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J L Probstfield

Publications and source records attributed to J L Probstfield.

At least 19 recordsLinked to original sources
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↗
PubMed1987

Smoking, physical activity, and other predictors of endurance and heart rate response to exercise in asymptomatic hypercholesterolemic men. The Lipid Research Clinics Coronary Primary Prevention Trial.

The association of known coronary risk factors with progressive submaximal treadmill exercise tolerance test performance was studied in 6,238 asymptomatic white 34-60-year-old hypercholesterolemic men screened between 1973 and 1976 for the Lipid Research Clinics Coronary Primary Prevention Trial. Cigarette smoking and habitual physical inactivity were each associated with a doubling of the rate of symptom-related discontinuation of the exercise test; the tests of sedentary smokers were discontinued at four times the rate observed for active nonsmokers. Smaller increases in heart rate were observed during exercise testing in physically active men and in smokers than in their sedentary and nonsmoking counterparts. Thus, smoking, like habitual physical activity, reduced the heart rate required to sustain a given external workload. However, the heart rates of smokers tended to remain elevated after exercise, while those of physically active men returned more rapidly toward resting levels. Age, Quetelet index, and low plasma levels of high density lipoprotein cholesterol were also strong predictors of decreased endurance, while resting heart rate and blood pressure levels were significant predictors of heart rate response. Comparison of these results with those previously reported for ischemic electrocardiographic changes in this cohort suggests that coronary risk factors may selectively influence specific aspects of exercise tolerance test performance.

Adult↗
PubMed1986

Successful program for recovery of dropouts to a clinical trial.

This is a report of a successful program to return dropout participants to active participation at a single clinic of a multicenter long-term clinical trial, the Coronary Primary Prevention Trial of the Lipid Research Clinics Program. The specific objectives were to re-engage dropouts into active participation and to have them resume study medication. Thirty-six men had been absent from the Baylor-Methodist Clinic for 10 months to over four years. The program focused on resolving the presenting problems: psychosocial, somatic, and drug adherence. It was based on six general principles with corresponding goals and employed 13 activities and procedures in a specific operational sequence for reinstitution of the Coronary Primary Prevention Trial protocol. Counseling techniques were used to improve protocol adherence. The recovery program was monitored bi-weekly by computer. The dropout group did not appear to exhibit any biases and approximated the remainder of the Baylor-Methodist cohort demographically. At six months into the recovery program, 90 percent of the dropouts had been recovered. Seventy percent of the recovered participants re-established medication-taking behavior. The mean rate of adherence to medication for all of the recovered group was 35 percent of the prescribed dose, 8 g per day. Review of the data for the cholesterol differential between the two treatment groups demonstrated a favorable effect of the reinstitution of the study medication. The program's methods are applicable to clinical practice.

Adult↗
PubMed1986

Predictive value of the exercise tolerance test for mortality in North American men: the Lipid Research Clinics Mortality Follow-up Study.

More than 3600 white men, from 30 to 79 years old and without a history of myocardial infarction, underwent submaximal treadmill exercise tolerance tests as part of their baseline evaluation for the Lipid Research Clinics Mortality Follow-up Study. The exercise test was conducted according to a common protocol and coded centrally; depression of the ST segment by at least 1 mm (visual coding) and/or 10 microV-sec (ST integral, computer coding) signified a positive test. Concurrent measurements of age, blood pressure, history of cigarette smoking, and plasma levels of lipids, lipoproteins, and glucose, as well as other coronary risk factors, were obtained. Cumulative mortality from cardiovascular disease was 11.9% (22/185) over 8.1 years mean follow-up among men with a positive exercise test vs 1.2% (36/2993) over 8.6 years mean follow-up among men with a negative test. Three-quarters (43) of these deaths were due to coronary heart disease. The relative risk for cardiovascular mortality associated with a positive exercise test was 9.3 before and 4.6 after age adjustment. Cardiovascular mortality rates were especially elevated (relative risk 15.6 before and 5.1 after age adjustment) among the 82 men whose exercise tests were adjusted "strongly" positive based on degree and timing of the ischemic electrocardiographic response. A positive exercise test was also moderately associated with noncardiovascular mortality; the relative risk for all-cause mortality was 7.2 before and 3.4 after age adjustment. The relative risk for cardiovascular mortality associated with a positive exercise test was not appreciably altered by covariance adjustment for known coronary risk factors other than age. A positive exercise test was a stronger predictor of cardiovascular death than were high plasma levels of low-density lipoprotein cholesterol, low plasma levels of high-density lipoprotein cholesterol, smoking, hyperglycemia, or hypertension. Its impact on risk of cardiovascular death was equivalent to that of a 17.4 year increment in age.

Adult↗
PubMed1986

High-density lipoprotein cholesterol and coronary heart disease in hypercholesterolemic men: the Lipid Research Clinics Coronary Primary Prevention Trial.

Plasma levels of high-density lipoprotein cholesterol (HDL-C) at entry and subsequent changes from these baseline levels were inversely predictive of coronary heart disease (CHD) end points in hypercholesterolemic men followed for 7 to 10 years in the Lipid Research Clinics Coronary Primary Prevention Trial, especially in the 1907 participants receiving cholestyramine. When the men in this cohort were compared, each 1 mg/dl increment in baseline HDL-C (mean 44.3 mg/dl) was associated with a 5.5% decrement in risk of "definite" CHD death or myocardial infarction (Z = -5.4), and each 1 mg/dl increase from baseline HDL-C levels (mean increase = 1.6 mg/dl) during the trial was associated with a 4.4% risk reduction (Z = -2.2). In the 1899 participants receiving placebo, the corresponding risk decrements were 3.4% and 1.1%. Although baseline HDL-C level (mean = 44.4 mg/dl) remained a significant risk predictor (Z = -3.8) in the placebo cohort, increases in HDL-C (mean increase 0.5 mg/dl) were not significantly predictive of CHD (Z = -0.6) unless "suspect" as well as "definite" end points were analyzed (Z = -2.0). When the associations between HDL-C (baseline plus change) and incidence of definite CHD end points within each treatment cohort were compared, their difference approached nominal significance (Z = 1.9). The results suggest a synergistic interaction, in which cholestyramine treatment reduced CHD risk most substantially in men maintaining the highest HDL-C levels.

Adult↗
PubMed1986

Detection of dyslipoproteinemia with the use of plasma total cholesterol and triglyceride as screening tests. The Lipid Research Clinics Program Prevalence Study.

The efficiency of screening for dyslipoproteinemias associated with hyperlipoproteinemia or with hypolipoproteinemia was examined in 8449 white examinees from the Lipid Research Clinics Prevalence Study. A two-stage lipid screening approach was used. A positive screening test for hyperlipidemia was defined as an elevated level of plasma total cholesterol or triglyceride at both visit 1 and visit 2. A positive screening test for hypolipidemia was defined as a reduced plasma total cholesterol level at both visits. The syndromes of dyslipoproteinemia were defined according to the lipoprotein pattern present at visit 2. When hyperlipidemia was used as a screening tool, generally only about one-half or less of the cases of hyperlipoproteinemia were detected (high proportion of false-negative results). Of all the hyperlipidemic participants, more than 80% had hyperlipoproteinemias (type I, IIa, IIb, III, IV, or V), and such lipid screening therefore provided a lower proportion of false-positive than false-negative results. Most of the participants (greater than 98%) without hyperlipoproteinemia were correctly identified (true negatives). The efficiency of screening for hypolipoproteinemia was in general poorer than that found for hyperlipoproteinemia. Our results were found to be related, in part, to the marked regression to the mean of plasma cholesterol and triglycerides at the extremes of the distributions and to the wide variety of dyslipoproteinemias that can be present within a given range of plasma cholesterol or triglyceride values. The results emphasize the importance of measuring plasma lipoproteins in the patient who is being evaluated for dyslipoproteinemia.

Adolescent↗
PubMed1985

Examination of medical professions for counseling on medication adherence.

The abilities of 68 professional staff members (physicians, physician assistants, dietitians, nurses, and counselors) from 12 clinics of the Coronary Primary Prevention Trial of the Lipid Research Clinics Program in 28 specific skills fundamental to interviewing and counseling for medication adherence were examined. Each staff member was provided with confidential data regarding his or her abilities, and each clinic's trial director received the group data for his or her staff's possession and use of these skills. Analyses of trial-wide data showed substantial differences among clinics in possession and use of the skills, with overall greater strength in interviewing skills, as compared with assessment and counseling skills. No professional group consistently possessed most or fewest of these skills. It is suggested that trained non-physician personnel could be used to complement physician efforts to counsel patients for medication adherence.

Adult↗