Circulating oxidized low density lipoprotein levels. A biochemical risk marker for coronary heart disease.

Recent studies have established oxidative modification of low density lipoprotein (LDL) as an important atherogenic factor. We examined the clinical relevance of circulating oxidized LDL (OxLDL) levels in atherosclerotic disease by an enzyme immunoassay with use of specific antibodies against OxLDL (FOH1a/DLH3) and apolipoprotein B. Plasma OxLDL levels were significantly higher in patients with coronary heart disease (n=65) than in control subjects (n=181; 201. 3+/-11.2 versus 112.4+/-3.3 U/dL, respectively; P<0.01). OxLDL levels were not associated with age, sex, total cholesterol, or apolipoprotein B levels in normal control subjects. Our results suggest that circulating OxLDL may be a possible biochemical risk marker for coronary heart disease.

Cholesterol flux in cholesterol ester-loaded macrophages in an in vitro perfusion system.

Cholesterol ester-loaded J774 macrophages attached to microcarrier beads were perfused or incubated with lipoproteins in vitro. Cholesterol influx was reduced by decreasing LDL cholesterol, efflux was promoted by increasing HDL cholesterol or by adding apolipoprotein A-I/phosphatidylcholine complexes to the perfusate or incubation medium. Addition of sera obtained from patients after LDL apheresis or plasma exchange resulted in much smaller increments in cell cholesterol than pretreatment sera, due to decreased influx, but efflux was unchanged despite the reduction in HDL cholesterol by plasma exchange. These data suggest that extracorporeal cholesterol removal promotes mobilization of intracellular cholesterol ester mainly by reducing cholesterol influx.

Treatment of homozygous patients with familial hypercholesterolemia by double-filtration plasmapheresis.

Two homozygous patients with familial hypercholesterolemia were treated by double-filtration plasmapheresis. The plasma separated by the first filter was subsequently led to the second filter of ethylene vinylalcohol co-polymer hollow fibers, which trap very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) preferentially to other plasma constituents. Serum, VLDL, IDL, LDL cholesterol levels decreased by 55, 68, 59 and 55%, respectively. HDL cholesterol levels decreased by 39%. Immunoglobulins and fibrinogen levels decreased significantly. Cutaneous and tendinous xanthomas became smaller. off

Coronary ectasia in a homozygous patient with familial hypercholesterolemia.

A 23-year-old man with homozygous familial hypercholesterolemia was found to have coronary ectasia by coronary angiography. This case showed generalized xanthomatosis and severe hyper low density lipoproteinemia, and his cultured skin fibroblasts showed LDL receptor activities compatible with the receptor-defective homozygous type of familial hypercholesterolemia. Coronary angiography showed fusiform aneurysmal involvements in the right coronary artery and left circumflex artery, and 50% stenosis in the right coronary artery and left anterior descending artery. Thus, homozygous familial hypercholesterolemia produces coronary ectasia as well as premature coronary stenosis.

A new low density lipoprotein apheresis system using two dextran sulfate cellulose columns in an automated column regenerating unit (LDL continuous apheresis).

We describe a new low density lipoprotein (LDL) apheresis system using dextran sulfate cellulose column in an automated column regenerating unit (LDL continuous apheresis). Two columns containing 150 ml of dextran sulfate cellulose were used, and the whole extracorporeal circulation was about 400 ml in volume. After 600 ml of plasma was adsorbed into the first column, the second column was used as an adsorbent and meanwhile the first column was regenerated. Thus, the 2 columns were used alternately without losing the potency of the columns. As the apparatus was automatically controlled by a computerized unit, no extra manipulation is necessary compared with the conventional single-column method. By treating 4-5 liters of plasma, non-high density lipoprotein (HDL)-cholesterol levels decreased by 63-71%, and HDL-cholesterol levels remained unchanged. Thus, this new method of LDL apheresis can safely reduce LDL-cholesterol to any desired level and will be applicable for the treatment of child and adult family hypercholesterolemic patients with severe coronary heart disease.

Effects of CS-514 (eptastatin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on serum lipid and apolipoprotein levels in heterozygous familial hypercholesterolemic patients treated by low density lipoprotein (LDL)-apheresis.

Nine heterozygous patients with familial hypercholesterolemia (FH) were treated by low density lipoprotein (LDL)-apheresis using dextran sulfate cellulose columns. After more than 3 procedures of LDL-apheresis without drug therapy, combination therapy with LDL-apheresis and CS-514 (eptastatin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme (HMG-CoA) reductase, at a dose of 10 mg twice daily was started. Pre- and post-apheresis serum cholesterol levels were decreased significantly by CS-514, from 289 +/- 24 mg/dl (mean +/- SEM) to 247 +/- 25 mg/dl and from 118 +/- 7 mg/dl to 106 +/- 9 mg/dl, respectively. Pre- and post-apheresis apolipoprotein B levels decreased significantly on CS-514 from 160 +/- 9 mg/dl to 138 +/- 8 mg/dl and from 58 +/- 6 mg/dl to 45 +/- 6 mg/dl, respectively. No adverse effects were observed during the combination therapy. Thus, the addition of an inhibitor of HMG-CoA reductase to LDL-apheresis is a useful method for further reducing serum cholesterol and apolipoprotein B levels in FH heterozygotes.

Deficiency of serum cholesteryl-ester transfer activity in patients with familial hyperalphalipoproteinaemia.

Lipoprotein patterns and cholesteryl ester transfer activity (CETA) were examined in 2 patients with familial hyperalphalipoproteinaemia (FHALP). The proband was a healthy 58-year-old Japanese male who had an HDL cholesterol of 7.83 mmol/l (301 mg/dl). His sister's HDL cholesterol was 4.52 mmol/l (174 mg/dl), which suggested that both were homozygous carriers of FHALP. In both subjects HDL showed a high cholesterol/apo A-I ratio and appeared to be a larger-sized particle than normal HDL on agarose gel chromatography. Two of the proband's children showed higher HDL cholesterol levels (1.74 mmol/l, 2.16 mmol/l) than normal, but another 2 children showed normal levels (1.48 mmol/l, 1.40 mmol/l). However, the ratios of HDL cholesterol to total cholesterol and to apo A-I in all children were higher than normal. These data suggest, but do not prove, that all his children were heterozygotes. Apo B levels in all of the family members studied were lower than normal (47-80 mg/dl). Deceased members of the same family had not died from cardiovascular disease. Cholesteryl-ester transfer activity was studied in both patients. When serum or lipoprotein deficient serum (d greater than 1.21) and [3H]cholesteryl ester labelled HDL3 were incubated in the presence of an LCAT inhibitor, there was no evidence of cholesteryl ester transfer from HDL to VLDL and/or LDL, unlike normal subjects. The deficiency of CETA in these patients with FHALP presumably accounted for the increase in particle size and cholesterol enrichment of HDL.

Acute increases in plasma oxidized low-density lipoprotein immediately after percutaneous transluminal coronary angioplasty.

To investigate the acute changes in plasma oxidized low-density lipoprotein before and immediately after coronary angioplasty, we studied 132 consecutive patients who successfully underwent this procedure. Plasma oxidized low-density lipoprotein levels were significantly increased immediately after coronary angioplasty in patients with stable angina pectoris as well as in those with acute coronary syndromes.

Effects of CS-514 on serum lipoprotein lipid and apolipoprotein levels in patients with familial hypercholesterolemia.

Effects of CS-514, a new competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on serum lipoprotein lipid and apolipoprotein levels were studied in 13 heterozygous patients with familial hypercholesterolemia. Treatment with 10 mg of CS-514 twice daily reduced total serum cholesterol, low-density lipoprotein (LDL), and intermediate-density lipoprotein (IDL) cholesterol levels by 25%, 33%, and 33%, respectively, and increased high-density lipoprotein (HDL) cholesterol levels by 15%. Apolipoprotein B, E, and C-II levels decreased by 24%, 20%, and 19%, and apolipoproteins A-I and A-II levels increased by 10% and 7%, respectively. One patient showed abnormally high levels of SGOT, SGPT, and serum alkaline phosphatase, which returned to normal levels immediately after the cessation of CS-514. No other adverse effects were observed. Thus, CS-514 reduces atherogenic lipoproteins and apolipoprotein B, and increases HDL and apolipoprotein A-I and A-II, and appears to be a useful drug for heterozygous familial hypercholesterolemia.

Goodpasture's-like syndrome and effect of extracorporeal membrane oxygenator support.

A 49-year-old man was admitted because of general fatigue, cough and hematuria. During the hospital course, acute renal failure, hemoptysis and dyspnea developed. A percutaneous renal biopsy revealed a diffuse crescentic glomerulonephritis, and direct immunofluorescence showed a linear pattern of IgG along the glomerular basement membrane. Although serum anti-glomerular basement membrane (anti-GBM) antibody was not detected. Goodpasture's-like syndrome was suspected, and methylprednisolone pulse therapy and plasmapheresis were administered. Concomitantly, extracorporeal membrane oxygenation (ECMO) was instituted because of deterioration in respiratory status due to a severe pulmonary hemorrhage despite maximal ventilatory support. Temporarily, the patient improved and ECMO was discontinued. ECMO may be a useful therapeutic support for hypoxia resulting from pulmonary hemorrhage in Goodpasture's syndrome (GPS) and Goodpasture's-like syndrome.

[Postoperative percutaneous coronary angioplasty for stenosed aortocoronary vein bypass].

This paper was presented to demonstrate the efficacy of postoperative PTCA for varying degree of stenosis aortocoronary bypass with saphenous vein grafts. The following conclusions were drown. 1. The success rate of postoperative PTCA for 15 grafts showed 88.8%. 2. The rate of success for PTCA was much more effective in patients within one year after bypass operations. The authors concluded that postoperative PTCA can be done with excellent rate of success. Therefore, postoperative cine-coronary angiography should be done to evaluate the state of the graft and to decide to perform possible postoperative PTCA in order to keep long time patency rate of saphenous vein grafts.

[A case of successful emergency coronary artery bypass grafting surgery for failed coronary angioplasty using percutaneous cardiopulmonary support].

This is the first Japanese case of the successful emergency coronary artery bypass grafting (CABG) surgery for failed percutaneous transluminal coronary angioplasty (PTCA) using percutaneous cardiopulmonary support (PCPS). A 81-year-old woman with old myocardial infarction and angina pectoris is presented. Her coronary angiogram showed the 90% and 50% stenosis of the right coronary artery (RCA) and the total occlusion of the left anterior descending artery (LAD). PTCA for the 90% stenosis of RCA was performed. But, during the balloon dilation, her heart rate and blood pressure decreased. PTCA was stopped. As her chest pain was worse, re-PTCA was tried, using PCPS. Under PCPS (3 l/min), the balloon dilation was performed safely and smoothly. But, the unexpected dissection of RCA occurred, and became larger rapidly. After 85 minutes, the emergency CABG was performed. By using PCPS, the stable hemodynamics was given till the operation. CABG to RCA and LAD was performed safely. After the surgery, the patient progressed well. PCPS was a very useful cardiopulmonary assist device.

[Simultaneous operation of aortic valve replacement and renal artery reconstruction in a patient of aortitis syndrome: a case report].

A 27-year-old female underwent concomitant aortic valve replacement and reconstruction of the right renal artery. She was diagnosed as aortitis syndrome with AR and 90% stenosis of the right renal artery by angiography. PRA were high, Ccr value was low, and renogram showed non-functioning pattern in the right kidney though normal pattern in the left. After CRP value was decreased by predonisolone, the operation was done in the inactive stage. Postoperative angiography showed good aortic valve function and patent renal artery graft. Postoperative PRA and Ccr became normal and the renogram was improved. Based on the result we recommended simultaneous operation can be done with minimal risk.

Impact of severe coronary disease associated or not associated with diabetes mellitus on outcome of interventional treatment using stents: results from HERZ (Heart Research Group of Kanazawa) analyses.

Percutaneous coronary intervention (PCI) using a drug-eluting stent (DES) leads to less re-stenosis than PCI using a bare metal stent (BMS), however there is still controversy whether use of a DES for severe coronary disease leads to an acceptable outcome in patients with diabetes mellitus (DM). In this study 8159 lesions were treated in 6739 patients (mean age 68.9 years) with coronary artery disease. Use of a DES significantly decreased the re-stenosis rate compared with BMS in both DM (9.6% versus 21.3%) and non-DM (9.5% versus 17.1%) patients. The re-stenosis rate was significantly higher in DM than in non-DM patients in the BMS group but not in the DES group. There was no statistically significant difference in event-free survival after stenting of patients with left main coronary artery (LMCA) disease between the BMS and DES groups. It was concluded that, compared with BMS, DES reduced re-stenosis in patients with DM, however, we advise careful treatment after using DES for severe coronary disease, including LMCA lesions, in patients with DM.

New variant of low density lipoprotein receptor gene. FH-Tonami.

A new variant of the low density lipoprotein receptor (LDLR) gene was ascertained through Southern blotting analysis of LDLR genes of 35 unrelated Japanese patients with heterozygous familial hypercholesterolemia (FH). This mutant gene had a 6 kilobase deletion which had eliminated only exon 15, an exon that encodes the O-linked sugar domain. The mutation was recognized in two patients with heterozygous FH. We refer to these patients as 'FH-Tonami', since they were both born in the Japanese district of Tonami. Although there is no evidence of a relation between families, the possibility of a common ancestor with FH does exist. Neonatal diagnosis of FH in two fetuses from one family was possible through analyses of their LDLR genes in cord blood samples at delivery.