Effects of acetylsalicylic acid alone or with omega-3 in patients with chronic coronary artery disease

INTRODUCTION AND OBJECTIVES: Antiplatelet agents such as acetylsalicylic acid (ASA) play a prominent role in preventing atherothrombosis. However, low-responsive patients who will not benefit from an increased dosage of this drug, which can cause bleeding and gastrointestinal irritation, need to be identified. Drugs such as omega-3 fatty acids, which enhance the vasodilating condition and diminish platelet aggregation, can potentiate the anti-aggregating effects of ASA, avoiding its side effects. Thus, we assessed the alternative use of 200mg/day of ASA and 100mg/day of this drug combined with 1g of omega-3 in 152 patients with chronic coronary artery disease. METHODS: Our analysis included platelet function (ASPItest), TBX2 concentrations (ELISA), and SNPs polymorphisms in the rs3842787 and rs3842798 regions of the PTGS1 gene of the COX-1 enzyme and the rs5918 region of the ITGB3 gene of the fibrinogen's receptor subunit glycoprotein IIIa. RESULTS: ASPItest detected 38 non-responders. The reduction of ASPItest values was more significant in this group than in responders and fell to levels of responders in non-responders of the 200mg/day treatment. A rare allele of rs3842787 is associated with a worse ASPItest response, and the rare allele of the rs5918 polymorphism with a worse response related to TBX2 concentration. Both treatments showed no statistically significant difference in hematuria or bleeding, constituting safe treatment alternatives, and omega-3 treatment reduced monocyte levels. CONCLUSIONS: Our results underscore the usefulness of pharmacogenetics for personalized treatments, avoiding gastrointestinal effects and undesirable bleeding.

Terapias anticoagulantes na doença renal crônica / Anticoagulant therapies in chronic renal disease

Os pacientes com doença renal crônica (DRC) têm tendências hemorrágicas e trombóticas e, por isso, a indicação de anticoagulantes é complexa nos indivíduos com fibrilação atrial (FA). A FA é a arritmia mais frequente na DRC, sendo o tromboembolismo e o ictus suas principais complicações. A introdução de novos anticoagulantes orais diretos (DOACs) tem se mostrado superior aos antagonistas da vitamina K, tanto na prevenção de tromboembolismos sistêmicos como no risco de sangramento. Contudo, devem ser prescritos com cautela nesse grupo de pacientes. Para os indivíduos com DRC e clearance renal entre 30 e 50 ml/min, as doses da dabigatrana e da rivaroxabana devem ser reduzidas, no caso de pacientes com elevado risco de sangramento, não havendo necessidade de reduzir as doses de apixabana e edoxabana. Em pacientes com clearance renal entre 15 e 29 ml/min o uso da dabigatrana é contraindicado, a rivaroxabana e a edoxabana não exigem ajuste terapêutico e a dose de apixabana deve ser ajustada. Nenhum dos DOACs é indicado em pacientes com clearance renal < 15 mg/min. Outro problema da terapêutica com os DOACs é o custo do medicamento, muito superior aos dos antagonistas da vitamina K, trazendo algumas implicações clínicas relevantes: suspensão terapêutica por restrições econômicas, que mesmo quando transitória, coloca o paciente em risco de eventos tromboembólicos devido à perda rápida de seus efeitos anticoagulantes e pela possibilidade de hipercoagulabilidade paradoxal. A maior parte da população é tratada em hospitais públicos e recebe os antagonistas de vitamina K. Por isso, enquanto a relação custo-efetividade dos DOACs não for esclarecida, a prevenção e o tratamento de pacientes com DRC e FA com os antagonistas de vitamina K estão consagrados e podem trazer benefícios para esse grupo de pacientes

Patients with chronic renal disease (CRD) have hemorrhagic and thrombotic tendencies, therefore the indication of anticoagulants is complex in individuals with atrial fibrillation (AF). AF is the most frequent arrhythmia in CRD, and thromboembolism and cerebral stroke are its main complications. The introduction of new oral anticoagulants (DOACs) has proven to be superior to vitamin K antagonists in preventing systemic thromboembolisms and bleeding risk. However, they should be prescribed with caution in this group of patients. For individuals with CRD and renal clearance between 30 and 50 ml/min, the doses of dabigatran and rivaroxaban should be reduced, in the case of patients with high risk of bleeding, and it is not necessary to reduce the doses of apixaban and edoxaban. In patients with renal clearance between 15 and 29 ml/min, the use of dabigatran is contraindicated, rivaroxaban and edoxaban do not require therapeutic adjustment, and the dose of apixaban should be adjusted. No DOACs is indicated in patients with renal clearance < 15 mg/min. Another problem with DOACs therapy is the cost of the medication, which is much higher than that of vitamin K antagonists, with some important clinical implications: therapeutic suspension due to economic restrictions, even if temporary, place the patient at risk of thromboembolic events due to the rapid loss of anticoagulant effects and the possibility of paradoxical hypercoagulability. Most of the population is treated in public hospitals, and receives vitamin K antagonists. Therefore, while the cost-effectiveness ratio of DOACs has not been clarified, prevention and treatment of patients with CRD and AF with vitamin K antagonists is consecrated, and can bring benefits for this group of patients

6-Month Outcomes in Patients With Implantable Cardioverter-Defibrillators Undergoing Renal Sympathetic Denervation for the Treatment of Refractory Ventricular Arrhythmias.

OBJECTIVES: This study aimed to assess 6-month outcomes in patients with implantable cardioverter-defibrillators (ICDs) undergoing renal sympathetic denervation (RSD) for refractory ventricular arrhythmias (VAs). BACKGROUND: ICDs are generally indicated for patients at high risk of malignant VAs. Sympathetic hyperactivity plays a critical role in the development, maintenance, and aggravation of VAs. METHODS: A total of 10 patients with refractory VA underwent RSD. Underlying conditions were Chagas disease (n = 6), nonischemic dilated cardiomyopathy (n = 2), and ischemic cardiomyopathy (n = 2). Information on the number of ventricular tachycardia (VT)/ventricular fibrillation (VF) episodes and device therapies (antitachycardia pacing/shocks) in the previous 6 months as well as 1 and 6 months post-treatment was obtained from ICD interrogation. RESULTS: The median number of VT/VF episodes/antitachycardia pacing/shocks 6 months before RSD was 28.5 (range 1 to 106)/20.5 (range 0 to 52)/8 (range 0 to 88), respectively, and was reduced to 1 (range 0 to 17)/0 (range 0 to 7)/0 (range 0 to 3) at 1 month and 0 (range 0 to 9)/0 (range 0 to 7)/0 (range 0 to 3) at 6 months afterward, respectively. There were no major procedure-related complications. Two patients experienced sustained VT within the first week; in both cases, no further episodes occurred during follow-up. Two patients were nonresponders: 1 with persistent idioventricular rhythm and 1 with multiple renal arteries and incomplete ablation. Three patients died during follow-up. None of the deaths was attributed to VA. CONCLUSIONS: In patients with ICDs and refractory VAs, RSD was associated with reduced arrhythmic burden with no procedure-related complications. Randomized controlled trials investigating RSD for treatment of refractory VAs in patients with increased sympathetic activity are needed.

6 Month Outcomes in Patients WithImplantable Cardioverter-DefibrillatorsUndergoing Renal SympatheticDenervation for the Treatment ofRefractory Ventricular Arrhythmias

This study aimed to assess 6-month outcomes in patients with implantable cardioverter-defibrillators(ICDs) undergoing renal sympathetic denervation (RSD) for refractory ventricular arrhythmias (VAs).BACKGROUND ICDs are generally indicated for patients at high risk of malignant VAs. Sympathetic hyperactivityplays a critical role in the development, maintenance, and aggravation of VAs.METHODS A total of 10 patients with refractory VA underwent RSD. Underlying conditions were Chagas disease (n » 6),nonischemic dilated cardiomyopathy (n » 2), and ischemic cardiomyopathy (n » 2). Information on the number ofventricular tachycardia (VT)/ventricular fibrillation (VF) episodes and device therapies (antitachycardia pacing/shocks) inthe previous 6 months as well as 1 and 6 months post-treatment was obtained from ICD interrogation.RESULTS The median number of VT/VF episodes/antitachycardia pacing/shocks 6 months before RSD was 28.5 (range1 to 106)/20.5 (range 0 to 52)/8 (range 0 to 88), respectively, and was reduced to 1 (range 0 to 17)/0 (range 0 to 7)/0 (range 0 to 3) at 1 month and 0 (range 0 to 9)/0 (range 0 to 7)/0 (range 0 to 3) at 6 months afterward, respectively.There were no major procedure-related complications. Two patients experienced sustained VT within the first week; inboth cases, no further episodes occurred during follow-up. Two patients were nonresponders: 1 with persistent idioventricularrhythm and 1 with multiple renal arteries and incomplete ablation. Three patients died during follow-up. Noneof the deaths was attributed to VA.CONCLUSIONS In patients with ICDs and refractory VAs, RSD was associated with reduced arrhythmic burden withno procedure-related complications. Randomized controlled trials investigating RSD for treatment of refractory VAs inpatients with increased sympathetic activity are needed.

Denervação Renal com Cateter Irrigado em Hipertensos Resistentes: Uma Estratégia Promissora? / Renal Denervation Using an Irrigated Catheter in Patients with Resistant Hypertension: A Promising Strategy?

Fundamento: A hipertensão arterial sistêmica constitui importante problema de saúde pública e significativa causa de mortalidade cardiovascular. A elevada prevalência e as reduzidas taxas de controle tensional despertaram o interesse por estratégias terapêuticas alternativas. A denervação simpática renal percutânea surgiu como perspectiva no tratamento de hipertensos resistentes. Objetivo: Avaliar a factibilidade e a segurança da denervação renal com cateter irrigado. Métodos: Dez hipertensos resistentes foram submetidos ao procedimento. O desfecho primário foi a segurança, avaliada por eventos adversos periprocedimento, função renal e anormalidade vascular renal aos 6 meses. Os desfechos secundários constituíram mudanças na pressão arterial (consultório e monitorização ambulatorial) e no número de anti-hipertensivos aos 6 meses. Resultados: A média de idade foi de 47,3 (± 12) anos, 90% eram mulheres. No primeiro caso, houve dissecção de artéria renal causada por trauma da bainha, fato que não se repetiu após ajuste técnico, demonstrando efeito da curva de aprendizado. Nenhum caso de trombose/infarto renal ou óbito foi reportado. Não se observou elevação dos níveis séricos de creatinina durante o seguimento. Aos 6 meses, diagnosticou-se um caso de estenose significativa de artéria renal, sem repercussão clínica. A denervação renal reduziu a pressão arterial de consultório, em média, em 14,6/6,6 mmHg (p = 0,4 tanto para pressão arterial sistólica como para a diastólica). A redução média da pressão arterial pela monitorização ambulatorial foi de 28/17,6 mmHg (p = 0,02 e p = 0,07 para pressão arterial sistólica e diastólica, ...

Background: Systemic hypertension is an important public health problem and a significant cause of cardiovascular mortality. Its high prevalence and the low rates of blood pressure control have resulted in the search for alternative therapeutic strategies. Percutaneous renal sympathetic denervation emerged as a perspective in the treatment of patients with resistant hypertension. Objective: To evaluate the feasibility and safety of renal denervation using an irrigated catheter. Methods: Ten patients with resistant hypertension underwent the procedure. The primary endpoint was safety, as assessed by periprocedural adverse events, renal function and renal vascular abnormalities at 6 months. The secondary endpoints were changes in blood pressure levels (office and ambulatory monitoring) and in the number of antihypertensive drugs at 6 months. Results: The mean age was 47.3 (± 12) years, and 90% of patients were women. In the first case, renal artery dissection occurred as a result of trauma due to the long sheath; no further cases were observed after technical adjustments, thus showing an effect of the learning curve. No cases of thrombosis/renal infarction or death were reported. Elevation of serum creatinine levels was not observed during follow-up. At 6 months, one case of significant renal artery stenosis with no clinical consequences was diagnosed. Renal denervation reduced office blood pressure levels by 14.6/6.6 mmHg, on average (p = 0.4 both for systolic and diastolic blood pressure). Blood pressure levels on ambulatory monitoring decreased by 28/17.6 mmHg (p = 0.02 and p = 0.07 for systolic and diastolic blood pressure, respectively). A mean reduction of 2.1 antihypertensive drugs was observed. Conclusion: Renal denervation is feasible and safe in the treatment of resistant systemic arterial hypertension. Larger studies are required to confirm our findings. .

Renal denervation using an irrigated catheter in patients with resistant hypertension: a promising strategy?

BACKGROUND: Systemic hypertension is an important public health problem and a significant cause of cardiovascular mortality. Its high prevalence and the low rates of blood pressure control have resulted in the search for alternative therapeutic strategies. Percutaneous renal sympathetic denervation emerged as a perspective in the treatment of patients with resistant hypertension. OBJECTIVE: To evaluate the feasibility and safety of renal denervation using an irrigated catheter. METHODS: Ten patients with resistant hypertension underwent the procedure. The primary endpoint was safety, as assessed by periprocedural adverse events, renal function and renal vascular abnormalities at 6 months. The secondary endpoints were changes in blood pressure levels (office and ambulatory monitoring) and in the number of antihypertensive drugs at 6 months. RESULTS: The mean age was 47.3 (± 12) years, and 90% of patients were women. In the first case, renal artery dissection occurred as a result of trauma due to the long sheath; no further cases were observed after technical adjustments, thus showing an effect of the learning curve. No cases of thrombosis/renal infarction or death were reported. Elevation of serum creatinine levels was not observed during follow-up. At 6 months, one case of significant renal artery stenosis with no clinical consequences was diagnosed. Renal denervation reduced office blood pressure levels by 14.6/6.6 mmHg, on average (p = 0.4 both for systolic and diastolic blood pressure). Blood pressure levels on ambulatory monitoring decreased by 28/17.6 mmHg (p = 0.02 and p = 0.07 for systolic and diastolic blood pressure, respectively). A mean reduction of 2.1 antihypertensive drugs was observed. CONCLUSION: Renal denervation is feasible and safe in the treatment of resistant systemic arterial hypertension. Larger studies are required to confirm our findings.

Tratamento medicamentoso atual / Current drug treatment

A elevada prevalência populacional de doença arterial coronária crônica propiciou a melhora dos métodos preventivos, diagnósticos e terapêuticos. A confirmação de isquemia, com ou sem sintomas, trouxe tratamento inovadores visando à redução de eventos agudos, melhora na qualidade de vida e aumento de sobrevida Estudos recentes comparam os resultados do tratamento clínico com outras intervenções e concluíram que o sucesso da intervenção clínica está embasado na otimização terapêutica. Definida a influência dos fatores de risco e os mecanismos fisiopatológicos da doença, o tratamento medicamentoso constitui a base e a sequência de todas as intervenções na doença arterial coronária crônica.

The high prevalence of patients with chronic coronary artery disease has led to the improvement of preventive, diagnostic and therapeutic methods. Confirmation of ischemia with or without symptoms, brought innovative treatment aimed at reducing acute events, improvement in quality of life and increased survival. Recent studies have compared the results of clinical treatment with other interventions and concluded that the success of clinical intervention is based on therapeutic optimization. Once established the inluence of risk factors and physiopathological mechanisms of the disease, drug treatment constitutes the basis and the sequence of all interventionns in chronic artery disease.

Condutas terapêuticas do Instituto Dante Pazzanese de Cardiologia / Therapeutics procedures of Instituto Dante Pazzanese de Cardiologia

Condutas Terapêuticas do Instituto Danta Pazzanese de Cardiologia alcança sua segunda edição, inteiramente reescrito, atualizado e ampliado.O livro mantém o seu caráter prático no manejo das doenças cardiovasculares, sendo seu principal objetivo o tratamento. Esta tão especial didática contribui para o fácil acesso aos temas abordados por parte de seus leitores: estudantes de medicina, médicos e, em especial, os residentes.Seu conteúdo é abrangente na medida em que está estruturado em 15 partes, 114 capítulos, num total de 1.476 páginas.Vale ressaltar o livro apresentar 2 editores, 4 editores associados e 154 colaboradores.Dá respaldo a essa abrangência sua equipe autoral, constituída por corpo clínico formado por médicos que completaram sua residência médica no próprio instituto, além de em face dessa formação constituírem pensamento médico extremamente homogêneo que se alonga nos textos e capítulos. Abrangência e homogeneidade de visão médica que excluem dualidade de conceitos, práticas e linhas terapêuticas. Condutas Terapêuticas do Instituto Danta Pazzanese de Cardiologia é livro que se tornará leitura obrigatória para todos os Cardiologistas, Residentes em Cardiologia, Clínicos e Residentes em Clínica Médica.

Leptin receptor gene polymorphisms are associated with adiposity and metabolic alterations in Brazilian individuals / Polimorfismos no gene do receptor de leptina são associados com adiposidade e alterações metabólicas em indivíduos brasileiros

OBJECTIVE: The aim of the study was to investigate whether adiposity and metabolic markers, such as leptin, glucose, and lipids, are influenced by leptin (LEP) and leptin receptor (LEPR) gene polymorphisms in a sample of our population. SUBJECTS AND METHODS: A group of 326 individuals of Caucasian-European descent, aged 30 to 80 years, 87 men and 239 women, 148 obese and 178 non-obese, was randomly selected at two clinical hospitals in the city of Sao Paulo, Brazil. All individuals declared their ethnic group as white during the initial interview. Anthropometric measurements, body mass index (BMI), and fat mass were evaluated. Blood samples were drawn for DNA extraction and measurements of leptin, soluble leptin receptor, glucose, and lipids. LEP -2548G>A and LEPR Lys109Arg (c.326A>G), Gln233Arg (c.668A>G) and Lys656Asn (c.1968G>C) polymorphisms were detected by PCR-RFLP. RESULTS: Increased leptin and serum lipids, and LEPR Arg223Arg (GG genotype) were associated with higher risk for obesity (p < 0.05), while reduced risk was found in LEPR Arg109Arg (GG genotype) carriers (OR: 0.38, 95%CI: 0.19-0.77, p = 0.007). Multiple linear regression analysis showed a relationship between LEPR 223Arg, increased waist circumference, and leptinemia (p < 0.05), while LEPR 109Arg was associated with high total cholesterol and triglycerides (p < 0.05). LEPR haplotype 3 (AGG: 109Lys/233Arg/656Lys) carriers have increased risk for obesity (OR: 2.56, 95% CI: 1.19-5.49, p = 0.017). Moreover, this haplotype was associated with increased BMI, waist circumference, and leptinemia (p < 0.05). CONCLUSIONS: LEPR polymorphisms are associated with obesity, hyperleptinemia, and atherogenic lipid profile, suggesting their potential role for leptin resistance and cardiovascular risk. Moreover, LEPR haplotype 3 confers susceptibility to adiposity and hyperleptinemia in our population.

OBJETIVO: O estudo teve por objetivo investigar a influência de polimorfismos nos genes da leptina (LEP) e do receptor de leptina (LEPR) na adiposidade e em marcadores metabólicos, como leptina, glicose e lipí­deos, em uma amostra de nossa população. SUJEITOS E MÉTODOS: Um grupo de 326 indivíduos com idade de 30 a 80 anos, 87 homens e 239 mulheres, 148 obesos e 178 não obesos, e de etnia branca foi selecionado aleatoriamente em dois hospitais clínicos da cidade de São Paulo, Brasil. Medidas antropométricas, índice de massa corporal (IMC) e gordura corporal foram avaliados. Amostras de sangue foram obtidas para extração de DNA e determinações de leptina, receptor de leptina solúvel, glicose e lipídeos. Os polimorfismos LEP -2548G>A e LEPR Lys109Arg (c.326A>G), Gln233Arg (c.668A>G) e Lys656Asn (c.1968G>C) foram detectados por PCR-RFLP. RESULTADOS: Leptina e lipídeos séricos aumentados e LEPR Arg223Arg (genótipo GG) foram associados com maior risco de obesidade (p < 0,05), enquanto foi encontrado risco reduzido de obesidade, em portadores de LEPR Arg109Arg (genótipo GG) (OR: 0,38, 95%CI: 0,19-0,77, p = 0,007). A análise de regressão linear múltipla mostrou relação entre o alelo LEPR 223Arg e circunferência abdominal e leptinemia aumentadas (p < 0,05), enquanto o alelo LEPR 109Arg foi associado com aumento de colesterol total e triglicerídeos (p < 0,05). Os portadores do haplotipo 3 do LEPR (AGG: 109Lys/233Arg/656Lys) tiveram maior risco aumentado para obesidade (OR: 2.56, 95% CI: 1.19-5.49, p = 0,017). Além disso, esse haplótipo foi associado com IMC, circunferência abdominal e leptinemia aumentados (p < 0,05). CONCLUSÕES: Polimorfismos de LEPR são associados com obesidade, hiperleptinemia e perfil lipídico aterogênico sugerindo seu papel potencial para a resistência à leptina e risco cardiovascular.

Interações medicamentaosas: definições e mecanismos / Drug interactions: definitions and mechanisms

Com mudanças na expectativa de vida, comorbidades edisponibilidade de novos fármacos, aumentou a ocorrênciade interações medicamentosas por mecanismos farmacocinéticose farmacodinâmicos. Para a biotransformação dosmedicamentos, os organismos desenvolveram sistemas enzimáticoscapazes de metabolizar e excretar esses produtos.Os polimorfismos genéticos dessas enzimas condicionamsua eficiência em metabolizar determinados medicamentos.A conjugação com moléculas solúveis em água, adicionadasao medicamento, facilitam sua excreção. Os transportadoresdesempenham importante papel no influxo, efluxo e na excreçãode medicamentos através dos sistemas biliar e urinário.O tratamento de doenças cardiovasculares frequentementeenvolve uso de múltiplos fármacos, principalmente nos pacientesidosos e portadores de comorbidades. Nesse sentido, éimportante o conhecimento dessas interações medicamentosas,frequentemente responsáveis pelos insucessos terapêuticos epela ocorrência de efeitos adversos...

With changes in life expectancy, co-morbidities and theavailability of new drugs, the occurrence of drug interactionsby pharmacokinetic and pharmacodynamic mechanisms hasincreased. For the bio-transformations of medications theorganisms have developed enzymatic systems able to metabolizeand excrete these products. The genetic polymorphisms ofthese enzymes affect their efficiency in metabolizing certaindrugs. The combination with water-soluble molecules addedto the medication facilitates the excretion. Transporters playan important role in the inflow, outflow and the excretion ofmedications through the biliary and urinary systems. Thetreatment of cardiovascular diseases often involves the useof multiple drugs especially in elderly patients and patientswith co-morbidities. In this sense, it is very important theknowledge about these drugs interactions which are oftenresponsible for the therapeutic failure and for the occurrenceof adverse effects...

Terapia personalizada: Contribuição da farmacogenômica cardiiovascular / Persolnalized therapy: contribution of the cardiovascular pharmacogenomics

A indicação terapêutica para prevenção e tratamentode doenças cardiovasculares apresenta uma variedadeampla de classes de fármacos com mecanismos deação (farmacodinâmica) e vias de biotransformação(farmacocinética) distintos. Estudos que investigaram arelação da genômica de várias populações com respostaterapêutica têm demonstrado perfis farmacogenômicosdiferenciais que tem contribuído de forma interessantetanto na terapia personalizada como em pesquisas clínicasmais direcionadas e melhor caracterizadas em diferentespopulações. Nesta revisão, discute-se o estado da arteda farmacogenômica e farmacogenética dos principaisfármacos utilizados no tratamento da doença cardiovascularcomo anticoagulantes, antiagregantes plaquetários,betabloqueadores, anti-hipertensivos e estatinas...

Therapeutic indication in the prevention and treatment ofcardiovascular diseases presents a variety of drug classeswith different mechanisms of action (pharmacodinamics)and metabolism pathways (pharmacokinetics).Studies thathave investigated the relationship of genomic data of severalpopulations with therapeutic response have demonstrated differentialpharmacogenornics profiles that have contributed inan interesting way to the personalized medicine as well as tonew drug discovery protocols in different populations. In thisreview we discuss the state of the art of pharmacogenomicsand pharmacogenetics of most drugs used in the treatment ofcardiovascular disease such as anticoagulants, antiplatelets,beta blockers, antihypertensives and statins...

Novel genes detected by transcriptional profiling from whole-blood cells in patients with early onset of acute coronary syndrome.

BACKGROUND: Genome-wide expression analysis using microarrays has been used as a research strategy to discovery new biomarkers and candidate genes for a number of diseases. We aim to find new biomarkers for the prediction of acute coronary syndrome (ACS) with a differentially expressed mRNA profiling approach using whole genomic expression analysis in a peripheral blood cell model from patients with early ACS. METHODS AND RESULTS: This study was carried out in two phases. On phase 1 a restricted clinical criteria (ACS-Ph1, n=9 and CG-Ph1, n=6) was used in order to select potential mRNA biomarkers candidates. A subsequent phase 2 study was performed using selected phase 1 markers analyzed by RT-qPCR using a larger and independent casuistic (ACS-Ph2, n=74 and CG-Ph2, n=41). A total of 549 genes were found to be differentially expressed in the first 48 h after the ACS-Ph1. Technical and biological validation further confirmed that ALOX15, AREG, BCL2A1, BCL2L1, CA1, COX7B, ECHDC3, IL18R1, IRS2, KCNE1, MMP9, MYL4 and TREML4, are differentially expressed in both phases of this study. CONCLUSIONS: Transcriptomic analysis by microarray technology demonstrated differential expression during a 48 h time course suggesting a potential use of some of these genes as biomarkers for very early stages of ACS, as well as for monitoring early cardiac ischemic recovery.

Leptin receptor gene polymorphisms are associated with adiposity and metabolic alterations in Brazilian individuals.

OBJECTIVE: The aim of the study was to investigate whether adiposity and metabolic markers, such as leptin, glucose, and lipids, are influenced by leptin (LEP) and leptin receptor (LEPR) gene polymorphisms in a sample of our population. SUBJECTS AND METHODS: A group of 326 individuals of Caucasian-European descent, aged 30 to 80 years, 87 men and 239 women, 148 obese and 178 non-obese, was randomly selected at two clinical hospitals in the city of Sao Paulo, Brazil. All individuals declared their ethnic group as white during the initial interview. Anthropometric measurements, body mass index (BMI), and fat mass were evaluated. Blood samples were drawn for DNA extraction and measurements of leptin, soluble leptin receptor, glucose, and lipids. LEP -2548G>A and LEPR Lys109Arg (c.326A>G), Gln233Arg (c.668A>G) and Lys656Asn (c.1968G>C) polymorphisms were detected by PCR-RFLP. RESULTS: Increased leptin and serum lipids, and LEPR Arg223Arg (GG genotype) were associated with higher risk for obesity (p < 0.05), while reduced risk was found in LEPR Arg109Arg (GG genotype) carriers (OR: 0.38, 95%CI: 0.19-0.77, p = 0.007). Multiple linear regression analysis showed a relationship between LEPR 223Arg, increased waist circumference, and leptinemia (p < 0.05), while LEPR 109Arg was associated with high total cholesterol and triglycerides (p < 0.05). LEPR haplotype 3 (AGG: 109Lys/233Arg/656Lys) carriers have increased risk for obesity (OR: 2.56, 95% CI: 1.19-5.49, p = 0.017). Moreover, this haplotype was associated with increased BMI, waist circumference, and leptinemia (p < 0.05). CONCLUSIONS: LEPR polymorphisms are associated with obesity, hyperleptinemia, and atherogenic lipid profile, suggesting their potential role for leptin resistance and cardiovascular risk. Moreover, LEPR haplotype 3 confers susceptibility to adiposity and hyperleptinemia in our population.

CD14 and IL6 polymorphisms are associated with a pro-atherogenic profile in young adults with acute myocardial infarction.

This study investigated the relationship of polymorphisms in genes encoding CD14, IL-6 and TLR4 with metabolic, inflammatory and endothelial markers in young adults with acute myocardial infarction (AMI). Glucose, lipids, nitrate and inflammatory markers, flow mediated vasodilatation (FMV) and flow mediated by nitrate (FMN) were evaluated in 102 AMI and 108 non-AMI (control group) young individuals (<45 years). CD14 -260C>T (rs2569190), IL6 -174G>C (rs1800795) and TLR4 c.896A>G (rs4986790) and TLR4 c.1196C>T (rs4986791) polymorphisms were analyzed by PCR-RFLP. Minor allele frequencies of CD14, IL6 and TLR4 polymorphisms were similar between AMI and control groups (p > 0.05). In AMI group, individuals carrying IL6 -174CC genotype had higher serum triglycerides, VLDL cholesterol and glucose compared to the IL6 -174GG/GC genotype carriers (p < 0.05). Multiple logistic analysis showed that IL6 -174CC genotype carriers had increased risk for hyperglycemia (>5.77 mmol/l) [OR: 6.75, 95 % CI: 1.80-24.40, p = 0.004] and hypertriglyceridemia (>2.68 mmol/l) [OR: 3.00, 95 % CI: 1.00-9.00, p = 0.043]. Moreover, CD14 -260TT genotype was associated with reduced serum HDL cholesterol [OR: 3.10, 95 % CI: 1.00-9.01, p = 0.044] and apolipoprotein AI [OR: 3.20, 95 % CI: 1.00-9.70, p = 0.038] in AMI group. Relationship between CD14 and IL6 variants and altered inflammatory and endothelial (nitrate, FMV and FMN) markers was not found in both AMI and control groups. The IL6 -174G>C and CD14 -260C>T polymorphisms are likely to be associated with a pro-atherogenic profile but not with increased inflammatory markers and endothelial dysfunction in young AMI patients.

Novel genes detected by transcriptional profiling from whole-bloodcells in patients with early onset of acute coronary syndrome

Background: Genome-wide expression analysis using microarrays has been sed as a research strategy to discovery new biomarkers and candidate genes for a number of diseases. We aim to find new biomarkers for the prediction of acute coronary syndrome (ACS) with a ifferentially expressed mRNA profiling approach using whole genomic expression analysis in a peripheral blood cell model from patients with early ACS.Methods and results: This study was carried out in two phases. On phase 1 a restricted clinical criteria (ACS-Ph1, n = 9 and CG-Ph1, n = 6) was used in order to select potential mRNA biomarkers candidates. A subsequent phase 2 study was performed using selected phase 1 markers analyzed by RT-qPCR using alarger and independent casuistic (ACS-Ph2, n = 74 and CG-Ph2, n = 41). A total of 549 genes were found to be differentially expressed in the first 48 h after the ACS-Ph1. Technical and biological validation further confirmed that ALOX15, AREG, BCL2A1, BCL2L1, CA1, COX7B, ECHDC3, IL18R1, IRS2, KCNE1, MMP9, MYL4 and TREML4, are differentially expressed in both phases of this study.Conclusions: Transcriptomic analysis by microarray technology demonstrated differential expression during a 48 h time course suggesting a potential use of some of these genes as biomarkers for very early stages of ACS, as well as for monitoring early cardiac ischemic recovery.

CD14 and IL6 polymorphisms are associated with a pro-atherogenic profile in young adults with acute myocardial infarction

Abstract This study investigated the relationship of polymorphismsin genes encoding CD14, IL-6 and TLR4 withmetabolic, inflammatory and endothelial markers in youngadults with acute myocardial infarction (AMI). Glucose,lipids, nitrate and inflammatory markers, flow mediatedvasodilatation (FMV) and flow mediated by nitrate (FMN)were evaluated in 102 AMI and 108 non-AMI (controlgroup) young individuals (% years). CD14 -260C[T(rs2569190), IL6 -174G[C (rs1800795) and TLR4c.896A[G (rs4986790) and TLR4 c.1196C[T (rs4986791)polymorphisms were analyzed by PCR–RFLP. Minor allelefrequencies of CD14, IL6 and TLR4 polymorphisms weresimilar between AMI and control groups (p[0.05). In AMIgroup, individuals carrying IL6 -174CC genotype hadhigher serum triglycerides, VLDL cholesterol and glucosecompared to the IL6 -174GG/GC genotype carriers(p84 2013-11-12