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J L Probstfield

Publications and source records attributed to J L Probstfield.

At least 19 recordsLinked to original sources
PubMed1995

Results of the primary outcome measure and clinical events from the Asymptomatic Carotid Artery Progression Study.

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have proven to be more effective in reducing levels of low density lipoprotein (LDL) cholesterol and to be better tolerated than other lipid-lowering compounds. Most of the trials evaluating the effects of these new agents on progression of atherosclerosis have not included individuals asymptomatic for cardiovascular disease and who have LDL cholesterol levels at or below the limits established by the National Cholesterol Education Program for initiating treatment. The Asymptomatic Carotid Artery Progression Study (ACAPS) tested the effect of the HMG-CoA reductase inhibitor, lovastatin, on early-stage carotid atherosclerosis (as detected by B-mode ultrasonography) in 919 asymptomatic men and women, 40-79 years of age, who had LDL cholesterol levels between the 60th and 90th percentiles. Participants randomized into this double-blind, placebo-controlled, factorially designed study received lovastatin (20-40 mg/day) or lovastatin-placebo and warfarin (1 mg/day), or warfarin-placebo over a 3-year period. The progression of the mean maximum intimal-medial thickness (IMT) over 12 walls of both carotid arteries represented the primary outcome. Lovastatin treatment was associated with a reduction in progression of mean maximum IMT (p < 0.001). Levels of LDL cholesterol were reduced by 28% (43.5 mg/dl [11.25 mmol/liter]) in the lovastatin group within 6 months (p < 0.0001) and remained stable throughout the follow-up period, whereas these levels remained essentially unchanged in the lovastatin-placebo group. The difference in incidence of major cardiovascular events for patients in the lovastatin-placebo group was significant: 5 versus 14, respectively (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Tolerability of enalapril initiation by patients with left ventricular dysfunction: results of the medication challenge phase of the Studies of Left Ventricular Dysfunction.

Although converting-enzyme inhibitors are useful for the treatment of congestive heart failure (CHF), there are concerns about adverse reactions especially on initiation of therapy. In the Studies of Left Ventricular Dysfunction, enalapril, 2.5 mg twice per day was given on an open-label outpatient basis for 7 days (mean 6.1, range 2 to 7, and median 7) as a prerandomization drug challenge to 7487 patients with left ventricular dysfunction (ejection fraction < or = 0.35). Four hundred forty-four (5.93%) patients reported side effects, including symptoms attributed to hypotension (in 166 patients [2.2%]). The majority (346 [77.9%] of 444 and 129 [77.7%] of 166 with symptoms attributed to hypotension) of patients who reported side effects were willing to participate in the study and to continue receiving enalapril. Thus only 98 (1.3%) of 7487 patients (0.5% because of symptoms attributed to hypotension) were not willing to continue because of side effects. Women and patients of CHF class III or IV were more likely to report side effects. In conclusion, enalapril is well tolerated by patients with left ventricular dysfunction; treatment can be initiated on an outpatient basis in the majority of patients.

Enalapril↗
PubMed1994

Plasma lipid effects of three common vegetable oils in reduced-fat diets of free-living adults.

We compared plasma lipid changes due to the polyunsaturated fatty acids (PUFAs) in partially hydrogenated soybean oil, corn oil, and sunflower oil fed in reduced-fat diets (22-26% of total energy). Each oil was the dominant fat in isoenergetic diets of centrally prepared foods consumed by 26 male and 35 female normolipidemic, free-living individuals. Test diets were consumed double-blind, alternating with self-selected diets for 5 wk each. The ranges of proportions of total fat were: 4.7-9.7% polyunsaturated fat, 8.9-14.2% monounsaturated fat and 5.4-7.4% saturated fat. All three diets lowered (P < 0.0001) total cholesterol (11%), LDL cholesterol (13%), and HDL cholesterol (10%), without triglyceride changes. We conclude that PUFAs at approximately 6% of total energy result in clinically relevant plasma cholesterol-lowering and that the proportion of polyunsaturated fat must be an important consideration when planning reduced-fat, reduced-saturated-fat diets.

Adult↗
PubMed1993

Statistical considerations in monitoring the Systolic Hypertension in the Elderly Program (SHEP).

The Systolic Hypertension in the Elderly Program (SHEP), a randomized, double-masked, placebo-controlled trial of 4736 persons, was designed to assess the efficacy of antihypertensive drug treatment to reduce the risk of fatal and nonfatal strokes among people age 60 and over with isolated systolic hypertension. The statistical method used in interim monitoring of results was conditional power (or stochastic curtailment). The findings did not become conclusive until near the completion of the trial, and therefore SHEP was continued to its scheduled closing date. The trial demonstrated a 36% reduction in the incidence of stroke in the active treatment group (P = .0003). In addition to evaluating overall efficacy of treatment, the monitoring process considered such other issues as nonstroke outcomes, lag time between first report of stroke and final confirmation of stroke diagnosis, consistency of results across subgroups, and completeness of follow-up. The purpose of this article is to review these factors with primary emphasis on the statistical aspects.

Aged↗
PubMed1993

Conclusions and implications of the systolic hypertension in the elderly program.

Isolated systolic hypertension has a higher prevalence with age and an associated excess cardiovascular risk. The Systolic Hypertension in the Elderly Program (SHEP) was a randomized, prospective, double blind clinical trial to assess the efficacy and safety of a antihypertensive regimen based on low dose diuretic therapy in reducing the five year combined incidence of fatal and nonfatal stroke. SHEP demonstrated a significant 36% reduction in stroke incidence. Also, 27% reduction in coronary heart disease incidence and a 32% reduction in major cardiovascular disease incidence were achieved. The benefits accrued to all subgroups identified based on baseline age, race, sex, blood pressure, serum cholesterol levels, and ECG abnormalities. A low-dose diuretic regimen should be the initial treatment of choice for most hypertensive patients, based on demonstrated reduction in risk for major cardiovascular events, its safety, acceptance by patients, and low cost.

Age Factors↗
PubMed1992

Effectiveness of low-dose colestipol therapy in patients with moderate hypercholesterolemia.

Recommended doses of bile-acid binding resins have an established hypocholesterolemic effect, but data on responses to low doses, especially in women and subjects with moderate hypercholesterolemia, are sparse. A double-blind, placebo-controlled, randomized trial of 3 low doses of colestipol hydrochloride was conducted in women and men with moderate hypercholesterolemia. Men and women with plasma low-density lipoprotein (LDL) cholesterol concentrations greater than 4 mmol/liter (155 mg/dl) and triglyceride concentrations less than 2.82 mmol/liter (250 mg/dl) were recruited for the study. Eligible patients (54 women and 98 men) were placed on the American Heart Association step I diet 6 weeks before randomization. Participants were subsequently assigned to 1 of 4 drug treatment groups (placebo, and 5, 10 and 15 g/day of colestipol in 2 divided doses) for an additional 12 weeks. Of the 152 patients randomized, 141 completed all aspects of the study. For the treatment groups--placebo, and 5, 10 and 15 g of colestipol--LDL cholesterol reductions (mmol/liter) were observed respectively (n = 141): 0.10 +/- 0.49 (2.7%), 0.65 +/- 0.41 (16.3%), 0.98 +/- 0.36 (22.8%) and 1.17 +/- 0.47 (27.2%) (p less than 0.001). Similar changes were observed in total cholesterol and apolipoprotein B concentrations. The apolipoprotein B/LDL cholesterol ratio increased significantly with increasing colestipol dosage. Modest but insignificant changes in plasma triglyceride levels occurred, and high-density lipoprotein cholesterol levels remained unchanged. A dose of 5 g/day of colestipol achieved 51% of the LDL cholesterol reduction noted with 15 g/day. Low-dose colestipol therapy is effective in the treatment of patients with moderate hypercholesterolemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Recruitment strategies in the studies of left ventricular dysfunction (SOLVD): strategies for screening and enrollment in two concurrent but separate trials. The SOLVD Investigators.

SOLVD was a double-masked, placebo-controlled trial whose initial sample size goal was to randomize 6100 participants into two concurrent trials: treatment and prevention. The objective was to determine if participants with severe left ventricular dysfunction (left ventricular ejection fraction < or = 35%, with congestive heart failure (2569) and participants without overt heart failure (4228) had improved survival with angiotensin-converting enzyme inhibitors. Participants were identified from cardiac catheterization, echocardiography and radionuclide laboratories, and inpatient units. The treatment trial recruitment goal was attained 13 months ahead of schedule while recruitment for the prevention trial was extended 11 months beyond the scheduled time. Recruitment of relatively asymptomatic participants with a low ejection fraction in a hospital-based trial necessitated novel strategies. Coronary care units and clinics for follow-up of acute cardiac conditions, not typically employed in studies of chronic diseases, were useful recruitment sources. Different approaches to encourage participation also needed to be employed. Expanding selected entry criteria was evaluated and the success of varying strategies was reviewed. The authors recommend tailoring of strategies to the target population, staffing flexibility, principal investigator involvement, and broad entry criteria in recruitment activities.

Cardiac Output↗
PubMed1991

The Lipid Research Clinics Coronary Primary Prevention Trial: design, results, and implications.

The Coronary Primary Prevention Trial (CPPT) was the major clinical investigation conducted in the Lipid Research Clinics (LRC) Program. There were 12 North American clinics involved in this joint double-blind protocol. The hypothesis tested was: lowering plasma cholesterol in middle-aged men with primary hypercholesterolemia [plasma total cholesterol greater than or equal to 265 mg/dl (6.88 mm/l)] who are otherwise healthy leads to a reduction in coronary heart disease (CHD) as manifest by a reduction in definite myocardial infarction (fatal and nonfatal) over a 7-year follow-up of all participants. The trial was conducted in 3806 male volunteers between the ages of 35 and 59, who were randomly assigned to two equal groups. The treatment group received a moderate cholesterol-lowering diet plus cholestyramine: the placebo group received an identical diet plus a placebo. The study medication was administered at 24 g daily in divided doses. The participants were followed up bimonthly for an average of 7.4 years. The diet (daily cholesterol intake of about 400 mg and a polyunsaturated fat/saturated fat ratio of 0.8) lowered plasma cholesterol by an average of 4%, as designed. The cholestyramine group experienced average plasma total cholesterol (TC) lowering and plasma low-density lipoprotein cholesterol (LDC-C) lowering 8.5% and 12.6% greater than the placebo group, respectively. This resulted in a 19% reduction in definite myocardial infarction (P less than 0.05). The trial results for CHD deaths, nonfatal myocardial infarction,new positive exercise stress tests (P less than 0.001) new-onset angina (P less than 0.01) and coronary artery bypass surgery (P less than 0.06) and coronary artery bypass surgery ((p less than 0.06) were consistent with and supportive of the main findings of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

High-density lipoprotein response to 5-alpha-dihydrotestosterone and testosterone in Macaca fascicularis: a hormone-responsive primate model for the study of atherosclerosis.

A decrease in high-density lipoprotein cholesterol (HDL-C), a major risk factor for coronary artery disease, occurs during puberty in males. Previous studies have shown this decrease with testosterone (T) therapy for adolescent males, but the mechanism of this effect is unknown and has not been studied in a non-human primate. Two adult male monkeys (Macaca fascicularis) were studied to determine simultaneous changes in plasma androgens and HDL-C during the phases precastration (Ci); postcastration (Cx); Cx and T therapy; Cx and dihydrotestosterone (DHT) therapy; and T and 5-alpha-reductase inhibitor therapy (4-MA). After castration, the HDL-C concentrations increased significantly in both animals (monkey A, 57.0 +/- 1.8 mg/dL SE to 66.6 +/- 2.2, P less than .005; monkey B, 62.9 +/- 1.6 to 80.2 +/- 1.7, P less than .001). T-propionate treatment produced a significant decrease in HDL-C (monkey A, 48.0 +/- 5.0, P less than .01; monkey B, 43.5 +/- 0.5, P less than .001), which was similar to HDL-C reductions seen when treated with a nonaromatizeable androgen, DHT-propionate (monkey A, 47.5 +/- 1.5, P less than .005; monkey B, 44.5 +/- 3.5, P less than .001). T and the 5-alpha-reductase inhibitor therapy did not increase HDL-C from the levels with T therapy alone (monkey A, 55.7 +/- 1.9, NS; monkey B, 57.3 +/- 0.3, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

5-alpha Reductase Inhibitors↗
PubMed1990

Systolic hypertension in the elderly: controlled or uncontrolled.

ISH is a distinct pathogenetic entity defined by SBP readings of greater than or equal to 160 and DBP less than 90 mmHg. The etiology, although not well understood, is in some manner related to a reduction in connective tissue elasticity of large blood vessels and an increase in aortic impedance or a decrease in aortic wall compliance. The pathophysiologic consequences include an increased resistance to systolic ejection of blood and a disproportionate increase in SBP. Although not directly related, there is an important increase in peripheral vascular resistance. The prevalence of ISH in several studies is about 7 percent in those over age 60 and increases with age to nearly 20 percent in those over age 80. There is higher prevalence in females and nonwhites. The guidelines for detection of ISH are similar to those for blood pressure evaluation in general. Precautions for detection and evaluation in the elderly include multiple blood pressure measurements in the fasting state and sitting and supine blood pressure measurements before and during therapy. Pseudohypertension, although rare, should be kept in mind. There is a clear risk associated with ISH for stroke, CVD, and premature death, which increases with age and rising levels of SBP. ISH can be controlled effectively with pharmacologic therapies. A reasonable goal is a 20 mmHg reduction in systolic pressure. Proof of reduced risk for stroke, CHD, and death in those with controlled ISH remains to be demonstrated. The SHEP pilot study has demonstrated feasibility of addressing this issue. The full-scale SHEP study addresses this issue and has completed recruitment of the desired sample size and is in follow-up phase. Scheduled completion is in 1991. While we wait for the SHEP full-scale trial results, the prudent approach is for nonpharmacologic therapy and use of pharmacologic agents in that group of patients who demonstrate a large cardiovascular risk burden or increasing symptoms specifically associated with hypertension. The decision to treat must be on an individual patient basis. Pharmacologic therapy is possible in most patients with few or no adverse effects. The "low and slow" approach to therapy is helpful in minimizing these adverse effects. Low-dose diuretics have been documented to be effective in blood pressure control. Chlorthalidone, 12.5 or 25 mg per day, is suggested. Other agents, such as beta-blockers, reserpine, ACE inhibitors, and calcium channel blockers, are best used as Step 2 agents.

Aged↗
PubMed1989

Adherence and its management in clinical trials: implications for arthritis treatment trials.

Adherence in clinical trials is a consistent problem regardless of the disease process or organ system under investigation. In this paper data and examples from clinical trials examining cardiovascular diseases are used as the basis for a review of various adherence principles. Issues reviewed include: the importance of adherence in clinical trials, an overall program for adherence in clinical trials, and specific issues in adherence from arthritis clinical trials. Special attention is given to a program for the prevention of reduced adherence for participants of a clinical trial as well as acute and chronic intervention plans for those with good adherence and those with reduced adherence in a clinical trial.

Arthritis↗
PubMed1989

Coronary heart disease morbidity and mortality in hypercholesterolemic men predicted from an exercise test: the Lipid Research Clinics Coronary Primary Prevention Trial.

A positive exercise electrocardiogram (ECG) has been proved to predict cardiovascular events in asymptomatic normolipidemic men. To study whether it is also predictive for hypercholesterolemic men, data from 3,806 asymptomatic hypercholesterolemic men in the Lipid Research Clinics Coronary Primary Prevention Trial were analyzed. All the men had performed a submaximal treadmill exercise test at baseline, before they were assigned to the cholestyramine or placebo treatment group. Because of missing or inconclusive data, 31 men were excluded from the analyses. A test was positive if the ST segment was displaced by greater than or equal to 1 mm (visual code) or there was greater than or equal to 10 microV-s change in the ST integral (computer code), or both. The prevalence of a positive test was 8.3%. During the 7 to 10 year (mean 7.4) follow-up period, the mortality rate from coronary heart disease was 6.7% (21 of 315) in men with a positive test and 1.3% (46 of 3,460) in men with a negative test (placebo and cholestyramine groups combined). The age-adjusted rate ratio for a positive test, compared with a negative test, was 6.7 in the placebo group and 4.8 in the cholestyramine group. With use of Cox's proportional hazards models, it was found that the risk of death from coronary heart disease associated with a positive test was 5.7 times higher in the placebo group and 4.9 times higher in the cholestyramine group after adjustment for age, smoking history, systolic blood pressure, high density lipoprotein cholesterol and low density lipoprotein cholesterol. A positive test was not significantly associated with nonfatal myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗
PubMed1989

High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies.

The British Regional Heart Study (BRHS) reported in 1986 that much of the inverse relation of high-density lipoprotein cholesterol (HDLC) and incidence of coronary heart disease was eliminated by covariance adjustment. Using the proportional hazards model and adjusting for age, blood pressure, smoking, body mass index, and low-density lipoprotein cholesterol, we analyzed this relation separately in the Framingham Heart Study (FHS), Lipid Research Clinics Prevalence Mortality Follow-up Study (LRCF) and Coronary Primary Prevention Trial (CPPT), and Multiple Risk Factor Intervention Trial (MRFIT). In CPPT and MRFIT (both randomized trials in middle-age high-risk men), only the control groups were analyzed. A 1-mg/dl (0.026 mM) increment in HDLC was associated with a significant coronary heart disease risk decrement of 2% in men (FHS, CPPT, and MRFIT) and 3% in women (FHS). In LRCF, where only fatal outcomes were documented, a 1-mg/dl increment in HDLC was associated with significant 3.7% (men) and 4.7% (women) decrements in cardiovascular disease mortality rates. The 95% confidence intervals for these decrements in coronary heart and cardiovascular disease risk in the four studies overlapped considerably, and all contained the range 1.9-2.9%. HDLC levels were essentially unrelated to non-cardiovascular disease mortality. When differences in analytic methodology were eliminated, a consistent inverse relation of HDLC levels and coronary heart disease event rates was apparent in BRHS as well as in the four American studies.

Adult↗
PubMed1989

The Systolic Hypertension in the Elderly Program (SHEP): an intervention trial on isolated systolic hypertension. SHEP Cooperative Research Group.

The Systolic Hypertension in the Elderly Program (SHEP) is a randomized double-blind placebo-controlled trial to determine if antihypertensive treatment of isolated systolic hypertension (ISH) [systolic blood pressure (SBP) greater than or equal to 160 mmHg, diastolic blood pressure (DBP) less than 90 mmHg] reduces the 5 year incidence of fatal and nonfatal stroke. Between March 1, 1985 and January 15, 1988, 4736 persons (target 4800) with ISH, age 60 years and over, were enrolled. Potential participants met blood pressure (BP) and age criteria. Those on antihypertensive medication prior to enrollment without documented diastolic hypertension had their medication tapered and discontinued, and then met BP criteria (33% of cohort). Stepped-care therapy with chlorthalidone and atenolol (alternative, reserpine) or matching placebos was initiated as first and second steps. At baseline the trial population was 43.1% male, 56.9% female; 13.9% black, 86.1% non-black. Also, the mean age was 71.6 years; the mean SBP was 170.3 mmHg and the mean DBP was 76.6 mmHg; 59.8% had codeable resting electrocardiographic abnormalities. The trial is now in follow-up phase with scheduled termination in 1991.

Aged↗
PubMed1987

Recruitment experience in clinical trials: literature summary and annotated bibliography.

A literature review was conducted to determine what problems exist in accruing adequate numbers of patients for clinical trials. Accrual rates are often not clearly reported, and most studies report that the time period for accrual was extended. Delays in recruitment have an impact on costs and workload throughout the trial. Other problems with the recruitment outcomes include miscalculations in the number of eligible participants in the total population, variations in yield from different types of recruitment sources, and level of community awareness. Planning for recruitment should be part of the overall trial design. Ideally, recruitment planning should be conducted in harmony between the national and local levels. Local community members should be involved. Data-based management of recruitment is necessary and should include a comprehensive data monitoring system with strong administrative support at both central and local levels. Recruitment goals and provisions for corrective action if recruitment lags should be included. Socioeconomic characteristics and attitudes of patients and physicians should be considered in recruitment efforts because they can affect patient participation during all phases of the study.

Bibliographies as Topic↗
PubMed1987

Recruitment in NHLBI population-based studies and randomized clinical trials: data analysis and survey results.

Data on screening and recruitment from current and previous NHLBI population-based studies (PBSs) and randomized clinical trials (RCTs) were examined. In only two of the studies examined was the projected recruitment completed within the planned recruitment period. The shape of the graph of the relation between enrollment of participants and time varies by study. A single summary statistic for measuring the efficiency of recruitment in RCTs and PBSs is proposed and applied to the examined studies. In addition to providing summary data on recruitment for several studies, this article reports the survey results of a questionnaire sent to the coordinating centers of currently and previously funded National Heart, Lung, and Blood Institute and Veteran's Administration studies. The purpose was to ascertain the desirability of recommending that a generic core of information be collected on recruitment and screening in future studies. Most respondents believed that comparing data collected uniformly and prospectively might be helpful in designing further studies. The variables most respondents believed to be potentially useful are described.

Clinical Trials as Topic↗