Effects of phytosterol supplementation on lipoprotein subfractions and LDL particle quality.

Phytosterols are natural components of plant-based foods used as supplements because of their known cholesterol-lowering effect. However, their effects on lipoprotein subfractions and the quality of the LDL particle have not been studied in greater detail. We aimed to evaluate the effects of phytosterols supplements on lipids, lipoproteins subfractions, and on the quality of LDL. A prospective, pilot-type, open label, cross-over study, randomized 23 males in primary prevention of hypercholesterolemia to receive diet or diet plus phytosterol (2.6 g in 2 doses, with meals) for 12 weeks, when treatments were switched for another 12 weeks. Lipoprotein subfractions were analyzed by electrophoresis in polyacrylamide gel (Lipoprint System®). The Sampson equation estimated the small and dense (sd) and large and buoyant (lb) LDL subfractions from the lipid profile. Quality of LDL particle was analyzed by Z-scan and UV-vis spectroscopy. Primary outcome was the comparison of diet vs. diet plus phytosterols. Secondary outcomes assessed differences between baseline, diet and diet plus phytosterol. Non-parametric statistics were performed with p < 0.05. There was a trend to reduction on HDL-7 (p = 0.05) in diet plus phytosterol arm, with no effects on the quality of LDL particles. Heatmap showed strong correlations (ρ > 0.7) between particle size by different methods with both interventions. Diet plus phytosterol reduced TC, increased HDL-c, and reduced IDL-B, whereas diet increased HDL7, and reduced IDL-B vs. baseline (p < 0.05, for all). Phytosterol supplementation demonstrated small beneficial effects on HDL-7 subfraction, compared with diet alone, without effects on the quality of LDL particles.This trial is registered in Clinical Trials (NCT06127732) and can be accessed at https://clinicaltrials.gov .

Association between Morning Surge and Left Ventricular Hypertrophy in Obese Hypertensive Patients. / Relação da Ascensão Matinal da Pressão Arterial com a Hipertrofia Ventricular Esquerda em Hipertensos Obesos.

BACKGROUND: Weight gain can trigger mechanisms that increase blood pressure. Nevertheless, obesity causes structural changes in the myocardium, including increased ventricular mass, atrial dilatation, and diastolic and systolic dysfunction. Additionally, blood pressure variations, like morning surge (MS) in obese hypertensive patients may have clinical relevance in cardiovascular events. Although morning blood pressure surge is a physiological phenomenon, excess MS can be considered an independent risk factor for cardiovascular events. OBJECTIVE: To evaluate MS values and their association with left ventricular hypertrophy (LVH) and nocturnal dipping (ND) in obese and non-obese hypertensive patients. METHODS: A cross-sectional study that evaluated BP measurements by ambulatory blood pressure monitoring (ABPM) and the presence of LVH by echocardiography in 203 hypertensive outpatients, divided into two groups: 109 non-obese and 94 obese hypertensives patients. The significance level was set at 0.05 in two-tailed tests. RESULTS: A MS above 20 mmHg by ABPM was detected in 59.2% of patients in the non-obese group and 40.6% in the obese group. LVH was found in 18.1% and 39.3% of patients in the non-obese and obese groups, respectively, p<0.001. In the "obese group", it was observed that a MS>16 mmHg was associated with LVH, [prevalence ratio: 2.80; 95%CI (1.12-6.98), p=0.03]. For the non-obese group, the cut-off point of MS for this association was >22 mmHg. CONCLUSION: High MS was positively associated with LVH, with a particular behavior in the hypertensive obese group.

Pharmacoinvasive Strategy in Elderly Up to 75 Years or Non-Elderly: Analysis of Biochemical and Cardiac Magnetic Resonance Imaging Parameters. / Estratégia Farmacoinvasiva em Idosos até 75 Anos ou Não Idosos: Análise de Parâmetros Bioquímicos e de Ressonância Nuclear Magnética Cardíaca.

BACKGROUND: Pharmacoinvasive strategy is an alternative when primary percutaneous coronary intervention (PCI) is not feasible. OBJECTIVES: This study aimed to evaluate the effects of early pharmacoinvasive strategy on the infarct size and left ventricular ejection fraction in elderly and non-elderly patients. The role of inflammatory markers was also examined. METHODS: Patients (n=223) with ST segment elevation myocardial infarction (STEMI) were prospectively included and submitted to pharmacological thrombolysis in the first six hours, and underwent coronary angiogram and PCI when necessary, in the first 24 hours. Blood samples were collected in the first day (D1) and after 30 days (D30). Cardiac magnetic resonance imaging (cMRI) was performed at D30. Significance was set at p<0.05. RESULTS: Elderly and non-elderly patients showed similar percentage of infarcted mass (13.7 [6.9-17.0] vs. 14.0 [7.3-26.0], respectively, p=0.13) (median [interquartile range]). However, elderly patients had better left ventricular ejection fraction (53 [45-62] vs. 49 [39-58], p=0.025). Titers of interleukin (IL)1beta, IL-4, IL-6, and IL-10 did not differ between D1 and D30, but elderly patients had higher titers for IL-18 at D1 and D30. Absolute numbers of B and T lymphocytes were similar in both groups at D1 and D30, but elderly patients had higher neutrophil/lymphocyte ratio at D30. Multivariate linear regression analysis of cMRI outcomes in the whole population showed that the independent predictors were not different between elderly and non-elderly patients. CONCLUSION: Pharmacoinvasive strategy in elderly patients was associated with small differences in inflammatory parameters, similar infarct size and better left ventricular function than non-elderly patients.

FUNDAMENTO: A estratégia farmacoinvasiva é uma alternativa na inviabilidade da intervenção coronária percutânea primária (ICP). OBJETIVOS: Este estudo teve como objetivo avaliar os efeitos da estratégia farmacoinvasiva precoce sobre o tamanho da área infartada e a fração de ejeção ventricular esquerda em pacientes idosos e não idosos. O papel dos marcadores inflamatórios também foi avaliado. MÉTODOS: Pacientes (n=223) com infarto do miocárdio com elevação do segmento ST (IAMCSST) foram prospectivamente incluídos e submetidos à trombólise medicamentosa nas primeiras seis horas, e à angiografia coronariana e à ICP, quando necessária, nas primeiras 24 horas. As amostras de sangue foram coletadas no primeiro dia (D1) e 30 dias após (D30). A ressonância magnética cardíaca foi realizada no D30. O nível de significância estatística foi estabelecido em p<0,05. RESULTADOS: Pacientes idosos e não idosos apresentaram porcentagem similares de massa infartada [13,7 (6,9-17,0) vs. 14,0 (7,3-26,0), respectivamente p=0,13)] [mediana (intervalo interquartil)]. No entanto, os pacientes idosos apresentaram maior fração de ejeção ventricular esquerda [53 (45-62) vs. 49 (39-58), p=0,025)]. As concentrações de interleucina (IL)1beta, IL-4, IL-6, e IL-10 não foram diferentes entre D1 e D30, mas pacientes idosos apresentaram níveis mais elevados de IL-18 em D1 e D30. O número absoluto de linfócitos B e T foram similares em ambos os grupos em D1 e D30, porém, pacientes idosos apresentaram uma razão neutrófilo-linfócito mais alta em D30. A análise de regressão linear multivariada dos desfechos de RMC de toda a população do estudo mostrou que os preditores independentes não foram diferentes entre pacientes idosos e não idosos. CONCLUSÃO: A estratégia farmacoinvasiva em pacientes idosos foi associada a pequenas diferenças nos parâmetros inflamatórios, tamanho do infarto similar, e melhor função ventricular esquerda em comparação a pacientes não idosos.

Estratégia Farmacoinvasiva em Idosos até 75 Anos ou Não Idosos: Análise de Parâmetros Bioquímicos e de Ressonância Nuclear Magnética Cardíaca / Pharmacoinvasive Strategy in Elderly Up to 75 Years or Non-Elderly: Analysis of Biochemical and Cardiac Magnetic Resonance Imaging Parameters

Resumo Fundamento A estratégia farmacoinvasiva é uma alternativa na inviabilidade da intervenção coronária percutânea primária (ICP). Objetivos Este estudo teve como objetivo avaliar os efeitos da estratégia farmacoinvasiva precoce sobre o tamanho da área infartada e a fração de ejeção ventricular esquerda em pacientes idosos e não idosos. O papel dos marcadores inflamatórios também foi avaliado. Métodos Pacientes (n=223) com infarto do miocárdio com elevação do segmento ST (IAMCSST) foram prospectivamente incluídos e submetidos à trombólise medicamentosa nas primeiras seis horas, e à angiografia coronariana e à ICP, quando necessária, nas primeiras 24 horas. As amostras de sangue foram coletadas no primeiro dia (D1) e 30 dias após (D30). A ressonância magnética cardíaca foi realizada no D30. O nível de significância estatística foi estabelecido em p<0,05. Resultados Pacientes idosos e não idosos apresentaram porcentagem similares de massa infartada [13,7 (6,9-17,0) vs. 14,0 (7,3-26,0), respectivamente p=0,13)] [mediana (intervalo interquartil)]. No entanto, os pacientes idosos apresentaram maior fração de ejeção ventricular esquerda [53 (45-62) vs. 49 (39-58), p=0,025)]. As concentrações de interleucina (IL)1beta, IL-4, IL-6, e IL-10 não foram diferentes entre D1 e D30, mas pacientes idosos apresentaram níveis mais elevados de IL-18 em D1 e D30. O número absoluto de linfócitos B e T foram similares em ambos os grupos em D1 e D30, porém, pacientes idosos apresentaram uma razão neutrófilo-linfócito mais alta em D30. A análise de regressão linear multivariada dos desfechos de RMC de toda a população do estudo mostrou que os preditores independentes não foram diferentes entre pacientes idosos e não idosos. Conclusão A estratégia farmacoinvasiva em pacientes idosos foi associada a pequenas diferenças nos parâmetros inflamatórios, tamanho do infarto similar, e melhor função ventricular esquerda em comparação a pacientes não idosos

Abstract Background Pharmacoinvasive strategy is an alternative when primary percutaneous coronary intervention (PCI) is not feasible. Objectives This study aimed to evaluate the effects of early pharmacoinvasive strategy on the infarct size and left ventricular ejection fraction in elderly and non-elderly patients. The role of inflammatory markers was also examined. Methods Patients (n=223) with ST segment elevation myocardial infarction (STEMI) were prospectively included and submitted to pharmacological thrombolysis in the first six hours, and underwent coronary angiogram and PCI when necessary, in the first 24 hours. Blood samples were collected in the first day (D1) and after 30 days (D30). Cardiac magnetic resonance imaging (cMRI) was performed at D30. Significance was set at p<0.05. Results Elderly and non-elderly patients showed similar percentage of infarcted mass (13.7 [6.9-17.0] vs. 14.0 [7.3-26.0], respectively, p=0.13) (median [interquartile range]). However, elderly patients had better left ventricular ejection fraction (53 [45-62] vs. 49 [39-58], p=0.025). Titers of interleukin (IL)1beta, IL-4, IL-6, and IL-10 did not differ between D1 and D30, but elderly patients had higher titers for IL-18 at D1 and D30. Absolute numbers of B and T lymphocytes were similar in both groups at D1 and D30, but elderly patients had higher neutrophil/lymphocyte ratio at D30. Multivariate linear regression analysis of cMRI outcomes in the whole population showed that the independent predictors were not different between elderly and non-elderly patients. Conclusion Pharmacoinvasive strategy in elderly patients was associated with small differences in inflammatory parameters, similar infarct size and better left ventricular function than non-elderly patients.

Relação da Ascensão Matinal da Pressão Arterial com a Hipertrofia Ventricular Esquerda em Hipertensos Obesos / Association between Morning Surge and Left Ventricular Hypertrophy in Obese Hypertensive Patients

Resumo Fundamento O aumento do peso frequentemente desencadeia mecanismos que elevam a pressão arterial. A obesidade causa mudanças estruturais no miocárdio, incluindo aumento da massa ventricular, dilatação atrial, bem como disfunções diastólicas e sistólicas. Além disso, variações pressóricas nos hipertensos obesos, como a ascensão matinal (AM), podem ter relevância clínica na prevenção dos eventos cardiovasculares. A AM da pressão arterial é um fenômeno fisiológico, que quando elevada pode ser considerada um fator de risco independente para eventos cardiovasculares. Objetivo Avaliar valores da elevação da AM e sua associação com a hipertrofia ventricular esquerda (HVE) e com o Descenso do Sono (DS) em obesos e não obesos hipertensos. Métodos Estudo transversal que avaliou medidas pressóricas à monitorização ambulatorial da pressão arterial (MAPA) e a presença de HVE, avaliada pela ecocardiografia, em 203 pacientes hipertensos em tratamento ambulatorial, separados em dois grupos: 109 não obesos e 94 hipertensos obesos. O nível de significância adotado foi de 0,05 em testes bicaudais. Resultados A AM acima de 20 mmHg à MAPA foi detectada em 59,2% dos pacientes do grupo "não obesos" e em 40,6% no grupo "obesos". A HVE foi encontrada em 18,1% no grupo dos não-obesos e em 39,3% no grupo de obesos, p<0,001. No grupo "obesos" foi observado que AM >16 mmHg esteve associada à HVE, com [razão de prevalência: 2,80; IC95% (1,12-6,98), p=0,03]. Para o grupo dos "não obesos", o ponto de corte da AM para essa associação foi >22 mmHg. Conclusão A AM elevada associou-se positivamente com HVE, com comportamento peculiar na população de hipertensos e obesos.

Abstract Background Weight gain can trigger mechanisms that increase blood pressure. Nevertheless, obesity causes structural changes in the myocardium, including increased ventricular mass, atrial dilatation, and diastolic and systolic dysfunction. Additionally, blood pressure variations, like morning surge (MS) in obese hypertensive patients may have clinical relevance in cardiovascular events. Although morning blood pressure surge is a physiological phenomenon, excess MS can be considered an independent risk factor for cardiovascular events. Objective To evaluate MS values and their association with left ventricular hypertrophy (LVH) and nocturnal dipping (ND) in obese and non-obese hypertensive patients. Methods A cross-sectional study that evaluated BP measurements by ambulatory blood pressure monitoring (ABPM) and the presence of LVH by echocardiography in 203 hypertensive outpatients, divided into two groups: 109 non-obese and 94 obese hypertensives patients. The significance level was set at 0.05 in two-tailed tests. Results A MS above 20 mmHg by ABPM was detected in 59.2% of patients in the non-obese group and 40.6% in the obese group. LVH was found in 18.1% and 39.3% of patients in the non-obese and obese groups, respectively, p<0.001. In the "obese group", it was observed that a MS>16 mmHg was associated with LVH, [prevalence ratio: 2.80; 95%CI (1.12-6.98), p=0.03]. For the non-obese group, the cut-off point of MS for this association was >22 mmHg. Conclusion High MS was positively associated with LVH, with a particular behavior in the hypertensive obese group.

Pharmaco-invasive Strategy in Myocardial Infarction: Descriptive Analysis, Presentation of Ischemic Symptoms and Mortality Predictors. / Estratégia Fármaco-Invasiva no Infarto do Miocárdio: Análise Descritiva, Apresentação de Sintomas Isquêmicos e Preditores de Mortalidade.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) is defined by symptoms accompanied by typical electrocardiogram changes. However, the characterization of ischemic symptoms is unclear, especially in subgroups such as women and the elderly. OBJECTIVES: To analyze the typification of ischemic symptoms, temporal metrics and observe the occurrence of in-hospital outcomes, in the analysis of predictive scores, in patients with STEMI, in a drug-invasive strategy. METHODS: Study involving 2,290 patients. Types of predefined clinical presentations: typical pain, atypical pain, dyspnea, syncope. We measured the time between the onset of symptoms and demand for care and the interval between arrival at the medical unit and thrombolysis. Odds-ratios (OR; CI-95%) were estimated in a regression model. ROC curves were constructed for mortality predictors. The adopted significance level (alpha) was 5%. RESULTS: Women had a high prevalence of atypical symptoms; longer time between the onset of symptoms and seeking care; delay between arrival at the emergency room and fibrinolysis. Hospital mortality was 5.6%. Risk prediction by Killip-Kimball classification: AUC: [0.77 (0.73-0.81)] in class ≥II. Subgroups studied [OR (CI-95%)]: women [2.06 (1.42-2.99); p=0.01]; chronic renal failure [3.39 (2.13-5.42); p<0.001]; elderly [2.09 (1.37-3.19) p<0.001]; diabetics [1.55 (1.04-2.29); p=0.02]; obese 1.56 [(1.01-2.40); p=0.04]: previous stroke [2.01 (1.02-3.96); p=0.04] correlated with higher mortality rates. CONCLUSION: Despite higher mortality rates in some subgroups, significant disparity persists in women, with delays in symptom recognition and prompt thrombolysis. We highlight the applicability of the Killip-Kimball score in prediction, regardless of the clinical presentation.

FUNDAMENTO: O infarto do miocárdio com elevação do segmento-ST (IAMCSST) é definido por sintomas acompanhados por alterações típicas do eletrocardiograma. Entretanto, a caracterização dos sintomas isquêmicos não é clara, principalmente em subgrupos, como mulheres e idosos. OBJETIVOS: Analisar a tipificação dos sintomas isquêmicos, métricas temporais e observar a ocorrência de desfechos intra-hospitalares, em análise dos escores preditivos, em pacientes com IAMCSST, em estratégia fármaco-invasiva. MÉTODOS: Estudo envolvendo 2.290 pacientes. Tipos de apresentações clínicas pré-definidas: dor típica, dor atípica, dispnéia, sincope. Medimos o tempo entre o início dos sintomas à demanda pelo atendimento e o intervalo entre a chegada à unidade-médica e trombólise. Odds-ratios (OR; IC-95%) foram estimadas em modelo de regressão. Curvas ROCs foram construídas para preditores de mortalidade. Nível de significância adotado (alfa) foi de 5%. RESULTADOS: Mulheres apresentaram alta prevalência de sintomas atípicos; maior tempo entre o início dos sintomas e a procura por atendimento; atraso entre a chegada ao pronto-socorro e a fibrinólise. A mortalidade hospitalar foi de 5,6%. Predição de risco pela classificação Killip-Kimball: AUC: [0,77 (0,73-0,81)] em classe ≥II. Subgrupos estudados [OR (IC-95%)]: mulheres [2,06 (1,42-2,99); p=0,01]; insuficiência renal crônica [3,39 (2,13-5,42); p<0,001]; idosos [2,09 (1,37-3,19) p<0,001]; diabéticos [1,55 (1,04-2,29); p=0,02]; obesos 1,56 [(1,01-2,40); p=0,04]; acidente vascular cerebral prévio [2,01 (1,02-3,96); p=0,04] correlacionaram-se com maiores taxas de mortalidade. CONCLUSÃO: Apesar das mais altas taxas de mortalidade em alguns subgrupos, disparidade significativa persiste nas mulheres, com atrasos no reconhecimento dos sintomas e trombólise imediata. Destaca-se a aplicabilidade do escore Killip-Kimball na predição, independentemente da apresentação clínica.

Estratégia Fármaco-Invasiva no Infarto do Miocárdio: Análise Descritiva, Apresentação de Sintomas Isquêmicos e Preditores de Mortalidade / Pharmaco-invasive Strategy in Myocardial Infarction: Descriptive Analysis, Presentation of Ischemic Symptoms and Mortality Predictors

Resumo Fundamento O infarto do miocárdio com elevação do segmento-ST (IAMCSST) é definido por sintomas acompanhados por alterações típicas do eletrocardiograma. Entretanto, a caracterização dos sintomas isquêmicos não é clara, principalmente em subgrupos, como mulheres e idosos. Objetivos Analisar a tipificação dos sintomas isquêmicos, métricas temporais e observar a ocorrência de desfechos intra-hospitalares, em análise dos escores preditivos, em pacientes com IAMCSST, em estratégia fármaco-invasiva. Métodos Estudo envolvendo 2.290 pacientes. Tipos de apresentações clínicas pré-definidas: dor típica, dor atípica, dispnéia, sincope. Medimos o tempo entre o início dos sintomas à demanda pelo atendimento e o intervalo entre a chegada à unidade-médica e trombólise. Odds-ratios (OR; IC-95%) foram estimadas em modelo de regressão. Curvas ROCs foram construídas para preditores de mortalidade. Nível de significância adotado (alfa) foi de 5%. Resultados Mulheres apresentaram alta prevalência de sintomas atípicos; maior tempo entre o início dos sintomas e a procura por atendimento; atraso entre a chegada ao pronto-socorro e a fibrinólise. A mortalidade hospitalar foi de 5,6%. Predição de risco pela classificação Killip-Kimball: AUC: [0,77 (0,73-0,81)] em classe ≥II. Subgrupos estudados [OR (IC-95%)]: mulheres [2,06 (1,42-2,99); p=0,01]; insuficiência renal crônica [3,39 (2,13-5,42); p<0,001]; idosos [2,09 (1,37-3,19) p<0,001]; diabéticos [1,55 (1,04-2,29); p=0,02]; obesos 1,56 [(1,01-2,40); p=0,04]; acidente vascular cerebral prévio [2,01 (1,02-3,96); p=0,04] correlacionaram-se com maiores taxas de mortalidade. Conclusão Apesar das mais altas taxas de mortalidade em alguns subgrupos, disparidade significativa persiste nas mulheres, com atrasos no reconhecimento dos sintomas e trombólise imediata. Destaca-se a aplicabilidade do escore Killip-Kimball na predição, independentemente da apresentação clínica.

Abstract Background ST-segment elevation myocardial infarction (STEMI) is defined by symptoms accompanied by typical electrocardiogram changes. However, the characterization of ischemic symptoms is unclear, especially in subgroups such as women and the elderly. Objectives To analyze the typification of ischemic symptoms, temporal metrics and observe the occurrence of in-hospital outcomes, in the analysis of predictive scores, in patients with STEMI, in a drug-invasive strategy. Methods Study involving 2,290 patients. Types of predefined clinical presentations: typical pain, atypical pain, dyspnea, syncope. We measured the time between the onset of symptoms and demand for care and the interval between arrival at the medical unit and thrombolysis. Odds-ratios (OR; CI-95%) were estimated in a regression model. ROC curves were constructed for mortality predictors. The adopted significance level (alpha) was 5%. Results Women had a high prevalence of atypical symptoms; longer time between the onset of symptoms and seeking care; delay between arrival at the emergency room and fibrinolysis. Hospital mortality was 5.6%. Risk prediction by Killip-Kimball classification: AUC: [0.77 (0.73-0.81)] in class ≥II. Subgroups studied [OR (CI-95%)]: women [2.06 (1.42-2.99); p=0.01]; chronic renal failure [3.39 (2.13-5.42); p<0.001]; elderly [2.09 (1.37-3.19) p<0.001]; diabetics [1.55 (1.04-2.29); p=0.02]; obese 1.56 [(1.01-2.40); p=0.04]: previous stroke [2.01 (1.02-3.96); p=0.04] correlated with higher mortality rates. Conclusion Despite higher mortality rates in some subgroups, significant disparity persists in women, with delays in symptom recognition and prompt thrombolysis. We highlight the applicability of the Killip-Kimball score in prediction, regardless of the clinical presentation.

Changes in lipoproteins associated with lipid-lowering and antiplatelet strategies in patients with acute myocardial infarction.

BACKGROUND: Despite lipid-lowering and antiplatelet therapy, the pattern of residual lipoproteins seems relevant to long-term cardiovascular outcomes. This study aims to evaluate the effects of combined therapies, commonly used in subjects with acute myocardial infarction, in the quality of low-density lipoprotein (LDL) particles. METHODS: Prospective, open-label trial, included patients with acute myocardial infarction. Patients were randomized to antiplatelet treatment (ticagrelor or clopidogrel) and subsequently to lipid-lowering therapy (rosuvastatin or simvastatin/ezetimibe) and were followed up for six months. Nonlinear optical properties of LDL samples were examined by Gaussian laser beam (Z-scan) to verify the oxidative state of these lipoproteins, small angle X-ray scattering (SAXS) to analyze structural changes on these particles, dynamic light scattering (DLS) to estimate the particle size distribution, ultra violet (UV)-visible spectroscopy to evaluate the absorbance at wavelength 484 nm (typical from carotenoids), and polyacrylamide gel electrophoresis (Lipoprint) to analyze the LDL subfractions. RESULTS: Simvastatin/ezetimibe with either clopidogrel or ticagrelor was associated with less oxidized LDL, and simvastatin/ezetimibe with ticagrelor to lower cholesterol content in the atherogenic subfractions of LDL, while rosuvastatin with ticagrelor was the only combination associated with increase in LDL size. CONCLUSIONS: The quality of LDL particles was influenced by the antiplatelet/lipid-lowering strategy, with ticagrelor being associated with the best performance with both lipid-lowering therapies. Trial registration: NCT02428374.

Role of Inflammation in Cardiac Remodeling After Acute Myocardial Infarction.

Atherosclerosis is defined as an inflammatory disease. Low-grade inflammation is present in all phases of the cardiovascular continuum, since the establishment of cardiovascular risk factors and ischemic heart disease until cardiovascular events, such as myocardial infarction, heart failure and death. Not all inflammatory pathways are linked to cardiovascular outcomes, and thus, not all anti-inflammatory approaches decrease cardiovascular events. The most common cause of ventricular remodeling and heart failure is ischemic heart disease. Biomarkers such as high-sensitivity C-reactive protein can identify individuals at risk of major cardiovascular complications, but this biomarker has no causal effect on cardiovascular disease. On the other hand, interleukin 6 appears to be causally associated with cardiovascular disease. CANTOS was the first proof of concept study showing that anti-inflammatory therapy reduces major cardiovascular outcomes. Based on many anti-inflammatory trials, only therapies acting on the NLRP3 inflammasome, or interleukin 1beta, showed benefits on cardiovascular disease. Ventricular remodeling, particularly after myocardial infarction seems also influenced by the intensity of inflammatory responses, suggesting that anti-inflammatory therapies may reduce the residual cardiovascular risk. Inflammasome (NLRP3) activation, subtypes of lymphocytes, interleukin 6, and some inflammatory biomarkers, are associated with larger infarct size and impaired ventricular function after myocardial infarction. Cardiovascular risk factors commonly present in patients with myocardial infarction, and advanced age are associated with higher inflammatory activity.

Atherosclerosis severity in patients with familial hypercholesterolemia: The role of T and B lymphocytes.

Background and aims: Familial hypercholesterolemia (FH) is characterized by lifelong exposure to high LDL-c concentrations and premature atherosclerotic cardiovascular disease; nevertheless, disease severity can be heterogeneous.We aimed at evaluating if the immune-inflammatory system could modulate atherosclerosis burden in FH. Methods: From a cohort of subjects with confirmed FH (Dutch Lipid Clinic Network and genotype), 92 patients receiving high-intensity lipid-lowering therapy (statin ± ezetimibe) were included. The extension and severity of coronary atherosclerosis was assessed by standardized reporting systems (CAD-RADS) for coronary computed tomography angiography (CCTA) and coronary artery calcium (CAC) scores. Lipids, apolipoproteins, anti-oxLDL and anti-apolipoprotein B-D peptide (anti-ApoB-D) autoantibodies (IgM and IgG), lymphocytes subtypes, platelet, monocyte and endothelial microparticles (MP), IgM levels (circulating or produced by B1 cells) and cytokines in the supernatant of cultured cells were determined. Multiple linear regression models evaluated associations of these biomarkers with CAC and CAD-RADS scores. Results: In univariate analysis CAC correlated with age, systolic blood pressure, TCD4+ cells, and titers of IgM anti-ApoB-D. In multiple linear regression [ANOVA F = 2.976; p = 0.024; R2 = 0.082), CD4+T lymphocytes (B = 35.289; beta = 0.277; p = 0.010; 95%CI for B 8.727 to 61.851), was independently associated with CAC. CAD-RADS correlated with age, systolic blood pressure, titers of IgM anti-ApoB-D, and endothelial MP in univariate analysis. In multiple linear regression, [ANOVA F = 2.790; p = 0.032; R2 = 0.119), only age (B = 0.027; beta = 0.234; p = 0.049; 95% CI for B 0.000 to 0.053) was independent predictor. Conclusions: In subjects with FH, under high-intensity lipid-lowering therapy, age and CD4+T cells were associated to atherosclerosis burden.

Prognostic role of neutrophil-to-lymphocyte ratio in patients with ST-elevation myocardial infarction undergoing to pharmaco-invasive strategy.

OBJECTIVES: We sought to determine the relationship between in-hospital mortality and the neutrophil-to-lymphocyte ratio (NLR) in patients with ST-elevation myocardial infarction (STEMI) undergoing with pharmaco-invasive strategy (PIS). BACKGROUND: Increased levels of white blood cells have been associated with adverse clinical outcomes in patients with (STEMI). NLR has recently emerged as a potent and more specific prognostic marker in predicting short- and long-term mortalityin patients undergoing primary percutaneous coronary intervention. This association has never been reported in patients managed with PIS. METHODS: Between March 2010 and October 2016, 1860 STEMI patients managed with PIS were consecutively included in a dedicated database. The study population was divided into tertiles based on the admission NLR values (lower: <4.0, intermediate: 4.0 to <7.3, and upper: ≥7.3). Co-primary endpoints were in-hospital mortality and MACE (death, non-fatal reinfarction or stent thrombosis). RESULTS: Patients in the upper NLR tertile had significantly higher in-hospital mortality (9.0% vs. 4.8% versus. 1.8%, p < 0.001) and MACE (11.6% vs. 8.0% versus 2.9%, p < 0.001) than patients with intermediate or low NLR. By multivariable logistic regression analysis, the upper NLR tertile was an independent predictor of MACE (odds radio [OR] 4.19, 95% confidence interval [95% CI] 2.23-7.88, p < 0.001) and in-hospital mortality [OR 3.32, 95% CI 1.19-9.28, p = 0.02]. CONCLUSION: High NLR values were independently associated with in-hospital MACE and death in STEMI patients submitted to a PIS. NLR might be a simple and useful risk stratification tool in this high-risk population.

Desempenho do eletrocardiograma no diagnóstico da hipertrofia ventricular esquerda em hipertensos idosos e muito idosos / Performance of the electrocardiogram in the diagnosis of left ventricular hypertrophy in older and very older hypertensive patients

Resumo Fundamento: A hipertrofia ventricular esquerda (HVE) é um importante fator de risco cardiovascular, independente da hipertensão arterial. Apesar da evolução dos exames de imagem, o eletrocardiograma (ECG) ainda é o mais utilizado na avaliação inicial, porém, com baixa sensibilidade. Objetivo: Avaliar o desempenho dos principais critérios eletrocardiográficos para HVE em indivíduos hipertensos idosos e muito idosos. Métodos: Em coorte de hipertensos foram realizados ECGs e EcoDopplercardiogramas (ECO), e separados em três grupos etários: <60 anos, Grupo I; 60-79 anos Grupo II; e ≥80 anos, Grupo III. Os critérios eletrocardiográficos mais utilizados foram aplicados para o diagnóstico da HVE: Perúgia; Peguero-Lo Presti; Gubner-Ungerleider; Narita; (Rm+Sm) x duração; Cornell voltagem; Cornell voltagem duração; Sokolow-Lyon voltagem; R de aVL ≥11 mm; RaVL duração. Na avaliação do desempenho desses critérios, além da sensibilidade (Sen) e especificidade (Esp), foram analisadas as "Odds Ratios diagnóstico" (DOR). Consideramos p-valor <0,05 para as análises, com testes bi-caudais. Resultados: Em 2.458 pacientes, a HVE estava presente pelo ECO em 781 (31,7%). Nos Grupos I e II, os melhores desempenhos foram para os critérios de Narita, Perúgia, (Rm+Sm) x duração, sem diferenças estatísticas entre eles. No Grupo III (muito idosos) os critérios de Perúgia e (Rm+Sm) x duração tiveram os melhores desempenhos: Perúgia [44,7/89,3; (Sen/Esp)] e (Rm+Sm) duração [39,4%/91,3%; (Sen/Esp), p<0,05)], com os melhores resultados de DOR:6,8. Isto sugere que nessa população de muito idosos esses critérios têm maior poder discriminatório para separar pacientes com HVE. Conclusão: Nos hipertensos muito idosos os critérios eletrocardiográficos de Perúgia e (Rm+Sm) x duração apresentaram os melhores desempenhos diagnósticos para HVE.

Abstract Background: Left ventricular hypertrophy (LVH) is an important cardiovascular risk factor, regardless of arterial hypertension. Despite the evolution of imaging tests, the electrocardiogram (ECG) is still the most used in the initial evaluation, however, with low sensitivity. Objective: To evaluate the performance of the main electrocardiographic criteria for LVH in elderly and very elderly hypertensive individuals. Methods: In a cohort of hypertensive patients, ECGs and doppler echocardiographies (ECHO) were performed and separated into three age groups: <60 years, Group I; 60-79 years Group II; and ≥80 years, Group III. The most used electrocardiographic criteria were applied for the diagnosis of LVH: Perugia; Pegaro-Lo Presti; Gubner-Ungerleider; Narita; (Rm+Sm) x duration; Cornell voltage; Cornell voltage duration; Sokolow-Lyon voltage; R of aVL ≥11 mm; RaVL duration. In evaluating the performance of these criteria, in addition to sensitivity (Sen) and specificity (Esp), the "Diagnostic Odds Ratios" (DOR) were analyzed. We considered p-value <0.05 for the analyses, with two-tailed tests. Results: In 2,458 patients, LVH was present by ECHO in 781 (31.7%). In Groups I and II, the best performances were for the criteria of Narita, Perugia, (Rm+Sm) x duration, with no statistical differences between them. In Group III (very elderly) the Perugia criteria and (Rm+Sm) x duration had the best performances: Perugia [44,7/89.3; (Sen/Esp)] and (Rm+Sm) duration [39.4%/91.3%; (Sen/Esp), p<0.05)], with the best PAIN results:6.8. This suggests that in this very elderly population, these criteria have greater discriminatory power to separate patients with LVH. Conclusion: In very elderly hypertensive patients, the Perugia electrocardiographic criteria and (Rm+Sm) x duration showed the best diagnostic performance for LVH.

Main differences between two highly effective lipid-lowering therapies in subclasses of lipoproteins in patients with acute myocardial infarction.

BACKGROUND: Large observational studies have shown that small, dense LDL subfractions are related to atherosclerotic cardiovascular disease. This study assessed the effects of two highly effective lipid-lowering therapies in the atherogenic subclasses of lipoproteins in subjects with ST-segment elevation myocardial infarction (STEMI). METHODS: Patients of both sexes admitted with their first myocardial infarction and submitted to pharmacoinvasive strategy (N = 101) were included and randomized using a central computerized system to receive a daily dose of simvastatin 40 mg plus ezetimibe 10 mg or rosuvastatin 20 mg for 30 days. Intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) subfractions were analysed by polyacrylamide gel electrophoresis (Lipoprint System) on the first (D1) and 30th days (D30) of lipid-lowering therapy. Changes in LDL and IDL subfractions between D1 and D30 were compared between the lipid-lowering therapies (Mann-Whitney U test). RESULTS: The classic lipid profile was similar in both therapy arms at D1 and D30. At D30, the achievement of lipid goals was comparable between lipid-lowering therapies. Cholesterol content in atherogenic subclasses of LDL (p = 0.043) and IDL (p = 0.047) decreased more efficiently with simvastatin plus ezetimibe than with rosuvastatin. CONCLUSIONS: Lipid-lowering therapy with simvastatin plus ezetimibe was associated with a better pattern of lipoprotein subfractions than rosuvastatin monotherapy. This finding was noted despite similar effects in the classic lipid profile and may contribute to residual cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02428374, registered on 28/09/2014.