Impact of free thyroxine levels and other clinical factors on bare metal stent restenosis

ABSTRACT Objective Thyroid hormones have both direct and indirect effects on thermogenesis such as modulating vascular smooth muscle cell proliferation. However, the influence of more subtle changes in thyroid hormones on coronary atherosclerosis remains a matter of speculation. Smooth muscle cells play a crucial role in the pathogenesis of in-stent restenosis (ISR). However, the relationship between free thyroxine (fT4) and ISR has not been studied. In the present study, we aimed to assess the role of preprocedural serum fT4 level on the development of ISR in patients undergoing coronary bare metal stent (BMS) implantation. Materials and methods We enrolled and analyzed clinical, biochemical, and angiographic data from 705 consecutive patients without a history of primary thyroid disease [mean age 60.3 ± 9.3 years, 505 (72%) male]; all patients had undergone BMS implantation and further control coronary angiography owing to stable or unstable angina pectoris. Patients were divided into 3 tertiles based on preprocedural serum fT4 levels. Results ISR was observed in 53 (23%) patients in the lowest tertile, 82 (35%) patients in the second tertile, and 107 (46%) patients in the highest fT4 tertile (p < 0.001). Using multiple logistic regression analysis, five characteristics emerged as independent predictors of ISR: diabetes mellitus, smoking, HDL-cholesterol, stent length, and preprocedural serum fT4 level. In receiver operating characteristics curve analysis, fT4 level > 1.23 mg/dL had 70% sensitivity and 73% specificity (AUC: 0.75, p < 0.001) in predicting ISR. Conclusion Higher preprocedural serum fT4 is a powerful and independent predictor of BMS restenosis in patients with stable and unstable angina pectoris.

Very Long-Term Prognostic Role of Admission BNP in Non-ST Segment Elevation Acute Coronary Syndrome / Papel Prognóstico a Muito Longo Prazo do BNP de Admissão na Síndrome Coronariana Aguda sem Elevação do Segmento ST

Abstract Background: BNP has been extensively evaluated to determine short- and intermediate-term prognosis in patients with acute coronary syndrome, but its role in long-term mortality is not known. Objective: To determine the very long-term prognostic role of B-type natriuretic peptide (BNP) for all-cause mortality in patients with non-ST segment elevation acute coronary syndrome (NSTEACS). Methods: A cohort of 224 consecutive patients with NSTEACS, prospectively seen in the Emergency Department, had BNP measured on arrival to establish prognosis, and underwent a median 9.34-year follow-up for all-cause mortality. Results: Unstable angina was diagnosed in 52.2%, and non-ST segment elevation myocardial infarction, in 47.8%. Median admission BNP was 81.9 pg/mL (IQ range = 22.2; 225) and mortality rate was correlated with increasing BNP quartiles: 14.3; 16.1; 48.2; and 73.2% (p < 0.0001). ROC curve disclosed 100 pg/mL as the best BNP cut-off value for mortality prediction (area under the curve = 0.789, 95% CI= 0.723-0.854), being a strong predictor of late mortality: BNP < 100 = 17.3% vs. BNP ≥ 100 = 65.0%, RR = 3.76 (95% CI = 2.49-5.63, p < 0.001). On logistic regression analysis, age >72 years (OR = 3.79, 95% CI = 1.62-8.86, p = 0.002), BNP ≥ 100 pg/mL (OR = 6.24, 95% CI = 2.95-13.23, p < 0.001) and estimated glomerular filtration rate (OR = 0.98, 95% CI = 0.97-0.99, p = 0.049) were independent late-mortality predictors. Conclusions: BNP measured at hospital admission in patients with NSTEACS is a strong, independent predictor of very long-term all-cause mortality. This study allows raising the hypothesis that BNP should be measured in all patients with NSTEACS at the index event for long-term risk stratification.

Resumo Fundamento: O BNP foi exaustivamente avaliado para a determinação do prognóstico em curto e médio prazo em pacientes com síndrome coronariana aguda, mas o seu papel para a mortalidade a longo prazo é incerta. Objetivo: Determinar o papel prognóstico a muito longo prazo do peptídeo natriurético do tipo B (BNP) para a mortalidade por todas as causas em pacientes com síndrome coronariana aguda sem supradesnivelamento do segmento ST (SCASSST). Métodos: Coorte de 224 pacientes consecutivos com SCASSST, prospectivamente atendidos no setor de emergência, em que se mediu o BNP na chegada para estabelecer o prognóstico ao longo do seguimento mediano de 9,34 anos para a mortalidade por todas as causas. Resultados: Diagnosticou-se angina instável em 52,2% e infarto do miocárdio sem supradesnivelamento do segmento ST em 47,8%. A mediana do BNP da admissão foi de 81,9 pg/mL (intervalo IQ = 22,2; 225) e a taxa de mortalidade correlacionou-se com quartis crescentes de BNP: 14,3; 16,1; 48,2; e 73,2% (p < 0,0001). A curva ROC revelou 100 pg/mL como o melhor ponto de corte de BNP para a predição de mortalidade (área sob a curva = 0,789, 95% CI = 0,723-0,854) sendo um forte preditor de mortalidade tardia: BNP < 100 = 17,3% vs. BNP ≥ 100 = 65,0%, RR = 3,76 (IC 95% = 2,49-5,63, p < 0,001). Na análise de regressão logística, idade>72 anos (OR = 3,79, IC 95% = 1,62-8,86, p = 0,002), BNP ≥ 100 pg/mL (OR = 6,24, IC 95% = 2,95-13,23, p < 0,001) e taxa de filtração glomerular estimada (OR = 0,98, IC 95% = 0,97-0,99, p = 0,049) foram preditores independentes de mortalidade tardia. Conclusões: O BNP medido na admissão hospitalar em pacientes com SCASSST é um forte preditor independente de mortalidade por todas as causas de muito longo prazo. Este estudo permite que se levante a hipótese de que o BNP deva ser medido em todos os pacientes com SCASSST no evento-índice para a estratificação de risco a longo prazo.

Interleukin-33, matrix metalloproteinase-9, and tissue inhibitor of matrix metalloproteinase-1 in myocardial infarction

BACKGROUND/AIMS: Acute coronary syndrome (ACS) is characterized by increased inflammatory processes and endothelial activation. We investigated the association between ACS and inflammatory mediators and matrix-degrading enzymes. METHODS: We prospectively enrolled 55 consecutive patients with ACS: 25 with unstable angina (UA) and 30 with non-ST elevated myocardial infarction (NSTEMI). For comparison, 25 age- and sex-matched subjects with no significant coronary artery stenosis were included as the control group. Peripheral serum levels of interleukin (IL)-33, matrix metalloproteinase (MMP)-9, tissue inhibitor of MMP-1, and C-reactive protein (CRP) were measured on admission, and at 12, 24, 48, and 72 hours after the initial evaluation. RESULTS: Compared to serum levels in the control group, serum levels of IL-33 decreased in the NSTEMI group (p < 0.05), and levels of MMP-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 increased in the UA group (p < 0.01, p < 0.05, respectively) and NSTEMI group (p < 0.05, p < 0.05, respectively). IL-33 levels were significantly lower on admission than at 12 hours after the initial evaluation (p < 0.05). IL-33 levels were negatively correlated with MMP-9 levels (r = -0.461, p < 0.05) and CRP levels (r = -0.441, p < 0.05). CONCLUSIONS: Elevated levels of MMP-9, TIMP-1, and decreased levels of IL-33 play a role in the development and progression of ACS.

Correlations between Coronary Plaque Tissue Composition Assessed by Virtual Histology and Blood Levels of Biomarkers for Coronary Artery Disease

PURPOSE: We investigated correlations of coronary plaque composition determined by virtual histology (VH) intravascular ultrasound (IVUS) and blood levels of biomarkers that represent the vulnerability of coronary plaques. MATERIALS AND METHODS: Pre- and postprocedural blood levels of high sensitivity C-reactive protein, soluble CD40 ligand (sCD40L), matrix metalloproteinase-9, and neopterin were measured in 70 patients with stable angina (SA) or unstable angina (UA) who were undergoing percutaneous coronary intervention (PCI) for single lesions. We evaluated the data for correlations between these biomarkers and necrotic core contents in PCI target lesions analyzed by VH. RESULTS: Clinical characteristics, IVUS, VH, and biomarker blood levels were not different between the SA and the UA group except for more frequent previous statin use (52.3% vs. 23.1%, p=0.017) and lower remodeling index in the SA group (0.98+/-0.09 vs. 1.10+/-0.070, p<0.001). Among the biomarkers evaluated, only pre-PCI neopterin level showed a weakly significant correlation with the absolute volume of the necrotic core (r=0.320, p=0.008). Pre- and post-PCI blood levels of sCD40L (r=0.220, p=0.072; r=0.231, p=0.062) and post-PCI blood level of neopterin (r=0.238, p=0.051) showed trends toward weakly positive correlations with the absolute volume of necrotic core. CONCLUSION: We found a weakly positive correlation between the pre-PCI neopterin level and necrotic core volume in the PCI-target lesion. The clinical implications of our findings need to be investigated in further studies.

Association of Lipoprotein-Associated Phospholipase A2 with Characteristics of Vulnerable Coronary Atherosclerotic Plaques

PURPOSE: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory enzyme expressed in atherosclerotic plaques. We investigated the association of circulating Lp-PLA2 with characteristics of vulnerable coronary atherosclerotic plaques. MATERIALS AND METHODS: We recruited 113 patients with either unstable angina (UA, n=59) and stable angina (SA, n=54) by coronary angiography. Thirty-six healthy subjects served as controls. Intravascular ultrasound (IVUS) was used to evaluate the characteristics of coronary atherosclerotic plaque, and serum Lp-PLA2 concentration was measured as well. RESULTS: Lp-PLA2 concentration was significantly higher in both UA and SA patients [(396+/-36) microg/L and (321+/-39) microg/L, respectively] compared with the controls [(127+/-49) microg/L, p<0.01], and higher in UA than SA group. IVUS findings showed that remodeling index (RI) (0.91+/-0.15 vs. 0.85+/-0.11, p=0.005) and eccentricity index (EI) (0.73+/-0.16 vs. 0.65+/-0.22, p=0.039) were larger in UA than in SA group, and fibrous caps were thicker in SA than UA group [(0.91+/-0.23) mm vs. (0.63+/-0.21) mm, p=0.032]. Moreover, Lp-PLA2 correlated positively with EI (r=0.439, p<0.01) and RI (r=0.592, p<0.05) in UA group. There was an inverse relationship between Lp-PLA2 and fibrous cap thickness in both UA (r=-0.587, p<0.001) and SA (r=-0.318, p<0.05) groups. The independent risk factors in UA group were Lp-PLA2 (OR=1.055, 95% CI: 1.03-1.08, p=0.013), LDL-cholesterol (OR=0.032, 95% CI: 0.00-0.05, p=0.041) and fibrous cap thickness (OR=0.008, 95% CI: 0.00-0.45, p=0.019). Lp-PLA2 was strongly associated with both EI and fibrous cap thickness in both groups. CONCLUSION: Serum level of Lp-PLA2 is associated with both eccentricity index and fibrous cap thickness in both UA and SA groups. Elevated levels of circulating Lp-PLA2 might to be a strong risk factor and more serious for unstable angina than stable angina.

Reduced plasma adiponectin levels relative to oxidized low density lipoprotein and nitric oxide in coronary artery disease patients

INTRODUCTION: Adiponectin is a circulating hormone that is produced exclusively by adipocytes and has antiinflammatory and anti-atherogenic properties. The hypothesis that there are differences in adiponectin levels between stable and unstable coronary-artery disease patients remains controversial. Furthermore, the potential relationships between the plasma adiponectin level and the inflammatory and non-inflammatory markers (oxidized low density lipoprotein and nitric oxide) in patients with stable and unstable coronary-artery disease relative to normal subjects have not been assessed. OBJECTIVES: To assess whether plasma adiponectin levels differ among patients with stable and unstable coronary-artery disease and among control subjects, and to correlate plasma adiponectin level with inflammatory and clinical risk factors (such as oxidized-LDL and nitric oxide) in these patients. METHODS: This study included 50 control subjects, 50 stable angina patients and 50 unstable angina patients with angiographically documented coronary-artery disease. Plasma adiponectin and oxidized-LDL levels were determined using an enzyme immunoassay. Plasma nitric oxide, high sensitivity C-reactive protein and lipid profile levels were also measured. RESULTS: Plasma adiponectin levels were lower in the unstable angina patients (4.9 ± 1.30 µg/mL) than in the stable angina patients (6.34 ± 1.0 µg/mL) or in the controls (9.25 ± 1.8 µg/mL); these levels were also significantly lower in stable angina patients versus controls (p<0.001). Plasma adiponectin levels were negatively correlated with oxidized-LDL, high sensitivity C-reactive protein, lipid profile and other clinical risk factors but positively correlated with nitric oxide. CONCLUSION: Plasma adiponectin levels were found to be lower in both stable and unstable angina patients relative to control subjects, and the correlation between plasma adiponectin and cardiovascular markers is weakened in these patients.

Comparação de biomarcadores inflamatórios entre pacientes diabéticos e não-diabéticos com angina instável / Comparación de biomarcadores inflamatorios entre pacientes diabéticos y no-diabéticos con angina inestable / Comparison of inflammatory biomarkers between diabetic and non-diabetic patients with unstable angina

FUNDAMENTO: Poucos estudos compararam a atividade inflamatória entre pacientes diabéticos e não-diabéticos com síndrome coronariana aguda, e ainda não foi publicado nenhum somente com portadores de angina instável (AI). OBJETIVO: Este estudo teve dois objetivos. Em primeiro lugar, comparar os níveis séricos de proteína C reativa (PCR) e interleucina - 6 (IL-6) em pacientes diabéticos e não-diabéticos com angina instável (AI) para determinar se a diferença na atividade inflamatória justifica o pior prognóstico nos pacientes diabéticos. Em segundo, avaliar a correlação entre os marcadores inflamatórios e o perfil metabólico em pacientes diabéticos e entre a resposta inflamatória e os desfechos hospitalares, como morte, infarto agudo do miocárdio, insuficiência cardíaca congestiva e tempo de hospitalização. MÉTODOS: Estudo de coorte prospectivo de 90 pacientes consecutivos admitidos na Unidade de Dor Torácica com angina instável. Os pacientes foram divididos em dois grupos: diabéticos e não-diabéticos. Os níveis séricos de PCR e IL-6, o perfil metabólico e a contagem de leucócitos foram obtidos na chegada ao hospital. RESULTADOS: Dos pacientes analisados, 42 (47 por cento) eram diabéticos (idade 62 ± 9) e 48 (53 por cento) não eram diabéticos (idade 63 ± 12). Não foram encontradas diferenças entre a mediana da PCR (1,78 vs. 2,23 mg/l, p = 0,74) e da IL-6 (0 vs. 0 pg/ml, p = 0,31) entre os dois grupos. Houve uma correlação positiva entre PCR e colesterol total (rs = 0, 21, p = 0, 05), PCR e colesterol LDL (r s = 0,22, p = 0,04) e PCR e contagem de leucócitos (r s = 0,32, p = 0,02) nos dois grupos. Nenhuma associação foi encontrada entre os marcadores inflamatórios e os desfechos hospitalares. CONCLUSÃO: Não encontramos diferença na atividade inflamatória entre os pacientes diabéticos e não-diabéticos com AI, o que indica que esse quadro clínico pode equilibrar a atividade inflamatória entre os dois grupos e aumentar a concentração de marcadores ...

BACKGROUND: Studies comparing inflammatory activity between diabetic and non-diabetic individuals with acute coronary syndrome are scarce, and none including only patients with unstable angina (UA) has been published to date. OBJECTIVE: We compared serum C-reactive protein (CRP), and interleukin-6(IL-6) between diabetic and non-diabetic patients with unstable angina (UA) to determine if difference in inflammatory activity is responsible for a worse prognosis in diabetic patients. We also evaluated the correlation between inflammatory markers and the metabolic profile in diabetic patients and the correlation between inflammatory response and in-hospital outcomes: death, acute myocardial infarction, congestive heart failure, and length of stay in hospital. METHODS: A prospective cohort study of 90 consecutive patients admitted to a chest pain unit with UA and divided into two groups, diabetic and non-diabetic. Serum CRP, IL-6, metabolic profile and leukocyte count were measured at hospital arrival. RESULTS: Forty-two patients (47 percent) were diabetic (age 62±9) vs. 48 (53 percent) non-diabetic (age 63±12). No differences between median C-reactive protein (1.78 vs. 2.23mg/l,p=0.74) and interleukin-6 (0 vs. 0pg/ml,p=0.31) were found between the two groups. There was a positive correlation between CRP and total cholesterol (rs = 0.21,p = 0.05), CRP and LDL-cholesterol (rs=0.22,p=0.04) and between CRP and leukocyte count (rs = 0.32, p = 0.02) in both groups. No associations were found between inflammatory markers and in-hospital outcomes. CONCLUSION: We found no difference in inflammatory activity between diabetic and non-diabetic patients with UA, suggesting that this clinical condition may result in balanced inflammatory activity between the two groups and increase acute-phase proteins independently of metabolic state.

FUNDAMENTO: Pocos estudios compararon la actividad inflamatoria entre pacientes diabéticos y no-diabéticos con síndrome coronario agudo, y todavía no se publicó ninguno que investigara solamente a los portadores de angina inestable (AI). OBJETIVO: Este estudio tuvo dos objetivos. En primer lugar, comparar los niveles séricos de proteína C reactiva (PCR) y interleuquina-6 (IL-6) en pacientes diabéticos y no-diabéticos con angina inestable (AI) para determinar si la diferencia en la actividad inflamatoria justifica el empeoramiento pronóstico en los pacientes diabéticos. En segundo, evaluar la correlación entre los marcadores inflamatorios y el perfil metabólico en pacientes diabéticos y entre la respuesta inflamatoria y los desenlaces hospitalarios, como muerte, infarto agudo de miocardio, insuficiencia cardiaca congestiva y tiempo de hospitalización. MÉTODOS: Estudio de cohorte prospectiva de 90 pacientes consecutivos, ingresados a la Unidad de Dolor Torácico con angina inestable. Se dividieron a los pacientes en dos grupos: diabéticos y no-diabéticos. Los niveles séricos de PCR e IL-6, el perfil metabólico y el conteo de leucocitos se obtuvieron al ingreso al hospital. RESULTADOS: De todos los pacientes analizados, 42 (47 por ciento) eran diabéticos (edad 62 ± 9) y 48 (53 por ciento) no eran diabéticos (edad 63 ± 12). No se encontraron diferencias entre la mediana de la PCR (1,78 vs. 2,23 mg/l, p = 0,74) y de la IL-6 (0 vs. 0 pg/ml, p = 0,31) entre los dos grupos. Hubo una correlación positiva entre la PCR y el colesterol total (rs = 0, 21, p = 0, 05), la PCR y el colesterol LDL (rs = 0,22, p = 0,04) y la PCR y el conteo de leucocitos (rs = 0,32, p = 0,02) en los dos grupos. No se encontró ninguna asociación entre los marcadores inflamatorios y los desenlaces hospitalarios. CONCLUSIÓN: No encontramos diferencia en la actividad inflamatoria entre los pacientes diabéticos y no-diabéticos con AI, lo que indica que ese cuadro clínico puede ...

Influence of folic acid on plasma homocysteine levels & arterial endothelial function in patients with unstable angina.

Background & objectives: High plasma homocysteine (Hcy) levels are known to be associated with coronary artery disease, but the precise level associated with an increased risk is yet controversial. Whether the beneficial effects of folic acid on arterial endothelial function persist over longer periods is not known. This study was carried out to assess whether folic acid supplementation could produce improvements in Hcy levels and arterial endothelial function in the patients with unstable angina (UA) and hyperhomocysteinaemia. Methods: The plasma Hcy levels of 52 cases with UA and 30 control subjects were measured by using high-performance liquid chromatography (HPLC) with fluorescence detection, plasma folic acid and vitamin B12 levels were also measured. The patients with hyperhomocysteinaemia were treated with 5 mg of folic acid for 8 wk, and then rechecked the plasma levels of Hcy, folic acid and vitamin B12 at the end of 4th and 8th wk. Arterial endothelial function was measured as flow-mediated dilation of the brachial artery using high-resolution B-mode ultrasound in 22 cases with UA and hyperhomocysteinaemia before and after folic acid treatment. Results: The plasma Hcy level was significant higher in the patients with UA than in the controls (19.2 ± 4.9 vs 10.7 ± 5.3 μmol/l, P<0.01). The plasma levels of folic acid and vitamin B12 were significant lower in the patients with UA than in the controls. There were 22(42.3%) patients with hyperhomocysteinaemia in UA group. After 4 and 8 wk of administration of folic acid, the Hcy level reduced by 20.3 and 55.3 per cent in the UA patients with hyperhomocysteinaemia, respectively. Flow-mediated dilation also improved significantly, from 6.4 ± 1.9 to 9.0 ± 1.2 per cent (P<0.05) after 8 wk treatment with folic acid. Interpretation & conclusions: Plasma Hcy level was elevated in patients with UA. Folic acid can reduce the plasma Hcy levels and improve arterial endothelial function in the UA patients with hyperhomocysteinaemia.

An assessment of neutrophils/lymphocytes ratio in patients suspected of acute coronary syndrome / Avaliação da relação neutrófilos/linfócitos em pacientes com suspeita de síndrome coronariana aguda

FUNDAMENTO: A contagem total de leucócitos é um marcador de risco independente para eventos cardiovasculares. A relação entre a contagem de neutrófilos e linfócitos (N/L) tem sido explorada como novo preditor de risco cardiovascular, mas seu papel diagnóstico na avaliação de pacientes com suspeita de síndrome coronariana aguda (SCA) é desconhecido. OBJETIVO: Avaliar o valor diagnóstico da relação N/L em pacientes admitidos com suspeita de SCA em uma Unidade de Dor Torácica (UDT). MÉTODOS: Foram avaliados 178 pacientes admitidos com dor torácica, seguindo fluxograma diagnóstico conforme aspectos clínicos, eletrocardiográficos e laboratoriais. Os diagnósticos estabelecidos foram: infarto agudo do miocárdio com (IAMEST) e sem elevação de segmento ST (IAMSEST), angina instável (AI) e dor não-cardíaca (NC). Contagens total e diferencial de leucócitos foram realizadas em amostra de sangue periférico coletada na admissão. RESULTADOS: Pacientes com dor diagnosticada como não-cardíaca apresentaram a menor relação N/L (n = 45; 3,0 ± 1,6), seguidos por AI (n = 65; 3,6 + 2,9), IAMSEST (n = 33; 4,8 ± 3,7) e IAMEST (n = 35; 6,9 ± 5,7) (p < 0,0001). A relação N/L acima de 5,7 (quartil mais elevado) teve especificidade de 91,1 por cento, com odds ratio de 4,51 (intervalo de confiança de 95 por cento [IC 95 por cento], 1,51 a 13,45) para um diagnóstico final de SCA, em comparação com os grupos em quartis menores. CONCLUSÃO: A relação N/L apresenta correlação com o diagnóstico final de pacientes admitidos com suspeita de SCA. Por ser um exame de baixo custo e com boa reprodutibilidade, novos estudos deverão elucidar se a relação poderá ter importância nos fluxogramas diagnósticos atualmente empregados.

BACKGROUND: Leukocytes total count is an independent risk marker for cardiovascular events. The ratio between neutrophils and lymphocytes (N/L) count has been investigated as a new predictor for cardiovascular risk, although its diagnostic role when assessing patients suspected of an acute coronary syndrome (ACS) condition is not yet known. OBJECTIVE: To evaluate the diagnostic power of N/L ratio in patients who have been admitted at a Chest Pain Unit (CPU) with the suspicion of ACS. METHODS: Evaluation was conducted in 178 patients admitted with chest pain. Diagnostic flowchart including clinical, electrocardiographic, and laboratory data. Diagnosis obtained was: acute myocardial infarction (AMI) with (AMI-STE) and with no segment T elevation (AMI-NSTE), unstable angina (UA ) and non-cardiac pain (NC). Total and differential leukocyte count was conducted in peripheral blood sample collected at admission. RESULTS: Patients diagnosed with non-cardiac pain reported the lowest N/L ratio (n=45; 3.0 ± 1.6), followed by UA (n=65; 3.6 ± 2.9), AMI-NSTE (n=33; 4.8 ± 3.7) and AMI-STE (n=35; 6.9 ± 5.7); p < 0.0001. N/L ratio above 5.7 (highest quartile) reported 91.1 percent specificity, 4.51 odds ratio (CI 95 percent 1.51 to 13.45) for the final diagnosis of ACS when compared to the groups at lower quartiles. CONCLUSION: The N/L ratio presents correlation with final diagnosis of patients with suspicion of ACS at admission. Considering this is a low cost, good reproductibility test, new studies should ellucidate whether the ratio may be of relevance for diagnosis flowcharts currently in use.

High sensitivity C-reactive protein and immunoglobulin G against chlamydia pneumoniae and chlamydial heart shock protein-60 in ischemic heart disease

Inflammation and infectious agents such as Chlamydia pneumoniae have been associated with cardiovascular disease. To evaluate the serum high sensitivity C - reactive protein [hs-CRP] and antibodies against Chlamydia pneumoniae and Chlamydial heat shock protein-60 [Cp-HSP60] in patients with ischemic heart disease [IHD]. 62 patients with IHD having either acute myocardial infarction [AMI; n=31] or unstable angina [UA; n=31] and 31 sex- and age- matched healthy subjects as a control group were enrolled in this study. Serum samples of participants were tested for the presence of hs-CRP and antibodies against C. pneumoniae and Cp-HSP60 using ELISA method. The seroprevalence of anti-C. pneumoniae antibody in AMI group [93.5%] or UA group [90.3%] was significantly higher than the control group [61.3%; p<0.001]. The seroprevalence of anti-Cp-HSP60 IgG was 22.6% in healthy subjects with mean end titer of 43.1 +/- 6.32. The seropositive rates of anti-Cp-HSP60 were 48.4%, 54.8% and 51.6% in AMI, UA and the overall IHD groups with mean end titers of 94 +/- 22.86, 113.8 +/- 24.25 and 103.9 +/- 16.57, respectively. Both the seroprevalence and the mean titer of anti-Cp-HSP60 in patients groups were significantly higher than those observed in the control group [p<0.04 and p<0.03, respectively]. Moreover, the mean serum hs-CRP levels was significantly higher in the IHD group as compared to the control group [21.6 Mu g/ml +/- 3.73 vs 2.5 Mu g/ml +/- 0.52; p<0.00001]. The mean serum hs-CRP levels of AMI [30.3 Mu g/ml +/- 6.07] or UA [12.9 Mu g/ml +/- 3.85] groups were also significantly higher than those observed in the control group [p<0.00001 and p<0.001, respectively]. Furthermore, the difference of the mean serum hs-CRP levels between AMI and UA groups was also significant [p<0.02]. These results showed that the seroprevalence of antibodies against C. pneumoniae and Cp-HSP60 and the serum levels of hs-CRP and anti-Cp-HSP60 IgG were higher in patients with IHD

Relationship between the serologic status of Helicobacter pylori with the presence of unstable angina

To determine whether unstable angina is co-related to seropositivity to chronic Helicobacter pylori [HP] infection. It is a case control, descriptive study conducted at CCU in Razi Hospital in Ahwaz a city southwest Iran, from 2004 to 2005.We measured serum HP- IgG levels of participants in CCU in a hospital. Blood samples were drawn during study period from 96 patients [mean age 56 years] with Unstable Angina [UA] according to American Heart Association criteria and from 96 participants free of cardiovascular disease [mean age 58 years] and stored at "20°C. Serology results were studied in relation to UA. Using chi squared test, odds ratios [OR] and 95% confidence intervals [CI] were calculated, adjusting for age, gender, and established risk factors. Seventy nine [82.3%] of patients with unstable angina and 55[61.1%] in the control group presented a positive anti HP-IgG. Odds ratio was 3 with 95% CI: 1.9 to 4.3. There was significant relation between HP-IgG positivity and unstable angina [P<0.001].There was no sex and age significant difference in HP-IgG positivity in patients and controls [P>0.05]. Our study revealed relationship between seropositivity of HP-IgG and unstable angina

Marcadores hemostáticos y de inflamación en síndromes coronarios agudos y su asociación con eventos cardiovasculares adversos / Haemostatic and inflammation markers in acute coronary syndromes and its relationship with adverse cardiovascular events

BACKGROUND: In acute coronary syndromes (ACS) interaction among several haemostatic (S and C protein, antitrhombin Ill, C protein resistance, plasminogen, alpha 2-antiplasmi and inflammatory factors (white cell blood count, fibrinogen, reactive C protein) could have association with recurrent thrombosis and recurrence ischemia, reinfarction, shock and cardiovascular mortality. METHODS: Prospective, controlled, with a six-year follow-up trial. END-POINT: Prove in acute phase and in a follow-up association among inflammatory, coagulation and fibrinolysis markers with cardiovascular adverse events. INCLUSION: a) ischemic chest pain at rest > 20 minutes with ST depression or elevation ACS, b) clinical stability. EXCLUSION: a) > 75 years-old, b) ACS secondary stress, hypertensive crisis, aortic stenosis, c) another acute vascular syndromes suggesting acute ischemia, d) Killip and Kimbal III o IV, e) ejection fraction < 35%, f) pre-hospital treatment with any medication that modify coagulation or fibrinolysis, c) inflammatory acute or chronic process. CONTROL GROUPS: Healthy individuals and stable chronic heart disease patients whose were matched by age and sex. In all patients with ischemic heart disease angiography, nuclear medicine or echocardiography stress tests were done. STATISTICS: Chi square, student t-test. Lineal, logistic and multivariate regression. Kaplan-Meier and Cox survival curves. Statistical significance: p < 0.05. RESULTS: 50 patients with non- or ST elevation ACS were enrolled. Regression logistic analysis indicated association among plasminogen, antithrombin III and C reactive-protein (p < 0.00001) with death. Protein C and S, protein C resistance and antithrombin III had correlation with death (p 0.0001) and recurrent ischemia (p < 0.0001). Multivariate analysis showed that antithrombin III, plasminogen, C reactive-protein and fibrinogen had significant correlation with death (p 0.001), cardiogenic shock (0.001), new ST-elevation myocardial infarction (0.001). CONCLUSION: These findings suggesting that in acute phase and in a follow-up of an ACS abnormal coagulation, inflammation and fibrinolysis markers had independent and direct relationship with cardiovascular adverse events.

Perfil dos hormônios tireoidianos nas síndromes coronarianas agudas / Thyroid hormone profile in acute coronary syndromes

OBJETIVO: Descrever o perfil hormonal tireoidiano em pacientes com síndromes coronarianas agudas (SCA), e nos grupos: 1) angina instável e/ou infarto agudo do miocárdio sem supradesnivelamento de segmento ST (AI/IAM sem supra ST); 2) infarto agudo do miocárdio com supradesnivelamento do segmento (IAM com supra ST), e nos pacientes que evoluíram ou não a óbito conforme os grupos. MÉTODOS: Foram estudados prospectivamente setenta pacientes portadores de SCA, internados na unidade coronariana do Hospital dos Servidores do Estado/RJ. As amostras sangüíneas foram coletadas nos primeiro, quarto e sétimo dias de internação. Exame clínico e eletrocardiograma foram realizados no período de internação. RESULTADOS: Dos 70 pacientes admitidos, 13 (18,6 por cento) apresentaram a "síndrome do eutireoidiano doente" (SED), que consiste na queda do hormônio T3 e ou T3 livre, aumento do hormônio T3 reverso (rT3) e inalteração dos hormônios TSH, T4 e T4 livre. Nos pacientes do grupo IAM com supra ST, observaram-se elevação precoce e maiores médias do hormônio tireoidiano T3 reverso (rT3) e menores médias dos hormônios T3 e T3 livre. Nos coronariopatas que evoluíram a óbito, observamos achados hormonais condizentes com os encontrado na SED, com valores médios expressivos dos hormônios rT3 e T3. CONCLUSÃO: Os resultados apresentados neste estudo mostram a importância do reconhecimento da "síndrome do eutireoidiano doente" nos pacientes coronariopatas, sugerindo associação com pior prognóstico nos pacientes com síndrome coronariana aguda.

OBJECTIVE: To describe thyroid hormone profile in patients with acute coronary syndromes (ACS), divided into two groups: 1) unstable angina and/or non-ST-segment elevation acute myocardial infarction (UA/NSTEMI); 2) ST-segment elevation acute myocardial infarction (STEMI), as well as in patients that progressed or not to death, according to the groups. METHODS: Seventy ACS patients admitted to the coronary care unit of the Hospital dos Servidores do Estado, Rio de Janeiro, were prospectively studied. Blood samples were collected on day 1 and on days 4 and 7 following admission. Clinical evaluation and electrocardiograms were performed during hospitalization. RESULTS: Of the 70 patients admitted, 13 (18.6 percent) had "euthyroid sick syndrome" (ESS), a condition characterized by decreased serum T3 and/or free T3, increased serum reverse T3 (rT3), plus normal serum TSH, T4, and free T4. Patients belonging to the STEMI group showed early elevations, in addition to higher mean reverse T3 (rT3) and lower mean T3 and free T3 levels. In coronary heart disease patients that progressed to death, hormonal findings were consistent with those found in the ESS, with more expressive rT3 and T3 mean values. CONCLUSION: Our results show the importance of recognizing the "euthyroid sick syndrome" in coronary heart disease patients, suggesting an association with poorer prognosis in patients with acute coronary syndrome.

Determinación cualitativa de marcadores de necrosis miocárdica desde la fase prehospitalaria del síndrome coronario agudo / Qualitative determination of markers for myocardiac necrosis during pre-hospital admission for acute coronary syndrome

Objetivo: medir el valor diagnóstico que tienen la troponina I, mioglobina y creatinfosfocinasa MB (CPK-MB) desde la fase de atención prehospitalaria, en pacientes con dolor torácico. Material y métodos: pacientes consecutivos que solicitaron atención prehospitalaria con ambulancia de terapia intensiva o que se encontraban en las primeras horas de hospitalización por dolor torácico. A todos se les realizó electrocardiograma de 12 derivaciones en la ambulancia o en el servicio de urgencias, y se les determinó nivel de creatinfosfocinasa sérica total (como patrón de referencia). Fueron distribuidos en cinco grupos: grupo I, 13 pacientes con infarto agudo del miocardio sin elevación del segmento ST; grupo II, 11 pacientes con angina inestable; grupo III, 14 pacientes con dolor torácico atípico para angina; grupo IV, cinco sujetos sanos; grupo V, cinco pacientes con infarto agudo del miocardio con elevación del segmento ST. Se hizo una evaluación cualitativa con un dispositivo automático de interpretación rápida para troponina I, mioglobina y CPK-MB. Resultados: 48 pacientes con edad promedio de 55 + 18 años: 25 hombres (52 %) y 23 mujeres (48 %). La mediana del tiempo de evolución de iniciados los síntomas fue de 3.5 horas (cuartiles 25, 75: 2 a 6). Para la troponina I, mioglobina y CPK-MB, la especificidad fue de 94, 91 y 94 %; la sensibilidad fue de 100 % para los tres marcadores, al igual que el valor predictivo negativo; el valor predictivo positivo fue de 89, 84 y 89 %, y el cociente de probabilidad de 8.7, 5.5 y 8.7, respectivamente. Conclusiones: desde la fase prehospitalaria, la troponina I, mioglobina y CPK-MB tienen alto valor diagnóstico en el síndrome coronario agudo. Su determinación es recomendable como parte del protocolo de diagnóstico y de gran ayuda para decidir la hospitalización y el tratamiento.

OBJECTIVE: We measured the diagnostic value of troponin I (TnI), mioglobin (Miog) and creatine kinase MB (CPK-MB) in patients with thoracic pain during the period of preadmission to the hospital. METHODS: We included patients who requested prehospital attention with intensive therapy ambulance or who were in the first hours of hospitalization for thoracic pain. A 12-lead electrocardiogram was carried out in the ambulance or in the emergency room. The levels of total creatine phosphokinase were determined (as reference pattern). Five study groups were included: group I, 13 patients with acute myocardial infarction without elevation of the ST segment; group II, 11 patients with unstable angina; group III, 14 patients with atypical thoracic pain for angina; group IV, five healthy patients; and group V, five patients with acute myocardial infarction with elevation of the ST segment. A qualitative evaluation was made with an automatic device for quick interpretation of TnI, Miog and CPK-MB. RESULTS: Forty eight patients were studied with an average age of 55+/-18 years, 25 men (52%) and 23 women (48%), average time of symptom evolution was 3.5 h (quartiles 2 and 6 h). Total level of CPK was taken as a reference pattern. Sensitivity of TnI, Miog, and CPK-MB was 100%, specificity was 94, 91 and 94%, respectively. Positive predictive value was 89, 84 and 89%, respectively. Negative predictive value was 100%. Likelihood of probability was 8.7, 5.5 and 8.7, respectively. CONCLUSIONS: TnI, Miog and CPK-MB have high diagnostic value in acute coronary syndrome (ACS) from the time of prehospital admission. Determination is advisable as part of the diagnostic protocol, which is of great importance in order to plan the hospitalization and treatment in this group of patients.

Análise de marcadores de estabilização da placa aterosclerótica após evento coronariano agudo / Inflammatory markers of atherosclerotic plaque stabilization after acute coronary event - temporal trends

OBJETIVO: Avaliar o tempo para a estabilização da placa aterosclerótica nas síndromes coronarianas agudas (SCA) utilizando-se marcadores inflamatórios. MÉTODOS: Estudo prospectivo, quarenta pacientes com SCA sem supradesnivelamento de ST versus quarenta indivíduos sem doença coronariana. Proteína C-reativa (PCR), fibrinogênio, fator VIIIc, interleucina-6 e TNF (fator de necrose tumoral)-alfa foram coletados na internação, na alta hospitalar e após três e seis meses. RESULTADOS: Comparada ao controle, a PCR foi significativamente maior na internação e na alta, mas não após três e seis meses. Os níveis de fibrinogênio não apresentaram variações, exceto aos seis meses, quando foi significativamente menor que o controle. O fator VIIIc não diferiu do controle na internação, mas foi significativamente maior na alta, e sem diferenças aos três e seis meses. A IL-6 foi significativamente maior que o controle em todos os períodos. Entretanto, houve queda significativa dos seus níveis entre a alta e três meses. O TNF-alfa não foi significativamente diferente do controle em nenhum momento. Somente a IL-6 se correlacionou significativa e independentemente com eventos cardiovasculares futuros. CONCLUSÃO: Quanto a PCR e fator VIIIc, sugere-se estabilização da placa em até três meses; a análise da IL-6 sugere estabilização a partir do terceiro mês, apesar de permanecer elevada em relação ao controle em até seis meses. Apenas a IL-6 mostrou valor prognóstico de eventos futuros em um ano.

Marcadores en la estratificación de los síndromes coronarios agudos / Risk marker stratification in coronary acute syndromes

Acute coronary syndromes have a heterogeneous clinical presentation with a broad spectrum for mortality and adverse events. It is mandatory to identify high risk groups for percutaneous coronary intervention and intensive antithrombotic treatment or common risk for standard treatment. In contemporaneous medicine it is important to get adequate risk stratification because the impact of hospitalary costs, antithrombotic and reperfusion treatment on health systems. The current pathophysiology of atherosclerosis is moving from a disease secondary to cholesterol deposit, to an inflammatory disease. In the stratification process, familiar history, chest pain, ST dynamic abnormalities, left ventricular wall motion abnormalities, all have predictive value. The association of indirect endothelial dysfunction, micro or macronecrosis and ventricular dysfunction markers increase this value. In our experience a close relationship among abnormal fibrinolysis, inflammation and anticoagulation proteins with adverse events has been proved in acute coronary syndromes. Other interesting finding--for it accessibility--in acute myocardial infarction under coronary percutaneous intervention is persistent ST elevation, leukocytes and fibrinogen predictive value. In population allelic polymorphisms -455A and -148T and fibrinogen ( >450 mg/dL) were associated with coronary disease. These polymorphisms improve risk stratification of coronary disease to establish a better secondary prevention and treatment.

Correlação entre marcadores bioquímicos e a cineangiocoronariografia em portadores de síndromes isquêmicas agudas sem supradesnivelamento de segmento ST / Correlation between biochemical markers and coronary angiography in patients with non-ST elevation acute coronary syndromes

OBJETIVO: Investigar associação entre marcadores bioquí¡micos (TN-I, PCRt e fibrinogênio) e achados cineangiocoronariográficos em portadores de síndrome isquêmica aguda sem supradesnivelamento de segmento ST (SIA sem supra ST). MÉTODOS: Obtida amostra sangüínea única para dosagem dos marcadores, e cineangiocoronariografia (CINE) realizada até 72 horas da internação. Análise univariada para investigar relação dos três marcadores com os achados na CINE, no grupo com artéria responsável pela isquemia (ARI) identificada, e análise multivariada para investigar relação desses marcadores com a presença de lesão aterosclerótica instável, apenas no grupo com obstrução coronariana >50 por cento. RESULTADOS: Estudo prospectivo, com 84 pacientes, 65,5 por cento do sexo masculino. No grupo onde identificou-se a ARI, os valores séricos dos três marcadores foram superiores, quando comparados aos grupos sem ARI identificada ou com coronárias normais. No grupo com ARI identificada, houve correlação entre fluxo TIMI e TN-I (p = 0,006), lesão aterosclerótica instável e TN-I e fibrinogênio (p = 0,02 e p = 0,01, respectivamente) e doença multiarterial e PCRt (p = 0,0005). Na análise multivariada, os três marcadores foram preditores independentes da presença de lesão aterosclerótica instável (p = 0,002, p = 0,003 e p = 0,007, respectivamente, para PCR, fibrinogênio e TN-I). CONCLUSÃO: Em portadores de SIA sem supra ST, a dosagem sérica de TN-I, PCR e fibrinogênio nas primeiras dez horas da internação se correlacionou a achados angiográficos.

Utilidad de la determinación cualitativa de troponina I y creatinfosfocinasa isoenzima MB en los síndromes isquémicos coronarios agudos / Usefulness of rapid bedside assay of cardiac troponin I and creatine phosphokinase-MB in acute ischemic coronary syndromes

Recently, a rapid bedside assay for quantitative determination of cTI and CPK-MB has been developed that provides a positive or negative result in 10 to 15 minutes allowing for a better therapeutic approach. The objective of our study was to validate the diagnostic usefulness of cardiac troponin I in patients with chest pain. We determined sensitivity, specificity, positive and negative predictive values in 40 patients that arrived to the hospital with chest pain. These patients were assigned to four different groups: Group A: Patients with acute myocardial infarction. Group B: Patients with unstable angina and normal ECG. Group C: Patients with atypical chest pain and normal ECG. Group D: Control. Eighteen (45%) patients were woman and 22 (55%) were men; age 54.1 +/- 26, range 32 to 85 years. In Group A, sensitivity, specificity, positive and negative predictive values for cTI were 95%, for CPK-MB, they were 40, 50, 90, 7.1%. For Group B, cTI: 64, 90, 90, 64%; CPK-MB: 50, 90, 87, 56%. Group C, cTI and CPK MB 25, 95, 50, 86%. Group D, cTI and CPK-MB: 50, 95, 50, 95%. This study suggests that the rapid bedside qualitative test through cardiac troponin I assessment is a test with higher predictive value for early diagnosis of acute myocardial infarction than CPK-MB.

Risk stratification in the patient with non ST segment elevation acute coronary syndrome

Patients hospitalized with unstable angina (UA) or with a non-ST segment elevation myocardial infarct (NSTEMI) are at increased risk of suffering refractory angina, recurrent myocardial infarct (MI), and death. These patients need to be evaluated more aggressively. According to the last published guidelines (2002) of UA/NSTEMI by the ACC/AHA Task Force, these patients should be categorized in a risk scale as: low, intermediate or high. This should be done in the initial evaluation, which includes: medical history, physical exam, an electrocardiogram (ECG) and cardiac markers. The TIMI risk score should also be used as complementary in this risk assessment. High risk patients, without contraindications, should be managed more aggressively with coronary angiography. On the other end, low risk patients, and some intermediate, may be evaluated more conservatively with early non-invasive studies for further assessment of ischemia and prognosis.

Biomarcadores coronarios y evolución clínica alejada en pacientes con síndromes coronarios agudos sin elevación del segmento ST / Coronary biomarkers and long-term clinical outcome in acute coronary syndrome without ST segment elevation

Background: The use of new biomarkers improved risk stratification for patients with acute coronary syndromes (ACS). Aim: To evaluate the relationship between multiple biomarkers and long-term clinical outcome in ACS without ST segment elevation. Patients and Methods: Consecutive patients presenting with suspected ACS were studied. On admission to the emergency room, serum was obtained to determine highly sensitive C reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), lipoprotein (a) (LPa) and soluble P selectin (sPS). Clinical endpoints were mortality and a composite endpoint of major adverse cardiovascular events (MACE) including death, re-infarction, and angina. Results: Seventy patients, aged 63±13 years, 54 males, were studied. Final diagnosis was unstable angina in 71% and non-ST-segment elevation myocardial infarction in 29%. MACE and mortality rate were 17% and 5.8%, respectively. We found higher plasma levels of hsCRP, ESR and Lp(a) in patients with MACE (p=0.032, p=0.015 and p=0.010, respectively). Plasma levels of hsCRP and ESR were also higher in patients who died during the follow up (p=0.002 y p=0.045, respectively). Conclusion: Plasma levels of inflammatory markers and atherosclerosis biomarkers are associated with a worse long-term clinical outcome in ACS without ST segment elevation. The inclusion of these biomarkers in the routine blood test on admission, could improve risk stratification of patients with ACS in the future.