Methods to assess relative reliability of diet records: minimum records for monitoring lipid and caloric intake.

A total of 252 diet records of 18 outpatients attending a lipid clinic were analyzed by a computer-assisted method to determine the minimum number of daily diet records that would be reliable for monitoring dietary adherence. Each subject recorded food intake in special diaries for 14 consecutive days between two clinic visits. All possible randomly selected combinations of 3, 4, 5, 7, 9, and 11 consecutive days of records in the 14-day period were analyzed for calories and lipids. Sets of records were said to be within a 95% confidence interval when the information yielded on any parameter differed by 5% or less from the mean values for the entire 14 days' records. All sets of records for 7, 9, and 11 days were in the 95% confidence range; therefore, 7 consecutive days of food recording were considered the minimum requirement for a 95% confidence limit. Out of 11 possible combinations of 4 consecutive day-sets of records, all but 3 sets were within 95% confidence limits. Consequently, 4 consecutive days of records were deemed acceptable as a reasonable compromise for minimal, reliable monitoring of diet compliance in outpatients for the nutrients studied.

Serum lipids in normo- and hyperlipidemics after methyldopa and propranolol.

We report on serum lipoprotein changes after antihypertensive therapy in nine subjects with type II hyperlipoproteinemia and eight subjects with normolipidemia. They received placebo for 6 wk, followed by random order crossover between methyldopa and propranolol for 6 mo. Physical activity, diet, and other drugs were monitored for constancy. No other antihypertensive drugs were used. Doses required for normalization of blood pressure ranged between 40 to 360 mg/day for propranolol and 500 to 2500 mg/day for methyldopa. Mean blood pressure was equally lowered to normal by both drugs. Triglyceride levels increased after propranolol and after methyldopa. Subjects with normocholesterolemia developed higher serum triglyceride levels after each drug, whereas such a change did not occur in patients with hypercholesterolemia. Low-density lipoprotein cholesterol levels were reduced by methyldopa only in patients with baseline hypercholesterolemia. There was no correlation between lipoprotein level changes, dose required of either drug, or propranolol blood levels. The baseline lipoprotein metabolism disorder appears more likely to determine the type of changes in serum lipoprotein levels after these antihypertensive drugs.

Low-dose colestipol plus probucol for hypercholesterolemia.

The hypocholesterolemic and adverse effects of colestipol, 20 g/day, and colestipol, 10 g/day combined with probucol, 1 g/day, were compared. A double-placebo, diet-controlled, crossover trial that lasted 19 months was undertaken on 22 hypercholesterolemic patients who had low-density lipoprotein (LDL) cholesterol levels greater than 180 mg/dl after 3 months of diet and placebo treatment. Uniformity of diet and physical activity were monitored throughout the study. Compared with baseline values after 3 months on diet-placebo treatment, "combined" therapy reduced LDL cholesterol by more than 20% in 15 patients, more than 25% in 9 patients and more than 45% in 2 patients. Treatment with "half-dose" colestipol and probucol resulted in the greatest mean LDL cholesterol reduction, from 239 mg/dl during diet-placebo period to 170 mg/dl; the difference was not statistically significantly different from the reduction to 180 mg/dl with 20 g of colestipol alone. Fifteen patients showed the greatest reduction in LDL cholesterol after combined therapy. Probucol produced statistically significant reductions in very low density lipoprotein and high-density lipoprotein cholesterol. The major gastrointestinal side effects of single therapy with colestipol (constipation) and probucol (diarrhea) were ameliorated or abolished by concomitant administration. Probucol-colestipol co-administration allowed a 50% reduction in the colestipol dosage, with similar efficacy and improved tolerability and reduced mean serum LDL cholesterol with a frequency and magnitude rarely seen with other hypocholesterolemic treatments. Hypercholesterolemic persons who cannot tolerate full doses of resins may receive equal benefit by half the dose if probucol is added to the regimen.

Probucol with colestipol in the treatment of hypercholesterolemia.

The effects of therapy with 1 g of probucol and 20 g of colestipol were compared with those of the drugs used singly on 47 patients with hypercholesterolemia in a double-blind, double-placebo, diet-controlled, crossover trial that lasted 18 months. The probucol and colestipol combination, but neither drug alone, reduced mean serum low-density-lipoprotein (LDL)-cholesterol levels from 242 +/- 51 (SE) mg/dL during the diet and placebo phase to 171 +/- 41 mg/dL. Probucol significantly lowered high-density-lipoprotein (HDL)-cholesterol levels and increased LDL:HDL-cholesterol ratios. Combination therapy did not change LDL:HDL cholesterol ratios. Probucol alone or in combination reduced very-low-density-lipoprotein cholesterol levels, despite concomitant elevations of serum triglyceride levels caused by colestipol in the combination protocol. Gastrointestinal side effects of single drugs were abolished when drugs were used in combination. Compared with the values in the diet-placebo phase, LDL-cholesterol levels were reduced by more than 20% in 81% of patients, by more than 30% in 49%, and by more than 40% in 17%. This drug combination proved to be safer and have greater hypocholesterolemic effects in more patients than other marketed drug treatments.

Electrocardiographic effects of probucol. A controlled prospective clinical trial.

Probucol is known to prolong QT intervals in some patients and to produce fatal arrhythmias in selected animal species. To assess the prevalence and clinical relevance of this effect in a controlled manner, we analyzed electrocardiograms (ECGs) and medical events in patients during a placebo-controlled crossover trial comparing single or combined administration of probucol and colestipol. Forty-two Type II hyperlipoproteinemic patients were studied for eighteen to twenty-four months. Two cardiologists independently read the tracings which were previously arranged randomly without names or dates. There were no statistical differences between the reports of the ECG parameters by the two cardiologists. The mean QTc interval of the entire patient population was lengthened after probucol administration without reaching statistical significance when compared to placebos or colestipol treatments. Forty-eight % of the patients showed lengthening of the QTc interval during probucol treatment by 11 to 70 msec increment over baseline placebo. The remaining had either no change or shortening of the interval. There were no statistically significant differences in means of R-R, PR, QRS, QTc or QoT intervals among placebo, probucol., colestipol and probucol plus colestipol treatments. It is concluded that probucol prolonged QT intervals in the electrocardiograms of about one half of patients receiving the drug with no other clinical or statistically significant evidence of cardiotoxicity or electrocardiographic effects.

The effect of variable fat diets and cholesterol-lowering drugs on Antithrombin III levels in hyperlipoproteinemic and normal subjects.

Functional and immunological Antithrombin III (AT III) levels were studied in normal and hyperlipoproteinemic subjects undergoing crossover therapeutic trials of either diets or hypocholesterolemic drugs. The diet trial subjects, 7 hyperlipoproteinemics and 15 normals, were randomly assigned to crossover between a high saturated fat diet (P/S ratio 1:8) and a high polyunsaturated fat diet (P/S ratio 4:1) for periods of 6-8 weeks, preceded by a baseline period on regular American diet (P/S ratio 1:1). For the drug trials, 33 type II A or B hyperlipoproteinemics were treated in random and double-blind fashion with Colestipol (20 gm/day) or both, for periods of 3 months, preceded by a double placebo period. Mean low density lipoprotein cholesterol levels were significantly different (p less than 0.001) between high saturated and high polyunsaturated fat diets (157 +/- 37 mg/dl vs 137 +/- 31 mg/dl respectively, mean +/- S.D.) and between placebo and drug treatment periods (226 +/- 51 mg/dl vs 183 +/- 44 mg/dl respectively, mean + S.D.). There was no difference in basal functional or immunological AT III levels between normal and hyperlipoproteinemics. AT III levels did not correlate significantly with cholesterol or triglyceride levels and remained unchanged despite significant reductions in serum cholesterol related to the diet and drug therapy. There appears to be no significant association between baseline or post treatment serum cholesterol levels and functional or immunological AT III. Thus, changes in AT III are unlikely to play a role in the link between hypercholesterolemia and thrombosis.