Correlation of serum lipoprotein(a) with the angiographic and clinical presentation of coronary artery disease

Dangas, George; Ambrose, John A.; D'Agate, David J.; Shao, John; Chockalingham, Selvakumar; Levine, Daniel; Smith, Donald A.

doi:10.1016/s0002-9149(98)00917-5

Cited by 34 publications

(16 citation statements)

References 21 publications

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“…It also suggests that additional and quantitatively signifi cant amounts of OxPL are formed in the vessel wall in situ and independently of those OxPL potentially carried by Lp(a). Consistent with the current fi ndings of the enhanced presence of Lp(a) in vulnerable plaques, a correlation was previously noted with plasma Lp(a) levels, apo(a) immunopositivity in atherectomy specimens, and the severity of the clinical presentation in patients with acute coronary syndromes ( 39 ). Indeed, as noted above, Lp(a) may well promote macrophage cell death via a CD36/TLR2-dependent process, thus contributing to plaque rupture ( 24 ).…”

Section: Discussionsupporting

confidence: 88%

Differential expression of oxidation-specific epitopes and apolipoprotein(a) in progressing and ruptured human coronary and carotid atherosclerotic lesions

Dijk

Kolodgie

Ravandi

et al. 2012

Journal of Lipid Research

136

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Oxidative pathways in the subendothelial space activate pro-infl ammatory, immunogenic, and atherogenic processes, resulting in endothelial dysfunction, plaque growth and destabilization, platelet activation, and thrombosis, ultimately leading to clinical events ( 1 ). A variety of oxidation-specifi c epitopes (OSE) are generated during oxidative modifi cation of plaque components. These epitopes are not only expressed on modifi ed lipoproteins but also on apoptotic cells and proteins in the extracellular matrix of atherosclerotic vessels ( 2 ).Extensive experimental data exists defi ning the role of oxidation in both progression and regression of atherosclerosis. Atherosclerotic lesions of hypercholesterolemic animal models, which represent primarily early and intermediate stage atherosclerosis, contain signifi cant amounts of OSE, often in proportion to plaque burden. OSE in the vessel wall of atherosclerotic animals can also be imaged with nuclear and magnetic resonance techniques using murine and human oxidation-specifi c antibodies, such as MDA2, E06, and IK17 ( 3-5 ). Dietary interventions in hypercholesterolemic animals that promote regression result in more rapid removal of OSE than apoB, which occurs prior to plaques diminishing signifi cantly in size, and is associated with markers of plaque stabilization, such Abstract The relationships between oxidation-specifi c epitopes (OSE) and lipoprotein (a) [Lp(a)] and progressive atherosclerosis and plaque rupture have not been determined. Coronary artery sections from sudden death victims and carotid endarterectomy specimens were immunostained for apoB-100, oxidized phospholipids (OxPL), apo(a), malondialdehyde-lysine (MDA), and MDA-related epitopes detected by antibody IK17 and macrophage markers. The presence of OxPL captured in carotid and saphenous vein graft distal protection devices was determined with LC-MS/MS. In coronary arteries, OSE and apo(a) were absent in normal coronary arteries and minimally present in early lesions. As lesions progressed, apoB and MDA epitopes did not increase, whereas macrophage, apo(a), OxPL, and IK17 epitopes increased proportionally, but they differed according to plaque type and plaque components. Apo(a) epitopes were present throughout early and late lesions, especially in macrophages and the necrotic core. IK17 and OxPL epitopes were strongest in late lesions in macrophagerich areas, lipid pools, and the necrotic core, and they were most specifi cally associated with unstable and ruptured plaques. Specifi c OxPL were present in distal protection devices. Human atherosclerotic lesions manifest a differential expression of OSEs and apo(a) as they progress, rupture, and become clinically symptomatic.

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Section: Discussionsupporting

confidence: 88%

Differential expression of oxidation-specific epitopes and apolipoprotein(a) in progressing and ruptured human coronary and carotid atherosclerotic lesions

Dijk

Kolodgie

Ravandi

et al. 2012

Journal of Lipid Research

136

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“…Significantly increased levels of Lp(a) are seldom found in patients with stable angina, confirming that Lp(a) does not produce serious lesions that might trigger the mechanism of effort angina. 27 Unstable angina has been previously associated with increased levels of L P (~) .~~…”

Section: Discussionmentioning

confidence: 99%

Lipoprotein(a) Is Related to the Extent of Lesions in the Coronary Vasculature and to Unstable Coronary Syndromes

Zampoulakis

Kyriakousi

Poralis

et al. 2000

Clinical Cardiology

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Background: Lp(a) is a highly atherogenic particle with a prothrombotic effect. Until now its relation to the extent and severity of the atheromatic lesions had not been established by standard procedures.Hyporhesis: This study examined the correlation of Lp(a) to the extent and severity of coronary artery disease (CAD) and its relation to unstable clinical events (not including sudden death).Methods: In 202 patients undergoing coronary angiography, plasma lipids were measured with the usual procedures and Lp(a) with the enzyme-linked immunosorbent assay. The extent of CAD was expressed in the number of diseased vessels and its severity in terms of the severity coefficient and the obstruction coefficient.Results: A very strong relationship between LP(a) and the number of diseased vessels (p = 0.0007) signifying diffuse atherosclerosis, but no relation with the severity of the lesions, was found. However, it was the only lipid that correlated significantly with the number of totally occluded vessels (p = 0.0003). The thrombogenic ability of Lp(a) was manifested by increased incidence of myocardial infarction and unstable angina episodes in patients with elevated Lp(a) (p = 0.01 57).Conclusion: Elevated Lp(a) predisposes to the extent of CAD and total occlusions but not to the severity of lesions. Patients with increased Lp(a) levels and unstable angina are at increased danger of suffering myocardial infarction. Thus, Lp(a) may predispose to plaque destabilization and thrombosis of noncritical lesions. Address for reprints:Prof. Dennis V. Cokkinos 356, Syngrou Ave. 176 74 Athens, Greece

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“…Assuming a 6-L plasma volume, this suggests that the absolute plasma Lp(a) content, on average, was increased by Ϸ500 mg during the time it takes to perform PCI. However, despite the fact that Lp(a) correlates with angiographic disease and has a predilection for and is enriched in unstable atherosclerotic plaques, 20,24 it seems unlikely that this amount of Lp(a) is derived from the site of plaque disruption alone.…”

Section: Tsimikas Et Al Oxldl and Lp(a) In Pci 3167mentioning

confidence: 99%

Percutaneous Coronary Intervention Results in Acute Increases in Oxidized Phospholipids and Lipoprotein(a)

et al. 2004

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Background-This study was performed to assess whether oxidized low-density lipoprotein (OxLDL) levels are elevated after percutaneous coronary intervention (PCI). Methods and Results-Patients (nϭ141) with stable angina pectoris undergoing PCI had serial venous blood samples drawn before PCI, after PCI, and at 6 and 24 hours, 3 days, 1 week, and 1, 3, and 6 months. Plasma levels of OxLDL-E06, a measure of oxidized phospholipid (OxPL) content on apolipoprotein B-100 detected by antibody E06, lipoprotein(a) [Lp(a)], autoantibodies to malondialdehyde (MDA)-LDL and copper-oxidized LDL (Cu-OxLDL), and apolipoprotein B-100 -immune complexes (apoB-IC) were measured. OxLDL-E06 and Lp(a) levels significantly increased immediately after PCI by 36% (PϽ0.0001) and 64% (PϽ0.0001), respectively, and returned to baseline by 6 hours. In vitro immunoprecipitation of Lp(a) from selected plasma samples showed that almost all of the OxPL detected by E06 was bound to Lp(a) at all time points, except in the post-PCI sample, suggesting independent release and subsequent reassociation of OxPL with Lp(a) by 6 hours. Strong correlations were noted between OxLDL-E06 and Lp(a) (rϭ0.68, PϽ0.0001). MDA-LDL and Cu-OxLDL autoantibodies decreased, whereas apoB-IC levels increased after PCI, but both returned to baseline by 6 hours. Subsequently, IgM autoantibodies increased and peaked at 1 month and then returned to baseline, whereas IgG autoantibodies increased steadily over 6 months. Conclusions-PCI results in acute plasma increases of Lp(a) and OxPL and results in short-term and long-term immunologic responses to OxLDL. OxPL that are released or generated during PCI are transferred to Lp(a), suggesting that Lp(a) may contribute acutely to a protective innate immune response. In settings of enhanced oxidative stress and chronically elevated Lp(a) levels, the atherogenicity of Lp(a) may stem from its capacity as a carrier of proinflammatory oxidation byproducts.

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Correlation of serum lipoprotein(a) with the angiographic and clinical presentation of coronary artery disease

Cited by 34 publications

References 21 publications

Differential expression of oxidation-specific epitopes and apolipoprotein(a) in progressing and ruptured human coronary and carotid atherosclerotic lesions

Differential expression of oxidation-specific epitopes and apolipoprotein(a) in progressing and ruptured human coronary and carotid atherosclerotic lesions

Lipoprotein(a) Is Related to the Extent of Lesions in the Coronary Vasculature and to Unstable Coronary Syndromes

Percutaneous Coronary Intervention Results in Acute Increases in Oxidized Phospholipids and Lipoprotein(a)

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