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Biomedical subjects

W J Mack

Publications and source records attributed to W J Mack.

At least 37 records · Page 2Linked to original sources
PubMed2000

Neuropathologic substrates of ischemic vascular dementia.

Ischemic vascular dementia (IVD) is a relatively uncommon entity, in the course of which multiple ischemic brain lesions result in progressive cognitive and memory impairment. Ischemic brain lesions may also aggravate the neuropsychologic deficit of Alzheimer disease (AD). In this review we summarize our experience based upon autopsy examination of the central nervous system in 20 patients (age range 68-92 years) enrolled in a longitudinal investigation of structural, neurochemical, functional neuroimaging, and neuropsychologic components of IVD, especially dementia associated with cerebral microvascular disease. While cystic infarcts were present in the CNS of 5 patients, the most commonly observed neuropathologic abnormalities were lacunar infarcts and microinfarcts--both types of lesion were encountered in over half of patients' brains. Evidence of (remote) hippocampal injury was found in 11/20 patients. Severe atherosclerosis and arterio/ arteriolosclerosis were both associated with the occurrence of multiple lacunar infarcts. Pronounced cerebral amyloid angiopathy (CAA) was noted in a single patient, who also showed other microscopic changes of severe AD. While fairly unusual as a nosologic entity, IVD appears to correlate with widespread small ischemic lesions distributed throughout the CNS. We furthermore propose an approach to quantifying the burden of ischemic vascular and parenchymal disease that may be associated with a dementia syndrome. A brief review of neuropathologic features of vascular dementia (both familial and sporadic) is presented.

Aged↗
PubMed2000

Transcranial Doppler monitoring during carotid endarterectomy: a technical case report.

We report a case involving a patient undergoing carotid endarterectomy in whom transcranial doppler monitoring demonstrated impaired cerebral blood flow during the initial dissection of the carotid artery, during cross-clamping of the carotid artery, and after the shunt was kinked inadvertently. Only when the carotid artery was cross-clamped were these ischemic changes also seen by electroencephalography. During the other episodes, the electroencephalography tracings demonstrated no detectable changes. This case illustrates the importance of using multiple modalities to determine the adequacy of cerebral blood flow and neuronal integrity.

Brain Ischemia↗
PubMed2000

Probucol reduces oxysterol formation in hypertensive rabbits.

The role of lipid peroxidation during the pathogenesis of atherosclerosis has been described through numerous studies and has provided compelling evidence for free radical-mediated processes that link hypertension with atherosclerosis. However, there remains only limited information concerning peroxidative processes in hypertension and their modulation by antioxidants. In the present study, the formation of cholesterol oxidation products was used as a measure of in vivo lipid peroxidation after hypertension induced by coarctation of the aorta in New Zealand White rabbits. The rabbits were fed a standard chow diet devoid of cholesterol or cholesterol oxidation products such that the measured cholesterol oxides in the plasma and aortic tissues would most plausibly arise from endogenous oxidation of cholesterol. After 12 weeks of hypertension, all of the measured cholesterol oxides increased significantly over baseline levels in the surgically coarctated animals; however, this increase was significantly less in hypertensive probucol-treated animals. Similarly, the cholesterol oxide content of aortic tissue from the surgically coarctated animals was significantly greater than that found in normotensive control aortas, and probucol treatment significantly reduced the increase in cholesterol oxide content of aortic tissue relative to that of hypertensive animals not receiving the antioxidant. These findings in hypertensive animals suggest that cholesterol oxidation products measured in plasma and aortic tissue can be derived from endogenous free radical activity and that this activity is enhanced under specific pathological conditions.

Animals↗
PubMed1999

Pathophysiology of triglyceride-rich lipoproteins in atherothrombosis: clinical aspects.

Invasive and noninvasive arterial imaging are important techniques used to study atherosclerosis and, specifically, to evaluate the atherogenecity of triglyceride-rich lipoproteins (TRL). Serial coronary angiography trials show significant benefit from lowering low-density lipoprotein cholesterol (LDL-C) which serves to retard lesion progression. Even with aggressive LDL-C reduction, however, up to half of patients demonstrate continued progression of atherosclerosis. Angiographic studies reveal that lowering LDL-C has the most impact on severe lesions, those > or = 50% diameter stenosis, whereas TRL (and their apolipoprotein markers) have been identified as a driving factor behind progression of mild-to-moderate lesions < 50% diameter stenosis. Quantitative coronary angiography (QCA) has demonstrated that progression of mild-to-moderate lesions are among the most significant predictors of clinical coronary events, and that lowering TRL reduces progression of coronary artery disease to the same degree as the lowering of LDL-C.

Clinical Trials as Topic↗
PubMed1999

A pooled analysis of case-control studies of thyroid cancer. IV. Benign thyroid diseases.

OBJECTIVE: To obtain more precise estimates of the association between thyroid cancer and benign thyroid diseases and to elucidate the role of potential confounders or effect modifiers. METHODS: The original data from 12 case-control studies from the United States, Asia, and Europe were pooled. Based on 2,094 women and 425 men with cancer of the thyroid and, respectively, 3,248 and 928 control subjects, odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were obtained by conditional regression models, conditioning on study and age at diagnosis, and adjusting for age and radiotherapy. RESULTS: A history of hypothyroidism was not associated with cancer risk (pooled ORs = 0.9, 95% confidence interval, CI: 0.7-1.3 in women and 1.7, 95% CI: 0.3-11.7 in men). ORs for hyperthyroidism were 1.4 (95% CI: 1.0-2.1) in women and 3.1 (95% CI: 1.0-9.8) in men. In women, however, risk was lower in the absence of or after allowance for history of goiter. Pooled ORs for a history of goiter were 5.9 (95% CI: 4.2-8.1) in women and 38.3 (95% CI: 5.0-291.2) in men. Risk for a history of benign nodules/adenomas was especially high (OR = 29.9, 95% CI: 14.5-62.0, in women; 18 cases versus 0 controls in men). The excess risk for goiter and benign nodules/adenomas was greatest within 2-4 years prior to thyroid cancer diagnosis, but an elevated OR was present 10 years or more before cancer. CONCLUSIONS: Goiter and benign nodules/adenomas are the strongest risk factors for thyroid cancer, apart from radiation in childhood.

Adenoma↗
PubMed1999

Diet, body size and menarche in a multiethnic cohort.

A multiethnic cohort of 1378 Southern California school girls aged 8-13 years was followed for 4 years to evaluate factors predicting age at menarche, a risk factor for breast cancer. Height and weight were measured and dietary intake was assessed using a semi-quantitative food frequency questionnaire. Of 939 girls providing data on menarcheal status, 767 were premenarcheal at the start of the study; 679 girls provided acceptable dietary data and were included in the analyses. Cox proportional hazards models were used to assess the relationship between diet, body size, ethnicity and age at menarche. Hispanic, Asian/Pacific Island and African-American girls were more likely to experience early menarche than non-Hispanic white girls. Tall (> 148.6 cm) versus short (< 135.9 cm) girls experienced earlier menarche (relative hazard (RH) = 2.9, 95% confidence interval (CI) 2.1-4.1) as did those with high Quetelet's index (QI, kg m(-2)) (> 20.7) versus low QI (< 16.1) (RH = 2.2, 95% CI 1.7-2.9). Of all the dietary variables analysed, only energy intake was related to age at menarche. High versus low energy intake (> 12,013 kJ vs < 7004 kJ) was associated with a delay in menarche (RH = 0.7, 95% CI 0.5-0.9); this finding was limited to a subset of heavy Hispanic girls who appeared to underreport their dietary intake.

Adolescent↗
PubMed1999

Reproductive and hormonal risk factors for thyroid cancer in Los Angeles County females.

We conducted an individually matched case-control study (292 pairs) of female thyroid cancer patients to examine the role of reproductive history and exogenous hormones in this disease. Radiation treatment to the head or neck [28 cases and 2 controls exposed; odds ratio (OR), 14.0; 95% confidence interval (CI), 3.5-121.3] and certain benign thyroid diseases (including adolescent thyroid enlargement, goiter, and nodules or tumors) were strongly associated with thyroid cancer. Irregular menstruation increased risk (OR, 1.8; 95% CI, 0.9-3.7). Age at menarche and pregnancy history were not related to disease. Women with natural menopause and hysterectomized women without oophorectomy had no increase in risk, but disease risk was elevated in women with bilateral oophorectomy (OR, 6.5; 95% CI, 1.1-38.1). In general, use of oral contraceptives and other exogenous estrogens was not associated with thyroid cancer. However, risk increased with number of pregnancies in women using lactation suppressants (P = 0.03) and decreased with duration of breastfeeding (P = 0.04). These data provide only limited support for the hypothesis that reproductive and hormonal exposures are responsible for the marked excess of thyroid cancer risk in adult females.

Adenocarcinoma, Follicular↗
PubMed1998

The role of carotid arterial intima-media thickness in predicting clinical coronary events.

BACKGROUND: Carotid arterial intima-media thickness is used as a noninvasive surrogate end point to measure progression of atherosclerosis, but its relation to coronary events has not been fully explored. OBJECTIVE: To determine whether carotid arterial intima-media thickness predicts coronary events. DESIGN: Long-term follow-up (average, 8.8 years) of a previously assembled cohort of persons who completed the 2-year Cholesterol Lowering Atherosclerosis Study, a randomized arterial imaging trial designed to study the effects of lipid lowering on progression of atherosclerosis. SETTING: University-based ultrasonography laboratory. PATIENTS: 146 men 40 to 59 years of age who had previously had coronary artery bypass graft surgery. MEASUREMENTS: Preintrusive atherosclerosis in the common carotid artery was evaluated every 6 months with B-mode ultrasonography, and intrusive atherosclerosis in the coronary arteries was evaluated at baseline and at 2 years with quantitative coronary angiography. After the trial, the incidences of coronary events (nonfatal acute myocardial infarction, coronary death, and coronary artery revascularization) were documented. RESULTS: For each 0.03-mm increase per year in carotid arterial intima-media thickness, the relative risk for nonfatal myocardial infarction or coronary death was 2.2 (95% CI, 1.4 to 3.6) and the relative risk for any coronary event was 3.1 (CI, 2.1 to 4.5) (P < 0.001). Absolute intima-media thickness was also related to risk for clinical coronary events (P < 0.02). Absolute thickness and progression in thickness predicted risk for coronary events beyond that predicted by coronary arterial measures of atherosclerosis and lipid measurements (P < 0.001). CONCLUSION: Noninvasive B-mode ultrasonographic measurement of progression of intima-media thickness in the distal common carotid artery is a useful surrogate end point for clinical coronary events.

Adult↗
PubMed1998

Triglyceride-rich lipoproteins and progression of atherosclerosis.

AIMS: To present data from the Cholesterol Lowering Atherosclerosis Study (CLAS) and the Monitored Atherosclerosis Regression Study (MARS) demonstrating the relationship between triglyceride-rich lipoproteins and progression of atherosclerosis. METHODS AND RESULTS: CLAS and MARS were randomized, placebo-controlled, arterial imaging trials designed to determine the effects of lipid lowering on the progress of atherosclerosis using coronary angiographic and carotid arterial wall intima-media thickness measurement end points. Included in each of these trials were specific measurements of triglyceride-rich lipoproteins in addition to the traditional lipid measurements. CONCLUSIONS: CLAS and MARS indicate that specific triglyceride-rich lipoproteins such as VLDL, IDL, apolipoprotein B-containing lipoprotein particles (i.e. lipoprotein Bc), and markers of triglyceride-rich lipoprotein metabolism (i.e. apolipoprotein C-III) are significantly related to progression of atherosclerosis. These specific triglyceride-rich lipoproteins are associated with the progression of atherosclerosis independently of HDL cholesterol levels. Importantly, there appears to be a differential effect of triglyceride-rich lipoproteins and cholesteryl-ester rich lipoproteins (i.e. LDL cholesterol) on the progression of mild/moderate and severe coronary artery lesions, respectively. This association not only suggests that certain risk factors may act early and others late in the athersclerotic process, but that triglyceride-rich lipoproteins are associated with progression of the lesions (mild/moderate lesions) which are predominantly responsible for clinical coronary events.

Angiography↗
PubMed1997

Intermediate-density lipoproteins and progression of carotid arterial wall intima-media thickness.

BACKGROUND: Although LDL cholesterol (LDL-C) is generally accepted to be a major risk factor for progression of atherosclerosis, the traditional measurement of LDL-C includes measurement of IDL. Little is known about the relationship between IDL and progression of atherosclerosis. Therefore, we investigated the association of plasma lipoprotein subclasses with progression of preintrusive carotid artery atherosclerosis in the Monitored Atherosclerosis Regression Study (MARS). METHODS AND RESULTS: MARS was a randomized, double-blind, placebo-controlled serial arterial imaging trial conducted in subjects 37 to 67 years old with angiographically defined coronary artery disease. Analytical ultracentrifugation was used to determine lipoprotein subclasses, including LDL (Sf 0 to 12), IDL (Sf 12 to 20), VLDL (Sf 20 to 400), and HDL (F1.20 0 to 9) in 188 subjects. Subjects were randomized to a cholesterol-lowering diet plus placebo or lovastatin 80 mg/d. The outcome measure, the annual progression rate of the distal common carotid artery far wall intima-media thickness determined by high resolution B-mode ultrasonography, was determined at baseline and every 6 months on trial. When the major apolipoprotein B-containing lipoproteins were measured independently, IDL (r=.21, P<.005) but not VLDL (r=-.09, P=.24) or LDL (r=.09, P=.26) was associated with the progression of carotid artery intimamedia thickness. CONCLUSIONS: These data provide further evidence for the role of triglyceride-rich lipoproteins in the progression of atherosclerosis and support the evidence that indicates that the risk of atherosclerosis attributable to LDL-C may in part be the result of lipoproteins in the IDL fraction (Sf 12 to 20) that is included within the traditional measurements of LDL-C.

Adult↗
PubMed1997

A comparison of quantitative computerized and human panel coronary endpoint measures: implications for the design of angiographic trials.

The Monitored Atherosclerosis Regression Study was a double-blind, 2-year, placebo-controlled, randomized, serial angiographic trial which tested reduction of low density lipoprotein-cholesterol with monotherapy using lovastatin on the progression of coronary atherosclerosis. Angiographic outcome was evaluated both by a panel of human readers who visually inspected matched film pairs to arrive at a global change score and by automated computerized vessel edge finding and lesion measurement (quantitative coronary angiography, QCA). In this paper, we model the association between QCA measures of coronary artery lesion change and the panel-based global change score. QCA measures included: per-patient changes in percent diameter stenosis and minimum lumen diameter averaged over all lesions; per-patient changes in average diameter and percent involvement averaged over all segments; the numbers of progressing and regressing lesions and new total occlusions; and the development of any new lesions. We found that when evaluating coronary artery lesion change, panelists evaluate changes in percent diameter stenosis for both low grade (< 50% diameter stenosis at baseline) and high grade (> or = 50% diameter stenosis at baseline) lesions as well as new total occlusions and the number of progressing lesions. Although computerized quantification of the size of a lesion at baseline and as an endpoint may be a more precise measure than that by human panel interpretation, QCA fails to incorporate many other important aspects of coronary angiographic change visualized over the entire coronary artery tree by a panel of human interpreters. Thus, the global change score provides a "multiple endpoint" for coronary angiographic trials which does not suffer from the problems of statistical analysis and interpretation of multiple hypothesis tests which usually accompany true multiple endpoint measures. Choice of either or both endpoints in preparing angiographic trials depends on careful consideration of the desired information as well as the cost of carrying out the endpoint analysis.

Anticholesteremic Agents↗
PubMed1997

Dietary and other lifestyle factors of women with brain gliomas in Los Angeles County (California, USA)

A population-based interview study in Los Angeles County (California, USA) of 94 women with intracranial gliomas and 94 individually matched neighborhood controls investigated the relationship to various sources of exposure to N-nitroso compounds and their precursors and to vitamins which inhibit the endogenous formation of these compounds. The study offers some support for the hypothesis that dietary sources of nitroso exposure relate to risk. Risk increased with increasing consumption of cured meats, most notably of bacon (odds ratio [OR] for the third tertile of intake = 6.6, 95 percent confidence interval [CI] = 1.9-22.5, P trend < 0.001). Risk was reduced with increasing intake of vegetables such as bell peppers (OR for third tertile = 0.2, CI = 0.1-0.7, P trend < 0.01). In addition, use of vitamin supplements appeared protective, and there was some suggestion that eating cured meats in combination with foods which inhibit endogenous nitrosation mitigates risk. Other potential sources of nitroso exposure such as smoking, cosmetics, and drinking water did not relate to risk. Despite the limitations of data on usual adult diet, it appears that dietary sources of nitroso compounds may be important in the development of gliomas.

Adult↗
PubMed1997

Influence of lifestyle modification on atherosclerotic progression determined by ultrasonographic change in the common carotid intima-media thickness.

The Monitored Atherosclerosis Regression Study (MARS) was a randomized, double-blind, placebo-controlled angiographic trial of lipid-lowering therapy in subjects with coronary artery disease. Subjects were counseled to follow a low-fat, low-cholesterol diet. At every clinic visit, data were obtained on body weight, dietary intake, alcohol consumption, and tobacco use. Semiannual determinations of early preintrusive atherosclerosis were made with high-resolution B-mode ultrasonography of the carotid artery intima-media thickness (IMT). We evaluated the effects of lifestyle modification (diet, alcohol, smoking, and weight loss) on the rate of carotid artery IMT progression on the 94 subjects randomly assigned to the placebo group. Dietary cholesterol, insoluble fiber, body mass index, and smoking were significant predictors of the annual rate of carotid artery IMT progression (P < 0.05). For subjects experiencing IMT progression, increased intakes of monounsaturated fat relative to saturated fat and stearic acid (18:0) consumption were significant predictors of a reduction in the annual rate of carotid artery IMT progression; for subjects experiencing IMT regression, male sex was a significant predictor of a reduction in the annual rate of carotid artery IMT regression. Modifications reducing body mass index by 5 kg/m2, quitting a 10 cigarette/d smoking habit, and reducing dietary cholesterol intake by 100 mg/d on average would reduce the annual rate of carotid wall IMT progression by 0.13 mm/y, which is equivalent to the maximum rate of IMT progression observed in the MARS placebo group. Progression of early preintrusive atherosclerosis can be reduced and overall regression can occur with dietary and lifestyle modification.

Adult↗
PubMed1997

The role of triglyceride-rich lipoprotein families in the progression of atherosclerotic lesions as determined by sequential coronary angiography from a controlled clinical trial.

We have demonstrated previously in a subset of Monitored Atherosclerosis Regression Study (MARS) subjects with hypercholesterolemia (190 to 295 mg/dL) and documented coronary artery disease that lovastatin significantly reduces cholesterol-rich lipoprotein B (LpB) but has little effect on complex, triglyceride-rich apolipoprotein (apo) B-containing LpBc (the sum of LpB:C, LpB:C:E and LpA-II:B:C:D:E) particles defined by their apolipoprotein composition. This differential effect of lovastatin on apoB-containing lipoprotein families offered the opportunity to determine in the same subset of MARS subjects the independent relationship of LpB and LpBc with the progression of coronary artery disease. Subjects randomized to either lovastatin (40 mg twice daily) or matching placebo were evaluated by coronary angiography before randomization and after 2 years of treatment, and the overall coronary status was judged by a coronary global change score. In the lovastatin-treated group, there were 22 nonprogressors (69%) and 10 progressors (31%), while in the placebo group 13 subjects (42%) were nonprogressors and 18 (58%) were progressors (P < .03). In the lovastatin-treated group, lipid and lipoprotein parameters did not differ between progressors and nonprogressors except for LpBc and LpA-II:B:C:D:E particle levels, which were statistically higher in progressors (P = .02). In the placebo-treated group, progressors differed from nonprogressors by having significantly higher levels of triglycerides (P = .03) and apoC-III in VLDL + LDL (P = .05), the characteristic constituents of triglyceride-rich lipoproteins. In the placebo- and lovastatin-treated groups combined, progressors had significantly higher on-trial levels of triglycerides (P = .003), VLDL cholesterol (P = .005), apoC-III in VLDL + LDL (P = .008), apoC-III (P = .01), apoB (P = .03), and total cholesterol (P = .04) than nonprogressors. Even after adjustment for treatment group, progressors in the combined placebo- and lovastatin-treated groups had significantly higher levels of LpBc, LpA-II:B:C:D:E, triglycerides, and apoC-III in VLDL + LDL than nonprogressors. Progressors in the placebo-treated, lovastatin-treated, and combined treatment groups had lower levels of LpA-1 but not LpA-I:A-II than non-progressors, and this difference reached statistical significance (P = .047) in the combined sample adjusted for treatment group. Results of this study show that elevated levels of triglyceride-rich LpBc in general and LpA-II:B:C:D:E in particular contribute significantly to the progression of coronary artery disease. Furthermore, they provide additional evidence for the potentially protective role of LpA-I particles in the atherogenic process and suggest that apolipoprotein-defined lipoprotein families may be more specific prognosticators of coronary artery atherosclerosis progression than lipids and apolipoproteins.

Adult↗
PubMed1996

Effect of supplementary antioxidant vitamin intake on carotid arterial wall intima-media thickness in a controlled clinical trial of cholesterol lowering.

BACKGROUND: There is accumulating experimental, epidemiological, and clinical evidence of an association between anti-oxidant vitamin intake and reduced risk of coronary heart disease. Using data from the Cholesterol Lowering Atherosclerosis Study (CLAS), we explored the association of self-selected supplementary antioxidant vitamin intake on the rate of progression of early preintrusive atherosclerosis. METHODS AND RESULTS: CLAS was an arterial imaging trial in which nonsmoking 40- to 59-year-old men with previous coronary artery bypass graft surgery were randomized to colestipol/niacin plus diet or placebo plus diet. The rate of progression of early preintrusive atherosclerosis was determined in 146 subjects using high-resolution B-mode ultrasound quantification of the distal common carotid artery far wall intima-media thickness (IMT). From the nutritional supplement database, 22 subjects had an on-trial average supplementary vitamin E intake of > or = 100 IU per day (high users) and 29 subjects had an average on-trial supplementary vitamin C intake of > or = 250 mg per day (high users). Within the placebo group, less carotid IMT progression was found for high supplementary vitamin E users when compared with low vitamin E users (0.008 versus 0.023 mm/y, P = .03). No effect of vitamin E within the drug group was found. No effect of vitamin C within the drug or placebo group was found. CONCLUSIONS: Supplementary vitamin E intake appears to be effective in reducing the progression of atherosclerosis in subjects not treated with lipid-lowering drugs while the process is still confined to the arterial wall (early preintrusive atherosclerosis).

Adult↗
PubMed1996

Reduction in carotid arterial wall thickness using lovastatin and dietary therapy: a randomized controlled clinical trial.

OBJECTIVE: To assess the effects of lipid-lowering therapy on the progression of early, preintrusive carotid arterial atherosclerosis. DESIGN: Randomized, double-blind, placebo-controlled, serial carotid arterial imaging trial. SETTING: University Atherosclerosis Research Unit. PATIENTS: 188 patients from the Monitored Atherosclerosis Regression Study who were 37 to 67 years of age and had angiographically defined coronary artery disease. INTERVENTION: Cholesterol-lowering diet plus placebo or lovastatin, 80 mg/d. MEASUREMENTS: High-resolution B-mode ultrasonographic quantification of the combined thickness of the distal common carotid arterial far wall intima-media complex (carotid arterial intima-media thickness) at baseline and every 6 months for as long as 4 years. RESULTS: The annual rate of change in carotid arterial intima-media thickness differed significantly between the lovastatin group and the placebo group at 2 and 4 years (P < 0.001). CONCLUSION: Lipid-lowering therapy reverses the progression of early, preintrusive atherosclerosis of the carotid artery. Both cholesterol-rich and triglyceride-rich lipoproteins correlate with the progression of early, preintrusive atherosclerosis of the carotid artery. These findings, together with earlier reports of the effects of lovastatin therapy on the progression of atherosclerosis of the coronary arteries, indicate that carotid arterial far wall intima-media thickness is a useful end point for anti-atherosclerosis trials.

Adult↗
PubMed1996

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.

Adult↗