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Biomedical subjects

D B Hunninghake

Publications and source records attributed to D B Hunninghake.

At least 55 records · Page 3Linked to original sources
PubMed1998

The cost of reaching National Cholesterol Education Program (NCEP) goals in hypercholesterolaemic patients. A comparison of atorvastatin, simvastatin, lovastatin and fluvastatin.

OBJECTIVE: Recognising the importance of treating hyperlipidaemia, the National Cholesterol Education Program (NCEP) has established widely accepted treatment goals for low density lipoprotein cholesterol (LDL-C). Medications used most commonly to achieve these LDL-C goals are HMG-CoA reductase inhibitors. The relative resource utilisation and cost associated with the use of reductase inhibitors of different LDL-C lowering efficacy are unknown, but are major health and economic concerns. The objective of this study was to determine the mean total cost of care to reach NCEP goals with various reductase inhibitors. DESIGN: In a randomised, 54-week, 30-centre controlled trial we compared resources used and costs associated with treating patients to achieve NCEP goals using 4 reductase inhibitors: atorvastatin, simvastatin, lovastatin and fluvastatin. PATIENTS AND PARTICIPANTS: The trial studied 662 patients; 318 had known atherosclerotic disease. INTERVENTIONS: Reductase inhibitor therapy was initiated at recommended starting doses and increased according to NCEP guidelines and package insert information. For patients who did not reach the goal at the highest recommended dose of each reductase inhibitor, the resin colestipol was added. MAIN OUTCOME MEASURES AND RESULTS: Patients treated with atorvastatin, compared-with other reductase inhibitors, were more likely to reach NCEP goals during treatment (p < 0.05), required fewer office visits (p < 0.001) and less adjuvant colestipol therapy (p = 0.001). Consequently, the mean total cost of care (1996 values) to reach NCEP goals was lower with atorvastatin [$US1064; 95% confidence interval (CI): $US953 to $US1176] compared with simvastatin ($US1471, 95% CI: $US1304 to $US1648), lovastatin ($US1972; 95% CI: $US1758 to $US2186) and fluvastatin ($US1542; 95% CI: $US1384 to $US1710). Results were similar for patients with or without known atherosclerotic disease. CONCLUSIONS: In patients requiring drug therapy for hypercholesterolaemia, NCEP LDL-C goals are achieved significantly more often using fewer resources with atorvastatin compared with simvastatin, lovastatin or fluvastatin.

Aged↗
PubMed1997

Rationale, design, and baseline characteristics of the Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT).

The Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial is the first angiographic clinical trial to be designed to test whether an agent can slow or even reverse the progression of early coronary atherosclerosis in patients with documented disease. In addition, a subset of patients are undergoing carotid ultrasound examinations, providing a unique opportunity to assess and correlate disease progression in 2 arterial beds.

Aged↗
PubMed1997

The efficacy and six-week tolerability of simvastatin 80 and 160 mg/day.

The hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin is the most effective of the currently approved hypolipidemic drugs and has been shown to reduce mortality and coronary morbidity in patients with coronary artery disease. For these patients the United States National Cholesterol Education Program advocates reducing low-density lipoprotein (LDL) cholesterol to <100 mg/dl. However, in some patients this cannot be achieved using monotherapy with simvastatin 40 mg/day, the current maximal recommended dose. To evaluate the effectiveness of extending the dosage range, 156 subjects with LDL cholesterol >160 mg/dl and triglycerides (TG) <350 mg/dl were randomized to simvastatin at doses of 40, 80, and 160 mg/day in a 26 week, double-blind, 3-period, complete block crossover study. Each active treatment period was 6 weeks in duration with intervening 2 week washout periods. Median reductions from baseline in LDL cholesterol were 41%, 47%, and 53% in the 40-, 80-, and 160-mg groups, respectively. The corresponding reductions in plasma TG were 21%, 23%, and 33%. High-density lipoprotein (HDL) cholesterol increased by 6% to 8% in each group. One patient (0.7%) taking 160 mg developed myopathy; 1 patient (0.7%) taking 80 mg, and 3 (2.1%) taking 160 mg had transaminase elevations > 3 times the upper limit of normal. No new or unexpected adverse effects were observed. We conclude that simvastatin at doses of 80 and 160 mg/day provides additional efficacy with a low short-term incidence of adverse effects; our results support the continued investigation of simvastatin at these doses.

Adult↗
PubMed1997

Recruitment for controlled clinical trials: literature summary and annotated bibliography.

This article is a literature summary and annotated bibliography of research on recruitment for controlled clinical trials published through 1995. It extends and revises a similar review published in this journal a decade ago. The current commentary focuses on intervening developments in recruitment, including diverse populations, HIV trials, primary prevention trials, recruitment strategies, overall planning and management, patient and physician attitudes, adherence, generalizability, and cost. Profound barriers may exist in the recruitment of diverse populations, involving language, cultural factors, beliefs about medical research, and the appropriateness of available protocols. Extensive literature exists on patient and physician barriers to participation. Trials in HIV-infected or AIDs-diagnosed individuals introduce special considerations, including issues of confidentiality, parallel track design, and populations difficult to define and track. Recruitment strategies such as patient registries, occupational screening, direct mail, and the media are now prominent in the literature. Successful planning and management of an overall recruitment plan include piloting strategies, monitoring recruitment by data tracking systems, and hiring quality staff. Generalizability of study results is influenced by the characteristics of participants and by their adherence to study protocol. With increasingly limited funding to conduct clinical trials, efforts to quantify and reduce recruitment costs are being made. While over 4000 titles were identified, primarily by MEDLINE literature search, the articles summarized emphasize data-supported and -confirmed conclusions, and broad coverage of disease areas. We annotate here 91 outstanding articles useful for formulation of overall recruitment approaches in clinical trials.

Clinical Trials as Topic↗
PubMed1997

Psyllium-enriched cereals lower blood total cholesterol and LDL cholesterol, but not HDL cholesterol, in hypercholesterolemic adults: results of a meta-analysis.

We conducted a meta-analysis to determine the effect of consumption of psyllium-enriched cereal products on blood total cholesterol (TC), LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) levels and to estimate the magnitude of the effect among 404 adults with mild to moderate hypercholesterolemia (TC of 5.17-7.8 mmol/L) who consumed a low fat diet. Studies of psyllium cereals were identified by a computerized search of MEDLINE and Current Contents and by contacting United States-based food companies involved in psyllium research. Published and unpublished studies were reviewed by one author and considered eligible for inclusion in the meta-analysis if they were conducted in humans, were randomized, controlled experiments, and included a control group that ate cereal providing </=3 g soluble fiber/d. Eight published and four unpublished studies, conducted in four countries, met the criteria. Analysis of a linear model was performed, controlling for sex and age. Female subjects were divided into two groups to provide a rough estimate of the effect of menopausal status (premenopausal = <50 y, postmenopausal = >/=50 y) on blood lipids. The meta-analysis showed that subjects who consumed a psyllium cereal had lower TC and LDL-C concentrations [differences of 0.31 mmol/L (5%) and 0.35 mmol/L (9%), respectively] than subjects who ate a control cereal; HDL-C concentrations were unaffected in subjects eating psyllium cereal. There was no effect of sex, age or menopausal status on blood lipids. Results indicate that consuming a psyllium-enriched cereal as part of a low fat diet improves the blood lipid profile of hypercholesterolemic adults over that which can be achieved with a low fat diet alone.

Adult↗
PubMed1997

Effect of pharmacologic lipid lowering on health-related quality of life in older persons: results from the Cholesterol Reduction in Seniors Program (CRISP) Pilot Study.

OBJECTIVE: To determine the effect of lovastatin therapy on health-related quality of life in older persons. DESIGN: A prospective, randomized, double blind clinical trial. SETTING: Four university medical center research clinics. PARTICIPANTS: There were 431 men and women, primarily 65 years of age or older, with low density lipoprotein levels greater than 159 mg/dL and less than 221 mg/dL. Exclusion criteria included a Mini-Mental state score less than 24 or presence of recent cardiovascular events or other serious chronic disease likely to shorten survival. INTERVENTION: All participants were administered the National Cholesterol Education Program step one diet and were then randomized to placebo, 20 mg lovastatin, or 40 mg lovastatin. MEASUREMENTS: Areas of health-related quality of life assessed in the Cholesterol Reduction in Seniors Program (CRISP) included: (1) physical functioning, (2) sleep behavior, (3) social support, (4) depression, (5) cognitive function, and (6) health perception. Three global change questions asked the patients to judge change in general health since starting the study diet or the study medication and change in ability to function or care for self. Although some patients were followed for a total of 12 months, all participants were followed for 6 months, and 6-month data have been used for the primary analysis in this paper. RESULTS: Patients treated with 20 mg of lovastatin had a 17% and 24% reduction in total cholesterol and LDL-cholesterol, respectively. Patients treated with the 40-mg lovastatin dose achieved reductions of 20% for total cholesterol and 28% for LDL-cholesterol. Complaints of possible adverse events were remarkably similar in the two active treatment groups and the placebo group. At 6 months of follow-up there were no statistically significant differences found in mean change scores from baseline between treatment groups on the health-related quality of life measures (physical functioning, sleep, social support, depression, cognitive function scales, health perception) or global questions. CONCLUSIONS: This study demonstrates that lovastatin was extremely well tolerated in an older cohort, both with regard to symptoms and to health-related quality of life.

Activities of Daily Living↗
PubMed1995

Effect of fluvastatin on intermediate density lipoprotein (remnants) and other lipoprotein levels in hypercholesterolemia.

The accelerated atherosclerosis in diseases associated with elevated remnant lipoprotein levels has directed interest toward the response of this lipoprotein species to lipid-lowering treatment. The effect of fluvastatin--a synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor--was compared with that of placebo on parameters of remnant metabolism in 57 patients with moderate hypercholesterolemia, but not heterozygous familial hypercholesterolemia, type III hyperlipidemia, or endogenous hypertriglyceridemia. Fluvastatin therapy resulted in decreases versus baseline in plasma total cholesterol, low density lipoprotein cholesterol (LDL-C) and LDL apolipoprotein (apo) B levels of 18%, 20%, and 18%, respectively (p < 0.01). Plasma parameters related to remnant metabolism were also significantly decreased: intermediate density lipoprotein by 43% and apo E by 22% (p < 0.01). The percent decrease in plasma intermediate density lipoprotein cholesterol level was twice that of LDL-C and 50% greater than the decrease seen in very low density lipoprotein cholesterol (VLDL-C), which was decreased by 28%. Total triglycerides were reduced by 11% and VLDL apo B by 24%, whereas high density lipoprotein cholesterol (HDL-C) rose significantly by 8%, HDL2-C by 24%, and HDL3-C by 3%. There were no increases in apo A-I levels compared with placebo nor any significant change in plasma lipoprotein(a) levels. The composition of LDL and VLDL particles did not appear to be altered by therapy, as assessed by the LDL-C:LDL-B, VLDL-C:VLDL-B, or triglyceride:VLDL-B ratios.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Practical management for hyperlipidemia.

Risk assessment, known coronary and other atherosclerotic disease, and lipid levels determine the potential need for drug therapy. Specific lifestyle objectives are strongly emphasized. Indications and regimens for newer and older drugs are offered.

Humans↗
PubMed1994

Changes in composition and distribution of LDL subspecies in hypertriglyceridemic and hypercholesterolemic patients during gemfibrozil therapy.

The effect of gemfibrozil (GEM) on composition and distribution of LDL subspecies in 10 hypertriglyceridemic (HTG) patients with triglyceride (TG) levels of 300-750 mg/dl and low density lipoprotein cholesterol (LDL-C) < 160 mg/dl, and 8 hypercholesterolemic (HC) patients with LDL-C > or = 190 mg/dl and TG < 200 mg/dl was investigated. Patients were randomized in a double-blind, crossover design to 12 week periods of placebo and 1200 mg/day GEM with an intervening washout period. All 7 LDL subspecies in the density range of 1.029 to 1.063 g/ml in the HTG group contained more TG (P < 0.01) and less free cholesterol (P < 0.05), while the proportion of cholesterol ester was lower only in LDL subspecies 1 to 3 (P < 0.05) as compared to the HC group. In HTG patients, GEM increased the proportion of cholesterol ester (P < 0.05) in all subfractions, while the proportion of free cholesterol was increased and TG was decreased in LDL subspecies 1 to 4 only (P < 0.05). GEM decreased the LDL subspecies score from 4.8 +/- 0.7 to 4.2 +/- 0.5, and the major LDL subclass density from 1.048 +/- 0.006 to 1.043 +/- 0.002 g/ml (P < 0.01) in HTG patients. GEM decreased TG levels to mean of 228 +/- 52 mg/dl in HTG patients, but there was no change in LDL phenotype. No significant changes in composition and distribution of LDL subspecies were noted in HC patients with GEM. We conclude that GEM significantly altered the composition and distribution of LDL subspecies with a shift from small dense LDL particles to large, less dense particles in HTG patients.

Adult↗
PubMed1994

Cholesterol lowering in the elderly. Results of the Cholesterol Reduction in Seniors Program (CRISP) pilot study.

BACKGROUND: Total and lipoprotein cholesterol levels continue to be predictors of coronary heart disease risk in men and women over 65 years old. Cholesterol-lowering trials, however, while sometimes including such subjects, have not concentrated on this age group. The Cholesterol Reduction in Seniors Program was a five-center pilot study to assess feasibility of recruitment and efficacy of cholesterol lowering in this age group. METHODS: The study was a randomized, double-masked clinical trial with placebo, 20-mg lovastatin, and 40-mg lovastatin arms. Major efforts were made to recruit women and minorities. Participants were followed up for 1 year on a cholesterol-lowering diet plus placebo or study drug. End points were changes in blood lipid levels. Data on other blood chemistry values, as well as quality-of-life measures and coronary heart disease morbidity and mortality, were also collected. RESULTS: Four hundred thirty-one subjects with low-density lipoprotein cholesterol levels greater than 4.1 and less than 5.7 mmol/L (159 and 221 mg/dL) were randomized, of whom 71% were women and 21% were African Americans; the mean age was 71 years. In the 20- and 40-mg lovastatin groups, total cholesterol levels fell 17% and 20%; low-density lipoprotein cholesterol levels fell 24% and 28%; triglyceride levels fell 4.4% and 9.9%, respectively. High-density lipoprotein cholesterol levels rose 7.0% and 9.0%, respectively. No changes were observed in the placebo group. Gender, race, and age did not significantly affect responses. Coronary heart disease morbidity and mortality data were collected but not analyzed for this study. CONCLUSION: Older subjects of both genders and a variety of racial and ethnic groups can be successfully recruited into a cholesterol-lowering trial. Lovastatin has effects similar to those reported in younger subjects in previous controlled trials. There is little advantage to the higher lovastatin daily dose. Side effects were remarkably low in all groups.

Aged↗
PubMed1994

The Eating Pattern Assessment Tool: a simple instrument for assessing dietary fat and cholesterol intake.

OBJECTIVE: This study describes the development of the self-administered Eating Pattern Assessment Tool (EPAT), which is designed to assess dietary fat and cholesterol intake and aid patients and health professionals in achieving control of blood cholesterol levels. DESIGN: Test-retest reliability of the instrument over five visits and concurrent validity testing compared with 4-day food records. SETTING AND SAMPLE: The instrument was tested at multiple sites of a large manufacturing corporation using 436 adult volunteers with approximately equal proportions of men and women from three socioeconomic levels. MAIN OUTCOME MEASURE: Development of the EPAT centered on creating an instrument that was simple and easy to use in a primary-care setting, that would provide a reliable assessment of intake of dietary fat and cholesterol among adults, and that would measure frequency of consumption of foods from high-fat and low-fat categories. ANALYSES: Test-retest reliability for repeated use was estimated by between-visit Pearson product-moment correlations of EPAT section scores. Concurrent validity was assessed by using product-moment correlation between EPAT section scores and mean daily B-scores obtained from 4-day food records. RESULTS: Test-retest reliability estimates were 0.91 between all adjacent pairs of visits and 0.83 between visits 1 and 5 (4 months). Validity was 0.56. APPLICATIONS/CONCLUSIONS: The EPAT is a simple, quick, self-administered tool using an easy scoring method for accurately assessing fat and cholesterol intake. It is a reliable and valid substitute for more time-consuming food records. EPAT also provides an efficient way to monitor eating patterns of patients over time and is arranged to provide an educational message that reinforces the consumption of recommended types and numbers of servings of low-fat foods.

Adult↗
PubMed1994

Long-term treatment of hypercholesterolemia with dietary fiber.

PURPOSE: To evaluate the hypocholesterolemic effects of long-term treatment (36 to 51 weeks) with a mixture of dietary fibers (guar gum, pectin, soy, pea, corn bran) administered twice a day. PATIENTS AND METHODS: Fifty-nine subjects with moderate hypercholesterolemia who completed a 15-week, placebo-controlled study with the dietary fiber were treated for an additional 36 weeks with 20 g/day of fiber. Subjects were counseled and monitored on a National Cholesterol Education Program (NCEP) Step-One Diet before starting and during treatment. Analyses of changes in lipoprotein values during the additional 36 weeks of treatment took into account changes in weight, diet, and other variables that might have affected the response to treatment. RESULTS: There were no significant effects on the levels of either triglycerides or high-density lipoprotein cholesterol (HDL-C). Levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and the LDL/HDL ratio were significantly reduced during treatment. The mean percentage reductions from baseline after 51 weeks of treatment were approximately 5% for TC, 9% for LDL-C, and 11% for the LDL/HDL ratio. Changes were apparent after 3 weeks of treatment, with the maximum reductions occurring by the 15th week of treatment. CONCLUSIONS: For subjects on a Step-One Diet who complied with the treatment regimen, the moderate cholesterol-lowering effects of the fiber persisted throughout the 36-to-51 week treatment period.

Chi-Square Distribution↗
PubMed1994

Diagnosis and treatment of lipid disorders.

A brief summary of the revised NCEP guidelines for the detection, evaluation, and treatment of high blood cholesterol levels in adults is presented. The major changes in the current guidelines are the inclusion of three categories of CHD risk, one for secondary prevention and two for primary prevention based upon a combination of LDL-c levels and the number of other risk factors. Age and gender are now considered in the determination of risk factors. There is more emphasis on the treatment of postmenopausal women and individuals 65 years of age or older and less emphasis on drug treatment in younger patients. HDL-c measurements are now routine in screening in the clinical setting and drugs that both lower LDL-c and increase HDL-c levels can be considered in high risk patients. According to the current guidelines, approximately 29% of the adult population should receive dietary therapy and approximately 7% may be candidates for drug therapy.

Aged↗
PubMed1994

Hypocholesterolemic effects of a dietary fiber supplement.

The cholesterol-lowering effects of a fiber supplement were evaluated in patients with mild to moderate hypercholesterolemia. After a 9-wk diet stabilization period, patients were randomly assigned to treatment with 10 or 20 g/d of the fiber supplement or with a matching placebo. Among patients who completed the 15-wk treatment period, total cholesterol, LDL cholesterol, and the ratio of LDL to HDL (LDL/HDL) were significantly reduced (P < 0.05) for the 10- (n = 40) and 20-g/d (n = 39) groups compared with the placebo group (n = 48). In the placebo group and 10- and 20-g/d groups, the percent changes in total cholesterol were 0.4%, -5.8%, and -4.9%, in LDL cholesterol were -0.4%, -8.1%, and -7.3%, and in LDL/HDL were 1.0%, -5.6%, and -8.7%, respectively. The fiber supplement had no significant effects (P > 0.05) on HDL cholesterol or triglycerides. The changes in lipoprotein concentrations could not be attributed to changes in diet or body weight because there were no significant changes in these variables during the 15-wk treatment period.

Adolescent↗
PubMed1994

Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group.

BACKGROUND: HMG CoA reductase inhibitors (or statins), a new class of lipid-lowering compounds, have raised expectations for more widespread use than that of the older lipid-lowering drugs. Not only are they more effective in lowering LDL cholesterol, but they are better tolerated as well. No data exist concerning the effect of statins on early carotid atherosclerosis and clinical events in men and women who have moderately elevated LDL cholesterol levels but are free of symptomatic cardiovascular disease. METHODS AND RESULTS: Lovastatin (20 to 40 mg/d) or its placebo was evaluated in a double-blind, randomized clinical trial with factorial design along with warfarin (1 mg/d) or its placebo. This report is limited to the lovastatin component of the trial. Daily aspirin (81 mg/d) was recommended for everyone. Enrollment included 919 asymptomatic men and women, 40 to 79 years old, with early carotid atherosclerosis as defined by B-mode ultrasonography and LDL cholesterol between the 60th and 90th percentiles. The 3-year change in mean maximum intimal-medial thickness (IMT) in 12 walls of the carotid arteries was the primary outcome; change in single maximum IMT and incidence of major cardiovascular events were secondary outcomes. LDL cholesterol fell 28%, from 156.6 mg/dL at baseline to 113.1 mg/dL at 6 months (P < .0001), in the lovastatin groups and was largely unchanged in the lovastatin-placebo groups. Among participants not on warfarin, regression of the mean maximum IMT was seen after 12 months in the lovastatin group compared with the placebo group; the 3-year difference was statistically significant (P = .001). A larger favorable effect of lovastatin was observed for the change in single maximum IMT but was not statistically significant (P = .12). Five lovastatin-treated participants suffered major cardiovascular events--coronary heart disease mortality, nonfatal myocardial infarction, or stroke--versus 14 in the lovastatin-placebo groups (P = .04). One lovastatin-treated participant died, compared with eight on lovastatin-placebo (P = .02). CONCLUSIONS: In men and women with moderately elevated LDL cholesterol, lovastatin reverses progression of IMT in the carotid arteries and appears to reduce the risk of major cardiovascular events and mortality. Results from ongoing large-scale clinical trials may further establish the clinical benefit of statins.

Adult↗
PubMed1994

Highlights of the new recommendations for hypercholesterolemia.

The patient who benefits most by aggressive efforts to reduce elevated LDL cholesterol is the one who is at greatest risk for a coronary event in the next 5 to 10 years. Thus, treatment decisions are based on risk-factor analysis and personal history.

Age Factors↗