Role of chemokines in promoting instability of coronary atherosclerotic plaques and the underlying molecular mechanism

Our aim was to investigate the role of chemokines in promoting instability of coronary atherosclerotic plaques and the underlying molecular mechanism. Coronary angiography and intravascular ultrasound (IVUS) were performed in 60 stable angina pectoris (SAP) patients and 60 unstable angina pectoris (UAP) patients. The chemotactic activity of monocytes in the 2 groups of patients was examined in Transwell chambers. High-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1), regulated on activation in normal T-cell expressed and secreted (RANTES), and fractalkine in serum were examined with ELISA kits, and expression of MCP-1, RANTES, and fractalkine mRNA was examined with real-time PCR. In the SAP group, 92 plaques were detected with IVUS. In the UAP group, 96 plaques were detected with IVUS. The plaques in the UAP group were mainly lipid 51.04% (49/96) and the plaques in the SAP group were mainly fibrous 52.17% (48/92). Compared with the SAP group, the plaque burden and vascular remodeling index in the UAP group were significantly greater than in the SAP group (P<0.01). Chemotactic activity and the number of mobile monocytes in the UAP group were significantly greater than in the SAP group (P<0.01). Concentrations of hs-CRP, MCP-1, RANTES, and fractalkine in the serum of the UAP group were significantly higher than in the serum of the SAP group (P<0.05 or P<0.01), and expression of MCP-1, RANTES, and fractalkine mRNA was significantly higher than in the SAP group (P<0.05). MCP-1, RANTES, and fractalkine probably promote instability of coronary atherosclerotic plaque.

The initiation of coronary angioplasty and stenting in a single outpatient centre in Barbados / La iniciación de la angioplastia y el estent de la arteria coronaria en un centro ambulatorio en Barbados

Percutaneous transluminal coronary angioplasty (PTCA) is a novel procedure to Barbadian healthcare. Only one centre in Barbados provides PTCA and stenting. This is a retrospective study aimed at describing the initial results of coronary angioplasty and stenting in the first 48 patients at the Carib-American Heart Centre and exploring the feasibility and safety of coronary angioplasty and stenting in Barbados. Forty-eight patients underwent PTCA during the period March 2002 to June 2004 inclusive, with or without intracoronary stenting. Most (64.6%) of the patients were male and 43.7% were diabetic. The most common vessels involved were the left anterior descending coronary artery (LAD) and the right coronary artery (RCA). In one patient, attempted stenting was unsuccessful but PTCA reduced stenosis. One patient had previous PTCA and stenting of the LAD and two patients had coronary artery bypass grafting (CABG) prior to the procedure. Twenty-one per cent of the patients treated had severe triple vessel disease. There were no cases of restenosis or acute vessel closure, during or immediately following the procedure that required emergency PTCA or CABG. All patients were discharged within 24 hours of the procedure. Procedural success was 100%. In conclusion, outpatient PTCA and stenting is safe and feasible in the Barbadian population. Coronary artery bypass grafting is still the procedure of choice for treating coronary artery disease (CAD) involving the left main coronary artery but PTCA is indicated in some cases of severe triple vessel disease.

La angioplastia coronaria transluminal percútanla (ACTP) es un procedimiento nuevo en la atención a la salud en Barbados. Sólo un centro en Barbados ofrece ACTP y estent (o cánula intraluminal de arteria coronaria). El presente trabajo es un estudio retrospectivo destinado a describir los resultados iniciales de la angioplastia y el estent coronarios en los primeros 48 pacientes en el Centro Caribe-americano de Cardiología, y explorar la factibilidad y seguridad de la angioplastia y el estent en Barbados. Cuarenta y ocho pacientes fueron sometidos a ACTP durante el periodo de marzo 2002 a junio 2004 inclusive, con o sin estent intracoronario. La mayor parte (64.6%) de los pacientes eran varones y un 43.7% eran diabéticos. Los vasos más comúnmente involucrados fueron la arteria coronaria descendente anterior izquierda (DAI) y la arteria coronaria derecha (ACD). En un paciente, el intento de estent no tuvo éxito, pero la ACTP redujo la estenosis. A un paciente le fue practicada previamente la ACTP y el estent de la DAI, y a dos pacientes se les realizó injerto de bypass de la arteria coronaria (IBAC) antes del procedimiento. El veintiún por ciento de los pacientes tratados tuvo enfermedad vascular triple. No hubo ningún caso de reestenosis o cierre vascular agudo, durante o inmediatamente después del procedimiento, que requiriera ACTP o IBAC de emergencia. Todos los pacientes fueron dados de alta dentro de las 24 horas tras el procedimiento. El éxito de los procedimientos fue del 100%. En conclusión, el estent y el ACTP ambulatorios son seguros y factibles para la población barbadense. El injerto de bypass de la arteria coronaria sigue siendo el procedimiento de elección para tratar casos de la enfermedad de la arteria coronaria (EAC) que involucren la arteria coronaria izquierda principal, pero la ACTP se indica en algunos casos de enfermedad vascular triple.

Isquemia silenciosa na doença coronariana estável em vigência de tratamento medicamentoso / Silent myocardial ischemia in patients with stable coronary artery disease receiving conventional antianginal drug therapy

FUNDAMENTO: Existem poucos dados sobre comportamento da isquemia miocárdica às atividades habituais na vigência da medicação em pacientes com doença coronariana. OBJETIVO: Estudar mecanismo gerador da isquemia miocárdica avaliando-se o comportamento da pressão arterial e da freqüência cardíaca em pacientes com doença aterosclerótica estável, medicados e com evidência de isquemia. MÉTODOS: Cinqüenta pacientes (40 homens) realizaram ambulatorialmente por 24 horas a monitorização eletrocardiográfica sincronizada com a monitorização da pressão arterial. RESULTADOS: Em 17 pacientes detectaram-se 35 episódios de isquemia miocárdica, com duração total de 146,3 minutos, ocorrendo relato de angina em cinco casos. Houve 29 episódios (100,3 minutos) durante o período de vigília, com 11 episódios (35,3+3,7 min) no período das 11 às 15 horas. A avaliação da pressão arterial e freqüência cardíaca nos três intervalos de 10 minutos posteriores ao momento de isquemia mostrou diferença estatisticamente significante (p<0,05), o que não ocorreu nos três intervalos anteriores. Entretanto, durante o momento isquêmico, percebeu-se elevação maior que 10 mmHg da pressão arterial e de cinco batimentos por minuto da freqüência cardíaca quando comparado ao intervalo de tempo entre 20 e 10 minutos anterior. A freqüência cardíaca média no início da isquemia durante teste ergométrico prévio ao estudo foi de 118,2+14,0, e de 81,1+20,8 batimentos por minuto na eletrocardiografia de 24 horas (p<0,001). CONCLUSÃO: A incidência de isquemia silenciosa é freqüente na doença coronária estável, relacionando-se com alterações da pressão arterial e da freqüência cardíaca, com diferentes limiares de isquemia para o mesmo paciente.

BACKGROUND: Few data are available on the behavior of myocardial ischemia during daily activities in patients with coronary artery disease receiving antianginal drug therapy. OBJECTIVE: To study the mechanism generating myocardial ischemia by evaluating blood pressure and heart rate changes in patients with stable atherosclerotic disease receiving drug therapy and with evidence of myocardial ischemia. METHODS: Fifty non-hospitalized patients (40 males) underwent 24-hour electrocardiographic monitoring synchronized with blood pressured monitoring. RESULTS: Thirty five episodes of myocardial ischemia were detected in 17 patients, with a total duration of 146.3 minutes; angina was reported in five cases. Twenty nine episodes (100.3 minutes) occurred during wakefulness, with 11 episodes (35.3 + 3.7 min) in the period from 11 a.m. to 3 p.m. Blood pressure and heart rate evaluation in the three ten-minute intervals following the ischemic episodes showed a statistically significant difference (p< 0.05), unlike that shown for the three intervals preceding the episodes. However, during the ischemic episode, a higher than 10-mmHg elevation in blood pressure and 5 beats per minute in heart rate were observed when compared with the time interval between 20 and 10 minutes before the episode. The mean heart rate at the onset of ischemia during the exercise test performed before the study was 118.2 + 14.0, and 81.1 + 20.8 beats per minute on the 24-hour electrocardiogram (p < 0.001). CONCLUSION: The incidence of silent myocardial ischemia is high in stable coronary artery disease and is related to alterations in blood pressure and heart rate, with different thresholds for ischemia for the same patient.

Curso de Atualização em Cardiologia: aula 2: Angina estável crônica / Actualization in Cargiology: class 2: stable chronic angina

A doença cardiovascular ainda é altamente prevalente no mundo inteiro, e a angina estável é uma de suas apresentações mais comuns. Três controvérsias principais são o manejo dos fatores de risco, o tratamento clínico e a intervenção. Com relação ao tratamento clínico, alé, de aspirina, inibidores da enzina conversora da angiotensina e betabloqueadores. A intervenção coronária percutânea alivia os sintomas sem prolongar a sobrevida além do tratamento clínico. Porém, dados de mortalidade favorecem a cirurgia de revascularização miocárdica em indivíduos com doença bivascular ou trivascular. Novas opções de tratamento sob investigação incluem drogas antianginosas, assim como a terapia celular. Assim, a angina de esforço precisa de uma ampla avaliação, mudanças no estilo de vida e tratamento individualizado para cada paciente.

Ativação plaquetária em formas clínicas distintas da doença arterial coronariana (papel da P-selectina e de outros marcadores nas anginas estável e instável) / Platelet activation in different clinical forms of the coronary artery disease (roll of P-selectin and others platelet markers in the stable and unstable angina) / Platelet activation in different clinical forms of the coronary artery disease (roll of P-selectin and others platelet markers in the stable and unstable angina)

OBJETIVO: Os marcadores da ativação plaquetária em geral se apresentam elevados na doença arterial coronariana. Desse modo, procuramos identificar a presença e as potenciais associações de diferentes marcadores da ativação plaquetária. MÉTODOS: Estudamos pacientes com angina instável (n=28), pacientes com angina estável (n=36) e pacientes sem doença arterial coronariana (n=30); sexo e idade foram estratificados. Os níveis sangüíneos da molécula de adesão P-selectina, do thromboxane B2 e de serotonina foram medidos por imunoensaios enzimáticos. RESULTADOS: Quando comparamos os grupos, os resultados foram: a P-selectina, o thromboxane B2 e os níveis do serotonina apresentaram-se significativamente mais elevados nos pacientes com angina instável do que nos pacientes com angina estável. CONCLUSÃO: Estes marcadores da ativação plaquetária podem, portanto, identificar formas instáveis de doença arterial coronariana.

OBJECTIVE: Markers of platelet activation are elevated in coronary artery disease. We sought to identify the presence and the potential associations of different markers of platelet activation. METHODS: We studied patients with unstable angina (n=28), patients with stable angina (n=36) and patients without coronary artery disease (n=30); sex and age matched. Blood levels of the adhesion molecule P-selectin, Thromboxane B2 and Serotonin were measured by enzyme immunoassays. RESULTS: When we compared the groups the results were: sP-selectin, thromboxane B2 and serotonin levels were significantly higher in patients with unstable angina than in patients with stable angina. CONCLUSION: These markers of platelet activation were able to identify unstable forms of coronary artery disease.

API expert consensus document on management of ischemic heart disease.

The incidence of coronary artery disease (CAD) has dramatically increased in India during the recent years. There are two facets of CAD: stable CAD and unstable CAD which includes patients with acute coronary syndrome (unstable angina, non-ST elevation myocardial infarction, ST elevation myocardial infarction). The treatment of stable CAD (stable angina) includes anti-anginal medication, medication to modify atherosclerosis and aggressive treatment of causative risk factors. Those patients with stable CAD who have symptoms refractory to medical treatment usually require coronary angiography to be followed by either percutaneous or surgical revascularization. Percutaneous coronary revascularization using drug eluting stents has been a major revolution during the last five years for symptomatic relief of angina in symptomatic CAD and can be applied to large subsets of patients. Off-pump surgical revascularization using arterial grafts is a major advance and bypass surgery continues to remain treatment of choice in diabetics with multi-vessel CAD, left main CAD and in patients with multivessel disease and impaired ventricles. Acute coronary syndromes are usually caused by plaque rupture with resultant thrombus and present as unstable angina, non-ST elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI). It is now increasingly realized that these patients (particularly the one with high risk) are best managed in advanced cardiac care centres with facilities for cardiac catheterization laboratory, percutaneous coronary interventions and coronary bypass surgery. In both, NSTEMI and STEMI aggressive medical management involving nitrates, ACE inhibitors, beta-blockers, dual anti-platelet agents, heparin and statins are recommended. High risk patients with NSTE-ACS require use of glycoprotein IIa / IIIb inhibitors along with early invasive approach involving coronary angiography, angioplasty using drug eluting stent and in some patients bypass surgery. Early reperfusion is key to management of patients presenting with STEMI. If facilities are available, primary percutaneous coronary intervention (angioplasty with stenting) is treatment of choice for patients with STEMI. In our country, thrombolysis still remains the most frequently utilized reperfusion therapy and all efforts should be devoted to provide this therapy at the earliest. All high risk patients with STEMI (including cardiogenic shock) are best treated in higher centres and these patients should be promptly transported to such centres. Early coronary angiography is recommended for majority of patients following thrombolysis for risk stratification and further treatment. In acute coronary syndromes there is drift towards early invasive treatment and this is reflected in marked increase in cardiac care (catheterization laboratories and cardiac surgery centers) facilities throughout India. All patients with CAD require life-long supervised treatment which includes medication, control of risk factors and lifestyle modification. Avoidance of smoking, heart healthy diet, proper exercise, ideal weight management are important for all the patients. Statins, ACE inhibitors, beta-blockers, antiplatelet agents have a great role to play in treatment and prevention and these drugs should be utilized under medical supervision. It is important that the medical profession play an important role in critically evaluating the use of diagnostic procedures and therapies as they are introduced and tested in the detection and management of cardiac disorders. The American College of Cardiology (ACC), American Heart Association (AHA), European Society of Cardiology (ESC), Society for Cardiovascular Angiography and Interventions (SCAI) and several other societies engage in production of guidelines in the area of cardiovascular diseases from time to time. These guidelines attempt to define practices that meet the needs of most patients in most circumstances. The aim of the guidelines is to improve the patient care. The ultimate judgement regarding the care of the particular patient is to be made by the clinician / healthcare provider keeping in mind all the circumstances. The incidence and prevalence of coronary artery disease (CAD) has increased tremendously in India during the last two decades and this change is largely attributable to lifestyle changes. There has also been a rapid progress in the treatment of CAD with proliferation of specialized cardiac care units, intensive care units, cardiac catheterization laboratories and facilities for bypass surgery. It is estimated that there are over 400 catheterization laboratories currently in India and nearly half of them are located in six major cities. The increase in disease and availability of facilities has resulted in a dramatic change and the focus is shifting from only medical treatment to invasive treatment. This document is an expert consensus document which has been prepared by going through the available guidelines and other relevant literature on the subject. The experts have performed a formal review of the literature and have weighed the strength of evidence for or against a particular therapy as it can be applied in Indian scenario. The consensus document deals with the management of ischemic heart disease (IHD) under following sections: 1) Stable Angina 2) Non ST Elevation Acute Coronary Syndrome (NSTE-ACS) 3) ST Elevation Acute Coronary Syndrome (STE-ACS) or Acute Myocardial Infarction (AMI).

Changes of Coronary Blood Flow in Vasospastic Angina under Cold Stimulation by Transthoracic Doppler Echocardiography

This study was done to evaluate changes of microvascular function under cold stimulation by measuring coronary flow velocities (CFVs) in vasospastic angina (VA) patients using transthoracic Doppler echocardiography (TTDE). 14 patients with VA and 15 healthy controls were included. CFVs were measured at the distal left anterior descending coronary artery by TTDE at baseline and under cold stimulation. Hyperemia was induced by intravenous adenosine infusion (140 microgram/kg/min). At baseline, CFVs and coronary flow reserve (CFR) were not different between controls and VA patients. Under cold stimulation, the degree of increment of CFV with adenosine was lower in VA patients than in controls. Comparing baseline with cold stimulation, coronary flow reserve (CFR) increased (3.1 +/-0.7 to 3.8 +/-1.0, p=0.06) in controls. In contrast, in VA patients, CFR was decreased (2.8 +/-0.9 to 2.6 +/-0.7, p=0.05) and coronary vascular resistance index markedly increased (0.35 to 0.43, p=0.01). Throughout the study, no patient experienced chest pain or ECG changes. In VA patients, CFR was preserved at baseline, but coronary blood flow increase in response to cold stimulation was blunted and CFR was decreased. These findings suggest that endothelial dependent vasodilation is impaired at the coronary microvascular and the epicardial artery level in VA under cold stimulation.

Síndrome Tako-Tsubo (Discinesia antero-apical transitoria): Primer caso descrito en América Latina y revisión de la literatura / Tako-Tsubo syndrome (transient antero-apical dyskinesia): first case reported in Latin America and review of the literature

El síndrome Tako-Tsubo es una entidad clínica de reciente descripción que simula un infarto agudo del miocardio. Comprende la asociación de dolor precordial con elevación de ST-T en derivaciones precordiales en ausencia de la oclusión de alguna arteria coronaria y con una deformación típica y reversible del ventrículo izquierdo como consecuencia de discinesia anteroapical con hipercinesia basal. Afecta predominantemente al sexo femenino y en una revisión de 2001 se refiere que sólo dos casos habían sido reportados en pacientes no japoneses. Presentamos un caso típico de síndrome Tako-Tsubo recurrente y desencadenado por estrés emotivo. Este es el primer caso informado de Latinoamérica, el que se complementa con una revisión actualizada de la literatura. Esta última sugiere que el síndrome Tako-Tsubo es más frecuente de lo sospechado, pero suele pasar desapercibido. Es importante reconocer este síndrome ya que su manejo y pronóstico es diferente al del infarto agudo del miocardio que resulta de la oclusión trombótica de una placa ateroesclerosa coronaria.

Tako-Tsubo syndrome (TTS) is a recently described entity that can mimic an acute myocardial infarction. It is characterized by anginal chest pain with ST-T elevation in precordial leads, no coronary obstruction on angiography, and as its distinctive feature, a reversible left ventricular antero-apical ballooning with basal hyperkinesis. TTS is more frequent in female and elderly patients and in an article published in 2001 it was mentioned that only two cases had been reported outside Japan. We describe a typical case of recurrent TTS triggered by intense emotional stress. This is the first case reported from Latin America. A review of the literature suggests that TTS is more frequent than previously thought but apparently due to lack of awareness of this entity it can go unrecognized. Identification of TTS is of clinical importance because its management and prognosis differs significantly from that of an acute myocardial infarction that results from the thrombotic occlusion of a coronary atherosclerotic plaque.

The circadian pattern of ischaemic heart disease events in Indian population.

A circadian variation of the onset of almost all ischaemic heart disease (IHD) manifestations with an increased incidence between 6:00 a.m. to 12:00 noon has been reported in several publications during the last decade. This study included 605 patients of various IHD subgroups, i.e., acute Q-wave myocardial infarction (n = 174), unstable angina (n = 266), non-Q myocardial infarction (n = 67), acute pulmonary oedema (n = 35) and sudden cardiac death (n = 63) proven to be due to IHD by electrocardiogram and/or autopsy. In overall, 33.55% (p < 0.0001) of patients had the IHD events with an increased frequency between 6:00 a.m. To 12:00 noon (2nd quarter of the day.) The distribution in the remaining, 1st 3rd and 4th quarters was 22.64%, 20.99% and 22.80%, respectively. Similar circadian rhythm (2nd quarter peak) was seen in males (n = 486), females (n = 119), patients ages < 60 years (n = 388), patients without past history of IHD (n = 434) and in those not on any medications (n = 359). However in patients with past history of IHD and diabetics, the circadian distribution did not differ from the random and the cases were distributed almost evenly in all the four quarters of the day. 39.08% of all the acute Q wave myocardial infarction (A-QMI), 33.45% of unstable angina and 36.5% of sudden cardiac deaths also occurred between 6:00 a.m. and 12:00 noon. However 51.42% cases of acute pulmonary oedema were encountered in the 4th quarter of the day and patients with non Q-myocardial infarction (non-QMI) did not show any particular pattern in relation to circadian rhythm. Thus it was inferred that in Indian population too the circadian pattern of IHD manifestations are similar to other population studies and morning appears to be the time, when the triggers (transient precipitating risk factors) that lead to these events are likely to be prominent. Study of these triggers and/or early morning pathophysiological changes may go a long way in understanding ischaemic heart disease and suggesting possible means of prevention.

Prueba de esfuerzo combinado para diagnóstico de cardiopatía isquémica / Treadmill in the diagnosis of ischemic cardiopathy

Para demostrar la utilidad de la prueba de esfuerzo combinado, se estudiaron 200 personas con sospecha de cardiopatía isquémica por infarto miocárdico, angina de pecho, arritmia cardiaca, alteraciones de repolarización o síntomas atípicas en personas con factores de riesgo coronario. La prueba fue realizada vigilando frecuencia cardiaca, tensión arterial y electrocardiograma en reposo y esfuerzo a uno, tres y siete minutos de recuperación. Se interrumpió al alcanzar la frecuencia cardiaca máxima o presentar infradesnivel de ST mayor de l mm, arritmia cardiaca o fatiga. La edad promedio fue 55.18 ñ 12 años, 151 varones y 59 mujeres, el producto de TA por FC fue 21651 ñ 6601. En 74.5 por ciento el resultado fue concluyente, por desnivel de ST menor de 2 mm en 33 por ciento y mayor de 2 mm en 13.5 por ciento. Arritmia cardiaca en 17.5 por ciento, maligna en 12 por ciento. La prueba de esfuerzo combinado es útil en el estudio de cardiopatía isquémica

Collateral arteries in the presence of obstructive coronary disease.

BACKGROUND. The clinical importance of coronary collaterals in the presence of obstructive coronary artery disease is not clearly defined. METHODS. We retrospectively analysed the clinical and angiographic features of 100 patients with > or = 90% luminal diameter stenosis involving at least one major coronary artery. Coronary collaterals were graded 0 to 4 (Nitzberg's classification) and studied to determine their influence on clinical parameters. RESULTS. Thirty patients had no collaterals (group I) and 70 showed collaterals (group II). There were no significant differences between groups I and II in age and sex distribution, prevalence of risk factors of coronary artery disease (hypertension, diabetes, smoking, hypercholesterolaemia), duration of symptoms of coronary artery disease and prior myocardial infarction. Groups I and II had similar types (left anterior descending 73% v. 71%; left circumflex 50% v. 50% and right coronary 37% v. 56%) and numbers of arteries involved (one 47% v. 41%; two 47% v. 40%; three 7% v. 19%). Group II had a significantly lower prevalence of rest angina (14% v. 47%, p = 0.002). This difference was also evident when the patients were re-classified according to the extent of flow through the collaterals. Those with good collateralization (Nitzberg grades 3 and 4) had a lower prevalence of rest angina (13%) compared to those with poor collateralization (Nitzberg grades 0 to 2; 35%, p = 0.02). CONCLUSION. Coronary artery collaterals may reduce the incidence of rest angina in patients with obstructive coronary artery disease.