P219Plasma oxidized low density lipoprotein, CD40 and p-selectin levels: relationship to diseases with and without atrial fibrillation:

Background/Aim: To investigate the role of oxidative stress (OS) in the development of chronic kidney disease (CKD) in atrial fibrillation (AF). Methods: We compared OS burden, determined at study inclusion as plasma concentrations of oxidized low-density lipoprotein (oxLDL), between stable AF patients (n = 256, mean age: 62.8 ± 9.3 years; 60.9% males) with preserved renal function, defined as an estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2, and a matched control group in sinus rhythm (n = 138, mean age: 61.5 ± 11.2 years; 60.9% males). During the prospective follow-up of AF patients, we investigated the association and prognostic validity of oxLDL for CKD development, diagnosed as a sustained decline in eGFR to <60 ml/min/1.73 m2. Results: AF patients had a higher mean oxLDL (76.2 ± 21.7 U/l) compared to sinus rhythm controls (61.6 ± 13.1 U/l; p < 0.001). AF presence independently predicted increased oxLDL levels in the study cohort [β = 14.7; 95% confidence interval (CI), 10.7-18.7; p < 0.001]. Over a median 4-year follow-up, 19.9% of AF patients developed CKD. Adjusting for all clinical covariates, oxLDL (per tertile) was associated with a hazard ratio of 2.17 for CKD occurrence (95% CI, 1.40-3.35; p < 0.001). AF patients in the upper oxLDL tertile (≥88.7 U/l) had a 3.70-fold (95% CI, 1.55-8.81) higher risk for CKD compared to the lower oxLDL tertile (<67.0 U/l) patients (p < 0.001). oxLDL improved discriminative validity (c-statistic increment: 0.041, 95% CI, 0.007-0.075, p = 0.017), and increased the net reclassification and integrated discrimination for CKD risk by 12.4 and 6.0%, respectively (both p < 0.001). Conclusions: oxLDL is increased in AF patients compared to sinus rhythm controls. oxLDL has an independent association and an incremental predictive value that might complement clinical CKD risk assessment in AF patients following further research.

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Prestroke statins use reduces oxidized low density lipoprotein level and improves clinical outcomes in patients with atrial fibrillation related acute ischemic stroke

10.21203/rs.2.10861/v1 ◽

2019 ◽

Author(s):

lanying he ◽

Ronghua Xu ◽

Jian Wang ◽

LIli Zhang ◽

Lijuan Zhang ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Confidence Interval ◽

Clinical Outcomes ◽

Odds Ratio ◽

Adjusted Odds Ratio ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Low Density ◽

Oxidized Low Density Lipoprotein

Abstract Background Atrial fibrillation (AF) is a common cause of cerebral infarction, which could lead to endothelial dysfunction, increased reactive oxygen species (ROS) and oxidized low density lipoprotein (Ox-LDL).AF is associated with higher mortality and more severe neurologic disability. Statins may exert neuroprotective effects that are independent of LDL-C lowering. The purpose of our study was to investigate whether prestroke statins use could reduce plasma Ox-LDL level and improve clinical outcomes in patients with AF related acute ischemic stroke(AIS). Methods This was a multicenter consecutive trial that involved four medical centers, 242 AIS patients with AF were identified, who underwent a comprehensive clinical investigation and a 72h-Holter electrocardiogram monitoring. All patients were divided into two groups: prestroke statins use and no prestroke statins use groups, who were followed up for 3 months. Ox-LDL was measured using enzyme-linked immunosorbent assay (ELISA) on admission and 3 months. The outcome was death or major disability (modified Rankin Scale score≥3) at 3 months after AIS. Results Plasma Ox-LDL level was significantly lower in prestroke statins use than in no prestroke statins use on admission (P=0.001). Plasma Ox-LDL level on admission were associated with 3-month outcome(P<0.05).In fully adjusted models, prestroke statins use was associated with reduced 3-month mortality (adjusted odds ratio, 0.43; 95% confidence interval, 0.20–0.93; P=0.031), major disability (adjusted odds ratio, 0.33; 95% confidence interval, 0.13–0.82; P=0.017), and composite outcome (adjusted odds ratio, 0.25; 95% confidence interval,0.11–0.56; P=0.001). Conclusions Prestroke statins use can reduce plasma Ox-LDL level and improve clinical outcomes in patients with AF related AIS.

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Prestroke statins use reduces oxidized low density lipoprotein levels and improves clinical outcomes in patients with atrial fibrillation related acute ischemic stroke

BMC Neurology ◽

10.1186/s12883-019-1463-7 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 3

Author(s):

Lanying He ◽

Ronghua Xu ◽

Jian Wang ◽

Lili Zhang ◽

Lijuan Zhang ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Clinical Outcomes ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Enzyme Linked Immunosorbent Assay ◽

Low Density ◽

Composite Outcome ◽

Oxidized Low Density Lipoprotein

Abstract Background Atrial fibrillation (AF) is a common cause of cerebral infarction, which could lead to endothelial dysfunction, increased reactive oxygen species (ROS) and oxidized low density lipoprotein (Ox-LDL).AF is associated with higher mortality and more severe neurologic disability. Statins may exert neuroprotective effects that are independent of LDL-C lowering. The purpose of our study was to investigate whether prestroke statins use could reduce plasma Ox-LDL levels and improve clinical outcomes in patients with AF-related acute ischemic stroke (AIS). Methods This was a multicenter prospective study that involved four medical centers, 242 AIS patients with AF were identified, who underwent a comprehensive clinical investigation and a 72 h-Holter electrocardiogram monitoring. All patients were divided into two groups: prestroke statins use and no prestroke statins use groups, who were followed up for 3 months. Plasma Ox-LDL levels were measured using enzyme-linked immunosorbent assay (ELISA) on admission and at 3 months. The outcome was death, major disability (modified Rankin Scale score ≥ 3), and composite outcome (death/major disability) at 3 months after AIS. Results One hundred thirty-six patients were in no prestroke statins use group, and 106 in prestroke statins use group. Plasma Ox-LDL levels were significantly lower in prestroke statins use than in no prestroke statins use on admission and at 3 months (P < 0.001). Plasma Ox-LDL levels on admission were associated with 3-month mortality [adjusted odds ratio (OR), 1.05; 95% confidence interval (CI), 0.99–1.12; P = 0.047]. In fully adjusted models, prestroke statins use was associated with reduced 3-month mortality [adjusted OR, 0.38; 95% CI, 0.16–0.91; P = 0.031)], major disability (adjusted OR, 0.38; 95% CI, 0.15–0.99; P = 0.047), and composite outcome (adjusted OR, 0.31; 95% CI, 0.17–0.74; P = 0.009). Conclusions Prestroke statins use can reduce plasma Ox-LDL levels and improve clinical outcomes in patients with AF-related AIS.

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PCSK9 Regulates Nox2-Mediated Platelet Activation via CD36 Receptor in Patients with Atrial Fibrillation

Antioxidants ◽

10.3390/antiox9040296 ◽

2020 ◽

Vol 9 (4) ◽

pp. 296 ◽

Cited By ~ 2

Author(s):

Vittoria Cammisotto ◽

Daniele Pastori ◽

Cristina Nocella ◽

Simona Bartimoccia ◽

Valentina Castellani ◽

...

Keyword(s):

Oxidative Stress ◽

Risk Factors ◽

Atrial Fibrillation ◽

Platelet Activation ◽

Cardiovascular Events ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Low Density ◽

Oxidized Low Density Lipoprotein ◽

Cd36 Receptor

Background: High levels of proprotein convertase subtilisin/kexin 9 (PCSK9) is predictive of cardiovascular events (CVEs) in atrial fibrillation (AF). We hypothesized that PCSK9 may directly induce platelet activation (PA). Methods: We measured platelet aggregation, recruitment, Thromboxane B2 (TxB2) formation and soluble P-selectin levels as markers of PA and soluble Nox2-derived peptide (sNox2-dp), H2O2, isoprostanes and oxidized Low-Density-Lipoprotein (oxLDL) to analyze oxidative stress (OS) in 88 patients having PCSK9 values < (n = 44) or > (n = 44) 1.2 ng/mL, balanced for age, sex and cardiovascular risk factors. Furthermore, we investigated if normal (n = 5) platelets incubated with PCSK9 (1.0–2.0 ng/mL) alone or with LDL (50 µg/mL) displayed changes of PA, OS and down-stream signaling. Results: PA and OS markers were significantly higher in patients with PCSK9 levels > 1.2 ng/mL compared to those with values < 1.2 ng/mL (p < 0.001). Levels of PCSK9 significantly correlated with markers of PA and OS. Platelets incubation with PCSK9 increased PA, OS and p38, p47 and Phospholipase A2 (PLA2) phosphorylation. These changes were amplified by adding LDL and blunted by CD36 or Nox2 inhibitors. Co-immunoprecipitation analysis revealed an immune complex of PCSK9 with CD36. Conclusions: We provide the first evidence that PCSK9, at concentration found in the circulation of AF patients, directly interacts with platelets via CD36 receptor and activating Nox2: this effect is amplified in presence of LDL.

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Oxidized Low-density Lipoprotein (ox-LDL) Cholesterol Induces the Expression of miRNA-223 and L-type Calcium Channel Protein in Atrial Fibrillation

Scientific Reports ◽

10.1038/srep30368 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 6

Author(s):

Fengping He ◽

Xin Xu ◽

Shuguo Yuan ◽

Liangqiu Tan ◽

Lingjun Gao ◽

...

Keyword(s):

Atrial Fibrillation ◽

Protein Expression ◽

Calcium Channel ◽

Ldl Cholesterol ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Calcium Currents ◽

Low Density ◽

Oxidized Low Density Lipoprotein ◽

Channel Protein

Abstract Atrial fibrillation (AF) is the most common sustained arrhythmia causing high morbidity and mortality. While changing of the cellular calcium homeostasis plays a critical role in AF, the L-type calcium channel α1c protein has suggested as an important regulator of reentrant spiral dynamics and is a major component of AF-related electrical remodeling. Our computational modeling predicted that miRNA-223 may regulate the CACNA1C gene which encodes the cardiac L-type calcium channel α1c subunit. We found that oxidized low-density lipoprotein (ox-LDL) cholesterol significantly up-regulates both the expression of miRNA-223 and L-type calcium channel protein. In contrast, knockdown of miRNA-223 reduced L-type calcium channel protein expression, while genetic knockdown of endogenous miRNA-223 dampened AF vulnerability. Transfection of miRNA-223 by adenovirus-mediated expression enhanced L-type calcium currents and promoted AF in mice while co-injection of a CACNA1C-specific miR-mimic counteracted the effect. Taken together, ox-LDL, as a known factor in AF-associated remodeling, positively regulates miRNA-223 transcription and L-type calcium channel protein expression. Our results implicate a new molecular mechanism for AF in which miRNA-223 can be used as an biomarker of AF rheumatic heart disease.

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Prestroke statins use reduces oxidized low density lipoprotein levels and improves clinical outcomes in patients with atrial fibrillation related acute ischemic stroke

10.21203/rs.2.10861/v2 ◽

2019 ◽

Author(s):

lanying he ◽

Ronghua Xu ◽

Jian Wang ◽

LIli Zhang ◽

Lijuan Zhang ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Clinical Outcomes ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Enzyme Linked Immunosorbent Assay ◽

Low Density ◽

Composite Outcome ◽

Oxidized Low Density Lipoprotein

Abstract Background: Atrial fibrillation (AF) is a common cause of cerebral infarction, which could lead to endothelial dysfunction, increased reactive oxygen species (ROS) and oxidized low density lipoprotein (Ox-LDL).AF is associated with higher mortality and more severe neurologic disability. Statins may exert neuroprotective effects that are independent of LDL-C lowering. The purpose of our study was to investigate whether prestroke statins use could reduce plasma Ox-LDL levels and improve clinical outcomes in patients with AF-related acute ischemic stroke (AIS). Methods: This was a multicenter prospective study that involved four medical centers, 242 AIS patients with AF were identified, who underwent a comprehensive clinical investigation and a 72h-Holter electrocardiogram monitoring. All patients were divided into two groups: prestroke statins use and n o prestroke statins use groups , who were followed up for 3 months. Plasma Ox-LDL levels were measured using enzyme-linked immunosorbent assay (ELISA) on admission and at 3 months. The outcome was death, major disability (modified Rankin Scale score≥3), and composite outcome (death/major disability) at 3 months after AIS. Results: 136 patients were in no prestroke statins use group, and 106 in prestroke statins use group . Plasma Ox-LDL levels were significantly lower in prestroke statins use than in no prestroke statins use on admission and at 3 months (P<0.001). Plasma Ox-LDL levels on admission were associated with 3-month mortality [adjusted odds ratio (OR), 1.05; 95% confidence interval(CI), 0.99-1.12; P=0.047]. In fully adjusted models, prestroke statins use was associated with reduced 3-month mortality [adjusted OR, 0.38; 95% CI, 0.16–0.91; P=0.031)], major disability (adjusted OR, 0.38; 95%CI, 0.15–0.99; P=0.047), and composite outcome (adjusted OR, 0.31; 95% CI,0.17–0.74; P=0.009). Conclusions: Prestroke statins use can reduce plasma Ox-LDL levels and improve clinical outcomes in patients with AF-related AIS.

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Prestroke statins use reduces oxidized low density lipoprotein levels and improves clinical outcomes in patients with atrial fibrillation related acute ischemic stroke

10.21203/rs.2.10861/v3 ◽

2019 ◽

Author(s):

lanying he ◽

Ronghua Xu ◽

Jian Wang ◽

LIli Zhang ◽

Lijuan Zhang ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Clinical Outcomes ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Enzyme Linked Immunosorbent Assay ◽

Low Density ◽

Composite Outcome ◽

Oxidized Low Density Lipoprotein

Abstract Background: Atrial fibrillation (AF) is a common cause of cerebral infarction, which could lead to endothelial dysfunction, increased reactive oxygen species (ROS) and oxidized low density lipoprotein (Ox-LDL).AF is associated with higher mortality and more severe neurologic disability. Statins may exert neuroprotective effects that are independent of LDL-C lowering. The purpose of our study was to investigate whether prestroke statins use could reduce plasma Ox-LDL levels and improve clinical outcomes in patients with AF-related acute ischemic stroke (AIS). Methods: This was a multicenter prospective study that involved four medical centers, 242 AIS patients with AF were identified, who underwent a comprehensive clinical investigation and a 72h-Holter electrocardiogram monitoring. All patients were divided into two groups: prestroke statins use and n o prestroke statins use groups , who were followed up for 3 months. Plasma Ox-LDL levels were measured using enzyme-linked immunosorbent assay (ELISA) on admission and at 3 months. The outcome was death, major disability (modified Rankin Scale score≥3), and composite outcome (death/major disability) at 3 months after AIS. Results: 136 patients were in no prestroke statins use group, and 106 in prestroke statins use group . Plasma Ox-LDL levels were significantly lower in prestroke statins use than in no prestroke statins use on admission and at 3 months (P<0.001). Plasma Ox-LDL levels on admission were associated with 3-month mortality [adjusted odds ratio (OR), 1.05; 95% confidence interval(CI), 0.99-1.12; P=0.047]. In fully adjusted models, prestroke statins use was associated with reduced 3-month mortality [adjusted OR, 0.38; 95% CI, 0.16–0.91; P=0.031)], major disability (adjusted OR, 0.38; 95%CI, 0.15–0.99; P=0.047), and composite outcome (adjusted OR, 0.31; 95% CI,0.17–0.74; P=0.009). Conclusions: Prestroke statins use can reduce plasma Ox-LDL levels and improve clinical outcomes in patients with AF-related AIS.

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