Treatment with beta-blockers is associated with lower levels of Lp-PLA2 and suPAR in carotid plaques

Asciutto, Giuseppe; Edsfeldt, Andreas; Dias, Nuno; Nilsson, Jan; Prehn, Cornelia; Adamski, Jerzy; Gonçalves, Isabel

doi:10.1016/j.carpath.2013.04.005

Cited by 16 publications

(16 citation statements)

References 30 publications

(21 reference statements)

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“…Thus, serial measurements after acute MI showed a minimal 15% average increase in suPAR levels, compared to a 365% increase in hsCRP levels suPAR appears to also be superior to hsCRP for prognostication of in‐hospital mortality in patients with severe sepsis and septic shock . There are no prospective data on interventions lowering suPAR levels; however, subjects on long‐term treatment with beta‐blockers were found to have lower levels of suPAR in their carotid endarterectomy specimens compared to those without beta‐blocker use …”

Section: Discussionmentioning

confidence: 99%

“…18 There are no prospective data on interventions lowering suPAR levels; however, subjects on long-term treatment with beta-blockers were found to have lower levels of suPAR in their carotid endarterectomy specimens compared to those without betablocker use. 19 suPAR has been extensively studied in the infectious disease and critical care populations, but its relationship to CVD and associated outcomes has only been recently explored. The majority of these studies performed in Europe have examined the relationship between suPAR and incident CVD in healthy community-based populations.…”

Section: Discussionmentioning

confidence: 99%

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Soluble Urokinase Plasminogen Activator Receptor Level Is an Independent Predictor of the Presence and Severity of Coronary Artery Disease and of Future Adverse Events

Eapen

Manocha

Ghasemzadeh

et al. 2014

JAHA

120

106

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IntroductionSoluble urokinase plasminogen activator receptor (suPAR) is an emerging inflammatory and immune biomarker. Whether suPAR level predicts the presence and the severity of coronary artery disease (CAD), and of incident death and myocardial infarction (MI) in subjects with suspected CAD, is unknown.Methods and ResultsWe measured plasma suPAR levels in 3367 subjects (67% with CAD) recruited in the Emory Cardiovascular Biobank and followed them for adverse cardiovascular (CV) outcomes of death and MI over a mean 2.1±1.1 years. Presence of angiographic CAD (≥50% stenosis in ≥1 coronary artery) and its severity were quantitated using the Gensini score. Cox's proportional hazard survival and discrimination analyses were performed with models adjusted for established CV risk factors and C‐reactive protein levels. Elevated suPAR levels were independently associated with the presence of CAD (P<0.0001) and its severity (P<0.0001). A plasma suPAR level ≥3.5 ng/mL (cutoff by Youden's index) predicted future risk of MI (hazard ratio [HR]=3.2; P<0.0001), cardiac death (HR=2.62; P<0.0001), and the combined endpoint of death and MI (HR=1.9; P<0.0001), even after adjustment of covariates. The C‐statistic for a model based on traditional risk factors was improved from 0.72 to 0.74 (P=0.008) with the addition of suPAR.ConclusionElevated levels of plasma suPAR are associated with the presence and severity of CAD and are independent predictors of death and MI in patients with suspected or known CAD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Soluble Urokinase Plasminogen Activator Receptor Level Is an Independent Predictor of the Presence and Severity of Coronary Artery Disease and of Future Adverse Events

Eapen

Manocha

Ghasemzadeh

et al. 2014

JAHA

120

106

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“…Lp-PLA 2 levels were observed to correlate with three lysoPCs (16:0, 18:0, and 18:1) in carotid plaques before and after adjusting for age, sex, hypertension, CAD, and statin usage [10]. A close association between circulating lysoPC (16:0) and the ba-PWV index of central arterial stiffness [25], [26], and serum IL-6, was reported in human subjects [14].…”

Section: Discussionmentioning

confidence: 75%

“…The activity of lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) was measured using a modification of a previously described, high-throughput radiometric activity assay [10]. Plasma malondialdehyde (MDA) was measured from thiobarbituric acid-reactive substances using the TBARS Assay Kit (Zepto-Metrix Co., Buffalo, NY, USA).…”

Section: Methodsmentioning

confidence: 99%

Prehypertension-Associated Elevation in Circulating Lysophosphatidlycholines, Lp-PLA2 Activity, and Oxidative Stress

et al. 2014

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Prehypertension is a risk factor for atherosclerosis. We investigated alterations in plasma metabolites that are associated with prehypertension. A group of 53 individuals was identified who remained within the range of prehypertension during repeated measurements in a 3-year period. This group was compared with the control group of 53 normotensive subjects who were matched for age and gender. Metabolomic profiles were analyzed with UPLC-LTQ-Orbitrap mass spectrometry. The prehypertensive group showed higher levels of lysophosphatidylcholines (lysoPCs) containing C14:0, C16:1, C16:0, C18:2, C18:1, C18:0, C20:5, C20:4, C20:3, and C22:6, higher circulating Lp-PLA2 activity, oxidized LDL (ox-LDL), interleukin 6 (IL-6), urinary 8-epi-PGF2α, and higher brachial-ankle pulse wave velocity (ba-PWV), before and after adjusting for BMI, WHR, smoking, alcohol consumption, serum lipid profiles, glucose, and insulin. LysoPC (16:0) was the most important plasma metabolite for evaluating the difference between control and prehypertensive groups, with a variable important in the projection (VIP) value of 17.173, and it showed a positive and independent association with DBP and SBP. In the prehypertensive group, the levels of lysoPC (16:0) positively and significantly correlated with ox-LDL, Lp-PLA2 activity, 8-epi-PGF2α, ba-PWV, and IL-6 before and after adjusting for confounding variables. Prehypertension-associated elevations in lysoPCs, Lp-PLA2 activity, ox-LDL, urinary 8-epi-PGF2α, IL-6, and ba-PWV could indicate increased oxidative stress from Lp-PLA2-catalyzed PC hydrolysis during increased LDL oxidation, thereby enhancing proinflammation and arterial stiffness.

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“…Indications for CEA have been previously described. 18 Patients with ipsilateral carotid artery occlusion, radiation induced primary carotid stenosis or restenosis after previous CEA or endovascular treatment were excluded. Patients were considered to have asymptomatic carotid disease if they had no amaurosis fugax (AF), transient ischemic attacks (TIAs) or stroke in the 6 months prior to surgery as assessed clinically by an independent accredited neurologist.…”

Section: Patient Datamentioning

confidence: 99%

Low levels of IgG autoantibodies against the apolipoprotein B antigen p210 increases the risk of cardiovascular death after carotid endarterectomy

Asciutto¹,

Dias²,

Edsfeldt³

et al. 2015

Atherosclerosis

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Low levels of IgG autoantibodies against the apolipoprotein B antigen p210 increases the risk of cardiovascular death after carotid endarterectomy.Asciutto, Giuseppe; Dias, Nuno; Edsfeldt, Andreas; Alm, Ragnar; Nordin Fredrikson, Gunilla; Goncalves, Isabel; Nilsson, Jan Link to publication Citation for published version (APA): Asciutto, G., Dias, N., Edsfeldt, A., Alm, R., Nordin Fredrikson, G., Goncalves, I., & Nilsson, J. (2015). Low levels of IgG autoantibodies against the apolipoprotein B antigen p210 increases the risk of cardiovascular death after carotid endarterectomy. Atherosclerosis, 239(2), 289-294. DOI: 10.1016289-294. DOI: 10. /j.atherosclerosis.2015 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Methods: Native (nat) and malondialdehyde (MDA)-modified apoB p210 autoantibodies (IgM-p210nat, IgG-p210nat, IgM-p210MDA and IgG-p210MDA) were analyzed by ELISA from plasma samples of 351 patients at the time they underwent CEA. The incidence of postoperative CV events was assessed using national registers.Results: A total of 52 non-fatal and 15 fatal CV events were registered during the follow-up period (35.1 ± 16.7 months). Patients who suffered from a fatal CV event had significantly lower plasma levels of IgG-p210nat and IgG-p210MDA. Kaplan-Meier curves of event-free survival showed increased CV mortality in patients with levels of IgG-p210nat and IgGp210MDA below the median (Log Rank 7.813, p .005 and 9.105, p .003 respectively). The association between low levels of p210 IgG and fatal post-operative CV events remained significant when adjusting for age, sex, total cholesterol, HDL cholesterol, smoking habits and hypertension in a Cox Proportional Hazard model (hazard ratios (HR) IgG-p210nat below median: HR 6.7 (95% C.I. 1.5-30.6, p .013) and IgG-p210MDA below median: HR 7.8 (95% C.I. 1.7-35.5, p .008).Conclusions: The present findings support the notion that autoantibodies against LDL antigens are involved in the atherosclerotic disease process and suggest that CEA patients with low levels of IgG-p210nat and IgG-p210MDA have an increased risk of post-operative CV death.

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Treatment with beta-blockers is associated with lower levels of Lp-PLA2 and suPAR in carotid plaques

Cited by 16 publications

References 30 publications

Soluble Urokinase Plasminogen Activator Receptor Level Is an Independent Predictor of the Presence and Severity of Coronary Artery Disease and of Future Adverse Events

Soluble Urokinase Plasminogen Activator Receptor Level Is an Independent Predictor of the Presence and Severity of Coronary Artery Disease and of Future Adverse Events

Prehypertension-Associated Elevation in Circulating Lysophosphatidlycholines, Lp-PLA2 Activity, and Oxidative Stress

Low levels of IgG autoantibodies against the apolipoprotein B antigen p210 increases the risk of cardiovascular death after carotid endarterectomy

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