Cardiovascular disease and cholesterol lowering therapy in women and men with molecularly defined heterozygous familial hypercholesterolemia from Brazil.

Background: Data on the epidemiology of familial hypercholesterolemia (FH) in developing regions based on contemporary, molecularly defined FH cohorts categorized by sex are scarce.

Objective: Evaluate the differences in cardiovascular disease (CVD) outcomes and lipid-lowering therapy (LLT) between men and women with molecularly defined heterozygous FH participating in a cascade screening program.

Methods: We included 794 adult FH patients (age 47 ± 15 years, 56.

Age- and sex-based heterogeneity in coronary artery plaque presence and burden in familial hypercholesterolemia: A multi-national study.

Objectives: Individuals with familial hypercholesterolemia (FH) are at an increased risk for coronary artery disease (CAD). While prior research has shown variability in coronary artery calcification (CAC) among those with FH, studies with small sample sizes and single-center recruitment have been limited in their ability to characterize CAC and plaque burden in subgroups based on age and sex. Understanding the spectrum of atherosclerosis may result in personalized risk assessment and tailored allocation of costly add-on, non-statin lipid-lowering therapies.

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.

Sex differences in the relationship between hepatic steatosis, mood and anxiety disorders.

Objective: To investigate the association between non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), mental symptoms (mood, anxiety disorders and distress) by sex.

Methods: This a cross-sectional study performed in working-age adults from a Health Promotion Center (primary care) in São Paulo, Brazil. Self-reported mental symptoms from rating scales (21-item Beck Anxiety Inventory, Patient Health Questionnaire-9, and K6 distress scale) were evaluated by hepatic steatosis (NAFLD and ALD).

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.

Cardiovascular disease onset in old people with severe hypercholesterolemia.

Background And Aims: Familial hypercholesterolemia (FH) variants are associated with higher atherosclerotic cardiovascular disease risk (ASCVD) even when compared with other forms of severe hypercholesterolemia, especially in young people. Lipid lowering therapies (LLT) may change hypercholesterolemia natural history. This study aimed at evaluating factors associated with occurrence of ASCVD in old severe hypercholesterolemics diagnosed or not with FH and undergoing LLT.

Screening of and 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 . 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.

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.

Neck circumference as a marker of body adiposity in young to middle-aged adults.

Objective: Neck circumference (NC) is a straightforward method for quantifying upper body adiposity without the limitations that other indices can have. Thus, this study aimed to analyze the relationship between NC, overall (body mass index [BMI]) and central obesity (waist circumference [WC]), and percentage of body fat (BF%) in men and women.

Methods: The associations with NC quartiles (first quartile: reference group), BMI ≥30 kg/m, WC (>102 cm for men and >88 cm for women), and high BF% (≥21 for men and ≥29 for women) were compared and analyzed by logistic regression models adjusted for demographic characteristics, cardiovascular risk factors, and lean mass.

The Role of RNA-Targeted Therapeutics to Reduce ASCVD Risk: What Have We Learned Recently?

Purpose Of Review: To discuss advances on the RNA-targeted therapies to treat dyslipidemia with the aim of reducing atherosclerotic cardiovascular disease (ASCVD).

Recent Findings: Genetic studies have paved the way for therapies that reduce translation of proteins that play causal roles in dyslipidemia and atherosclerosis like proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein B-100 (apoB), apolipoprotein(a) [apo(a)], apolipoprotein C3 (apoC3), and angiopoietin-like 3 (ANGPTL3). Either antisense oligonucleotide (ASO) therapies and small interfering RNA (siRNA) molecules inhibit protein synthesis and consequently improve dyslipidemia.

Familial hypercholesterolemia and cardiovascular disease in older individuals.

Background And Aims: Familial hypercholesterolemia (FH) is characterized by high LDL-cholesterol (LDL-C) and early atherosclerotic cardiovascular disease (ASCVD). With a lipid lowering therapy (LLT), most individuals with FH may have a longer ASCVD-free survival. However, there is scant data about older individuals with FH.

Vascular age derived from coronary artery calcium score on the risk stratification of individuals with heterozygous familial hypercholesterolaemia.

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.

Reducing cardiovascular risk in patients with familial hypercholesterolemia: Risk prediction and lipid management.

Familial hypercholesterolemia (FH) is a frequent genetic disorder characterized by elevated low-density lipoprotein (LDL)-cholesterol (LDL-C) levels and early onset of atherosclerotic cardiovascular disease. FH is caused by mutations in genes that regulate LDL catabolism, mainly the LDL receptor (LDLR), apolipoprotein B (APOB) and gain of function of proprotein convertase subtilisin kexin type 9 (PCSK9). However, the phenotype may be encountered in individuals not carrying the latter monogenic defects, in approximately 20% of these effects of polygenes predominate, and in many individuals no molecular defects are encountered at all.

Subclinical coronary atherosclerosis and cardiovascular risk stratification in heterozygous familial hypercholesterolemia patients undergoing statin treatment.

Purpose Of Review: To discuss the heterogeneity of atherosclerotic cardiovascular disease (ASCVD) risk in heterozygous familial hypercholesterolemia and evidence and limitations of clinical risk scores and subclinical coronary atherosclerosis (SCA) imaging to evaluate risk.

Recent Findings: Risk evaluation in contemporary familial hypercholesterolemia cohorts needs to consider the cause of the familial hypercholesterolemia phenotype, for example the presence of autosomal molecular defects that impart a greater ASCVD risk than in polygenic hypercholesterolemia, prospective follow-up and the impact of statin treatment. As atherosclerosis is multifactorial, clinical scores like the Montreal familial hypercholesterolemia score and SAFEHEART risk equation have been proposed to stratify ASCVD in statin-treated, molecularly defined familial hypercholesterolemia individuals.

Coronary Artery Calcium and Cardiovascular Events in Patients With Familial Hypercholesterolemia Receiving Standard Lipid-Lowering Therapy.

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.

Health related quality of life in individuals at high risk for familial hypercholesterolemia undergoing genetic cascade screening in Brazil.

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.

Familial hypercholesterolemia prevalence in an admixed racial society: Sex and race matter. The ELSA-Brasil.

Background And Aims: 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.

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.

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.