ISSN:0009-7322    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background The cytoskeleton plays an important role in maintaining cell structure and integrity. Defects in cytoskeletal proteins can cripple cell strength and may cause cardiomyopathy. We analyzed heart tissues from subjects with dilated cardiomyopathy for abnormalities in the cardiac cytoskeleton. Metavinculin, a cardiac isoform of the cytoskeletal protein vinculin, connects actin microfilaments to the intercalated disk and membrane costameres of the heart.Methods and Results Metavinculin and vinculin transcripts and protein were analyzed by polymerase chain reaction (PCR) and Western blotting. Thirty-three human heart specimens were studied, including 5 normal controls, 4 subjects with ischemic cardiomyopathy, 1 with X-linked cardiomyopathy, and 23 with idiopathic dilated cardiomyopathy (IDC). PCR of cardiac cDNA detected absence of the metavinculin transcript in cardiac tissue from a subject with IDC. PCR of genomic DNA showed that the metavinculin exon was present but not utilized in the cardiac transcript. Western blot analysis demonstrated absence of metavinculin protein in the heart from this subject. Immunostaining of cardiac vinculin in this heart showed disorganized intercalated disk structures. Metavinculin deficiency was associated with normal cardiac expression of the cytoskeletal proteins vinculin, alpha-actinin, and dystrophin. Normal metavinculin expression in the other heart specimens suggests that the defect is specific in the IDC subject identified.Conclusions These results demonstrate an association between metavinculin deficiency and dilated cardiomyopathy due to a defect in alternative mRNA splicing. (Circulation. 1997;95:17-20.)

ISSN:0009-7322    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background Hyperhomocysteinemia has been substantiated as a risk factor for occlusive vascular disease. A common mutation (nucleotide 677 C[right arrow]T) has been described recently in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, which results in a valine for alanine substitution, a thermolabile enzyme, and a tendency to elevate plasma homocysteine levels and which has been proposed to contribute importantly to coronary artery disease.50% diameter obstruction, prior myocardial infarction, or restenosis after coronary angioplasty. Plasma folate concentrations in control subjects (n = 90) and patients (n = 208) showed closely similar distributions.Conclusions Although it is accepted that moderate hyperhomocysteinemia significantly increases the risk for coronary, cerebrovascular, and peripheral vascular diseases, our data suggest that a mutation of the MTHFR gene, which has been associated with a thermolabile form of the enzyme and with hyperhomocysteinemia in subjects with plasma folate below the median, does not appear to be significantly associated with risk for premature coronary artery disease or for restenosis after coronary angioplasty. (Circulation. 1997;95:21-23.)

ISSN:0009-7322    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background The aim of the present study was to estimate the cost-effectiveness of populationwide approaches to reduce serum cholesterol levels in the US adult population.Methods and Results This cost-effectiveness analysis was made from data from the literature and the Coronary Heart Disease Policy Model and was based on the US population age 35 to 84 years. Study interventions were populationwide programs to reduce serum cholesterol levels with costs and cholesterol-lowering effects similar to those reported from the Stanford Three-Community Study, the Stanford Five-City Project, and in North Karelia, Finland. The main outcome measures were cost-effectiveness ratios, defined as the change in projected cost divided by the change in projected life-years when the population receives the intervention compared with the population without the intervention. A populationwide program with the costs ($4.95 per person per year) and cholesterol-lowering effects (an average 2% reduction in serum cholesterol levels) of the Stanford Five-City Project would prolong life at an estimated cost of only $3200 per year of life saved. Under a wide variety of assumptions, a populationwide program would achieve health benefits at a cost equivalent to that of many currently accepted medical interventions. Such programs would also lengthen life and save resources under many scenarios, especially if the program affected persons with preexisting heart disease or altered other coronary risk factors.Conclusions Populationwide programs should be part of any national health strategy to reduce coronary heart disease. (Circulation. 1997;95:24-30.)

ISSN:0009-7322    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background Smoking is a major risk factor for cardiovascular morbidity and mortality. Because previous studies have shown that smoking affects vasomotor response, we hypothesized that smoking may also acutely alter aortic elastic properties.Methods and Results We studied 40 male current and long-term smokers who underwent diagnostic cardiac catheterization for chest-pain evaluation. Twenty subjects (age, 48 +/- 2 years, mean +/- SEM) were randomly assigned to smoking and 20 (age, 47 +/- 2 years) to sham smoking studies. Aortic elastic properties were studied with the determination of the aortic pressure-diameter relation before smoking, every minute for the first 5 minutes after the initiation of smoking or sham smoking, and every 5 minutes for the following 15 minutes. Instantaneous diameter of the thoracic aorta was measured with a special ultrasonic dimension catheter developed in our laboratory and previously validated. Instantaneous aortic pressure was measured at the same site as was diameter with a Millar micromanometer. Smoking was associated with significant changes in the aortic pressure-diameter relation that denote deterioration of the elastic properties and were maintained during the whole study period: the slope of the pressure-diameter loop became steeper (baseline, 35.43 +/- 1.38; minute 1, 45.26 +/- 1.65; peak at minute 10, 46.36 +/- 1.69 mm Hg/mm; P <.001) and aortic distensibility decreased (baseline, 2.08 +/- 0.12; minute 1, 1.60 +/- 0.08; nadir at minute 5, 1.54 +/- 0.07 x 10 sup -6 cm2[center dot] dyne sup -1; P < .001). In contrast, no changes in aortic elasticity indexes were observed with sham smoking.Conclusions Smoking is associated with an acute deterioration of aortic elastic properties. This effect of smoking may contribute to the unfavorable consequences of smoking on the cardiovascular system. (Circulation. 1997;95:31-38.)

ISSN:0009-7322    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background Oral estrogen replacement therapy (ERT) is known to stimulate the synthesis of angiotensinogen. The effects of such therapy on renin, ACE, and aldosterone are less clear. This seems noteworthy, however, since further activation of the system could be disadvantageous to postmenopausal women who replace estrogen in the context of heart failure, coronary artery disease, or hypertension.Methods and Results Estrogen status and components of the renin-angiotensin system were examined in a population-based sample of postmenopausal women and age-matched men. Renin was quantified immunoradiometrically, ie, independent of substrate abundance; aldosterone, angiotensinogen, and ACE activity were determined by standard methods. Renin levels were lower in women with ERT (n = 107; 12.0 +/- 0.7 mU/L) compared with women without ERT (n = 223; 16.6 +/- 0.9 mU/L; P = .001) or men (n = 342, 20.5 +/- 1.5 mU/L, P < .0001). In contrast, angiotensinogen was higher in women with ERT (1.36 +/- 0.08 mg/L) compared with women without ERT (1.03 +/- 0.02 mg/L; P < .0001) or compared with men (0.97 +/- 0.01 mg/L; P < .0001). Renin suppression was seen with either oral or transdermal estrogen replacement (-30% and -31%, respectively; both P < .001). In contrast, the increase of angiotensinogen was limited to women taking oral estrogens (+58%, P < .001). Multivariate analysis revealed that these estrogen effects were independent of age, body mass index, blood pressure, and/or antihypertensive medication. Finally, only marginal differences between groups were observed for serum ACE activity and aldosterone.Conclusions Aside from a well-documented induction of angiotensinogen, ERT is related to a substantial suppression of renin, a phenomenon that might have received little attention because of widely used indirect measurements of the hormone. (Circulation. 1997;95:39-45.)

ISSN:0009-7322    

出版商:OVID    

年代:1997

数据来源: OVID