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. Funding Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron

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

Combination therapy with lercanidipine and enalapril in the management of the hypertensive patient: an update of the evidence

Christina Antza,1 Stella Stabouli,2 Vasilios Kotsis1 1Hypertension Center, Third Department of Medicine, Papageorgiou Hospital, 2First Department of Pediatrics, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece Abstract: Hypertension is an important risk factor for premature death as it increases the probability of stroke, myocardial infarction, and heart failure. Antihypertensive drugs can decrease cardiovascular (CV) morbidity and mortality. The majority of hypertensive patients need more than one antihypertensive agent to attain blood pressure (BP) targets. Monotherapy can effectively reduce BP only in 20%–40% of patients. Multiple mechanisms including increased peripheral vascular resistance, increased cardiac work, and hypervolemia are involved in the pathogenesis of hypertension. Targeting multiple pathways may more potently reduce BP. Increasing the dose of a single agent in many cases does not provide the expected BP-lowering effect because the underlying mechanism of the BP increase is either different or already corrected with the lower dose. Moreover, drugs acting on different pathways may have synergistic effects and thus better control hypertension. It is well known that diuretics enhance the actions of renin–angiotensin aldosterone system and activate it as a feedback to the reduced circulated blood volume. The addition of a renin–angiotensin aldosterone system blocker to a diuretic may more effectively reduce BP because the system is upregulated. Reducing the maximal dose of an agent may also reduce possible side effects if they are dose dependent. The increased prevalence of peripheral edema with higher doses of calcium channel blockers (CCBs) is reduced when renin–angiotensin aldosterone system blockers are added to CCBs through vein dilation. The effectiveness of the combination of enalapril with lercanidipine in reducing BP, the safety profile, and the use of the combination of angiotensin-converting enzyme inhibitors with CCBs in clinical trials with excellent CV hard end point outcomes make this combination a promising therapy in the treatment of hypertension. Keywords: angiotensin-converting enzyme inhibitors, calcium channel blockers, hypertension, lercanidipine, enalapri

Cardiovascular, renal and liver protection with novel antidiabetic agents beyond blood glucose lowering in type 2 diabetes: Consensus article from the European Society of Hypertension Working Group on Obesity, Diabetes and the High-risk Patient

The prevalence of type 2 diabetes (T2D) has increased over the past few decades. T2D has a strong genetic propensity that becomes overt when a patient is exposed to a typical Western lifestyle, gain weight and becomes obese, whereas weight loss protects from the development of T2D. Except of lifestyle modifications, the choice of the appropriate treatment is essential in the management of patients with T2D and appears critical for the obese population with T2D. The new pharmacological approach for the treatment of T2D, sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists, seems to be effective not only in the management of T2D but also for weight loss, reduction of blood pressure and improvement of nonalcoholic fatty liver disease. Sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 analogues reduced cardiovascular risk, prevented cardiovascular disease and mortality, thereby playing an important role in the treatment of obese patients with hypertension and T2D. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved

Prevalence of non-coronary heart disease in patients with familial hyperc-holesterolemia: An analysis from the HELLAS-FH

Aims: Despite the established link between familial hypercholesterolemia (FH) and increased risk of coronary heart disease (CHD), its association with other common atherosclerotic and metabolic diseases has not been extensively studied. The aim of this study was to report the prevalence of peripheral arterial disease (PAD) [i.e., common carotid artery disease (CCAD) and lower extremity arterial disease (LEAD)], aortic valve stenosis, chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) in patients with FH. Materials & Methods: This was a cross-sectional study retrieving data from the Hellenic Familial Hypercholes-terolemia Registry (HELLAS-FH). Results: A total of 1,633 adult patients (850 males) with heterozygous FH (HeFH) were included (mean age 51.3±14.6 years at registration and 44.3±15.9 years at diagnosis). Any common carotid artery stenosis (CCAS) was diagnosed in 124 out of 569 patients with available related data (21.8%), while the prevalence of CCAD (defined as a CCAS ≥50%) was 4.2%. The median (interquartile range-IQR) CCAS was 30% (20-40), whereas the median (IQR) carotid intima-media thickness (CIMT) was 0.7 (0.1-1.4) mm. LEAD was reported in 44 patients (prevalence 2.7%). The prevalence of aortic valve stenosis and CKD was 2.0% and 6.4%, respec-tively. NAFLD was present in 24% of study participants. Conclusion: HeFH is associated with a relatively high prevalence of any CCAS and CCAD. The prevalence of LEAD, CKD and aortic valve stenosis was relatively low, whereas the prevalence of NAFLD was similar to that of the general population. © 2021 Bentham Science Publishers

Characteristics and management of 1093 patients with clinical diagnosis of familial hypercholesterolemia in Greece: Data from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH)

Background and aims: Although familial hypercholesterolemia (FH) is one of the most common genetic disorders, it remains largely underdiagnosed and undertreated. The Hellenic Atherosclerosis Society has established the Hellenic Familial Hypercholesterolemia (HELLAS-FH) Registry, part of the Familial Hypercholesterolemia Studies Collaboration (FHSC), to evaluate the characteristics and management of patients with FH in Greece. Methods: Patients with diagnosed FH were recruited by a network of sites throughout Greece. The prevalence of cardiovascular disease (CVD) risk factors, as well as management of FH, was recorded. Results: This interim analysis included 1093 patients (556 male; 950 adults). The median age of FH diagnosis was 42.2 years (interquartile range 27.2–53.0). A family history of CVD was present in 47.8%, while 21.1% of patients had a personal history of CVD. At diagnosis, low-density lipoprotein cholesterol (LDL-C) was 241 ± 76 mg/dL in adults and 229 ± 57 mg/dL in children. Overall, 63.1% of the patients were receiving hypolipidemic drug treatment, mainly statins, at inclusion in the registry. Mean LDL-C of patients receiving drug treatment was 154 ± 76 mg/dL in adults and 136 ± 47 mg/dL in children. The majority of treated patients (87.9%) did not achieve LDL-C targets. Conclusions: FH in Greece is characterized by a significant delay in diagnosis and a high prevalence of both family and personal history of established CVD. The vast majority of FH patients do not achieve LDL-C targets. Improved awareness and management of FH are definitely needed. © 2018 Elsevier B.V

Association between lipoprotein(a) concentrations and atherosclerotic cardiovascular disease risk in patients with familial hypercholesterolemia: an analysis from the HELLAS-FH

Aims:: Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) in the general population. However, such a role in patients with familial hypercholesterolemia (FH) is less documented. The purpose of this study was to evaluate the association between Lp(a) concentrations and ASCVD prevalence in adult patients with FH. Methods:: This was a cross-sectional study from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). Patients were categorized into 3 tertiles according to Lp(a) levels. Results:: A total of 541 adult patients (249 males) with possible/probable/definite FH heterozygous FH (HeFH) were included (mean age 48.5 ± 15.0 years at registration, 40.8 ± 15.9 years at diagnosis). Median (interquartile range) Lp(a) concentrations in the 1st, 2nd and 3rd Lp(a) tertile were 6.4 (3.0–9.7), 22.4 (16.0–29.1) and 77.0 (55.0–102.0) mg/dL, respectively. There was no difference in lipid profile across Lp(a) tertiles. The overall prevalence of ASCVD was 9.4% in the first, 16.1% in the second and 20.6% in the third tertile (p = 0.012 among tertiles). This was also the case for premature ASCVD, with prevalence rates of 8.5, 13.4 and 19.8%, respectively (p = 0.010 among tertiles). A trend for increasing prevalence of coronary artery disease (8.3, 12.2 and 16.1%, respectively; p = 0.076 among tertiles) was also observed. No difference in the prevalence of stroke and peripheral artery disease was found across tertiles. Conclusions:: Elevated Lp(a) concentrations are significantly associated with increased prevalence of ASCVD in patients with possible/probable/definite HeFH. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature