摘要:

Background This study aimed to determine if cholesterol-lowering therapy improves endothelium-dependent coronary vasomotion in patients with hypercholesterolemia.Methods and Results Nine patients with hypercholesterolemia were studied before and after cholesterol-lowering therapy with pravastatin (an inhibitor of HMG-CoA reductase) for 6+-3 months, which lowered serum cholesterol from 272+-8 to 187+-16 mg/dL (P<.01). Control patients with serum cholesterol of 218+-23 mg/dL also were studied twice in a similar interval (8+-2 months) with no cholesterol-lowering drugs. Acetylcholine (the endothelium-dependent vasodilator) and papaverine and nitrate (endothelium-independent vasodilators) were infused into the study coronary artery. Changes in the diameter of the epicardial coronary artery and coronary blood flow were assessed by quantitative coronary arteriography and an intracoronary Doppler catheter. In patients with hypercholesterolemia, acetylcholine-induced vasoconstriction of the epicardial artery was less (P<.05) and the acetylcholine-induced increases in coronary blood flow were greater (P<.001) after than before pravastatin. In control patients, responses of the epicardial coronary artery and coronary blood flow to acetylcholine did not change over the follow-up period. The vasomotor responses to papaverine or nitrate were similar between the two groups, and no interval changes in their responses were noted in either group.Conclusions These results suggest that cholesterol-lowering therapy with pravastatin may improve endothelium-dependent coronary vasomotion, which may possibly contribute to the improvement of myocardial perfusion as well as the regression of coronary atherosclerosis. (Circulation. 1994;89:2519-2524.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Abnormal vascular reactivity represents a fundamental disturbance in vascular biology with the development of atherosclerosis. Because endothelial vasodilator function plays a pivotal role in controlling vasomotor tone, we hypothesized that atherosclerotic wall thickening might directly interfere with deficient endothelium-mediated dilation and thereby contribute to the abnormal reactivity of atherosclerotic arteries in vivo.75th percentile) demonstrated a significantly blunted constrictor response to acetylcholine (P<.01 at the maximal acetylcholine concentration) compared with segments from patients with HDL cholesterol <75th percentile. The degree of constriction or dilation in response to the acetylcholine infusion correlated with the response to cold pressor testing (r=.75, P<.0001). Again, the cold pressor test-induced constrictor response was significantly (P<.05) blunted in segments from patients with elevated HDL cholesterol serum levels compared with those from patients with HDL cholesterol <75th percentile despite equal degrees of atherosclerotic wall thickening.Conclusions Coronary vasomotor responses to the endothelium-dependent dilator acetylcholine and to sympathetic stimulation by cold pressor test correlate with local atherosclerotic wall thickening. Thus, the degree of abnormal local vascular reactivity is closely related to the extent of atherosclerotic "plaque load" in human epicardial arteries in vivo. Elevated HDL cholesterol serum levels ameliorate abnormal vasoconstriction at any given extent of atherosclerotic wall thickening, suggesting that HDL cholesterol exerts a beneficial effect on abnormal vascular reactivity, a fundamental functional disturbance associated with coronary atherosclerosis. (Circulation. 1994;89:2525-2532.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background The objective of this study was to examine the relation of high-density lipoprotein cholesterol (HDL-C) to coronary heart disease in Japanese men whose serum total cholesterol is low by Western standards.=5.69 mmol/L (mean total cholesterol, 6.26 mmol/L).Conclusions Coronary heart disease incidence is inversely related to HDL-C in urban Japanese middle-aged men, whose mean total cholesterol (5.10 mmol/L) is relatively low. (Circulation. 1994;89:2533-2539.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background The purpose of the study was to examine the association between physical activity and 23-year incidence of coronary heart disease morbidity and mortality. This cohort study continues to follow 8006 Japanese-American men who were 45 to 68 years of age and living on Oahu, Hawaii, in 1965, for the development of coronary heart disease morbidity and mortality.Methods and Results The Framingham physical activity index was calculated by summing the product of average hours spent at each activity level and a weighting factor based on oxygen consumption. Study subjects were divided into tertiles of physical activity index at baseline. Relative risks and 95% confidence intervals (CI) for incidence of coronary heart disease morbidity and mortality were obtained using the Cox model. After age adjustment and using the lowest physical activity index tertile as a reference group, the relative risk for coronary heart disease incidence for the highest tertile of physical activity was 0.83 (CI, 0.70 to 0.99). After adjusting for age, hypertension, smoking, alcohol intake, diabetes, cholesterol, and body mass index, the relative risk was 0.95 and CI included 1 (CI, 0.80 to 1.14). For coronary heart disease mortality, the age-adjusted relative risk was 0.74 (CI, 0.56 to 0.97) and 0.85 (CI, 0.65 to 1.13) after risk factor adjustment.Conclusions The results suggest that the impact of physical activity index on coronary heart disease is mediated through its effects on hypertension, diabetes, cholesterol, and body mass index. These findings support the hypothesis that physical activity is inversely associated with coronary heart disease morbidity and mortality and suggest that physical activity interventions in middle-aged men, by improving cardiovascular risk factor levels, may have significant public health implications in the prevention of coronary heart disease. (Circulation. 1994;89:2540-2544.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Estrogen replacement therapy has been associated with a reduction in cardiovascular events in postmenopausal women. One of the mechanisms responsible may be a beneficial effect of estrogen on coronary vascular function. We therefore studied the short-term effects of estrogen on coronary artery dimensions and microvascular resistance in postmenopausal women.Methods and Results Twenty postmenopausal women 61+-7 years old participated in this study. Seven had angiographic evidence of atherosclerosis of the left coronary artery. Coronary artery diameters were measured by quantitative coronary angiography. Blood flow velocity was measured with a Doppler wire placed in a proximal left coronary artery segment. Left coronary artery infusions of acetylcholine (range, 10 sup -8 to 10 sup -5 mol/L estimated delivered concentrations) and of adenosine (n=18) and sodium nitroprusside (n=10) were performed before and during concomitant continuous intracoronary infusion of 17 beta -estradiol to test endothelium-dependent and independent vasodilation, respectively. Intracoronary infusion of estradiol increased coronary sinus estradiol levels from postmenopausal (16+-11 pg/mL) to premenopausal (282+-121 pg/mL) levels. Estradiol did not affect basal coronary artery diameter, blood flow, or resistance. Epicardial coronary artery constriction induced by acetylcholine infusion in the control study (maximum, 10+-15% from baseline) was prevented during repeat acetylcholine infusion with concomitant estradiol administration (P<.001). Estradiol potentiated the vasodilator coronary microvascular response to acetylcholine as manifest by significantly greater coronary flow (P<.001) and lower coronary resistance (P<.02). The reduction in coronary resistance from baseline in response to acetylcholine was significantly potentiated by estradiol (P=.01), with a mean decrease in coronary vascular resistance during acetylcholine infusion of 20+-38% before and 35+-33% during concomitant estradiol administration. The effect of estradiol on coronary dynamics was similar in women with and women without angiographically apparent left coronary artery atherosclerosis and was most prominent in women with the most impaired responses to acetylcholine at both the epicardial (r=-.72, P<.001) and microvascular (r=-.59, P=.006) coronary artery levels. In contrast, estradiol did not affect the coronary epicardial or microvascular vasodilator responses to adenosine or sodium nitroprusside.Conclusions Physiological levels of 17 beta -estradiol acutely and selectively potentiate endothelium-dependent vasodilation in both large coronary conductance arteries and coronary microvascular resistance arteries of postmenopausal women. This effect may contribute to the reduction in cardiovascular events observed with estrogen replacement therapy. (Circulation. 1994;89:2545-2551.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Regional Thallium-201 activity after resting injection, imaged early and after redistribution, reflects viable myocardium and can predict improved isotope uptake as well as regional and global ventricular function after revascularization. Technetium-99m-sestamibi, a perfusion tracer with favorable imaging characteristics, has distinct kinetics compared with Thallium-201, demonstrating minimal redistribution; this property may give Thallium-201 an advantage for detecting viable myocardium, particularly in segments with resting hypoperfusion. The purpose of this study was to compare regional activities of Thallium-201 and Technetium-99m-sestamibi after resting injections in patients with coronary artery disease and regional or global left ventricular dysfunction and to assess their comparative abilities for predicting recovery of severe regional ventricular dysfunction after revascularization.Methods and Results Qualitative and quantitative comparisons of rest and redistribution Thallium-201 activity and sestamibi activity 1 hour after rest injection were performed in 31 patients with coronary artery disease and left ventricular dysfunction. Quantitative analysis of three short-axis tomograms per patient was performed by use of circumferential profiles that allowed analysis of 12 segments per patient. Two-dimensional echocardiography was used to assess wall motion and thickening in segments corresponding to the single photon emission computed tomography data. Concordance between regional Thallium-201 activity at redistribution imaging and regional sestamibi activity by semiquantitative visual analysis demonstrated concordant regional activity in 87% of segments; among discordant segments, no significant skew was seen, indicating enhanced uptake of one agent over the other. Quantitative analysis for all segments showed significant correlation (r=.86, P<.001) between quantitative regional Thallium-201 redistribution activity and 1-hour post-rest injection sestamibi activity in individual segments. Eighteen of these patients were revascularized, and echocardiography was repeated 20+-16 days later; segments exhibiting significant regional ventricular dysfunction before revascularization were classified as having reversible or irreversible dysfunction on the basis of the change in wall motion and thickening. Thallium-201 and sestamibi regional activities were similar in those segments with reversible (72+-11% (percent of peak activity) versus 75+-9%, respectively, P=NS) as well as irreversible ventricular dysfunction (51+-11% versus 50+-8%, P=NS). Positive (75% versus 80% for Thallium-201 and sestamibi, respectively) and negative (92% versus 96%, respectively) predictive values for recovery of regional ventricular dysfunction after revascularization were similar for the two agents.Conclusions In patients with coronary artery disease and left ventricular dysfunction, quantified sestamibi activity 1 hour after rest injection parallels redistribution Thallium-201 activity after a resting injection, suggesting that uptake and subsequent handling of sestamibi are more complex than can be explained by a pure flow tracer with no redistribution. Quantitative analysis of regional activities of both Thallium-201 and sestamibi after resting injections can differentiate viable from nonviable myocardium, and the two agents comparably predict reversibility of significant regional wall motion abnormalities after revascularization in such patients to a similar degree. (Circulation. 1994;89:2552-2561.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Patency of the infarct-related artery (IRA) after acute myocardial infarction (AMI) may not reflect the magnitude of tissue perfusion. In animal models of AMI, myocardial cellular necrosis has been associated with extensive capillary damage. Because myocardial contrast echocardiography (MCE) can define the spatial distribution of microvascular perfusion, we hypothesized that it could be used in patients after recent AMI to distinguish myocardial regions that have an intact microvasculature and thus are viable from those without an intact microvasculature and thus are not viable.Methods and Results One hundred five patients with a recent AMI (range, 1 day to 4 weeks; median, 8 days) who were undergoing cardiac catheterization were included in the study. Two-dimensional echocardiography was performed at baseline and repeated 1 month later to assess regional function within the infarct zone (scores of 1 to 5 indicating normal to dyskinetic segments, respectively). MCE was performed in the cardiac catheterization laboratory to assess microvascular perfusion within the infarct bed. A contrast score index was derived by assigning scores to individual segments within the infarct zone (0, 0.5, and 1 denoting no, intermediate, and homogeneous contrast effect, respectively) and deriving the average score within the infarct bed. Revascularization was performed as clinically indicated. Although the baseline wall motion score and the contrast score index were similar in the 90 patients with a patent IRA and the 15 patients with an occluded IRA (median+-1 interquartile range, 3+-1 versus 3.5+-1; P=.41), wall motion score 1 month later was significantly better in those with open IRAs compared with those with closed IRAs (2+-2 versus 3+-2, P=.05). In the 90 patients with an open IRA, a strong correlation was noted between wall motion score 1 month later and the contrast score index (rho =-.64, P<.001). On multivariate analysis, the best correlate of the 1-month wall motion score was the contrast score index.Conclusions In patients studied in the cardiac catheterization laboratory between 1 day and 4 weeks after AMI, an intact microvasculature as identified by MCE indicates myocardial regions that improve function 1 month later. This study demonstrates that microvascular patency is closely associated with myocardial cellular viability after AMI in humans. (Circulation. 1994;89:2562-2569.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Previous postmortem studies have demonstrated compensatory enlargement of atherosclerotic arteries in animal models and patients. Conclusions regarding these changes were drawn based on a comparison of the dimensions of diseased arteries in one group of subjects with the dimensions of normal arteries in another group. This method admits potential confounding variables, such as demographics and other disease states, which might also have an impact on arterial size.Methods and Results Using intravascular ultrasound, we studied a total of 62 paired, adjacent normal and diseased sites in the superficial femoral arteries of 20 patients undergoing peripheral vascular interventions. Morphological assessment was performed using a computer-based image analysis system. Measurements were made of the cross-sectional area of the arterial lumen, the atherosclerotic plaque, and the outer border of the artery. These dimensions were then compared to determine the effects of progressive atherosclerosis on arterial morphology. Luminal cross-sectional area decreased from 21.1+-2.2 mm2in normal segments to 16.7+-0.8 mm2(P=.0001) in adjacent atherosclerotic segments. Similarly, minimal luminal diameter decreased from 5.7+-0.2 to 5.0+-0.1 mm2, and maximal luminal diameter decreased from 6.2+-0.2 to 5.7+-0.2 mm2. At these same sites, total arterial area was 32.9+-1.6 and 37.9+-1.9 mm2(P=.0001) in normal and diseased segments, respectively. Minimal and maximal arterial diameters demonstrated similar increases (7.3+-0.2 to 7.7+-0.2 mm2(P=.0015) and 7.6+-0.2 to 8.3+-0.2 mm2(P=.0001), respectively). Regression analysis disclosed correlation of the cross-sectional area of plaque to the total arterial area (R=.70, P=.0001).Conclusions Human arteries enlarge in response to progressive atherosclerosis. This compensatory mechanism results in an increase in arterial size that is proportionate to the cross-sectional area of plaque that has accumulated in the vessel. Intravascular ultrasound demonstrates that this process is focal compensatory enlargement at discrete sites of atherosclerotic narrowing immediately adjacent to more normal areas in which arterial size is smaller. (Circulation. 1994;89:2570-2577.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background From pathological studies of coronary arteries, it has been recognized that progressive plaque development may be compensated for by an increase of the arterial diameter. However, the dynamics of this process have not been investigated, and it is not known whether compensatory dilatation is a general pathomechanism in human arteries.Methods and Results Using a high-resolution duplex scanner and subsequent three-dimensional plaque reconstruction, we prospectively studied the effect of carotid plaque development on the vascular geometry in 32 patients at 6- to 12-month intervals. Plaque progression in 41% (n=26) of studies was associated with an increase of the vessel diameter between 0.4 and 1.2 mm in 76% (n=20). Among 36 unchanged plaque developments, enlargement of the arterial diameter was assessed in only 28% (n=10) (P<.001).Conclusions Our data suggest that increasing plaque volume is significantly associated with enlargement of carotid artery segments, which compensates for arterial narrowing in early stages of the disease. (Circulation. 1994;89:2578-2581.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Enteroviral RNA sequences have been demonstrated in the myocardium of patients with myocarditis or dilated cardiomyopathy from presentation to end-stage disease. The prognosis of heart muscle disease has not previously been evaluated in relation to the detection of enterovirus in myocardial biopsy tissue.Methods and Results We studied 123 consecutive patients with heart muscle disease prospectively. Multiple endomyocardial biopsy samples taken from all patients during diagnostic cardiac catheterization were classified histologically and were examined for enteroviral RNA by use of an enterovirus group-specific hybridization probe. Three enterovirus-negative patients with cardiac amyloidosis were excluded from subsequent analysis. Enteroviral RNA sequences were detectable in 41 (34%) of the remaining 120 patients (group A), while 79 (66%) had no virus detected (group B). The groups did not differ significantly in age, sex, symptomatic presentation, or hemodynamic characteristics; duration of symptoms was significantly shorter in group A (7.8+-9.6 versus 14.9+-19.0 months, P<.05). At follow-up (mean, 25 months; range, 11 to 50 months), patients from group A had an increased mortality compared with those in group B (25% versus 4%, respectively; P=.02). Mortality was also statistically greater in patients with symptomatic cardiac failure (P=.02), those with elevated left ventricular end-diastolic pressures (P=.03), and those in New York Heart Association functional classes III and IV (P=.05). Multivariate regression analysis, however, showed that only the presence of enterovirus RNA and symptomatic heart failure were of independent prognostic value.Conclusions These data demonstrate that the detection of enterovirus RNA in the myocardium of patients with heart muscle disease at the time of initial investigation is associated with an adverse prognosis and that the presence of enterovirus RNA is an independent predictor of clinical outcome. (Circulation. 1994;89:2582-2589.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID