0000000000022189
AUTHOR
Raul D. Santos
An International Atherosclerosis Society Position Paper: global recommendations for the management of dyslipidemia.
An international panel of the International Atherosclerosis Society has developed a new set of recommendations for management of dyslipidemia. The panel identifies non-high density lipoprotein cholesterol (non-HDL-C) as the major atherogenic lipoprotein. Primary and secondary prevention are considered separately. Optimal levels for atherogenic lipoproteins are derived for the two forms of prevention. For primary prevention, the recommendations emphasize lifestyle therapies to reduce atherogenic lipoproteins; drug therapy is reserved for higher risk subjects. Risk assessment is based on estimation of lifetime risk according to differences in baseline population risk in different nations or r…
The Relationship between COVID-19 and Hypothalamic-Pituitary-Adrenal Axis: A Large Spectrum from Glucocorticoid Insufficiency to Excess-The CAPISCO International Expert Panel.
Coronavirus disease 2019 (COVID-19) is a highly heterogeneous disease regarding severity, vulnerability to infection due to comorbidities, and treatment approaches. The hypothalamic–pituitary–adrenal (HPA) axis has been identified as one of the most critical endocrine targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that might significantly impact outcomes after infection. Herein we review the rationale for glucocorticoid use in the setting of COVID-19 and emphasize the need to have a low index of suspicion for glucocorticoid-induced adrenal insufficiency, adjusting for the glucocorticoid formulation used, dose, treatment duration, and underlying health problems. We a…
Targeting PCSK9 for therapeutic gains: Have we addressed all the concerns?
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) regulates the expression of low-density lipoprotein (LDL)-receptors, through reducing their recycling by binding to the receptor along with LDL and targeting it for lysosomal destruction. PCSK9 also enhances the degradation of very-low-density-lipoprotein receptor (VLDLR) and lipoprotein receptor-related protein 1 (LRP-1) in a LDL-receptor independent manner. This role in lipid homeostasis presents PCSK9 as an attractive target for the therapeutic management of familial hypercholesterolemia as well as other refractory dyslipidaemias. However, PCSK9 mediates multifarious functions independent of its role in lipid homeostasis, which can be…
Predicting intention to participate in self-management behaviors in patients with Familial Hypercholesterolemia: A cross-national study
Abstract Rationale Familial Hypercholesterolemia (FH) is a genetic condition that predisposes patients to substantially increased risk of early-onset atherosclerotic cardiovascular disease. FH risks can be minimized through regular participation in three self-management. Behaviors physical activity, healthy eating, and taking cholesterol lowering medication. Objective The present study tested the effectiveness of an integrated social cognition model in predicting intention to participate in the self-management behaviors in FH patients from seven countries. Method Consecutive patients in FH clinics from Australia, Hong Kong, Brazil, Malaysia, Taiwan, China, and UK (total N = 726) completed m…
Overview of the current status of familial hypercholesterolaemia care in over 60 countries - The EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)
PubMed: 30270054
Health literacy in familial hypercholesterolemia: A cross-national study.
Background High rates of inadequate health literacy are associated with maladaptive health outcomes in chronic disease including increased mortality and morbidity rates, poor treatment adherence and poor health. Adequate health literacy may be an important factor in the effective treatment and management of familial hypercholesterolemia, and may also be implicated in genetic screening for familial hypercholesterolemia among index cases. The present study examined the prevalence and predictors of health literacy in familial hypercholesterolemia patients attending clinics in seven countries. Design Cross-sectional survey. Methods Consecutive FH patients attending clinics in Australia, Brazil,…
The Effect of Bariatric Surgery on Circulating Levels of Lipoprotein (a): A Meta-analysis.
Background. Obesity, especially severe obesity, is associated with a higher risk of atherosclerotic cardiovascular disease (ASCVD) morbidity and mortality. Bariatric surgery is a durable and effective weight loss therapy for patients with severe obesity and weight-related comorbidities. Elevated plasma levels of lipoprotein (a) (Lp(a)) are causally associated with ASCVD. The aim of this meta-analysis was to analyze whether bariatric surgery is associated with Lp(a) concentrations. Methods. A literature search in PubMed, Scopus, Embase, and Web of Science was performed from inception to May 1st, 2021. A random-effects model and the generic inverse variance weighting method were used to compe…
Pooling and expanding registries of familial hypercholesterolaemia to assess gaps in care and improve disease management and outcomes: Rationale and design of the global EAS Familial Hypercholesterolaemia Studies Collaboration
WOS: 000393031600001
Proprotein Convertase Subtilisin Kexin Type 9 Inhibition for Autosomal Recessive Hypercholesterolemia—Brief Report
Objective— Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors lower low-density lipoprotein (LDL) cholesterol in the vast majority of patients with autosomal dominant familial hypercholesterolemia. Will PCSK9 inhibition with monoclonal antibodies, in particular alirocumab, be of therapeutic value for patients with autosomal recessive hypercholesterolemia (ARH)? Approach and Results— Primary lymphocytes were obtained from 28 genetically characterized ARH patients and 11 controls. ARH lymphocytes treated with mevastatin were incubated with increasing doses of recombinant PCSK9 with or without saturating concentrations of alirocumab. Cell surface LDL receptor expression measured…
Treatment effect of alirocumab according to age group, smoking status, and hypertension: Pooled analysis from 10 randomized ODYSSEY studies
Background: Age, smoking, hypercholesterolemia, and hypertension are major risk factors for atherosclerotic cardiovascular disease. Objective: We examined whether the effects of alirocumab on low-density lipoprotein cholesterol (LDL-C) differed according to age, hypertension, or smoking status. Methods: Data were pooled from 10 Phase 3 ODYSSEY randomized trials (24–104 weeks’ duration) in 4983 people with heterozygous familial hypercholesterolemia (FH) or non–familial hypercholesterolemia (3188 on alirocumab, 1795 on control [620 on ezetimibe and 1175 on placebo]). Most participants received concomitant maximum tolerated statin therapy. In 8 trials, the alirocumab dose was increased from 75…
Effects of medication, treatment, and behavioral beliefs on intentions to take medication in patients with familial hypercholesterolemia
Although familial hypercholesterolemia (FH) can be effectively managed using cholesterol-lowering medication, patients often fall short of complete treatment adherence. Identifying the psychological factors associated with self-regulation of FH medication is important to inform interventions to maximize adherence. The aim of the present study was to test an integrated psychological model in predicting FH patients' intentions to take medication.FH patients attending clinics in seven countries were invited to participate in a cross-sectional survey study. Consenting patients (N = 551) completed self-report measures of generalized beliefs about medication overuse and harms, beliefs in treatmen…
Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)
Background The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally. Methods Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Dat…
Reconnoitering the Role of Long-Noncoding RNAs in Hypertrophic Cardiomyopathy: A Descriptive Review
Hypertrophic cardiomyopathy (HCM) is the most common form of hereditary cardiomyopathy. It is characterized by an unexplained non-dilated hypertrophy of the left ventricle with a conserved or elevated ejection fraction. It is a genetically heterogeneous disease largely caused by variants of genes encoding for cardiac sarcomere proteins, including MYH7, MYBPC3, ACTC1, TPM1, MYL2, MYL3, TNNI3, and TNNT23. Preclinical evidence indicates that the enhanced calcium sensitivity of the myofilaments plays a key role in the pathophysiology of HCM. Notably, this is not always a direct consequence of sarcomeric variations but may also result from secondary mutation-driven alterations. Long non-coding R…
Familial hypercholesterolaemia: A global call to arms
Familial Hypercholesterolaemia (FH) is the commonest autosomal co-dominantly inherited condition affecting man. It is caused by mutation in one of three genes, encoding the low-density lipoprotein (LDL) receptor, or the gene for apolipoprotein B (which is the major protein component of the LDL particle), or in the gene coding for PCSK9 (which is involved in the degradation of the LDL-receptor during its cellular recycling). These mutations result in impaired LDL metabolism, leading to life-long elevations in LDL-cholesterol (LDL-C) and development of premature atherosclerotic cardiovascular disease (ASCVD) [1], [2] and [3]. If left untreated, the relative risk of premature coronary artery d…
Effects of medication, treatment, and behavioral beliefs on intentions to take medication in patients with familial hypercholesterolemia
Background and aims Although familial hypercholesterolemia (FH) can be effectively managed using cholesterol-lowering medication, patients often fall short of complete treatment adherence. Identifying the psychological factors associated with self-regulation of FH medication is important to inform interventions to maximize adherence. The aim of the present study was to test an integrated psychological model in predicting FH patients' intentions to take medication. Methods FH patients attending clinics in seven countries were invited to participate in a cross-sectional survey study. Consenting patients (N = 551) completed self-report measures of generalized beliefs about medication overuse a…
Translational Research for Improving the Care of Familial Hypercholesterolemia: The “Ten Countries Study” and Beyond
Familial hypercholesterolemia (FH) is the most common and serious form of inherited hyperlipidaemia. Dominantly inherited with high penetrance, untreated FH leads to premature death from coronary artery disease due to accelerated atherosclerosis from birth. Despite its importance, there is still a major shortfall in awareness, detection and treatment of FH worldwide. International models of care for FH have recently been published, but their effective implementation requires the garnering of more knowledge about the condition. The “Ten Countries Study” aims to investigate diagnostic, epidemiological and service aspects, as well as physician practices and patient experiences of FH in several…
Promoting a Syndemic Approach for Cardiometabolic Disease Management During COVID-19: The CAPISCO International Expert Panel
Efforts in the fight against COVID-19 are achieving success in many parts of the world, although progress remains slow in other regions. We believe that a syndemic approach needs to be adopted to address this pandemic given the strong apparent interplay between COVID-19, its related complications, and the socio-structural environment. We have assembled an international, multidisciplinary group of researchers and clinical practitioners to promote a novel syndemic approach to COVID-19: the CArdiometabolic Panel of International experts on Syndemic COvid-19 (CAPISCO). This geographically diverse group aims to facilitate collaborative-networking and scientific exchanges between researchers and …
Translational Research for Improving the Care of Familial Hypercholesterolemia: The “Ten Countries Study” and Beyond
Familial hypercholesterolemia (FH) is the most common and serious form of inherited hyperlipidaemia. Dominantly inherited with high penetrance, untreated FH leads to premature death from coronary artery disease due to accelerated atherosclerosis from birth. Despite its importance, there is still a major shortfall in awareness, detection and treatment of FH worldwide. International models of care for FH have recently been published, but their effective implementation requires the garnering of more knowledge about the condition. The "Ten Countries Study" aims to investigate diagnostic, epidemiological and service aspects, as well as physician practices and patient experiences of FH in several…
Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: Consensus Statement of the European Atherosclerosis Society
AIMS: The first aim was to critically evaluate the extent to which familial hypercholesterolaemia (FH) is underdiagnosed and undertreated. The second aim was to provide guidance for screening and treatment of FH, in order to prevent coronary heart disease (CHD).METHODS AND RESULTS: Of the theoretical estimated prevalence of 1/500 for heterozygous FH, <1% are diagnosed in most countries. Recently, direct screening in a Northern European general population diagnosed approximately 1/200 with heterozygous FH. All reported studies document failure to achieve recommended LDL cholesterol targets in a large proportion of individuals with FH, and up to 13-fold increased risk of CHD. Based on prev…
Post-COVID syndrome, inflammation, and diabetes
The raging COVID-19 pandemic is in its third year of global impact. The SARS CoV 2 virus has a high rate of spread, protean manifestations, and a high morbidity and mortality in individuals with predisposing risk factors. The pathophysiologic mechanisms involve a heightened systemic inflammatory state, cardiometabolic derangements, and varying degrees of glucose intolerance. The latter can be evident as significant hyperglycemia leading to new -onset diabetes or worsening of preexisting disease. Unfortunately, the clinical course beyond the acute phase of the illness may persist in the form of a variety of symptoms that together form the so-called "Long COVID" or "Post-COVID Syndrome". It i…
Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society
Item does not contain fulltext AIMS: Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights into the heterogeneity of genetic defects and clinical phenotype of HoFH, and the availability of new therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) critically reviewed available data with the aim of providing clinical guidance for the recognition and management of HoFH. METHODS AND RESULTS: Early diagn…
Worldwide experience of homozygous familial hypercholesterolaemia:retrospective cohort study
[Background]: Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder resulting in extremely elevated low-density lipoprotein cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Current guidance about its management and prognosis stems from small studies, mostly from high-income countries. The objective of this study was to assess the clinical and genetic characteristics, as well as the impact, of current practice on health outcomes of HoFH patients globally.
Molecular and pro-inflammatory aspects of COVID-19: The impact on cardiometabolic health
Obesity, type 2 diabetes (T2DM), hypertension (HTN), and Cardiovascular Disease (CVD) often cluster together as "Cardiometabolic Disease" (CMD). Just under 50% of patients with CMD increased the risk of morbidity and mortality right from the beginning of the COVID-19 pandemic as it has been reported in most countries affected by the SARS-CoV2 virus. One of the pathophysiological hallmarks of COVID-19 is the overactivation of the immune system with a prominent IL-6 response, resulting in severe and systemic damage involving also cytokines such as IL2, IL4, IL8, IL10, and interferon-gamma were considered strong predictors of COVID-19 severity. Thus, in this mini-review, we try to describe the…