The upcoming epidemic of heart failure in South Asia

Currently, South Asia accounts for a quarter of the world population, yet it already claims ≈60% of the global burden of heart disease. Besides the epidemics of type 2 diabetes mellitus and coronary heart disease already faced by South Asian countries, recent studies suggest that South Asians may also be at an increased risk of heart failure (HF), and that it presents at earlier ages than in most other racial/ethnic groups. Although a frequently underrecognized threat, an eventual HF epidemic in the densely populated South Asian nations could have dramatic health, social and economic consequences, and urgent interventions are needed to flatten the curve of HF in South Asia. In this review, we discuss recent studies portraying these trends, and describe the mechanisms that may explain an increased risk of premature HF in South Asians compared with other groups, with a special focus on highly relevant features in South Asian populations including premature coronary heart disease, early type 2 diabetes mellitus, ubiquitous abdominal obesity, exposure to the world’s highest levels of air pollution, highly prevalent pretransition forms of HF such as rheumatic heart disease, and underdevelopment of healthcare systems. Other rising lifestyle-related risk factors such as use of tobacco products, hypertension, and general obesity are also discussed. We evaluate the prognosis of HF in South Asian countries and the implications of an anticipated HF epidemic. Finally, we discuss proposed interventions aimed at curbing these adverse trends, management approaches that can improve the prognosis of prevalent HF in South Asian countries, and research gaps in this important field

Locus for severity implicates CNS resilience in progression of multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that results in significant neurodegeneration in the majority of those affected and is a common cause of chronic neurological disability in young adults(1,2). Here, to provide insight into the potential mechanisms involved in progression, we conducted a genome-wide association study of the age-related MS severity score in 12,584 cases and replicated our findings in a further 9,805 cases. We identified a significant association with rs10191329 in the DYSF-ZNF638 locus, the risk allele of which is associated with a shortening in the median time to requiring a walking aid of a median of 3.7 years in homozygous carriers and with increased brainstem and cortical pathology in brain tissue. We also identified suggestive association with rs149097173 in the DNM3-PIGC locus and significant heritability enrichment in CNS tissues. Mendelian randomization analyses suggested a potential protective role for higher educational attainment. In contrast to immune-driven susceptibility(3), these findings suggest a key role for CNS resilience and potentially neurocognitive reserve in determining outcome in MS

Home-based exercise program in the indeterminate form of Chagas disease (PEDI-CHAGAS study): A study protocol for a randomized clinical trial

BackgroundChagas disease (CD) is a neglected endemic disease with worldwide impact due to migration. Approximately 50–70% of individuals in the chronic phase of CD present the indeterminate form, characterized by parasitological and/or serological evidence of Trypanosoma cruzi infection, but without clinical signs and symptoms. Subclinical abnormalities have been reported in indeterminate form of CD, including pro-inflammatory states and alterations in cardiac function, biomarkers and autonomic modulation. Moreover, individuals with CD are usually impacted on their personal and professional life, making social insertion difficult and impacting their mental health and quality of life (QoL). Physical exercise has been acknowledged as an important strategy to prevent and control numerous chronic-degenerative diseases, but unexplored in individuals with the indeterminate form of CD. The PEDI-CHAGAS study (which stands for “Home-Based Exercise Program in the Indeterminate Form of Chagas Disease” in Portuguese) aims to evaluate the effects of a home-based exercise program on physical and mental health outcomes in individuals with indeterminate form of CD.Methods and designThe PEDI-CHAGAS is a two-arm (exercise and control) phase 3 superiority randomized clinical trial including patients with indeterminate form of CD. The exclusion criteria are <18 years old, evidence of non-Chagasic cardiomyopathy, musculoskeletal or cognitive limitations that preclude the realization of exercise protocol, clinical contraindication for regular exercise, and regular physical exercise (≥1 × per week). Participants will be assessed at baseline, and after three and 6 months of follow-up. The primary outcome will be QoL. Secondary outcomes will include blood pressure, physical fitness components, nutritional status, fatigability, autonomic modulation, cardiac morphology and function, low back pain, depression and anxiety, stress, sleep quality, medication use and adherence, and biochemical, inflammatory and cardiac biomarkers. Participants in the intervention group will undergo a home-based exercise program whilst those in the control group will receive only general information regarding the benefits of physical activity. Both groups will receive the same general nutritional counseling consisting of general orientations about healthy diets.ConclusionThe findings from the present study may support public health intervention strategies to improve physical and mental health parameters to be implemented more effectively in this population.Clinical trial registration[https://ensaiosclinicos.gov.br/rg/RBR-10yxgcr9/], identifier [U1111-1263-0153]

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

THE ASSOCIATION OF HEARING IMPAIRMENT WITH PHYSICAL ACTIVITY AND FUNCTION IN OLDER AGE

Background: Hearing impairment affects two-thirds of adults older than 70. Since hearing impairment is associated with poorer physical function and walking endurance, adults with hearing impairment might be at increased risk of mobility disability. Objectives: The overarching goal of this dissertation is to investigate the association of hearing impairment with objectively measured physical activity (aim 1) and function (balance, gait speed, lower extremity strength) and walking endurance (aims 2 and 3). Methods: We conducted a systematic review of the association between hearing impairment and objectively-measured physical activity. We assessed the association between hearing impairment and physical function assessed with two performance batteries (short physical performance battery [SPPB], and Health Aging and Body Composition PPB [HABCPPB]), and walking endurance using two long distance walks (two-minute walk, and 400-m walk). Moreover, we evaluated the role of vestibular function as a confounder of these associations, and the differences in these outcomes between hearing aid users and nonusers. Results: Five studies investigated the association between hearing and physical activity using NHANES data (2003-06). The included studies in our review had several limitations in the analysis and interpretation of accelerometry data. Aims 2 and 3 indicate that hearing impairment is associated with poorer physical function (particularly with balance) and a faster rate of decline in SPPB and HABCPPB scores. Both analyses also showed that participants with hearing impairment had slower walking endurance and aim 3 found that participants with moderate or greater hearing impairment increased their time to complete a long-distance (400-m) walk at a faster rate that participants with normal hearing. We saw no attenuation in these associations after the adjustment for vestibular function. Finally, among participants with hearing impairment, hearing aid users were faster to walk 400-m than nonusers. Conclusions: Across multiple studies, older adults with hearing impairment experience decline in physical functioning at a faster rate than those with normal hearing, suggesting they may be more susceptible to mobility impairments and disability. Little is known about the association between hearing loss and objectively measured physical activity. More research is needed to address this gap

THE ASSOCIATION OF HEARING IMPAIRMENT WITH PHYSICAL ACTIVITY AND FUNCTION IN OLDER AGE

Background: Hearing impairment affects two-thirds of adults older than 70. Since hearing impairment is associated with poorer physical function and walking endurance, adults with hearing impairment might be at increased risk of mobility disability. Objectives: The overarching goal of this dissertation is to investigate the association of hearing impairment with objectively measured physical activity (aim 1) and function (balance, gait speed, lower extremity strength) and walking endurance (aims 2 and 3). Methods: We conducted a systematic review of the association between hearing impairment and objectively-measured physical activity. We assessed the association between hearing impairment and physical function assessed with two performance batteries (short physical performance battery [SPPB], and Health Aging and Body Composition PPB [HABCPPB]), and walking endurance using two long distance walks (two-minute walk, and 400-m walk). Moreover, we evaluated the role of vestibular function as a confounder of these associations, and the differences in these outcomes between hearing aid users and nonusers. Results: Five studies investigated the association between hearing and physical activity using NHANES data (2003-06). The included studies in our review had several limitations in the analysis and interpretation of accelerometry data. Aims 2 and 3 indicate that hearing impairment is associated with poorer physical function (particularly with balance) and a faster rate of decline in SPPB and HABCPPB scores. Both analyses also showed that participants with hearing impairment had slower walking endurance and aim 3 found that participants with moderate or greater hearing impairment increased their time to complete a long-distance (400-m) walk at a faster rate that participants with normal hearing. We saw no attenuation in these associations after the adjustment for vestibular function. Finally, among participants with hearing impairment, hearing aid users were faster to walk 400-m than nonusers. Conclusions: Across multiple studies, older adults with hearing impairment experience decline in physical functioning at a faster rate than those with normal hearing, suggesting they may be more susceptible to mobility impairments and disability. Little is known about the association between hearing loss and objectively measured physical activity. More research is needed to address this gap

Epidemiology, risk factors, and opportunities for prevention of cardiovascular disease in individuals of South Asian ethnicity living in Europe

South Asian (SA)individuals represent a large, growing population in a number of European countries. These individuals, particularly first-generation SA immigrants, are at higher risk of developing type 2 diabetes, atherogenic dyslipidaemia, and coronary heart disease than most other racial/ethnic groups living in Europe. SAs also have an increased risk of stroke compared to European-born individuals. Despite a large body of conclusive evidence, SA-specific cardiovascular health promotion and preventive interventions are currently scarce in most European countries, as well as at the European Union level. In this narrative review, we aim to increase awareness among clinicians and healthcare authorities of the public health importance of cardiovascular disease among SAs living in Europe, as well as the need for tailored interventions targeting this group – particularly, in countries where SA immigration is a recent phenomenon. To this purpose, we review key studies on the epidemiology and risk factors of cardiovascular disease in SAs living in the United Kingdom, Italy, Spain, Denmark, Norway, Sweden, and other European countries. Building on these, we discuss potential opportunities for multi-level, targeted, tailored cardiovascular prevention strategies. Because lifestyle interventions often face important cultural barriers in SAs, particularly for first-generation immigrants; we also discuss features that may help maximise the effectiveness of those interventions. Finally, we evaluate knowledge gaps, currently available risk stratification tools such as QRISK-3, and future directions in this important field