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Biomedical subjects

G B Mancini

Publications and source records attributed to G B Mancini.

At least 37 records · Page 2Linked to original sources
PubMed1998

Role of angiotensin-converting enzyme inhibition in reversal of endothelial dysfunction in coronary artery disease.

Angiotensin-converting enzyme (ACE) inhibitors have shown unexpected benefits in the prevention of ischemic events in patients with hypertension and congestive heart failure. In addition to these clinical observations, there is a growing body of knowledge about the molecular and cellular effects of ACE inhibitors. For example, ACE inhibition prevents stimulation of smooth muscle cell angiotensin II receptors, thereby blocking both contractile and proliferative actions. Angiotensin II blockade also diminishes the production of superoxide anion, which inactivates ambient nitric oxide. ACE inhibition of kininase II inhibits the breakdown of bradykinin, a direct stimulant of nitric oxide release from the intact endothelial cell. Thus, at the cellular level within the vasculature, ACE inhibition shifts the balance of ongoing mechanisms in favor of those promoting vasodilatory, antiaggregatory, antithrombotic, and antiproliferative effects. These effects underlie the potential benefits of ACE inhibition in the therapy of ischemia and atherosclerosis. Some data is available in humans to show that these effects can be sustained for months, thereby maintaining improved endothelial function and, presumably, allowing the initiation of steps that might alter the progression of atherosclerosis. Definitive information is not yet available in humans to show that ACE inhibition clearly alters the progression of atherosclerosis or diminishes coronary events in uncomplicated coronary disease. This promising area of investigation is, however, the subject of multiple clinical trials, which should provide clarification of this important question in coming years.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Influence of smoking status on progression of endothelial dysfunction. TREND Investigators. Trial on Reversing Endothelial Dysfunction.

BACKGROUND: Cigarette smoking is a major risk factor for developing coronary artery disease and is associated with increased coronary morbidity and mortality in patients with established atherosclerosis. This report describes the influence of smoking on coronary endothelial function in normotensive patients with coronary artery disease, but without left ventricular dysfunction, severe hypercholesterolemia, or insulin-dependent diabetes mellitus. METHODS: Placebo-treated patients (n = 54) from a larger study assessing coronary endothelial function were classified at baseline as smokers or nonsmokers for this subgroup analysis. Patients underwent coronary angiography at baseline and again after 6-month follow-up. RESULTS: At baseline, there was a trend for a greater decrease in target segment diameter (n = 54) in smokers compared with nonsmokers (-17.2 +/- 5.3% vs. -8.0 +/- 2.5%, acetylcholine 10(-4) mol/l). All measured coronary artery segments (n = 202) showed similar responses (-7.3 +/- 2.7% vs. -3.8 +/- 1.3%, acetylcholine 10(-4) mmol/l, for smokers vs. nonsmokers, respectively). After 6 months, smokers showed an even greater vasoconstrictor response to acetylcholine whereas nonsmokers did not (-21.7 +/- 5.3% vs. -8.3 +/- 2.5%, acetylcholine 10(-4) mmol/l). The vasodilatory response to nitroglycerin was similar in smokers and nonsmokers. CONCLUSIONS: In current smokers, a marked decline in endothelium-dependent vasomotor response was observed over a 6-month period.

Acetylcholine↗
PubMed1998

Tibial osteotomy for varus gonarthrosis. A 10- to 21-year followup study.

From 1975 to 1986, 102 high tibial osteotomies for varus gonarthrosis were performed in 99 patients. Fifty-eight patients (60 knees) were reviewed at an average followup of 15 years (range, 10-21 years); of the remaining 41 patients, seven had a knee replacement, 18 had died, and 16 were lost to followup. The results, assessed according to the scoring system of the Hospital for Special Surgery and including the seven patients who underwent a knee replacement, were excellent or good in 37 (55%) knees and fair or poor in 30 (45%). Twenty-six patients of the current study previously were reviewed in 1986, with an average followup of 8 years, using the same clinical and radiographic criteria. In this group of 26 patients, excellent and good results decreased from 73% in 1986 to 46% in 1996. The knees in these 26 patients with a followup greater than 15 years had a statistically significant higher percentage of fair and poor results. No statistically significant differences in the results were found according to the amount of correction. Radiographic controls at followup were available for 45 of the 60 knees; a loss of correction greater than 5 degrees was observed in 11 knees. The results of this long-term followup study show that high tibial osteotomy for gonarthrosis allows a long period (range, 10-15 years) of relief of pain, good range of motion, and function in a large number of patients. Results tend to deteriorate with time, particularly after 15 years.

Adult↗
PubMed1997

Effects of quinapril on coronary blood flow in coronary artery disease patients with endothelial dysfunction. TREND Investigators. Trial on Reversing Endothelial Dysfunction.

This pilot study evaluates the effects of quinapril, an angiotensin-converting enzyme inhibitor with high tissue-binding affinity, on microvascular endothelial function in patients with mild (<40% narrowing) coronary artery disease and epicardial endothelial dysfunction. Patients randomized to quinapril had a trend suggesting an increase in endothelium-dependent coronary blood flow response.

Acetylcholine↗
PubMed1997

Rationale, design, and baseline characteristics of the Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT).

The Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial is the first angiographic clinical trial to be designed to test whether an agent can slow or even reverse the progression of early coronary atherosclerosis in patients with documented disease. In addition, a subset of patients are undergoing carotid ultrasound examinations, providing a unique opportunity to assess and correlate disease progression in 2 arterial beds.

Aged↗
PubMed1997

Novel methodology for echocardiographic quantification of cardiac shape.

BACKGROUND: Left ventricular (LV) shape is a major determinant of cardiac physiology with important prognostic implications. Current techniques are limited in their ability to characterize shape. Regional curvature analysis is a recently developed method that is free of idealized shape assumptions and is applicable globally or regionally. OBJECTIVE: To measure the change in regional curvature from diastole to systole to determine whether modifications of this methodology can be applied to study LV shape noninvasively, and to compare this method with other shape analysis methods. ANIMALS: Seventeen normal dogs underwent transthoracic echocardiography. LV dimensions were measured at end-diastole and end-systole. LV endocardial outlines were traced from apical four-chamber views. LV short to long axis (D/L) ratios and eccentricity index (E) were calculated. Regional curvatures were determined using customized software. Reproducibility of regional curvature was also determined. MAIN RESULTS: LV regional curvature values were consistent among animals at diastole and systole in all areas. Regional curvature showed divergence in different areas. D/L ratios showed a 7% decrease from diastole to systole, whereas E demonstrated a 10% increase. However, regional curvature exhibited a 39% change, suggesting that this methodology is more sensitive. Duplicate curvature values from same or different cardiac cycles were highly reproducible. CONCLUSIONS: Quantitative regional curvature analysis can be applied with echocardiography to study LV shape. This methodology is more sensitive than current methods, is reproducible and may be applicable to the noninvasive study of shape changes in cardiac disease.

Analysis of Variance↗
PubMed1996

Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease. The TREND (Trial on Reversing ENdothelial Dysfunction) Study.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors may exert some of their benefits in the therapy of hypertension, congestive heart failure, and acute myocardial infarction by their improvement of endothelial dysfunction. TREND (Trial on Reversing ENdothelial Dysfunction) investigated whether quinapril might improve endothelial dysfunction in normotensive patients with coronary artery disease and no heart failure, cardiomyopathy, or major lipid abnormalities so that confounding variables that affect endothelial dysfunction could be minimized. METHODS AND RESULTS: Using a double-blind, randomized, placebo-controlled design, we measured the effects of quinapril (40 mg daily) on coronary artery diameter responses to acetylcholine using quantitative coronary angiography. The primary response variable was the net change in the acetylcholine-provoked constriction of target segments between the baseline (prerandomization) and 6-month follow-up angiograms. The constrictive responses to acetylcholine were comparable in the placebo (n = 54) and quinapril (n = 51) groups at baseline. After 6 months, only the quinapril group showed significant net improvement in response to incremental concentrations of acetylcholine (4.5 +/- 3.0% [mean +/- SEM] versus -0.1 +/- 2.8% at 10(-6) mol/L and 12.1 +/- 3.0% versus -0.8 +/- 2.9% at 10(-4) mol/L, quinapril versus placebo, respectively; overall P = .002). CONCLUSIONS: TREND shows that ACE inhibition with quinapril improved endothelial dysfunction in patients who were normotensive and who did not have severe hyperlipidemia or evidence of heart failure. These benefits of ACE inhibition are likely due to attenuation of the contractile effects and superoxide-generating effects of angiotensin II and to enhancement of endothelial cell release of nitric oxide secondary to diminished breakdown of bradykinin.

Acetylcholine↗
PubMed1996

[Reduction of cardiovascular events with pravastatin. A pooled analysis of clinical events within the scope of the Pravastatin Atherosclerosis Intervention Program].

BACKGROUND: It has been documented that the HMG coenzyme A reductase inhibitors, or statins, can decrease cardiovascular events and mortality in patients with clinical coronary disease and moderately to severely elevated lipid levels. Additional data are required to demonstrate a reduction of vascular events in coronary patients with less than severely elevated lipid levels and in subgroups of this population. METHODS AND RESULTS: Clinical data from four atherosclerosis regression trials that evaluated pravastatin were pooled for a predetermined analysis of the effect of that agent on the risk of coronary events. All trials were double-masked, placebo-controlled designs that used pravastatin as monotherapy for 2 to 3 years. The 1891 participants in the trials had evidence of atherosclerosis and mildly to moderately elevated lipid levels. For fatal or nonfatal myocardial infarction, there was a 62% reduction in events attributable to pravastatin (p = .001). This effect was evident in younger and older patients, men and women, and patients with and without histories of hypertension and prior infarction. There was a 46% reduction in all-cause mortality (p = 17), which, although not statistically significant, is consistent with the results of other statin trials. There also was a 62% reduction in the risk of fatal or nonfatal stroke (p = .054). CONCLUSIONS: These pooled results provide strong evidence that pravastatin reduces the risk of cardiovascular events in patients with atherosclerotic disease and mildly to moderately elevated lipid levels. The benefit for reducing myocardial infarction is evident in older and younger patients, men and women, and patients with and without histories of hypertension and prior infarction.

Adult↗
PubMed1996

Emerging concepts: angiotensin-converting enzyme inhibition in coronary artery disease.

Angiotensin-converting enzyme (ACE) inhibitors have played a highly beneficial role in the therapy of hypertension and congestive heart failure. Detailed analysis of some of the heart failure trials in patients with these diseases has uncovered unexpected benefits in the prevention of cardiovascular events. Paralleling these observations are the rapidly accruing basic studies describing important molecular and cellular effects of these agents. For example, ACE inhibition will prevent stimulation of smooth muscle cell angiotensin II receptors, thereby blocking both contractile and proliferative actions. In addition, ACE inhibition of kininase II inhibits the breakdown of bradykinin. Bradykinin is a direct stimulant of nitric oxide release from the intact endothelial cell. Thus, at the cellular level ACE inhibition shifts the balance of ongoing mechanisms in favor of those promoting vasodilatory, antiaggregatory, antithrombotic, and antiproliferative effects. These effects underlie the potential benefits of ACE inhibition in the therapy of coronary artery disease and atherosclerosis.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

'Unqualified success' and 'unmitigated failure': number-needed-to-treat-related concepts for assessing treatment efficacy in the presence of treatment-induced adverse events.

BACKGROUND: Common indices for the quantal assessment of treatment efficacy are reviewed. The absolute risk reduction is a practical index for public health considerations. Its reciprocal has been termed the 'Number Needed to Treat' (NNT), representing the health effort that must on average be expended to accomplish one tangible treatment target. We extend the NNT to evaluate outcome combinations of treatment benefits versus treatment harms. METHODS: We describe the mathematical context of the NNT, and extend it to evaluate outcome combinations (treatment success/failure with/without treatment-induced adverse effects) in a treated population. These extensions are carried out assuming either independence or positive association between treatment benefit and treatment harm. A method is provided for calculating the standard errors of these extended NNT values. Applications to cost-effectiveness analysis are discussed. RESULTS: We calculate NNT in three recent therapeutic studies. The results of a trial of the prevention of strokes with warfarin in patients with non-valvular atrial fibrillation are analysed to evaluate treatment success (stroke prevention) against treatment-induced bleeds. An NNT-related cost-benefit analysis is also carried out. We also analyse the results of a study of two modalities of chemotherapeutic treatment in small-cell lung cancer, and of two modalities of surgical intervention in the treatment of cholelithiasis. CONCLUSIONS: The NNT are useful in direct evaluation of outcome-specific treatment benefits versus treatment-induced harms. They may also be used in cost-effectiveness analyses and are helpful in guiding public health programmes towards the identification of optimal treatment strategies.

Anticoagulants↗
PubMed1995

Effects of vitamin E on endothelial function in men after myocardial infarction.

This study showed that endothelial dysfunction is present in men 3 to 6 months after myocardial infarction, but was unable to show any improvement in endothelial function after 3 months of therapy with vitamin E 800 IU/day. Further studies are necessary to determine whether higher doses or a longer course of vitamin E, or whether other antioxidant agents with or without lipid-modifying activity, would improve endothelial function.

Acetylcholine↗
PubMed1995

Pravastatin limitation of atherosclerosis in the coronary arteries (PLAC I): reduction in atherosclerosis progression and clinical events. PLAC I investigation.

OBJECTIVES: This study was designed to evaluate the effect of pravastatin on progression of coronary atherosclerosis and ischemic events in patients with coronary artery disease and mild to moderate hyperlipidemia. BACKGROUND: Few clinical trial data support the use of lipid-lowering therapy in patients with coronary artery disease and mild to moderate elevations in cholesterol levels. METHODS: Four hundred eight patients (mean age 57 years) with coronary artery disease and low density lipoprotein (LDL) cholesterol > or = 130 mg/dl (3.36 mmol/liter) but < 190 mg/dl ([4.91 mmol/liter]) despite diet were randomized in a 3-year study to receive pravastatin or placebo. Atherosclerosis progression was evaluated by quantitative coronary arteriography. RESULTS: Baseline mean LDL cholesterol was 164 mg/dl (4.24 mmol/liter). Pravastatin decreased total and LDL cholesterol and triglyceride levels by 19%, 28% and 8%, respectively, and increased high density lipoprotein cholesterol by 7% (p < or = 0.001 vs. placebo for all lipid variables). Progression of atherosclerosis was reduced by 40% for minimal vessel diameter (p = 0.04), particularly in lesions < 50% stenosis at baseline. There was a consistent although not statistically significant effect on mean diameter and percent diameter stenosis. There were also fewer new lesions in those assigned pravastatin (p < or = 0.03). Myocardial infarction was reduced during active treatment (8 in the pravastatin group, 17 in the placebo group; log-rank test, p < or = 0.05; 60% risk reduction), with the benefit beginning to emerge after 1 year. CONCLUSIONS: In patients with coronary artery disease and mild to moderate cholesterol elevations, pravastatin reduces progression of coronary atherosclerosis and myocardial infarction. The time course of event reduction increases the potential for a relatively rapid decrease in the clinical manifestations of coronary artery disease with lipid lowering.

Aged↗
PubMed1995

Reduction in cardiovascular events during pravastatin therapy. Pooled analysis of clinical events of the Pravastatin Atherosclerosis Intervention Program.

BACKGROUND: It has been documented that the HMG coenzyme A reductase inhibitors, or statins, can decrease cardiovascular events and mortality in patients with clinical coronary disease and moderately to severely elevated lipid levels. Additional data are required to demonstrate a reduction of vascular events in coronary patients with less than severely elevated lipid levels and in subgroups of this population. METHODS AND RESULTS: Clinical data from four atherosclerosis regression trials that evaluated pravastatin were pooled for a predetermined analysis of the effect of that agent on the risk of coronary events. All trials were double-masked, placebo-controlled designs that used pravastatin as monotherapy for 2 to 3 years. The 1981 participants in the trials had evidence of atherosclerosis and mildly to moderately elevated lipid levels. For fatal or nonfatal myocardial infarction, there was a 62% reduction in events attributable to pravastatin (P = .001). This effect was evident in younger and older patients, men and women, and patients with and without histories of hypertension and prior infarction. There was a 46% reduction in all-cause mortality (P = .17), which, although not statistically significant, is consistent with the results of other statin trials. There also was a 62% reduction in the risk of fatal or nonfatal stroke (P = .054). CONCLUSIONS: These pooled results provide strong evidence that pravastatin reduces the risk of cardiovascular events in patients with atherosclerotic disease and mildly to moderately elevated lipid levels. The benefit for reducing myocardial infarction is evident in older and younger patients, men and women, and patients with and without histories of hypertension and prior infarction.

Age Factors↗
PubMed1995

An update on lipid-lowering therapy.

New information on the effects of lipid-lowering drugs is reviewed with an emphasis on special groups that benefit from specific drug therapy. Although it has been shown that the diet may further enhance the effectiveness of lipid-lowering drugs, compliance to diet and drugs remains an important issue and the large individual variations in dietary responses should be studied more extensively. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors are safe and effective in different populations such as in women, elderly people and in special cases of secondary hyperlipidaemia. More widespread implementation of screening programmes to identify suitable patients for lipid-lowering therapy may help prevent the excess utilization of health care resources.

Aged↗
PubMed1995

Angiographic trials of lipid-lowering therapy: an update.

The value of specific LDL apheresis in drug-resistant cases of hyperlipidaemia is reviewed, as well as new data on the prevention of new lesion formation, efficacy of therapy based on initial lipid levels, and the consequences of lipid lowering in the angioplasty setting. Studies undertaken in the carotid and femoral bed are included, as is a brief discussion of the use of probucol as an adjunct to lipid-lowering therapy. These studies have emerged on a backdrop of data focused more on reduction of clinical events than on morphologic changes. Studies on the clinical impact of lipid-lowering therapy are included to provide a linkage between the rationale and conclusions of the angiographic trials with the emerging demonstration that cholesterol lowering does indeed reduce both cardiovascular and total mortality without inducing significant noncardiovascular morbidity or mortality.

Arteriosclerosis↗