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

Recent developments in paediatric neuraxial blocks

Paediatric anaesthesia and paediatric regional anaesthesia are intertwined. Almost all surgeries unless contradicted could be and should be supplemented with a regional block. The main objective of this review is to elaborate on the recent advances of the central neuraxial blocks, such as application of ultrasound guidance and electrical stimulation in the pursuit of safety and an objective end point. This review also takes account of the traditional technique and understand the benefits as well the risk of each as compared with the recent technique. The recent trends in choosing the most appropriate peripheral block for a given surgery thereby sparing the central neuroaxis is considered. A penile block for circumcision or a sciatic block for unilateral foot surgery, rather than caudal epidural would have a better risk benefit equation. Readers will find a special mention on the recent thoughts on continuous epidural analgesia in paediatrics, especially its rise and fall, yet its unique importance. Lastly, the issue of block placements under sedation or general anaesthesia with its implication in this special population is dealt with. We conducted searches in MEDLINE (PubMed) and assessed the relevance of the abstracts of citations identified from literature searches. The search was carried out in English, for last 10 years, with the following key words: Recent advances in paediatric regional anaesthesia; ultrasound guidance for central neuraxial blocks in children; role of electrical stimulation in neuraxial blocks in children; complications in neuraxial block. Full-text articles of potentially relevant abstracts were retrieved for further review

Association of <i>CYBA G640A</i> variation with coronary artery disease in Indians

<p><b>Introduction</b>: Oxidative stress induces atherosclerosis by triggering an inflammatory cascade within the vascular wall.</p> <p><b>Objective</b>: To investigate the role of pro-oxidant and antioxidant gene variations with CAD in Indian subjects.</p> <p><b>Materials & methods</b>: It’s a case-control study and genotyping for the variants <i>MPO G-463A, CYBA G640A, SOD2 Val16Ala</i> and <i>CAT C-262T</i> were performed by conventional PCR techniques.</p> <p><b>Results</b>: Only <i>CYBA G640A</i> variant allele was found to be significantly (<i>p</i> = 0.0075) associated with CAD.</p> <p><b>Conclusion</b>: Although <i>CYBA G640A</i> variation was found to be significant, a larger study is needed to validate these results and establish its role as a biomarker.</p

Platelet polymorphisms: frequency distribution and association with coronary artery disease in an Indian population

Platelets play a critical role in normal blood hemostasis and thrombus formation in myocardial infarction (MI). Several polymorphisms of genes involved in platelet activation and fibrinolysis have been reported to be associated with MI. The aim of the present study was to determine the frequency distribution and association of polymorphisms in these genes with coronary artery disease (CAD) among Indians. A case-control genetic association study was performed for polymorphisms in platelet glycoprotein receptors (GPIIb/IIIa [HPA1a/1b], GPIb-IX-V [VNTR], and GPIa/IIa [C807T]), fibrinogen &#946;-chain (BclI), &#945;-chain (A&#945;312), tissue plasminogen activator (tPA) [I/D] and plasminogen activator inhibitor-I (PAI-1) [4G/5G] in 473 healthy controls and 446 patients with stable and unstable angina. Genotyping was either by PCR-based restriction endonuclease digestion or allele-specific primers. The I allele frequency of the tPA I/D polymorphism was significantly higher in our patients (&#967;2=7.33, P&lt;0.01) and no other polymorphisms varied significantly between patients and controls. Also, none of the polymorphisms seemed to affect the severity of the disease, the only exception being the mutant alleles of &#946; chain of fibrinogen gene, which were significantly elevated in single vessel disease. This is the first study to evaluate the role of gene polymorphisms in both the thrombotic and fibrinolytic pathway in the Indian population and suggests that tPA I/D polymorphism confers CAD risk in our population

Blood pressure related to age: The India ABPM study

The present paper reports trends in office blood pressure (BP) measurement (OBPM) and ambulatory blood pressure measurement (ABPM) with age in a large multi‐center Indian all comers’ population visiting primary care physicians. ABPM and OBPM data from 27 472 subjects (aged 51 ± 14 years, males 68.2%, treated 45.5%) were analyzed and compared. Individual differences between OBPM and ABPM patterns were compared for patients according to 10‐year age categories. Results showed that systolic (S) BP values started to increase with age from the age of 40, BP variability (SD) increased from the age of 30 years. Diastolic (D) BP values started to decrease from the age of 50 years. Mean OBPM values were higher than daytime ABPM values (all P < .001) in all age‐groups. The prevalence of white coat hypertension (WCH) and masked hypertension (MH) was based on OBPM and daytime, 24‐hour, and nighttime average BPs together. WCH decreased with age from 15.1% and 12.4% in treated and untreated subjects at the youngest age to 7.2% and 6.9% in the oldest age, respectively. MH prevalence was higher for untreated than for treated subjects but remained similar for all age‐groups (range of 18.6%‐21.3%). The prevalence of reverse dippers increased with age from the youngest to oldest group with 7.3%‐34.2% (P < .001 for trend). Dippers prevalence decreased from 42.5% to 17.9% from the youngest to oldest age‐groups, respectively (P < .001 for trend). These findings confirm that BP patterns show clear differences in trends with age, particularly regarding nighttime BP

Blood pressure related to age: The India ABPM study

The present paper reports trends in office blood pressure (BP) measurement (OBPM) and ambulatory blood pressure measurement (ABPM) with age in a large multi‐center Indian all comers’ population visiting primary care physicians. ABPM and OBPM data from 27 472 subjects (aged 51 ± 14 years, males 68.2%, treated 45.5%) were analyzed and compared. Individual differences between OBPM and ABPM patterns were compared for patients according to 10‐year age categories. Results showed that systolic (S) BP values started to increase with age from the age of 40, BP variability (SD) increased from the age of 30 years. Diastolic (D) BP values started to decrease from the age of 50 years. Mean OBPM values were higher than daytime ABPM values (all P < .001) in all age‐groups. The prevalence of white coat hypertension (WCH) and masked hypertension (MH) was based on OBPM and daytime, 24‐hour, and nighttime average BPs together. WCH decreased with age from 15.1% and 12.4% in treated and untreated subjects at the youngest age to 7.2% and 6.9% in the oldest age, respectively. MH prevalence was higher for untreated than for treated subjects but remained similar for all age‐groups (range of 18.6%‐21.3%). The prevalence of reverse dippers increased with age from the youngest to oldest group with 7.3%‐34.2% (P < .001 for trend). Dippers prevalence decreased from 42.5% to 17.9% from the youngest to oldest age‐groups, respectively (P < .001 for trend). These findings confirm that BP patterns show clear differences in trends with age, particularly regarding nighttime BP