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Biomedical subjects

E J Whitney

Publications and source records attributed to E J Whitney.

12 recordsLinked to original sources
PubMed2001

Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TEXCAPS): additional perspectives on tolerability of long-term treatment with lovastatin.

This study presents the long-term safety data from AFCAPS/TexCAPS, the first primary prevention trial to demonstrate that men and women with average levels of low-density lipoprotein cholesterol (LDL-C) and below average levels of high-density lipoprotein cholesterol (HDL-C) can significantly benefit from long-term treatment to lower LDL-C; lovastatin 20 to 40 mg/day reduced the risk of a first acute major coronary event (fatal or nonfatal myocardial infarction, unstable angina, or sudden death) by 37% (p = 0.00008). This double-blind randomized, placebo-controlled trial, in 6,605 generally healthy middle-aged and older men and women, had prespecified end point and cancer analyses. All analyses were intention-to-treat. Safety monitoring included history, physical examination, and laboratory studies (including hepatic transaminases and creatine phosphokinase [CPK]). All participants, even those who discontinued treatment, were contacted annually for vital status, cardiovascular events, and cancer history. After an average of 5.2 years of follow-up, there were 157 deaths (80 receiving lovastatin and 77 receiving placebo; relative risk [RR] 1.04; 95% confidence interval [CI] 0.76 to 1.42; p = 0.82); of which 115 were noncardiovascular (RR 1.21; CI 0.84 to 1.74; p = 0.31), and of these, 82 were due to cancer (RR 1.41; CI 0.91 to 2.19; p = 0.13). There were no significant differences between treatment groups in overall cancer rates, discontinuations for noncardiovascular adverse experiences, or clinically important elevations of hepatic transaminases or CPK. Among those who used cytochrome P450 isoform (CYP3A4) inhibitors, there were no treatment group differences in the frequency of clinically important muscle-related adverse events. Treatment with lovastatin 20 to 40 mg daily for primary prevention of coronary heart disease was well tolerated and reduced the risk of first acute coronary events without increasing the risk of either noncardiovascular mortality or cancer.

Aged↗
PubMed2001

Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS): efficacy and tolerability of long-term treatment with lovastatin in women.

The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) is the first coronary heart disease (CHD) primary prevention trial of the cholesterol-reducing agents called "statins" to include women. For 5608 men and 997 postmenopausal women without clinical evidence of cardiovascular disease (CVD) who had average low-density lipoprotein cholesterol (LDL-C) and below average high-density lipoprotein cholesterol (HDL-C), 20-40 mg/day lovastatin reduced first acute major coronary events (AMCEs) 37% (for those receiving placebo and lovastatin, respectively, 183 and 116 first AMCEs defined as fatal or nonfatal myocardial infarction [MI], unstable angina, or sudden cardiac death; relative risk [RR] 0.63; 95% confidence interval [95% CI] 0.50, 0.79; p < 0.001). Statistically significant reductions in prespecified secondary end points (coronary revascularizations, unstable angina, MI, cardiovascular end point events, and coronary end point events) were also associated with lovastatin treatment in the overall cohort. This paper provides results in women, a prespecified subgroup. Among women, 20-40 mg/day lovastatin reduced LDL-C 25% and increased HDLC 9% (p < 0.001). A prespecified analysis revealed consistency with the overall results regardless of gender (i.e., there were no statistical differences between men and women in risk reduction for first AMCEs with lovastatin). However, the number of women who had an AMCE was small, and there was insufficient power to detect a treatment group difference among women (7 of 499 vs. 13 of 498 first AMCEs in those receiving lovastatin and placebo, respectively; RR 0.54; 95% CI 0.22, 1.35; p = 0.183). Numerical reductions in all prespecified secondary end points were observed for women treated with lovastatin, but again, the numbers of events were small and the differences were not statistically significant. Chronic long-term treatment with lovastatin was well tolerated, with no treatment group differences in the frequency of cancer, muscle symptoms, and clinically important liver enzyme elevations. In AFCAPS/TexCAPS, a consistent pattern of numerical reductions in all prespecified primary and secondary cardiovascular end points was observed in women treated with lovastatin for primary prevention of CHD. However, because of the small number of events, there was insufficient power to detect significant treatment group differences. Lovastatin treatment was associated with statistically significant decreases in LDL-C and increases in HDL-C, and chronic long-term treatment with 20-40 mg/day lovastatin was well tolerated in women.

Aged↗
PubMed2000

Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS): baseline characteristics and comparison with USA population.

BACKGROUND: Results of the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) demonstrated that treatment with lovastatin, in addition to modifications of diet and lifestyle, reduced the rate of first acute major coronary events compared with placebo in a cohort that included participants with average to mildly elevated total levels of cholesterol, and below average levels of high-density lipoprotein cholesterol, women, and elderly subjects. OBJECTIVE: To describe the baseline characteristics of the study's cohort. DESIGN: This was a double-blind, placebo-controlled, primary-prevention trial in which Americans with average to mildly elevated total levels of cholesterol [4.65-6.83 mmol/l (180-264 mg/dl)] and no clinical evidence of atherosclerotic cardiovascular disease were randomly allocated either 20-40 mg/day lovastatin or placebo in addition to a low-saturated fat, low-cholesterol diet. Baseline characteristics of the study cohort are described, and the characteristics of a USA reference population based upon NHANES III data are provided for comparison. RESULTS: The study includes 5608 men (85%) and 997 women (15%) with mean total cholesterol level 5.71 +/- 0.54 mmol/l (221 +/- 21 mg/dl), low-density lipoprotein cholesterol level 3.88 +/- 0.44 mmol/l (150 +/- 17 mg/dl), high-density lipoprotein cholesterol 0.96 +/- 0.15 mmol/l (37 +/- 6 mg/dl), and median triglyceride level 1.78 +/- 0.86 mmol/l (158 +/- 76 mg/dl). The mean age is 58 years (ranges 45-73 years for men and 55- 73 years for women). The participants are 89% white, 7% Hispanic, and 3% black. CONCLUSION: Results from AFCAPS/TexCAPS will be applicable to large segments of populations; in the USA alone, eight million share the demographic and baseline-lipid-level characteristics of the study cohort.

Aged↗
PubMed1997

Effect of gemfibrozil +/- niacin +/- cholestyramine on endothelial function in patients with serum low-density lipoprotein cholesterol levels <160 mg/dl and high-density lipoprotein cholesterol levels <40 mg/dl.

We studied endothelial function using the brachial artery ultrasound model in 100 subjects from the Armed Forces Regression Study, a placebo-controlled, angiographic regression trial in subjects with normal or modestly elevated low-density lipoprotein (LDL) cholesterol and low levels of high-density lipoprotein (HDL) cholesterol treated for 30 months with gemfibrozil and (if necessary) niacin and/or cholestyramine to raise HDL by 25% and lower LDL to < 110 mg/dl. Although the treatment group had highly significant improvements in LDL and HDL cholesterol, there was no difference between the 2 groups in flow-mediated dilation (treatment vs control 6.9 +/- 6.5% vs 6.3 +/- 7.3%) or nitroglycerin-induced dilation (12.4 +/- 9.6% vs 11.9 +/- 7.4%, all p = NS). Treatment and control subjects without a history of hypertension had flow-mediated dilation similar to that of a normal reference population (10.6 +/- 8.3% vs 8.4 +/- 4.5%), whereas subjects with a history of systemic hypertension had markedly impaired flow-mediated dilation that was not significantly improved with treatment (treatment vs control, 6.0 +/- 5.5% vs 4.3 +/- 5.9%, p = 0.2). Thus, nonhypertensive subjects with angiographic coronary disease and low HDL cholesterol had normal endothelial function in the brachial artery model. Patients with a history of hypertension had marked endothelial dysfunction despite blood pressure treated to normal levels, and this dysfunction is not attenuated by pharmacologic therapy for dyslipidemia.

Aged↗
PubMed1996

Effect of a combination of gemfibrozil and niacin on lipid levels.

To determine the effect of the combination of niacin and gemfibrozil on the lipid profile, a retrospective review was conducted of 161 patients who were prescribed a combination of gemfibrozil and niacin for 6 to 12 months at a community-based lipid clinic. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, ratio of total cholesterol to HDL, alanine aminotransferase (ALT), and weight were measured at entry to the clinic, 2 months after dietary instruction, during single-agent therapy, and during combination therapy. Mean doses of niacin and gemfibrozil were 1,229 mg/day and 1,200 mg/day, respectively. Patient weight decreased significantly after dietary instruction and after institution of combination therapy. There were no significant changes in ALT levels with either single-agent therapy or with combination therapy. The combination of niacin and gemfibrozil produced marked and significant changes in lipid levels: total cholesterol and LDL decreased by 14%, HDL increased by 24%, the ratio of total cholesterol to HDL decreased by 30%, and triglycerides decreased by 52%. The combination of niacin and gemfibrozil in the setting of dietary instruction has a marked beneficial effect on serum lipid levels, and was most effective in patients with initial levels of HDL < 40 mg/dL, triglycerides > 250 mg/dL, and LDL > 160 mg/dL. No episodes of ALT elevation or symptomatic myositis were seen.

Diet Therapy↗
PubMed1993

Changing presentation of coronary heart disease in an inpatient population within the U.S. military health care system.

This study examines the changing presentation of coronary heart disease (CHD) in an inpatient population at Brooke Army Medical Center. The specific objectives of the study were to examine the presentation of CHD in a population unbiased by diagnosis-related group (DRG) reimbursements and to assess the importance of unstable angina and prior history of disease in the presentation of CHD. One thousand fifteen discharges in 1985 and 1,304 discharges in 1990 with the diagnosis of CHD were reviewed by cardiologists for evidence of symptomatic heart disease at the time of hospitalization. Forty percent of these charts were accepted into this study. The presentation rates of CHD were 1% with sudden death, 26% with myocardial infarction, 64% with angina, and 9% with congestive heart failure (CHF). During the study period, stable angina, Q-wave infarctions, and the myocardial infarction case fatality rate decreased (p < 0.05) and CHF and non-Q wave infarcts increased (p < 0.001). However, unstable angina was the most common presentation of CHD, and differences (p < 0.05) were noted in the presentation of CHD in patients with and without a prior history of disease. This study demonstrates the significance of unstable angina and prior history of CHD in an environment free of bias from DRG reimbursements.

Adult↗
PubMed1992

The case for unstable angina pectoris as a primary end point in primary prevention studies.

Coronary artery disease (CAD) primary end point definitions used in previous prevention trials are reviewed, as well as trends over time for CAD mortality, incidence and hospital discharges to see if new primary end points should be considered. CAD mortality has shown a dramatic decline in the U.S. in the last 20 years, whereas the decrease in the incidence of acute myocardial infarction (AMI) is less consistent. The decline in CAD incidence and mortality has been attributed to changes in lifestyle and increased medical/surgical intervention. Hospital discharge rates for CAD have risen during the past decade. In addition, although the rate of discharge for AMI appears to have stabilized, the rates for angina, and more dramatically for unstable angina, have increased. Unstable angina made up 4% of CAD discharges in 1980, and increased to 25% of CAD discharges in 1989. Because of these trends, future trials that rely solely on AMI as a primary end point will not reflect the actual experience with CAD presentation in the U.S. Given the greater availability of methods to diagnose unstable angina more accurately, and because of its high risk pathology, it is concluded that unstable angina should receive serious consideration as a primary end point in future primary prevention trials.

Adult↗
PubMed1992

A retrospective review of the use of lipid-lowering agents in combination, specifically, gemfibrozil and lovastatin.

We conducted a retrospective review examining lipid profiles, creatine phosphokinase (CK) levels, and alanine aminotransferase levels (ALT) in patients receiving the combination of gemfibrozil and lovastatin. Serum lipid levels were significantly improved with therapy over those before therapy. Of the 70 patients receiving the combination, 5 experienced mild elevations in CK, 1 a mild elevation in ALT, and 1 mild elevations in both. No patient reported muscle weakness or muscle pain. The combination of these two medications appeared to be at least additive, highly effective, and well tolerated. The mean total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels decreased from 278, 306, and 180 mg% to 200, 151, and 129 mg%, respectively, and the mean high-density lipoprotein cholesterol levels increased from 34 to 40 mg%. This retrospective data analysis suggests that the combination of gemfibrozil and lovastatin may be safe in patients with normal renal function when the dosage of lovastatin is limited and when CK and ALT levels are monitored carefully.

Aged↗
PubMed1991

Reversibility of fixed atherosclerotic lesions with aggressive risk factor modification.

Seven patients with atherosclerotic coronary artery disease documented by coronary angiography and exercise stress testing were treated with the American Heart Association Step II Diet, a walking program, and combination drug therapy with niacin, cholestyramine, gemfibrozil, and/or lovastatin. As a result of this intervention, there was a mean weight loss of 24.7 pounds, a mean reduction in cholesterol from 297 mg% to 167 mg%, a mean increase in high density lipoprotein cholesterol from 33 mg% to 55 mg%, and a mean reduction in triglyceride levels from 248 mg% to 58 mg%. Repeat exercise stress testing and coronary angiography were performed 2 years after the initial catheterization. Photographs of end-diastolic frames were compared utilizing the same views with the same magnification. In six of the seven patients, there was a mean increase in luminal area at the greatest stenosis of 1.3 mm2 in eight lesions present at initial catheterization. In four of these six patients, there was evidence for improvement in coronary blood flow manifested by improvement in electrocardiogram (ECG) exercise stress testing and/or exercise thallium stress testing. In one patient, there was a mean decrease in luminal area at greatest stenosis of 1.35 mm2 in two lesions and the development of an additional plaque in an area which was previously normal. In addition, this patient had evidence for progression by ECG exercise stress testing. Aggressive risk factor modification can reverse what were previously considered "fixed" atherosclerotic lesions in selected patients.

Aged↗
PubMed1983

Chest pain variant asthma.

We present the cases of three patients who initially presented with chest pain but were ultimately diagnosed as having asthma. None had audible wheezing. A diagnosis of asthma was entertained and ultimately supported by a clinical response to bronchodilator therapy. Only one patient had significant but intermittent documentable reversible airway obstruction, while another had marked sensitivity to methacholine bronchial challenge. Two patients required short courses of oral corticosteroids before symptom ablation.

Adolescent↗