RESUMO
The mechanism for dynamic left ventricular outflow tract obstruction (LVOTO) after acute coronary syndromes (ACS) is thought to be apical infarction with compensatory hyperkinesia of the residual normally perfused basal segments of the myocardium. However, herein, we report a patient with ACS and dynamic LVOTO (peak gradient of 250 mm Hg at rest) that could not be secondary to apical akinesia. We propose a potential alternative mechanism leading to dynamic LVOTO in ACS, namely, the interplay between sigmoid septum, basal hyperkinesis, and outflow tract narrowing induced by afterload reduction due to acute myocardial ischemia itself.
Assuntos
Síndrome Coronariana Aguda , Cardiopatias Congênitas , Obstrução do Fluxo Ventricular Externo , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/diagnóstico por imagem , Humanos , Hipercinese , Obstrução do Fluxo Ventricular Externo/complicações , Obstrução do Fluxo Ventricular Externo/diagnóstico por imagemRESUMO
BACKGROUND: Adverse effects of dietary intake of trans-fatty acids (TFA) on the incidence of coronary artery disease (CAD) are well recognized in Western countries. The risk of TFA, however, has not been well clarified in Japan. We investigated the association of serum TFA concentration with serum lipid profile, coronary risk factors, and prevalence of CAD. METHODSâANDâRESULTS: A total of 902 patients, who were hospitalized at Kobe University Hospital from July 2008 to March 2012 and gave written informed consent, were enrolled in this study. Among them, 463 patients had CAD, and 318 patients had metabolic syndrome (MetS). Serum TFA, elaidic acid (trans-9-C18:1) and linolelaidic acid (trans-9, 12-C18:2), were measured on gas chromatography/mass spectrometry. Serum TFA level had a positive correlation with body mass index, waist circumference, low-density lipoprotein cholesterol, triglycerides, and apolipoprotein B48, and an inverse correlation with age and high-density lipoprotein cholesterol. Fasting serum TFA, by age quartile in the young generation with CAD and/or MetS, was higher than that in patients without CAD and/or MetS. On multivariate logistic regression, TFA was identified as a CAD risk after adjustment for classical risk factors. CONCLUSIONS: Serum TFA concentration was elevated in young patients with CAD and/or MetS. Diet-derived TFA may cause a serious health problem, particularly in the young generation in Japan.
Assuntos
Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/induzido quimicamente , Doença da Artéria Coronariana/epidemiologia , Gorduras na Dieta/efeitos adversos , Ácidos Graxos trans/sangue , Fatores Etários , Idoso , HDL-Colesterol/sangue , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Ácido Oleico/sangue , Ácidos Oleicos , PrevalênciaRESUMO
BACKGROUND: Despite the establishment of guidelines for the secondary prevention of coronary artery diseases, many patients still develop restenosis after stent implantation. Therefore, novel and noninvasive serum biomarkers that can identify restenosis-prone conditions are necessary to improve the follow-up and treatment of patients with coronary artery disease. Of late, considerable attention is being focused on metabolomics, which is the comprehensive analysis of low-molecular-weight metabolites. This study investigated the use of serum metabolomics in the identification of biomarkers of restenosis. METHODS AND RESULTS: Gas chromatography/mass spectrometry was used to obtain the serum metabolomic profiles of male patients hospitalized for follow-up coronary angiography 6 months after stent implantation; 23 patients presented with major restenotic lesions (≥75% obstruction), 47 with minor restenotic lesions (≤50% obstruction), and 16 with de novo atherosclerotic lesions. Of 83 serum metabolites analyzed, molecules - isobutylamine, sarcosine, homoserine, ribulose, taurine, glutamine, glucose, and tryptophan - in the major restenosis group were significantly different from those in the minor restenosis group. Differences in correlation among these metabolites imply possible alternations in the activated metabolic pathways. CONCLUSIONS: This study provides the first line of evidence for the use of serum metabolic profiling in the identification of specific biomarkers of stent restenosis.
Assuntos
Reestenose Coronária/sangue , Metabolômica/métodos , Stents , Idoso , Biomarcadores/sangue , Angiografia Coronária , Reestenose Coronária/diagnóstico por imagem , Seguimentos , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We herein report the total course and autopsy findings of a woman who complained of chest discomfort and had plasma B-type natriuretic peptide 43 pg/mL and left ventricular outflow tract obstruction (with a resting pressure gradient of 181 mmHg) due to sigmoid septum at 73 years of age. Betaxolol and verapamil decreased her pressure gradient to 14 mmHg, but the pressure gradient (101 mmHg) again worsened. The betaxolol dose was increased and cibenzoline was added, resulting in a pressure gradient ≤21 mmHg. An autopsy was performed after death from a urinary tract infection at 80 years of age. The absence of any disarray of cardiac myocytes was confirmed.
Assuntos
Cardiomiopatia Hipertrófica/fisiopatologia , Colo Sigmoide/fisiopatologia , Cardiopatias Congênitas/fisiopatologia , Hipertrofia/fisiopatologia , Obstrução do Fluxo Ventricular Externo/fisiopatologia , Idoso , Autopsia , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Causas de Morte , Colo Sigmoide/diagnóstico por imagem , Evolução Fatal , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Humanos , Hipertrofia/diagnóstico por imagem , Obstrução do Fluxo Ventricular Externo/diagnóstico por imagemRESUMO
BACKGROUND: Epidemiological studies have demonstrated that trans fatty acids (TFAs) are a risk for coronary artery disease. However, the precise mechanism underlying the proatherogenic effect of TFA has not been completely elucidated. To obtain better understanding of the impact of TFA on vascular diseases, this study investigated the effect of TFA on oxidative stress using a mouse model of atherosclerosis. METHODS: Low-density lipoprotein (LDL) receptor knockout mice were fed with diet containing 0.5% cholesterol (control), 0.5% cholesterol+5% elaidic acids (Trans group), and 0.5% cholesterol+5% oleic acids (Cis group) for 8 weeks. Atherosclerotic lesion and oxidative stress in aortic wall were evaluated. In vitro experiments using smooth muscle cells were performed to corroborate in vivo findings. RESULTS: The atherosclerotic lesion area was significantly larger in Trans group than that in control or Cis group. Lipoprotein fractionation was similar among groups, while plasma oxidized LDL level and superoxide production in the vessel wall were markedly increased in Trans group. Elaidic acids were accumulated in a variety of tissues including liver and adipose tissue, which was associated with the high level of inflammatory cytokines in these tissues and plasma. Aortic wall from Trans group showed augmented expression of reactive oxygen species and NAPDH oxidase (p22phox) in smooth muscle cells. In vitro experiments confirmed that elaidic acids upregulated expression of NADPH oxidase and inflammatory cytokines in cultured smooth muscle cells. CONCLUSION: Excessive intake of TFA contributes to the progression of atherosclerosis by evoking inflammation and oxidative stress in mice.
Assuntos
Aterosclerose/etiologia , Hiperlipidemias/complicações , Ácidos Graxos trans/efeitos adversos , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/patologia , Aterosclerose/sangue , Aterosclerose/patologia , Modelos Animais de Doenças , Hiperlipidemias/sangue , Hiperlipidemias/patologia , Inflamação/induzido quimicamente , Lipoproteínas LDL/sangue , Masculino , Camundongos Knockout , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Receptores de LDL/genéticaRESUMO
OBJECTIVE: Granular leukocyte-derived myeloperoxidase (MPO) promotes oxidation of lipoproteins, while paraoxonase 1 (PON1) has antioxidant properties for high-density lipoprotein (HDL). We evaluated their effects on coronary risk stratification and function of lipoproteins. METHODS AND RESULTS: A total 158 patients who had previously undergone percutaneous coronary intervention and who had been hospitalized for coronary re-angiography were enrolled. Coronary lesions (restenosis or de novo lesion) were observed in 84 patients but not associated with conventional lipid profile. In contrast, serum MPO levels and PON1 activities were significantly associated with the prevalence of coronary lesions. The high MPO/PON1 ratio, when cutoff values were set at 1.59, was independently correlated with restenosis (odds ratio 6.4, 95% CI 2.2-19.3, P = 0.001) and de novo lesions (odds ratio 3.5, 95% CI 1.3-9.4, P = 0.014). We isolated HDL from patients with high or low MPO/PON1 ratio, and compared anti-inflammatory properties of HDL. Human umbilical vein endothelial cells were stimulated with inflammatory cytokine, and the expression of vascular cell adhesion molecule-1 (VCAM-1) was evaluated. HDL isolated from patients with low serum MPO/PON1 ratio inhibited VCAM-1 expression significantly greater than that with high MPO/PON1 ratio. We also demonstrated that the cholesterol efflux capacity of apolipoprotein B-depleted serum from patients with high MPO/PON1 ratio was significantly decreased than that with low MPO/PON1 ratio. CONCLUSIONS: MPO/PON1 ratio could be a useful marker for secondary prevention of coronary artery disease through modulation of HDL function.
Assuntos
Arildialquilfosfatase/sangue , Doença da Artéria Coronariana/enzimologia , Lipoproteínas HDL/sangue , Peroxidase/sangue , Idoso , Biomarcadores/sangue , Células Cultivadas , Distribuição de Qui-Quadrado , Colesterol/metabolismo , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Feminino , Células Endoteliais da Veia Umbilical Humana/enzimologia , Humanos , Mediadores da Inflamação/metabolismo , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Razão de Chances , Intervenção Coronária Percutânea , Valor Preditivo dos Testes , Recidiva , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
BACKGROUND: To identify new therapeutic targets for coronary artery disease (CAD), we investigated whether fasting serum concentration of apolipoprotein (apo) B48 could be a marker for CAD. METHODS: Patients with CAD were divided into those with new-onset CAD [i.e., those receiving percutaneous coronary intervention (PCI) for the first time] and those with chronic CAD (i.e., those receiving follow-up coronary angiography). Fasting serum biochemical analyses were performed on admission and 6 months after the PCI. RESULTS: On admission, serum LDL-C concentrations in patients with chronic CAD (n=138), presumably receiving statin treatment, were lower than in patients with new-onset CAD (n=50, p<0.02) or without CAD (n=71, p<0.001). Nevertheless, apoB48 was higher in CAD patients than in those without CAD (p<0.001). After adjusting for classic cardiovascular risk factors, multivariate logistic regression analyses showed apoB48 to be an independent predictor of coronary risk in new-onset or chronic CAD, irrespective of the LDL-C levels. Moreover, apoB48 was markedly increased during the follow-up period in CAD patients having new lesion progression after the prior PCI. CONCLUSION: Fasting serum apoB48 concentration could be a marker of new onset as well as chronic CAD, and predict new lesion progression in secondary prevention.