounding comorbidities. Methods A population-based retrospective cohort study was conducted using Longitudinal Health Insurance Database 2000 (LHID2000). We established AMD and non-AMD cohorts from January 1, 2000 to December 31, 2012 to determine the diagnosis of PD. A total of 20,848 patients were enrolled, with 10,424 AMD patients and 10,424 controls matched for age, sex, and index year at a 1:1 ratio. The follow-up period was from the index date of AMD diagnosis to the diagnosis of PD, death, withdrawal from the insurance program, or end of 2013. Multivariable Cox regression analysis was performed to examine the hazard ratio (HR) and 95% confidence interval (CI) for the risk of PD between the AMD and non-AMD cohorts. Result After adjusting for potential confounders, there was a higher risk of developing PD in the AMD cohort than in the non-AMD cohort (adjusted HR = 1.35, 95% CI = 1.16–1.58). A significant association could be observed in both female (aHR = 1.42, 95% CI = 1.13–1.80) and male (aHR = 1.28, 95% CI = 1.05–1.57) patients, aged more than 60 years (60–69: aHR = 1.51, 95% CI = 1.09–2.09, 70–79: aHR = 1.30, 95% CI = 1.05–1.60; 80–100: aHR = 1.40, 95% CI = 1.01–1.95), and with more than one comorbidity (aHR = 1.40, 95% CI = 1.20–1.64). A significant association between increased risk of PD and AMD was observed among patients with comorbidities of osteoporosis (aHR = 1.68, 95% CI = 1.22–2.33), diabetes (aHR = 1.41, 95% CI = 1.12–1.78) and hypertension (aHR = 1.36, 95% CI = 1.15–1.62) and medications of statin (aHR = 1.42, 95% CI = 1.19–1.69) and calcium channel blocker (CCB) (aHR = 1.32, 95% CI = 1.11–1.58). The cumulative incidence of PD was significantly higher over the 12-year follow-up period in AMD cohort (log-rank test, p < 0.001). Conclusions Patients with AMD may exhibit a higher risk of PD than those without AMD.

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Primary hemostatic disorders drive early and late major bleedings of patients with atrial fibrillation after transcatheter aortic valve replacement

European Heart Journal ◽

10.1093/eurheartj/ehab724.1631 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

K Matsushita ◽

B Marchandot ◽

S Hess ◽

M Kibler ◽

C Sato ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cox Regression ◽

Academic Research ◽

Surrogate Marker ◽

Bleeding Complications ◽

Rank Test ◽

Bleeding Events ◽

Major Life ◽

Cox Regression Analysis ◽

The Impact

Abstract Introduction Patients with atrial fibrillation (AF) are likely to have multiple co-morbidities and receive anticoagulants after TAVR, which lead to a poor prognosis including bleeding events. Closure time adenosine diphosphate (CT-ADP) is a primary hemostasis point-of-care test used as a surrogate marker of high molecular weight (HMW) multimers defect of Von Willebrand factor (VWF). Our prior studies suggest that prolongation of CT-ADP (>180 seconds) after TAVR is a major determinant of early and late major/life-threatening bleeding complications (MLBCs). Purpose To evaluate the impact of post-procedural CT-ADP >180sec on bleeding events in AF patients. Methods We included 878 patients from our prospective TAVR registry between 2010 and 2019. Bleeding complications were assessed according to the VARC-2 (Valve Academic Research Consortium-2) criteria. Major adverse cardiac and cerebrovascular events (MACCE) was defined as a composite of all-cause death, myocardial infarction, stroke, and heart failure hospitalization within 1-year after TAVR. Ongoing primary haemostasis disorder was defined by post-procedure CT-ADP >180sec. Primary endpoint was the occurrence of MLBCs during the first year and the second endpoint was 1-year MACCE. Results Patients with AF had a higher incidence of all-cause mortality (15% vs. 8%, p=0.002), MACCE (29% vs. 20%, p=0.002), and MLBCs (20% vs. 12%, p=0.001) within 1-year compared to non-AF patients. When the cohort was split into 4 subgroups according to AF and CT-ADP >180sec, patients with AF and CT-ADP >180sec had the highest risk of MLBCs (log-rank test; p<0.001) (Figure). Multivariate Cox regression analysis confirmed that the patients with AF and CT-ADP >180sec had 4.6-fold higher risk of MLBCs within 1 year compared to non-AF patients with CT-ADP ≤180sec (hazard ratio: 4.60; 95% confidence interval: 2.18 - 9.68; p<0.001). Conclusion Among TAVR patients, AF with post-procedural CT-ADP >180 sec was identified as a strong independent predictor of MLBCs at 1-year follow-up. Our study suggest that persistent primary haemostasis disorders contribute to a higher risk of bleeding events particularly in AF patients and may be considered for a tailored and risk-adjusted antithrombotic therapy after TAVR. FUNDunding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Dr Matsushita received a grant from Edwards Lifesciences.

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Chemoradiation-related lymphopenia and its association with survival in patients with anal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.3 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 3-3

Author(s):

Grace Lee ◽

Daniel W. Kim ◽

Vinayak Muralidhar ◽

Devarati Mitra ◽

Nora Horick ◽

...

Keyword(s):

Cancer Patients ◽

Anal Cancer ◽

Cox Regression ◽

Cox Model ◽

Rank Test ◽

Anal Squamous Cell Carcinoma ◽

Cox Regression Analysis ◽

Risk Of Death ◽

Kaplan Meier ◽

Increased Risk

3 Background: While treatment-related lymphopenia (TRL) is common and associated with poorer survival in multiple solid malignancies, little data exists for anal cancer. We evaluated TRL and its association with survival in anal cancer patients treated with chemoradiation (CRT). Methods: A retrospective analysis of 140 patients with non-metastatic anal squamous cell carcinoma (SCC) treated with definitive CRT was performed. Total lymphocyte counts (TLC) at baseline and monthly intervals up to 12 months after initiating CRT were analyzed. Multivariable Cox regression analysis was performed to evaluate the association between overall survival (OS) and TRL, dichotomized by G4 TRL ( < 0.2k/μl) two months after initiating CRT. Kaplan-Meier and log-rank tests were used to compare OS between patients with versus without G4 TRL. Results: Median time of follow-up was 55 months. Prior to CRT, 95% of patients had a normal TLC ( > 1k/μl). Two months after initiating CRT, there was a median of 71% reduction in TLC from baseline and 84% of patients had TRL: 11% G1, 31% G2, 34% G3, and 8% G4. On multivariable Cox model, G4 TRL at two months was associated with a 3.7-fold increased risk of death (p = 0.013). On log-rank test, the 5-year OS rate was shorter in the cohort with versus without G4 TRL at two months (32% vs. 86%, p < 0.001). Conclusions: TRL is common and may be another prognostic marker of OS in anal cancer patients treated with CRT. The association between TRL and OS supports the hypothesis that host immunity plays an important role in survival among patients with anal cancer. These results support ongoing efforts of randomized trials underway to evaluate the potential role of immunotherapy in localized anal cancer.

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Clinical Significance of B-Type Natriuretic Peptide Levels at 3 Months after Atrial Fibrillation Ablation

Diseases ◽

10.3390/diseases9030049 ◽

2021 ◽

Vol 9 (3) ◽

pp. 49

Author(s):

Sen Matsumoto ◽

Yasuharu Matsunaga-Lee ◽

Masashi Ishimi ◽

Mamoru Ohnishi ◽

Nobutaka Masunaga ◽

...

Keyword(s):

Atrial Fibrillation ◽

Regression Analysis ◽

Natriuretic Peptide ◽

Roc Curve ◽

Cox Regression ◽

Significant Prognostic Factor ◽

Cox Regression Analysis ◽

Af Ablation ◽

Increased Risk ◽

The Impact

The role of B-type natriuretic peptide (BNP) levels as a predictor of arrhythmia recurrence (AR) after atrial fibrillation (AF) ablation remains unclear. In this study, we investigated the association of BNP levels before and 3 months after ablation with the risk of AR. A total of 234 patients undergoing their first session of AF ablation were included (68% male, mean age of 69 years). The cut-off value for discriminating AR was determined based on the maximum value of the area under the receiver operating characteristic (ROC) curve. The impact of BNP levels on AR was evaluated using Cox regression analysis. ROC curve analysis showed that the area under the curve for BNP at 3 months after the procedure was larger (0.714) compared to BNP levels before ablation (0.593). Elevated levels of BNP 3 months after the procedure (>40.5 pg/mL, n = 96) was associated with a higher risk of AR compared to those without elevated levels (34.4% vs. 10.9%, p < 0.01). Multivariate Cox regression analysis revealed that elevated BNP levels were associated with an increased risk of AR (hazard ratio 2.43; p = 0.014). Elevated BNP levels 3 months after AF ablation were a significant prognostic factor in AR, while baseline BNP levels were not.

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Underweight Is A Major Risk Factor of Atrial Fibrillation In Asian People With Type 2 Diabetes Mellitus

10.21203/rs.3.rs-853188/v1 ◽

2021 ◽

Author(s):

Jung-Chi Hsu ◽

Yen-Yun Yang ◽

Shu-Lin Chuang ◽

Yi-Wei Chung ◽

Lian-Yu Lin

Keyword(s):

Diabetes Mellitus ◽

Atrial Fibrillation ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Regression Model ◽

Cox Regression ◽

Rank Test ◽

Obesity Class ◽

Increased Risk

Abstract Background: Atrial fibrillation (AF) is prevalent in patients with type 2 diabetes mellitus (T2DM). Obesity commonly accompanies with T2DM and increases AF incidence. However, the dose-relationship of body mass index (BMI) and the risk of AF has seldom been studied in diabetes patients.Methods: This cohort study was conducted utilizing a database from National Taiwan University Hospital, a tertiary medical center in Taiwan. Between 2014 and 2019, a total of 64339 adult patients with T2DM were enrolled for analysis. The BMI was measured and categorized into several groups including underweight (BMI <18.5), normal range (18.5≤BMI <24), overweight (24≤BMI <27), obesity class 1 (27≤BMI <30), obesity class 2 (30≤BMI <35), and obesity class 3 (BMI≥35). Multivariate Cox regression models and spline regression model were employed to estimate the relationship between BMI and the risk of AF in patients with T2DM.Results: The incidence rate of AF was 1.97 per 1000 person-year during a median follow-up period of 70.7 months. In multivariate Cox regression model, by using normal BMI as reference group, individuals with underweight (HR 1.47, 95%CI 1.19-1.81, p<0.001) was significantly associated with increased risk of AF while overweight was significantly associated with reduced risk of AF (HR 0.83, 95%CI 0.76-0.91, p<0.001). The Kaplan-Meier analysis showed that the risk of AF was highest in the underweight group, followed by obesity class 3, while the overweight group had the least incidence of AF (log-rank test, p<0.001). Cubic restrictive spline model showed a “J-shaped” or “L-shape” relationship between BMI and the risk AF.Conclusions: We found that underweight carries the highest risk of AF in Asian patients with T2DM.

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Abstract 15220: Development of a Prediction Model for Atrial Fibrillation in Patients With Heart Failure and Preserved Ejection Fraction: Secondary Analysis of Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (topcat) Trial

Circulation ◽

10.1161/circ.142.suppl_3.15220 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Khaled Elkholey ◽

Zain Ul Abideen Asad ◽

Lampros Papadimitriou ◽

Udho THADANI ◽

Stavros Stavrakis

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

High Risk ◽

Ejection Fraction ◽

Risk Score ◽

Cox Regression ◽

Risk Groups ◽

Preserved Ejection Fraction ◽

Cox Regression Analysis ◽

Increased Risk

Background: Atrial fibrillation (AF) is a common comorbidity in heart failure with preserved ejection fraction (HFpEF) and portends an increased risk of cardiovascular events. We sought to identify predictors and develop a risk score of incident AF among patients with HFpEF. Methods: This was an exploratory, post-hoc analysis of the TOPCAT trial. Patients without known AF were included. Cox regression was used to identify independent predictors of incident AF. A risk score was derived from the weighed sum of the regression coefficients of each independent risk factor in the final model using Cox regression analysis. Results: A total of 2174 patients (mean age 67.0±9.4 years; female 55%) without known AF at baseline were included. During a median follow-up of 3 years, 102 (4.7%) patients developed new onset AF. Diabetes (HR=2.1, 95% CI 1.4-3.1; p=0.0002), peripheral arterial disease (HR=2.0, 95% CI 1.2-3.4; p=0.006), elevated (>144meq/dL) sodium (HR=2.1, 95% CI 1.4-3.1; p=0.0002) independently predicted incident AF, whereas current use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was protective (HR=0.61, 95% CI 0.38-0.99, p=0.048). Based on the simplified risk score which included these 4 variables, annualized AF incidence rates were 0.8%, 1.8%, and 3.6% in the low (score=0), intermediate (score=1 or 2), and high-risk (score >2) groups, respectively (log rank P<0.0001; Figure). Compared to the low risk group, the intermediate and high risk groups had a 2.5-fold and 5-fold increase in the risk of incident AF, respectively (HR=2.5, 95% CI 1.5-4.0, p=0.0003 and HR=4.9, 95% CI 2.9-9.4, p<0.0001, respectively). Model discrimination was good (c-statistic=0.67; 95% CI 0.61-0.72). Conclusions: A simplified risk score derived from clinical and laboratory characteristics predicts incident AF in patients with HFpEF and, upon further validation, may be used clinically for risk stratification or for AF screening in high risk groups. Figure

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P5506Proprotein convertase subtilisin/kexin 9 (PCSK9) and lipopolysaccharide (LPS) in patients with atrial fibrillation. A biomarker post-hoc analysis from the ATHERO-AF cohort

European Heart Journal ◽

10.1093/eurheartj/ehz746.0456 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

P Pignatelli Spinazzola ◽

A Farcomeni ◽

D Pastori ◽

F Violi

Keyword(s):

Atrial Fibrillation ◽

Nadph Oxidase ◽

Rank Test ◽

Post Hoc Analysis ◽

Increased Risk ◽

Post Hoc ◽

First Time ◽

Nadph Oxidase Activation

Abstract Background Proprotein convertase subtilisin/kexin 9 (PCSK9) and lipopolysaccharides (LPS) are emerging as novel risk factors for cardiovascular events (CVEs). In vitro evidence suggested that PCSK9 production may be elicited by LPS via oxidative stress, However, their relationship in patients with atrial fibrillation (AF) has not been investigated. Methods Post-hoc analysis of a prospective, single centre cohort study of 907 patients with non-valvular AF. At baseline, PCSK9, LPS and NADPH oxidase (sNOX2-dp) were measured. We also assessed adherence to Mediterranean Diet (Med-Diet). PCSK9 and LPS were correlated to incidence of CVEs. Results At multivariate analysis, with PCSK9 above the median as dependent variable we found that high adherence to Med-Diet and antiplatelet drugs were inversely correlated to PCSK9 (odds ratio [OR] 0.737 95% Confidence interval [CI] 0.643–0.845 p=0.001 and OR 0.437 95% CI 0.219–0.871 p=0.017 respectively), while sNOX2-dp and LPS concentrations (OR 1.759 C.I. 95% 1.167–2.650, p=0.007 and OR 1.727 C.I. 95% 1.147–2.600 p=0.009 respectively) were directly correlated. In particular use of oil and wine were negatively associated to high PCSK9 levels (OR 0.376 95% CI 0.185–0.763, p=0.001 and OR 0.460 95% CI 0.289–0.733 p=0.007, respectively). Patients with concomitant high PCSK9 and LPS (highest tertile for both) had and increased risk of CVEs as compared to those with low levels (lowest tertile for both) with 48 and 29 CVEs in each group respectively (Log-Rank test, p=0.022) Conclusion This study demonstrated for the first time in vivo that circulating levels of PCSK9 are associated with high LPS concentration and NADPH oxidase activation. Concomitant increase of PCSK9 and LPS increased the risk of CVEs.

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