Effects of growth hormone deficiency on body composition and biomarkers of cardiovascular risk after definitive therapy for acromegaly.

BACKGROUND: Both growth hormone (GH) excess and GH deficiency are associated with abnormalities in body composition and biomarkers of cardiovascular risk in patients with pituitary disorders. However, the effects of developing GH deficiency after definitive treatment of acromegaly are largely unknown. OBJECTIVE: To determine whether development of GH deficiency after definitive therapy for acromegaly is associated with increased visceral adiposity and biomarkers of cardiovascular risk compared with GH sufficiency after definitive therapy for acromegaly. DESIGN: Cross-sectional. PATIENTS: We studied three groups of subjects, all with a history of acromegaly (n = 76): subjects with subsequent GH deficiency (GHD; n = 31), subjects with subsequent GH sufficiency (GHS; n = 25) and subjects with active acromegaly (AA; n = 20). No study subjects were receiving somatostatin analogues, dopamine agonists or hGH. MEASUREMENTS: Body composition (by DXA), abdominal adipose tissue depots (by cross-sectional CT), total body water (by bioimpedance analysis) and carotid intima-media thickness (IMT) were measured. Fasting morning serum was collected for high-sensitivity C-reactive protein (hsCRP), lipids and lipoprotein levels. An oral glucose tolerance test was performed, and homoeostasis model of assessment-insulin resistance (HOMA-IR) was calculated. RESULTS: Abdominal visceral adipose tissue, total adipose tissue and total body fat were higher in subjects with GHD than GHS or AA (P < 0·05). Subcutaneous abdominal fat was higher, and fibrinogen and IMT were lower in GHD (but not GHS) than AA (P < 0·05). Patients with GHD had the highest hsCRP, followed by GHS, and hsCRP was lowest in AA (P < 0·05). Fasting glucose, 120-min glucose, fasting insulin, HOMA-IR and per cent total body water were lower in GHD and GHS than AA (P < 0·05). Triglycerides were higher in GHS than AA (P < 0·05). Lean body mass, mean arterial pressure, total cholesterol, HDL and LDL were comparable among groups. CONCLUSIONS: Development of GHD after definitive treatment of acromegaly may adversely affect body composition and inflammatory biomarkers of cardiovascular risk but does not appear to adversely affect glucose homoeostasis, lipids and lipoproteins, or other cardiovascular risk markers.

The genome of the social amoeba Dictyostelium discoideum.

The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.

The QUinapril Ischemic Event Trial (QUIET): evaluation of chronic ACE inhibitor therapy in patients with ischemic heart disease and preserved left ventricular function.

Angiotensin-converting enzyme inhibitors improve endothelial function, inhibit experimental atherogenesis, and decrease ischemic events. The Quinapril Ischemic Event Trial was designed to test the hypothesis that quinapril 20 mg/day would reduce ischemic events (the occurrence of cardiac death, resuscitated cardiac arrest, nonfatal myocardial infarction, coronary artery bypass grafting, coronary angioplasty, or hospitalization for angina pectoris) and the angiographic progression of coronary artery disease in patients without systolic left ventricular dysfunction. A total of 1,750 patients were randomized to quinapril 20 mg/day or placebo and followed a mean of 27 +/- 0.3 months. The 38% incidence of ischemic events was similar for both groups (RR 1.04; 95% confidence interval 0.89 to 1.22; p = 0.6). There was also no significant difference in the incidence of patients having angiographic progression of coronary disease (p = 0.71). The rate of development of new coronary lesions was also similar in both groups (p = 0.35). However, there was a difference in the incidence of angioplasty for new (previously unintervened) vessels (p = 0.018). Quinapril was well tolerated in patients after angioplasty with normal left ventricular function. Quinapril 20 mg did not significantly affect the overall frequency of clinical outcomes or the progression of coronary atherosclerosis. However, the absence of the demonstrable effect of quinapril may be due to several limitations in study design.

Low-density lipoprotein apheresis therapy during pregnancy.

Pregnancy in patients with severe hypercholesterolemia and coronary artery disease results in multiple problems both for mother and fetus; the most potent agents for low-density lipoprotein (LDL) cholesterol reduction, the HMG-CoA reductase inhibitors (statins) cannot be used during pregnancy. We present a case in which LDL apheresis via heparin-induced extracorporeal LDL precipitation was employed safely and efficaciously during pregnancy in a woman with heterozygous familial hypercholesterolemia and stable coronary artery disease.

Implementing a therapeutic massage program in a tertiary and ambulatory care VA setting: the healing power of touch.

The ancient practice of massage to promote healing has a place in contemporary health care. This article discusses the implementation of a nurse-run therapeutic massage service at the Denver Veterans Administration Medical Center. Program background, evaluation, future plans, and lessons learned are described.

Angiotensin-converting enzyme inhibition as antiatherosclerotic therapy: no answer yet. QUIET Investigators. QUinapril Ischemic Event Trial.

Angiotensin-converting enzyme inhibitors have proven to be of clinical benefit in congestive heart failure. Whether they also provide benefit to patients with coronary artery disease in the absence of congestive heart failure via an antiatherosclerotic mechanism is a question the QUinapril Ischemic Event Trial quantitative coronary angiography (QCA) study attempted to answer: 1,750 patients with normal left ventricular function who were undergoing coronary angiography and angioplasty were randomized to 20 mg/day of quinapril versus placebo and followed for 3 years for cardiac end points. A randomly selected subgroup of the total cohort underwent follow-up angiography. The primary QCA end point was the categorical designation of progression versus nonprogression, defined either by QCA or by a cardiac event in patients selected for the QCA trial who had no usable follow-up x-ray film. Secondary end points in patients with 2 angiograms were: new stenosis development, change in minimum lumen diameter index, and change in percent diameter stenosis index. There were 119 progressors among 243 placebo-treated patients (49%) and 111 progressors among 234 quinapril-treated patients (47%) (p = NS). There were 44 patients with new stenosis development in the placebo group (19%) and 50 (22%) in the quinapril group (p = NS). Change in minimum lumen diameter index was -0.21+/-0.03 mm in the placebo group and -0.18+/-0.03 mm in the quinapril group (p = NS). Finally, change in percent diameter stenosis index was +5.1+/-1.0 in the placebo group and +3.5+/-1.0 in the quinapril group (p = NS). Potential confounders of this trial are presented and discussed.

Non-pharmacological lowering of low-density lipoprotein by apheresis and surgical techniques.

In the past year, new data have appeared on the long-term benefits of low-density lipoprotein apheresis in severely hypercholesterolemic patients who are refractory to lipid-lowering drug therapy. Such data are critical for clinical decision-making, because they confirm the hypothesis that the dramatic reduction in low-density lipoprotein made possible by this technique produces clear-cut clinical benefits. Because of its efficacy and low incidence of side-effects, apheresis for severe drug-refractory hypercholesterolemia has superseded surgical approaches, such as liver transplantation or ileal bypass.

Baseline clinical and angiographic data in the Quinapril Ischemic Event (QUIET) Trial.

The QUinapril Ischemic Event Trial (QUIET) is the first prospective, double-blind, placebo-controlled trial to investigate the long-term antiatherosclerotic effects of angiotensin-converting enzyme inhibition. Normotensive, nonhyperlipidemic subjects (1,750) with normal left ventricular systolic function were randomly assigned to treatment or placebo at percutaneous transluminal coronary angioplasty (PTCA). The primary end point is time to first cardiac ischemic event. Baseline clinical characteristics are (mean +/- SD): age 58 +/- 9 years; blood pressure 123 +/- 15/74 +/- 10 mm Hg; low density lipoprotein cholesterol 124 +/- 27 mg/dL; high density lipoprotein cholesterol 37 +/- 10 mg/dL; and triglycerides 167 +/- 91 mg/dL. In addition, 81% are men; 22% are current smokers; 49% give a history of myocardial infarction. Baseline angiographic characteristics are (mean +/- SD): left ventricular ejection fraction 59% +/- 11%; per patient diameter stenosis (excluding the PTCA segment) 49% +/- 31%; 8.9 +/- 3.5 analyzable segments per patient (excluding the PTCA segment), 3.8 +/- 2.3 of which have visible stenosis. Including the PTCA segment, 52% have single vessel disease and 48% have multivessel disease. Baseline angiographic data for non-PTCA segments will be correlated with cardiac ischemic events which occur after 6 months. Up to 500 subjects will undergo follow-up angiography with quantitative coronary angiographic analysis (QCA) of baseline and follow-up films. The primary QCA end point will be per-patient categorical designation as progressor or nonprogressor based on the presence or absence of > or = 400 microns narrowing in > or = 1 vessels that did not undergo PTCA.

Progression of coronary artery disease predicts clinical coronary events. Long-term follow-up from the Cholesterol Lowering Atherosclerosis Study.

BACKGROUND: Progression of coronary artery disease is assumed to be a surrogate end point for clinical coronary events. Because no single method or measure for a coronary angiographic end point is uniformly accepted as optimal, the utility and validity of surrogate end points for predicting clinical coronary events remain unsettled. METHODS AND RESULTS: The Cholesterol Lowering Atherosclerosis Study randomized 162 nonsmoking, 40- to 59-year-old men with previous coronary artery bypass graft surgery to colestipol/niacin plus diet or placebo plus diet. Atherosclerosis change on 2-year coronary angiograms was evaluated by a consensus panel and by quantitative coronary angiography (average per-subject change in percent diameter stenosis [%S] and minimum lumen diameter [MLD). With all three end points, the benefit of colestipol/niacin treatment on coronary artery atherosclerosis has been reported. Annual follow-up for an average of 7 years (range, 6.3 months to 10 years) has been carried out on all subjects who completed the 2-year angiogram. Clinical coronary events (need for revascularization, nonfatal acute myocardial infarction, and coronary death) have been documented. Risk of clinical coronary events was positively related to coronary lesion progression for all three surrogate end points (P<.05). New lesion formation in bypass grafts (P=.02) and progression of mild/moderate lesions ( < 50%S) were predictive of clinical coronary events (P<.01). Change in MLD contributed significantly to the prediction of clinical coronary events beyond a model with %S alone (P<.05). CONCLUSIONS: In this population of nonsmoking men with previous bypass surgery, both the consensus panel- and quantitative coronary angiography-based end points of coronary artery disease progression predict clinical coronary events. Subjects who demonstrate greater coronary artery lesion progression have an increased risk of future clinical coronary events. Design of shorter, smaller trials of antiatherosclerotic agents is justified.

Serial coronary angiographic evidence that antioxidant vitamin intake reduces progression of coronary artery atherosclerosis.

OBJECTIVE: To explore the association of supplementary and dietary vitamin E and C intake with the progression of coronary artery disease. DESIGN: A subgroup analysis of the on-trial antioxidant vitamin intake database acquired in the Cholesterol Lowering Atherosclerosis Study, a randomized, placebo-controlled, serial angiographic clinical trial evaluating the risk and benefit of colestipol-niacin on coronary artery disease progression. SETTING: Community- and university-based cardiac catheterization laboratories. SUBJECTS: A total of 156 men aged 40 to 59 years with previous coronary artery bypass graft surgery. INTERVENTION: Supplementary and dietary vitamin E and C intake (nonrandomized) in association with cholesterol-lowering diet and either colestipol-niacin or placebo (randomized). OUTCOME: Change per subject in the percentage of vessel diameter obstructed because of stenosis (%S) determined by quantitative coronary angiography after 2 years of randomized therapy on all lesions, mild/moderate lesions (< 50%S), and severe lesions (> or = 50%S). RESULTS: Overall, subjects with supplementary vitamin E intake of 100 IU per day or greater demonstrated less coronary artery lesion progression than did subjects with supplementary vitamin E intake less than 100 IU per day for all lesions (P = .04) and for mild/moderate lesions (P = .01). Within the drug group, benefit of supplementary vitamin E intake was found for all lesions (P = .02) and mild/moderate lesions (P = .01). Within the placebo group, benefit of supplementary vitamin E intake was not found. No benefit was found for use of supplementary vitamin C exclusively or in conjunction with supplementary vitamin E, use of multivitamins, or increased dietary intake of vitamin E or vitamin C. CONCLUSIONS: These results indicate an association between supplementary vitamin E intake and angiographically demonstrated reduction in coronary artery lesion progression. Verification from carefully designed, randomized, serial arterial imaging end point trials is needed.

Effects of lovastatin on ApoA- and ApoB-containing lipoproteins. Families in a subpopulation of patients participating in the Monitored Atherosclerosis Regression Study (MARS).

To establish whether lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, exhibits a specific effect on apolipoprotein (apo) A- and apoB-containing lipoproteins, 63 subjects, a subset of the 270 Monitored Atherosclerosis Regression Study (MARS) patients with hypercholesterolemia (190 to 295 mg/dL) and documented coronary artery disease, were randomized into either lovastatin 40 mg twice daily or matching placebo tablets twice daily. Both groups consumed a diet containing 27% calories as fat (polyunsaturated fat/saturated fat ratio, 2.85) and a daily cholesterol intake of less than 250 mg. The plasma lipid and apolipoprotein profiles were determined at the time of randomization and after 2 years of treatment, and the levels of apoA- and apoB-containing lipoprotein families were measured after 2 years of treatment. After this treatment period, the drug group was characterized in comparison with the placebo group by significantly reduced levels of total cholesterol (33%), triglycerides (30%), very-low-density lipoprotein cholesterol (36%), low-density lipoprotein cholesterol (43%), apoB (36%), apoC-III (18%), and apoE (17%) and slightly but insignificantly increased levels of high-density lipoprotein cholesterol (6%) and apoA-I (1%). The 2-year levels of lipoprotein containing apoA-I but no apoA-II (LpA-I) and lipoprotein containing both apoA-I and apoA-II (LpA-I/A-II) particles separated by immunoaffinity chromatography on an anti-apoA-II immunosorber did not differ between the two treatment groups. However, the apoB-containing lipoprotein (Lp) families defined by apolipoprotein composition and separated by immunoaffinity chromatography on anti-apoA-II and anti-apoC-III immunosorbers were affected in a selective manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Triglyceride- and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression as assessed by quantitative coronary angiography in a controlled trial of lovastatin.

BACKGROUND: The Monitored Atherosclerosis Regression Study, a randomized, double-blind, placebo-controlled, 2-year trial of lovastatin monotherapy, found that coronary lesions < 50% diameter stenosis (%S) and coronary lesions > or = 50% S at baseline had different responses to therapy. We now report on clinical, lipid, and nonlipid risk factors of treatment response in these lesion subsets. METHODS AND RESULTS: Two hundred seventy subjects, 37 to 67 years old, with plasma total cholesterol (TC) 190 to 295 mg/dL (4.91 to 7.63 mmol/L) and total triglyceride < 500 mg/dL (5.65 mmol/L) were randomized to low-fat, low-cholesterol diet and either lovastatin 80 mg/d or placebo. Logistic regression was used to model the association between risk factors and coronary lesion progression in mild/moderate (< 50% S) and severe (> or = 50% S) lesions in 220 angiogram pairs analyzed by computer quantitative coronary angiography. In the placebo group, risk factors (P < .05) for the progression of mild/moderate lesions were triglycerides and TC/high-density lipoprotein cholesterol (HDL-C). Risk factors for the progression of severe lesions were HDL-C (negative), low-density lipoprotein cholesterol (LDL-C)/HDL-C, and TC/HDL-C. TC/HDL-C was the predominant risk factor for both mild/moderate and severe lesions in the multivariate analysis. In the lovastatin group, with aggressive lowering of LDL-C and TC below 85 mg/dL and 156 mg/dL, respectively, risk factors for mild/moderate lesions included triglycerides and very-low-density lipoprotein-LDL-associated apolipoprotein C-III (apo C-III-heparin precipitate), a marker of triglyceride-rich lipoprotein particles. Apo C-III-heparin precipitate was the predominant risk factor in the multivariate analysis. Risk factors for severe lesions were LDL-C, LDL-C/HDL-C, TC/HDL-C, and apo B; LDL-C/HDL-C was the predominant risk factor. CONCLUSIONS: These results indicate that triglyceride-rich lipoproteins and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression, respectively. These results add to the growing evidence of the importance of triglyceride-rich lipoproteins as a risk factor for coronary artery disease and the need for treatment in the progression of atherosclerosis.

Developmental changes in narrative and non-narrative discourse in children with and without brain injury.

This study presents a set of narrative and non-narrative tasks and analytic procedures for examining the discourse development of children with perinatal brain injury and typically developing children. Three oral discourse genres were collected at ages 5, 6, and 7: script, picture description, and replica play narration. Genre performances were assessed for the presence of hypothesized genre features. Results suggest these tasks and procedures are able to characterize development in discourse abilities for both a normative group and for children with perinatal brain injury. The group of children with brain injury produced shorter discourse performance with more off-task talk. This group also showed difficulty in fully differentiating the various genre types and in creating integrated discourse performances. However, most of these children demonstrated considerable growth in control of genre features over this time period. The possible utility of these tasks and procedures for clinical assessment is discussed.

Coronary angiographic changes with lovastatin therapy. The Monitored Atherosclerosis Regression Study (MARS).

OBJECTIVE: To assess the effects of lipid-lowering therapy with lovastatin on coronary angiographic findings in patients with coronary artery disease and to compare the findings with those of two lipid-lowering angiographic trials using similar end points. DESIGN: Randomized, double-blind, placebo-controlled, multicenter coronary angiographic trial. SETTING: Community- and university-based cardiac catheterization laboratories. PARTICIPANTS: A total of 270 patients, 37 to 67 years old, with total cholesterol ranging from 4.92 to 7.64 mmol/L (190 to 295 mg/dL) and angiographically defined coronary artery disease. INTERVENTION: A cholesterol-lowering diet and either lovastatin, 80 mg/day, or placebo. OUTCOME: Per-patient change in percent diameter stenosis as determined by quantitative coronary angiography (primary end point). Global change score, based on the consensus of blinded expert readers regarding angiographic change (secondary endpoint). RESULTS: Lovastatin lowered total cholesterol level by 32%, low-density lipoprotein cholesterol by 38%, and the apolipoprotein B by 26% and raised the high-density lipoprotein cholesterol by 8.5% (P < 0.001). Average percent diameter stenosis increased 2.2% in placebo recipients and 1.6% in lovastatin recipients (P > 0.20). For lesions 50% or greater, average percent diameter stenosis increased 0.9% in placebo recipients and decreased 4.1% in lovastatin recipients (P = 0.005). The mean global change score was +0.9 (indicating progression) in the placebo group and +0.4 in the lovastatin group (P = 0.002); 13 placebo recipients and 28 lovastatin recipients had global change scores indicating regression (P < 0.02). CONCLUSION: Treatment with lovastatin plus diet slows the rate of progression and increases the frequency of regression in coronary artery lesions (by global change score), especially in more severe lesions (by quantitative angiography). This is the third lipid-lowering trial to show a benefit using the global change score, an end point predictive of clinical coronary events. Differences between two of these trials, using quantitative coronary angiographic end points, may have theoretical bearing on the mechanisms by which lipid-lowering therapy operates at the level of the arterial wall.

Femoral and coronary angiographic trials.

A number of large-scale clinical trials have demonstrated that lipid-altering therapy is associated with a reduced risk of coronary artery disease events. The mechanism of benefit has been postulated to be related to favorable effects at the level of the arterial wall. Angiography allows direct examination of the effects of lipid-altering therapy on the arterial wall and extensive angiographic trial data are now available. Coronary angiographic trials, employing various patient populations, therapies and endpoint measures, have demonstrated slowed progression and increased regression of atherosclerosis in the coronary tree. Femoral artery trials (which might be considered as surrogate for coronary artery trials) have also shown significant regression of atherosclerosis in treated patients. There are pros and cons for all of the various atherosclerosis change measurement techniques, but coronary artery disease events remain the "bottom line" of concern. In this regard, the Program on the Surgical Control of the Hyperlipidemias (POSCH) trial is valuable since the 3-year human consensus panel-derived global coronary change score predicted subsequent coronary events. Yet to be determined are which quantitative coronary angiography measures predict events. Finally, given the number of therapeutic questions that remain, the most promising opportunity for future antiatherosclerosis research may lie in the use of ultrasound to evaluate changes in the carotid arteries.

The Monitored Atherosclerosis Regression Study (MARS). Design, methods and baseline results.

OBJECTIVE: The Monitored Atherosclerosis Regression Study (MARS) was designed to evaluate the effect of cholesterol lowering by monotherapy with an HMG-CoA reductase inhibitor on progression/regression of atherosclerosis in subjects with angiographically documented coronary artery disease. The purpose of this paper is to present the design, methods, and baseline results of MARS. DESIGN: MARS is a prospective, randomized, double-blind, placebo-controlled trial with baseline, 2-year, and 4-year coronary angiography as well as carotid, brachial, and popliteal ultrasonography. SETTING: Outpatient clinics at the University of Southern California School of Medicine and the University of Wisconsin School of Medicine. SUBJECTS: Two hundred seventy participants of both sexes were recruited directly from the cardiac catheterization laboratory or by chart review of patients having undergone cardiac catheterization in the past. Subjects were considered eligible if they had angiographically demonstrable atherosclerosis in 2 or more coronary artery segments, unaltered by angioplasty, with at least 1 lesion > or = 50% but < 100% diameter stenosis (%S). The inclusion range for total cholesterol (TC) was between 190 and 295 mg/dL. Exclusion factors were: triglycerides > or = 500 mg/dL; premenopausal females; uncontrolled hypertension; diabetes mellitus; untreated thyroid disease; liver dysfunction; renal insufficiency; congestive heart failure; major arrhythmia; left ventricular conduction defects; or any life-threatening disease. INTERVENTION: Subjects were placed on a low-fat, low-cholesterol diet and either 40 mg b.i.d. lovastatin (Mevacor) or placebo. Randomization was stratified by sex, smoking status, and TC. MAIN OUTCOME MEASURES: Per-subject average change in %S as determined by quantitative coronary angiography (QCA) is the primary angiographic endpoint. Secondary endpoints are: categorical analyses of the proportion of subjects with progression; human panel reading of coronary angiograms; and change in minimum lumen diameter (MLD) in mm by QCA. Carotid, brachial, and popliteal ultrasonography is also being performed. RESULTS: The subjects randomized into MARS are 91.5% male with an age range of 37 to 67 years (mean age 57.9 years). For the cohort, baseline lipids are (mean +/- SD): TC, 231 +/- 24 mg/dL; low-density lipoprotein cholesterol (LDL-C) by ultracentrifugation, 153 +/- 24 mg/dL; LDL-C, by calculation, 157 +/- 23 mg/dL; high-density lipoprotein cholesterol (HDL-C), 43 +/- 10 mg/dL; and triglycerides, 160 +/- 73 mg/dL. There were no significant differences between treatment groups in baseline lipid levels or baseline angiographic characteristics. CONCLUSIONS: MARS baseline data show adequacy of randomization with comparability of lovastatin and placebo groups in demographic, lipid, and angiographic characteristics.

Evaluation of human panelists in assessing coronary atherosclerosis.

The Cholesterol Lowering Atherosclerosis Study, a randomized, angiographic clinical trial, has demonstrated the beneficial effect of niacin/colestipol therapy on coronary and femoral atherosclerosis. The primary outcome was a panel-determined consensus score evaluating global coronary changes determined angiographically at 2 years. This article presents an evaluation of interreader agreement in independently assessing the status of native coronary arteries and overall coronary condition. Parameters include 1) identification of the presence of lesions and lesion changes; 2) estimation of lesion severity (percent stenosis) and amount of change in lesion severity; and 3) global assessment of change in coronary status. Readers independently agreed on 1) presence of lesions (82%) and change in lesions (51%); 2) percent stenosis +/- 10% (76%) and change in stenosis +/- 10% (81%); and 3) global assessment of change in coronary status within one step (96%). Results of these analyses may be useful in effectively designing angiographic trials that use a panel of human evaluators as well as computerized methods for angiographic interpretation.

Beneficial effects of colestipol-niacin on coronary atherosclerosis. A 4-year follow-up.

The Cholesterol Lowering Atherosclerosis Study (CLAS) was a randomized, placebo-controlled, angiographic trial testing combined colestipol-niacin therapy in 162 subjects. Two-year results (CLAS-I) showed decreased atherosclerosis progression and increased regression. We now describe a subgroup of 103 subjects treated for 4 years (CLAS-II). Changes in blood lipid, lipoprotein-cholesterol, and apolipoprotein levels were maintained, and at 4 years significantly more drug-treated subjects demonstrated nonprogression (52% drug- vs 15% placebo-treated) and regression (18% drug- vs 6% placebo-treated) in native coronary artery lesions. Significantly fewer drug-treated subjects developed new lesions in native coronary arteries (14% drug- vs 40% placebo-treated) and bypass grafts (16% drug- vs 38% placebo-treated). These results confirm CLAS-I findings and indicate that regression can continue for 4 years. They reaffirm the need for early initiation of vigorous long-term lipid lowering therapy in coronary bypass subjects.