Role of different determinants of psychological distress in acute coronary syndromes

Objectives. The aim of this study was to examine the prevalence of psychological distress and of its major determinants in acute coronary patients and in a control group.Background. The prevalence and major determinants of psychological distress in acute coronary patients are not clear.Methods. One hundred and thirty cardiac patients (110 men, age 56 ± 9; 85 with acute myocardial infarction and 45 with unstable angina) and 102 controls hospitalized for acute trauma (70 men, age 55 ± 9 years) were studied and the level of psychological distress estimated by a Modified Maastricht Questionnaire, self-ratings and ratings by a close relative. Major determinants of psychological distress were assessed by the Life Events Assessment, the Social Support Questionnaire and the Ways of Coping Checklist.Results. The average level of psychological distress was significantly higher (p < 0.001) in coronary patients than in controls in all tests (self-evaluation = 7.1 ± 2.3 vs 4.3 ± 2.4; relative-evaluation = 7.4 ± 2.4 vs 4.2 ± 2.5; Modified Maastricht Questionnaire = 91 ± 32 vs 59 ± 30). Cardiac patients reported significantly higher (p < 0.05) levels of social isolation (28.9 ± 11.1 vs 23.4 ± 8.8), self-blame (7.2 ± 1.9 vs 5.8 ± 1.6) and avoidance (21.1 ± 3.5 vs 18.9 ± 3) and more painful life events (3.9 ± 3.8 vs 2.6 ± 2.2), than controls. However, not all patients had evidence of distress; indeed, cluster analysis identified a subgroup that comprised 75% of controls and 25% of cardiac patients with no determinants eliciting distress, while the other four subgroups, with one or more determinants of distress, comprised about 75% of patients and only 25% of controls.Conclusions. These results show that a high level of psychological distress is detectable in about 75% of patients with acute myocardial infarction or unstable angina and is related to one or more major determinants.     

Guiding catheter thrombectomy during percutaneous coronary interventions for acute coronary syndromes.

Despite the advancements in the pharmacological and mechanical treatment of acute coronary syndromes, intracoronary thrombus and distal embolization remain among the major limitations of percutaneous transluminal coronary interventions. We describe three cases in which intragraft or intracoronary thrombus was completely aspirated during PTCI using the guiding catheter. In the first case, a 4-cm-long unfragmented embolized thrombus was effectively and completely aspirated from a saphenous vein graft, with immediate restoration of normal flow. In the second case, multiple fragments of embolized thrombus were aspirated from a large right coronary artery, while in the third case, intragraft thrombus was electively aspirated. In each case, the index lesions were then successfully stented without complications. Cathet. Cardiovasc. Intervent. 49:192-196, 2000.     

Medical treatment for acute coronary syndromes

The medical treatment of acute coronary syndromes with thrombolytic, antithrombin, and antiplatelet agents is a major area of research and a vast topic for clinical review. This review summarizes important recent findings on the background of existing pathological and clinical knowledge to provide an understanding of the basis of current therapy and the new therapies that are likely to be introduced in the near future. Current controversies regarding the management of these conditions and the choice between medical, interventional, and combined strategies in different situations are also discussed.     

Guidelines for the acute coronary syndromes

Traditional measures employed in the immediate management of patients presenting with an acute coronary syndrome have markedly reduced the risk of early death or myocardial infarction. Further incremental benefit is seen with the substitution of enoxaparin for unfractionated heparin, and in the use of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention. However, the evidence for benefit from the glycoprotwin IIb/IIIa inhibitors with medical management alone is unconvincing. Newer data also suggest an aggressive approach to the high-risk patient offers a better ultimate outcome than a conservative one.     

Inflammation and acute coronary syndromes

The presence of inflammatory infiltrates in unstable coronary plaques suggests that inflammatory processes may contribute to the pathogenesis of these syndromes. In patients with unstable angina, coronary atherosclerotic plaques are characterized by the presence of macrophages, and to a lesser extent, T-lymphocytes, at the immediate site of either plaque rupture or superficial erosion; moreover, the rupture-related inflammatory cells are activated, indicating ongoing inflammation at the site of plaque disruption. These observations are confirmed by clinical studies demonstrating activated circulating neutrophils, lymphocytes and monocytes, and increased concentrations of pro-inflammatory cytokines, such as interleukin (IL) 1 and 6, and of acute phase reactants in patients with unstable angina and myocardial infarction. In particular elevated levels of C-reactive protein are associated with an increased risk of in-hospital and 1 to 2 years new coronary events in patients with unstable angina, but are also associated with an increased long-term risk of death and myocardial infarction in apparently normal subjects. Thus, accumulating evidence suggests that inflammation may cause local endothelial activation and, possibly, plaque fissure, leading to unstable angina and infarction. Although no information is yet available on the causes of inflammation and on its localization, these novel lines of research may open the way to a different approach to the patient with acute coronary syndromes.     

Lipids and acute coronary syndromes

Eccentric atherogenic plaques which cause only insignificant narrowing of the diameter of coronary arteries are the cause of 60-80% of all acute coronary syndromes. The plaque becomes unstable (vulnerable) due to cytokines released by macrophages in the lipid rich core. Weakening of the fibrous capsule of the core then leads to rupture of the plaque and subsequently to intracoronary thrombosis with a wide spectrum of ischaemia or even necrosis of the myocardium. Secondary preventive studies (4S, LIPID, CARE), morphological non-mortality studies (e.g. AVERT, REGRESS, LCAS) and primary preventive studies (WOSCOPS, AFCAPS/TexCAPS) revealed that statins reduce significantly, as compared with placebo, total and LDL-cholesterol by 20-35% and lead in subsequent years to a significant decline of the relative risk of the general and coronary mortality and morbidiy by 20-40%. They prevent progression and may lead to regression of coronary sclerosis. They do not act by mere reduction of the cholesterol level but also by their extralipid effects which stabilize the plaque. 80% of patients with coronary syndrome have cholesterol levels between 6.0 and 7.5 mmol/l, similarly as ca 40% of healthy middle aged persons. The difference is in the risk caused either by the presence of ischaemic heart disease or in healthy subjects by the cumulation of several coronary risk factors. A special risk group are the remaining 20% patients. They include subjects with a cholesterol level above 8 mmol/l who must be treated more aggressively, similarly as patients after a venous aortocoronary bypass. Subjects with slightly elevated LDL-cholesterol values but high triacylglycerol levels and lower HDL-cholesterol levels have also an atherogenic risk. This applies not only to postmenopausal women, elderly people, obese and diabetic subjects, hypertensive subjects with insulin resistance but also to young subjects. In the latter reduction of triacylglycerols is indicated. In coronary patients a combination of statins and fibrates may be used. Basic hypolipidaemic treatment for reduction of the atherothrombotic risk are statins. Despite statin treatment the prospective mortality and morbidity of coronary patients is still high and it is necessary to make an effort to achieve target lipid levels. Recent studies provide new findings, further progress and stricter therapy are foreseen.     

Inflammation and acute coronary syndromes

A great variety of stimuli, such as free radicals, oxidized LDL or some bacteria or virus infections, can act upon the vascular surface and lead to the development of an acute inflammatory reaction. There is more and more evidence supporting the hypothesis that the mechanism responsible for the transformation of a non-complicated atherosclerotic lesion into an hemorrhagic and ulcerated lesion, with the subsequent acute and unstable clinical status, is due to the onset of an inflammatory reaction. Many studies have tried to investigate the presence of any systemic marker able to predict the prognosis of patients at risk from developing acute events, and to distinguish them from those in stable status. The increase of the levels of C-reactive-protein has been related to the development of acute coronary syndromes, though often the results obtained in the different studies have had a quite poor prognostic value when applied to the general population. The lack of direct association between the increase of the levels of C-reactive-protein and Troponin I seems to rule out the possibility that the inflammatory stimulus might be the consequence of an irreversible injury, even though there is no doubt that severe ischemia is likely to play an active role in this sense.     

Metabolic causes and prevention of ventricular fibrillation during acute coronary syndromes

The mechanisms leading to ventricular fibrillation that occur during acute myocardial ischemia are ill understood. Whether primary ventricular fibrillation is due to a transient imbalance of electrolytes, an alteration of membrane permeability, electrical re-entry phenomena, or other factors, one overriding influence is the development of regional myocardial energy crises. Acute alteration in the balance of substrate supply may lead, during greatly reduced blood flow, to instability of myocardial electrical conduction with the development of re-entry circuits. An immediate response to the angor animi and initial symptoms of an acute coronary syndrome is a rapid and marked increase in catecholamine release, which leads to adipose tissue lipolysis with an acute increase in plasma free fatty acid concentrations, suppression of insulin activity, and a reduction in glucose uptake by the myocardium. The utilization of free fatty acids instead of glucose by the ischemic myocardium could precipitate regional oxygen or energy crises. Prevention therefore should focus on minimizing the catecholamine response and providing the myocardium with an optimum supply of energy substrates. Since catecholamines are inotropic, the aim should be to redress the imbalance of substrate availability by controlling adipose lipolysis with reduction of plasma free fatty acid concentrations, increasing the availability of glucose, or both. Other approaches include inhibition of acylcarnitine transport and manipulation of fatty acid intermediaries. To combat primary ventricular fibrillation, preventive treatment must be established within 6 to 10 hours of the onset of ischemia. There is already experimental and clinical evidence that antilipolytic drugs decrease the incidence of ventricular fibrillation, but their potential has not been explored extensively.     

Bivalirudin for percutaneous coronary intervention and in acute coronary syndromes

This review focuses on the use of bivalirudin as a replacement anticoagulant for heparin in patients undergoing percutaneous coronary intervention, or who are being treated for unstable angina pectoris, ST-elevation, or non-ST-elevation myocardial infarction. Potential advantages of bivalirudin include a lack of dependence on antithrombin III for anticoagulant activity, the ability to inactivate both fibrin-bound and soluble thrombin, a lack of aggregatory effects on platelets, a predictable anticoagulant response without monitoring, and a wider therapeutic window. Clinical trial results to date suggest that bivlirudin is at least as effective as heparin with superior safety due to lower bleeding rates.     

Restoration of flow in acute coronary obstructive syndromes: consequences of different management strategies

Although much necessary evidence is not yet available, there is sufficient information from recent therapeutic trials to necessitate a nationwide review of the management of acute coronary obstructive syndromes. On the basis of present information it is evident that, in addition to heparin, all patients suffering from suspected acute myocardial infarction should receive immediate low dose aspirin which should be continued for one to six months. This treatment, if generally applied, can be expected to save 1200 lives per year in Canada at negligible cost. Addition of intravenous streptokinase infusion to all patients (in whom there are no contraindications) available for treatment from 0 to 24 h from the onset, can be expected to save an additional 1088 lives at an additional cost of approximately $11,000 per life. Other thrombolytic agents involve additional cost and the gains in terms of mortality are not yet demonstrated. The evidence for thrombolytic treatment in acute unstable angina is still uncertain but the treatment of all cases with aspirin from the earliest possible moment is clearly indicated.     

Physiopathology of acute coronary syndromes

Coronary atherosclerosis and its thrombotic complications represent one of the leading causes of lesions usually consists of successive acute episodes, either silent or in the form of an acute coronary syndrome such as unstable angina, non-Q-wave myocardial infarctions, transmural myocardial infarctions or sudden death. This mode of progression does not exclude phases of regression, or more frequently stabilization of plaques, which, depending on their haemodynamic repercussions, are then responsible for chronic myocardial ischaemia. Acute coronary syndrome (ACS) correspond to the same pathophysiological process: rupture of an atheromatous plaque initiating harmful thrombotic, inflammatory and vasomotor phenomena. This is not a new concept, but progress over recent years suggests that the composition and biology of the plaque are factors involved more in the initiation of ACS than the size of the plaque. "Soft" lesions, rich in lipids, are clearly not only the most unstable lesions, but also the most thrombogenic because of their large tissue factor content. After describing the structure of vulnerable plaques, the authors discuss the causes of their rupture and the resulting cascade or events, responsible for life-threatening clinical situations.     

Proteomics of acute coronary syndromes

Acute coronary syndromes (ACS), such as unstable angina, acute myocardial infarction, and sudden cardiac death, are commonly associated with the presence of vulnerable plaques in coronary arteries. Rupture or erosion of vulnerable plaques results in the formation of luminal thrombi due to the physical contact between platelets and thrombogenic elements within the atherosclerotic lesions. Considering the socioeconomic burden of ACS, it is imperative that the scientific community achieves a clear understanding of the multifaceted pathophysiology of vulnerable atheroma to identify accurate prognostic biomarkers and therapeutic targets. The analytical power of modern proteomic technologies could facilitate our understanding of vulnerable plaques and lead to the discovery of novel therapeutic targets and diagnostic biomarkers.