摘要:

Background The pathomorphological substrate of complicated coronary atherosclerotic lesions underlying unstable angina is characterized by a localized chronic inflammatory process. Functionally, coronary lesions associated with unstable angina demonstrate an enhanced vasoreactivity. Endothelin-1 is a potent vasoconstrictor peptide produced not only by endothelial cells but also by macrophages and polymorphonuclear leukocytes, the cell types characteristic of inflammation.Methods and Results By use of immunohistochemical techniques, we examined the presence of endothelin-1 in coronary atherosclerotic plaque tissue obtained by directional coronary atherectomy of primary lesions from 50 consecutive patients. The tissue specimens of 43 of 50 patients (86%) demonstrated endothelin-1-like immunoreactivity. Endothelin-1-like immunoreactivity preferentially localized to macrophage-rich areas, to hypercellular regions rich in microvessels, and to plaque areas with evidence of prior hemorrhage. Double-immunolabeling revealed that both macrophages (HAM56 positive) and intimal smooth muscle cells (alpha -actin positive) demonstrated cytoplasmic immunostaining for endothelin-1. Semiquantitative analysis of endothelin-1-like immunostaining revealed significantly (P<.005) higher staining grades in active (1.86+-0.15, n=40) compared with nonactive lesions (0.78+-0.35, n=10): endothelin-1 staining grades were significantly (P<.001) lower in patients with stable angina (0.69+-0.19, n=13) than in patients with crescendo angina (1.82+-0.30, n=11), with angina at rest (2.08+-0.21, n=12), or with angina after myocardial infarction (2.0+-0.26, n=14).Conclusions Endothelin-1 immunostaining of atherosclerotic tissue localizes predominantly with plaque components indicative of chronic inflammatory processes. The increased tissue endothelin-1-like immunoreactivity in active coronary atherosclerotic lesions may provide a clue to the mechanisms of increased vasoreactivity of the culprit lesion in acute ischemic syndromes, which is the clinical substrate of the active coronary atherosclerotic plaque. (Circulation. 1995;91:941-947).

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background The mechanisms underlying rapid angiographic progression of coronary artery disease are still unknown. Intravascular thrombosis with or without plaque rupture may be involved.=25 mg/dL were found in 14 of 21 patients (67%) with rapid progression of coronary artery disease but in only 19 of 58 (33%) in the group without progression (P=.007). The respective median Lp(a) concentrations were 66 mg/dL (range, 2 to 139) and 13 mg/dL (range, 2 to 211; P=.01).Conclusions Lp(a) appears to be a risk factor for the rapid angiographic progression of coronary artery disease. The pathophysiological link between Lp(a) and rapid progression may be an interference with thrombolysis through the partial structural homology of Lp(a) with plasminogen. (Circulation. 1995;91:948-950).

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background A positive association was previously reported between angiotensin-converting enzyme (ACE) gene polymorphism and several cardiovascular diseases, such as myocardial infarction, left ventricular hypertrophy, and restenosis after percutaneous transluminal coronary angioplasty. Plasma ACE activity and carotid-wall thickening measured by ultrasonography were related, and it was postulated that long-term exposure to high levels of plasma ACE could be involved in structural changes of the arterial wall. In addition, angiotensinogen gene mutation was recently reported to be associated with essential hypertension and preeclampsia. There exists a possibility that the renin-angiotensin system plays an important role in the progress of cardiovascular diseases in humans. Therefore, we examined the association between the molecular variant of the angiotensinogen gene and coronary atherosclerosis.25% luminal diameter obstruction on average according to multiple coronary angiographic views. Angiotensinogen gene molecular variants were designated AA, Aa, and aa. The a allele indicated thymine-cytosine transition at nucleotide 704 in exon 2. Genomic DNA was extracted from peripheral blood leukocytes. Polymerase chain reaction was performed to amplify the concerned region of the angiotensinogen gene. After restriction enzyme digestion, it was possible to distinguish the molecular variant of the angiotensinogen gene. The frequencies of these genotypes were 7.3%, 26.8%, and 65.9% in the patients and 18.8%, 31.9%, and 49.3% in the control subjects for the AA, Aa, and aa allelles, respectively. There was an excess in the a allele among patients (P<.01).Conclusions We found a significant association between coronary atherosclerosis and a molecular variant of the angiotensinogen gene. The results suggested that the molecular variant of the angiotensinogen gene could be a new risk factor for coronary atherosclerosis. (Circulation. 1995;91:951-954).

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Mutations of mitochondrial DNA have been demonstrated as causes of human mitochondrial diseases. While these disorders typically involve multiple organs, the effect of mitochondrial mutations on the heart has not been systematically studied.Methods and Results We studied mitochondrial mutations and cardiac changes in 17 patients with Kearns-Sayre syndrome; ocular myopathy; myoclonus epilepsy with ragged red fibers (MERRF); and mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). Cardiac involvement was evaluated by chest radiograph, ECG, His-bundle electrogram, and echocardiogram. All 3 patients with Kearns-Sayre syndrome had large deletions of mitochondrial DNA and disturbances in cardiac conduction. ECG abnormalities were found in 2 of 6 patients with ocular myopathy who showed large deletions of mitochondrial DNA. All 3 patients with MERRF had an A-to-G mutation at nucleotide position 8344; 2 had cardiomegaly, asymmetrical septal hypertrophy, and diffuse hypokinesis of the left ventricle. One patient with asymmetrical septal hypertrophy developed dilated cardiomyopathy 2 years later. All 5 patients with MELAS had an A-to-G mutation at nucleotide position 3243, and 2 had symmetrical left ventricular hypertrophy with or without abnormal wall motion.Conclusions The clinical features of cardiac involvement in mitochondrial diseases vary in the different subgroups of these disorders. Particular mitochondrial mutations can cause characteristic cardiac abnormalities. (Circulation. 1995;91:955-961).

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Amyloidosis is a disorder of protein metabolism characterized by extracellular accumulation of abnormal protein fibrils. Different proteins form the fibrils in different forms of the disease, and the condition can be acquired or hereditary. Involvement of the heart is quite common, producing a serious and usually fatal cardiomyopathy. Cardiac amyloidosis is often diagnosed late, and cardiac biopsy together with proper histological examination is essential. Contrary to previous perceptions, there is much recent evidence of effective treatment for several different types of systemic and cardiac amyloidosis, including the most common hereditary form caused by mutations in the transthyretin gene. Chemical and genetic typing of amyloid is therefore of considerable clinical importance.Methods and Results Seven members in two generations of an Italian family presented with cardiac disease inherited as an autosomal dominant and were found to have systemic amyloidosis. Angina pectoris-like pain, an unusual feature in cardiac amyloidosis, was a prominent symptom, possibly related to partial obliteration of the distal coronary arteries by amyloid infiltration. There were also cases of sudden cardiac death. Peripheral and autonomic neuropathy, which are the usual features of hereditary amyloidosis, were present in only two cases, and a diagnosis of acquired, immunoglobulin light chain (AL type) amyloidosis was suspected in the index case before the family history emerged. In fact, the amyloid fibrils were composed of transthyretin, and the two affected individuals from whom DNA was available were both heterozygotes for a single base change in exon 3 of the transthyretin gene, encoding substitution of Lys for the wild-type Thr residue at position 59 in the mature protein. This mutation has not previously been reported.Conclusions We have identified a novel mutation in the transthyretin gene encoding 59 sup Thr(arrow right)Lys associated with autosomal dominant hereditary systemic amyloidosis in an Italian kindred in whom cardiac involvement was the major feature. This family illustrates the difficulty in diagnosis of cardiac amyloid, the variable clinical phenotype in hereditary amyloidosis even within a family, and the importance of precise fibril typing for correct management in this condition. (Circulation. 1995;91:962-967).

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Restenosis rates are high when coronary angioplasty is performed in patients with unstable angina. The relative contributions of local and systemic factors to this excess risk of restenosis are unclear. To assess these, we compared changes in minimal lumen diameter and the incidence of restenosis, determined by quantitative coronary angiography, after coronary angioplasty at culprit and nonculprit lesions dilated in the course of a single procedure in patients with unstable angina.50% stenosis at follow-up), restenosis occurred at 67% of culprit lesions and at 32% of nonculprit lesions (P<.01).Conclusions The greater loss in minimal lumen diameter and the consequent higher rate of restenosis at culprit compared with nonculprit lesions suggest that local "lesion-related" factors are an important determinant of the high rate of restenosis when coronary angioplasty is performed in patients with unstable angina. (Circulation. 1995;91:968-972).

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Intermittent transdermal nitroglycerin therapy is effective in the treatment of stable angina and prevents the development of tolerance. Previous investigations have suggested that removal of nitroglycerin patches may be associated with a decrease in anginal threshold. This study examines the effect of nitroglycerin patch removal on anginal threshold in a group of patients with stable angina.Methods and Results Twelve patients with stable angina were enrolled in a randomized, double-blind, placebo-controlled, crossover study. These patients had reproducible treadmill walking times and were taking no other long-acting antianginal medications or vasodilators. They received 0.8 mg/h transdermal nitroglycerin or wore a matching placebo patch for 5 to 7 days and then crossed over to the other treatment arm of the study. Transdermal nitroglycerin was applied at 8:00 pm and removed at 8:00 am each day. On the last day of each treatment period, patients underwent treadmill exercise testing at 8:00 am (before patch removal) and at 2, 4, and 6 hours after patch removal. The primary end point was the treadmill walking time until moderate angina (P2). Other end points included the treadmill walking time until onset of angina (P1), the amount of ST segment depression at P1 and P2, and treadmill walking time until the development of 1 mm ST depression. Heart rate, systolic blood pressure, and the rate-pressure product were determined at rest before exercise and at P1 and P2. At 8:00 am P1 and P2 were not significantly affected by active nitroglycerin compared with placebo, indicating the development of tolerance. Removal of the active transdermal nitroglycerin patch was associated with a significant decrease in the time to P1 at 2, 4, and 6 hours after patch removal compared with placebo. There was also a decrease in the time to P2 after active patch removal that was statistically significant compared with placebo at 2 and 4 hours and was of borderline significance at 6 hours. There were no differences in heart rate, blood pressure, or amount of ST segment depression at either P1 or P2 after active compared with placebo patch removal.Conclusions In patients with stable angina pectoris, intermittent transdermal nitroglycerin therapy is associated with a decrease in anginal threshold for 4 to 6 hours after patch removal. Although the cause of this phenomenon remains uncertain, it may be due to counterregulatory responses that develop during nitroglycerin patch application. (Circulation. 1995;91:973-978).

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Although patients with diabetes mellitus constitute an important segment of the population undergoing coronary angioplasty, the outcome of these patients has not been well characterized.Methods and Results Data for 1133 diabetic and 9300 nondiabetic patients undergoing elective angioplasty from 1980 to 1990 were analyzed. Diabetics were older and had more cardiovascular comorbidity. Insulin-requiring (IR) diabetics had diabetes for a longer duration and worse renal and ventricular functions compared with non-IR subjects. Angiographic and clinical successes after angioplasty were high and similar in diabetics and nondiabetics. In-hospital major complications were infrequent (3%), with a trend toward higher death or myocardial infarction in IR diabetics. Five-year survival (89% versus 93%) and freedom from infarction (81% versus 89%) were lower, and bypass surgery and additional angioplasty were required more often in diabetics. In diabetics, only 36% survived free of infarction or additional revascularization compared with 53% of nondiabetics, with a marked attrition in the first year after angioplasty, when restenosis is most common. Multivariate correlates of decreased 5-year survival were older age, reduced ejection fraction, history of heart failure, multivessel disease, and diabetes. IR diabetics had worse long-term survival and infarction-free survival than non-IR diabetics.Conclusions Coronary angioplasty in diabetics is associated with high success and low complication rates. Although long-term survival is acceptable, diabetics have a higher rate of infarction and a greater need for additional revascularization procedures, probably because of early restenosis and late progression of coronary disease. The most appropriate treatment for these patients remains to be determined. (Circulation. 1995;91:979-989).

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Both thallium scintigraphy and dobutamine echocardiography have been used to assess myocardial viability. However, thallium uptake and the inotropic response to dobutamine are expressions of different cellular phenomena. The present study was undertaken to investigate the relation between the two methods in patients with chronic coronary artery disease and left ventricular dysfunction to derive insights into the mechanisms related to myocyte viability.Methods and Results Thirty patients (28 men and 2 women; age, 59+-10 years) with chronic coronary artery disease and impaired left ventricular systolic function at rest (mean ejection fraction, 32+-9%) were included in the study. Patients underwent transesophageal echocardiography during incremental doses of dobutamine from 2.5 to a maximum of 40 micrograms x kg sup -1 x min sup -1 and single photon emission computed tomographic thallium scintigraphy using a stress-redistribution-reinjection protocol. The left ventricle was divided into 16 segments for analysis of echocardiographic and thallium images. Segmental myocardial contractile function was graded as normal, hypokinesis, akinesis, or dyskinesis at each incremental dose of dobutamine. Thallium uptake in each myocardial segment was graded on a 5-point scale from 0 (absent) to 2 (normal) for each of the stress, redistribution, and reinjection images. A segment was considered viable if the assigned thallium score was 1 or higher (normal uptake or only mild to moderate defect) in any of the stress, redistribution, or reinjection images. Among 472 myocardial segments available for analysis, 311 had resting wall motion abnormalities, of which 56% (173/311) showed contractile improvement with dobutamine (usually first observed at <=10 micrograms x kg sup -1 x min sup -1) and 84% (262/311) were considered viable by thallium scintigraphy (P<.0001). Of the 262 segments considered viable by thallium, 167 (64%) had a contractile improvement with dobutamine; in contrast, only 6 of the 49 segments (12%) considered nonviable by thallium had a positive dobutamine response (P<.0001). Furthermore, a positive inotropic response to dobutamine was significantly related to the magnitude of thallium uptake: the proportion of segments with a positive dobutamine response rose with increasing magnitude of thallium uptake (P<.001). The disagreement between the two tests was related primarily to segments considered viable by thallium that did not show contractile improvement with dobutamine.Conclusions These findings demonstrate the existence of a relation between thallium uptake and the inotropic response to dobutamine in patients with chronic coronary artery disease and left ventricular dysfunction. However, the proportion of segments showing a positive response to dobutamine is significantly lower than those with thallium uptake, suggesting that the cellular mechanisms responsible for a positive inotropic response to adrenergic stimulation require a higher degree of myocyte functional integrity than those responsible for thallium uptake. (Circulation. 1995;91:990-998).

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background We previously reported that major depression in patients in the hospital after a myocardial infarction (MI) substantially increases the risk of mortality during the first 6 months. We examined the impact of depression over 18 months and present additional evidence concerning potential mechanisms linking depression and mortality.=10 per hour (odds ratio, 29.1; 95% CI, 6.97 to 122.07; P<.00001).=10 PVCs per hour. This result is compatible with the literature suggesting an arrhythmic mechanism as the link between psychological factors and sudden cardiac death and underscores the importance of developing screening and treatment programs for post-MI depression. (Circulation. 1995;91:999-1005).

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID