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Introduction Familial hypercholesterolemia (FH) is a common genetic cause of premature coronary artery disease (CAD), especially myocardial infarction, related to lifetime exposure to high concentrations of low-density lipoprotein cholesterol (LDL-C). It is a severe form of genetic dyslipidemia in which approximately 85% of men and 50% of women may experience a coronary event before 65 years of age if not properly treated. FH is considered a public health problem because of the high prevalence (approximately 1:200-300 in the general population) [...]

Introduction: Familial hypercholesterolemia (FH) is associated with early onset of cardiovascular disease (CVD) and mortality. Lipid lowering treatment (LLT) may change the natural history of FH, however there is scant information about elderly individuals (older than 60 years) with FH. This study describes characteristics of elderly FH individuals presenting or not CVD. Hypothesis: Monogenic defects are important markers of CVD risk and initiation and long-term use of lipid lowering therapy (LLT) is relevant to minimize this risk. Methods: Cross-sectional analysis of clinical and laboratory of molecularly proven elderly FH (FH+) and non-affected (FH-) individuals attending a cascade screening program. FH+ were divided in those presenting or not CVD (defined as previous myocardial infarction or ischemic stroke, carotid or coronary revascularization and angina with stenosis ≥50% on angiography). Results: From 4,111 genotyped individuals, 462 (11.2%) elders were included (198 FH+ and 264 FH-). There was predominance of females in either groups, however with more men in FH+ 37.4% vs. 24.2%, p=0.002. No differences were seen between FH+ and FH- regarding age, [median (%25;75%)] 66 (62;71) and 66 (63;71) years, p=0.68; use of LLT 88.5% vs. 91.5%, p=0.29 and high intensity LLT 61.7 % vs. 55.8%, p=0.20, respectively. Despite longer LLT duration in FH+ 11(7;20) vs. 7 (3;13) years, p Conclusions: The genetic diagnosis of FH was associated with higher rates of CVD and early CVD vs. FH- hypercholesterolemics. Elders with FH+ who survived despite late LLT initiation have a worse CVD history than FH- elders, emphasizing the relevance of a monogenic defect as cause of long-lasting hypercholesterolemia and CVD risk, particularly in men.

Introduction: Familial hypercholesterolemia (FH) is characterized by premature atherosclerosis (ATH). Coronary calcium score (CAC) reflects coronary plaque burden. Lipoprotein(a) [Lp(a)] increases ATH risk in FH. Little is known about the association of CAC and Lp(a) in heterozygous FH. Hypothesis: Lp(a) could be associated with CAC presence in HeFH independently of LDL-c and age. Methods: Molecularly confirmed primary prevention FH individuals that were submitted to CAC and Lp(a) evaluation were included. LDL-c was corrected by Lp(a)-cholesterol. Binary logistic regression analysis with CAC presence as dependent variable was used to evaluate determinants of CAC. Spearman correlation and area under ROC curve (AUC) were calculated for Lp(a) discrimination of CAC presence. Results: We included 217 FH [65.4% female, 43.9±13.6 years, LDL-c 237±76 mg/dL, median Lp(a) 29 mg/dL (interquartile range: 53)]. CAC was present in 98 (45.1%) individuals. In univariate analysis CAC associated with (OR, 95%CI): age (1.09, 1.062-1.120, p Conclusions: Lp(a) is weakly correlated to CAC in FH and the association of LDL-c and Lp(a) with CAC is different according to Lp(a) levels. This suggests that Lp(a) may not be associated with plaque burden in FH.

Severe hypertriglyceridemia (HTG) is a rare condition defined as fasting triglyceride (TG) levels >885 mg/dL. Besides the association between mild-moderate HTG and cardiovascular disease (CVD), severe HTG is a known risk factor for acute pancreatitis (AP). The factors predisposing patients with severe HTG to AP are not completely clear. Purpose Compare patients with severe HTG with and without AP and identify factors predisposing to AP. Methods We performed a retrospective search of patients with severe, refractory HTG in our hospital database over the last 10 years. Inclusion criteria: at least one TG≥2,000mg/dL and the latest on-therapy TG≥1,000mg/dL. Results From 692 patients with at least one TG≥1,000 mg/dL, 27 met the inclusion criteria. Nineteen (70%) were male, mean age 53±14 y-old. The median maximum TG value was 3,384mg/dL and the latest on-therapy TG was 1,791 mg/dL despite fibrate use; 70,4% were diabetics (44% insulin users; 41% had previous CVD). Patients with AP were younger, with higher fasting glucose and lower HDL-C. However, there were no differences between the AP and no AP groups, regarding maximum and latest TG, diagnosis of diabetes and treated HbA1C. Conclusion In this cohort of patients with severe, refractory HTG, those with AP were significantly younger, suggesting a greater genetic role for HTG in this group. There were no other relevant diferences between the AP and no AP groups. Conceivably, other unrecognized factors were at play accounting for the AP events. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Zerbini Foundation, FAPESP (The The São Paulo Research Foundation)

Made available in DSpace on 2018-12-11T17:20:49Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-05-01. Added 1 bitstream(s) on 2019-10-09T18:31:47Z : No. of bitstreams: 1 S0066-782X2018000500430.pdf: 320822 bytes, checksum: b0ab9929be9bf6e13d602b9291e13418 (MD5) 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. (Arq Bras Cardiol. 2018; 110(5):430-437). Instituto do Coração (InCor)-Faculdade de Medicina da Universidade de São Paulo Hospital Regional de Ferraz de Vasconcelos-Osiris Florindo Departamento de Farmacologia do Instituto de Biociências de Botucatu Universidade Estadual Paulista (UNESP) Departamento de Farmacologia do Instituto de Biociências de Botucatu Universidade Estadual Paulista (UNESP)

Background and aims There is controversy on the accuracy of different diagnostic criteria for familial hypercholesterolemia (FH). The aim of this study is to assess the performance of different clinical criteria used to identify individuals for FH genetic cascade screening in Brazil. Methods All index cases (IC) registered in the Hipercol Brasil program between 2011 and 2016 were analyzed. Inclusion criteria were age ≥18 years and elevated LDL-cholesterol (LDL-C) levels, with a conclusive result in the genetic test, whether positive or negative. Initially, we tested the multivariable association between clinical and laboratory markers and the presence of an FH causing mutation. Then, we analyzed sensitivity, specificity, positive and negative predictive values for the LDL-C quartile distribution, LDL-C as a continuous variable, as well as the performance measures for the Dutch Lipid Clinic Network (DLCN) score to identify a mutation. Results Overall, 753 ICs were included and an FH causing mutation was found in 34% (n = 257) of the subjects. After multivariable analysis, LDL-C as a continuous variable, tendon xanthomas and corneal arcus were independently associated with the presence of FH mutations. LDL-C values ≥ 230 mg/dL (5.9 mmol/L) had the best tradeoff between sensitivity and specificity to diagnose a mutation. The DLCN score presented a better performance than LDL-C to identify a mutation, area under the ROC curve were 0.744 (95% CI: 0.704–0.784) and 0.730 (95% CI: 0.687–0.774), respectively, p=0.014. Conclusions In our population, LDL ≥230 mg/dL is a feasible criterion to indicate ICs to genetic testing.

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.

Heterozygous familial hypercholesterolemia (HeFH), an autosomal dominant genetic disorder affecting nearly 1 in 250 individuals, is a major cause of premature atherosclerotic cardiovascular disease (ASCVD) ([1][1]). In the absence of treatment, patients with HeFH manifest a nearly 20-fold higher

Background Familial hypercholesterolemia (FH) is a genetic disorder associated with high risk of early major cardiovascular events (MACE) that can impact on elderly's self-appraisal of health-related quality of life (HRQoL), however, this association is unclear. Purpose This study evaluated HRQoL of elder individuals (from 60 to 88 years old), index cases (IC) and first-degree relatives (FDR) at high risk of FH. Methods From 1030 participants of FH genetic cascade screening, 250 were ≥60 and 205 were eligible for this study. Data collection was performed before awareness of molecular diagnosis results. Individuals were divided into 4 groups according to molecular diagnosis: IC with (IC+) and without (IC-) identified mutations (n=38 and n=54, respectively), and their affected (FDR+, n=74) and non-affected (FDR-, n=39) FDR. HRQoL measurements, mental (MCS) and physical component (PCS) scores, were carried out with the SF-12 questionnaire. Associations were tested by multivariate models. Results The mean age was 68±7 years, 32.2% were men, MACE had occurred in 47.8%. HRQoL dimensions measure (variance of physical, mental and health quality component scores) did not differ between FH and non-FH individuals. Lower PCS were associated with female sex (p=0.043), lower education (p=0.047), previous MACE occurrence (p Conclusion HRQol in elder suspected FH individuals relates more to a consequence of elevated cholesterol levels i.e. MACE and co-morbidities rather than molecular defects or pharmacological treatment.

Introduction Familial hypercholesterolemia (FH) is characterized by elevated levels of LDL-C and early cardiovascular disease (CVD). However, the risk of CVD in HF is variable. The Montreal score was designed to stratify cardiovascular risk in the FH population. Coronary calcium score (CAC) is a tool that can be used to optimize CVD risk assessment in FH. Purpose The objective of this study is to evaluate whether CAC is superior to the Montreal score in cardiovascular risk discrimination in FH. Methods We Included 206 patients with molecular diagnosis of FH (36.4% men, mean age 45±14 years, mean baseline LDL-C: 269±70 mg/dL). All patients underwent CAC and were treated with maximum tolerated statin therapy. We evaluated cardiovascular risk factors and calculated Montreal score as prior publication. Cox regression analysis was performed to test the association of CAC with the incidence of cardiovascular events. CAC was transformed into LogCAC + 1 to optimize the distribution of the CAC as previously described. Area under the ROC curve was calculated for Montreal score and CAC. Results Patients were followed by a median of 3.7 years (interquartile range: 2.7 to 6.8 years). Mean Montreal score was 22±8, median of 22. CAC was positive in 105 individuals (51%) and 15 CVD events (7.2%) had occurred. Montreal score above the median was associated with CAC (OR: 8.36, 95% CI: 4.47–15.62, p100: 17±7, 23±7, 30±4, p Conclusion The Montreal score is associated with CAC in FH, however CAC is superior than this clinical score in predicting the occurrence of CVD in FH.

Aims The objective of this study was to evaluate if vascular age derived from coronary artery calcium (CAC) score improves atherosclerosis cardiovascular disease (ASCVD) risk discrimination in primary prevention asymptomatic heterozygous familial hypercholesterolaemia (FH) patients undergoing standard lipid-lowering therapy. Methods and results Two hundred and six molecularly confirmed FH individuals (age 45 ± 14 years, 36% males, baseline LDL-cholesterol 6.2 ± 2.2 mmol/L; 239 ± 85mg/dL) were followed by 4.4 ± 2.9 years (median: 3.7 years, interquartile ranges 2.7–6.8). CAC measurement was performed, and lipid-lowering therapy was optimized according to FH guidelines. Vascular age was derived from CAC and calculated according to the Multi Ethnic Study of Atherosclerosis algorithm. Risk estimation based on the Framingham equations was calculated for both biological (bFRS) and vascular (vaFRS) age. During follow-up, 15 ASCVD events (7.2%) were documented. The annualized rate of events for bFRS 20% was respectively: 8.45 [95% confidence interval (CI) 3.17–22.52], 23.28 (95% CI 9.69–55.94), and 28.13 (95% CI 12.63–62.61) per 1000 patients. The annualized rate of events for vaFRS 20% was respectively: 0, 0, and 50.37 (95% CI 30.37–83.56) per 1000 patients. vaFRS presented a better discrimination for ASCVD events compared to bFRS 0.7058 (95% CI 0.5866–0.8250) vs. vaFRS 0.8820 (95% CI 0.8286–0.9355), P = 0.0005. Conclusion CAC derived vascular age can improve ASCVD risk discrimination in primary prevention FH subjects. This tool may help further stratify risk in FH patients already receiving lipid-lowering medication who might be candidates for further treatment with newer therapies.

Introducao A doenca cardiovascular (DCV) e a principal causa de morte no Brasil e no mundo, determinando aumento da morbidade e incapacidade ajustadas pelos anos de vida. Embora as taxas de mortalidade e disability-adjusted life year (DALY) padronizadas por idade estejam diminuindo no Brasil, possivelmente como resultado de politicas de saude bem-sucedidas, o numero total destas esta aumentando principalmente devido ao envelhecimento e adoecimento da populacao. A presenca dos fatores de risco classicos (hipertensao, dislipidemia, obesidade, sedentarismo, tabagismo, diabetes e [...]

Objectives The aim of this study was to evaluate the role of coronary artery calcium (CAC) as a predictor of atherosclerotic cardiovascular disease (ASCVD) (fatal or not myocardial infarction, stroke, unstable angina requiring revascularization, and elective myocardial revascularization) events in asymptomatic primary prevention molecularly proven heterozygous familial hypercholesterolemia (FH) subjects receiving standard lipid-lowering therapy. Background FH is associated with premature ASCVD. However, the clinical course of ASCVD in subjects with FH is heterogeneous. CAC score, a marker of subclinical atherosclerosis burden, may optimize ASCVD risk stratification in FH. Methods Subjects with FH underwent CAC measurement and were followed prospectively. The association of CAC with ASCVD was evaluated using multivariate analysis. Results A total of 206 subjects (mean age 45 ± 14 years, 36.4% men, baseline and on-treatment low-density lipoprotein cholesterol 269 ± 70 mg/dl and 150 ± 56 mg/dl, respectively) were followed for a median of 3.7 years (interquartile range: 2.7 to 6.8 years). CAC was present in 105 (51%), and 15 ASCVD events (7.2%) were documented. Almost half of events were hard outcomes, and the others were elective myocardial revascularizations. The annualized rates of events per 1,000 patients for CAC scores of 0 (n = 101 [49%]), 1 to 100 (n = 62 [30%]) and >100 (n = 43 [21%]) were, respectively, 0, 26.4 (95% confidence interval: 12.9 to 51.8), and 44.1 (95% confidence interval, 26.0 to 104.1). In multivariate Cox regression analysis, log(CAC score + 1) was independently associated with incident ASCVD events (hazard ratio: 3.33; 95% CI: 1.635 to 6.790; p = 0.001). Conclusions CAC was independently associated with ASCVD events in patients with FH receiving standard lipid-lowering therapy. This may help further stratify near-term risk in patients who might be candidates for further treatment with newer therapies.

Familial hypercholesterolemia (FH) is a genetic disorder associated with high cardiovascular burden of disease. FH prevalence may vary widely across populations and data in race/ethnically diverse and admixed populations is scarce. ELSA-Brasil epidemiology may be widely generalizable in this regard, and we calculated the ELSA-Brasil FH prevalence and its variation according to age, sex and race/ethnicity.In 14,460 individuals aged from 35 to 75 years from the ELSA-Brasil cohort baseline, we classified FH according to the Dutch Lipid Clinic Network criteria score ≥6 (probable and definite FH). LDL-C levels were adjusted for statin use. We calculated the overall ELSA-Brasil FH prevalence and the weighted prevalence for age, sex and race/ethnic categories. We extrapolated those frequencies to the Brazilian population weighting for age-sex-race/ethnicity according to the 2015 Statistics and Geography Brazilian Institute survey.The overall FH prevalence per 1000 individuals in ELSA-Brasil was 3.8 (2.9, 4.9) or 1 in 263. The age/sex/race-ethnicity-weighted FH prevalences were: male, 3.0 (1.7, 4.4) or 1 in 333; female, 4.1 (3.0, 5.2) or 1 in 244 (p0.001). White race prevalence was 2.4 (1.9, 3.0) or 1 in 417; Brown, 4.9 (4.0, 5.9) or 1 in 204; and Black 6.4 (41.1, 8.7) or 1 in 156 (p0.001). The weighted extrapolation for the Brazilian population derived similar magnitude frequencies.FH affects 1 in 263 in ELSA-Brasil and affects disproportionally more Brown (1 in 204), and Black (1 in 156), than White (1 in 417). Weighted extrapolation for the Brazilian population derived similar magnitude frequencies.

Familial hypercholesterolemia is characterized by elevated plasma cholesterol and early coronary arterial disease onset. However, few studies investigated the association of heterozygous familial hypercholesterolemia with peripheral arterial disease.In a cross sectional study 202 heterozygous familial hypercholesterolemia patients (91% confirmed by molecular diagnosis) were compared to 524 normolipidemic controls. Peripheral arterial disease was diagnosed by ankle-brachial index values ≤0.90.Compared with controls, familial hypercholesterolemia patients were older, more often female, with higher rates of hypertension, diabetes, previous coronary disease and higher total cholesterol levels. Smoking (previous and former) was more common among controls. The prevalence of peripheral arterial disease was 17.3 and 2.3% respectively in familial hypercholesterolemia and controls (p0.001). Results persisted after matching familial hypercholesterolemia and controls by a propensity score. Regression analyses demonstrated that age (odds ratio- OR = 1.03 95% CI 1.00-1.05, p = 0.033), previous cardiovascular disease (OR = 3.12 CI 95% 1.56-6.25, p = 0.001) and familial hypercholesterolemia diagnosis (OR = 5.55 CI 95% 2.69-11.44, p0.001) were independently associated with peripheral arterial disease. Among familial hypercholesterolemia patients, age (OR 1.05, 95% CI 1.02-1.09, p = 0.005), intermittent claudication (OR 6.32, 95% CI 2.60-15.33, p0.001) and smoking (OR 2.44, 95% CI 1.08-5.52, p = 0.032) were associated with peripheral arterial disease.Peripheral arterial disease is more frequent in familial hypercholesterolemia than in normolipidemic subjects and it should routine screened in these individuals even if asymptomatic. However, its role as predictor of cardiovascular events needs to be ascertained prospectively.

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.

BACKGROUND AND AIMS Familial hypercholesterolemia (FH) is a genetic disorder associated with high risk of early major cardiovascular events (MACE) that can impact the health related quality of life (HRQoL), however, this association is unclear. This study evaluated HRQoL in index cases (IC) and first-degree relatives (FDR) of individuals at high risk of FH undergoing genetic cascade screening. METHODS Data collection was performed before awareness of molecular diagnosis results. Individuals were divided into four groups according to the molecular diagnosis: IC with (IC+) and without (IC-) identified mutations (n = 93 and n = 175, respectively), and affected (FDR+, n = 231) and non-affected (FDR-, n = 159) FDR of IC+. HRQoL measurements, mental (MCS) and physical component (PCS) scores were carried out with SF-12 questionnaire. Associations were tested by generalized linear models. RESULTS The mean age was 49 ± 15 years, 42.2% were men, MACE had occurred in 30.7%. Overall, both PCS and MCS did not differ between FH and non-FH individuals, however, IC trended to have lower PCS independent of FH presence (p=0.003). Lower PCS were associated with female sex (p=0.018), lower education (p

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

MENSAGEM DOS COORDENADORES Departamento de Aterosclerose da Sociedade Brasileira de Cardiologia (SBC), acompanhando o amplo cenario de publicacoes cientificas sobre o tratamento das dislipidemias e prevencao da aterosclerose, bem como a importância de seu impacto sobre o risco cardiovascular, e reconhecendo a necessidade de atualizacao de sua ultima diretriz, publicada em 2013, em conformidade com as recomendacoes da SBC, reuniu um comite de especialistas, da clinica e do laboratorio clinico, a partir de janeiro de 2016, para a elaboracao deste [...]

To evaluate functional and compositional properties of HDL in subjects from a kindred of genetic apoA-I deficiency, two homozygotes and six heterozygotes, with a nonsense mutation at APOA1 codon -2, Q[-2]X, were recruited together with age- and sex-matched healthy controls (n = 11). Homozygotes displayed undetectable plasma levels of apoA-I and reduced levels of HDL-cholesterol (HDL-C) and apoC-III (5.4% and 42.6% of controls, respectively). Heterozygotes displayed low HDL-C (21 ± 9 mg/dl), low apoA-I (79 ± 24 mg/dl), normal LDL-cholesterol (132 ± 25 mg/dl), and elevated TG (130 ± 45 mg/dl) levels. Cholesterol efflux capacity of ultracentrifugally isolated HDL subpopulations was reduced (up to -25%, P < 0.01, on a glycerophospholipid [GP] basis) in heterozygotes versus controls. Small, dense HDL3 and total HDL from heterozygotes exhibited diminished antioxidative activity (up to -48%, P < 0.001 on a total mass basis) versus controls. HDL subpopulations from both homozygotes and heterozygotes displayed altered chemical composition, with depletion in apoA-I, GP, and cholesteryl ester; enrichment in apoA-II, free cholesterol, and TG; and altered phosphosphingolipidome. The defective atheroprotective activities of HDL were correlated with altered lipid and apo composition. These data reveal that atheroprotective activities of HDL particles are impaired in homozygous and heterozygous apoA-I deficiency and are intimately related to marked alterations in protein and lipid composition.

Statin-Associated Autoimmune Myopathy (SAAM) is an exceptionally rare condition with an estimated prevalence of 2 or 3 in 100,000 patients treated with statins. The mechanisms underlying the development of 3-hydroxy-3-methyl-glutaryl-CoA reductase autoimmunity remain unknown. A 61-year-old man

Heterozygous familial hypercholesterolemia (FH) is characterized by high LDL cholesterol levels and premature coronary heart disease onset. Nonetheless, the course of coronary disease events in heterozygous FH subjects is variable. The presence and severity of subclinical atherosclerosis predicts cardiovascular event onset and may help reclassify the risk of clinical events in the general population. In this review, we discuss the possible use of subclinical coronary, carotid and aortic atherosclerosis testing in heterozygous FH subjects for cardiovascular risk stratification and treatment. Many FH subjects present an increased and precocious burden of subclinical vascular disease in comparison to normolipidemic subjects. These subjects may be at higher risk of cardiovascular events and might deserve more aggressive lipid-lowering treatment. Nevertheless, routine screening of imaging biomarkers for FH subjects in clinical practice remains to be determined in prospective trials.

Achilles tendon xanthomas (ATX) are a sign of long-term exposure to high blood cholesterol in familial hypercholesterolemia (FH) patients, which have been associated with cardiovascular disease. We evaluated the ATX association with the presence and extent of subclinical coronary atherosclerosis in heterozygous FH patients.102 FH patients diagnosed by US-MEDPED criteria (67% with genetically proven FH), with median LDL-C 279 mg/dL (interquartile range: 240; 313), asymptomatic for cardiovascular disease, underwent computed tomography angiography and coronary artery calcium (CAC) quantification. Subclinical coronary atherosclerosis was quantified by CAC, segment-stenosis (SSS) and segment-involvement (SIS) scores. Adjusted Poisson regression was used to assess the association of ATX with subclinical atherosclerosis burden as continuous variables.Patients with ATX (n = 21, 21%) had higher LDL-C and lipoprotein(a) [Lp(a)] concentrations as well as greater CAC scores, SIS and SSS (p 0.05). After adjusting for age, sex, smoking, hypertension, previous statin use, HDL-C, LDL-C and Lp(a) concentrations, there was an independent positive association of ATX presence with CAC scores (β = 1.017, p 0.001), SSS (β = 0.809, p 0.001) and SIS (β = 0.640, p 0.001).ATX are independently associated with the extension of subclinical coronary atherosclerosis quantified by tomographic scores in FH patients.

The ankle-brachial index (ABI) is a marker of subclinical atherosclerosis related to health-adverse outcomes. ABI is inexpensive compared to other indexes, such as coronary calcium score and determination of carotid artery intima-media thickness (IMT). Our objective was to identify how the ABI can be applied to primary care. Three different methods of calculating the ABI were compared among 13,921 men and women aged 35 to 74 years who were free of cardiovascular diseases and enrolled in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). The ABI ratio had the same denominator for the three categories created (the highest value for arm systolic blood pressure), and the numerator was based on the four readings for leg systolic blood pressure: the highest (ABI-HIGH), the mean (ABI-MEAN), and the lowest (ABI-LOW). The cut-off for analysis was ABI20% without the inclusion of ABI

Visceral abdominal fat has been associated to cardiovascular risk factors and coronary artery disease (CAD). Computed tomography (CT) coronary angiography is an emerging technology allowing detection of both obstructive and nonobstructive CAD adding information to clinical risk stratification. The aim of this study was to evaluate the association between CAD and adiposity measurements assessed clinically and by CT. We prospectively evaluated 125 consecutive subjects (57% men, age 56.0+/-12 years) referred to perform CT angiography. Clinical and laboratory variables were determined and CT angiography and abdominal CT were performed in a 64-slice scanner. CAD was defined as any plaque calcified or not detected by CT angiography. Visceral and subcutaneous adiposity areas were determined at different intervertebral levels. CT angiography detected CAD in 70 (56%) subjects, and no association was found with usual anthropometric adiposity measurements (waist and hip circumferences and body mass index). Otherwise, CT visceral fat areas (VFA) were significantly related to CAD. VFA T12-L1 values > or =145cm(2) had an odds ratio of 2.85 (95% CI 1.30-6.26) and VFA L4-L5 > or =150cm(2) had a 2.87-fold (95% CI 1.31-6.30) CAD risk. The multivariate analysis determined age and VFA T12-L1 as the only independent variables associated to CAD. Visceral fat assessed by CT is an independent marker of CAD determined by CT angiography.

Despite the cardiovascular benefit of statin therapy in primary and secondary prevention, introduction of statin may be challenging when baseline serum liver enzymes (LE) are elevated. A primary prevention 62 y-old obese woman with high LDL-C, hypertension and diabetes, presented with LE > 3x upper

There is heterogeneity on the risk of cardiovascular disease (CVD) in Familial hypercholesterolemia (FH). We tested whether coronary artery calcification (CAC) improves CVD risk stratification in FH. 207 consecutive molecularly proven asymptomatic FH patients (36% men, age 49.2±14.1 years

Our purpose is to provide a framework for diagnosing the inherited causes of marked high-density lipoprotein (HDL) deficiency (HDL cholesterol levels

Mailing address: Marcio Hiroshi Miname • Rua Guimaraes Passos, 738 – 04107-031 – Sao Paulo, SP Brazil E-mail: marciominame@cardiol.br Manuscript received August 7, 2006; revised received January 23, 2007; accepted February 16, 2007.

Obesity is a public health concern associated with comorbidities like dyslipidemia, type 2 diabetes mellitus, systemic hypertension, obstructive sleep apnea, a low-grade pro inflammatory state and non-alcoholic fatty liver disease (NAFLD) [1]. A recent survey from the US National Health and Nutrition Examination (NHANES) show that 34.9% of adults were obese between 2011 and 2012 [2]. This same survey shows that obesity starts early in younger ages: 8.1% of infants and toddlers had an elevated weight for their length and 16.9% of 2e19 years old were indeed obese [2]. Obesity is the major risk factor for the development of NAFLD. NAFLD is defined by the accumulation of liver fat >5% per liver weight, in the presence of

Background: There is little knowledge about familial hypercholesterolemia in Brazil. This study presents the first results of genetic cascade screening performed in the city of Sao Paulo. Material and methods: Two-hundred and forty-eight suspected index cases were initially included. DNA was extracted from peripheral blood and the complete coding sequence of low-density lipoprotein receptor, exon 7 of proprotein convertase subtilisin/kexin type 9 gene and part of exon 26 of apolipoprotein B genes were sequenced. Multiplex Ligation-dependent Probe Amplification was performed on cases where a causal mutation was not identified through sequencing. After the identification of a causal mutation screening in first-degree relatives was pursued. Results: From 248 index cases, a mutation was found in 125 individuals (50.4%). 394 relatives were included in the cascade screening program and a mutation was identified in 59.4%. Seventy different causal mutations in the low-density lipoprotein receptor gene (97.2%) and 2 in the apolipoprotein B gene (2.8%) were found. No mutations were encountered in the proprotein convertase subtilisin/kexin type 9 gene. Mutations in exons 14 and 4 were the most prevalent and, 10 cases of true homozygotes (8 index cases and 2 relatives) and 1 compound heterozygote were identified. The most frequent mutation found was of Lebanese origin, the p.(Cys681*) mutation in exon 14 (8.5%). Conclusion: Genetic familial hypercholesterolemia cascade screening is feasible in Brazil and leads to identification of a mutation in approximately half of the index cases with higher rates of success in their relatives.

Background: Postprandial triglycerides (TG) are associated with severe coronary artery disease (CAD), though the underlying mechanisms remain unclear. In this study, we have investigated the effect of clinical and laboratory parameters on the association between postprandial TG and CAD detected by coronary computed tomographic angiography (CTA). Methods: We enrolled 130 patients without previous diagnosis of CAD, (85 with CAD detected by CTA and 45 without); who underwent an oral fat tolerance test. We studied the postprandial lipemia measuring TG from time 0h, 2h, 4h and 6h to analyze the TG change over time. We used a longitudinal multivariable linear mixed effects model with the log of the TG (lnTG) as the primary outcome due to non normal distribution of TG. To evaluate the effect of the other parameters on the longitudinal changes in the TG, each variable has been individually included in the model to evaluate for changes in the lnTG over time. Results: Patients with CAD were older (56.5 ± 6.8 vs 50.4 ± 7.1 years, p Conclusion: Patients with CAD had an impaired postprandial metabolism, due to a delayed TG clearance. This association was partially explained by the lower fasting HDL-C. Thus, the contribution of postprandial TG metabolism to the development of CAD, may be partially, related to the low fasting HDL-C concentrations.

Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by an elevation in the serum levels of total cholesterol and of low-density lipoproteins (LDL- c). Known to be closely related to the atherosclerotic process, FH can determine the development of early obstructive lesions in different arterial beds. In this context, FH has also been proposed to be a risk factor for peripheral arterial disease (PAD). Objective: This observational cross-sectional study assessed the association of PAD with other manifestations of cardiovascular disease (CVD), such as coronary artery and cerebrovascular disease, in patients with heterozygous FH. Methods: The diagnosis of PAD was established by ankle-brachial index (ABI) values ≤ 0.90. This study assessed 202 patients (35% of men) with heterozygous FH (90.6% with LDL receptor mutations), mean age of 51 ± 14 years and total cholesterol levels of 342 ± 86 mg /dL. Results: The prevalences of PAD and previous CVD were 17% and 28.2 %, respectively. On multivariate analysis, an independent association between CVD and the diagnosis of PAD was observed (OR = 2.50; 95% CI: 1.004 - 6.230; p = 0.049). Conclusion: Systematic screening for PAD by use of ABI is feasible to assess patients with FH, and it might indicate an increased risk for CVD. However, further studies are required to determine the role of ABI as a tool to assess the cardiovascular risk of those patients.

Background: Studies have demonstrated the association of severe anatomical coronary artery disease (CAD) with postprandial triglycerides (TG) concentrations. Nevertheless the relationship between less severe atherosclerosis plaque burden and postprandial TG is less established. Objective: to study the relationship between postprandial TG and CAD detected by coronary computed tomographic angiography (CTA). Material and methods: 130 patients who underwent an oral fat tolerance test were enrolled (85 with CAD detected by CTA and 45 without). Postprandial lipemia was studied by measuring TG from T0h to T6h with 2-h intervals, and analyzed the TG change over time using a longitudinal multivariable linear mixed effects model with the log normal of the TG as the primary outcome. Results: The majority of individuals with CAD had non-obstructive disease (63.3%) Patients with CAD had a slower clearance of postprandial TG change from 4 h to 6 h (p < 0.05) compared to patients without CAD. These results remained significant after adjustment for fasting TG and glucose, age, gender, body mass index, and waist circumference. However, those differences did not reach statistical significance after adjustment for fasting HDL-C. Conclusion: Patients with mild (

[Figure][1] An asymptomatic 20-year-old man presented with a history of high plasma cholesterol levels and gigantic tendinous xanthomas over the extensor tendons of his metacarpophalangeal joints and patellas (A to C) . Laboratory tests showed total cholesterol of 785 mg/dl, low-density

Objective In familial hypercholesterolemia (FH), the metabolism and anti-atherogenic functions of HDL can be affected by the continuous interactions with excess LDL amounts. Here, lipid transfers to HDL, an important step for HDL intravascular metabolism and for HDL role in reverse cholesterol transport (RCT) were investigated in FH patients. Methods Seventy-one FH patients (39 ± 15 years, LDL-cholesterol = 274 ± 101; HDL-cholesterol = 50 ± 14 mg/dl) and 66 normolipidemic subjects (NL) (38 ± 11 years, LDL-cholesterol = 105 ± 27; HDL-cholesterol = 52 ± 12 mg/dl) were studied. In vitro, lipid transfers were evaluated by incubation of plasma samples (37 °C, 1 h) with a donor lipid nanoemulsion labeled with 3H-triglycerides (TG) and 14C-unesterified cholesterol (UC) or with 3H-cholesteryl ester (EC) and 14C-phospholipids (PL). Radioactivity was counted at the HDL fraction after chemical precipitation of apolipoprotein (apo) B-containing lipoproteins and the nanoemulsion. Data are % of total radioactivity measured in the HDL fraction. Results Transfer of UC to HDL was lower in FH than in NL (5.6 ± 2.1 vs 6.7 ± 2.0%, p = 0.0005) whereas TG (5.5 ± 3.1 vs 3.7 ± 0.9%, p = 0.018) and PL (20.9 ± 4.6 vs 18.2 ± 3.7 %, p = 0.023) transfers were higher in FH. EC transfer was equal. By multivariate analysis, transfers of all four lipids correlated with HDL-cholesterol and with apo A-I. Conclusion FH elicited marked changes in three of the four tested lipid transfers to HDL. The entry of UC into HDL for subsequent esterification is an important driving force for RCT and reduction of UC transfer to HDL was previously associated to precocious coronary heart disease. Therefore, in FH, HDL functions can be lessened, which can also contribute to atherogenesis.

Background: Hypercholesterolemia induces early microcirculatory functional and structural alterations that are reversible by cholesterol reduction. Real time myocardial contrast echocardiography (RTMCE) and vascular ultrasound evaluate the effects of hyperlipidemia on peripheral and central blood flow reserve. This study investigated the effects of lipid-lowering therapy on coronary and peripheral artery circulation in patients with familial hypercholesterolemia (FH). Methods: RTMCE and vascular ultrasound were performed in 10 healthy volunteers (validation group) at baseline and after 12-week clinical observation, and in 16 age- and sex-matched FH patients without obstructive coronary artery disease (CAD) by computed tomography angiography at baseline and after 12-week atorvastatin treatment. Indexes of relative myocardial blood flow (MBF) were obtained at rest and during adenosine infusion. Results: In validation group, there was no significant difference between flow-mediated dilation (FMD) at baseline and after 12 weeks (0.15 ± 0.02 vs. 0.14 ± 0.03; P = 0.39). Similarly, no differences were observed in MBF reserve at baseline and after 12 weeks (3.31 ± 0.63 vs. 3.48 ± 0.89; P = 0.89). FMD was blunted in FH patients, at baseline, as compared with validation group (0.08 ± 0.04 vs. 0.15 ± 0.02; P