Update on Sitosterolemia and Atherosclerosis.

PURPOSE OF REVIEW: The purpose of this review was to summarize important and updated information on sitosterolemia. Sitosterolemia is an inherited lipid disorder consisting of high levels of plasma plant sterols. This sterol storage condition is caused by biallelic loss-of-function genetic variants in either ABCG5 or ABCG8, leading to increased intestinal absorption and decreased hepatic excretion of plant sterols. Clinically, patients with sitosterolemia usually exhibit xanthomatosis, high levels of plasma cholesterol, and premature atherosclerotic disease, but presentation can be highly heterogeneous. Therefore, recognition of this condition requires a high level of suspicion, with confirmation upon genetic diagnosis or through measurement of plasma phytosterols. Treatment of sitosterolemia with both a plant sterol-restricted diet and the intestinal cholesterol absorption inhibitor ezetimibe can reduce efficiently the levels of plasma plant sterols, consisting in the first-line therapy for this disease. RECENT FINDINGS: Since hypercholesterolemia is often present in individuals with sitosterolemia, it is important to search for genetic variants in ABCG5 and ABCG8 in patients with clinical criteria for familial hypercholesterolemia (FH), but no variants in FH implicated genes. Indeed, recent studies have suggested that genetic variants in ABCG5/ABCG8 can mimic FH, and even when in heterozygosis, they may potentially exacerbate the phenotype of patients with severe dyslipidemia. Sitosterolemia is a genetic lipid disorder characterized by increased circulating levels of plant sterols and clinically manifested by xanthomatosis, hematologic disorders, and early atherosclerosis. Awareness about this condition, a rare, but commonly underdiagnosed and yet treatable cause of premature atherosclerotic disease, is imperative.

Updates on the Use of Subclinical Atherosclerosis to Predict Risk of Cardiovascular Events in Heterozygous Familial Hypercholesterolemia.

PURPOSE OF REVIEW: The high variability of cardiovascular risk in heterozygous familial hypercholesterolemia (HeFH) is a challenge for therapeutical management. Subclinical cardiovascular imaging represents a tool to overcome this challenge. The purpose of this review is to update the reader on the most recent findings on the non-invasive detection of atherosclerotic burden by carotid doppler ultrasound (US), coronary artery calcium (CAC) score, and computed tomography coronary angiography (CTCA) for the optimization of risk stratification in HeFH subjects. RECENT FINDINGS: Carotid ultrasound (US) proved its efficacy in the long-term follow-up of HeFH children treated early on with statins, showing a significant reduction of atherosclerotic progression compared to untreated unaffected siblings. The added value of CAC score has been confirmed to predict the risk of cardiovascular events and improve risk stratification provided by available risk equations in asymptomatic HeFH subjects from large prospective cross-national cohorts. Additionally, CTCA provides detailed information on plaque quality and stability, but its role in primary prevention HeFH subjects needs to be further explored. Cardiovascular imaging for the detection of subclinical atherosclerotic cardiovascular disease in HeFH is a promising tool to improve diagnostic and therapeutical management of this undertreated and late-diagnosed disease.

Insights into the Role of Inflammation in the Management of Atherosclerosis.

Atherosclerosis is the biological basis of ischemic heart disease and ischemic stroke, the leading causes of death in the world. After decades of studies, the understanding of atherosclerosis has evolved dramatically, and inflammation has been recognized as one of the most relevant pillars in all phases of atherosclerotic disease. Nevertheless, only recently, the trial CANTOS, and subsequent outcome studies with colchicine, finally provided proof-of-concept evidence that anti-inflammatory therapies were able to reduce cardiovascular events with no influence on lipid levels. These landmark studies inaugurated an era of clinical and pre-clinical studies of immunomodulatory strategies focused on reduction of cardiovascular risk. Although there are promising results in the field, selection of the most appropriate immunomodulatory therapy and identification of patients who could benefit the most, are still enormous challenges. Further research is imperative before we can finally advance towards regular use of anti-inflammatory agents to reduce atherosclerotic events in our clinical practice.

SLCO1B1 haplotypes are not associated with atorvastatin-induced myalgia in Brazilian patients with familial hypercholesterolemia.

PURPOSE: Recent studies reported the association of SLCO1B1 haplotypes with the development of musculoskeletal side effects during simvastatin use. The aim was to evaluate the pharmacogenetic association of SLCO1B1 haplotypes with atorvastatin-induced myalgia in a sample of individuals on high-dose atorvastatin regimens. METHODS: One hundred and forty-three patients with familial hypercholesterolemia were followed for at least 12 months while receiving atorvastatin. Genotypes for the rs2306283 (c.A388G) and rs4149056 (c.T521C) polymorphisms were detected by high-resolution melting analysis. These markers form four distinct haplotypes (*1A, *1B, *5 and *15). RESULTS: During the follow-up period, 14 (9.8%) patients developed myalgia and 16 (11.2%) presented CK levels more than 3 times the upper limit of the normal range. No association of the SLCO1B1 rs2306283 and rs4149056 genotypes or haplotypes with the presence of myalgia or creatine kinase (CK) values was found. Presence of rs2306283 AG + GG genotypes was not associated with increased risks of myalgia or abnormal CK values (OR 2.08, 95% CI 0.62-7.00, p = 0.24 and OR 0.51, 95% CI 0.21-1.26, p = 0.15 respectively). The presence of rs4149056 TC + CC genotypes was also not associated with increased risk of myalgia or abnormal CK values (OR 2.24, 95% CI 0.47-10.72, p = 0.31 and OR 1.51, 95% CI 0.57-3.96, p = 0.41 respectively). CONCLUSIONS: Our findings reaffirm that the SLCO1B1 genetic risk appears to be greater in those patients receiving simvastatin compared with those receiving atorvastatin. This suggests that the importance of SLCO1B1 haplotypes depends on the specific statin that has been used.

Screening of ABCG5 and ABCG8 Genes for Sitosterolemia in a Familial Hypercholesterolemia Cascade Screening Program.

BACKGROUND: Sitosterolemia is a rare autosomal recessive disorder caused by homozygous or compound heterozygous variants in ABCG5/ABCG8. The disease is characterized by increased plasma plant sterols. Small case series suggest that patients with sitosterolemia have wide phenotypic heterogeneity with great variability on either plasma cholesterol levels or development of atherosclerotic cardiovascular disease. The present study aims to characterize the prevalence and clinical features of sitosterolemia participating in a familial hypercholesterolemia genetic cascade screening program. METHODS: From 443 familial hypercholesterolemia index cases, 260 were negative for familial hypercholesterolemia genes and were sequenced for the ABCG5/8 genes. Clinical and laboratory characteristics of affected individuals were determined. RESULTS: Eight (3.1%) index cases were found to be homozygous or compound heterozygous variant for ABCG5/ABCG8 genes, confirming the genetic diagnosis of sitosterolemia. Screening their relatives led to the identification of 6 additional confirmed sitosterolemia cases (3 homozygous and 3 compound heterozygous variant) and 18 carriers (heterozygous). The mean age of identified sitosterolemia cases (n=14) was 37.2±19.8 years, 50% were females, and 78.6% (all adults) presented either clinical or subclinical atherosclerotic cardiovascular disease. As expected, affected individuals presented elevated plasma plant sterol levels (mean ß-Sitosterol and campesterol, respectively, 160.3±107.1 and 32.0±19.6 µg/mL) and the highest plasma LDL (low-density lipoprotein)-cholesterol was 269.0±120.0 mg/dL (range: 122-521 mg/dL). LDL-cholesterol mean reduction with therapy among cases was 65%. Eighty-three percent (83%) of identified sitosterolemia patients presented hematologic abnormalities. CONCLUSIONS: Testing genes associated with sitosterolemia in the molecular routine workflow of a familial hypercholesterolemia cascade screening program allowed the precise diagnosis of sitosterolemia in a substantial number of patients with varying LDL-C levels and high incidence of early atherosclerotic cardiovascular disease and hematologic abnormalities.

Prevalence of Metabolic Syndrome and Framingham Risk Score in Apparently Healthy Vegetarian and Omnivorous Men.

BACKGROUND: Recent studies have shown a lower prevalence of metabolic syndrome (MSyn) in vegetarians (VEG) despite the inconclusive evidence from others. OBJECTIVE: To verify the association between diet and other lifestyle characteristics and the prevalence of MSyn, cardiovascular risk factors (CRF), and Framingham Risk Score (FRS) in apparently healthy VEG and omnivorous (OMN) men. METHODS: In this cross-sectional study, 88 apparently healthy men ≥ 35 years, 44 VEG and 44 OMN, were assessed for anthropometric data, blood pressure, blood lipids, glucose, C-reactive protein (CRP) and FRS. To test the association between lifestyle and MSyn, Student t test, chi-square test, and multiple logistic regression model were used. A significance level of 5% was considered in all statistical analyses. RESULTS: Several CRF were significantly lower in VEG than in OMN: body mass index, systolic blood pressure, diastolic blood pressure, fasting serum total cholesterol, LDL-cholesterol, apolipoprotein b, glucose, and glycated hemoglobin (all p < 0.05). The FRS mean was lower in VEG than in OMN (2.98 ± 3.7 vs 4.82 ± 4.8, p = 0.029). The percentage of individuals with MSyn was higher among OMN than among VEG (52.3 vs.15.9%) (p < 0.001). The OMN diet was associated with MSyn (OR: 6.28 95%CI 2.11-18.71) and alterations in most MSyn components in the multiple regression model independently of caloric intake, age and physical activity. CONCLUSION: The VEG diet was associated with lower CRF, FRS and percentage of individuals with MSyn.

Reduced subclinical carotid vascular disease and arterial stiffness in vegetarian men: The CARVOS Study.

BACKGROUND: Dietary habits play an important role in the development of atherosclerosis, the most important cause of morbidity and mortality in the world. The objective of this study was to verify if vegetarian (VEG) diet could be related a better profile of subclinical vascular disease evaluated by arterial stiffness and functional and structural properties of carotid arteries, compared to omnivorous (OMN) diet. METHODS: In this cross-sectional study, 44 VEG and 44 OMN apparently healthy men ≥35years of age, in order to not have confounding risk factors of subclinical atherosclerosis, were assessed for anthropometric data, blood pressure, blood lipids, glucose, C reactive protein (CRP), and arterial stiffness determined by carotid-femoral pulse wave velocity (PWV). Also, carotid intima-media thickness (c-IMT) and distensibility were evaluated. RESULTS: VEG men had lower body mass index, systolic and diastolic blood pressures, fasting serum total cholesterol, LDL and non-HDL-cholesterol, apolipoprotein B, glucose and glycated hemoglobin values in comparison with OMN individuals (all p values <0.05). Markers of vascular structure and function were different between VEG and OMN: PWV 7.1±0.8m/s vs. 7.7±0.9m/s (p<0.001); c-IMT 593±94 vs. 661±128µm (p=0.003); and relative carotid distensibility 6.39±1.7 vs. 5.72±1.8% (p=0.042), respectively. After a multivariate linear regression analysis, a VEG diet was independently and negatively associated with PWV (p value 0.005). CONCLUSIONS: A VEG diet is associated with a more favorable cardiovascular diseases biomarker profile and better vascular structural and functional parameters.

Brazilian guidelines on prevention of cardiovascular disease in patients with diabetes: a position statement from the Brazilian Diabetes Society (SBD), the Brazilian Cardiology Society (SBC) and the Brazilian Endocrinology and Metabolism Society (SBEM).

BACKGROUND: Since the first position statement on diabetes and cardiovascular prevention published in 2014 by the Brazilian Diabetes Society, the current view on primary and secondary prevention in diabetes has evolved as a result of new approaches on cardiovascular risk stratification, new cholesterol lowering drugs, and new anti-hyperglycemic drugs. Importantly, a pattern of risk heterogeneity has emerged, showing that not all diabetic patients are at high or very high risk. In fact, most younger patients who have no overt cardiovascular risk factors may be more adequately classified as being at intermediate or even low cardiovascular risk. Thus, there is a need for cardiovascular risk stratification in patients with diabetes. The present panel reviews the best current evidence and proposes a practical risk-based approach on treatment for patients with diabetes. MAIN BODY: The Brazilian Diabetes Society, the Brazilian Society of Cardiology, and the Brazilian Endocrinology and Metabolism Society gathered to form an expert panel including 28 cardiologists and endocrinologists to review the best available evidence and to draft up-to-date an evidence-based guideline with practical recommendations for risk stratification and prevention of cardiovascular disease in diabetes. The guideline includes 59 recommendations covering: (1) the impact of new anti-hyperglycemic drugs and new lipid lowering drugs on cardiovascular risk; (2) a guide to statin use, including new definitions of LDL-cholesterol and in non-HDL-cholesterol targets; (3) evaluation of silent myocardial ischemia and subclinical atherosclerosis in patients with diabetes; (4) hypertension treatment; and (5) the use of antiplatelet therapy. CONCLUSIONS: Diabetes is a heterogeneous disease. Although cardiovascular risk is increased in most patients, those without risk factors or evidence of sub-clinical atherosclerosis are at a lower risk. Optimal management must rely on an approach that will cover both cardiovascular disease prevention in individuals in the highest risk as well as protection from overtreatment in those at lower risk. Thus, cardiovascular prevention strategies should be individualized according to cardiovascular risk while intensification of treatment should focus on those at higher risk.

Fatty acid and cholesterol concentrations in usually consumed fish in Brazil.

BACKGROUND: Several studies have demonstrated clinical benefits of fish consumption for the cardiovascular system. These effects are attributed to the increased amounts of polyunsaturated fatty acids in these foods. However, the concentrations of fatty acids may vary according to region. OBJECTIVE: The goal of this study was to determine the amount of,cholesterol and fatty acids in 10 Brazilian fishes and in a non-native farmed salmon usually consumed in Brazil. METHODS: The concentrations of cholesterol and fatty acids, especially omega-3, were determined in grilled fishes. Each fish sample was divided in 3 sub-samples (chops) and each one was extracted from the fish to minimize possible differences in muscle and fat contents. RESULTS: The largest cholesterol amount was found in white grouper (107.6 mg/100 g of fish) and the smallest in badejo (70 mg/100 g). Omega-3 amount varied from 0.01 g/100 g in badejo to 0.900 g/100 g in weakfish. Saturated fat varied from 0.687 g/100 g in seabass to 4.530 g/100 g in filhote. The salmon had the greatest concentration of polyunsaturated fats (3.29 g/100 g) and the highest content of monounsaturated was found in pescadinha (5.98 g/100 g). Whiting and boyfriend had the best omega-6/omega 3 ratios respectively 2.22 and 1.19, however these species showed very little amounts of omega-3. CONCLUSION: All studied Brazilian fishes and imported salmon have low amounts of saturated fat and most of them also have low amounts of omega-3.

Prevalence of Metabolic Syndrome and Framingham Risk Score in Apparently Healthy Vegetarian and Omnivorous Men / Prevalência de Síndrome Metabólica e Escore de Risco de Framingham em Homens Vegetarianos e Onívoros Aparentemente Saudáveis

Abstract Background: Recent studies have shown a lower prevalence of metabolic syndrome (MSyn) in vegetarians (VEG) despite the inconclusive evidence from others. Objective: To verify the association between diet and other lifestyle characteristics and the prevalence of MSyn, cardiovascular risk factors (CRF), and Framingham Risk Score (FRS) in apparently healthy VEG and omnivorous (OMN) men. Methods: In this cross-sectional study, 88 apparently healthy men ≥ 35 years, 44 VEG and 44 OMN, were assessed for anthropometric data, blood pressure, blood lipids, glucose, C-reactive protein (CRP) and FRS. To test the association between lifestyle and MSyn, Student t test, chi-square test, and multiple logistic regression model were used. A significance level of 5% was considered in all statistical analyses. Results: Several CRF were significantly lower in VEG than in OMN: body mass index, systolic blood pressure, diastolic blood pressure, fasting serum total cholesterol, LDL-cholesterol, apolipoprotein b, glucose, and glycated hemoglobin (all p < 0.05). The FRS mean was lower in VEG than in OMN (2.98 ± 3.7 vs 4.82 ± 4.8, p = 0.029). The percentage of individuals with MSyn was higher among OMN than among VEG (52.3 vs.15.9%) (p < 0.001). The OMN diet was associated with MSyn (OR: 6.28 95%CI 2.11-18.71) and alterations in most MSyn components in the multiple regression model independently of caloric intake, age and physical activity. Conclusion: The VEG diet was associated with lower CRF, FRS and percentage of individuals with MSyn.

Resumo Fundamento: Estudos recentes mostraram menor prevalência de Síndrome Metabólica (SM) em vegetarianos (VEG), apesar de evidências inconclusivas de outros. Objetivo: Verificar associação entre dieta e características do estilo de vida e a prevalência de SM, fatores de risco cardiovascular (FRCV) e Escore de Framingham (EF) em homens VEG e onívoros (ONI) aparentemente saudáveis. Métodos: Neste estudo transversal, 88 homens aparentemente saudáveis ≥ 35 anos, VEG (n = 44) e ONI (n = 44), foram avaliados quanto a dados antropométricos, pressão arterial, lípides plasmáticos, glicemia, proteína C reativa e EF. Para testar associação entre estilo de vida e SM, o teste t de Student, o teste qui-quadrado e a regressão logística múltipla foram utilizados. Foi considerado nível de significância de 5% em todas as análises estatísticas. Resultados: Os níveis dos FRCV avaliados foram menores nos VEG do que nos ONI: índice de massa corporal, pressão arterial sistólica e diastólica, colesterol total, LDL-colesterol, apolipoproteína b, glicemia e hemoglobina glicada (p < 0,05). O EF foi menor nos VEG do que nos ONI (2,98 ± 3,7 vs. 4,82 ± 4,8; p = 0,029). A porcentagem de indivíduos com SM foi maior entre ONI do que entre VEG (52,3 vs.15,9%) (p < 0,001). A dieta ONI foi associada com a SM (OR: 6,28 IC95% 2,11-18,71) e alterações na maioria dos componentes da SM no modelo de regressão logística múltipla, independentemente de ingestão calórica, idade e atividade física. Conclusão: A dieta VEG foi associada com menores taxas de FRC e menores EF e porcentagem de indivíduos com SM.

Diretriz brasileira baseada em evidências sobre prevenção de doenças cardiovasculares em pacientes com diabetes: posicionamento da Sociedade Brasileira de Diabetes (SBD), da Sociedade Brasileira de Cardiologia (SBC) e da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) / Brazilian evidence-based guideline on cardiovascular disease prevention in patients with diabetes: positioning of the Brazilian Society of Diabetes (SBD), the Brazilian Society of Cardiology (SBC) and the Brazilian Society of Endocrinology and Metabology (SBEM)

Resumo Fundamentação: desde o primeiro posicionamento da Sociedade Brasileira de Diabetes (SBD) sobre diabetes e prevenção cardiovascular, em 2014,1 importantes estudos têm sido publicados na área de prevenção cardiovascular e tratamento do diabetes,2 os quais contribuíram para a evolução na prevenção primária e secundária nos pacientes com diabetes. Ferramentas de estratificação de risco mais precisas, novos fármacos hipolipemiantes e novos antidiabéticos com efeitos cardiovasculares e redução da mortalidade, são parte desta nova abordagem para os pacientes com diabetes. O reconhecimento de que o diabetes é uma doença heterogênea foi fundamental, sendo claramente demonstrado que nem todos os pacientes diabéticos pertencem a categorias de risco alto ou muito alto. Um porcentual elevado é composto por pacientes jovens, sem os fatores de risco clássicos, os quais podem ser classificados adequadamente em categorias de risco intermediário ou mesmo em baixo risco cardiovascular. O presente posicionamento revisa as melhores evidências atualmente disponíveis e propõe uma abordagem prática, baseada em risco, para o tratamento de pacientes com diabetes. Estruturação: perante este desafio e reconhecendo a natureza multifacetada da doença, a SBD uniu-se à Sociedade Brasileira de Cardiologia (SBC) e à Sociedade Brasileira de Endocrinologia e Metabolismo (SBEM), e formou um painel de especialistas, constituído por 28 cardiologistas e endocrinologistas, para revisar as melhores evidências disponíveis e elaborar uma diretriz contendo recomendações práticas para a estratificação de risco e prevenção da Doença Cardiovascular (DVC) no Diabetes Melito (DM). As principais inovações incluem: (1) considerações do impacto de novos hipolipemiantes e das novas medicações antidiabéticas no risco cardiovascular; (2) uma abordagem prática, baseada em fator de risco, para orientar o uso das estatinas, incluindo novas definições das metas da Lipoproteína de Baixa Densidade-colesterol (LDL-colesterol) e colesterol não Lipoproteína de Alta Densidade HDL; (3) uma abordagem baseada em evidências, para avaliar a isquemia miocárdica silenciosa (IMS) e a aterosclerose subclínica em pacientes com diabetes; (4) as abordagens mais atuais para o tratamento da hipertensão; e (5) recomendação de atualizações para o uso de terapia antiplaquetária. Esperamos que esta diretriz auxilie os médicos no cuidado dedicado aos pacientes com diabetes. Métodos: inicialmente, os membros do painel foram divididos em sete subcomitês para definirem os tópicos principais que necessitavam de uma posição atualizada das sociedades. Os membros do painel pesquisaram e buscaram no PubMed estudos clínicos randomizados e metanálises de estudos clínicos e estudos observacionais de boa qualidade, publicados entre 1997 e 2017, usando termos MeSH: [diabetes], [diabetes tipo 2], [doença cardiovascular], [estratificação de risco cardiovascular] [doença arterial coronária], [rastreamento], [isquemia silenciosa], [estatinas], [hipertensão], [ácido acetilsalicílico]. Estudos observacionais de baixa qualidade, metanálises com alta heterogeneidade e estudos transversais não foram incluídos, embora talvez tenham impactado no Nível de Evidência indicado. A opinião de especialistas foi usada quando os resultados das buscas não eram satisfatórios para um item específico. É importante salientar que este posicionamento não teve a intenção de incluir uma revisão sistemática rigorosa. Um manuscrito preliminar, destacando recomendações de graus e níveis de evidência (Quadro 1), foi esboçado. Este passo levou a várias discussões entre os membros dos subcomitês, que revisaram os achados e fizeram novas sugestões. O manuscrito foi, então, revisto pelo autor líder, encarregado da padronização do texto e da inclusão de pequenas alterações, sendo submetido à apreciação mais detalhada pelos membros dos comitês, buscando uma posição de consenso. Depois desta fase, o manuscrito foi enviado para a banca editorial e edição final, sendo encaminhado para publicação. Quadro 1 Graus de recomendações e níveis de evidências adotados nesta revisão Grau de recomendação Classe I A evidência é conclusiva ou, se não, existe consenso de que o procedimento ou tratamento é seguro e eficaz Classe II Há evidências contraditórias ou opiniões divergentes sobre segurança, eficácia, ou utilidade do tratamento ou procedimento Classe IIa As opiniões são favoráveis ao tratamento ou procedimento. A maioria dos especialistas aprova Classe IIb A eficácia é bem menos estabelecida, e as opiniões são divergentes Classe III Há evidências ou consenso de que o tratamento ou procedimento não é útil, eficaz, ou pode ser prejudicial Níveis de Evidência A Múltiplos estudos clínicos randomizados concordantes e bem elaborados ou metanálises robustas de estudos clínicos randomizados B Dados de metanálises menos robustas, um único estudo clínico randomizado ou estudos observacionais C Opinião dos especialistas

Critérios diagnósticos e estratificação de risco na hipercolesterolemia familiar / Criteria diagnosis and risk stratification of familial hypercholesterolemia

A hipercolesterolemia familiar (HF) é uma doença genética relativamente comum caracterizada por níveis elevados de LDL-colesterol (LDL-C) e, por conseguinte, associada a risco de desenvolvimento prematuro de doença cardiovascular aterosclerótica. O tratamento hipolipemiante reduz significativamente o risco cardiovascular desses pacientes, tornando fundamental a identificação precoce desses indivíduos, seguida de tratamento adequado assim que possível. Para tanto, existem escores diagnósticos de HF, como o escore holandês Dutch Lipid Clinic Network, que avalia níveis de LDL-C, antecedente familiar e/ou pessoal de evento cardiovascular isquêmico e a presença de sinais físicos, como xantomas. Uma vez feito o diagnóstico de HF, torna-se muito importante a estratificação de risco desses pacientes. A identificação de fatores de risco associados (como tabagismo,diabetes mellitus, hipertensão arterial, aumento de Lp(a), entre outros) aliada ao uso de métodos para detecção de doença aterosclerótica subclínica em indivíduos com HF pode auxiliar na identificação daqueles que têm maior risco cardiovascular e são candidatos a estratégias mais agressivas de redução de LDL-C. Nesse artigo, revisamos os principais critérios diagnósticos de HF e a estratificação de risco desses pacientes

Familial hypercholesterolemia (FH) is a relatively common genetic disease that is characterized by elevated LDL-cholesterol (LDL-C) levels. As a consequence, it is associated with the risk of premature development of atherosclerotic cardiovascular disease.Lipid-lowering therapies significantly reduces the cardiovascular risk in these patients, making early identification of these individuals essential, followed by adequate treatment as soon as possible. There are diagnostic scores of FH for this purpose, such as the Dutch Lipid Clinic Network score, which evaluates LDL-C levels, family history and/or personal history of ischemic cardiovascular event and the presence of physical signs, such as xanthomas. Once FH has been diagnosed, it is very important to stratify the risk in these patients. The identification of associated risk factors (such as smoking, diabetes mellitus, high blood pressure, elevated Lp(a), among others), together with the use of methods to detect subclinical atherosclerotic disease in individuals with FH, can assist in the identification of those with a higher cardiovascular risk, and who are therefore candidates for more aggressive strategies to reduce LDL-C. This article gives a review of the main diagnostic criteria of FH, and the risk stratification in these patients

Fatty Acid and Cholesterol Concentrations in Usually Consumed Fish in Brazil / Concentração de Ácidos Graxos e Colesterol de Peixes Habitualmente Consumidos no Brasil

Background: Several studies have demonstrated clinical benefits of fish consumption for the cardiovascular system. These effects are attributed to the increased amounts of polyunsaturated fatty acids in these foods. However, the concentrations of fatty acids may vary according to region. Objective: The goal of this study was to determine the amount of,cholesterol and fatty acids in 10 Brazilian fishes and in a non-native farmed salmon usually consumed in Brazil. Methods: The concentrations of cholesterol and fatty acids, especially omega-3, were determined in grilled fishes. Each fish sample was divided in 3 sub-samples (chops) and each one was extracted from the fish to minimize possible differences in muscle and fat contents. Results: The largest cholesterol amount was found in white grouper (107.6 mg/100 g of fish) and the smallest in badejo (70 mg/100 g). Omega-3 amount varied from 0.01 g/100 g in badejo to 0.900 g/100 g in weakfish. Saturated fat varied from 0.687 g/100 g in seabass to 4.530 g/100 g in filhote. The salmon had the greatest concentration of polyunsaturated fats (3.29 g/100 g) and the highest content of monounsaturated was found in pescadinha (5.98 g/100 g). Whiting and boyfriend had the best omega-6/omega 3 ratios respectively 2.22 and 1.19, however these species showed very little amounts of omega-3. Conclusion: All studied Brazilian fishes and imported salmon have low amounts of saturated fat and most of them also have low amounts of omega-3. .

Fundamento: Inúmeros estudos demonstram os efeitos benéficos do consumo de peixe para o aparelho cardiovascular. Isso seria decorrente da presença de ácidos graxos poli-insaturados nesses alimentos. Contudo, as concentrações desses nutrientes podem variar conforme a região. Objetivo: Analisar a composição e a quantidade de colesterol e ácidos graxos de peixes brasileiros e do salmão de cativeiro, habitualmente consumidos em nosso meio. Métodos: Foi analisada a concentração de colesterol e ácidos graxos, particularmente o ômega-3, de 10 tipos diferentes de peixes grelhados, sendo um deles o salmão. Cada amostra foi composta por três subamostras (“postas”), e cada uma retirada de uma porção, do início, do meio e do final do peixe, com o objetivo de minimizar problemas com relação a possíveis diferenças entre as porções musculares e de gorduras. Resultados: O maior teor de colesterol encontrado foi no cherne (107,6 mg/100 g), e o menor foi no badejo (70 mg/100 g). A concentração de ômega-3 variou de 0,01 g/100 g no badejo a 0,900 g/100 g na pescadinha. Já a gordura saturada variou de 0,687 g/100 g no pirarucu a 4,530 g/100 g no filhote. O salmão apresentou a maior quantidade de gordura poli-insaturada (3,29 g/100 g), e a pescadinha, o maior teor de gordura monoinsaturada (5,98 g/100 g). Quando avaliada as relações ômega 6/3, as melhores foram as do badejo (2,22) e do namorado (1,19), no entanto essas espécies apresentam muito pouca quantidade de ômega-3. Conclusão: Todos os peixes brasileiros estudados e o salmão importado têm baixos teores de gordura saturada, contudo a maioria desses peixes também tem baixos teores de ômega-3. .

Oligonucleotídeos antisense para hipercolesterolemia e hipertrigliceridemia / Antisense oligonucleotide for hypercholesterolemia and hypertrigliceridemi

A hipercolesterolemia representa um dos principais fatores de risco para doença cardiovascular. Atualmente, as estatinas constituem a principal terapia farmacológica para seu tratamento. Contudo, existe um nicho de pacientes quemotivaram a busca por novas terapias hipolipemiantes: os intolerantes a estatinas e os pacientes com dislipidemias genéticas graves, sendo esse último grupo representado principalmente pela hipercolesterolemia familiar. Os oligonucleotídeos antisense são pequenas sequências de ácido nucleico de fita única que se ligam via hibridização de Watson-Crick no seu RNA complementar, levando à inibição da síntese da proteína que seria codificada por essa região do RNA. Atualmente, essa tecnologia está sendo utilizada para tratamento de diferentes doenças, inclusive das dislipidemias. A inibição da síntese da apolipoproteínaB com uso de oligonucleotídeo antisense (mipomersen) é uma realidade hoje em dia. Seu efeito se traduz na redução significativa do LDL-colesterol. O mipomersen faz parte do arsenal terapêutico aprovado pelo FDA para tratamento da hipercolesterolemia familiar homozigótica. Outras regiões proteicas das lipoproteínas, como apolipoproteína CIII e apolipoproteína(a), também são alvos de oligonucleotídeos antisense e podem representar novas medicações no combate a doença cardiovascular.

Hypercholesterolemia is a major risk factor for cardiovascular disease. Currently statins are the main pharmacological therapy for its treatment. However, there is a subgroup of patients who motivated the search for new lipid-lowering therapies: intolerant to statins and patients with severe genetic dyslipidemias, this last group represented primarily by familial hypercholesterolemia. Antisense oligonucleotides are short sequences of single-stranded nucleic acids which bind via Watson-Crick hybridization to its complementary RNA, leading to protein synthesis inhibition that would be encoded by this region of RNA.Currently this technology is used to treat various diseases including dyslipidemias. The inhibition of synthesis of apolipoprotein B with use of antisense oligonucleotide (mipomersen) is a reality today. Its effect is reflected insignificant reduction of LDL-cholesterol. The mipomersenis a medication approved by FDA for treatment of homozygous familial hypercholesterolemia. Other protein regions of lipoproteins such as apolipoprotein CIII and apolipoprotein(a) are also targets of antisense oligonucleotides and may represent new medications to reduce cardiovascular disease.

Tratamento atual das dislipidemias / Current treatment of dyslipidemia

A dislipidemia representa um dos principais fatores de risco para o desenvolvimento da aterosclerose. A identificação da etiologia da dislipidemia consiste em uma das principais etapas do seu manejo clínico. O tratamento deve levar em consideração a estratificação de risco cardiovascular de cada paciente: quanto maior o risco, maior o benefício de um tratamento mais intensivo. As maiores evidências de benefícios são vistas com a classe das estatinas. É importante considerar que a meta primária de tratamento deve ser focada no LDL-colesterol, exceto em casos extremos de triglicérides muito elevados, em que o risco de pancreatite deve ser levado em consideração e a redução de triglicérides deve ser prioritária. A elevação do HDL-colesterol deforma “artificial” por enquanto não apresenta benefício de forma robusta, porém novas medicações estão em estudo e podem trazer novas perspectivas nesse contexto.

Dyslipidemia is one of the main risk factors for the development of atherosclerosis. The identification of the etiology of dyslipidemia is one of the main steps of clinical management. The treatment should consider the stratification of cardiovascular risk for each patient: the higher the risk, the greater the benefit of a more intensive treatment. Statins are the drugs where the benefits for the treatment of dyslipidemia were stronger. The primary goal of treatment should be focused on LDL-cholesterol, except in cases of very high triglycerides, whose risk of associated pancreatitis should be taken into consideration and reduction of triglycerides should be the priority. Artificial elevation of HDL-cholesterol does not have shown reduction of cardiovascular disease, but new drugs are under study and can bring new perspectives in this regard.

Como avaliar atualmente risco de doença cardiovascular de forma adequada / How to currently evaluate cardiovascular disease risk appropriately

A doença cardiovascular é a principal causa de morbimortalidade no mundo. A prevenção de eventos cardiovasculares engloba a estratificação de risco cardiovascular. A estratificação de risco baseada apenas em escores clínicos pode ser insuficiente pra uma avaliação de risco mais precisa. A incorporação de novos biomarcadores, sejam laboratoriais ou de método de imagem, auxilia a otimizar a estratificação de risco intermediário. O "life time risk" pode auxiliar na estratificação de indivíduos considerados de baixo risco, mas com fatores de risco presentes. Dessa forma, dentro do possível, precisamos individualizar a estratificação de risco de cada paciente, a fim de torná-lo mais acurado possível.

Cardiovascular disease is the leading cause of morbidity and mortality worldwide. Prevention of cardiovascular events includes cardiovascular risk stratification . Risk stratification based only on clinical scores may be insufficient for a more accurate risk assessment. the incorporation of new biomarkers, either laboratory or imaging method, helps to optimize risk stratification, particularly in those initially classified as intermediate risk. The "life time risk" can aid in the stratification of individuals considered initially at low risk, but with risk factors. Thus, if possible, we need to individualize the risk stratification of each patient in order to make it accurate as possible.