James H. Zavoral

Treatment of refractory familial hypercholesterolemia by low-density lipoprotein apheresis using an automated dextran sulfate cellulose adsorption system

A subgroup of patients with familial hypercholesterolemia (FH) respond inadequately to standard diet and drug therapy, and are therefore at high risk for the premature development or progression of coronary artery disease. This study evaluated low-density lipoprotein (LDL) cholesterol and lipoprotein (a) removal in a multicenter, controlled trial with a new LDL apheresis procedure (Liposorber LA-15 System). The study comprised patients with FH who had not responded adequately to diet and maximal drug therapy. There were 54 patients with heterozygous FH (45 randomized to treatment and 9 control subjects) and 10 with homozygous FH (all of whom received LDL apheresis). The study included three 6-week treatment phases and a 4-week rebound phase. Treatments were administered at 7- to 14-day intervals. Mean acute reductions in LDL cholesterol were 76% in heterozygous FH patients and 81% in homozygous ones. Time-averaged levels of LDL cholesterol were reduced 41% (243 to 143 mg/dl) in heterozygous FH patients and 53% (447 to 210 mg/dl) in homozygous ones. The substantial acute reduction of lipoprotein (a) (means: 65%, heterozygous FH; 68%, homozygous FH) has not been reported with other therapies. The Liposorber LA-15 System represents an important therapeutic option in FH patients who respond inadequately to diet and drug therapy.

Cardiac arrest in young, ostensibly healthy patients: Clinical, hemodynamic, and electrophysiologic findings

This study examines the clinical, hemodynamic, and electrophysiologic findings in a unique group of 11 young (aged 15 months to 29 years) survivors of a cardiac arrest. All patients were previously in good health, and cardiac arrest was the initial manifestation of cardiac disease in all. Overt clinical and hemodynamic abnormalities were not as common as previously reported, and in some instances apparent cardiac abnormalities failed to provide a link to cardiac arrest. No patient had congenital heart disease or hypertrophic cardiomyopathy. However, during multicatheter electrophysiologic study, sustained tachyarrhythmia was reproducibly initiated in 8 of 11 patients (73%). Young, ostensibly healthy patients who survive cardiac arrest form a diverse group. Diligent programmed intracardiac electrical stimulation may demonstrate life-threatening tachycardias in these patients. Treatment to prevent recurrence of cardiac arrest is difficult in this group of patients. However, the ability to initiate tachycardia in the electrophysiologic laboratory may be useful in the management of these patients.

Efficacy of fluvastatin, a totally synthetic 3-hydroxy-3-methylglutaryl coeezyme a reduefase inhibitor

Abstract The Fluvastatin Long-Term Extension Trial (FLUENT) was designed to assess the safety and efficacy of fluvastatin over a prolonged period of time. In this way, FLUENT represents a clinical scenario that is closer to office-based chronic treatment of hyperlipidemic patients. A total of 918 patients with severe primary hypercholesterolemia (mean baseline low density lipoprotein cholesterol [LDL-C], 227 mg/dL) were enrolled into the study and received open-label fluvastatin, 20 or 40 mg daily, depending on response. Results of the first year of treatment have been published previously and showed statistically significant changes in LDL-C (−30.7%), total cholesterol (−21.9%), and high density lipoprotein cholesterol (HDL-C; +3.5%). Of the original number of patients completing the 1-year study, 761 completed a second year of evaluation; the results are presented here. Any patient who did not achieve LDL-C levels of ≤ 130 mg/dL could receive cholestyramine (usually 8 g/day) or fluvastatin up to 80 mg/day. At the end of the 2-year period there were significant changes in LDL-C with fluvastatin (20 mg/day, −25.4%; 40 mg/day, −30.6%; 80 mg/ day, −33.7%; p

Elevated levels of sphingolipids in type II (a+b) hyperlipoproteinemia

Abstract The levels of sphingomyelin, neutral glycosphingolipids and gangliosides were studied in normal and type II hyperproteinemic plasmas. Sphingomyelin levels were elevated and there was an excellent correlation between cholesterol and sphingomyelin (r=0.86). The correlation between cholesterol and the remainder of the phospholipids (i.e., total phospholipid minus sphingomyelin) was significantly less than that between cholesterol and sphingomyelin. The other sphingolipids were also elevated. The four neutral glycosphingolipids were from 37 to 100 percent higher than normal (p

1277 TYPE I HYPERLIPIDEMIA IN A CAMBODIAN FAMILY

Four children and both parents were evaluated for hypertriglyceridemia (HTG)when “cream of tomato soup” blood was discovered on a routine screen. The parents, 31 and 36, and the children, ages 3-9, were asymptomatic without history of abdominal pain or xanthomas. Their diet was native Cambodian with American supplementation. They cooked with pork fat, ate ice cream and standard school lunches without symptoms. Three of the children and the father had elevated fasted triglycerides (TG) (2780, 4170, 2930, and 372 mg% - father). The mothers TG was 92 mg%. The HDL-cholesterol (HDL-C) was low in three children with Type I and in the father (12, 13, 12, and 20 mg% - father). The mothers HDL-C was 37 mg%. Utilizing radioimmunoassay, Apo CII was normal in all patients, apo AI was low in the 3 Type I children and in the HTG father. Post heparin hepatic lipase was normal in all patients 7.9-21.3, normals ±2 S.D. 2.5-32.5 μm FFA/ml/hr. Extra hepatic lipase (EHL) was decreased in the 3 Type I children and the HTG father 2.9-9.6, normal ±2 S.D., 11.9-29.9 μm FFA/ml/hr. There was a strong correlation between decreased HDL-C, decreased apo AI, and decreased EHL in this family. Type I hyperlipidemia was discovered in 3 children and decreased EHL in these 3 children and their father who are from Cambodia without xanthomata or symptoms of pancreatitis such as abdominal pain.