Pathogenesis of acute coronary syndromes

Coronary artery diseases may categorized into asymptomatic disease, angina pectoris, myocardial infarction, chronic heart failure, and sudden coronary death. Unstable angina, acute myocardial infarction, and sudden cardiac death are known as the acute coronary syndromes. Coronary atheroma is unstable in the patients with acute coronary syndromes. Stable plaques will be unstable when dynamic alterations occur. The alterations are plaque rupture, plaque hemorrhage, coronary thrombosis and vasospasm. They act each other. We analysed the histopathology of coronary arteries who died of acute myocardial infarction in 85 cases. It showed that the risk factors of plaque rupture are clusters of form cells, eccentric plaque with soft lipid rich core, and thinning of fibrous cap in atheroma. Most of these cases ruptured at edge of the atheroma.     

Increased oxidation of LDL in patients with coronary artery disease is independent from dietary vitamins E and C

There is increasing experimental evidence that oxidation of LDL plays a major role in the pathogenesis of coronary artery disease (CAD). However, results from clinical studies on LDL oxidation and CAD are not consistent. In most studies only single plasma factors of LDL oxidation have been determined. We studied 207 patients who underwent coronary angiography. They were divided into subjects with CAD (n = 137) and those without CAD (n = 70). We determined the susceptibility of LDL to in vitro oxidation (lag phase), potential prooxidative and antioxidative plasma factors (plasma vitamin E, LDL vitamin E, ascorbate, iron, copper, ferritin, and ceruloplasmin), and markers of in vivo LDL oxidation (autoantibodies to malondialdehyde-modified LDL, oxidized LDL, and thiobarbituric acid-reactive substances), plasma lipids and lipoproteins, smoking habits, and other coronary risk factors in both groups. The lag phase was significantly shorter in patients with CAD than in patients without CAD (101 +/- 38.6 versus 119 +/- 40.6 minutes, P < .01). There was no correlation between the lag phase and the other oxidation parameters or the coronary risk factors. In multivariate regression analyses the lag phase remained significant in all tested models. Our data suggest that a short lag phase of LDL oxidation might be an independent risk factor of CAD.     

Atherosclerosis, with special reference to vitamin E

The relationship between atherosclerosis and fat soluble vitamin, especially vitamin E is reviewed on the basis of oxidised modification of low density lipoprotein (LDL). Data now support the notion that the oxidised LDL is present in the blood and arterial wall and antioxidant drugs such as probucol and vitamin E, beta-carotene, may prevent the progression of atherosclerosis. LDL alpha-tocopherol levels are generally correlated to the plasma concentrations and supplementation with alpha-tocopherol increases its content in LDL. There is a significant correlation between the LDL alpha-tocopherol level and the resistance to oxidative modification. Epidemiological data also shows the relation between low levels of plasma vitamin E and the increased incidence of coronary heart disease. Clinical application of vitamin E should be clarified in detail to inhibit the progression of atherosclerosis.     

C-reactive protein as a marker for acute coronary syndromes

BACKGROUND: For several years, acute coronary syndromes have been perceived as causing the most hospital admissions, and even hospital mortality. The syndrome of unstable angina frequently progresses to acute myocardial infarction but its pathogenesis is poorly understood, and prognosis determination is still problematic. We tested the hypothesis that measurement of the C-reactive protein in patients admitted for chest pain could be a marker for acute coronary syndromes. METHODS AND RESULTS: We studied 110 patients admitted with suspected ischaemic heart disease, but without elevated serum creatine-kinase levels at the time of hospital admission. Patients were subsequently divided into two groups based on their final diagnosis: group 1 comprised patients with unstable angina; group 2 patients with acute myocardial infarction. We measured the C-reactive protein at the time of hospital admission. The concentration of C-reactive protein was elevated in 59% of the patients with a final diagnosis of acute myocardial infarction, and in 5% of the patients with a final diagnosis of unstable angina, (P < 0.001). CONCLUSION: This study indicates that C-reactive protein levels measured at the time of admission in patients with suspected ischaemic heart disease could be a marker for acute coronary syndromes, and helpful in identifying patients at high risk for acute myocardial infarction. Measurement of C-reactive protein may have practical clinical significance in the management of patients hospitalized for suspected acute coronary syndromes.     

Early morning dystonia in Parkinson''s disease

Proliferation of arterial smooth muscle cells has held center stage as the culprit in restenosis for almost two decades. Many strategies for combating restenosis target smooth muscle replication. However, none have proven beneficial in clinical trials. Indeed, inhibition of smooth muscle proliferation in human patients might produce the undesired effect of destabilizing vulnerable atherosclerotic plaques because these cells furnish the collagen responsible for the biomechanical strength of the plaque. Actually, in some cases the benefit of angioplasty may depend on stimulating smooth muscle replication and collagen elaboration, converting an "unstable" to a more stable plaque. Moreover, recent clinical and experimental evidence suggests that restenosis depends less on neointimal hyperplasia than on constrictive remodeling (i.e., advential scarring, producing a smaller lumen), a process independent of smooth muscle replication. The recognition that plaques vulnerable to disruption often do not produce flow-limiting stenoses highlights a need for reassessment of the strategies to treat or prevent the acute coronary syndromes. We should strive to treat aggressively risk factors such as hyperlipidemia whose control appears to stabilize plaques. Trials are even underway comparing such risk factor management with coronary artery intervention. If we could identify potentially unstable atheroma before they are evident, clinically, we might even contemplate angioplasty of nonsignificant stenoses to induce smooth muscle cell proliferation and reinforce the plaque's fibrous cap. This proposal may seem preposterous, yet we perform "primary" angioplasty every day in patients with an acute myocardial infarction whose "culprit" lesions underlying the thrombus are often not critical. Our knowledge of the biology of restenosis has lagged behind our practice of coronary intervention. Advances in understanding the biology of the complications of interventional therapy, hand in hand with technical advances, should help us to devise more rational and enduring approaches to benefiting our patients.     

Radioimmunotherapy of orthotopically transplanted pancreatic cancer with 131I-labeled chimeric monoclonal antibody Nd2

Recent study demonstrated high susceptibility of plasma LDL to lipid peroxidative modification in patients with variant angina. Oxidized stress state, especially oxidized LDL, may induce coronary artery spasm by its impairing effect of endothelium-dependent arterial relaxation, but precise mechanisms remain unclear. Study subjects included 93 patients who underwent coronary angiographic examination: 12 patients with coronary artery spasm provoked by ergonovine without organic stenosis (group I), 11 patients who did not demonstrate coronary artery spasm or organic stenosis (group II) and 70 patients with organic coronary artery stenosis (group III). Levels of plasma HDL-cholesterol and apoA-I in group I were similar to those in III but were significantly lower than those in II, although the other plasma lipid parameters were not different among the three groups. The levels of TBARS in plasma and HDL were significantly higher in group I than in II or III (2.94+/-1.56 vs. 1.91+/-0.35 or 2.23+/-0.89 nmol MDA/ml and 1.23+/-1.00 vs. 0.54+/-0.37 or 0.70+/-0.63 nmol MDA/mg protein; P < 0.05), although the levels of TBARS in LDL were not significantly different. In the monitoring curve of diene production during copper-induced lipid peroxidation of HDL, its propagation slope was steeper and levels of maximum diene absorbance was higher in group I as compared with that in II or III, but not found in those of LDL. These results suggested that high susceptibility of HDL to lipid peroxidative modification in group I may contribute to the genesis of coronary artery spasm, and oxidized HDL rather than oxidized LDL is more likely to be related to coronary artery spasm.     

Impaired platelet production of nitric oxide predicts presence of acute coronary syndromes

BACKGROUND: Thrombus formation within a coronary vessel is the acute precipitating event in most acute coronary syndromes. Recently, constitutive nitric oxide synthase (cNOS) has been identified in human platelets, and platelet-derived nitric oxide has been shown to inhibit platelet recruitment after aggregation. However, its role in regulating platelet responses under normal or pathologic conditions has not yet been elucidated. METHODS and RESULTS: We examined nitric oxide (NO) production by platelets isolated from 87 patients undergoing coronary angiography, 37 with stable angina and 50 with unstable angina or a myocardial infarction within 2 weeks. After stimulation with 5 micromol/L ADP, platelet aggregation and NO production were simultaneously measured with an NO-selective microelectrode adapted for use in a standard platelet aggregometer. Mean (+/-SEM) platelet-derived NO production was 1.78+/-0.36 pmol/10(8) and 0.26+/-0.05 pmol/10(8) platelets in coronary patients with stable angina and acute coronary syndromes, respectively (P=0. 0001). By logistic regression analysis, heparin treatment (odds ratio 6.6, CI 1.9 to 22.8, P=0.003), lower platelet-NO production (odds ratio 4.0, CI 1.3 to 11.5, P=0.01), and extent of atherosclerosis (odds ratio 1.5, CI 1.1 to 2.0, P=0.02) were independent predictors of an acute coronary syndrome. In the subset of patients with angiographic evidence of atherosclerosis (n=83), logistic regression demonstrated that platelet NO production (odds ratio 3.9, CI 1.3 to 11.1, P=0.01) and heparin treatment (odds ratio 6.4, CI 1.9 to 22.0, P=0.004) were independent predictors of an acute coronary syndrome, whereas extent of atherosclerosis was not. CONCLUSIONS: In summary, aggregating platelets from patients with acute coronary syndromes produce less NO. Since platelet aggregation and thrombus formation are implicated in unstable angina and myocardial infarction, impaired platelet-derived NO production may contribute to the development of acute coronary syndromes.     

Advances in the medical management of acute coronary syndromes

Many advances in the treatment of acute coronary syndromes have been realized over recent years. In ST elevation myocardial infarction, new aggressive thrombolytic regimens improve early reperfusion and improve survival. The current focus is on bolus thrombolysis, glycoprotein IIb/IIIa inhibition, and low-molecular-weight heparin as adjuncts. In unstable angina and non-ST elevation myocardial infarction, two major advances are IIb/IIIa inhibition and low-molecular-weight heparin, each of which significantly improves the outcome of patients and which have just been approved for use by the Food and Drug Administration. Following acute coronary syndromes, cholesterol lowering with statin drugs has a major effect, even in the large group of patients with average cholesterol levels. Use of clopidogrel, a more potent antiplatelet agent than aspirin, appears to decrease recurrent ischemic events, which has highlighted the potential benefits of oral IIb/IIIa inhibitors, which are much more potent antiplatelet agents. An additional focus has been on ensuring that patients actually receive the currently available medications. With a great number of new medical treatments, the outcome of patients with acute coronary syndromes has improved and will continue to improve as we enter the next millennium.     

Clinical characteristics determining the mode of presentation in patients with acute coronary syndromes

OBJECTIVES: The purpose of this study was to examine clinical characteristics of patients with acute coronary syndromes to identify factors that influence the mode of presentation. BACKGROUND: In acute coronary syndromes, presentation with myocardial infarction or unstable angina has major prognostic implications, yet clinical factors affecting the mode of presentation are not well defined. METHODS: A prospective cohort study was made of 1,111 patients with acute coronary syndromes. Baseline demographic, clinical and biochemical data were compared in groups with myocardial infarction (n = 633) and unstable angina (n = 478). RESULTS: The risk of myocardial infarction relative to unstable angina was increased by age >70 years (odds ratio [OR] 2.21; 95% confidence interval [CI] 1.33 to 3.66), male gender (OR 1.56; CI 1.13 to 2.16) and cigarette smoking (OR 1.49; CI 1.09 to 2.03). A rise in admission creatinine from the 10th to the 90th centile of the distribution also increased the odds of myocardial infarction (OR 1.30; CI 1.05 to 1.94). Conversely, the risk of myocardial infarction relative to unstable angina was reduced by previous treatment with aspirin (OR 0.37; CI 0.27 to 0.52), hypertension (OR 0.64; CI 0.47 to 0.86) and previous acute coronary syndromes (OR 0.36; CI 0.26 to 0.51) and revascularization procedures (OR 0.36; CI 0.21 to 0.62). CONCLUSIONS: The clinical presentation of acute coronary syndromes may be influenced by various factors that have the potential to influence the coagulability of the blood, the collateralization of the coronary circulation and myocardial mass. Myocardial infarction is favored by cigarette smoking, advanced age and renal impairment, while unstable angina is favored by treatment with aspirin, hypertension, previous revascularization and previous coronary syndromes.     

The acute coronary ischemic syndromes--the central role of thrombosis

The postulate that thrombotic coronary occlusion was the underlying pathophysiologic event in the acute coronary ischemic syndromes was developed over the years 1912-60. This concept prompted the development of anticoagulant and thrombolytic therapies and the use of acetylsalicylic acid in such patients. A central role for coronary thrombus came to be questioned in the 1970s and the use of anticoagulants dramatically decreased and thrombolytic therapy was little used. Coronary angiographic studies among patients during the early hours of evolving myocardial infarction re-established the etiologic role of coronary thrombosis in the acute coronary ischemic syndromes, and were supplemented by careful autopsy studies. The concepts of meta-analysis lead to more accurate interpretations of earlier randomized, controlled trials of anticoagulant, antiplatelet and thrombolytic therapies. Large clinical trials have provided confirmatory evidence and have established the benefits of antiplatelet and thrombolytic agents in the acute ischemic syndromes. The benefit of long term anticoagulation following myocardial infarction has been demonstrated, although the benefit during the acute in-hospital phase of myocardial infarction is still uncertain. Currently, clinical trials are evaluating new antithrombins, antiplatelet agents, and thrombolytic agents and regimens among patients with unstable angina, acute myocardial infarction, and undergoing angioplasty for complex coronary lesions.     

Sudden coronary death. Frequency of active coronary lesions, inactive coronary lesions, and myocardial infarction

BACKGROUND: The reported frequency of active coronary lesions (plaque rupture and coronary thrombosis) in sudden death due to coronary artery atherosclerosis (sudden coronary death) has varied from < 20% to > 80% of cases in previous series. In hearts lacking an active coronary lesion, sudden death has usually been attributed to a healed myocardial infarction. The purpose of the present study was to determine the frequency of active and inactive coronary lesions and myocardial infarction in individuals with sudden coronary death. METHODS AND RESULTS: The hearts of persons who died as a result of sudden coronary death underwent perfusion-fixation and postmortem angiography. An active coronary lesion was defined as a disrupted plaque, luminal fibrin/platelet thrombus, or both. We defined an inactive lesion as having a cross-sectional luminal stenosis of > or = 75% with neither plaque disruption nor luminal thrombus. Ninety hearts were examined (from 72 men and 18 women; mean age at the time of death, 51 +/- 10 years). Acute myocardial infarction was present in 19 (21% [acute myocardial infarction only in 9, both acute and healed myocardial infarction in 10]), healed myocardial infarction only in 37 (41%), and no myocardial infarction in 34 (38%). Active coronary lesions were identified in 51 (57%): acute thrombi plus disrupted plaques in 27, acute thrombi only in 21, and disrupted plaques only in 3. In hearts with acute myocardial infarction, active coronary lesions were significantly more prevalent than in hearts with only healed myocardial infarction or hearts lacking an acute or a healed myocardial infarction (89%, 46%, and 50%, respectively; P < .005). Hearts without acute or healed myocardial infarction and without active lesions were similar to hearts with active lesions with respect to heart weight and severity of epicardial coronary disease. CONCLUSIONS: Acute changes in coronary plaque morphology (thrombus, plaque disruption, or both) were found in 57% of cases of sudden coronary death. In hearts with myocardial scars and no acute infarction, active coronary lesions were identified in 46% of cases. Neither myocardial infarction (acute or healed) nor an active coronary lesion was present in 19% of hearts.     

Endothelin and big endothelin in coronary heart disease and acute coronary syndromes

Endothelin (ET), the most potent endogenous vasoconstrictor with mitogenic potency, is generated from its precursor big-endothelin (BET) in a proteolytic process and discussed as a pathogenetic factor in coronary artery disease and in the acute coronary syndromes. Several studies documented elevated plasma endothelin concentrations in acute myocardial infarction, but conflicting results were reported in patients with stable and unstable angina. Only few studies determined big endothelin, although it half-life and plasma concentrations are higher in comparison to endothelin. ET and BET levels (Radioimmunoassay, Biomedica GmbH, Vienna) were determined in patients with stable angina (SAP, n = 20), unstable angina (IAP, n = 12), acute myocardial infarction (AMI, n = 12) and healthy subjects (NP, n = 11). The concentrations of ET and BET (median (minimum-maximum) in fmol/ml) of the patients with stable angina (SAP: ET 0.7 (0.3-1.1); BET 1.7 (0.7-2.9)), unstable angina (IAP: ET 1.0(0.5-1.7); BET 2.5 (1.3-4.1)) and acute myocardial infarction (AMI: ET 1.2 (0.6-2.3); BET 3.6 (3.2-5.3)) showed a significant difference compared to controls (NP: ET 0.5 (0.4-0.7); BET 1.4 (1.1-1.7)) (SAP vs. NP: ET p < 0.01; BET p < 0.05; IAP and AMI vs. NP: ET and BET p < 0.001). Also, the concentrations of the peptides differed significantly dependent on the clinical severity of coronary artery disease (AMI vs. SAP: ET and BET p < 0.001; AMI vs. IAP: BET p < 0.05; IAP vs. SAP: ET p < 0.05; BET p < 0.01). Twelve of 15 patients with big endothelin concentrations over 3 fmol/ml suffered acute myocardial infarction. Seven of 12 patients with AMI showed elevated ET and BET concentrations before the increase of creatinecinase. There was no correlation between number of risk factors per patient, cholesterin and subfractions, severity of CAD classified in one-two-three-vessel disease or coronary score according to modified criteria of the American Heart Association (AHA). We conclude that in patients with coronary artery disease endothelin and big endothelin levels are elevated and related to the clinical and not to the morphological severity of coronary artery disease. Big endothelin is the more sensitive parameter in comparison to endothelin and indicates a severe course of myocardial ischemia in patients with unstable angina. The development of assays with the possibility of a quick determination of the peptides may be valuable for risk stratification of acute coronary events.     

Lipoprotein(a) as a risk predictor for cardiac mortality in patients with acute coronary syndromes

AIMS: Raised lipoprotein(a) concentrations are considered to be a risk factor for atherothrombotic diseases. We examined whether baseline concentrations were a risk factor for an adverse outcome in patients admitted with acute coronary syndromes. METHODS AND RESULTS: Five hundred and nineteen patients admitted with suspected acute coronary syndromes were studied and followed prospectively for a median of 3 years. The prognostic significance of a baseline lipoprotein(a) concentration of > or = 30 mg x dl(-1) or lower for subsequent cardiac death was assessed in patients with myocardial infarction (266) and unstable angina (197) and compared with other variables in regression models. In patients with myocardial infarction, a baseline lipoprotein(a) concentration of > or =30 mg x dl(-1) was associated with a 62% increase in subsequent cardiac death compared to the lower concentration group (29.8% vs 18.6%, Log rank P=0.04). In a multivariate regression model a baseline lipoprotein(a) concentration of > or = 30 mg x dl(-1) retained its significance as an independent predictor of cardiac death (P=0.037). In patients with unstable angina, baseline concentrations of > or = 7.9 mg x dl(-1) were found to be significant predictors of cardiac death in univariate (P=0.021) and multivariate (P=0.035) regression models. CONCLUSION: Baseline lipoprotein(a) concentrations in patients admitted with acute coronary syndromes are associated with an increased risk of cardiac death. For patients with myocardial infarction a concentration of > or = 30 mg x dl(-1) appears appropriate as a risk discriminator; for patients admitted with unstable angina, however, much lower concentrations of lipoprotein(a) appear to be prognostically important.     

Accumulation of amphotericin B in human macrophages enhances activity against Aspergillus fumigatus conidia: quantification of conidial kill at the single-cell level

Several cardiac serum markers such as cardiac myosin light chain, creatine kinase MB, and cardiac troponins have been shown to be elevated in patients with acute myocardial infarction. These markers are well utilized as clinical indicators for diagnosis and prognosis of myocardial necrosis. Recent studies have strongly indicated that cardiac structural protein troponin T and I are predictive of future cardiac events in patients with acute coronary syndromes including unstable angina pectoris. Immunoassays have also been developed to measure serum levels of cardiac troponins in recent years. These biochemical markers may be useful as a guide for intervention in the near future.     

ACE inhibitors use in patients with acute coronary syndrome

Angiotensin converting enzyme (ACE) inhibitors (ACE-I) reduce the incidence of re-infarction in patients with myocardial infarction (MI), and the DD genotype for the ACE gene is an independent risk factor of MI. These findings suggest involvement of ACE in the natural history of coronary plaques and in the pathogenesis of acute coronary syndrome (ACS). ACE-I potentially prevent coronary plaque rupture by suppressing angiotensin II-induced vasoconstriction and sympathetic nerve activity. Actions of ACE-I on risk factors, including insulin resistance, may retard the progression of atheromatous changes in the coronary artery. Furthermore, ACE-I attenuate contractile dysfunction due to myocardial stunning and hibernation, while it augments anti-infarct tolerance of the myocytes afforded by preconditioning. These actions on the myocardium may also be beneficial in ACS. Although favorable effects of ACE-I on the mortality rate of MI patients has been established, the benefit of chronic therapy with ACE-I for patients who have coronary artery disease without MI remains to be clarified.     

Vulnerable plaque: pathobiology and clinical implications

PURPOSE: To review the pathobiology and clinical implications of vulnerable coronary atherosclerotic plaques and to discuss the identification of vulnerable plaques and mechanisms of plaque stabilization. DATA SOURCES: English-language articles in the MEDLINE database that were published from 1966 to the present, identified by using the terms atherosclerotic plaque, myocardial revascularization, and plaque stabilization. Selected references cited in identified articles were reviewed. STUDY SELECTION: Experimental, clinical, and basic research studies related to coronary atherosclerotic plaques. DATA SYNTHESIS: Rupture at the site of a vulnerable atherosclerotic plaque is the most frequent cause of acute coronary syndromes. Typically, such plaque does not cause high-grade stenosis and has a large lipid core and a thin fibrous cap that is often infiltrated by inflammatory cells. Mechanical stresses contribute to plaque vulnerability, and certain triggers may cause plaque disruption directly. The most important consequence of plaque rupture is thrombosis. No method reliably identifies plaques prone to rupture. The reduction of coronary events by lipid-lowering agents despite only modest luminal changes suggests that these agents have a plaque-stabilizing effect. Surgical or percutaneous revascularization does not address the basic biology of coronary atherosclerosis and therefore may have little effect on plaque vulnerability. CONCLUSIONS: Improved understanding of the biology of atheromatous plaques has led to the concept of plaque vulnerability. Identification and stabilization of vulnerable plaques are important new directions in the treatment of coronary atherosclerosis. The relative benefits of aggressive medical therapy aimed at plaque stabilization should be compared with those of revascularization in the management of chronic coronary artery disease.     

Twenty-four-hour pharmacokinetics of rectal acetaminophen in children: an old drug with new recommendations

Oxidized low density lipoprotein (LDL) and acetyl LDL are recognized by the scavenger receptor class A type I/II (SR-AI/II) on macrophages and liver endothelial cells. Several investigators have suggested that there are additional receptors specific for oxidized LDL, but characterization of these alternate receptors for oxidized LDL and evaluation of their quantitative importance in uptake of oxidized LDL has been difficult because of overlapping ligand specificity with SR-AI/II. The purpose of this study was to determine the importance of SR-AI/II in the removal of modified LDL from the bloodstream in vivo. The clearance rate of oxidized LDL from plasma in normal mice was very rapid, and > 90% of injected dose was removed from the blood within 5 min. Clearance rates of oxidized LDL were equally high in SR-AI/II knockout mice, indicating that this receptor is not required for removal of oxidized LDL from plasma. Surprisingly, there was no difference in the clearance rate of acetyl LDL in wild-type and SR-AI/II knockout animals. The plasma clearance of radioiodinated acetyl LDL was almost fully blocked by a 50-fold excess of unlabeled acetyl LDL, but the latter only inhibited oxidized LDL clearance by approximately 5%. Both modified LDLs were cleared mostly by the liver, and there was no difference in the tissue distribution of modified LDL in control and knockout mice. Studies in isolated nonparenchymal liver cells showed that Kupffer cells accounted for most of the uptake of oxidized LDL. Extensively oxidized LDL and LDL modified by exposure to fatty acid peroxidation products were efficient competitors for the uptake of labeled oxidized LDL by SR-AI/II-deficient Kupffer cells, while acetyl LDL and malondialdehyde-modified LDL were relatively poor competitors.     

A review of transpersonal theory and its application to the practice of psychotherapy

BACKGROUND: A large proportion of deaths among patients with myocardial infarction occurs within the first 24 hours after presentation. It is not clear whether this phenomenon is also true of patients without ST-segment elevation who may or may not have infarction at the time of presentation. Thrombin activity may also be greatest during the first 24 hours after plaque rupture. Accordingly, this study was designed to examine the pattern of early ischemic events among patients with acute coronary syndromes and to determine whether the direct thrombin inhibitor desirudin (r-hirudin) would be most effective during this period. METHODS AND RESULTS: Among the 11,142 patients enrolled in GUSTO-II, death or (re)infarction occurred within 24 hours in 210 patients (1.7%), representing 19% of the 1135 deaths that had occurred by 30 days. Death or (re)infarction occurred within 24 hours in 113 patients (2. 7%) with ST-segment elevation and in 97 patients without ST-segment elevation (1.2%, P <.001), representing 26% and 14% of the 30-day event rates, respectively, for the 2 enrollment strata. Among patients with ST-segment elevation, most of these events were deaths, whereas among patients without ST-segment elevation, most events were (re)infarctions. Death or (re)infarction by 24 hours occurred in 80 (1.3%) patients treated with desirudin and 130 (2.1%) patients treated with heparin (P =.01). This finding predominantly consisted of prevention of death among patients with ST-segment elevation and of (re)infarction among patients without ST-segment elevation. CONCLUSIONS: These findings have important implications for early triage of patients with acute coronary syndromes and for the development of new therapies directed at stabilizing the unstable atherosclerotic plaque.     

Thrombosis in ischemic heart disease

Thrombus formation on a fissured or disrupted atherosclerotic plaque is the main pathogenetic mechanism for the acute coronary syndromes of myocardial infarction and unstable angina. Myocardial infarction results from an acute total occlusion of the artery, while unstable angina is secondary in most cases to mural thrombus formation. Thrombus formation has also been implicated in chronic atherosclerotic disease progression and in restenosis following coronary angioplasty. Therapeutic measures to treat thrombus rely on the ability of drugs to either prevent thrombus extension, dissolve its fibrin component, or prevent further platelet aggregation. Other measures rely on the ability of intracoronary techniques to open coronary arteries. The primary prevention of intracoronary thrombus formation is evolving. Measures to stabilize plaques or to reduce hypercoagulability are being tested or have been tested in recent trials.     

Evaluation of myocardial perfusion and fatty acid uptake using a single injection of iodine-123-BMIPP in patients with acute coronary syndromes

The purpose of this study was to clarify the possibility of simultaneous evaluation of myocardial perfusion and fatty acid metabolism using a single injection of 123I-beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) in patients with acute coronary syndromes. METHODS: Thirty patients with unstable angina pectoris (UAP group) and 15 patients with acute myocardial infarction (MI group) were studied. BMIPP dynamic SPECT was performed 2 min after the injection of BMIPP (185 MBq), and images were obtained every 3 min for 15 min with a three-head gamma camera. Conventional BMIPP SPECT was also performed 30 min after the injection. Serial BMIPP and resting 201TI images were compared. RESULTS: A 201TI-BMIPP mismatch between 30-min BMIPP and resting 201TI images was observed in 27 of 30 patients in the UAP group and 8 of 15 patients in the MI group, respectively. However, a 201TI-BMIPP mismatch between early (2-5-min) BMIPP and resting 201TI images was observed in only 2 of 30 patients in the UAP group and in only 2 of 15 patients in the MI group, respectively. The kappa statistics of tracer uptake between early BMIPP and resting 201TI images showed good concordance in UAP (kappa = 0.823) and MI (kappa = 0.765) groups, respectively. These results indicated that initial distribution of BMIPP reflects myocardial perfusion in patients with acute coronary syndromes. CONCLUSION: Myocardial perfusion and fatty acid metabolism can be evaluated simultaneously using a single injection of BMIPP, when images are taken soon (2-5 min) and long after the injection in patients with acute coronary syndromes.