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Biomedical subjects

S J Boccuzzi

Publications and source records attributed to S J Boccuzzi.

31 records · Page 2Linked to original sources
PubMed1995

Effects of cholesterol lowering on the progression of coronary atherosclerosis in women. A Canadian Coronary Atherosclerosis Intervention Trial (CCAIT) substudy.

BACKGROUND: Although coronary disease is the leading cause of death in women and its clinical features differ from those in men, very few women have been included in angiographic trials of cholesterol lowering. METHODS AND RESULTS: Sixty-two women with diffuse but not necessarily severe coronary atherosclerosis documented on a recent angiogram and with fasting serum cholesterol between 220 and 300 mg/dL were enrolled in a double-blind, placebo-controlled trial. More than one half had a history of hypertension, approximately one quarter were diabetics, and one third were current smokers. All women received dietary counseling. Lovastatin or placebo was begun at 20 mg/d and was titrated if necessary to 40 and then to 80 mg during the first 16 weeks to attain a fasting LDL cholesterol < or = 130 mg/dL. The mean lovastatin dose was 34 mg/d. Total and LDL cholesterol decreased by 24% and 32%, respectively, in lovastatin-treated women but by < 3% in women receiving placebo. Coronary arteriography was repeated after 2 years in 54 women (87%), and their 394 lesions were measured "blindly" on pairs of film with an automated computerized quantitative system. Progression, defined as a worsening in minimum diameter of one or more stenoses by > or = 0.4 mm, occurred in 7 of 25 lovastatin-treated women and 17 of 29 placebo-treated women (28% versus 59%, P = .031). New coronary lesions developed in 1 lovastatin-treated woman and 13 placebo-treated women (4% versus 45%, P < .001). The outcome for each of the angiographic end points was not significantly different between the women and the 245 men who completed the trial. CONCLUSIONS: Lovastatin slows the progression of coronary atherosclerosis and prevents the development of new coronary lesions in women.

Adult↗
PubMed1995

Beneficial effects of cholesterol-lowering therapy on the coronary endothelium in patients with coronary artery disease.

BACKGROUND: Impaired endothelium-mediated relaxation contributes to vasospasm and myocardial ischemia in patients with coronary artery disease. We hypothesized that cholesterol-lowering therapy with the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor lovastatin could improve endothelium-mediated responses in patients with coronary atherosclerosis. METHODS: In a randomized, double-blind, placebo-controlled trial, we studied coronary endothelial responses in 23 patients randomly assigned to either lovastatin (40 mg twice daily; 11 patients) or placebo (12 patients) plus a lipid-lowering diet (American Heart Association Step 1 diet). Patients were studied 12 days after randomization and again at 5 1/2 months. These patients had total cholesterol levels ranging from 160 to 300 mg per deciliter (4.1 to 7.8 mmol per liter) and were undergoing coronary angioplasty. At the initial and follow-up studies, patients received serial intracoronary infusions (in a coronary artery not undergoing angioplasty) of acetylcholine to assess endothelium-mediated vasodilatation. The responses of the coronary vessels were analyzed with quantitative angiography. RESULTS: The patients in the placebo and lovastatin groups had similar responses to acetylcholine at a mean of 12 days of therapy (expressed as the percentage of change in diameter in response to acetylcholine doses of 10(-9) M, 10(-8) M, 10(-7) M, and 10(-6) M). In the placebo group, the respective mean (+/- SE) changes were 1 +/- 2, 0 +/- 2, -2 +/- 4, and -19 +/- 4 percent; in the lovastatin group, they were -2 +/- 2, -4 +/- 4, -12 +/- 5, and -16 +/- 7 percent (P = 0.32). (Coronary-artery constriction is reflected by negative numbers). The responses to acetylcholine in the placebo group after a mean of 5.5 months of therapy were -3 +/- 3, -1 +/- 2, -8 +/- 4, and -18 +/- 5 percent, respectively; there was significant improvement in the lovastatin group, which had responses of 3 +/- 3, 3 +/- 3, 0 +/- 2, and 0 +/- 3 percent (P = 0.004). CONCLUSIONS: Cholesterol lowering with lovastatin significantly improved endothelium-mediated responses in the coronary arteries of patients with atherosclerosis. Such improvement in the local regulation of coronary arterial tone could potentially relieve ischemic symptoms and signal the stabilization of the atherosclerotic plaque.

Acetylcholine↗
PubMed1995

Prognosis after hospitalization for acute myocardial infarction not accompanied by typical ischemic chest pain. The Multicenter Diltiazem Postinfarction Trial Research Group.

PURPOSE: Although ischemic-type chest pain generally identifies acute myocardial infarction (AMI), some patients are hospitalized for AMI without this symptom. Long-term mortality and morbidity after AMI presenting with alternative warning symptoms have not been examined previously. We therefore assessed the prognostic implications of the absence of typical chest pain as well as other recognized risk predictors in patients hospitalized with AMI. PATIENTS AND METHODS: Data were obtained during the Multicenter Diltiazem Postinfarction Trial. Pain status and other baseline characteristics were determined prospectively by study coordinators according to simple, prespecified criteria. Patients were then examined every 3 to 4 months until trial completion. We applied chi-square methods, life-table analysis, and multivariate analysis to assess the strength and independence of prognostic power associated with each baseline variable. RESULTS: Of 2,464 patients enrolled 3 to 15 days after enzyme-documented AMI, 115 patients lacked typical ischemic-type chest in on presentation (the "nonpainful" group). After 25 months' mean follow-up, cardiac mortality was 20% for nonpainful patients and 10% for 2,349 patients with typical pain (the "painful" group), P < 0.001. Similar increments were seen in total deaths (27% nonpainful versus 13% painful, P < 0.001) and cardiac events, namely, cardiac death or nonfatal reinfarction (24% nonpainful versus 17% painful, P = 0.001). Late congestive heart failure was more frequent (17% nonpainful versus 7% painful, P < 0.001), but unstable angina was less (6% nonpainful versus 16% painful, P = 0.005). At outset, nonpainful patients had more left ventricular dysfunction and diabetes mellitus. However, nonpainful AMI predicted worse outcome even when these problems were absent. Logistic regression confirmed greater cardiac death risk in the nonpainful group (hazard ratio = 2.05) and showed that predictive power of nonpainful status was independent of baseline ejection fraction, Holter data, concomitant diabetes mellitus, and other covariates. CONCLUSIONS: Patients hospitalized with nonpainful AMI are much more likely to experience late cardiac death or congestive heart failure than are patients with painful AMI. In part, this probably reflects more ventricular damage with alternative warning symptoms such as dyspnea. However, our data suggest that defective perception of warning pain also provides a long-term risk to life that is independent of previously known predictors of poor outcome.

Adult↗
PubMed1994

Lack of effect of lovastatin on restenosis after coronary angioplasty. Lovastatin Restenosis Trial Study Group.

BACKGROUND: Experimental and clinical observations suggest that lowering serum lipid levels may reduce the risk of restenosis after coronary angioplasty. We report the results of a prospective, randomized, double-blind trial evaluating whether lowering lipid levels with lovastatin can prevent or delay restenosis after angioplasty. METHODS: Seven to 10 days before angioplasty, we randomly assigned eligible patients to receive lovastatin (40 mg orally twice daily) or placebo. Patients who underwent successful, complication-free, first-time angioplasty of a native vessel (the index lesion) continued to receive therapy for six months, when a second coronary angiogram was obtained. The primary end point was the extent of restenosis of the index lesion, as assessed by quantitative coronary arteriography. Of 404 patients randomly assigned to study groups, 384 underwent angioplasty; 354 of the procedures were successful, and 321 patients underwent angiographic restudy at six months. RESULTS: At base line, the patients in the lovastatin group (n = 203) and the placebo group (n = 201) were similar with respect to demographic clinical, angiographic, and laboratory characteristics. At base line the mean (+/- SD) degree of stenosis, expressed as a percentage of the diameter of the vessel, was 64 +/- 11 percent in the lovastatin group, as compared with 63 +/- 11 percent in the placebo group (P = 0.22). Despite a 42 percent reduction in the serum level of low-density lipoprotein cholesterol in the lovastatin group, after six months of treatment the amount of stenosis seen in the second angiogram was 46 +/- 20 percent in the placebo group, as compared with 44 +/- 21 percent in the lovastatin group (P = 0.50). Similarly, there were no significant differences in minimal luminal diameter or other measures of restenosis. A trend was noted toward more myocardial infarctions in the lovastatin group, as a result of acute vessel closure or restenosis at the site of angioplasty, but there were no other important differences between the two groups in the frequency of fatal or nonfatal events at six months. CONCLUSIONS: Treatment with high-dose lovastatin initiated before coronary angioplasty does not prevent or delay the process of restenosis in the first six months after the procedure.

Angioplasty, Balloon, Coronary↗
PubMed1994

Effects of monotherapy with an HMG-CoA reductase inhibitor on the progression of coronary atherosclerosis as assessed by serial quantitative arteriography. The Canadian Coronary Atherosclerosis Intervention Trial.

BACKGROUND: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors are widely prescribed for hyperlipidemia, yet their effect on the evolution of coronary atherosclerosis has not been defined. METHODS AND RESULTS: To address this issue, 331 patients with diffuse but not necessarily severe coronary atherosclerosis documented on a recent arteriogram and with fasting serum cholesterol between 220 and 300 mg/dL were enrolled in a randomized, double-blind, placebo-controlled trial. All patients received intensive dietary counseling. Lovastatin or placebo was begun at 20 mg/d and was titrated to 40 and 80 mg during the first 16 weeks to attain a fasting low-density lipoprotein (LDL) cholesterol < or = 130 mg/dL. The mean lovastatin dose was 36 mg/d. Coronary arteriography was repeated after 2 years. In 299 patients (90%), 3858 coronary segments containing 2309 stenoses were measured blindly on pairs of films with an automated computerized quantitative system. Total and LDL cholesterol decreased by 21 +/- 11% and 29 +/- 11%, respectively, in the lovastatin-treated group but changed by < 2% in placebo patients. The primary end point, coronary change score, defined as the per-patient mean of the minimum lumen diameter changes (follow-up minus baseline angiogram) for all lesions measured, excluding those < 25% on both films, worsened by 0.09 +/- 0.16 mm in the placebo group and by 0.05 +/- 0.13 mm in the lovastatin group (P = .01). Progression (a worsening in minimum diameter of one or more stenoses by > or = 0.4 mm) with no regression at other sites occurred in 48 of 146 lovastatin and 76 of 153 placebo patients (33% versus 50%, P = .003). New coronary lesions developed in 23 lovastatin and 49 placebo patients (P = .001). The beneficial effect of treatment was most pronounced in the more numerous, milder lesions and in patients whose baseline total or LDL cholesterol levels were above the group median. CONCLUSIONS: Lovastatin slows the progression of coronary atherosclerosis and inhibits the development of new coronary lesions.

Canada↗
PubMed1992

Background and methods for the lovastatin restenosis trial after percutaneous transluminal coronary angioplasty. The Lovastatin Restenosis Trial Study Group.

Restenosis remains a critical limitation of percutaneous transluminal coronary angioplasty (PTCA). Recent experimental and clinical data have suggested that lovastatin, an hydroxymethylglutaryl coenzyme A reductase inhibitor, may reduce the rate of restenosis through reduction of low density-lipoprotein (LDL) cholesterol or possibly by direct effects. Lovastatin may therefore produce favorable alterations in endothelial healing, resulting in a decreased smooth muscle cell proliferative response to injury after angioplasty. Emory University, in conjunction with Merck Research Laboratories, has initiated a 10-center double-blinded, placebo-controlled, randomized trial to assess the effect of both pretreatment and aggressive lipid lowering with lovastatin in reducing the rate of restenosis. Lovastatin achieves approximately 75% of its effect on LDL cholesterol by 1 week. Thus, patients scheduled for PTCA are randomly assigned pretreatment with lovastatin, 40 mg twice daily, or placebo 7 to 10 days before PTCA. Therapy is continued for 6 months, at which time repeat coronary arteriography is performed. A detailed safety algorithm was designed, with patients receiving lovastatin and matching placebo back-titrated on a 1:1 basis for LDL cholesterol less than 50 mg/dl. The power is a 90%, alpha = 0.05, 2-tailed test to reduce restenosis from 30 to 15%. The sample size is 360 patients in the 2 arms; allowing for a 10% dropout rate, approximately 400 patients will be randomized. Patients with successful PTCA, less than 50% residual diameter stenosis and greater than or equal to 20% diameter stenosis reduction are analyzed for restenosis at 4 to 6 months by quantitative coronary arteriography.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1991

Long-term safety and efficacy profile of simvastatin.

Simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, has been administered to approximately 2,400 patients with primary hypercholesterolemia with a mean follow-up of 1 year in controlled clinical studies and their open extensions. Approximately 10% of this population received simvastatin for a period of greater than or equal to 2 years. The population on whom this safety analysis is based had a mean age of 50 years; 62% were men and approximately 27% had preexisting coronary artery disease. Simvastatin was titrated to the maximal daily dose of 40 mg each evening in 56% of the study population (last recorded dose). The most frequently reported drug-related clinical adverse experiences were constipation (2.5%), abdominal pain (2.2%), flatulence (2.0%) and headaches (1%). Persistent elevations of serum transaminase levels greater than 3 times the upper limit of normal were observed in only 1% of this cohort with only 0.1% of the total population requiring discontinuation of therapy. There were no clinically apparent episodes of hepatitis. Discontinuation of therapy due to myopathy was extremely rare (0.08%). Only minimal increases in the frequency of lens opacities (1%) were observed from baseline to the last lens examination during follow-up, consistent with the expected increase in lens opacity development due to normal aging. Patients who were greater than or equal to 65 years old had a clinical and laboratory safety profile comparable to the nonelderly population.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Diltiazem increases late-onset congestive heart failure in postinfarction patients with early reduction in ejection fraction. The Adverse Experience Committee; and the Multicenter Diltiazem Postinfarction Research Group.

The Multicenter Diltiazem Postinfarction Trial (MDPIT) reported no consistent diltiazem effect on new or worsened congestive heart failure (CHF) during 12-52 months' follow-up after acute myocardial infarction. This was puzzling in light of the observation that patients with findings suggesting left ventricular dysfunction (LVD) at baseline on diltiazem had more cardiac events (cardiac mortality or recurrent nonfatal infarction) than such patients on placebo. We hypothesized that diltiazem increased the frequency of late CHF as well as of cardiac events, but only in patients predisposed by LVD. Using the same characterizing variables as the primary MDPIT analysis, we found that patients with pulmonary congestion, anterolateral Q wave infarction, or reduced ejection fraction (EF) at baseline were more likely to have CHF during follow-up than those without these markers of LVD. CHF was particularly frequent in the patients with LVD who were randomized to diltiazem. Among those with a baseline EF of less than 0.40, late CHF appeared in 12% (39/326) receiving placebo and 21% (61/297) receiving diltiazem (p = 0.004). Life table analysis in patients with an EF of less than 0.40 confirmed more frequent late CHF in those taking diltiazem (p = 0.0017). In addition, the diltiazem-associated rise in the frequency of late CHF was progressively greater with increasingly severe decrements in baseline EF. This diltiazem effect was absent in patients with pulmonary congestion at baseline but an EF of 0.40 or more, suggesting a unique association between diltiazem-related late CHF and systolic LVD.(ABSTRACT TRUNCATED AT 250 WORDS)

Diltiazem↗
PubMed1989

Noninvasive and angiographic evaluation of coronary artery disease in patients with peripheral vascular disease.

The accuracy of exercise testing for detection of coronary artery disease in a population with a high incidence of claudication was evaluated in 58 consecutive patients with abdominal aortic aneurysms or lower extremity occlusive disease. Each patient was evaluated by history and physical examination, symptom-limited testing with exercise treadmill, arm ergometry and exercise radionuclide ventriculography. An algorithm was designed that retrospectively examined the results of each test in a stepwise fashion to simulate a clinical decision-making process. The results of the clinical examination, each of the exercise tests and the noninvasive diagnostic algorithm were compared with the results of coronary arteriography. The predictive accuracy of the clinical evaluation was 36%, treadmill stress testing 57%, treadmill stress plus arm ergometry 74%, exercise radionuclide ventriculography 57% and the noninvasive diagnostic algorithm 89%. When discriminant analysis was applied to all of the exercise variables, no individual test improved the accuracy of the noninvasive diagnostic algorithm. When the analysis considered only individual variables without the algorithm, the model correctly classified only 67% of the patients. Thus, accurate noninvasive evaluation of coronary artery disease is possible in patients with severe peripheral vascular disease when care is taken to design exercise protocols that allow adequate stress on the cardiovascular system.

Adult↗
PubMed1987

Serial acquisition of data to predict one-year mortality rate after acute myocardial infarction.

Eight hundred sixty-six patients with acute myocardial infarction (AMI) were enrolled in a prospective study to determine optimal predictors of long-term prognosis. During 12-month (mean) follow-up there were 65 cardiac deaths and 21 nonfatal repeat AMIs. Twenty-nine variables (from the history, physical examination, serum chemistries, ambulatory monitor, radionuclide ventriculogram and exercise test) were arranged into in 5 sequential groups according to the time at which results became available during hospitalization. Multivariate analysis (logistic regression) and receiver-operator characteristic curves were used to assess improvement in prediction of mortality or repeat AMI by addition of each group of variables. The first group of independent predictors included rales, left bundle branch block and symptom status at 1 month before admission. Addition of information from ambulatory monitoring or serum chemistry did not improve prediction. Radionuclide ejection fraction made a statistically significant, independent contribution to mortality prediction. Of the final group the only exercise test variable that contributed independently to prediction was whether the patients took the test. However, receiver-operator characteristic curves showed that improvement in sensitivity and specificity by addition of information from the radionuclide scan and exercise test was clinically insignificant. Our results imply that costly tests after AMI should be reserved for specific indications and not applied universally for prognosis. Although these tests were highly predictive individually, each test generally added little to preexisting prognostic information.

Follow-Up Studies↗
PubMedDate not supplied

Reduced coronary events in simvastatin-treated patients with coronary heart disease and diabetes or impaired fasting glucose levels: subgroup analyses in the Scandinavian Simvastatin Survival Study.

BACKGROUND: Patients with diabetes mellitus (DM) have a marked increase in coronary heart disease (CHD) events relative to those without DM. In a previous report from the Scandinavian Simvastatin Survival Study using a clinical case definition of DM (n = 202), simvastatin-treated patients had significantly fewer CHD events compared with placebo-treated control subjects. OBJECTIVE: To examine the effect of simvastatin therapy on CHD in patients with DM and impaired fasting glucose levels. METHODS: Using the 1997 American Diabetes Association diagnostic criteria, we assessed the effect of simvastatin therapy post hoc for an average of 5.4 years in Scandinavian Simvastatin Survival Study patients with normal fasting glucose (n = 3237), impaired fasting glucose (n = 678), and DM (n = 483). RESULTS: Simvastatin-treated patients with DM had significantly reduced numbers of major coronary events (relative risk [RR] = 0.58; P = .001) and revascularizations (RR = 0.52; P = .005). Total (RR = 0.79; P = .34) and coronary (RR = 0.72; P = .26) mortality were also reduced in DM, but not significantly, due to small sample size. In impaired fasting glucose (IFG) subjects, simvastatin use significantly reduced the number of major coronary events (RR = 0.62; P = .003), revascularizations (RR = 0.57; P = .009), and total (RR = 0.57; P = .02) and coronary (RR = 0.45; P = .007) mortality. CONCLUSION: Our results extend previous findings in patients with DM to a larger cohort, confirming the benefit of cholesterol lowering with simvastatin treatment on CHD events. In addition, significant decreases in total mortality, major coronary events, and revascularizations were observed in simvastatin-treated patients with impaired fasting glucose levels. These results strongly support the concept that cholesterol lowering with simvastatin therapy improves the prognosis of patients with elevated fasting glucose levels (> or =6.0 mmol/L [> or =110 mg/ dL]) or DM and known CHD.

Anticholesteremic Agents↗