Search PubMed⌕ Search

Biomedical subjects

R C Pasternak

Publications and source records attributed to R C Pasternak.

At least 19 recordsLinked to original sources
PubMed1996

Effect of combination therapy with lipid-reducing drugs in patients with coronary heart disease and "normal" cholesterol levels. A randomized, placebo-controlled trial. Harvard Atherosclerosis Reversibility Project (HARP) Study Group.

BACKGROUND: Combination drug therapy has been shown to decrease cholesterol levels in hyperlipidemic patients. However, its efficacy has not been well studied in patients previously considered to be normolipidemic, many of whom are now candidates for this therapy. OBJECTIVE: To determine the efficacy and tolerability of multidrug therapy designed to improve low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels in patients with coronary heart disease and average lipid levels. DESIGN: Randomized, placebo-controlled, 2.5-year trial comparing patients receiving usual care with patients receiving stepped-care drug therapy. INTERVENTION: Stepped-care therapy (pravastatin, nicotinic acid, cholestyramine, and gemfibrozil) to decrease total cholesterol levels to less than 4.1 mmol/L (160 mg/dL) and the ratio of LDL cholesterol to HDL cholesterol to less than 2.0. SETTING: 2 academic, urban, tertiary care hospitals. PATIENTS: 91 patients (80 men and 11 women) with coronary heart disease, a mean age of 60 years, total cholesterol levels less than 6.4 mmol/L (250 mg/dL) at baseline, and ratios of total cholesterol to HDL cholesterol greater than 4.0 at baseline. MEASUREMENTS: Fasting serum lipoprotein profile, fasting apolipoprotein levels, and frequency of adverse effects. Patients were assessed every 6 weeks during drug titration and every 3 months thereafter. RESULTS: Mean lipid levels at baseline were as follows: total cholesterol, 5.5 mmol/L (214 mg/dL); LDL cholesterol, 3.6 mmol/L (140 mg/dL); HDL cholesterol, 1.1 mmol/L (42 mg/dL); and triglycerides, 1.8 mmol/L (159 mg/dL). With pravastatin, changes in levels from baseline were -22% for total cholesterol, -32% for LDL cholesterol +8% for HDL cholesterol, and -15% for triglycerides (P < 0.001 for all comparisons). With the addition of 1.5 g of nicotinic acid, additional changes were -6% for total cholesterol (P < 0.002). -11% for LDL cholesterol, +8% for HDL cholesterol, and -10% for triglycerides (P < 0.001 for all comparisons). With 2.25 to 3 g of nicotinic acid, these changes were -7% for total cholesterol (P = 0.007), -14% for LDL cholesterol (P < 0.001), +6% for HDL cholesterol (P = 0.02), and -13% for triglycerides (P = 0.03). With cholestyramine, total cholesterol and LDL cholesterol levels were unchanged compared with the previous step; the change in HDL cholesterol level was -8% (P = 0.03); and the change in triglyceride level was +46% (P < 0.001). With gemfibrozil, total cholesterol level was unchanged; the additional change in LDL cholesterol level was +12% (P = 0.09); the change in HDL cholesterol level was +12% (P = 0.03); and the change in triglyceride level was -37% (P < 0.001). Apolipoprotein B levels decreased by 25% overall (P < 0.001); lipoprotein(a) levels did not change significantly. Adverse effects were primarily attributable to nicotinic acid or cholestyramine. In 18 of the 35 patients (50%) whose baseline LDL cholesterol levels were greater than 3.35 mmol/L (130 mg/dL), pravastatin decreased LDL cholesterol levels to 2.6 mmol/L (100 mg/dL) or less by 6 weeks; 70% of patients needed combination therapy to reach this National Cholesterol Education Program goal during the 2.5 years of the study. Adding nicotinic acid to pravastatin produced LDL cholesterol levels of 2.6 mmol/L or less in 15 more of these 35 patients, so that 94% (n = 33) of the patients receiving these two drugs reached this goal. CONCLUSIONS: To reach current goals for LDL cholesterol levels, most normolipidemic patients with coronary heart disease in this study needed combination therapy. Pravastatin with nicotinic acid and pravastatin with gemfibrozil are well-tolerated combinations that can maintain target LDL cholesterol levels, decrease triglyceride levels, and increase HDL cholesterol levels. Adding resin to these combinations produced no further benefit.

Algorithms↗
PubMed1995

The influence of pretreatment low density lipoprotein cholesterol concentrations on the effect of hypocholesterolemic therapy on coronary atherosclerosis in angiographic trials. Harvard Atherosclerosis Reversibility Project Research Group.

Angiographic trials of coronary atherosclerosis treatment have demonstrated that lowering low density lipoprotein (LDL) cholesterol concentrations improves coronary artery stenosis. Most patients in previous trials have had at least mildly elevated LDL. Recently, however, the Harvard Atherosclerosis Reversibility Project (HARP) did not find such benefit in patients with lower baseline LDL levels compared with previous trials. We reviewed and analyzed all cholesterol-lowering trials that used angiographic endpoints. Unifactorial trials of hypocholesterolemic dietary or drug therapy demonstrated that the higher the baseline LDL, the greater the improvement in quantitatively determined stenosis in the treatment group compared with the controls (r = .83). Considering the change in stenosis in the treatment group alone, regression was more common in trials in which baseline mean LDL was > 170 mg/dl (> 4.4 mmol/liter), whereas progression occurred when baseline mean LDL was < 170 mg/dl (< 4.4 mmol/liter). HARP had the lowest baseline LDL (137 mg/dl [3.54 mmol/liter]), and showed no tendency for improvement in lesions. In contrast to the influence of baseline LDL levels, neither a low LDL level achieved on treatment nor a large percentage reduction in LDL was related to improvement in lesions. Sample size differences between HARP and the other trials are unlikely to be a major explanatory factor, since trials of comparable sample size to HARP, but with higher initial LDL, demonstrated favorable results. We conclude that coronary lesions that develop in the context of average LDL levels show less angiographic improvement in response to substantial LDL reduction than lesions in hypercholesterolemic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Controlled trial of fish oil for regression of human coronary atherosclerosis. HARP Research Group.

OBJECTIVES: This randomized clinical trial tested whether fish oil supplements can improve human coronary atherosclerosis. BACKGROUND: Epidemiologic studies of populations whose intake of oily fish is high, as well as laboratory studies of the effects of the polyunsaturated fatty acids in fish oil, support the hypothesis that fish oil is antiatherogenic. METHODS: Patients with angiographically documented coronary heart disease and normal plasma lipid levels were randomized to receive either fish oil capsules (n = 31), containing 6 g of n-3 fatty acids, or olive oil capsules (n = 28) for an average duration of 28 months. Coronary atherosclerosis on angiography was quantified by computer-assisted image analysis. RESULTS: Mean (+/- SD) baseline characteristics were age 62 +/- 7 years, plasma total cholesterol concentration 187 +/- 31 mg/dl (4.83 +/- 0.80 mmol/liter) and triglyceride levels 132 +/- 70 mg/dl (1.51 +/- 0.80 mmol/liter). Fish oil lowered triglyceride levels by 30% (p = 0.007) but had no significant effects on other plasma lipoprotein levels. At the end of the trial, eicosapentaenoic acid in adipose tissue samples was 0.91% in the fish oil group compared with 0.20% in the control group (p < 0.0001). At baseline, the minimal lumen diameter of coronary artery lesions (n = 305) was 1.64 +/- 0.76 mm, and percent narrowing was 48 +/- 14%. Mean minimal diameter of atherosclerotic coronary arteries decreased by 0.104 and 0.138 mm in the fish oil and control groups, respectively (p = 0.6 between groups), and percent stenosis increased by 2.4% and 2.6%, respectively (p = 0.8). Confidence intervals exclude improvement by fish oil treatment of > 0.17 mm, or > 2.6%. CONCLUSIONS: Fish oil treatment for 2 years does not promote major favorable changes in the diameter of atherosclerotic coronary arteries.

Adipose Tissue↗
PubMed1994

Effect on coronary atherosclerosis of decrease in plasma cholesterol concentrations in normocholesterolaemic patients. Harvard Atherosclerosis Reversibility Project (HARP) Group.

Lipid-lowering therapy ameliorates coronary atherosclerosis in patients with raised concentrations of low-density-lipoprotein (LDL) cholesterol. We have investigated whether a similar benefit can be obtained in normocholesterolaemic patients. We studied 79 normocholesterolaemic patients with coronary heart disease (70 male, 9 female), mean age 58 years, all non-smokers, with mean total cholesterol concentration 5.5 mmol/L. All patients received diet therapy and were randomly assigned placebo (39) or active treatment (40) with pravastatin, nicotinic acid, cholestyramine, and gemfibrozil stepwise as needed to reach the specified goal (total cholesterol < or = 4.1 mmol/L, ratio of LDL/high-density-lipoprotein [HDL] cholesterol < or = 2.0). Coronary angiograms at baseline and after 2.5 years of treatment were analysed by computer-assisted quantitative techniques. There was no significant difference in coronary atherosclerosis during follow-up between the active treatment and placebo groups; the mean minimum diameter narrowed significantly but to the same extent in both groups (change baseline to 2.5 years 0.14 [SD 0.42] and 0.15 [0.42] mm, respectively, both p < 0.001). Similarly, the change in percentage stenosis did not differ between the groups (2.1 [10.6] vs 2.4 [10.3]%). By multiple regression analysis, the adjusted difference between the groups was a 0.04 mm (95% CI -0.04 to 0.12 mm) increase in minimum diameter and a 0% (-1.7 to 1.7) change in percentage stenosis. The groups differed significantly in plasma lipids (% change in active minus % change in placebo group: -28% total cholesterol, -41% LDL-cholesterol, 13% HDL-cholesterol, -26% triglycerides, -31% apolipoprotein B, all p < 0.001). Thus, intensive pharmacological treatment of normocholesterolaemic patients has significant effects on plasma lipid concentrations but no angiographically measurable benefit on the coronary arteries.

Anticholesteremic Agents↗
PubMed1994

Effects of heparin and cardiac catheterization on serum lipoprotein and triglyceride levels.

This study determined whether heparin administration and procedures involving heparin significantly affect lipid measurement. Serum lipid and lipoprotein analyses (total cholesterol, triglycerides, high-density lipoprotein [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol, apolipoprotein B, and apolipoprotein A-I) were performed at baseline and at several time points after (1) intravenous heparin or placebo in 6 healthy volunteers (group 1), (2) cardiac catheterization with heparin in 26 patients (group 2), and (3) peripheral angiography without heparin in 11 patients (group 3). In group 1, after heparinization, triglycerides decreased 50 +/- 12 mg/dl (-57%, p < 0.001 vs baseline and placebo) at 60 minutes. No changes were observed in other lipid or lipoprotein fractions. After cardiac catheterization (group 2), however, decreases were observed not only in triglycerides (58 +/- 26 mg/dl [-40%]), but also in total cholesterol (28 +/- 12 mg/dl [-14%]), LDL cholesterol (19 +/- 22 mg/dl [-15%]), apolipoprotein B (13 +/- 9 mg/dl [-14%]), and apolipoprotein A-I (21 +/- 14 mg/dl [-17%]) (p < 0.001 vs baseline for all), and HDL cholesterol (4 +/- 7 mg/dl [-3%], p = 0.07). With the exception of triglycerides, these values remained significantly decreased for > or = 24 hours. The change in HDL was variable: Whereas most patients had a decrease (n = 24), 2 patients had a dramatic increase (> 100%) after administration of heparin. Similar decreases in total cholesterol, LDL cholesterol, and apolipoproteins B and A-I were observed in group 3 undergoing peripheral angiography without heparin.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins↗
PubMed1993

Cost-effectiveness of a smoking cessation program after myocardial infarction.

OBJECTIVES: The purpose of this study was to evaluate the cost-effectiveness of a smoking cessation program initiated after acute myocardial infarction. BACKGROUND: The value of allocating health care resources to smoking cessation programs after myocardial infarction has not been compared with the value of other currently accepted interventions. METHODS: A model was developed to examine the cost-effectiveness of a recently reported smoking cessation program after an acute myocardial infarction. The cost was estimated by considering the resources necessary to implement the program, and the effectiveness was expressed as discounted years of life saved. Years of life saved were estimated by modeling life expectancy using a single declining exponential approximation of life expectancy based on data from published reports. RESULTS: The cost-effectiveness of the nurse-managed smoking cessation program was estimated to be $220/year of life saved. In a one-way sensitivity analysis, the cost-effectiveness of the program remained < $20,000/year of life saved if the program decreased the smoking rate by only 3/1,000 smokers (baseline assumption 26/100 smokers), or if the program cost as much as $8,840/smoker (baseline assumption $100). In a two-way sensitivity analysis, even if the cost of the program were as high as $2,000/participant, the cost-effectiveness of the program would be < $10,000/year of life saved so long as the program helped an additional 12 smokers quit for every 100 enrolled. CONCLUSIONS: Over a wide range of estimates of costs and effectiveness, a nurse-managed smoking cessation program after acute myocardial infarction is an extremely cost-effective intervention. This program is more cost-effective than beta-adrenergic antagonist therapy after myocardial infarction.

Analysis of Variance↗
PubMed1993

Natural history of coronary atherosclerosis using quantitative angiography in men, and implications for clinical trials of coronary regression. The Harvard Atherosclerosis Reversibility Project Study Group.

Previous studies of the natural history of coronary disease generally relied on estimates of percent stenosis derived from visual assessment of the coronary angiogram. In a study of 26 patients, serial quantitative angiography was performed 3 years apart to determine changes in both absolute measurements of the luminal diameter and relative percent stenosis. Initially, the mean minimal diameter of 74 coronary obstructions was 1.94 +/- 0.09 mm, the mean "normal" reference diameter was 3.06 +/- 0.11 mm, and the mean percent stenosis was 37%. At follow-up, there was a mild reduction of 0.12 +/- 0.04 mm (6%) in the minimal diameter (p < 0.005), and an increase in percent stenosis to 39% (p = 0.03). The average diameter of 85 arterial segments without a focal obstruction either initially or at follow-up showed mild but significant progression (-0.11 +/- 0.04 mm; p = 0.02). Using a minimal change of 0.27 mm in arterial diameter as a categoric variable, progression occurred in 26% of 74 arterial segments, no significant change in 65%, and regression in 9%. The only significant determinant of disease progression was the initial severity of disease. Obstructed arteries with a larger initial minimal diameter and presumably milder disease progressed more rapidly than did those with a smaller diameter (r = -0.42; p = 0.0002). There was no effect of age on the rate of progression (r = 0.02; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization↗
PubMed1993

Amlodipine once a day in stable angina: double-blind crossover comparison with placebo.

Although calcium antagonists form a mainstay of therapy in patients with angina pectoris, the currently available agents have significant limitations. Nifedipine, diltiazem, and verapamil are all high-clearance agents with significant hepatic extraction and rapid clearance, leading to limited and short-lived bioavailability necessitating frequent daily administration. In contrast, amlodipine, a dihydropyridine calcium antagonist, has a long half-life of 35-50 h (compared with 3 to 4 h elimination half-life of diltiazem, verapamil, and nifedipine). After oral doses, the relative bioavailability of amlodipine is high (64%) and absorption is smooth, with peak plasma levels being achieved 6-12 h postdose. Bioavailability is not affected by the consumption of food. In common with other dihydropyridine calcium antagonists, amlodipine is eliminated mainly by metabolism. None of the metabolites of amlodipine has significant calcium antagonist effects in humans. In contrast to verapamil or diltiazem, amlodipine has no effect on sinus or atrioventricular node and little or no effect on the resting heart rate. Amlodipine does not have any appreciable negative inotropic effect with the relevant clinical dose. Other clinical studies have shown amlodipine to be effective when used once-daily in chronic stable angina and vasospastic angina. Comparative studies indicate that the antianginal efficacy of amlodipine is comparable to the beta blocker nadolol and the benzothiazepine calcium antagonist diltiazem. Amlodipine has also been found to provide improved antianginal effects when combined to treatment with beta blockers and/or long-acting nitrates. Treatment with amlodipine either as monotherapy or combined with other antianginal therapy for up to 26 weeks shows that efficacy is maintained, with no evidence of tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

High-density lipoprotein subfractions.

High-density lipoprotein (HDL) consists of a heterogeneous group of particles defined either by size or by apolipoprotein content. Subfractions of HDL appear to have distinct but interrelated metabolic functions, including facilitation of cholesteryl ester transfer to low- and very-low-density lipoproteins, modulation of triglyceride-rich particle catabolism, and, possibly, removal of cholesterol from peripheral tissues. Like HDL cholesterol, HDL subfractions are widely affected by a variety of factors. Subfractions also are markers for epidemiologic risk for coronary artery disease. Because they provide information about the physiologic processes of cholesterol metabolism, HDL subfractions are emerging as an increasingly important tool in the study of the relationship between lipids and cardiovascular disease.

Cholesterol↗
PubMed1993

Relation of vessel wall shear stress to atherosclerosis progression in human coronary arteries.

The purpose of this study was to determine the relation between vessel wall shear stress and the rate of atherosclerosis progression. Quantitative angiography was used to calculate the change in coronary arterial diameter over 3.0 years in patients enrolled in the Harvard Atherosclerosis Reversibility Project pilot study (n = 20 arterial segments). Vessel wall shear stress was calculated by means of a validated finite-difference model of the Navier-Stokes' equation that assumes a coronary flow rate of 8 ml/sec. The correlation between vessel wall shear stress and the change in arterial diameter at multiple points (mean, 70) along the length of the artery was then calculated for each of the 20 segments with a focal stenosis. In 15 of the 20 arterial segments there was a significant correlation (p < 0.05) between low shear stress and an increased rate of atherosclerosis progression. A Fisher's z transformation was then used to combine the correlation coefficients from all 20 segments. Low shear stress was significantly correlated (z = 0.37 +/- 0.00074, p < 0.0001) with an increased rate of atherosclerosis progression. This serial quantitative evaluation of human coronary arteries is consistent with previous data that have suggested that low shear stress promotes atherosclerosis progression. Variations in local vessel wall shear stress may explain the previously reported near-independent rate of atherosclerosis progression in multiple lesions within the same patient despite exposure to the same circulating lipoprotein values and systemic hemodynamics.

Computer Simulation↗
PubMed1992

Cost effectiveness of thrombolytic therapy with streptokinase in elderly patients with suspected acute myocardial infarction.

BACKGROUND: There is a lack of consensus among cardiologists about the potential benefit of thrombolytic therapy for suspected acute myocardial infarction in older patients. To investigate this issue, we constructed a decision-analytic model for patients 75 years of age or older who present with ST-segment elevation within six hours of the onset of symptoms suggesting acute myocardial infarction. METHODS: The variables incorporated in this model were the probability that the patient has an acute myocardial infarction, the probability of in-hospital death among patients with acute myocardial infarction who do not receive thrombolytic therapy, the probability of a fatal or incapacitating complication resulting from thrombolytic therapy, and the expected relative reduction in the risk of death associated with thrombolytic therapy in patients with acute myocardial infarction. Our analyses were based primarily on the use of streptokinase as the thrombolytic agent. RESULTS: Given our base-line assumptions, the probability of dying in the hospital was 21.4 percent if thrombolytic therapy was given and 24.4 percent if it was not given. In one-way sensitivity analyses, thrombolytic therapy decreased the risk of dying if the probability that the patient had an acute myocardial infarction was assumed to be greater than 9 percent, if the probability of dying in the hospital after an acute myocardial infarction without thrombolytic therapy was assumed to be greater than 3 percent, if the rate of fatal or incapacitating complications due to thrombolytic therapy was assumed to be 4 percent or less, or if the relative reduction in the risk of death associated with thrombolytic therapy was assumed to be greater than 1 percent. On the basis of our base-line assumptions, our estimate of the cost effectiveness of streptokinase therapy (the cost per year of life saved) for an 80-year-old patient with suspected acute myocardial infarction was $21,200. For a wide range of assumptions about risks, benefits, and costs, the cost per year of life saved remained less than $55,000. CONCLUSIONS: Within the limitations imposed by the assumptions used in our analysis, thrombolytic therapy with streptokinase was found to be a beneficial and cost-effective treatment for suspected acute myocardial infarction in elderly patients in a wide variety of clinical circumstances.

Age Factors↗
PubMed1992

Quantitative angiographic and statistical methods to assess serial changes in coronary luminal diameter and implications for atherosclerosis regression trials.

The purpose of this study was (1) to determine a threshold for categorizing individual coronary lesions as either significantly progressing or regressing, (2) to determine whether multiple lesions within individual patients progress at independent rates, and (3) to calculate sample sizes for atherosclerosis regression trials. Seventeen patients with 46 significant lesions (2.7 lesions/patient) underwent repeat coronary arteriography 3.0 years apart. With use of the standard error of the mean change in diameter from initial to repeat catheterization across 5 pairs of consecutive end-diastolic frames, individual lesions were categorized as either significantly (p less than 0.01) progressing or regressing if there was a 0.27 mm change in minimum diameter or a 7.8 percent point change in percent stenosis. The mean diameter change of a sample of lesions can also be analyzed as a continuous variable using either the lesions or the patient as the primary unit of analysis. A lesion-specific analysis can be accomplished using a multiple regression model that accounts for the intraclass correlation (rho) in the degree of change among multiple lesions within individual patients. The intraclass correlations in percent stenosis (rho = 0.01) and minimum diameter (rho = -0.24) were low, indicating that disease progression in different lesions within individual patients is nearly independent. With use of this model, 50 patients per treatment group would permit the detection of a 5.5% difference between treatment group means in the change in minimum diameter and a 2.7% percentage point (not percent) difference in the change in percent stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1992

Selection of patients for coronary angiography and coronary revascularization early after myocardial infarction: is there evidence for a gender bias?

OBJECTIVE: To determine whether a gender bias exists in the selection of patients for diagnostic and therapeutic cardiovascular procedures early after myocardial infarction. DESIGN: A retrospective cohort study. SETTING: A community-based tertiary care teaching hospital. PATIENTS: A total of 2473 consecutive patients with a principal discharge diagnosis of acute myocardial infarction and a peak creatine kinase MB fraction of at least 4%. MEASUREMENTS: Comparison of men and women regarding the frequency with which they underwent various cardiac procedures. RESULTS: Women had coronary angiography during hospitalization for myocardial infarction much less frequently than men (odds ratio, 0.55; 95% Cl, 0.46 to 0.65), but the age-adjusted rates were similar in women and men (odds ratio, 0.91; Cl, 0.75 to 1.12). An abnormal ejection fraction (less than 50%) was equally frequent in women and men who underwent left ventriculography (odds ratio, 0.85; Cl, 0.56 to 1.30). Among patients who had coronary angiography, women had a significantly lower rate of severe coronary artery disease, defined as either a left main stenosis of more than 50%, three-vessel disease, or two-vessel disease with a proximal left anterior descending stenosis of more than 70% (odds ratio, 0.67; Cl, 0.48 to 0.93). When adjustments were made for age, women had percutaneous transluminal coronary angioplasty as often as men (odds ratio, 1.16; Cl, 0.83 to 1.62) but had coronary artery bypass graft surgery significantly less frequently (odds ratio, 0.58; Cl, 0.37 to 0.91). When adjustments were made for age and the severity of coronary artery disease, the difference in rates was of borderline significance (odds ratio, 0.65; Cl, 0.41 to 1.01). CONCLUSIONS: No evidence of a difference in the rate of coronary angiography early after myocardial infarction between women and men was found after age adjustment. Among patients who have cardiac catheterization early after myocardial infarction, women and men are equally likely to have angioplasty, but women are less likely than men to have coronary artery bypass surgery.

Adult↗