Métodos não invasivos para identificação da doença aterosclerótica: desafios para prevenção da doença e eventos clínicos

Atherosclerosis is a chronic inflammatory disease that affects essentially all arterial beds including the aorta, coronaries, carotids, and peripheral arteries. It is the main cause of death in the western hemisphere, due to cardiovascular syndromes such as myocardial infarction, heart failure, and cerebrovascular accidents. Very substantial economic and human resources have been used on treatments of its complications, including imaging studies, coronary bypass surgery, catheter interventions, pacemakers, and medical treatments. Treating complications, however, are remedial actions. A better alternative is to prevent the development of atherosclerosis, or at least to identify patients who are at risk of acute events and intervene before they occur. The aims of this review are to discuss the predictive value of traditional and emerging risk factors, as well as the role of noninvasive diagnostic methods for coronary atherosclerosis, including exercise stress test, echo stress test, duplex ultrasound, computed tomography, and magnetic resonance. A combination of serum biomarkers and noninvasive approaches is of practical utility for identifying early disease. It is to be expected that future developments will soon perfect our ability to identify the vulnerable patient and allow a more individualized approach.A aterosclerose é uma doença inflamatória crônica que afeta essencialmente todas as artérias incluindo a aorta, coronárias, carótidas e artérias periféricas. É a causa principal de morte no hemisfério ocidental, devido as síndromes cardiovasculares, tais como o infarto do miocárdio, insuficiência cardíaca e acidentes cerebrovasculares. Quantidades enormes de recursos econômicos e humanos são usadas em tratamentos de suas complicações, inclusive estudos de imagem, cirurgias coronárias, intervenções com cateteres, marcapasso e tratamentos médicos. Tratar complicações, entretanto, são ações a posteriori. Uma alternativa melhor seria prevenir o desenvolvimento da aterosclerose, ou pelo menos identificar os pacientes que tenham risco de eventos agudos e intervir antes de sua ocorrência. O objetivo desta revisão é discutir o valor prognóstico dos fatores de riscos tradicionais e emergentes, e o papel dos métodos diagnósticos não invasivos para a doença coronária - teste de esforço, eco estresse, ultra-sonografia dúplex, tomografia computadorizada e a ressonância magnética. A combinação de marcadores biológicos e de métodos não invasivos, é de grande utilidade na identificação precoce da doença aterosclerótica. Futuros desenvolvimentos logo aperfeiçoarão nossa capacidade de identificar o paciente vulnerável e nos permitir um manejo mais individualizado

Comparison of Non-Invasive Methods for the Detection of Coronary Atherosclerosis

BACKGROUND: Non-invasive detection of atherosclerosis is critical for its prevention. OBJECTIVE: To correlate non-invasively detectable indicators of coronary atherosclerosis, or Coronary Artery Disease (i.e., classical risk factors, hs-CRP test results, carotid intima-media thickness, endothelial function, ankle-brachial index and calcium score by computed tomography) with the extent of coronary disease assessed by the Friesinger index from conventional coronary angiography. METHODS: We conducted a prospective study of 100 consecutive patients, mean age 55.1 ± 10.7 years, 55% men and 45% women. Patients with acute coronary syndrome, renal dialytic insufficiency, collagen disease and cancer were not included. All patients were subjected to clinical evaluation and laboratory tests. Endothelial function of the brachial artery and carotid artery were evaluated by high-resolution ultrasound; ankle-brachial index and computed tomography for coronary determination of calcium score were also performed, and non-HDL cholesterol and TG/HDL-c ratio were calculated. All patients were subjected to coronary angiography at the request of the assistant physician. We considered patients without an obstructive lesion (< 29% stenosis) demonstrated by coronary angiography to be normal. RESULTS: Univariate analysis showed that calcium score, HDL-c, TG/HDL ratio and IMT were significantly correlated with the Friesinger index. However, multivariate analysis indicated that only calcium score and low HDL-c levels correlated significantly with the extension of CAD. On the other hand, hs-CRP, LDL-c, flow-mediated dilation, and Framingham score did not correlate with the Friesinger index. ROC analysis showed that calcium score, HDL-c and TG-HDL ratio accurately predicted extensive CAD in a statistically significant manner. CONCLUSION: It is possible to approximately determine the presence and extent of CAD by non-invasive methods, especially by calcium score, HDL-c and TG/HDL-c ratio assays

Selective Cyclooxygenase-2 Inhibition Protects Against Myocardial Damage in Experimental Acute Ischemia

BACKGROUND: Acute myocardial infarction is associated with tissue inflammation. Early coronary reperfusion clearly improves the outcome but may help propagate the inflammatory response and enhance tissue damage. Cyclooxygenase-2 is an enzyme that catalyzes the initial step in the formation of inflammatory prostaglandins from arachidonic acid. Cyclooxygenase-2 levels are increased when ischemic cardiac events occur. The overall function of COX-2 in the inflammatory process generated by myocardial ischemic damage has not yet been elucidated. GOAL: The objective of this study was to determine whether a selective cyclooxygenase-2 inhibitor (rofecoxib) could alter the evolution of acute myocardial infarction after reperfusion. METHODS AND RESULTS: This study was performed with 48 mongrel dogs divided into two groups: controls and those treated with the drug. All animals were prepared for left anterior descending coronary artery occlusion. The dogs then underwent 180 minutes of coronary occlusion, followed by 30 minutes of reperfusion. Blood samples were collected from the venous sinus immediately before coronary occlusion and after 30 minutes of reperfusion for measurements of CPK-MB, CPK-MBm and troponin I. During the experiment we observed the mean blood pressure, heart rate and coronary flow. The coronary flow and heart rate did not change, but in the control group, there was blood pressure instability, in addition to maximal levels of CPK-MB post-infarction. The same results were observed for CPK-MBm and troponin I. CONCLUSION: In a canine model of myocardial ischemia-reperfusion, selective inhibition of Cyclooxygenase-2 with rofecoxib was not associated with early detrimental effects on the hemodynamic profile or the gross extent of infarction; in fact, it may be beneficial by limiting cell necrosis

Hormone replacement therapy increases levels of antibodies against heat shock protein 65 and certain species of oxidized low density lipoprotein

Hormone replacement therapy (HRT) reduces cardiovascular risks, although the initiation of therapy may be associated with transient adverse ischemic and thrombotic events. Antibodies against heat shock protein (Hsp) and oxidized low density lipoprotein (LDL) have been found in atherosclerotic lesions and plasma of patients with coronary artery disease and may play an important role in the pathogenesis of atherosclerosis. The aim of the present study was to assess the effects of HRT on the immune response by measuring plasma levels of antibodies against Hsp 65 and LDL with a low and high degree of copper-mediated oxidative modification of 20 postmenopausal women before and 90 days after receiving orally 0.625 mg equine conjugate estrogen plus 2.5 mg medroxyprogesterone acetate per day. HRT significantly increased antibodies against Hsp 65 (0.316 ± 0.03 vs 0.558 ± 0.11) and against LDL with a low degree of oxidative modification (0.100 ± 0.01 vs 0.217 ± 0.02) (P<0.05 and P<0.001, respectively, ANOVA). The hormone-mediated immune response may trigger an inflammatory response within the vessel wall and potentially increase plaque burden. Whether or not this immune response is temporary or sustained and deleterious requires further investigation.Universidade de São Paulo Faculdade de Medicina Instituto do CoraçãoUniversidade Federal de São Paulo (UNIFESP) Departamento de BiofísicaUniversidade de São Paulo Instituto de Ciências Biomédicas IV Departamento de Imunologia and Instituto de Medicina Tropical da Universidade de São PauloUNIFESP, Depto. de BiofísicaSciEL

Evidence that the degree of obstructive sleep apnea may not increase myocardial ischemia and arrhythmias in patients with stable coronary artery disease

There is controversy regarding whether obstructive sleep apnea is responsible for triggering myocardial ischemia, arrhythmias and heart rate variability in patients with coronary artery disease. OBJETIVE: The objective of this study was to identify relationships between sleep apnea, myocardial ischemia and cardiac arrhythmia in patients with coronary artery disease. METHODS: Fifty-three patients with stable coronary disease underwent simultaneous polysomnography and electrocardiographic Holter recording. The apnea-hypopnea index (AHI) was defined as the number of apneas/hypopneas per hour of sleep. Patients were divided into a Control group (AHI15, n=23 pts) and an Apnea group (AHI>;15, n=30 pts). A subgroup of 13 patients with an AHI>;30 (Severe Apnea group) was also studied. We analyzed ischemic episodes (ST-segment depressions >;1 mm, >; 1 min), heart rate variability and the occurrence of arrhythmias during wakefulness and sleep. RESULTS: Baseline clinical characteristics among the groups were similar except for higher blood pressure in the Apnea groups (

Cardioprotection conferred by exercise training is blunted by blockade of the opioid system

OBJECTIVES: To investigate the effect of opioid receptor blockade on the myocardial protection conferred by chronic exercise and to compare exercise training with different strategies of myocardial protection (opioid infusion and brief periods of ischemia-reperfusion) preceding irreversible left anterior descending coronary ligation. INTRODUCTION: The acute cardioprotective effects of exercise training are at least partly mediated through opioid receptor-dependent mechanisms in ischemia-reperfusion models. METHODS: Male Wistar rats (n = 76) were randomly assigned to 7 groups: (1) control; (2) exercise training; (3) morphine; (4) intermittent ischemia-reperfusion (three alternating periods of left anterior descending coronary occlusion and reperfusion); (5) exercise training+morphine; (6) naloxone (a non-selective opioid receptor blocker) plus morphine; (7) naloxone before each exercise-training session. Myocardial infarction was established in all groups by left anterior descending coronary ligation. Exercise training was performed on a treadmill for 60 minutes, 5 times/week, for 12 weeks, at 60% peak oxygen (peak VO2). Infarct size was histologically evaluated. RESULTS: Exercise training significantly increased exercise capacity and &#916;VO2 (VO2 peak - VO2 rest) (p<0.01 vs. sedentary groups). Compared with control, all treatment groups except morphine plus naloxone and exercise training plus naloxone showed a smaller infarcted area (p<0.05). No additional decrease in infarct size occurred in the exercise training plus morphine group. No difference in myocardial capillary density (p = 0.88) was observed in any group. CONCLUSIONS: Exercise training, morphine, exercise training plus morphine and ischemia-reperfusion groups had a smaller infarcted area than the control group. The effect of chronic exercise training in decreasing infarct size seems to occur, at least in part, through the opioid receptor stimulus and not by increasing myocardial perfusio

Value of adenosine infusion for infarct size determination using real-time myocardial contrast echocardiography

BACKGROUND: Myocardial contrast echocardiography has been used for determination of infarct size (IS) in experimental models. However, with intermittent harmonic imaging, IS seems to be underestimated immediately after reperfusion due to areas with preserved, yet dysfunctional, microvasculature. The use of exogenous vasodilators showed to be useful to unmask these infarcted areas with depressed coronary flow reserve. This study was undertaken to assess the value of adenosine for IS determination in an open-chest canine model of coronary occlusion and reperfusion, using real-time myocardial contrast echocardiography (RTMCE). METHODS: Nine dogs underwent 180 minutes of coronary occlusion followed by reperfusion. PESDA (Perfluorocarbon-Exposed Sonicated Dextrose Albumin) was used as contrast agent. IS was determined by RTMCE before and during adenosine infusion at a rate of 140 mcg·Kg(-1)·min(-1). Post-mortem necrotic area was determined by triphenyl-tetrazolium chloride (TTC) staining. RESULTS: IS determined by RTMCE was 1.98 ± 1.30 cm(2 )and increased to 2.58 ± 1.53 cm(2 )during adenosine infusion (p = 0.004), with good correlation between measurements (r = 0.91; p < 0.01). The necrotic area determined by TTC was 2.29 ± 1.36 cm(2 )and showed no significant difference with IS determined by RTMCE before or during hyperemia. A slight better correlation between RTMCE and TTC measurements was observed during adenosine (r = 0.99; p < 0.001) then before it (r = 0.92; p = 0.0013). CONCLUSION: RTMCE can accurately determine IS in immediate period after acute myocardial infarction. Adenosine infusion results in a slight better detection of actual size of myocardial damage