Diagnostic Performance of Combined Noninvasive Coronary Angiography and Myocardial Perfusion Imaging Using 320-MDCT: The CT Angiography and Perfusion Methods of the CORE320 Multicenter Multinational Diagnostic Study

OBJECTIVE. Coronary MDCT angiography has been shown to be an accurate noninvasive tool for the diagnosis of obstructive coronary artery disease (CAD). Its sensitivity and negative predictive value for diagnosing percentage of stenosis are unsurpassed compared with those of other noninvasive testing methods. However, in its current form, it provides no information regarding the physiologic impact of CAD and is a poor predictor of myocardial ischemia. CORE320 is a multicenter multinational diagnostic study with the primary objective to evaluate the diagnostic accuracy of 320-MDCT for detecting coronary artery luminal stenosis and corresponding myocardial perfusion deficits in patients with suspected CAD compared with the reference standard of conventional coronary angiography and SPECT myocardial perfusion imaging. CONCLUSION. We aim to describe the CT acquisition, reconstruction, and analysis methods of the CORE320 study.

Penetration of cefuroxime in subcutaneous tissue during coronary artery bypass grafting surgery

A sensitive and rapid HPLC assay for determining cefuroxime penetration in the subcutaneous tissue near to surgical incision of patients submitted to coronary artery bypass grafting (CABC) with or without cardiopulmonary bypass (CPB) was performed. Blood and subcutaneous tissue samples were collected from 14 patients. in four periods during surgery. The analytical method presented linearity from 0.5 to 100 mu g/g. LOQ = 0.50 mu g/g, LOD = 0.25 mu g/g. intra- and interday precision (%CV) ranged from 4.9 to 8.9% and 6.4 to 9.9%, respectively, and intra-and interday accuracy expressed as % of the nominal concentration ranged from 87.1 to 104.6% and 94.8 to 103.8%, respectively (mean of three concentrations). Relative recovery was 98.4%. Tissue/plasma ratios obtained for CPB and non-CPB were, respectively: 14.6% vs 19.0% (0.6 h); 15.7% vs 15.7% (2.1 h); 22.5% vs 19.9% (3.6 h); 15.7% vs 18.8% (4.5 h). Data obtained indicate that tissue/plasma ratio remains unchanged in CPB and non-CPB patients during all period of surgery and the CPB does not affect the penetration of cefuroxime in tissues close to the surgical wound. (C) 2009 Elsevier B.V. All rights reserved.

The Bypass Angioplasty Revascularization Investigation 2 Diabetes Randomized Trial of Different Treatment Strategies in Type 2 Diabetes Mellitus With Stable Ischemic Heart Disease Impact of Treatment Strategy on Cardiac Mortality and Myocardial Infarction

Background-The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial in 2368 patients with stable ischemic heart disease assigned before randomization to percutaneous coronary intervention or coronary artery bypass grafting strata reported similar 5-year all-cause mortality rates with insulin sensitization versus insulin provision therapy and with a strategy of prompt initial coronary revascularization and intensive medical therapy or intensive medical therapy alone with revascularization reserved for clinical indication(s). In this report, we examine the predefined secondary end points of cardiac death and myocardial infarction (MI). Methods and Results-Outcome data were analyzed by intention to treat; the Kaplan-Meier method was used to assess 5-year event rates. Nominal P values are presented. During an average 5.3-year follow-up, there were 316 deaths (43% were attributed to cardiac causes) and 279 first MI events. Five-year cardiac mortality did not differ between revascularization plus intensive medical therapy (5.9%) and intensive medical therapy alone groups (5.7%; P = 0.38) or between insulin sensitization (5.7%) and insulin provision therapy (6%; P = 0.76). In the coronary artery bypass grafting stratum (n = 763), MI events were significantly less frequent in revascularization plus intensive medical therapy versus intensive medical therapy alone groups (10.0% versus 17.6%; P = 0.003), and the composite end points of all-cause death or MI (21.1% versus 29.2%; P = 0.010) and cardiac death or MI (P = 0.03) were also less frequent. Reduction in MI (P = 0.001) and cardiac death/MI (P = 0.002) was significant only in the insulin sensitization group. Conclusions-In many patients with type 2 diabetes mellitus and stable ischemic coronary disease in whom angina symptoms are controlled, similar to those enrolled in the percutaneous coronary intervention stratum, intensive medical therapy alone should be the first-line strategy. In patients with more extensive coronary disease, similar to those enrolled in the coronary artery bypass grafting stratum, prompt coronary artery bypass grafting, in the absence of contraindications, intensive medical therapy, and an insulin sensitization strategy appears to be a preferred therapeutic strategy to reduce the incidence of MI. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305. (Circulation. 2009;120:2529-2540.)

Classification System of Raman Spectra using Cluster Analysis to Diagnose Coronary Artery Lesions

The traditional methods employed to detect atherosclerotic lesions allow for the identification of lesions; however, they do not provide specific characterization of the lesion`s biochemistry. Currently, Raman spectroscopy techniques are widely used as a characterization method for unknown substances, which makes this technique very important for detecting atherosclerotic lesions. The spectral interpretation is based on the analysis of frequency peaks present in the signal; however, spectra obtained from the same substance can show peaks slightly different and these differences make difficult the creation of an automatic method for spectral signal analysis. This paper presents a signal analysis method based on a clustering technique that allows for the classification of spectra as well as the inference of a diagnosis about the arterial wall condition. The objective is to develop a computational tool that is able to create clusters of spectra according to the arterial wall state and, after data collection, to allow for the classification of a specific spectrum into its correct cluster.

Matrix metalloproteinase-9 genotypes and haplotypes are associated with multiple sclerosis and with the degree of disability of the disease

Multiple sclerosis (MS) is an autoimmune disease causing severe neurological disability. This study was carried out in order to determine whether the MMP-9 C(-1562)T and (CA)(13-25) polymorphisms are associated with MS. A total of 165 patients (92 whites/73 mulattos) and 191 controls (96 whites/95 mulattos) were enrolled in the study. While no difference in C(-1562)T polymorphism was observed between MS and healthy subjects, (CA)(n) genotypes and alleles were associated with MS. Moreover, the haplotypes are not associated with MS but seem to be relevant to the clinical status of MS. Thus the (CA)(n) polymorphism may contribute to MS susceptibility, but C(-1562)T and (CA)(n) haplotypes may modulate disease severity. (c) 2009 Elsevier B.V. All rights reserved.

Diabetes and Vascular Disease: Basic Concepts of Nitric Oxide Physiology, Endothelial Dysfunction, Oxidative Stress and Therapeutic Possibilities

The vascular manifestations associated with diabetes mellitus (DM) result from the dysfunction of several vascular physiology components mainly involving the endothelium, vascular smooth muscle and platelets. It is also known that hyperglycemia-induced oxidative stress plays a role in the development of this dysfunction. This review considers the basic physiology of the endothelium, especially related to the synthesis and function of nitric oxide. We also discuss the pathophysiology of vascular disease associated with DM. This includes the role of hyperglycemia in the induction of oxidative stress and the role of advanced glycation end-products. We also consider therapeutic strategies.

Right coronary artery fistula to the coronary sinus and right atrium associated with giant right coronary enlargement detected by transthoracic echocardiography

We present the case of a 54-year-old female with a previous history of lung fibrosis secondary to methotrexate used for rheumatoid arthritis who was referred to cardiology evaluation due to precordial pain. Echocardiography showed biatrial enlargement with an enlarged coronary sinus and tubular image posterior to the heart. On the coronary angiogram, the right coronary artery was enlarged, and a distal fistula was identified. The patient underwent a contrast enhanced cardiac computed tomography which demonstrated an aneurysmatic right coronary artery with a distal fistula to the right atrium and coronary sinus. As the chest pain did not recur and there was a high risk of the intervention to correct coronary fistula, the patient remained on conservative treatment.

Cardiovascular Disease Parameters in Periodontitis

Background: Recently, there has been an increasing in the impact of oral health on atherosclerosis and subsequent cardiovascular disease. The aim of this study is to investigate the association between chronic periodontitis and cardiovascular risk markers. Methods: Forty patients with periodontitis and 40 healthy gender-, body mass index-, and age-matched individuals were compared by measuring total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, levels of cytokines, antibodies against oxidized low-density lipoprotein, thiobarbituric acid reactive substances, total and differential white blood cell counts, and the non-linear index of refraction. Results: The levels of triglycerides and high-density lipoprotein in periodontitis patients were significantly higher and lower, respectively (P=0.002 and P=0.0126), compared to controls. Total cholesterol, low-density lipoprotein, and lipid peroxide levels were the same in both groups (P = 0.2943, P = 0.1284, and P = 0.067, respectively). Interleukin (IL)-6 and -8, antibodies against oxidized low-density lipoprotein, and leukocyte and neutrophil counts were significantly higher in periodontitis patients (P<0.05). The value of the non-linear index of refraction of low-density lipoprotein solutions was higher in the controls (P = 0.015) compared to individuals with periodontitis. Conclusion: Our results confirmed and further strengthened the suggested association between coronary artery disease and periodontitis. J Periodontol 2009;80:378-388.

Anticorpos contra LDL-ox e síndrome coronariana aguda

FUNDAMENTO: A oxidação da lipoproteína de baixa densidade (LDL-ox) induz à formação de epítopos imunogênicos na molécula. A presença de autoanticorpos contra a LDL-ox tem sido demonstrada no soro de pacientes com doença arterial coronariana (DAC). Contudo, o papel desses autoanticorpos na fisiopatologia das síndromes coronarianas agudas (SCA) e o seu significado clínico permanecem indefinidos. OBJETIVO: Avaliar a associação entre autoanticorpos contra a LDL-ox e SCA. MÉTODOS: Os títulos de imunoglobulina G autoanticorpos contra a LDL-ox por cobre (antiLDL-ox) e contra o peptídeo sintético D derivado da apolipoproteína B (antipeptD) foram determinados por ensaio imunoenzimático (ELISA) em 90 pacientes, nas primeiras 12h de SCA (casos) e em 90 pacientes com DAC crônica (controles). RESULTADOS: Os resultados mostraram que os títulos de antiLDL-ox foram significativamente mais elevados (p = 0,017) nos casos (0,40 ± 0,22), do que nos controles (0,33 ± 0,23). Por outro lado, os títulos de antipeptD foram significativamente menores (p < 0,01) nos casos (0,28 ± 0,23) do que nos controles (0,45 ± 0,30). A diferença dos títulos de ambos anticorpos entre os dois grupos estudados foi independente de idade, sexo, hipertensão arterial, diabete melito, dislipidemia, índice de massa corporal, tabagismo, perfil lipídico, uso de estatinas e história familiar de DAC. CONCLUSÃO: Os resultados mostraram que os títulos de antiLDL-ox foram significativamente mais elevados nos pacientes com síndrome coronariana aguda quando comparados aos pacientes com doença arterial coronariana e podem estar associados à instabilidade da placa aterosclerótica.

Impacto da proteína-C reativa no risco cardiovascular de adolescentes

FUNDAMENTO: Vários estudos sugerem que a proteína-C reativa (PCR) se correlaciona com doença arterial coronariana em adultos. Entretanto, essa associação ainda é pouco explorada em adolescentes. OBJETIVO: Avaliar a associação entre a PCR e os fatores de risco cardiovascular em adolescentes obesos. MÉTODOS: Oitenta e quatro adolescentes (12,6 ± 1,3 anos), ambos os sexos, foram distribuídos nos grupos Eutrófico (n = 28), Sobrepeso (n = 28) e Obeso (n = 28), segundo o índice de massa corpórea (IMC). A concentração de PCR (ELISA ultrassensível), o perfil lipídico e o conteúdo de anticorpos anti-LDLox (ELISA) foram determinados após jejum de 12h. RESULTADOS: Os grupos foram semelhantes quanto a idade (p = 0,13) e sexo (p = 0,83). Colesterol total, HDL-C, CT/HDL-C e LDL-C/HDL-C apresentaram diferenças significativas entre os grupos Eutrófico e Obeso. Não houve variação significativa no conteúdo de anticorpos anti-LDLox. Os valores de PCR foram diferentes entre os três grupos (p < 0,01). PCR apresentou associação significativa com IMC (β = 2,533), CB (β = 2,645) e CC (β = 2,945), CT (β = 0,006), LDL-C (β = 0,006) e anticorpos anti-LDLox (β = 0,383) e negativa entre HDL-C (β = -0,017). CONCLUSÃO: Os resultados indicam que a PCR se associa significativamente com marcadores de risco cardiovascular em adolescentes.

Tecnologias para investigação da DAC: relação entre publicações científicas e utilização clínica

FUNDAMENTO: Apesar de algumas evidências sugerirem associação entre a exposição de uma tecnologia na literatura científica e sua difusão na prática clínica, poucos estudos avaliaram essa associação. OBJETIVO: O objetivo deste estudo é analisar se o padrão de publicação científica sobre duas tecnologias competitivas utilizadas na avaliação da doença arterial coronária (DAC) reflete o que ocorre na prática clínica. MÉTODOS: Avaliou-se o número de artigos científicos publicados anualmente na literatura médica (interesse científico global na tecnologia) sobre duas tecnologias utilizadas na avaliação da doença arterial coronária: tomografia computadorizada por feixe de elétrons e tomografia computadorizada com múltiplos detectores. Foi também analisado o número de países que publicam anualmente artigos científicos sobre essas tecnologias (interesse geográfico na tecnologia). RESULTADOS: A tomografia computadorizada por feixe de elétrons (electron beam computed tomography - EBCT) apresentou ápice de "interesse científico global" em 2001, com 127 artigos publicados. Após esse ápice, o "interesse científico global" diminuiu cerca de 50% em 2008. Em oposição, o "interesse científico global" pela tomografia computadorizada com múltiplos detectores (multidetector computed tomography - MDCT) aumentou progressivamente até 2007, com 454 artigos publicados nesse ano. O "interesse científico geográfico" pela EBCT teve ápice em 2002, com 14 países publicando sobre essa tecnologia. Após esse ápice, "o interesse científico geográfico" declinou em quase 25% até 2008, com 11 países publicando artigos sobre essa tecnologia. Em oposição, o "interesse científico geográfico" pela MDCT aumentou progressivamente até 2008, com 37 países publicando artigos sobre ela. CONCLUSÃO: A literatura científica médica é compatível com a substituição da EBCT pela MDCT na avaliação da DAC.

Impacto da Proteína-C reativa no risco cardiovascular de adolescentes

Vários estudos sugerem que a proteína-C reativa (PCR) se correlaciona com doença arterial coronariana em adultos. Entretanto, essa associação ainda é pouco explorada em adolescentes. Avaliar a associação entre a PCR e os fatores de risco cardiovascular em adolescentes obesos. Oitenta e quatro adolescentes (12,6 ± 1,3 anos), ambos os sexos, foram distribuídos nos grupos Eutrófico (n = 28), Sobrepeso (n = 28) e Obeso (n = 28), segundo o índice de massa corpórea (IMC). A concentração de PCR (ELISA ultrassensível), o perfil lipídico e o conteúdo de anticorpos anti-LDLox (ELISA) foram determinados após jejum de 12h. Os grupos foram semelhantes quanto a idade (p = 0,13) e sexo (p = 0,83). Colesterol total, HDL-C, CT/HDL-C e LDL-C/HDL-C apresentaram diferenças significativas entre os grupos Eutrófico e Obeso. Não houve variação significativa no conteúdo de anticorpos anti-LDLox. Os valores de PCR foram diferentes entre os três grupos (p < 0,01). PCR apresentou associação significativa com IMC (β = 2,533), CB (β = 2,645) e CC (β = 2,945), CT (β = 0,006), LDL-C (β = 0,006) e anticorpos anti-LDLox (β = 0,383) e negativa entre HDL-C (β = -0,017). Os resultados indicam que a PCR se associa significativamente com marcadores de risco cardiovascular em adolescentes

Lipid Metabolism in Subclinical Hypothyroidism: Plasma Kinetics of Triglyceride-Rich Lipoproteins and Lipid Transfers to High-Density Lipoprotein Before and After Levothyroxine Treatment

Background: Subclinical hypothyroidism (SCH) has been associated with atherosclerosis, but the abnormalities in plasma lipids that can contribute to atherogenesis are not prominent. The aim of this study was to test the hypothesis that patients with normocholesterolemic, normotriglyceridemic SCH display abnormalities in plasma lipid metabolism not detected in routine laboratory tests including abnormalities in the intravascular metabolism of triglyceride-rich lipoproteins, lipid transfers to high-density lipoprotein (HDL), and paraoxonase 1 activity. The impact of levothyroxine (LT4) treatment and euthyroidism in these parameters was also tested. Methods: The study included 12 SCH women and 10 matched controls. Plasma kinetics of an artificial triglyceride-rich emulsion labeled with radioactive triglycerides and cholesteryl esters as well as in vitro transfer of four lipids from an artificial donor nanoemulsion to HDL were determined at baseline in both groups and after 4 months of euthyroidism in the SCH group. Results: Fractional clearance rates of triglycerides (SCH 0.035 +/- 0.016 min(-1), controls 0.029 +/- 0.013 min(-1), p=0.336) and cholesteryl esters (SCH 0.009 +/- 0.007 min(-1), controls 0.009 +/- 0.009 min(-1), p=0.906) were equal in SCH and controls and were unchanged by LT4 treatment and euthyroidism in patients with SCH, suggesting that lipolysis and remnant removal of triglyceride-rich lipoproteins were normal. Transfer of triglycerides to HDL (SCH 3.6 +/- 0.48%, controls 4.7 +/- 0.63%, p=0.001) and phospholipids (SCH 16.2 +/- 3.58%, controls 21.2 +/- 3.32%, p=0.004) was reduced when compared with controls. After LT4 treatment, transfers increased and achieved normal values. Transfer of free and esterified cholesterol to HDL, HDL particle size, and paraoxonase 1 activity were similar to controls and were unchanged by treatment. Conclusions: Although intravascular metabolism of triglyceride-rich lipoproteins was normal, patients with SCH showed abnormalities in HDL metabolism that were reversed by LT4 treatment and achievement of euthyroidism.

The C242T polymorphism of the p22-phox gene (CYBA) is associated with higher left ventricular mass in Brazilian hypertensive patients

Background: Reactive oxygen species have been implicated in the physiopathogenesis of hypertensive end-organ damage. This study investigated the impact of the C242T polymorphism of the p22-phox gene (CYBA) on left ventricular structure in Brazilian hypertensive subjects. Methods: We cross-sectionally evaluated 561 patients from 2 independent centers [Campinas (n = 441) and Vitoria (n = 120)] by clinical history, physical examination, anthropometry, analysis of metabolic and echocardiography parameters as well as p22-phox C242T polymorphism genotyping. In addition, NADPH-oxidase activity was quantified in peripheral mononuclear cells from a subgroup of Campinas sample. Results: Genotype frequencies in both samples were consistent with the Hardy-Weinberg equilibrium. Subjects with the T allele presented higher left ventricular mass/height(2.7) than those carrying the CC genotype in Campinas (76.8 +/- 1.6 vs 70.9 +/- 1.4 g/m(2.7); p = 0.009), and in Vitoria (45.6 +/- 1.9 vs 39.9 +/- 1.4 g/m(2.7); p = 0.023) samples. These results were confirmed by stepwise regression analyses adjusted for age, gender, blood pressure, metabolic variables and use of anti-hypertensive medications. In addition, increased NADPH-oxidase activity was detected in peripheral mononuclear cells from T allele carriers compared with CC genotype carriers (p = 0.03). Conclusions: The T allele of the p22-phox C242T polymorphism is associated with higher left ventricular mass/height(2.7) and increased NADPH-oxidase activity in Brazilian hypertensive patients. These data suggest that genetic variation within NADPH-oxidase components may modulate left ventricular remodeling in subjects with systemic hypertension.

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and high plasma homocysteine in chronic hepatitis C (CHC) infected patients from the Northeast of Brazil

Background/Aim: Hyperhomocysteinemia due to Methylenetetrahydrofolate Reductase (MTHFR) gene, in particular the C677T (Ala222Val) polymorphism were recently associated to steatosis and fibrosis. We analyzed the frequency of MTHFR gene in a cross-sectional study of patients affected by Chronic Hepatitis C (CHC) from Northeast of Brazil. Method: One hundred seven-four untreated patients with CHC were genotyped for the C677T MTHFR. Genomic DNA was extracted from peripheral blood cells and the C677T MTHFR polymorphism was identified by PCR-RFLP. The homocysteine (Hcy) levels were determined by chemiluminescence method. All patients were negative for markers of Wilson's disease, hemochromatosis and autoimmune diseases and have current and past daily alcohol intake less than 100 g/week. Results: Among subjects infected with CHC genotype non-1 the frequency of MTHFR genotypes TT was 9.8% versus 4.4% genotype 1 (p = 0.01). Nevertheless, association was found between the MTHFR genotype TT x CT/CC polymorphism and the degree of steatosis and fibrosis in both hepatitis C genotype (p < 0.05). A significant difference was found on plasma Hcy levels in patients with steatosis regardless of HCV genotype (p = 0.03). Conclusion: Our results indicate that plasma Hcy levels is highly prevalent in subjects with chronic hepatits C with steatosis regardless of HCV genotype and vitamin deficiency. The presence of genotype TT of MTHFR C677T polymorphism was more common in CHC genotype non-1 infected patient regardless of histopathological classification and genotype TT+CT frequencies were significant in the presence of fibrosis grade 1+2 and of steatosis in CHC infected patients from the northeast of Brazil regardless of HCV genotype. The genetic susceptibility of MTHFR C677T polymorphism should be confirmed in a large population.