BACKGROUND:Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder characterized by severe hypertriglyceridemia (sHTG) due to variants in canonical genes (LPL [lipoprotein lipase], APOA5, APOC2, GPIHBP1, and LMF1); its genotype distribution in Latin America remains scarcely reported. Given limited access to genetic testing and frequent negative results in clinically consistent cases, clinical scores and lipid ratios have been proposed to predict FCS. OBJECTIVE:This study aimed to outline the genetic, clinical, and biochemical characteristics, as well as the performance of scoring systems, in a Latin American cohort of patients with sHTG. METHODS:Genetic, clinical, and biochemical data were obtained in 77 individuals with sHTG (TG >10 mmol/L), including 28 genetically diagnosed FCS and 49 multifactorial chylomicronemia syndrome (MCS). Triglyceride/total cholesterol (TG/TC), TG/apolipoprotein B (apoB) ratios, and Moulin and North American Familial Chylomicronemia Score (NAFCS) scores were calculated. RESULTS:Among patients with FCS, non-LPL monogenic defects were present in 64% of patients (n = 18), with variants in APOA5 (n = 11), GPIHBP1 (n = 3), APOC2 (n = 2), and LMF1 (n = 2). Diagnosis was frequently delayed, and body mass index overlapped across groups. Biochemical biomarkers showed good diagnostic performance, with AUCs of 0.767 (95% CI: 0.640-0.876; P < .0001) for TG/TC and 0.790 (95% CI: 0.651-0.906; P < .0001) for TG/apoB. Moulin score showed high sensitivity (91.3%), whereas NAFCS score showed high specificity (90.9%). CONCLUSION:This large multicenter Latin American study of sHTG reveals a distinct genetic landscape from other regions. It also supports the performance of clinical scores and the discriminatory accuracy of biochemical indices.
In Latin America, obesity rates are among the highest in the world. Currently, people with obesity (PWO) receive suboptimal care due to several challenges and barriers. The international ACTION-IO study aimed to identify perceptions, attitudes and behaviours of PWO and healthcare providers (HCP), and to assess potential barriers to effective obesity care. The aim of this subanalysis of the Chilean cohort was to compare their characteristics, perceptions, attitudes and behaviours according to the percentage of weight loss (lower weight loss [LWL; ≤10%] or higher weight loss [HWL; >10%] of basal weight). The ACTION-IO survey was completed by 1000 Chilean PWO and 200 HCPs. Mean age of PWO was 38 years (range 18-75); 62% were female. The majority had class I obesity. HWL subgroup represented 17.2% of all Chilean subset. Specific characteristics of patients with HWL were identified (higher educational level, lower proportion of class III obesity, preference for consulting obesity specialists, considering conversations with HCP as very helpful). HWL patients reported higher rates of favourable outcomes following HCP advice and a higher probability of attending scheduled follow-up visits. Certain demographic and behavioural variables (educational level, consultation to obesity specialists, adherence to HCP advice, follow-up scheduled visits and becoming aware of the obesity state) may identify PWO with a higher probability of a greater weight loss.
Weight stigma, defined as pervasive misconceptions and stereotypes associated with higher body weight, is both a social determinant of health and a human rights issue. It is imperative to consider how weight stigma may be impeding health promotion efforts on a global scale. The World Obesity Federation (WOF) convened a global working group of practitioners, researchers, policymakers, youth advocates, and individuals with lived experience of obesity to consider the ways that global obesity narratives may contribute to weight stigma. Specifically, the working group focused on how overall obesity narratives, food and physical activity narratives, and scientific and public-facing language may contribute to weight stigma. The impact of weight stigma across the lifespan was also considered. Taking a global perspective, nine recommendations resulted from this work for global health research and health promotion efforts that can help to reduce harmful obesity narratives, both inside and outside health contexts.
COVID-19 is a pandemic disease caused by a coronavirus, designed as SARS CoV-2, whose clinical presentation is widely variable, with most patients having mild or no symptoms, but others developing a malign disease with multi-organ failure and even death. Accumulating data from different populations have shown that obesity is a risk factor for a severe evolution of the disease, however, the mechanisms that explain this association are not clearly understood. An ominous evolution of COVID-19 has been attributed to an exacerbated inflammatory response, designed as "cytokine storm" with augmented production of cytokines/chemokines through the activation of toll-like receptors (TLR) by pathogen-associated molecular patterns, that triggers an inflammatory downstream response, mediated in part by the adaptor molecule, myeloid differentiation factor 88 (MyD88). Previous studies have reported an increased expression of MyD88 and TLRs in people with obesity, mainly in those with metabolic complications. Therefore, we hypothesize, that an underlying increased Myd88/TLR signaling may predispose to patients with obesity to develop an exaggerated and dangerous inflammatory reaction against SARS CoV-2 infection, explaining at least in part, the higher severity of COVID-19. In addition, MyD88/TLR signaling in people with obesity could have a role in the development of several chronic diseases.
BACKGROUND:Most of the Chilean population has overweight or obesity. The ACTION-IO survey identified the perceptions, attitudes, and barriers to effective obesity care in people with obesity (PwO) and healthcare professionals (HCPs).AIM:To report the results of the survey in Chile.MATERIAL AND METHODS:An online survey was conducted in 11 countries. In Chile, eligible PwO were adults with a body mass index ≥ 30 kg/m2. Eligible HCPs were physicians involved in direct patient care.RESULTS:The survey was completed by 1,000 PwO and 200 HCPs in Chile. Seventy four percent of PwO and 95% of HCPs agreed that obesity was a chronic disease. Most PwO (79%) assumed responsibility for their own weight loss, while 47% of HCPs considered weight loss to be the sole responsibility of their patients. Both 82% of PwO and 97% of HCPs believed that lack of exercise was a key barrier to weight loss. Sixty six percent of PwO and 58% HCPs noted that the cost of weight management medications, programs, and services was another barrier. Compared with HCPs, more PwO felt that genetic factors prevented weight loss (26 and 44% respectively). Few HCPs (19%) thought that their patients were motivated to lose weight, while 55% of PwO reported being motivated. Most (70%) PwO had discussed their weight problem with their HCP in the past 5 years, and of those that had not, 89% want their HCP to start a discussion about weight.CONCLUSIONS:Chilean data reveal misconceptions among PwO and HCPs about obesity and highlights the need to improve education about its biologic background and clinical management.
Background: The care of people with obesity is often suboptimal due to both physician and patient perceptions about obesity itself and clinical barriers. Using data from the ACTION-IO study, we aimed to identify factors that might improve the quality of obesity care through adoption of the 3D approach (Discussion, Diagnosis and Direction [follow-up]) by healthcare professionals (HCPs). Methods: An online survey was completed by HCPs in 11 countries. Exploratory beta regression analyses identified independent variables associated with each component of the 3D approach. Results: Data from 2,331 HCPs were included in the statistical models. HCPs were significantly more likely to initiate weight discussions and inform patients of obesity diagnoses, respectively, if (odds ratio [95% confidence interval]): they recorded an obesity diagnosis in their patient's medical notes (1.59, [1.43-1.76] and 2.16 [1.94-2.40], respectively); and they were comfortable discussing weight with their patients (1.53 [1.39-1.69] and 1.15 [1.04-1.27]). HCPs who reported feeling motivated to help their patients lose weight were also more likely to initiate discussions (1.36 [1.21-1.53]) and schedule follow-up appointments (1.21 [1.06-1.38]). By contrast, HCPs who lacked advanced formal training in obesity management were less likely to inform patients of obesity diagnoses (0.83 [0.74-0.92]) or schedule follow-up appointments (0.69 [0.62-0.78]). Conclusion: Specific actions that could improve obesity care through the 3D approach include: encouraging HCPs to record an obesity diagnosis; providing tools to help HCPs feel more comfortable initiating weight discussions; and provision of training in obesity management. Clinical trial registration: NCT03584191.
Background: People with obesity (PwO) often struggle to achieve and maintain weight loss. This can perpetuate and/or be influenced by feelings of low motivation. This analysis from ACTION-IO data identified factors associated with PwO motivation to lose weight. Methods: PwO completed an online survey in 11 countries. Exploratory multinomial logistic regression analyses identified independent variables associated with self-report of feeling motivated versus not motivated to lose weight. Results: Data from 10,854 PwO were included (5,369 motivated; 3,312 neutral; 2,173 not motivated). Variables associated with feeling motivated versus not motivated included (odds ratio [95% confidence interval]): acknowledgement of healthcare professional (HCP) responsibility to contribute to weight loss (2.32 [1.86-2.88]), comfort in talking to their HCP about weight (1.46 [1.24-1.72), agreement that it is easy to lose weight (1.73 [1.30-2.31]), and a goal of reducing risks from excess weight (1.45 [1.22-1.73]). Conversely, if PwO considered obesity less important than other diseases they were less likely to report feeling motivated (0.49 [0.41-0.58]). PwO who reported being motivated to lose weight were more likely to exercise >= 5 times a week versus <1 time a week (2.77 [2.09-3.68]) than those who reported they were not motivated. Conclusions: Positive interactions with HCPs, self-efficacy, setting goals and knowledge of the importance of weight management, in addition to regular exercising, may increase PwO motivation for weight loss. Appropriate HCP support may help PwO who are ready to engage in weight management. Clinical trial registration: : NCT03584191.
It is very well known that low-density lipoprotein cholesterol (LDL-C) is one of the main risk factors for atherosclerosis cardiovascular disease (ASCVD), and statins have shown a key role in the prevention and reduction of the burden of cardiovascular disease. However, most high-risk patients do not achieve LDL-C goals with conventional lipid-lowering treatment (LLT) and require additional drugs. Moreover, some patients develop side effects to statins, limiting its use, and making the attainment of treatment goals more difficult. 1 Rosenson R.S. Baker S. Banach M. et al. Optimizing cholesterol treatment in patients with muscle complaints. J Am Coll Cardiol. 2017; 70: 1290-1301 Crossref PubMed Scopus (120) Google Scholar
Despite decades of unequivocal evidence that waist circumference provides both independent and additive information to BMI for predicting morbidity and risk of death, this measurement is not routinely obtained in clinical practice. This Consensus Statement proposes that measurements of waist circumference afford practitioners with an important opportunity to improve the management and health of patients. We argue that BMI alone is not sufficient to properly assess or manage the cardiometabolic risk associated with increased adiposity in adults and provide a thorough review of the evidence that will empower health practitioners and professional societies to routinely include waist circumference in the evaluation and management of patients with overweight or obesity. We recommend that decreases in waist circumference are a critically important treatment target for reducing adverse health risks for both men and women. Moreover, we describe evidence that clinically relevant reductions in waist circumference can be achieved by routine, moderate-intensity exercise and/or dietary interventions. We identify gaps in the knowledge, including the refinement of waist circumference threshold values for a given BMI category, to optimize obesity risk stratification across age, sex and ethnicity. We recommend that health professionals are trained to properly perform this simple measurement and consider it as an important ‘vital sign’ in clinical practice.
In March of 2020, the World Health Organization declared the SARS‐Cov2 2019 (COVID‐19) outbreak a global pandemic after documenting community scale transmission in every region, including Latin America. The risk factors associated with severity of disease include older age, diabetes, hypertension, cardiovascular and lung diseases, and immune suppression. Additional evidence strongly suggests that obesity is also a risk factor for severe forms of COVID‐19 disease, while other types of malnutrition increase the risk of hospitalization from influenza‐like diseases, regardless of the causative agent of the illness (1). Although detailed data are not yet available on the impact of under nutrition in the evolution of COVID‐19, given the known inflammatory response caused by this condition, it is reasonable to expect a suboptimal immune response and higher risk of severity, as found with obesity (2).
Objective: Characterize homozygous familial hypercholesterolemia (HoFH) individuals from Iberoamerica. Approach and Results: In a cross-sectional retrospective evaluation 134 individuals with a HoFH phenotype, 71 adults (age 39.3 +/- 15.8 years, 38.0% males), and 63 children (age 8.8 +/- 4.0 years, 50.8% males) were studied. Genetic characterization was available in 129 (96%). The majority (91%) were true homozygotes (true HoFH, n=79, 43.0% children, 46.8% males) or compound heterozygotes (compound heterozygous familial hypercholesterolemia, n=39, 51.3% children, 46.2% males) with putative pathogenic variants in theLDLR. True HoFH due toLDLRvariants had higher total (P=0.015) and LDL (low-density lipoprotein)-cholesterol (P=0.008) compared with compound heterozygous familial hypercholesterolemia. Children with true HoFH (n=34) tended to be diagnosed earlier (P=0.051) and had a greater frequency of xanthomas (P=0.016) than those with compound heterozygous familial hypercholesterolemia (n=20). Previous major cardiovascular events were present in 25 (48%) of 52 children (missing information in 2 cases), and in 43 (67%) of 64 adults withLDLRvariants. Children who are true HoFH had higher frequency of major cardiovascular events (P=0.02), coronary heart (P=0.013), and aortic/supra-aortic valve diseases (P=0.022) than compound heterozygous familial hypercholesterolemia. In adults, no differences were observed in major cardiovascular events according to type ofLDLRvariant. From 118 subjects withLDLRvariants, 76 (64%) had 2 likely pathogenic or pathogenic variants. In 89 subjects with 2LDLRvariants, those with at least one null allele were younger (P=0.003) and had a greater frequency of major cardiovascular events (P=0.038) occurring at an earlier age (P=0.001). Conclusions: There was a high frequency of cardiovascular disease even in children. Phenotype and cardiovascular complications were heterogeneous and associated with the type of molecular defect.
Aims: In people with obesity (PwO), body weight loss of ≥5% is generally considered to be clinically meaningful. Some PwO do receive treatment and guidance from healthcare professionals (HCPs), but there remains a substantial unmet medical outcomes and weight maintenance need. To identify aspects that might contribute to a successful weight loss outcome (WLO; ≥5% body weight loss maintained for ≥1 year), we investigated the characteristics and experience of PwO with and without successful WLOs using data from the ACTION-IO study (NCT03584191). Methods: An online survey was completed by adults with obesity and HCPs in 11 countries: Australia, Chile, Israel, Italy, Japan, Mexico, Saudi Arabia, South Korea, Spain, UAE and UK. A successful WLO was defined as ≥5% body weight loss in the past 3 years maintained for ≥1 year. Results: A total of 14,502 PwO completed the survey. General characteristics were similar between those who had a successful WLO (n=1,559; 11%) vs those who had not (n=12,943; 89%): 53% vs 52% were male; the mean age was 49 vs 48 years; the mean number of comorbidities was 2.0 vs 1.8. The mean number of serious weight loss attempts was 4 for both groups. However, more PwO who had a successful WLO weighed themselves every day (20%) compared with those who had not had a successful WLO (10%). In terms of interactions with HCPs, more PwO who had a successful WLO had discussed weight (58%) with an HCP within the past 5 years than those who did not have a successful WLO (53%). In addition, more PwO who had a successful WLO compared with those who did not had been diagnosed with obesity (42% vs 35%) and had subsequent direction through the scheduling of a follow-up appointment (25% vs 21%). Conclusions: A 3D approach from HCPs (diagnosis, discussion and direction) appears to be a key element in facilitating a successful WLO. Neither gender, nor age, nor number of weight loss attempts was associated with a successful WLO.
Rodrigo Alonso Ada Cuevas Pedro Mata 1Department of Nutrition, Clínica Las Condes, Santiago, Chile; 2Familial Hypercholesterolemia Foundation, Madrid, Spain Abstract: Lomitapide is an inhibitor of MTP, an enzyme located in the endoplasmic reticulum of hepatocytes and enterocytes. This enzyme is responsible for the synthesis of very low-density lipoproteins in the liver and chylomicrons in the intestine. Lomitapide has been approved by the US Food and Drug Administration, European Medicines Agency, and other regulatory agencies for the treatment of hypercholesterolemia in adult patients with homozygous familial hypercholesterolemia. Clinical trials have shown that lomitapide reduces low-density-lipoprotein cholesterol levels by around 40% in homozygous familial hypercholesterolemia patients on treatment with statins with or without low-density-lipoprotein apheresis, with an acceptable safety and tolerance profile. The most common adverse events are gastrointestinal symptoms that decrease in frequency with long-term treatment, and the increase in liver fat remains stable. This review analyzes the clinical use, efficacy, and tolerability of lomitapide.
Lomitapide is an inhibitor of MTP, an enzyme located in the endoplasmic reticulum of hepatocytes and enterocytes. This enzyme is responsible for the synthesis of very low-density lipoproteins in the liver and chylomicrons in the intestine. Lomitapide has been approved by the US Food and Drug Administration, European Medicines Agency, and other regulatory agencies for the treatment of hypercholesterolemia in adult patients with homozygous familial hypercholesterolemia. Clinical trials have shown that lomitapide reduces low-density-lipoprotein cholesterol levels by around 40% in homozygous familial hypercholesterolemia patients on treatment with statins with or without low-density-lipoprotein apheresis, with an acceptable safety and tolerance profile. The most common adverse events are gastrointestinal symptoms that decrease in frequency with long-term treatment, and the increase in liver fat remains stable. This review analyzes the clinical use, efficacy, and tolerability of lomitapide.
Background and Aims: Homozygous Familial Hypercholesterolemia (HoFH) is a rare disorder, affecting 1 in 300,000 to 1,000,000 people in the general population. It is estimated that there are 600 to 1,800 HoFH in the Ibero-America, most of them not diagnosed and/or not treated adequately. The objective of this work is to describe molecular characteristics of HoFH diagnosis in Argentina, Brazil, Chile, Colombia, Mexico, Portugal, Spain, and Uruguay.
Findings from epidemiological studies over the past 30 years have shown that visceral adipose tissue, accurately measured by CT or MRI, is an independent risk marker of cardiovascular and metabolic morbidity and mortality. Emerging evidence also suggests that ectopic fat deposition, including hepatic and epicardial fat, might contribute to increased atherosclerosis and cardiometabolic risk. This joint position statement from the International Atherosclerosis Society and the International Chair on Cardiometabolic Risk Working Group on Visceral Obesity summarises the evidence for visceral adiposity and ectopic fat as emerging risk factors for type 2 diabetes, atherosclerosis, and cardiovascular disease, with a focus on practical recommendations for health professionals and future directions for research and clinical practice. We discuss the measurement of visceral and ectopic fat, pathophysiology and contribution to adverse health outcomes, response to treatment, and lessons from a public health programme targeting visceral and ectopic fat. We identify knowledge gaps and note the need to develop simple, clinically applicable tools to be able to monitor changes in visceral and ectopic fat over time. Finally, we recognise the need for public health messaging to focus on visceral and ectopic fat in addition to excess bodyweight to better combat the growing epidemic of obesity worldwide.