ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Abstract—Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term “vulnerable patient” may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document focuses on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—This study was aimed at verifying whether activation of platelets might represent a source of interleukin (IL)-1&bgr; levels in hypercholesterolemia. To this purpose, we compared the effects of a short-term treatment with simvastatin or low-dose aspirin on circulating levels of this cytokine.Methods and Results—Fifty patients with hypercholesterolemia were randomly allocated to receive an 8-week therapeutic course of simvastatin 20 mg daily (n=25) or aspirin 100 mg daily (n=25). Baseline soluble (s) P-selectin directly correlated with IL-1&bgr; (P<0.0001) and C-reactive protein (CRP) (P<0.05) but not with von Willebrand factor, total cholesterol, or LDL cholesterol levels. Furthermore, sP-selectin (P<0.02) and IL-1&bgr; (P<0.0001) levels were independently related to CRP by multiple regression analysis. Both drugs were associated with comparable, significant reductions in IL-1&bgr; and sP-selectin. Simvastatin, but not aspirin treatment, significantly lowered CRP levels (P<0.05). The change in IL-1&bgr; levels correlated with the change in sP-selectin in patients randomized to either simvastatin (Rho, 0.42;P<0.05) or aspirin (Rho, 0.42;P<0.05). In contrast, the simvastatin-induced change in IL-1&bgr; did not correlate with the change in CRP levels.Conclusions—This study suggests that platelets might contribute to IL-1&bgr; production in hypercholesterolemia, thus providing an additional link between inflammation and the prothrombotic state in this setting.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—In addition to being a risk marker for cardiovascular disease, much recent data suggest that C-reactive protein (CRP) promotes atherogenesis. Decreased endothelial NO and prostacyclin (PGI2) contribute to a proatherogenic and prothrombotic state. We have shown that CRP decreases endothelial NO synthase expression and bioactivity in human aortic endothelial cells (HAECs). PGI2is a potent vasodilator and inhibitor of platelet aggregation. Hence, the aim of this study was to examine the effect of CRP on PGI2release from HAECs and human coronary artery endothelial cells (HCAECs).Methods and Results—HAECs and HCAECs were incubated with human CRP (0 to 50 &mgr;g/mL for 24 hours). The release of PGF-1&agr;, a stable product of PGI2, was also assayed in the absence and presence of a potent agonist, A23187. CRP significantly decreased PGF-1&agr; release from HAECs under basal (48% decrease,P<0.001; n=5) and stimulated (26% decrease,P<0.01; n=5) conditions. CRP had no effect on PGI2synthase (PGIS) mass. By increasing both superoxide and inducible NO synthase, CRP resulted in increased nitration of PGIS by peroxynitrite. The increased nitration and decreased activity of PGIS by CRP was reversed with peroxynitrite scavengers.Conclusions—Thus, CRP decreases PGI2release from HAECs by inactivating PGIS via nitration, additionally contributing to its atherogenicity.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Several enzymes that hydrolyze angiotensin I (Ang I) and Ang II to Ang-(1-7) have been identified, but their relative importance in the intact human heart is not known.Methods and Results—Intracoronary (IC)123I-Ang I was administered to 4 heart transplantation recipients. Arterial and coronary sinus (CS) samples were taken before and after coadministration of IC enalaprilat.123I-Ang metabolites were separated by high-pressure liquid chromatography, and123I-Ang-(1-7) and123I-Ang II were quantified across the myocardial circulation.123I-Ang II formation (as measured by fractional conversion) at steady state was 0.43±0.05 and was reduced to 0.042±0.02 after IC enalaprilat (P<0.01). The fractional conversion of123I-Ang-(1-7) was 0.198±0.032 but was reduced to 0.06±0.01 during IC enalaprilat (P<0.01). Net Ang II production at steady state was 2720±704 pg/min. Ang-(1-7) production was 3489±768 pg/min. After IC enalaprilat, Ang II production fell to 436±66.8 pg/min (P<0.05 versus Ang II production). After suppression of Ang II production with enalaprilat, there was net uptake of Ang-(1-7): −289±144 pg/min (P<0.05).Conclusions—Ang-(1-7) was formed in the intact human myocardial circulation and was decreased when Ang II formation was suppressed. These data indicate that the major pathway for Ang-(1-7) generation in the intact human heart was dependent on substrate availability of Ang II. Ang-(1-7)–forming enzymes that demonstrate substrate preference for Ang II are likely to play an important role in the regulation of Ang-(1-7) formation in the intact human heart.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—We studied the benefits and risks of adding clopidogrel to different doses of aspirin in the treatment of patients with acute coronary syndrome (ACS).Methods and Results—In the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial, 12 562 patients with ACS using aspirin, 75 to 325 mg daily, were randomized to clopidogrel or placebo for up to 1 year. In this analysis, patients were divided into the following 3 aspirin dose groups: ≤100 mg, 101 through 199 mg, and ≥200 mg. The combined incidence of cardiovascular death, myocardial infarction, or stroke was reduced by clopidogrel regardless of aspirin dose, as follows: ≤100 mg, 10.5% versus 8.6% (relative risk [RR], 0.81 [95% CI, 0.68 to 0.97]); 101 to 199 mg, 9.8% versus 9.5% (RR, 0.97 [95% CI 0.77 to 1.22]); and ≥200 mg, 13.6% versus 9.8% (RR, 0.71 [95% CI, 0.59 to 0.85]). The incidence of major bleeding increased with increasing aspirin dose both in the placebo group (1.9%, 2.8%, and 3.7%, respectively;P=0.0001) and the clopidogrel group (3.0%, 3.4%, and 4.9%, respectively;P=0.0009); thus, the excess risk with clopidogrel was 1.1%, 1.2%, and 1.2%, respectively. The adjusted hazard ratio for major bleeding for the highest versus the lowest dose of aspirin was 1.9 (95% CI 1.29 to 2.72) in the placebo group, 1.6 (95% CI 1.19 to 2.23) in the clopidogrel group, and 1.7 (95% CI 1.36 to 2.20) in the combined group.Conclusions—In patients with ACS, adding clopidogrel to aspirin is beneficial regardless of aspirin dose. Bleeding risks increase with increasing aspirin dose, with or without clopidogrel, without any increase in efficacy. Our findings suggest that the optimal daily dose of aspirin may be between 75 and 100 mg, with or without clopidogrel.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Despite diffuse effects of sex hormones on the cardiovascular system, few prospective studies have examined the relationship of plasma androgens and estrogens with risk of cardiovascular disease (CVD) in postmenopausal women.Methods and Results—A nested case-control study was performed among women in the Women’s Health Study. Two hundred women who developed CVD were matched 1:1 by age, smoking, and postmenopausal hormone therapy (HT) to controls who remained free of CVD. We measured testosterone, estradiol, and sex hormone binding globulin (SHBG) levels and calculated free androgen index (FAI), free estradiol index, and the FAI/free estradiol index ratio. Results were stratified by HT use. Among HT nonusers, cases had significantly higher androgen profiles (higher median FAI and lower SHBG levels) than controls. After adjustment for age, smoking, use of aspirin, vitamin E, and alcohol, family history of myocardial infarction, and physical activity, nonusers in the lowest SHBG quartile had an OR of 2.25 (95% CI, 1.03 to 4.91) for CVD, and there were significant trends across FAI quartiles (Pfor trend=0.03). Additional adjustment for body mass index, hypertension, diabetes, and elevated cholesterol eliminated associations with SHBG and FAI. Among women using HT, no significant differences in hormones or SHBG were observed among women who developed CVD and controls.Conclusions—Among HT nonusers, lower SHBG and higher FAI levels were noted among postmenopausal women who developed CVD events, but this was not independent of body mass index and other cardiovascular risk factors. Estradiol levels were not associated with risk of CVD in HT users or nonusers.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Functional status and quality of life are important outcomes in the evaluation of revascularization approaches for symptomatic coronary artery disease. Few data are available regarding the comparative improvement in disease-specific health status after CABG versus percutaneous coronary intervention (PCI) in the era of coronary stenting.Methods and Results—Cardiac-specific health status was evaluated at baseline and at 6 and 12 months after intervention with the Seattle Angina Questionnaire (SAQ) in patients randomized to stent-assisted PCI (n=488) versus CABG (n=500) in the Stent or Surgery trial. Scores for physical limitation, angina frequency, and quality of life improved significantly for both treatment groups at 6 months (range of improvement from 13.6 to 34.7 points) and 12 months (14.3 to 38.2 points; allP<0.001). CABG patients had greater improvement than those assigned to PCI, although the magnitude of the difference decreased over time (difference at 6 months, 4.03 to 6.48 points; 12 months, 2.05 to 2.93 points). A component of this reduction is accounted for by PCI-arm patients who required repeat intervention. Differences between treatment groups were greatest for the 6-month angina frequency scores (difference=6.48 points; 95% CI 3.96 to 8.99). Overall, treatment satisfaction was high and did not differ significantly between groups.Conclusions—Both CABG and stent-assisted PCI dramatically improved cardiac-related health status in patients with multivessel disease at 6- and 12-month follow-up. During the first postprocedure year, patients’ angina burden and physical limitations were alleviated to a greater extent with CABG.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID