Myocardial infarction and the open-artery hypothesis.
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Biomedical subjects
Publications and source records attributed to Richard A Lange.
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Despite aspirin's and clopidogrel's proven benefit in reducing cardiovascular (CV) events, recurrent CV events still occur in patients receiving antiplatelet therapy. Many of these patients are resistant or only partially responsive to the antiplatelet effects of aspirin and clopidogrel, as determined by standard platelet assays. However, current clinical guidelines do not support routine screening for aspirin or clopidogrel resistance, in part because determination of the most appropriate screening test has not been established. This review attempts to (1) describe the phenomena of clinical aspirin and clopidogrel resistance (ie, treatment failure), (2) discuss the complexity of defining and identifying aspirin and clopidogrel resistance, (3) identify factors that may be responsible for aspirin and clopidogrel resistance, (4) outline several standard platelet function assays and their limitations, and (5) describe potential new antiplatelet therapies that may benefit aspirin- or clopidogrel-resistant patients.
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To determine the effect of glucose-insulin-potassium infusion on circulating levels of free fatty acids in the setting of contemporary management of ST-elevation myocardial infarction, we randomly assigned 20 patients who were undergoing primary angioplasty to glucose-insulin-potassium infusion or to standard care. Treatment with glucose-insulin-potassium was associated with significantly lower levels of free fatty acid after 24 hours compared with standard care.
Patients with coronary artery disease (CAD) and concomitant left bundle branch block have increased mortality compared with those with CAD but without left bundle branch block. We retrospectively analyzed the extent of CAD in 200 patients with left bundle branch block referred for coronary angiography. Only 13% had left main or 3-vessel CAD. These findings were irrespective of left ventricular (LV) function. Of the 65 patients with normal LV function, only 5 (8%) had left main or 3-vessel disease, and of the 135 patients with depressed LV function, only 21 (16%) had left main or 3-vessel disease.
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CONTEXT: Homocysteine is emerging as a novel marker of atherothrombosis. Its role as an independent risk factor for cardiovascular disease is generally accepted. There is scanty data correlating homocysteine levels measured by immunoassay with cardiovascular disease. We previously validated a fluorescence polarization immunoassay for measuring homocysteine, which compared favorably with high performance liquid chromatography. OBJECTIVE: To determine if homocysteine levels measured by immunoassay correlate with extent of atherosclerotic burden, as represented by degree of coronary artery stenosis determined by coronary angiography. DESIGN: Fasting plasma samples were obtained from patients undergoing coronary angiography (N = 165). Homocysteine levels were measured by immunoassay and coronary artery stenosis was determined by coronary angiography. RESULTS: Median coronary artery stenosis for the 3 homocysteine subgroups, less than 1.35, 1.35 to 6.75, and greater than 6.75 mg/L (<10, 10-15, and >15 micromol/L), was 75%, 90%, and 99%, respectively (P = .01 for trend). Also, folate and vitamin B12 levels decreased with increasing homocysteine levels (P = .01 and .04, respectively, for trend). Spearman's correlation showed a significant association between homocysteine level and coronary artery stenosis (r = 0.20; P = .009). When men and women were examined separately, the correlation was significant only for women (r = 0.30; P = .01). CONCLUSION: Homocysteine levels, as measured by immunoassay, show a positive correlation with cardiovascular disease in women. Thus, this is a valid measure of atherosclerotic burden and, therefore, a reliable addition to the established laboratory repertoire for the assessment of cardiovascular disease.
As cocaine abuse has become widespread, it has been associated with various cardiovascular complications, including angina pectoris, myocardial infarction, and sudden cardiac death. Cocaine's principal effects on the cardiovascular system are mediated via alpha-adrenergic stimulation and include (a) an increase in the determinants of myocardial oxygen demand (heart rate and systemic arterial pressure) and (b) a concomitant decrease in myocardial oxygen supply (caused by vasoconstriction of the epicardial coronary arteries). Cocaine-induced coronary arterial vasoconstriction is enhanced at sites of atherosclerotic narrowing. Delayed or recurrent vasoconstriction of the coronary arteries may occur hours after the serum cocaine concentration has declined and appears to be caused by cocaine's major metabolites. Beta-adrenergic blocking agents may exacerbate cocaine-induced coronary arterial vasoconstriction, thereby increasing the magnitude of myocardial ischemia. Concomitant cigarette smoking exacerbates the deleterious effects of cocaine on myocardial oxygen supply and demand substantially.
Previous evidence suggests that the monoclonal antibody abciximab may have a more potent anticoagulant effect than small-molecule glycoprotein (GP) IIb/IIIa inhibitors. We prospectively reviewed collected heparin dose, activated clotting time (ACT), and corresponding clinical outcome data from The Do Tirofiban and ReoPro Give Similar Efficacy Outcome Trial (TARGET), a direct comparison of tirofiban versus abciximab in patients who underwent percutaneous intervention. Of the 4,809 patients enrolled in the trial, 3,739 patients (78%) had an ACT measured after the administration of GP IIb/IIIa and heparin (peak procedural ACT); this formed the population for the present study. Mean total heparin dose was 75 +/- 32 and 76 +/- 31 U/kg in the tirofiban and abciximab groups, respectively. The resultant mean peak ACTs were 296 +/- 91 and 299 +/- 89 seconds (p = 0.09). In a subset of patients with both baseline ACT (before any heparin or GP IIb/IIIa therapy) and peak procedural ACT measurements, the difference in ACT between these time points was 80 +/- 97 vs 82 +/- 101 seconds (p = 0.44) for the tirofiban and abciximab groups, respectively. After adjusting for patients' weight, weight-adjusted heparin dose, and method of ACT measurement in a multiple linear regression analysis, the type of GP IIb/IIIa inhibitor was not predictive of the peak ACT (p = 0.24). When stratified by ACT quartile, no statistically significant difference in bleeding or ischemic end points between the tirofiban and abciximab cohorts was observed. In this large contemporary percutaneous coronary intervention trial, there was no observed difference in the anticoagulant effect of tirofiban and abciximab, as measured by the ACT, or in the incidence of bleeding or ischemic complications in each ACT quartile.
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