Correction to: Reduced oxidized LDL in T2D plaques is associated with a greater statin usage but not with future cardiovascular events

Abstract Background Type 2 diabetes (T2D) patients are at a greater risk of cardiovascular events due to aggravated atherosclerosis. Oxidized LDL (oxLDL) has been shown to be increased in T2D plaques and suggested to contribute to plaque ruptures. Despite intensified statin treatment during the last decade the higher risk for events remains. Here, we explored if intensified statin treatment was associated with reduced oxLDL in T2D plaques and if oxLDL predicts cardiovascular events, to elucidate whether further plaque oxLDL reduction would be a promising therapeutic target. Methods Carotid plaque OxLDL levels and plasma lipoproteins were assessed in 200 patients. Plaque oxLDL was located by immunohistochemistry. Plaque cytokines, cells and scavenger receptor gene expression were quantified by Luminex, immunohistochemistry and RNA sequencing, respectively. Clinical information and events during follow-up were obtained from national registers. Results Plaque oxLDL levels correlated with markers of inflammatory activity, endothelial activation and plasma LDL cholesterol (r = 0.22-0.32 and p ≤ 0.01 for all). T2D individuals exhibited lower plaque levels of oxLDL, sLOX-1(a marker of endothelial activation) and plasma LDL cholesterol (p = 0.001, p = 0.006 and p = 0.009). No increased gene expression of scavenger receptors was identified in T2D plaques. The lower oxLDL content in T2D plaques was associated with a greater statin usage (p = 0.026). Supporting this, a linear regression model showed that statin treatment was the factor with the strongest association to plaque oxLDL and plasma LDL cholesterol (p < 0.001 for both). However, patients with T2D more frequently suffered from symptoms and yet plaque levels of oxLDL did not predict cardiovascular events in T2D (findings are summarized in Fig. 1a). Conclusions This study points out the importance of statin treatment in affecting plaque biology in T2D. It also implies that other biological components, beyond oxLDL, need to be identified and targeted to further reduce the risk of events among T2D patients receiving statin treatment.

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Differences in phenotype, genotype and cardiovascular events between patients with probable and definite heterozygous familial hypercholesterolemia

Personalized Medicine ◽

10.2217/pme-2018-0135 ◽

2019 ◽

Vol 16 (6) ◽

pp. 467-478

Author(s):

Ye-Xuan Cao ◽

Bing-Yang Zhou ◽

Di Sun ◽

Sha Li ◽

Yuan-Lin Guo ◽

...

Keyword(s):

Familial Hypercholesterolemia ◽

Cardiovascular Events ◽

Oxidized Ldl ◽

Low Density Lipoprotein ◽

Survival Rates ◽

Gene Mutations ◽

Density Lipoprotein ◽

Heterozygous Familial Hypercholesterolemia ◽

Lipid Clinic ◽

Kaplan Meier

Aim: To investigated the potential differences between probable and definite heterozygous familial hypercholesterolemia (HeFH) patients diagnosed by Dutch Lipid Clinic Network criteria. Methods: Clinical characteristics, lipid profile, severity of coronary artery stenosis and gene mutations were compared. Kaplan–Meier curve was performed to evaluate the cardiovascular events. Results: Overall, 325 participants were included and divided into two groups: probable (n = 233) and definite HeFH (n = 92). Definite HeFH patients had higher low-density lipoprotein cholesterol (LDL-C), oxidized-LDL and proprotein convertase subtilisin/kexin 9 levels, and higher prevalence of tendon xanthomas. The incidence of genetic mutations was statistically higher in definite HeFH than probable HeFH patients. The coronary stenosis calculated by Gensini score was statistically severer in definite HeFH patients. The best LDL-C threshold for predicting mutations was 5.14 mmol/l. Definite HeFH had lower event-free survival rates. Conclusion: Definite HeFH patients had higher severity of phenotype and genotype, and higher risk of cardiovascular events.

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Anti-Oxidized LDL Antibodies and Coronary Artery Disease: A Systematic Review

Antioxidants ◽

10.3390/antiox8100484 ◽

2019 ◽

Vol 8 (10) ◽

pp. 484 ◽

Cited By ~ 3

Author(s):

Victor J. van den Berg ◽

Maxime M. Vroegindewey ◽

Isabella Kardys ◽

Eric Boersma ◽

Dorian Haskard ◽

...

Keyword(s):

Systematic Review ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Cardiovascular Events ◽

Oxidized Ldl ◽

Full Text Review ◽

Electronic Database Search ◽

Artery Disease ◽

Relationship Of ◽

The Relationship

Antibodies to oxidized LDL (oxLDL) may be associated with improved outcomes in cardiovascular disease. However, analysis is restricted by heterogenous study design and endpoints. Our objective was to conduct a comprehensive systematic review assessing anti-oxLDL antibodies in relation to coronary artery disease (CAD). Through a systematic literature search, we identified all studies assessing the relationship of either, IgG or IgM ox-LDL/ copper-oxLDL/ malondialdehyde-LDL, with coronary atherosclerosis or cardiovascular events in populations with, and without, established CAD. Systematic review best practices were adhered to and study quality was assessed. An initial electronic database search identified 2059 records, which was subsequently followed by abstract and full-text review. Finally, we included 18 studies with over 1811 patients with CAD. The studies varied according to populations studied, conventional cardiovascular risk factors and interventional modalities used to assess CAD. IgM anti-oxLDL antibodies were found to indicate protection from more severe CAD and possibly cardiovascular events, whilst the relationship with IgG is more complex and difficult to elucidate, with studies reporting divergent results. In this systematic review, there is evidence that suggests a relationship between anti-oxLDL antibodies and CAD, especially for the IgM subclass. However, further studies, with well-characterized prospective cohorts, will be important to clarify these associations.

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Lectin-like oxidized-LDL receptor-1 (LOX-1) polymorphisms influence cardiovascular events rate during statin treatment

International Journal of Cardiology ◽

10.1016/j.ijcard.2006.07.045 ◽

2007 ◽

Vol 119 (1) ◽

pp. 41-47 ◽

Cited By ~ 12

Author(s):

L. Puccetti ◽

A.L. Pasqui ◽

F. Bruni ◽

M. Pastorelli ◽

F. Ciani ◽

...

Keyword(s):

Cardiovascular Events ◽

Oxidized Ldl ◽

Ldl Receptor ◽

Statin Treatment

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Relationship between Metabolic Syndrome and its Diagnosis and Treatment of Hypertension Strategy

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.474-476.211 ◽

2011 ◽

Vol 474-476 ◽

pp. 211-214

Author(s):

Xing Shou Pan ◽

Zhao He Huang ◽

Jing Sheng Lan

Keyword(s):

Metabolic Syndrome ◽

Cardiovascular Events ◽

Oxidized Ldl ◽

Integrated Control ◽

Treatment Strategies ◽

Hypertensive Patients ◽

Treatment Of Hypertension ◽

Close Relationship ◽

Low Hdl ◽

The Relationship

Explore the relationship between hypertension and metabolic syndrome, and treatment strategies. On the relationship between hypertension and metabolic syndrome were analyzed retrospectively, and how to conduct clinics for certain summary. Metabolic syndrome and hypertension exists a close relationship. Hypertensive patients with low HDL-C and high LDL-C level; whether oxidized LDL is high value or low value, MS group the incidence of cardiovascular disease is always higher than non-MS group. MS in blood pressure is an important component of integrated control of MS, can effectively prevent the occurrence of cardiovascular events and diabetes.

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Relationship of IgG and IgM autoantibodies and immune complexes to oxidized LDL with markers of oxidation and inflammation and cardiovascular events: results from the EPIC-Norfolk Study

The Journal of Lipid Research ◽

10.1194/jlr.m015776 ◽

2011 ◽

Vol 52 (10) ◽

pp. 1829-1836 ◽

Cited By ~ 87

Author(s):

Amir Ravandi ◽

S. Matthijs Boekholdt ◽

Ziad Mallat ◽

Philippa J. Talmud ◽

John J. P. Kastelein ◽

...

Keyword(s):

Immune Complexes ◽

Cardiovascular Events ◽

Oxidized Ldl ◽

Relationship Of

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We-W44:3 Lectin-like oxidized-LDL receptor-1 (LOX-1) polymorphism is associated with increased rate of cardiovascular events during statin treatment

Atherosclerosis Supplements ◽

10.1016/s1567-5688(06)81325-5 ◽

2006 ◽

Vol 7 (3) ◽

pp. 333

Author(s):

G. Todiere ◽

F. Bruni ◽

A.L. Pasqui ◽

M. Pastorelli ◽

F. Ciani ◽

...

Keyword(s):

Cardiovascular Events ◽

Oxidized Ldl ◽

Ldl Receptor ◽

Statin Treatment

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Relationship Between Oxidized LDL, IgM, and IgG Autoantibodies to ox-LDL Levels With Recurrent Cardiovascular Events in Swedish Patients With Previous Myocardial Infarction

Angiology ◽

10.1177/0003319713512720 ◽

2013 ◽

Vol 65 (10) ◽

pp. 932-936 ◽

Cited By ~ 6

Author(s):

M. Crisby ◽

L. Henareh ◽

Stefan Agewall

Keyword(s):

Myocardial Infarction ◽

Cardiovascular Events ◽

Oxidized Ldl ◽

Previous Myocardial Infarction

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Plasma Protein Profile of Carotid Artery Atherosclerosis and Atherosclerotic Outcomes

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.120.315597 ◽

2021 ◽

Author(s):

Lars Lind ◽

Bruna Gigante ◽

Yan Borné ◽

Tobias Feldreich ◽

Jerzy Leppert ◽

...

Keyword(s):

Ischemic Stroke ◽

Carotid Artery ◽

Cardiovascular Events ◽

Mendelian Randomization ◽

Oxidized Ldl ◽

Protein Profile ◽

Density Lipoprotein ◽

Carotid Artery Atherosclerosis ◽

Mendelian Randomization Analysis ◽

Randomization Analysis

Objective: To identify causal pathophysiological mechanisms for atherosclerosis and incident cardiovascular events using protein measurements. Approach and Results: Carotid artery atherosclerosis was assessed by ultrasound, and 86 cardiovascular-related proteins were measured using the Olink CVD-I panel in 7 Swedish prospective studies (11 754 individuals). The proteins were analyzed in relation to intima-media thickness in the common carotid artery (IMT-CCA), plaque occurrence, and incident cardiovascular events (composite end point of myocardial infarction or ischemic stroke) using a discovery/replication approach in different studies. After adjustments for traditional cardiovascular risk factors, 11 proteins remained significantly associated with IMT-CCA in the replication stage, whereas 9 proteins were replicated for plaque occurrence and 17 proteins for incident cardiovascular events. NT-proBNP (N-terminal pro-B-type natriuretic peptide) and MMP (matrix metalloproteinase)-12 were associated with both IMT-CCA and incident events, but the overlap was considerably larger between plaque occurrence and incident events, including MMP-12, TIM-1 (T-cell immunoglobulin and mucin domain 1), GDF (growth/differentiation factor)-15, IL (interleukin)-6, U-PAR (urokinase plasminogen activator surface receptor), LOX-1 (lectin-like oxidized LDL [low-density lipoprotein] receptor 1), and TRAIL-R2 (TNF [tumor necrosis factor]-related apoptosis-inducing ligand receptor 2). Only MMP-12 was associated with IMT-CCA, plaque, and incident events with a positive and concordant direction of effect. However, a 2-sample Mendelian randomization analysis suggested that increased MMP-12 may be protective against ischemic stroke ( P =5.5×10 −7 ), which is in the opposite direction of the observational analyses. Conclusions: The present meta-analysis discovered several proteins related to carotid atherosclerosis that partly differed in their association with IMT-CCA, plaque, and incident atherosclerotic disease. Mendelian randomization analysis for the top finding, MMP-12, suggests that the increased levels of MMP-12 could be a consequence of atherosclerotic burden rather than the opposite chain of events.

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