J. Péricles Esteves

Anti-inflammatory effect of atorvastatin (80 mg) in unstable angina pectoris and non–Q-wave acute myocardial infarction

In this randomized trial, C-reactive protein increased during the first 5 days of an acute coronary syndrome in patients treated with placebo, but this phenomenon was not observed in those randomized to atorvastatin 80 mg/day. This suggests that short-term statin therapy inhibits inflammation in patients with non-ST-elevation acute coronary syndromes.

Prognostic value of cytokines and chemokines in addition to the GRACE Score in non-ST-elevation acute coronary syndromes.

BACKGROUND Increased cytokine and chemokine levels are associated with cardiovascular events in patients with non-ST-elevation acute coronary syndromes (ACS), but the incremental prognostic value of these inflammatory markers is not known. We determined if cytokine and chemokine assessment adds prognostic information to the GRACE Score in patients with ACS. METHODS Five cytokines (interleukin (IL)-1beta, IL-6, IL-10, IL-12p70, and tumor necrosis factor (TNF)-alpha soluble receptor I), five chemokines (IL-8, CCL5, CXCL9, CCL2, and CXCL10) and C-reactive protein (CRP) were measured at admission of 87 patients admitted with ACS. RESULTS During hospitalization, the incidence of cardiovascular events was 13% (7 deaths, 1 nonfatal acute myocardial infarction, and 3 refractory unstable angina). Individuals who developed events had significantly greater levels of CRP, IL-1beta, IL-12, TNF-alpha, IL-8, CXCL9 and CCL2, compared with those free of events. Thus, these markers were used to build an Inflammatory Score, by the input of one point for each of these variables above the 75th percentile. After adjustment for the GRACE Score, the Inflammatory Score independently predicted events (OR=1.80; 95% CI=1.12-1.88). Incorporation of the Inflammatory Score into the GRACE Score promoted a C-statistics improvement from 0.77 (95% CI=0.58-0.96) to 0.85 (95% CI=0.71-1.0). Net reclassification improvement obtained with GRACE-Inflammatory Score was 13% (P=0.007), indicating a significant reclassification. When only CRP was incorporated into GRACE, the increase on C-statistics was not relevant (from 0.77 to 0.80). CONCLUSION Cytokines and chemokines measured at admission add prognostic information to the GRACE Score in patients admitted with ACS.

HDL-cholesterol level provides additional prognosis in acute coronary syndromes☆

In the setting of acute coronary syndromes, plasma lipids have not been defined as prognostic variables, however little research has been dedicated to this specific issue. In order to test the independent predictive value for in-hospital events of low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol and triglycerides measured at hospital admission, 97 individuals with unstable angina or non-ST-elevation acute myocardial infarction were evaluated. In-hospital events, defined as death, non-fatal myocardial infarction or recurrent unstable angina, were significantly predicted by HDL-cholesterol (C-statistics=0.69; 95% CI=0.55-0.83, P=0.018), contrary to LDL-cholesterol (C-statistics=0.40; 95% CI=0.24-0.56, P=0.23) and triglycerides (C-statistics=0.48; 95% CI=0.31-0.65, P=0.83). The best HDL-cholesterol cut-off point was 32 mg/dl, with a 33% incidence of events in patients with HDL-cholesterol < or =32 mg/dl, compared with only 9% in those with HDL-cholesterol>32 mg/dl (P=0.003). Logistic regression analysis showed HDL-cholesterol< or =32 mg/dl (OR=3.6; 95% CI=1.0-14; P=0.05) and TIMI Risk Score (OR=2.3; 95% CI=1.4-2.9, P=0.001) as the independent predictors of events. Furthermore, the addition of HDL-cholesterol to TIMI Risk Score improved its C-statistic from 0.81 to 0.85. In conclusion, as opposed to LDL-cholesterol and triglycerides, HDL-cholesterol level adds prognostic value to the prediction of in-hospital recurrent events during non-ST-elevation acute coronary syndromes.

Proteína C-reativa e prognóstico em síndromes coronarianas agudas: revisão sistemática e metanálise

Despite the association between high-sensitivity C-reactive protein (CRP) and recurrent events in non-ST elevation acute coronary syndromes (ACS), routine determination of this marker has not been recommended. In order to verify whether the current scientific evidence justifies the inclusion of CRP for risk stratification at hospital admission of patients with ACS, we carried out a systematic review and meta-analysis of the studies indexed in MEDLINE, SciELO or LILACS, with the following inclusion criteria: prospective cohort design and assessment of the prognostic value of CPR, as measured using a high-sensitivity method at the moment of hospital admission of patients with ACS. Nineteen studies met the inclusion criteria. In relation to the long-term follow-up, there was a consistent association between CRP and cardiovascular events, with an overall odds ratio (OR) of 4.6 (95% CI = 2.3 - 7.6) and overall multivariate OR of 2.5 (95% CI = 1.8-3.4). As for the short-term, nine studies were positive and six were negative, with an overall OR of 1.65 (95% CI = 1.2-2.3). The overall multivariate OR was not obtained for the short-term follow-up, because this measurement was described only in three heterogeneous studies. Only two short-term studies analyzed the incremental predictive value of CRP in relation to multivariate models, with contradicting results. In conclusion, the small number of assessments of the incremental value of CRP, in conjunction with controversial results regarding the independent predictive value of CRP for short-term events does not support the recommendation of the routine use of CRP for risk stratification at admission of patients with ACS.A despeito da associacao entre proteina C-reativa de alta sensibilidade (PCR) e eventos recorrentes em sindromes coronarianas agudas sem supradesnivel do segmento ST (SCA), a medida rotineira deste marcador nao tem sido recomendada. No intuito de avaliar se as evidencias cientificas atuais justificam a incorporacao da PCR para estratificacao de risco na admissao hospitalar de pacientes com SCA, realizamos revisao sistematica e metanalise dos trabalhos indexados no MEDLINE, SCIELO ou LILACS, com os seguintes criterios de inclusao: desenho de coorte prospectiva e avaliacao do valor prognostico da PCR, mensurada por metodo de alta sensibilidade, no momento da admissao hospitalar de pacientes com SCA. Dezenove estudos preencheram os criterios de inclusao. Em relacao ao seguimento de longo prazo, houve associacao consistente entre PCR e eventos cardiovasculares, com odds ratio (OR) global de 4,6 (95% IC = 2,3-7,6) e OR global multivariado de 2,5 (95% IC = 1,8-3,4). Quanto ao curto prazo, 9 estudos foram positivos e 6 estudos negativos, com OR global de 1,65 (95% IC = 1,2-2,3). O OR global multivariado nao foi obtido para o seguimento de curto prazo, pois esta medida foi descrita em apenas tres trabalhos heterogeneos. Somente dois trabalhos, de curto prazo, fizeram analise do valor preditor incremental da PCR em relacao a modelos multivariados, com resultados contraditorios. Em conclusao, a escassez de avaliacao do valor incremental da PCR, aliada a resultados controversos quanto ao valor preditor independente para eventos de curto prazo, nao recomenda a utilizacao rotineira de PCR para estratificacao de risco na admissao de SCA.

Does acute hyperglycemia add prognostic value to the GRACE score in individuals with non-ST elevation acute coronary syndromes?

BACKGROUND It is not known in what extent admission glucose improves risk stratification of the GRACE Score in patients with non-ST-segment elevation acute coronary syndromes (ACS). We tested the hypothesis that admission glucose adds relevant prognostic information to the GRACE Score. METHODS Consecutive patients admitted with ACS had plasma glucose measured at admission and cardiovascular events were defined as death, non-fatal myocardial infarction or non-fatal refractory angina during hospitalization. RESULTS Among the 148 patients studied, 11.5% developed cardiovascular events. Patients in the forth quartile of admission glucose (> or =175mg/dl) had a greater incidence of events, compared with those in the first 3 quartiles (22% vs. 8.1%; RR=2.7; 95%CI 1.1-6.4; P=0.03). Plasma glucose remained a predictor of events, after adjustment for diabetes (P=0.03). After adjustment for the GRACE Score, glucose in the forth quartile lost its predictive value (P=0.29). Plasma glucose added to GRACE did not improve the C-statistics (0.82; 95%CI 0.75-0.88), as compared with the original Score (0.81; 95%CI 0.74-0.87). Net reclassification improvement by new score was -0.03 (P=0.86), indicating no useful reclassification. CONCLUSION Despite its association with adverse events, admission plasma glucose does not improve GRACEs accuracy to predict in-hospital events in patients with ACS.

Effect of atorvastatin (80 mg) on recurrent ischemia in unstable angina pectoris or Non–ST-Elevation acute myocardial infarction

A body of evidence has suggested that many cellular actions of statin therapy may acutely improve endothelial function even before affecting the lipid profile.1 Statins can acutely enhance nitric oxide bioavailability via their lipid-independent actions by upregulating endothelial nitric oxide synthase.2 In this randomized clinical trial, we evaluated the effect of high-dose atorvastatin on myocardial ischemia measured by ST-segment monitoring during the first 2 days after an episode of unstable angina pectoris (UAP) or non–Q-wave acute myocardial infarction (AMI). • • • Patients admitted to the coronary care unit of Portuguese Hospital, Salvador, Brazil, due to UAP or non–Q-wave AMI from December 2000 to March 2002 were considered candidates for the study. Inclusion criteria were defined as onset of chest discomfort in the previous 48 hours in patients with electrocardiographic changes consisting of transient ST-segment depression ( 0.05 mV), T-wave inversion ( 0.1 mV) and/or positive troponin I ( 1.0 ng/dl). Patients with positive troponin results were defined as having AMI, otherwise they were characterized as UAP. Patients were excluded if they had left bundle branch block, any liver disease, history of statin intolerance, pregnancy, or lactation. The study was approved by the local ethic committee and all participants provided written informed consent. A first blood sample to measure plasma lipids was drawn before initiation of therapy. The enrolled patients were submitted to a randomized, double-blind, placebo-controlled program with either 80 mg of atorvastatin or placebo administered once a day. ST-segment recording (Holter) was performed during the first 2 days of therapy and treatment efficacy was primarily assessed by comparing the amount of ischemia measured by Holter in the 2 groups. After 5 days, experimental therapy was withdrawn and another blood sample was taken for evaluation of the drug effect on plasma lipids. Cardiovascular events during hospitalization, defined as the composite of death, nonfatal AMI, and recurrent UAP, were also recorded. No other type of lipid-lowering therapy was offered to the patients during the first 5 days. Continuous 2-channel electrocardiographic recordings was performed by a calibrated amplitude-modulated cassette recorder (Dynamis 3000, Sao Paulo, Brazil) to detect reversible ST-segment shifts compatible with ischemia, which was defined as a 0.1 mV ST-segment depression or elevation measured 80 ms after the J point, lasting 1 minute and separated by the last episode by 1 minute. Number of ischemic episodes and total ischemia duration was measured in each patient. Ischemic burden was defined as the product of ischemic duration in minutes by the ST-segment depression in millimeters.3 The time from the first episode of ischemia was also recorded. Commercial enzymatic methods were used for the determination of total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides (Dimension Clinical Chemistry System; Dade-Behring, Newark, Delaware).4 HDL cholesterol was determined by the same method used for total cholesterol after precipitation of apolipoprotein B containing lipoproteins with magnesium phosphotungstate. Low-density lipoprotein (LDL) cholesterol was calculated by Friedewald’s formula. Duration of ischemia, number of ischemic epidodes, ischemic burden, and time to the first ischemic episode in each patient were compared between the 2 groups by Wilcoxon’s rank-sum test. The prevalence of patients with ischemia and of patients with 60 minutes of ischemia were compared between the 2 groups by Fisher’s exact test. Baseline characteristics were compared by unpaired Student’s t test for continuous variables and by chi-square or Fisher’s exact tests for categorical variables. Wilcoxon’s sign-rank test was utilized for the paired analysis of plasma lipid changes after therapy in each group. Cardiovascular events were compared between the 2 groups by the chi-square test. Nonparametric tests were applied in most situations because Holter variables were not normally distributed. Analysis of variance and logistic regression were utilized to adjust Holter variables to baseline differences between the groups. We calculated a sample size of 50 patients per group, based on a 2-sided of 5% and a statistical power of 85%, assuming that a 50% reduction in duration of ischemia with atorvastatin would be clinically significant. We based this calculation on the previously described 11 9 minutes of ischemia per patient with UAP per 24 hours.5 One hundred patients were randomized (64 12 years; 51 men); 55 had AMI and 45 had UAP. Fifty From the School of Medicine, Federal University of Bahia, Salvador; Cardiology Division, Portuguese Hospital, Salvador; and Heart Institute (InCor), University of Sao Paulo Medicine School, Sao Paulo, Brazil. Dr. Correia’s address is: Rua do Taruma 90/1002, Salvador BA, Brazil 41.810-440. E-mail: lucorrei@terra.com.br. Manuscript received November 22, 2002; revised manuscript received and accepted February 24, 2003.

Prevalência e preditores de embolia pulmonar em pacientes com insuficiência cardíaca agudamente descompensada

FUNDAMENTO: Nao existe descricao da prevalencia de Embolia Pulmonar (EP) em pacientes internados por quadro classico de Insuficiencia Cardiaca descompensada (IC). OBJETIVO: Em pacientes internados por IC, (1) descrever a prevalencia de EP, e (2) avaliar a acuracia diagnostica dos Escores de Wells e de Genebra. METODOS: Pacientes internados primariamente por IC realizaram sistematicamente cintilografia pulmonar de ventilacao/perfusao, sendo EP definida por laudo de alta probabilidade. Para fins de interpretacao, definimos baixa probabilidade clinica de EP como prevalencia < 5%, de acordo com dados da literatura. No calculo do tamanho amostral, 49 pacientes seriam necessarios para fornecer um intervalo de confianca 95% com ± 10% de precisao, estimando uma prevalencia a priori de 15%. RESULTADOS: Em 51 pacientes estudados, seis apresentaram cintilografia de alta probabilidade, resultando em prevalencia de 12% (95% IC = 5% - 23%). Os Escores de Wells e de Genebra apresentaram area abaixo da curva ROC de 0,53 (95% IC = 0,27 - 0,80; p = 0,80) e 0,43 (95% IC = 0,13 - 0,73; p = 0,56), respectivamente, indicando ausencia de acuracia para o diagnostico de EP. Alternativamente, variaveis relacionadas a IC mostraram tendencia a associacao com EP e um modelo exploratorio formado por esse tipo de variavel apresentou acuracia diagnostica para EP (ROC = 0,81; 95% IC = 0,66 - 0,96; p = 0,01). CONCLUSAO: (1) A despeito da ausencia de suspeita primaria, pacientes internados com IC possuem probabilidade clinica intermediaria de EP concomitante; (2) Os escores usualmente utilizados para estimar a probabilidade clinica de EP nao se aplicam a populacao com IC e futuros modelos preditores devem contemplar variaveis relacionadas a esta sindrome.

Valor prognóstico da troponina I de alta sensibilidade versus troponina T nas síndromes coronarianas agudas

BACKGROUND Despite superior diagnostic accuracy of high-sensitivity cardiac troponins, their prognostic value has not been validated against conventional cardiac troponins. OBJECTIVE To test the prognostic value of high-sensitivity cardiac troponin I (hs-cTnI), compared with conventional cardiac troponin T (cTnT) in the setting of non-ST elevation acute coronary syndromes. METHODS At hospital admission, a plasma sample was collected from 103 consecutive patients with unstable angina or non-ST elevation acute myocardial infarction. In this sample, troponin was measured both by hs-cTnI and cTnT methods. Their prognostic value was compared as to the occurrence of major cardiovascular events, defined as a combination of death, nonfatal acute myocardial infarction or refractory unstable angina during hospitalization. RESULTS During median hospitalization of 8 days (interquartile range = 5 - 11), the incidence of cardiovascular events was 10% (5 deaths, 3 non-fatal myocardial infarctions and 2 non-fatal refractory anginas). High-sensitivity troponin I significantly predicted cardiovascular events, with a C-statistics of 0.73 (95% CI = 0.59 - 0.87), similarly to cTnT (0.70; 95% CI = 0.55 - 0.84) - P = 0.75. The definition of positive cardiac marker that provided the best prognostic accuracy was hs-cTnI > 0.055 µg/L and cTnT > 0.010 µg/L, with equal sensitivity of 90% and specificity of 52% for both assays. Positive hs-cTnI was associated with 17% incidence of events, compared with 2% in patients with negative hs-cTnI (P = 0.02). CONCLUSION High-sensitivity troponin I predicts cardiovascular events similarly to conventional troponin T in the setting of non-ST-elevation ACS.

Moderate renal dysfunction is not associated with elevated Troponin T in acute coronary syndromes

FUNDAMENTO: A interpretacao dos resultados de troponina em pacientes com sindromes coronarianas agudas (SCA) e doenca renal e dificultada pelo fato de que a disfuncao renal aumenta os niveis de troponina, independente da necrose miocardica. Embora tenha sido demonstrado que a doenca renal em estagio terminal esta associada com niveis elevados de troponina T cardiaca (TnT), ainda nao e conhecido se esse biomarcador e alterado por niveis menos graves de disfuncao renal. OBJETIVO: Avaliar se disfuncao renal moderada esta associada com elevacao dos niveis de TnT em pacientes com SCA. METODOS: Um total de 145 individuos com SCA e clearance de creatinina > 30 ml/min foram estudados. O clearance de creatinina foi estimado atraves da formula de Cockcroft-Gault e a TnT foi medida na admissao hospitalar. Disfuncao renal moderada foi definida como clearance de creatinina de 30-59 ml/min e TnT positiva como niveis > 0,01 ug/l. RESULTADOS: Nenhuma correlacao foi observada entre o clearance de creatinina e TnT (r = - 0,06, P=0,45). Os niveis de TnT foram similares entre individuos no primeiro (mediana=0,05 ug/l), segundo (mediana=0 ug/l), terceiro (mediana=0,07 ug/l) e quarto quartis (mediana=0 ug/l) de clearance de creatinina - P=0,63. De forma similar, nao houve diferenca nos valores de troponina entre individuos com disfuncao renal moderada (mediana=0,02 ug/l) e individuos com funcao renal normal/quase normal (mediana=0,03 ug/l) - P=0.63. A prevalencia de TnT positiva foi similar entre individuos com disfuncao renal moderada e funcao renal normal/quase normal (55% vs 52%, P=0,65). CONCLUSAO: Disfuncao renal moderada nao esta associada com elevacao dos niveis de TnT em pacientes com SCA. (Arq Bras Cardiol 2010; 95(5): 600-605)

Análise de Causalidade da Relação entre Sangramento e Letalidade de Síndromes Coronarianas Agudas Causality Analysis of the Relationship Between Bleeding and Lethality in Acute Coronary Syndromes

Background: Hemorrhagic events in Acute Coronary Syndromes (ACS) have been independently associated with death in international multicenter registries. However, that association has not been tested in Brazil and the true causal relationship between bleeding and death has not been completely shown.