Arteriosclerose, aterosclerose, arteriolosclerose e esclerose calcificante da média de Monckeberg: qual a diferença? / Arteriosclerosis, atherosclerosis, arteriolosclerosis, and Monckeberg medial calcific sclerosis: what is the difference?

Resumo A principal causa de óbito na contemporaneidade são as doenças cardiovasculares. Arteriosclerose, aterosclerose, arteriolosclerose e arteriosclerose de Monckeberg são termos frequentemente utilizados como sinônimos, mas traduzem alterações distintas. O objetivo desta revisão foi discutir os conceitos de arteriosclerose, aterosclerose, arteriolosclerose e esclerose calcificante da média de Monckeberg. O termo arteriosclerose é considerado mais genérico, significando o enrijecimento e a consequente perda de elasticidade da parede arterial, abarcando os demais tipos. A aterosclerose é uma doença inflamatória secundária a lesões na camada íntima, que tem como principal complicação obstrução crônica e aguda do lúmen arterial. A arteriolosclerose se refere ao espessamento das arteríolas, particularmente relacionada à hipertensão arterial sistêmica. Já a esclerose calcificante da média de Monckeberg designa a calcificação, não obstrutiva, da lâmina elástica interna ou da túnica média de artérias musculares. As calcificações vasculares, que incluem lesões ateroscleróticas e a esclerose calcificante da média de Monckeberg, vêm sendo estudadas como um fator de risco para a morbimortalidade cardiovascular.

Abstract Cardiovascular diseases are the main cause of death in contemporary times. Arteriosclerosis, atherosclerosis, arteriolosclerosis, and Monckeberg's arteriosclerosis are terms that are often used interchangeably, but they refer to different vascular pathologies. The objective of this study is to review the concepts of atherosclerosis, atherosclerosis, arteriosclerosis and Monckeberg medial calcific sclerosis (MMCS). The term arteriosclerosis is more generic, meaning the stiffening and consequent loss of elasticity of the arterial wall, and encompasses the other terms. Atherosclerosis is an inflammatory disease secondary to lesions in the intimal layer and whose main complication is acute and chronic obstruction of the arterial lumen. Arteriolosclerosis refers to thickening of arterioles, particularly in association with systemic arterial hypertension. MMCS refers to non-obstructive calcification in the internal elastic lamina or the tunica media of muscular arteries. Vascular calcifications, which include atherosclerotic lesions and MMCS, have been studied as a risk factor for cardiovascular morbidity and mortality.

Age Related Hemodynamic Blood Pressure Changes for Cardiovascular Disease and Stroke: A Mini-review.

The blood pressure (BP) changes with the advancement of age from the predominant diastolic BP (DBP) in the young to the predominant systolic BP (SBP) in the older person. This shift is due to the stiffening of the large arteries as a result of the ageing process and the replacement of the elastic fibers with collagen fibers resulting in the loss of compliance and the elastic recoil of these vessels. The end result is augmentation in pulse wave velocity (PWV) and widening of pulse pressure (PP). The SBP rises linearly with the advancement of age whereas, the DBP rises up to the age 50 years and begins to decline after the age of 60 years leading to a progressive increase in PP. These hemodynamic changes of BP are frequently associated with an increased incidence in cardiovascular disease (CVD) and strokes. Several studies have shown an inverse relationship between DBP and CVD, whereas no such a relationship has been demonstrated for stroke. However, recently, an inverse relationship has been reported between DBP and stroke for subjects 50 years of age or older. The implications of BP changes with age as they are related to CVD and strokes will be discussed in this mini review. It appears from these recent findings that in treating the hypertension in the elderly to reduce CVD and stroke, care should be taken not to allow the DBP to drop below 55-80 mmHg, since below this DBP level the incidence of CVD and strokes increase.

Función y disfunción endotelial / Endothelial function and dysfunction

El endotelio es el principal regulador de la homeostasis vascular, modula el balance vasoconstricción/vasodilatación, inhibe la proliferación/migración de células musculares de la pared vascular (VSMC), y también modula la hemostasia. La disfunción endotelial es un evento que precede los cambios morfológicos característicos de la aterogénesis y contribuye al desarrollo de complicaciones de la placa ateroesclerótica. Además, la evidencia disponible indica que el desarrollo de disfunción endotelial participa en el daño cardiovascular en condiciones que abarcan desde procesos fisiológicos como el envejecimiento, hasta procesos fisiopatológicos diversos como hipertensión arterial, insuficiencia cardíaca, insuficiencia renal, diabetes mellitus, coagulación intravascular, preeclampsia, enfermedades inflamatorias y la apnea del sueño(1, 2). El objetivo del presente artículo es revisar brevemente la función endotelial, definir disfunción endotelial en un contexto amplio y presentar los mecanismos generales que conducen a disfunción endotelial en relación a las enfermedades cardiovasculares más prevalentes.

The endothelium is the main regulator for vascular homeostasis. The functions of the endothelium include regulation of the balance between vasoconstriction and vasodilation, inhibition of proliferation and migration of smooth muscle cells (VSMC) from the vascular wall and modulation of hemostasis. Endothelial dysfunction precedes the morphological changes characteristic of atherogenesis and contributes to the development atherosclerotic plaques. Also, current evidence indicates that the development of endothelial dysfunction is associated with cardiovascular damage in several physiological conditions such as arterial hypertension, heart and renal failure, diabetes mellitus, intravascular coagulation, preeclampsia, inflammatory disease and sleep apnea (1,2). The purpose of this article is to provide a brief review of endothelial dysfunction, broadly define endothelial dysfunction, and to present general mechanisms that are correlated with endothelial dysfunction in most prevalent cardiovascular diseases.

Correlación de los resultados del SPECT de perfusión miocárdica con 99mmTc-MIBI con la presencia de factores de riesgo aterosclerótico, en pacientes iguales o mayores a 40 años de edad: resultados preliminares / Correlation of myocardial perfusion SPECT with Tc-99m MIBI in presence of atherosclerotic risk factors

Objetivo: Conocer la combinación de Factores Mayores de Riesgo Aterosclerótico (FMRA) que nos sugeriría remitir directamente al paciente a coronariografía, para la optimización del uso del SPECT de Perfusión Miocárdica (SPECTPM). Material y Método: Se analizaron 577 SPECTPM, 345(59.8 por ciento) fueron masculinos, edad media: 62.26años y 79pacientes(13.7 por ciento) fueron asintomáticos. Resultados: 448(77.64 por ciento) SPECTPM fueron positivos y 129(22.36 por ciento) negativos, el FMRA más frecuente la HTA (68.80 por ciento) y el que más se asocio con SPECTPM positivo el habito de fumar, no existió riesgo significativo de SPECTPM positivo para ninguno de los FMRA estudiados, ni sus combinaciones. Conclusiones: La presente investigación sugiere que teniendo en cuenta la alta especificidad, valor predictivo negativo y valor pronostico del SPECTPM, deben realizarse coronariografía solo a los pacientes sintomáticos con resultado positivo de SPECTPM, por tanto todos los pacientes deben realizarse un SPECTPM previo a la realización de la angiografía, por tener alta probabilidad de tener resultados negativos.

Objective: Know the combination of FMRA that would suggest us to remit the patient directly to coronariography, for the optimization of the use of the SPECTPM. Material and Method: 577 SPECTPM were analyzed, 345(59.8 percent) they were masculine, mean age: 62.26 years and 79(13.7 percent) asymptomatic. Results: Positive SPECTPM 448(77.64 percent) and negative 129(22.36 percent), the most frequent FMRA was HTA(68.80 percent) and the one that was most associated with positive SPECTPM was the smoking habit. There wasn’t any significant risk of positive SPECTPM for none of the FMRA studied, not even in their combinations. Conclusions: Keeping in mind the high specificity, predictive negative value and prognostic value of the SPECTPM, this investigation paper recommends that only patients with a positive result of SPECTPM should undergo a coronariography. Therefore, all patients with angina pectoris should have a SPECTPM before undergoing an angiography, because there is a high probability of having negative results.

Elastic properties of aorta are impaired in patients with slow coronary flow phenomenon.

BACKGROUND: Increased stiffening and decreased distensibility of the large arteries are associated with the presence of coronary artery disease and has been related to increased cardiovascular mortality in different populations. AIM: Aim of this present study was to investigate the elastic properties of the aortic wall in patients with slow coronary flow phenomenon. MATERIAL AND METHOD: We studied 20 patients with slow coronary flow phenomenon (age: 40+/-12 years)and 15 normal control subjects by echocardiography. Aortic strain (%) and distensibility (10(-3) mmHg(-1)) were calculated from the echocardiographically-derived thoracic Ao diameters (mm). The measurement of pulse pressure was obtained by cuff sphygmomanometry. RESULTS: There was no difference in the left ventricular ejection fraction, left ventricular end-diastolic and end-systolic diameters, left atrial diameters, left ventricular mass index between patients with slow coronary flow phenomenon and control groups. Maximal aortic diastolic diameter was increased in patients with slow coronary flow phenomenon compared with control group (p<0.05). Ao distensibility and Ao strain were lower in the patients with slow coronary flow phenomenon compared with control group (p<0.05). CONCLUSION: Reduced thoracic aortic elastic properties in patients with slow coronary flow phenomenon,assessed by echocardiography, apart from demonstrating subclinical atherosclerosis may also contribute to the etiopathogenesis of the slow coronary flow phenomenon necessitating more aggressive primary preventive measure.

Green tea polyphenols inhibit oxidized LDL-induced NF-KB activation in human umbilical vein endothelial cells.

AIM: To examine the anti-inflammatory effects of green tea polyphenols on oxLDL-mediated TNFalpha expression and NF-KB activation in the human umbilical vein endothelial cells (HUVECs). METHODS: We postulate that green tea polyphenols regulate TNF-alpha gene expression by modulating NF-KB activation through their inhibition effect on IKB Kinase (IKK) activity and as scavenger of free radicals. Pretreatment of green tea polyphenols reduced oxLDL-induced production of proinflammatory cytokine TNF-alpha and NF-KB activation in dose dependent manner (p < 0.05). Post hoc comparison test with Mann Whitney between various dosage of green tea polyphenols in inhibition of NF-KB activation showed significant result (p < 0.05). RESULTS: In TNF-alpha expression, there was also declined TNF-alpha productions (p 0.09; 0.2 vs 0.4mg/ml: ns). The effect of green tea polyphenols on TNF-alpha expression were determined by Mann-Whitney test. There is significant difference between the first dose (0.1mg/ml) vs 0.2mg/ml polyphenols (p=0.009); between 0.1 vs 0.4 mg/ml polyphenols (p=0.009). There was no difference when the dose was increased from 0.2 mg/ml to 0,4 mg/ml polyphenols (0.141). In this study, green tea polyphenols showed significant effects on the inhibition of TNF-alpha through NF-KB activation pathway in HUVECs with oxidized LDL. CONCLUSION: Green tea polyphenol can be used to prevent the development of atherosclerosis.

The expression and down stream effect of lectin like-oxidized low density lipoprotein 1 (LOX-1) in hyperglycemic state.

The lesions of atherosclerosis represent a series of highly specific cellular and molecular responses. Low density lipoprotein (LDL), which may be modified by oxidation, glycation, aggregation, association with proteoglycans, or incorporation into immune complexes, is a major cause of injury to the endothelium and vascular smooth muscle cells (VSMC).The major major cell types involved in atherogenesis, macrophages and VSMC, are activated by pro-inflammatory stimuli including modified LDL. Modified LDL induces inflammatory responses in macrophages, migration and proliferation of SMC, and triggers foam cell formation. Scavenger receptors, including LOX-1, play a key role in foam cell formation by mediating the uptake of modified LDL. LOX-1 expression is detected in endothelial cells of early atherosclerosis lesions of human carotid arteries. Advanced lesions showed LOX-1 expression not only in endothelial cells but also in macrophages and more frequently in VSMC, and may be involved in foam cell transformation in macrophages and VSMC. The metabolic abnormalities that characterize diabetes, particularly hyperglycemia, free fatty acids, and insulin resistance, provoke molecular mechanisms that alter the function and structure of blood vessels. These include increased oxidative stress, intracellular signal transduction disturbances, and activation of the receptor for advanced glycation end products (R-AGE). Data showed that LOX-1 expression is enhanced by proatherogenic factors relevant to human diabetes, including high glucose, oxLDL, advance glycation end products, and C-reactive protein. LOX-1 expression increased also through oxygen species (ROS), endothelin-1 (ET-1), tumor necrosis factor-alpha (TNF-alpha), shear stress, activation of protein kinase-C (PKC), angiotensin-II (ANG-II), and through inflammatory pathways.

Antioxidant status and lipid peroxidation end products in patients of type 1 diabetes mellitus.

BACKGROUND AND OBJECTIVE: In Type 1 diabetes mellitus (DM), hyperglycemia is considered a primary cause of diabetic vascular complications and is associated with oxidative stress. The role of antioxidants, particularly alpha tocopherol, in Type 1 DM and its contribution in the development of vascular complications is not clear. Therefore, the present study aims to investigate the relationship between antioxidant status (alpha tocopherol) and lipid peroxidation end products (malondialdehyde; MDA) in the plasma of 20 Type 1 DM and 20 nondiabetic healthy control subjects. MATERIAL AND METHOD: Lipid levels in all subjects were analyzed spectrophotometrically by enzymatic reagent kits. Plasma MDA was assessed by spectrofluorometry, whereas plasma alpha tocopherol was estimated by high performance liquid chromatography in Type 1 DM as well as in the control subjects of matched sex and ages. The results of Type 1 DM were compared with a control group using unpaired Student's t-test. The correlations between fasting plasma glucose and other laboratory parameters were assessed by Pearson rank correlation coefficient. RESULTS: The plasma MDA concentration was significantly higher in Type 1 diabetic patients as compared to controls, (p < 0.01). A significantly reduced plasma antioxidant status of Type 1 DM patients was found only in alpha tocopherol / total lipid as compared to controls (p < 0.05). However, no significant difference was observed in plasma a tocopherol and a tocopherol / total cholesterol (p > 0.05) as compared to the control subjects. The positive correlation between MDA and FPG was demonstrated in Type 1 diabetic compared with normal subjects. CONCLUSION: We conclude that antioxidant supplementation may be necessary for treatment to reduce oxidative stress for diabetic complication protection in Type 1 DM.

Biological significance of essential fatty acids.

Essential fatty acids (EFAs)--linoleic acid (LA) and alpha-linolenic acid (ALA) are critical for human survival. EFAs are readily available in the diet. But, to derive their full benefit, EFAs need to be metabolized to their respective long-chain metabolites. EFAs not only form precursors to respective prostaglandins (PGs), thromboxanes (TXs), and leukotrienes (LTs), but also give rise to lipoxins (LXs), resolvins, isoprostanes, and hydroxy- and hydroperoxyeicosatetraenoates. Certain PGs, TXs, and LTs have pro-inflammatory actions whereas LXs and resolvins are anti-inflammatory in nature. Furthermore, EFAs and their long-chain metabolites modulate the activities of angiotensin converting and HMG-CoA reductase enzymes, enhance acetylcholine levels in the brain, increase the synthesis of endothelial nitric oxide, augment diuresis, and enhance insulin action. Thus, EFAs and their metabolites may function as endogenous ACE and HMG-CoA reductase inhibitors, nitric oxide enhancers, beta-blockers, diuretics, anti-hypertensive, and anti-atherosclerotic molecules. In addition, EFAs and their long-chain metabolites react with nitric oxide (NO) to yield respective nitroalkene derivatives that exert cell-signaling actions via ligation and activation of peroxisome proliferator-activated receptors (PPARs). Thus, EFAs and their derivatives have varied biological actions that may have relevance to their involvement in several physiological and pathological processes.

Association of serum albumin and homocysteine levels and cardio-ankle vascular index in patients with continuous ambulatory peritoneal dialysis

BACKGROUND: The cardio-ankle vascular index (CAVI) is a newly developed arteriosclerotic measurement that has been proposed as an alternative to aortic pulse-wave velocity (PWV). The present study used the CAVI to identify the main factors associated with arteriosclerosis in continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: Fifteen CAPD patients were enrolled in the study. The CAVI is independent of the pressure and vascular reflection between the heart valve and the ankle. Serum albumin, uric acid, total calcium, phosphorus, lipid levels, high-sensitivity C-reactive protein and homocysteine concentrations in CAPD patients were measured using standard methods. Total body fat mass, truncal and non-truncal fat mass and lean body mass were measured using dual energy X-ray absorptiometry with a Lunar DPX-L scanner. RESULTS: CAPD patients had a mean CAVI of 9.37+/-3.16 m/sec, which was higher than the general population. The CAVI was negatively correlated with the serum albumin concentration (r=-0.548; p=0.034). Stepwise regression analysis showed that both the serum albumin concentration (beta=-0.643, p=0.013) and the serum homocysteine level (beta=0.486, p=0.004) were independently associated with the CAVI. CONCLUSIONS: An increase in CAVI was independently associated with both serum albumin and homocysteine level.

Efeitos da atorvastatina, fluvastatina, pravastatina e simvastatina sobre a função endotelial, a peroxidação lipídica e a aterosclerose aórtica em coelhos hipercolesterolêmicos / Effects of atorvastatin, fluvastatin, pravastatin, and simvastatin on endothelial function, lipid peroxidation, and aortic atherosclerosis in hypercholesterolemic rabbits

OBJETIVO: Comparar os efeitos da atorvastatina, fluvastatina, pravastatina e simvastatina sobre a função endotelial, a aterosclerose aórtica e o teor de malonodialdeído (MDA) nas LDL nativas, oxidadas e na parede arterial de coelhos hipercolesterolêmicos, depois que as doses destas estatinas foram ajustadas para reduzir o colesterol total plasmático a valores similares. MÉTODOS: Coelhos machos, foram separados em grupos de 10 animais (n=10), chamados hipercolesterolêmico (controle), atorvastatina, fluvastatina, pravastatina e normal. A exceção do grupo normal, os animais foram alimentados com ração padrão acrescida de colesterol a 0,5 por cento e óleo de coco a 2 por cento durante 45 dias. As drogas foram administradas a partir do 15° dia do início do experimento e no 30° dia, as doses foram ajustadas, através do controle do colesterol plasmático, para obter valores semelhantes em cada grupo. Ao final do experimento foi dosado o colesterol plasmático e as lipoproteinas e retirado um segmento de aorta torácica para estudo da função endotelial, da peroxidação lipídica e exame histológico para medida da aterosclerose aórtica. RESULTADOS: As estatinas reduziram significantemente o colesterol total plasmático, as LDL-colesterol e a aterosclerose aórtica. O teor de MDA também foi significantemente reduzido nas LDL nativas e oxidadas, assim como na parede arterial. O relaxamento-dependente do endotélio foi significantemente maior no grupo tratado em comparação ao hipercolesterolêmico. CONCLUSÃO: As estatinas, em doses ajustadas, tiveram efeito significante e similar em reduzir a peroxidação lipídica nas LDL e na parede arterial, na regressão da aterosclerose aórtica e na reversão da disfunção endotelial.

Nitric oxide and the resolution of inflammation: implications for atherosclerosis

The ubiquitous free radical, nitric oxide (NO), plays an important role in many biological processes including the regulation of the inflammatory response. Alterations in NO synthesis by endogenous systems likely influence inflammatory processes occurring in a wide range of diseases including many in the cardiovascular system (e.g. atherosclerosis). Progression of inflammatory conditions depends not only upon the recruitment and activation of inflammatory cells but also upon their subsequent removal from the inflammatory milieu. Apoptosis, or programmed cell death, is a fundamental process regulating inflammatory cell survival and is critically involved in ensuring the successful resolution of an inflammatory response. Apoptosis results in shutdown of secretory pathways and renders effete, but potentially highly histotoxic, cells instantly recognisable for non-inflammatory clearance by phagocytes (e.g., macrophages). However, dysregulation of apoptosis and phagocytic clearance mechanisms can have drastic consequences for development and resolution of inflammatory processes. In this review we highlight the complexities of NO-mediated regulation of inflammatory cell apoptosis and clearance by phagocytes and discuss the molecular mechanisms controlling these NO mediated effects. We believe that manipulation of pathways involving NO may have previously unrecognised therapeutic potential for limiting or resolving inflammatory and cardiovascular disease.

Fisiopatologia e aspectos inflamatórios da aterosclerose / Physiopathology and inflammatory aspects of atherosclerosis

O objetivo deste trabalho foi apresentar e avaliar o que tem se descoberto recentemente sobre fisiopatologia, epidemiologia e aspectos inflamatórios envolvidos na aterosclerose dentro de uma pespectiva multidisciplinar. Foram realizadas compilações bibliográficas sobre artigos científicos originais e de revisão em revistas indexadas no Medline no período de 1970 ao atual que envolvesse assuntos relacionados à aterosclerose. A revisão sugere que a aterosclerose é uma doença multifatorial com forte componente genético, ambiental e de resposta inflamatória, associada ao envelhecimento. No entanto, ainda a sua etiologia não está completamente esclarecida. O entendimento da biologia básica da inflamação na aterosclerose proporcionaria um melhor suporte clínico que poderia alterar o caminho da prática da medicina preventiva e propiciar benefícios para a saúde pública.

Novas perspectivas no tratamento das dislipidemias / New perspectives on dislipidemia therapy

As projeções da Organização Mundial de Saúde indicam que a morbidade e a mortalidade causadas pela doença cardiovascular, nas próximas décadas, se constituirão na primeira causa de morte em todo o mundo. No Brasil, a doença aterosclerótica coronariana e cerebrovascular já são a primeira causa de incapacidade e morte, correspondendo a 32,1 por cento de todas as causas, enquanto em outros países essas taxas vêm aumentando, particularmente no leste da Europa, no sudoeste da Ásia e na América do Sul. As dislipidemias desempenham um importante papel neste cenário porque participam ativamente da fisiopatologia do processo aterosclerótico, sendo reconhecidas na atualidade como um dos maiores fatores de risco modificáveis para o desenvolvimento da doença arterial coronariana. Conseqüentemente, reduzir o LDL-colesterol tornou-se o alvo terapêutico a ser atingido na busca do tratamento e da prevenção desta doença. Diversos estudos de intervenção com as vastatinas e com os fibratos, entre outras drogas hipolipemiantes, demonstraram redução de eventos cardiovasculares em pacientes de alto, médio e baixo riscos, tornando essas medicações a primeira escolha para o tratamento dessas anormalidades...

Hipercolesterolemia familiar / Familial hypercholesterolemia

A hipercolesterolemia familiar é uma doença genética, caracterizada por elevações dos níveis de colesterol plasmático, resultante da fração que não é removida adequadamente da circulação. São descritas mais de 600 mutações envolvidas nos mecanismos de síntese e expressão dos receptores da lipoproteína de baixa densidade (LDL), o que se traduz em redução ou em não funcionamento desses mecanismos. A forma de transmissão da mutação é autossômica dominante, o que resulta em dois fenótipos distintos: a forma homozigótica, rara, com prevalência de 1 em 1 milhão de indivíduos e valores de LDL-Colesterol acima de 600 mg/dl, além da presença de aterosclerose precoce, com acometimento cardiovascular já na primeira infância e adolescência; e a forma heterozigótica, mais frequente, que acomete 1 em 500 indivíduos, em que os níveis de LDL-colesterol plasmático se situam, geralmente entre 200 mg/dl e 400 mg/dl, e na ausência de tratamento adequado a doença coronariana vai se estabelecer em homens antes dos 50 anos e em mulheres antes dos 60 anos. o diagnóstico é estabelecido por meio de critérios clínicos e pode ser confirmado pela determinação da mutação. O tratamento, bem como as metas lipídicas a serem alcançadas, baseiam-se na estratificação de risco desses pacientes, o qual avalia, entre outros fatores, a presença de aterosclerose subclínica por meio da avaliação do complexo íntima média da carótida e do cálcio coronário. O diagnóstico de hipercolesterolemia familiar permite a identificação dessa doença em outros componentes assintmáticos em uma mesma família, podendo-se estabelecer o tratamento adequado da hipercolesterolemia, o que irá prevenir eventos cardiovasculares futuros

A doença arterial coronariana sob o prisma da genética molecular / A genetic view of the coronary artery disease

A biologia molecular evolui de forma vertiginosa e atualmente é tida como ferramenta indispensável na compreensão de doenças complexas e multifatoriais como a doença arterial coronariana. Tal abordagem gera uma nova forma de avaliação de doenças conhecidas e propicia a criação de novas técnicas, novos métodos diagnósticos e possíveis abordagens terapêuticas, interferindo diariamente no desfecho clínico final do paciente. O número de publicações em genética cardiovascular aumentou cinco vezes nos últimos 20 anos e a descoberta de novos polimorfismos e mutações bem como marcadores de inflamação, coagulação e genes relacionados ao metabolismo lipídico contribuem para se conhecer cada vez mais os aspectos intrínsecos envolvidos na aterosclerose. Este artigo irá abordar os principais avanços nessa área, identificando os polimorfismos mais comuns e sua relevância clínica segundo grandes ensaios e meta-análises,bem como fazer um breve racional acerca do desenho atual dos ensaios clínicos em biologia molecular