SUMMARY Long-term effects of diet and colestipol (a bile acid sequestrant) were studied in 25 patients with familial type 1I hyperlipoproteinemia. Serum lipids and body weights of an initial group of 30 patients were stabilized by low cholesterol-saturated fat-refined carbohydrate diet and the patients were then randomized into placebo and drug-treatment groups. After explaining that the drug is nontoxic and effective in lowering serum lipids, total cholesterol (C) and low-density lipoprotein cholesterol (LDL-C), colestipol (30 g/day) and diet were given to the 25 patients who remained in the long-term follow-up program. The treatment resulted in highly significant lowering of serum lipids (mg/dl, mean ± SEM): C and LDL-C from 412.7 ± 24.4 and 331.1 ± 22.8 to 270 ± 11.0 and 188.1 ± 13.8, respectively (p < 0.001 in each instance) over 7-71/2 years. Although we observed no absolute increase in high density lipoprotein (HDL), the HDL/LDL ratio was elevated. Long-term colestipol and diet treatment reduced the xanthoma size and stabilized serially angiographically visualized atherosclerotic lesions in 21 of the 25 patients who showed a satisfactory hypolipemic response. It did not cause nutritional or metabolic disturbances.COLESTIPOL, a tetraethylene-pentamine and epichlorhydrin copolymer, is a synthetic anionic bile acid-binding resin which sequestrates bile acids in the intestinal tract to reduce their reabsorption.1 2 This stimulates an increased rate of hepatic sterol synthesis. However, if increased hepatic cholesterol biosynthesis is insufficient to compensate for the exaggerated cholesterol degradation into bile acids, hepatic cholesterol pool may be reduced,3 and will result in lowering of plasma cholesterol concentration. Several colestipol studies of different durations in man have reported serum cholesterol reductions of 14-20% from the pretreatment or placebo treatment levels.2' [4][5][6][7][8] Since hypercholesterolemia in patients with familial type II hyperlipoproteinemia is caused at least partially by a decrease in cholesterol-rich low density

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SUMMARY The hypolipidemic effect of PAS-C-diet treatment was studied in 63 patients with Types Ila and IIb hyperlipoproteinemia for 6-36 months. Serum lipids and body weights of all patients were stabilized by a low cholesterol-saturated fat-refined carbohydrate diet before the initiation of an eight-week placebo-drug single-blind crossover study. During the placebo period the plasma lipids levels, mean ± SD: cholesterol 355 ± 63.5 mg%, triglyceride 141 ± 68.7 mg%, and LDL-cholesterol 279 ± 56.8 mg% were lowered to 274 ± 53.1 mg%, 98 ± 40.6 mg%, and 209 ± 52.9 mg%, respectively (P < 0.001 in each instance), with 7.5-11.0 grams of OF ALL THE HYPERLIPOPROTEINEMIC DIS-ORDERS, Types IIh, and "Ib have been shown to confer the highest risk of developing coronary artery disease'`6 and to be resistant to treatment.' I Although the beneficial effect of hypolipidemic therapy has not been conclusively determined, it is generally agreed that vigorous treatment aimed at lowering serum cholesterol and triglyceride concentrations might help to prevent or delay the occurrence of atherosclerotic complications.In using para-aminosalicylic acid (PAS) in antituberculous therapy, a number of observers have reported on its hypocholesterolemic effect.8'-The development of a highly purified preparation by recrystallizing the drug in vitamin C (PAS-C) has greatly improved its taste and absorption, while reducing its undesirable gastrointestinal effects of gastric irritation, diarrhea, and steatorrhea."' 1 'This report deals with the use of PAS-C in combination with diet in the attempt to: 1) achieve significant lowering of serum cholesterol and triglyceride levels in 63 patients with Type II hyperlipoproteinemia for 6-36 months, and 2) determine the side effects and acceptance of the drug by patients on a long-term basis. Patients and Methods of Study PatientsPatients were referred to the clinic because of resistant hypercholesterolemia with or without clinical ischemic heart or peripheral vascular disease. Affected family members of the propositi were diagnosed by screening. The age range DietTo prepare patients for the treatment, all of them were asked to sign an informed consent before they were given instruction to go on a low cholesterol and limited saturated fat-simple carbohydrate ("therapeutic") diet'5 with interruption of previous drug therapy for a minimum of four weeks.Adherence to the diet was periodically reviewed and patients were encouraged throughout the course of PAS-C treatment. MethodsIn single-blind crossover study, PAS-C and placebo administration were alternated with each successive patient entering the trial to form two groups. Sixty-three patients from two study groups who have completed the placebo period of the initial single-blind study and went on to take the drug for six or more months were included in this evaluation. Three baseline plasma lipid-lipoprotein determinations were made before the patient started to receive placebo or drug and at bi-weekly intervals afterward for four weeks. On starting PAS-C, ...