RESUMO
BACKGROUND: Although there is strong evidence supporting the use of statin therapy after myocardial infarction (MI), some mechanistic gaps exist regarding the benefits of this therapy at the very onset of MI. Among the potential beneficial mechanisms, statins may improve myocardial electrical stability and reduce life-threatening ventricular arrhythmia, as reported in stable clinical conditions. This study was designed to evaluate whether this mechanism could also occur during the acute phase of MI. METHODS: Consecutive patients with ST-segment elevation MI were treated without statin (n = 57) or with a simvastatin dose of 20 to 80 mg (n = 87) within the first 24 hours after MI symptom onset. Patients underwent digital electrocardiography within the first 24 hours and at the third and fifth days after MI. The QTC dispersion (QTcD) was measured both with and without the U waves. RESULTS: Although QTcD values were equivalent between the groups at the first day (80.6 ± 36.0 vs 80.0 ± 32.1; P = 0.36), they were shorter among individuals using simvastatin than in those receiving no statins on the third (90.4 ± 38.6 vs 86.5 ± 36.9; P = .036) and fifth days (73.1 ± 31 vs 69.2 ± 32.6; P = .049). We obtained similar results when analyzing the QTcD duration including the U wave. All values were adjusted by an ANCOVA model after propensity-score matching. CONCLUSIONS: Statins administered within 24 hours of ST-segment elevation MI reduced QTc dispersion, which may potentially attenuate the substrate for life-threatening ventricular arrhythmias.
Assuntos
Potenciais de Ação/efeitos dos fármacos , Antiarrítmicos/administração & dosagem , Arritmias Cardíacas/prevenção & controle , Frequência Cardíaca/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Sinvastatina/administração & dosagem , Idoso , Antiarrítmicos/efeitos adversos , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Esquema de Medicação , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Sinvastatina/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
Hyperglycemia during myocardial infarction (MI) has a strong and direct association with mortality. In stable patients and experimental models, statins favor the elevation of glycaemia. The present study investigated whether short-course treatment with statins during MI can influence glucose homeostasis and thus the clinical outcome. In this prospective study, euglycemic hyperinsulinemic clamp (EHC) was performed at second (D2) and sixth (D6) day after MI in patients randomized to simvastatin (S)10 or 80 mg/day during hospitalization (n = 27). In addition, patients (n = 550) were treated without (WS) or with simvastatin (S) at 20, 40 or 80 mg/day had HOMA2S on admission (D1) and fifth (D5) day after MI. According to EHC, insulin sensitivity increased by 20 ± 60% in S10 and decreased by -6 ± 28% in S80 (p = 0.025). Consistently, the changes in HOMA2S between D1 and D5 were 40 ± 145% (WS), 22 ± 117% (S20), 16 ± 61% (S40) and -2% ± 88% (S80) (p = 0.001). In conclusion, statin during the acute phase of MI reduces insulin sensitivity in a dose-dependent manner.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Resistência à Insulina , Insulina/metabolismo , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Sinvastatina/administração & dosagem , Adulto , Esquema de Medicação , Feminino , Hospitalização , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/metabolismo , Sinvastatina/farmacologia , Adulto JovemRESUMO
BACKGROUND: Myocardial infarction (MI) elicits an intense acute inflammatory response that is essential for cardiac repair. However, an excessive inflammatory response also favors myocardial apoptosis, cardiac remodeling, and cardiovascular mortality. Omega-3 polyunsaturated fatty acids (ω-3) bear anti-inflammatory effects, which may mitigate the inflammatory response during MI. This study investigated whether ω-3 intake is associated with attenuation of the MI-related inflammatory response and cardiac remodeling. METHODS: ST-elevation MI (STEMI) patients (n = 421) underwent clinical, biochemical, nutritional, 3D echocardiogram, Cardiac Magnetic Resonance imaging (CMRi) at 30 days and 3D echocardiogram imaging at six months after the MI. Blood tests were performed at day one (D1) and day five (D5) of hospitalization. Changes in inflammatory markers (ΔD5-D1) were calculated. A validated food frequency questionnaire estimated the nutritional consumption and ω-3 intake in the last 3 months before admission. RESULTS: The intake of ω-3 below the median (< 1.7 g/day) was associated with a short-term increase in hs-C-reactive protein [OR:1.96(1.24-3.10); p = 0.004], Interleukin-2 [OR:2.46(1.20-5.04); p = 0.014], brain-type natriuretic peptide [OR:2.66(1.30-5.44); p = 0.007], left-ventricle end-diastolic volume [OR:5.12(1.11-23.52)]; p = 0.036] and decreases in left-ventricle ejection fraction [OR:2.86(1.47-6.88); p = 0.017] after adjustment for covariates. No differences were observed in the extension of infarcted mass obtained by CMRi. CONCLUSION: These findings suggest that a reduced daily intake of ω-3 may intensify outcome-determining mechanisms after STEMI, such as acute inflammatory response and late left ventricular remodeling. TRIAL REGISTRATION: Clinical Trial Registry number and website: NCT02062554 .
Assuntos
Ácidos Graxos Ômega-3/farmacologia , Inflamação/sangue , Inflamação/etiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Remodelação Ventricular/fisiologia , Biomarcadores/sangue , Brasil , Estudos de Coortes , Ecocardiografia Tridimensional/métodos , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND AIMS: Coronary reperfusion with HDL from healthy volunteers attenuates ischemia and reperfusion injury in animal models. In myocardial infarction (MI) patients, such an interaction is unclear. Hence, our first objective was to verify if there is interaction between HDL-C and MI mass in patients and the role of coronary reperfusion in the interaction. Furthermore, we investigated whether the effect in MI size of reperfusion with HDL obtained from healthy participants or MI patients could differ. METHODS: HDL-C was measured the first day after MI and MI mass was quantified by cardiac magnetic resonance (nâ¯=â¯94) and peak CKMB (nâ¯=â¯393). In an ex vivo rat heart model, we compared MI area and dP/dt max after coronary reperfusion with HDL from MI patients or healthy volunteers. RESULTS: HDL-C above the median (35â¯mg/dL) was associated with higher peak CKMB [255 (145-415) vs. 136 (84-287) UI/L; p = 0.02], higher MI mass [17 (9-21) vs. 10 (6-14) g; p < 0.01] and lower left ventricular ejection fraction [47 (34-53) vs. 51 (43-59); p = 0.02] than their counterparts. In restricted cubic spline and multivariate linear regression, HDL-C was directly associated with peak CKMB (p < 0.01) and MI mass (p < 0.01) only in reperfused patients with time to reperfusion <4â¯h. Reperfusion with healthy HDL, but not from MI patients, reduced MI mass (p < 0.01) and improved dP/dt max (p = 0.02). CONCLUSIONS: In MI patients undergoing early coronary reperfusion, HDL-C levels at admission are directly associated with MI size. In contrast to healthy HDL, reperfusion with HDL from MI patients do not reduce MI area in an ex vivo animal model.
Assuntos
HDL-Colesterol/sangue , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Revascularização Miocárdica , Miocárdio/patologia , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Idoso , Animais , Biomarcadores/sangue , Creatina Quinase Forma MB/sangue , Modelos Animais de Doenças , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/diagnóstico por imagem , Traumatismo por Reperfusão Miocárdica/patologia , Revascularização Miocárdica/efeitos adversos , Estudos Prospectivos , Ratos Wistar , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/patologia , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: Chronic dysglycemia was recently identified as a predictor for adverse outcomes in patients with ST-elevation myocardial infarction (STEMI) treated by percutaneous coronary intervention. Data for non-diabetic patients who underwent thrombolysis is scarce. In this context, we aimed to study the effect of HbA1c on cardiovascular outcome after STEMI. METHODS: A prospective cohort of 326 non-diabetic STEMI individuals was used for the analyses. We measured plasma glucose, hemoglobin A1c [HbA1c], lipid profile, C-reactive protein (CRP), and nitrate/nitrite (NOx) upon admission and five days after STEMI (D5). Flow-mediated dilation (FMD) was performed 30 days after STEMI. During clinical follow-up, we assessed patients for incident diabetes (progression to HbA1c ≥ 6.5%) and major adverse cardiac events (MACE), defined as a composite of fatal and non-fatal MI, sudden cardiac death, and angina requiring hospitalization. RESULTS: Using ROC-curve analysis, a 5.8% HbA1c best predicted MACE with a sensitivity of 75% and specificity of 53% (AUC 0.673, p = 0.001). Patients were categorized as high HbA1c if ≥ 5.8% and low HbA1c if <5.8%. Compared with patients with low HbA1c, those with high HbA1c presented with 20% higher CRP-D5 (p = 0.009) and 19% higher ΔCRP (p = 0.01), a 32% decrease in ΔNOx (p < 0.001), and 33% lower FMD (p < 0.001). After a median follow-up of 1.9 (1.1-2.8) years, patients with high HbA1c had more incident diabetes (HR 2.3 95% CI 1.01-5.2; p = 0.048) and MACE (HR 3.32 95% CI 1.09-10.03; p = 0.03). CONCLUSION: Non-diabetic STEMI patients with high HbA1c present with decreased endothelial function and increased inflammatory response and long-term risk of MACE.
Assuntos
Endotélio Vascular/fisiopatologia , Hemoglobinas Glicadas/análise , Infarto do Miocárdio/sangue , Idoso , Glicemia/análise , Artéria Braquial/patologia , Proteína C-Reativa/análise , Angiografia Coronária , Diabetes Mellitus , Dieta , Feminino , Seguimentos , Humanos , Inflamação , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Óxido Nítrico/química , Admissão do Paciente , Intervenção Coronária Percutânea , Estudos Prospectivos , Curva ROC , Fatores de Risco , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
AIM/BACKGROUND: Abundant evidence shows that coronary artery calcification (CAC) is a strong marker of structural and functional changes within the artery wall. Thus far, the implications of CAC in patients with acute coronary syndromes remain unclear. We aimed to investigate whether the CAC score is associated with impaired reperfusion during the acute phase of ST-elevation myocardial infarction (STEMI). METHODS: We enrolled 60 consecutive STEMI patients to undergo cardiac computed tomography for assessment of the CAC score within 1 week after STEMI. Coronary thrombus burden, coronary blood flow (TIMI flow), and myocardial blush grade (MBG) were evaluated systematically. Patients with maximal TIMI flow and MBG were grouped as optimal reperfusion (n=27) and their counterparts as no-reflow (NR, n=33). RESULTS: There were no differences in the clinical characteristics between groups. Patients in the NR group had higher heart rate, coronary angiographic severity, and CAC score. CAC score greater than 100 was associated independently with the presence of NR (odds ratio 4.4, 95% confidence interval 1.17-16.3). The CAC score of nonculprit coronary arteries was higher in NR individuals than in their counterparts (P=0.04). In addition, the CAC score of the isnfarct-related artery correlated negatively with the TIMI-flow rate (r=-0.54, P<0.001) and with the MBG (r=-0.32, P=0.04). CONCLUSION: The CAC score is associated with the presence of the NR phenomenon in STEMI patients.
Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Infarto do Miocárdio/terapia , Fenômeno de não Refluxo/epidemiologia , Intervenção Coronária Percutânea , Calcificação Vascular/diagnóstico por imagem , Idoso , Brasil/epidemiologia , Angiografia Coronária , Doença da Artéria Coronariana/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X , Calcificação Vascular/epidemiologiaRESUMO
OBJECTIVE: Recent data suggests that cholesteryl ester transfer protein (CETP) activity may interact with acute stress conditions via inflammatory-oxidative response and thrombogenesis. We investigated this assumption in patients with ST-elevation myocardial infarction (STEMI). METHODS: Consecutive patients with STEMI (n = 116) were enrolled <24-h of symptoms onset and were followed for 180 days. Plasma levels of C-reactive protein (CRP), interleukin-2 (IL-2), tumor necrosis factor (TNFα), 8-isoprostane, nitric oxide (NOx) and CETP activity were measured at enrollment (D1) and at fifth day (D5). Flow-mediated dilation (FMD) was assessed by ultrasound and coronary thrombus burden (CTB) was evaluated by angiography. RESULTS: Neither baseline nor the change of CETP activity from D1 to D5 was associated with CRP, IL-2, TNFα, 8-isoprostane levels or CTB. The rise in NOx from D1 to D5 was inferior [3.5(-1; 10) vs. 5.5(-1; 12); p < 0.001] and FMD was lower [5.9(5.5) vs. 9.6(6.6); p = 0.047] in patients with baseline CETP activity above the median value than in their counterparts. Oxidized HDL was measured by thiobarbituric acid reactive substances (TBARS) in isolated HDL particles and increased from D1 to D5, and remaining elevated at D30. The change in TBARS content in HDL was associated with CETP activity (r = 0.72; p = 0.014) and FMD (r = -0.61; p = 0.046). High CETP activity at admission was associated with the incidence of sudden death and recurrent MI at 30 days (OR 12.8; 95% CI 1.25-132; p = 0.032) and 180 days (OR 3.3; 95% CI 1.03-10.7; p = 0.044). CONCLUSIONS: An enhanced CETP activity during acute phase of STEMI is independently associated with endothelial dysfunction and adverse clinical outcome.
Assuntos
Proteínas de Transferência de Ésteres de Colesterol/sangue , Endotélio Vascular/fisiopatologia , Lipoproteínas HDL/sangue , Infarto do Miocárdio/sangue , Oxigênio/química , Substâncias Reativas com Ácido Tiobarbitúrico/química , Idoso , Angiografia , Proteína C-Reativa/metabolismo , Dinoprosta/análogos & derivados , Dinoprosta/sangue , Endotélio Vascular/patologia , Feminino , Humanos , Interleucina-2/sangue , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Estudos Prospectivos , Sistema de Registros , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue , Doenças Vasculares/patologiaRESUMO
OBJECTIVE: Acute phase response modifies high-density lipoprotein (HDL) into a dysfunctional particle that may favor oxidative/inflammatory stress and eNOS dysfunction. The present study investigated the impact of this phenomenon on patients presenting ST-elevation myocardial infarction (STEMI). METHODS: Plasma was obtained from 180 consecutive patients within the first 24-h of onset of STEMI symptoms (D1) and after 5 days (D5). Nitrate/nitrite (NOx) and lipoproteins were isolated by gradient ultracentrifugation. The oxidizability of low-density lipoprotein incubated with HDL (HDLaoxLDL) and the HDL self-oxidizability (HDLautox) were measured after CuSO4 co-incubation. Anti-inflammatory activity of HDL was estimated by VCAM-1 secretion by human umbilical vein endothelial cells after incubation with TNF-α. Flow-mediated dilation (FMD) was assessed at the 30(th) day (D30) after STEMI. RESULTS: Among patients in the first tertile of admission HDL-Cholesterol (<33 mg/dL), the increment of NOx from D1 to D5 [6.7(2; 13) vs. 3.2(-3; 10) vs. 3.5(-3; 12); p = 0.001] and the FMD adjusted for multiple covariates [8.4(5; 11) vs 6.1(3; 10) vs. 5.2(3; 10); p = 0.001] were higher than in those in the second (33-42 mg/dL) or third (>42 mg/dL) tertiles, respectively. From D1 to D5, there was a decrease in HDL size (-6.3 ± 0.3%; p < 0.001) and particle number (-22.0 ± 0.6%; p < 0.001) as well as an increase in both HDLaoxLDL (33%(23); p < 0.001) and HDLautox (65%(25); p < 0.001). VCAM-1 secretion after TNF-a stimulation was reduced after co-incubation with HDL from healthy volunteers (-24%(33); p = 0.009), from MI patients at D1 (-23%(37); p = 0.015) and at D30 (-22%(24); p = 0.042) but not at D5 (p = 0.28). CONCLUSION: During STEMI, high HDL-cholesterol is associated with a greater decline in endothelial function. In parallel, structural and functional changes in HDL occur reducing its anti-inflammatory and anti-oxidant properties.
Assuntos
Endotélio Vascular/patologia , Lipoproteínas HDL/sangue , Infarto do Miocárdio/sangue , Óxido Nítrico/química , Oxigênio/sangue , Vasodilatação , Idoso , Antioxidantes/química , Área Sob a Curva , Glicemia/química , Estudos de Casos e Controles , Feminino , Humanos , Inflamação , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Oxigênio/química , Fenótipo , Estudos Prospectivos , Substâncias Reativas com Ácido Tiobarbitúrico , Resultado do TratamentoRESUMO
Enhanced systemic inflammatory activity (SIA) during myocardial infarction (MI) and the extent of the peri-infarct zone characterized by cardiac magnetic resonance imaging (CMRi) are both associated with increased risk of life-threatening arrhythmias and sudden cardiac death. The present study investigated the existence of association between these two phenomena in 98 patients (55 ± 10 years) with ST segment elevation MI. Plasma levels of C-reactive protein (CRP), interleukin-2 (IL-2), and tumor necrosis factor (TNF) were measured on admission (D1) and on the fifth day post-MI (D5). CMRi was performed 2 weeks after MI to quantify peri-infarct zone (PIZ). Between D1 and D5, the increase in CRP (6.0 vs. 5.6 times; p = 0.02), IL-2 (3.6 vs. 3.4 times; p = 0.04) and tumor necrosis factor type α (TNF-α; 4.6 vs. 3.9 times; p = 0.001) were higher in patients with PIZ above the median than in the counterparts. PIZ was correlated with CRP-D5 (r = 0.69), delta-CRP (r = 0.7), IL-2-D5 (r = 0.5), delta-IL-2 (r = 0.6), TNF-α (r = 0.5), delta-TNF-α (r = 0.4; p = 0.0001). Enhanced activation of SIA during the acute phase of MI is directly related with generation of PIZ.
Assuntos
Arritmias Cardíacas/patologia , Morte Súbita Cardíaca/patologia , Inflamação/imunologia , Infarto do Miocárdio/imunologia , Infarto do Miocárdio/patologia , Proteína C-Reativa/metabolismo , Angiografia Coronária , Feminino , Coração/fisiopatologia , Humanos , Interleucina-2/sangue , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fator de Necrose Tumoral alfa/sangueRESUMO
OBJECTIVE: Often, as diabetes mellitus type 2 (T2DM) evolves insidiously, prevention is commenced late and diagnosis is made when vascular damage has been set. Hence, our hypothesis is that T2DM awareness may influence the outcome of atherothrombotic events. METHODS: A consecutive cohort of patients manifesting ST-elevation myocardial infarction (MI) was classified according to the presence and awareness of the diagnosis of T2DM: known diabetes (kT2DM, n = 72), unknown diabetes (uT2DM, n = 80) and no diabetes (ND, n = 333). Medical history, laboratory data, and angiographic findings including myocardial blush grade (MBG) were prospectively obtained. The primary endpoint was in-hospital death and secondary endpoint was major adverse cardiac events (MACE) defined as sudden cardiac death, fatal MI and nonfatal MI that occurred from 30 days of study entry onwards. RESULTS: With the exception of glycated hemoglobin (p = 0.001) and triglycerides (p = 0.04), no differences were found between groups for all other biochemical, clinical or angiographic admission characteristics. Myocardial tissue reperfusion defined as MBG 3 was observed in 62% in the ND group, 50% in the kT2DM group and 23% in the uT2DM group (p = 0.01). All-cause in-hospital mortality was higher in uT2DM (16.7%) than in kT2DM (8.4%) and both groups had a higher mortality rate as compared with the ND group (3.8%, p = 0.01). During follow-up (653 ± 26 days), the incidence of MACE was higher in uT2DM than in kT2DM and in both compared to the ND group (p = 0.002). CONCLUSION: Unawareness of T2DM diagnosis is strongly associated with a poor short- and long-term outcome after MI.