Young Sup Byun

MCP-1 binds to oxidized LDL and is carried by lipoprotein(a) in human plasma

Lipoprotein oxidation plays an important role in pathogenesis of atherosclerosis. Oxidized low density lipoprotein (OxLDL) induces profound inflammatory responses in vascular cells, such as production of monocyte chemoattractant protein-1 (MCP-1) [chemokine (C-C motif) ligand 2], a key chemokine in the initiation and progression of vascular inflammation. Here we demonstrate that OxLDL also binds MCP-1 and that the OxLDL-bound MCP-1 retains its ability to recruit monocytes. A human MCP-1 mutant in which basic amino acids Arg-18 and Lys-19 were replaced with Ala did not bind to OxLDL. The MCP-1 binding to OxLDL was inhibited by the monoclonal antibody E06, which binds oxidized phospholipids (OxPLs) in OxLDL. Because OxPLs are carried by lipoprotein(a) [Lp(a)] in human plasma, we tested to determine whether Lp(a) binds MCP-1. Recombinant wild-type but not mutant MCP-1 added to human plasma bound to Lp(a), and its binding was inhibited by E06. Lp(a) captured from human plasma contained MCP-1 and the Lp(a)-associated endogenous MCP-1 induced monocyte migration. These results demonstrate that OxLDL and Lp(a) bind MCP-1 in vitro and in vivo and that OxPLs are major determinants of the MCP-1 binding. The association of MCP-1 with OxLDL and Lp(a) may play a role in modulating monocyte trafficking during atherogenesis.

Relationship of Oxidized Phospholipids on Apolipoprotein B-100 to Cardiovascular Outcomes in Patients Treated With Intensive Versus Moderate Atorvastatin Therapy: The TNT Trial

BACKGROUND Oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) is a biomarker of increased risk for major adverse cardiovascular events (MACE) in community cohorts, but its role in patients with stable coronary heart disease (CHD) is unknown. OBJECTIVES This study sought to examine the relationship between these oxidative biomarkers and cardiovascular outcomes in patients with established CHD. METHODS In a random sample from the TNT (Treating to New Targets) trial, OxPL-apoB levels were measured in 1,503 patients at randomization (after an 8-week run-in period taking atorvastatin 10 mg) and 1 year after being randomized to atorvastatin 10 or 80 mg. We examined the association between baseline levels of OxPL-apoB and MACE, defined as death from CHD, nonfatal myocardial infarction, resuscitation after cardiac arrest, and fatal/nonfatal stroke, as well as the effect of statin therapy on OxPL-apoB levels and MACE. RESULTS Patients with events (n = 156) had higher randomization levels of OxPL-apoB than those without events (p = 0.025). For the overall cohort, randomization levels of OxPL-apoB predicted subsequent MACE (hazard ratio [HR]: 1.21; 95% confidence interval: 1.04 to 1.41; p = 0.018) per doubling and tertile 3 versus tertile 1 (hazard ratio: 1.69; 95% confidence interval [CI]: 1.14 to 2.49; p = 0.01) after multivariate adjustment for age, sex, body mass index, among others, and treatment assignment. In the atorvastatin 10-mg group, tertile 3 was associated with a higher risk of MACE compared to the first tertile (HR: 2.08; 95% CI: 1.20 to 3.61; p = 0.01) but this was not significant in the atorvastatin 80-mg group (HR: 1.40; 95% CI: 0.80 to 2.46; p = 0.24). CONCLUSIONS Elevated OxPL-apoB levels predict secondary MACE in patients with stable CHD, a risk that is mitigated by atorvastatin 80 mg. (A Study to Determine the Degree of Additional Reduction in CV Risk in Lowering LDL Below Minimum Target Levels [TNT]; NCT00327691).

Non-invasively measured aortic wave reflection and pulse pressure amplification are related to the severity of coronary artery disease

BACKGROUND Augmentation index (AIx) and pulse pressure amplification (PPA, here the aortic/brachial pulse pressure ratio) are an age-related emerging risk factor for cardiovascular disease. However, it has not been clearly shown that AIx and PPA predict a high risk of coronary artery disease (CAD). OBJECTIVES The aim of the study was to investigate the association between non-invasively measured aortic wave reflection (AWR) and PPA and CAD. METHODS The study group consisted of 80 patients who were admitted to our institute for elective coronary angiography. We non-invasively measured augmentation pressure (AP), AIx, and PPA using radial applanation tonometry. RESULTS When the extent of CAD was divided by no or minimal CAD, 1- or 2- and 3-vessel disease (VD), there was a significant association between the extent of CAD and AIx and PPA in patients aged <65 years, but not in patients aged ≥ 65 years. In multivariate regression analysis after controlling the traditional risk factors, the odds ratio of having 3VD was significant in patients aged <65 years: 2.15 (1.04-4.44; p=0.039) per 5% increase of AIx and 2.02 (1.15-3.55; p=0.015) per 0.05 increase of PPA, but not in patients aged ≥ 65 years. The severity of CAD expressed as a Gensini score showed a significant correlation with AP, AIx, and PPA in patients aged <65 years, but not in patients aged ≥ 65 years. CONCLUSION Increasing of non-invasively measured AWR and PPA is related to the severity of CAD, particularly in younger patients up to 65 years of age.

Primary Cardiac Lymphoma Presenting With Atrioventricular Block

Primary cardiac lymphomas (PCL) are extremely rare. Clinical manifestations may be variable and are attributed to location. Here, we report on a case of PCL presenting with atrioventricular (AV) block. A 55 year-old male had experienced chest discomfort with unexplained dyspnea and night sweating. His initial electrocardiogram (ECG) revealed a first degree AV block. Along with worsening chest discomfort and dyspnea, his ECG changed to show second degree AV block (Mobitz type I). Computed tomography (CT) scan showed a cardiac mass (about 7 cm) and biopsy was performed. Pathologic finding confirmed diffuse large B-cell lymphoma. The patient was treated with multi-drug combination chemotherapy (R-CHOP: Rituximab, cyclophoshamide, anthracycline, vincristine, and prednisone). After treatment, ECG changed to show normal sinus rhythm with complete remission on follow-up CT scan.

Prediction of Coronary Artery Disease in Patients With Lower Extremity Peripheral Artery Disease

Coronary artery disease (CAD) is a major determinant of long-term prognosis in patients with peripheral artery disease (PAD). We investigated the predictors of CAD in patients with lower extremity PAD.A total of 107 patients with PAD who underwent peripheral and simultaneous coronary angiography were reviewed. PAD was defined as (≥ 50%) stenosis associated with claudication or critical limb ischemia. PAD was divided into proximal and distal lesions. CAD was defined as angiographically significant (≥ 50%) stenosis of coronary arteries.The prevalence of CAD in patients with PAD was 62% (67/107), and of this 62%, only 13% (9/67) had angina and 72% (48/67) had multi-vessel disease. Diabetes significantly increased the risk of CAD in patients with PAD and the odds ratio of having multi-vessel CAD was 2.5 (1.1-5.9, P = 0.037) in multivariate regression analysis. The patients with multi-vessel CAD had more cardiovascular risk factors than those with normal, minimal and single CAD (P = 0.032). Interestingly, the prevalence of proximal PAD was higher in the normal or single CAD group than the multi-vessel CAD group, whereas both proximal and distal involvement of PAD was higher in the multi-vessel CAD group.Diabetes, multi-cardiovascular risk factors, and involvement of both proximal and distal lesions significantly increased the risk of multi-vessel CAD. Therefore, simultaneous CAD evaluation should be considered in patients with lower extremity PAD having diabetes, multi-cardiovascular risk factors, or multi-level disease.

Non-lipid effects of rosuvastatin-fenofibrate combination therapy in high-risk Asian patients with mixed hyperlipidemia

OBJECTIVE The aim of this study is to compare the non-lipid effects of rosuvastatin-fenofibrate combination therapy with rosuvastatin monotherapy in high-risk Asian patients with mixed hyperlipidemia. METHODS A total of 236 patients were initially screened. After six weeks of diet and life style changes, 180 of these patients were randomly assigned to receive one of two regimens: rosuvastatin 10 mg plus fenofibrate 160 mg or rosuvastatin 10 mg. The primary outcome variables were the incidences of muscle or liver enzyme elevation. The patients were followed for 24 weeks during drug treatment and for an additional four weeks after drug discontinuation. RESULTS The rates of the primary outcome variables were similar between the two groups (2.8% and 3.9% in the combination and the rosuvastatin groups, respectively, p=1.00). The combination group had more, but not significantly, common treatment-related adverse events (AEs) (13.3% and 5.6%, respectively) and drug discontinuation due to AEs (10.0% and 3.3%, respectively) than the rosouvastatin group. Combination therapy was associated with higher elevations in homocysteine, blood urea nitrogen, and serum creatinine, whereas elevation in alanine aminotransferase was greater in the rosuvastatin group. Leukocyte count and hemoglobin level decreased to a greater extent in the combination group. The combination group showed greater reductions in TG and elevation in HDL-cholesterol. CONCLUSION In our study population, the rosuvastatin-fenofibrate combination resulted in comparable incidences of myo- or hepatotoxicity as rosuvastatin monotherapy. However, this combination may need to be used with caution in individuals with underlying pathologies such as renal dysfunction (NCT01414803).

Effect of Aspiration Thrombectomy on Microvascular Dysfunction in ST-Segment Elevation Myocardial Infarction With an Elevated Neutrophil Count.

Background and Objectives Aspiration thrombectomy (AT) during primary percutaneous coronary intervention (PCI) is an effective adjunctive therapy for ST-segment elevation myocardial infarction (STEMI). An elevated neutrophil count in STEMI is associated with microvascular dysfunction and adverse outcomes. We evaluated whether AT can improve microvascular dysfunction in patients with STEMI and an elevated neutrophil count. Subjects and Methods Seventy patients with STEMI undergoing primary PCI from August 2007 to February 2009 in our institution were classified by tertiles of neutrophil count on admission (<5,300/mm3, 5,300-7,600/mm3, and >7,600/mm3). The angiographic outcome was post-procedural thrombolysis in myocardial infarction (TIMI) flow grade. Microvascular dysfunction was assessed by TIMI myocardial perfusion (TMP) grade and ST-segment resolution on electrocardiography 90 minutes after PCI. The clinical outcome was major adverse cardiac event (MACE), defined as cardiac death, re-infarction, and target lesion revascularization at 9 months. Results There were no significant differences in the clinical characteristics and pre- and post-procedural TIMI flow grades between the neutrophil tertiles. As the neutrophil count increased, a lower tendency toward TMP grade 3 (83% vs. 52% vs. 54%, p=0.06) and more persistent residual ST-segment elevation (>4 mm: 13% vs. 26% vs. 58%, p=0.005) was observed. The 9-month MACE rate was similar between the groups. On subgroup analysis of AT patients (n=52) classified by neutrophil tertiles, the same tendency toward less frequent TMP grade 3 (77% vs. 56% vs. 47%, p=0.06) and persistent residual ST-segment elevation (>4 mm: 12% vs. 28% vs. 53%, p=0.05) was observed as neutrophil count increased. Conclusion A higher neutrophil count at presentation in STEMI is associated with more severe microvascular dysfunction after primary PCI, which is not improved with AT.

A Case of Primary Cardiac Lymphoma Mimicking Acute Coronary and Aortic Syndrome

Primary cardiac lymphoma (PCL) is a rare disorder, but the incidence is increasing and its clinical manifestations are various. We report a case of PCL, which mimics an acute coronary and aortic syndrome. A 51 year-old female was presented with chest pain radiating to the back. Her initial electrocardiogram revealed T wave inversion in the leads of V 5-6, II, III and aVF. Additionally, cardiac troponin-T was slightly elevated. Chest radiography showed marked mediastinal widening. Computed tomography scan showed a huge pericardial mass. The histopathologic findings of the mass were compatible with diffuse large B cell lymphoma. She died of refractory ventricular tachycardia, probably, due to an extensive infiltration of PCL to the myocardium.

The relation of non-invasively and invasively assessed aortic pulsatile indices to the presence and severity of coronary artery disease

Abstract Objectives. The aim of the study was to assess the relationship between non-invasively (NIA) and invasively assessed (IA) aortic pulsatile indices and the presence and severity of coronary artery disease (CAD). Subjects and Methods. The study group consisted of 58 patients who were admitted to our institute for elective coronary angiography (CAG). We measured the aortic systolic, diastolic and mean blood pressure (BP) using non-invasive and invasive techniques. We assessed the pulsatile indices of the aortic pressure waveform (APW) including pulse pressure (PP), fractional PP (FPP, the ratio of PP to mean BP) and pulsatility index (PI, the ratio of PP to diastolic BP). The severity of CAD was assessed by Gensini score. Results. IA aortic PP, FPP and PI were significantly higher in patients with CAD than without CAD, but NIA indices did not show significant differences between two groups. After multivariate stepwise adjustment, the odds ratio (OR) and confidence interval (CI) of having significant CAD was: PP per 10 mmHg, OR = 2.51 (95% CI 1.12–5.63); FPP per 0.1, OR = 3.30 (95% CI 1.25–8.72); and PI per 0.1, OR = 1.88 (95% CI 1.09–3.23). In linear regression analysis, IA aortic systolic BP (SBP), PP, FPP and PI were significantly correlated with Gensini score, but NIA indices were not correlated. The NIA aortic PP was lower than IA aortic PP (mean difference: 6.1 ± 15.8 mmHg). Conclusion. IA aortic PP, FPP and PI were related to the presence and severity of CAD, but NIA assessed indices of APW were not related. NIA aortic PP underestimated IA aortic PP.

Primary Cardiac Angiosarcoma Presenting With Cardiac Tamponade

Primary cardiac angiosarcoma is a very rare disease with a poor prognosis. We report a case of a patient with a primary cardiac angiosarcoma who presented with cardiac tamponade; the angiosarcoma was successfully resected surgically.