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Aims: The availability of novel lipid-lowering therapies (LLTs) has remarkably changed the clinical management of homozygous familial hypercholesterolaemia (HoFH). The impact of these advances was evaluated in a cohort of 139 HoFH patients followed in a real-world clinical setting., Methods and Results: The clinical characteristics of 139 HoFH patients, along with information about LLTs and low-density lipoprotein cholesterol (LDL-C) levels at baseline and after a median follow-up of 5 years, were retrospectively retrieved from the records of patients enrolled in the LIPid transport disorders Italian GEnetic Network-Familial Hypercholesterolaemia (LIPIGEN-FH) Registry. The annual rates of major atherosclerotic cardiovascular events (MACE-plus) during follow-up were compared before and after baseline. Additionally, the lifelong survival free from MACE-plus was compared with that of the historical LIPIGEN HoFH cohort. At baseline, LDL-C level was 332 ± 138 mg/dL. During follow-up, the potency of LLTs was enhanced and, at the last visit, 15.8% of patients were taking quadruple therapy. Consistently, LDL-C decreased to an average value of 124 mg/dL corresponding to a 58.3% reduction (Pt < 0.001), with the lowest value (∼90 mg/dL) reached in patients receiving proprotein convertase subtilisin/kexin type 9 inhibitors and lomitapide and/or evinacumab as add-on therapies. The average annual MACE-plus rate in the 5-year follow-up was significantly lower than that observed during the 5 years before baseline visit (21.7 vs. 56.5 per 1000 patients/year; P = 0.0016)., Conclusion: Our findings indicate that the combination of novel and conventional LLTs significantly improved LDL-C control with a signal of better cardiovascular prognosis in HoFH patients. Overall, these results advocate the use of intensive, multidrug LLTs to effectively manage HoFH., Competing Interests: Conflict of interest: Mar.A. received research grant support from Amryt Pharmaceutical, Amgen, IONIS, Akcea Therapeutics, Daiichi-Sankyo, Novartis, Pfizer, and Regeneron; served as a consultant for Amgen, Akcea Therapeutics, Daiichi-Sankyo, and Ultragenyx; and received fees for lecturing, congress participation, and advisory board participation from Amgen, Amryt Pharmaceutical, Daiichi-Sankyo, Regeneron, Sanofi, Amarin, and Ultragenyx. R.A. received consulting fees from GSK-Galaxosmithline. Si.B. received fees for lectures from SOBI; detains stock options of Eli Lilly, UnitedHealth, Novo Nordisk, Merck, and Thermo Fisher Scientific; and received grants for meeting participation from Novartis. M.B. received fees for lectures from Menarini, Servier, Alfasigma, Neopharmed, Aurora, Biopharma, Amryt, Novartis, Sanofi, and Viatris and received fees for participations in meeting from Ultragenyx, Daiichi-Sankyo, Lusofarmaco, and Sanofi. Carubbi F received grants for lectures and meeting participation from Amgen and Amryt, received funding for grants from Sanofi and Amgen, and received funding for data monitoring and lectures from Sanofi. A.L.C. received funding for consulting, lectures, and meeting attendance from Amgen, AstraZeneca, Aegerion, Amryt, Daiichi-Sankyo, Esperion, Kowa, Ionis Pharma, Mylan, Merck, Menarini, Novartis, Recordati, Regeneron, Sandoz, Sanofi, and Viatris and also received research grants from Sanofi, Eli Lilly, Amgen, Menarini, Sanofi-Regeneron, and Mylan. L.D. received personal fees for public speaking or consultancy or grant support from Amryt Pharmaceutical, Akcea Therapeutics, SOBI, AuroraBiopharma, Novartis, Amarin, Daiichi-Sankyo, Bayer, and Sandoz. F.F. received consulting funds from Merck. G.I. received funds for research grants from Amryt and Ultragenix; lecture fees from Novartis, Sanofi, Lusofarmaco, and Agaton; funds for meeting attendance from Ultragenix; and funds for data monitoring from Novartis, Agaton, and Sanofi; G.M. received research grants from Daiichi-Sankyo and Novartis; lecture fees from Amgen, Eli Lilly, and Neopharmed; fund for meeting attendance from Amgen; and funds for data monitoring from Sanofi-Aventis, Daiichi-Sankyo, Amrin, and Novo Nordisk. F.N. received fees for consulting, lectures, and data monitoring from Sanofi. C.P. received fees for lectures from SOBI. L.P. received fees for lectures from Amgen, Sanofi, and Amryt and received funding for meeting attendance from Sanofi, Ultragenyx, and Daiichi-Sankyo; D.T. received fees for lectures from SOBI. J.P.W. received fees for lectures from Servier, Novartis, Daiichi-Sankyo, Sanofi, and Amgen and received funding for meeting attendance from Daiichi-Sankyo, Amgen, and MSD. A.Z. received fees for lectures from Amgen, Sanofi, Amarin, Amryt, Abbott, Viatris, Novartis, Daiichi-Sankyo, Alfasigma, and Servier. The other authors have no conflicts of interest to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

This 2023 statement updates clinical guidance for homozygous familial hypercholesterolaemia (HoFH), explains the genetic complexity, and provides pragmatic recommendations to address inequities in HoFH care worldwide. Key strengths include updated criteria for the clinical diagnosis of HoFH and the recommendation to prioritize phenotypic features over genotype. Thus, a low-density lipoprotein cholesterol (LDL-C) >10 mmol/L (>400 mg/dL) is suggestive of HoFH and warrants further evaluation. The statement also provides state-of-the art discussion and guidance to clinicians for interpreting the results of genetic testing and for family planning and pregnancy. Therapeutic decisions are based on the LDL-C level. Combination LDL-C-lowering therapy-both pharmacologic intervention and lipoprotein apheresis (LA)-is foundational. Addition of novel, efficacious therapies (i.e. inhibitors of proprotein convertase subtilisin/kexin type 9, followed by evinacumab and/or lomitapide) offers potential to attain LDL-C goal or reduce the need for LA. To improve HoFH care around the world, the statement recommends the creation of national screening programmes, education to improve awareness, and management guidelines that account for the local realities of care, including access to specialist centres, treatments, and cost. This updated statement provides guidance that is crucial to early diagnosis, better care, and improved cardiovascular health for patients with HoFH worldwide., Competing Interests: Conflict of interest Potential conflicts of interest outside the submitted work are summarized as follows. The following authors report participation in trials; receipt of fellowships, or grants for travel, research or staffing support; and/or personal honoraria for consultancy or lectures/speaker’s bureau from: Abbott (K.A.-R., M.K., K.K.R., R.D.S., L.S.T.); Abdi-Ibrahim (M.K., L.S.T.); Acasti (D.G., R.A.H.); Ache (R.D.S.); Actelion (L.S.T.); Aegerion (M.A., E.B., D.G., M.H.-S.); Akcea (M.A., E.B., A.L.C., D.G., R.A.H., K.G.P.); Alexion Pharma France (E.B.); Alfasigma (M.A.); Amarin (M.A., M.Av., A.L.C., L.M.); Amgen (M.A., M.Av., E.B., T.F., D.G., M.H.-S., R.A.H., M.K., L.M., K.G.P., F.J.R., K.K.R., R.D.S., L.S.T., G.F.W., A.W.); Amryt (M.A., M.Av., MC, M.K., L.M., J.E.R.v.L., R.D.S., A.W.); Arrowhead (R.A.H., G.F.W.); Ascent Development (M.H.-S.); Astellas (M.H.-S.); AstraZeneca (A.L.C., D.G., M.K., K.K.R., R.D.S., G.F.W.); Bayer (M.K., L.S.T.); Biolab (R.D.S.); Boehringer Ingelheim (D.G., M.H.-S., K.K.R.); Cerenis (D.G.); CRISPR Therapeutics (K.K.R.); Daiichi-Sankyo (M.Av., E.B., A.L.C., M.H.-S., M.K., L.M., K.G.P., K.K.R., L.S.T.); Dalcor Pharma (D.G.); Danone (E.B.); Deva (M.K.); Esperion (A.L.C., D.G., K.K.R., R.D.S., G.F.W.); Gemphire (D.G.); Genfit (E.B.); Genzyme (A.L.C.); Getz Pharma (R.D.S.); GlaxoSmithKline (D.G.); HDL Therapeutics (D.G.); HLS Therapeutics (R.A.H.); Ionis Pharmaceuticals (E.B., A.L.C., D.G., M.K.); Ironwood (D.G.); Jansen (M.K.); Kowa (A.L.C., D.G., M.H.-S., K.K.R., R.D.S.); LIB Therapeutics (R.A.H., M.K., F.J.R.); Libbs (R.D.S.); Eli Lilly/Lilly (A.L.C., D.G., M.K., K.K.R.); Medpace (M.H.-S., M.K.); Menarini (A.L.C.); Merck (A.L.C., M.K., R.D.S., L.S.T.); MSD (E.B., M.H.-S., K.G.P.); Mylan (M.A., E.B., A.L.C.); Nestlé (D.G.); New Amsterdam (K.K.R.); Novartis (K.A.-R., M.A., M.Av., E.B., A.L.C., T.F., D.G., M.H.-S., R.A.H., M.K., L.M., K.G.P., K.K.R., J.E.R.v.L., F.J.R., R.D.S., L.S.T., G.F.W., A.W.); NovoNordisk (M.K., K.K.R., R.D.S., L.S.T.); Pfizer (M.A., A.L.C., D.G., R.A.H., M.K., K.K.R., R.D.S., L.S.T., G.F.W.); PTC (R.D.S.); Recordati (A.L.C., M.H.-S., M.K., L.S.T.); Regeneron (M.A., A.L.C., MC, D.G., R.A.H., K.G.P., F.J.R., K.K.R., A.W.); REGENXBIO (M.C.); Resverlogix (K.K.R.); Sandoz (A.L.C.); Sanofi (K.A.-R., M.A., A.L.C., T.F., D.G., M.H.-S., R.A.H., M.K., L.M., K.G.P., F.J.R., K.K.R., R.D.S., L.S.T., G.F.W.); Sanofi/Genzyme (M.Av.); Sanofi-Regeneron (E.B.); SCIBE Therapeutics (K.K.R.); Servier (E.B., L.M., L.S.T.); Sigma Tau (A.L.C.); Silence Therapeutics (E.B., K.G.P., K.K.R., G.F.W., A.W.); Sobi Takeda (M.Av.); The Medicine Company (D.G., M.H.-S.); Ultragenyx (R.A.H.); UniQure (D.G.); and Vaxxinity (K.K.R.). ESG Stroes reports honoraria for lectures/advisory board R.D.S. paid to his institution from Amarin, Amgen, Daiichi-Sankyo, Esperion, IONIS/Akcea, Novartis, Novo-Nordisk, and Sanofi-Regeneron. Manuscripts have been published in collaboration with non-academic co-authors by L.S.T. (Fitbit), and G.F.W. (Amgen). T.F. is supported by the project National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES, ID Project No. LX22NPO5104)—Funded by the European Union—Next Generation EU. D.G. is supported by Canadian Cardiovascular Research Network and the Institut de cardiologie de Montréal. Equity interests are reported by K.K.R. (Cargene Therapeutics and Pemi31 Therapeutics) and J.K.S. (AstraZeneca and GSK). K.K.R. is President of the European Atherosclerosis Society. L.S.T. is Past-President of the European Atherosclerosis Society and an Editorial Board Member, The European Heart Journal. L.C.H. has no disclosures., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Leucocyte telomere length (LTL) shortening is a marker of cellular senescence and associates with increased risk of cardiovascular disease (CVD). A number of cardiovascular risk factors affect LTL, but the correlation between elevated LDL cholesterol (LDL-C) and shorter LTL is debated: in small cohorts including subjects with a clinical diagnosis of familial hypercholesterolaemia (FH). We assessed the relationship between LDL-C and LTL in subjects with genetic familial hypercholesterolaemia (HeFH) compared to those with clinically diagnosed, but not genetically confirmed FH (CD-FH), and normocholesterolaemic subjects., Methods and Results: LTL was measured in mononuclear cells-derived genomic DNA from 206 hypercholesterolaemic subjects (135 HeFH and 71 CD-FH) and 272 controls. HeFH presented shorter LTL vs. controls (1.27 ± 0.07 vs. 1.59 ± 0.04, P = 0.045). In particular, we found shorter LTL in young HeFH as compared to young controls (<35 y) (1.34 ± 0.08 vs. 1.64 ± 0.08, P = 0.019); moreover, LTL was shorter in statin-naïve HeFH subjects as compared to controls (1.23 ± 0.08 vs. 1.58 ± 0.04, P = 0.001). HeFH subjects presented shorter LTL compared to LDL-C matched CD-FH (1.33 ± 0.05 vs. 1.55 ± 0.08, P = 0.029). Shorter LTL was confirmed in leucocytes of LDLR-KO vs. wild-type mice and associated with lower abundance of long-term haematopoietic stem and progenitor cells (LT-HSPCs) in the bone marrow. Accordingly, HeFH subjects presented lower circulating haematopoietic precursors (CD34 + CD45dim cells) vs. CD-FH and controls., Conclusions: We found (i) shorter LTL in genetically determined hypercholesterolaemia, (ii) lower circulating haematopoietic precursors in HeFH subjects, and reduced bone marrow resident LT-HSPCs in LDLR-KO mice. We support early cellular senescence and haematopoietic alterations in subjects with FH., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: To obtain safety and efficacy data of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in a real-life setting in high cardiovascular (CV) risk patients with heterozygous familial hypercholesterolaemia (HeFH) or very-high low-density lipoprotein cholesterol (LDL-C) levels despite maximally tolerated dose of statin ± other lipid-lowering therapies (MTD ± LLTs). ODYSSEY APPRISE was a prospective, single-arm, Phase 3b open-label (≥12 weeks to ≤ 30 months) European/Canadian study with alirocumab., Methods and Results: Patients received alirocumab 75 or 150 mg every 2 weeks, with dose adjustment based on physician's judgment. In total, 994 patients were enrolled and treated. The mean [standard deviation (SD)] duration of alirocumab exposure was 72.4 (42.5) weeks. Patients with HeFH were younger [mean (SD) age of 53.8 (11.6) vs. 61.6 (10.1) years], more likely to be female (41.7% vs. 29.1%) and had higher baseline LDL-C compared with non-familial hypercholesterolaemia (non-FH) patients [mean (SD) of 5.1 (1.7) vs. 4.1 (1.1) mmol/L]. The overall incidence of treatment-emergent adverse events (TEAEs) was 71.6%; common TEAEs included nasopharyngitis (7.8%), myalgia (7.1%), and headache (6.2%). At Week 12, mean (SD) LDL-C was reduced by 54.8 (20.1)% from baseline [2.6 (1.2) mmol/L], maintained for the trial duration. LDL-C was reduced below 1.8 mmol/L and/or by ≥50% reduction from baseline in 69.1% of patients overall, and for 64.7 and 77.4% of the HeFH and non-FH subgroups, respectively., Conclusion: In a real-life setting in patients with hypercholesterolaemia and high CV risk, alirocumab was generally well tolerated and resulted in clinically significant LDL-C reductions., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Recent advances in human genetics, together with a large body of epidemiologic, preclinical, and clinical trial results, provide strong support for a causal association between triglycerides (TG), TG-rich lipoproteins (TRL), and TRL remnants, and increased risk of myocardial infarction, ischaemic stroke, and aortic valve stenosis. These data also indicate that TRL and their remnants may contribute significantly to residual cardiovascular risk in patients on optimized low-density lipoprotein (LDL)-lowering therapy. This statement critically appraises current understanding of the structure, function, and metabolism of TRL, and their pathophysiological role in atherosclerotic cardiovascular disease (ASCVD). Key points are (i) a working definition of normo- and hypertriglyceridaemic states and their relation to risk of ASCVD, (ii) a conceptual framework for the generation of remnants due to dysregulation of TRL production, lipolysis, and remodelling, as well as clearance of remnant lipoproteins from the circulation, (iii) the pleiotropic proatherogenic actions of TRL and remnants at the arterial wall, (iv) challenges in defining, quantitating, and assessing the atherogenic properties of remnant particles, and (v) exploration of the relative atherogenicity of TRL and remnants compared to LDL. Assessment of these issues provides a foundation for evaluating approaches to effectively reduce levels of TRL and remnants by targeting either production, lipolysis, or hepatic clearance, or a combination of these mechanisms. This consensus statement updates current understanding in an integrated manner, thereby providing a platform for new therapeutic paradigms targeting TRL and their remnants, with the aim of reducing the risk of ASCVD., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Context: Type 1a and 1b glycogenosis [glycogen storage disorder (GSD)1a, GSD1b] are rare diseases generally associated with malnutrition. Although abnormal substrate oxidation rates and elevated energy expenditures might contribute to malnutrition, this issue has not been investigated., Objective: To investigate whether abnormal resting energy expenditure (REE) and substrate oxidation rate characterize patients with GSD1., Design: Cross-sectional study., Setting: Outpatient referral center for rare diseases and laboratory of clinical nutrition at the University Hospital of Palermo., Patients: Five consecutive patients with GSD1 (4 type a, 1 type b; 3 men, 2 women; age range, 19 to 49 years)., Main Outcome Measures: The usual clinical procedures for patients with malnutrition, including REE and basal substrate oxidation rate (both indirect calorimetry), body composition (bioimpedance method), muscle strength (hand-grip test), and the usual laboratory tests, were performed., Results: Malnutrition was clearly diagnosed in 2 patients (1 GSD1a and 1 GSD1b), with REE elevated in all five patients, and especially, in the two malnourished patients (+124% and +32.1% vs predictive values using Harris-Benedict equations). The two malnourished patients also exhibited lower basal protein oxidation rates (7.7% and 6.6%) than the nourished patients (range, 12.1% to 24.7%), with higher carbohydrate or lipid oxidation rates. Additionally, the two malnourished patients exhibited higher blood concentrations of lactic acid than the nourished patients., Conclusions: According to data obtained from our small sample of patients with GSD1, elevated REEs seem to be a common characteristic that might contribute to malnutrition. Low basal protein oxidation rates and elevated blood lactic acid concentrations appear to be associated with malnutrition., (Copyright © 2019 Endocrine Society.)

Atherosclerotic cardiovascular disease still represents the leading cause of death in Western countries. A wealth of scientific evidence demonstrates that increased blood cholesterol levels have a major impact on the outbreak and progression of atherosclerotic plaques. Moreover, several cholesterol-lowering pharmacological agents, including statins and ezetimibe, have proved effective in improving clinical outcomes. This document focuses on the clinical management of hypercholesterolaemia and has been conceived by 16 Italian medical associations with the support of the Italian National Institute of Health. The authors discuss in detail the role of hypercholesterolaemia in the genesis of atherosclerotic cardiovascular disease. In addition, the implications for high cholesterol levels in the definition of the individual cardiovascular risk profile have been carefully analysed, while all available therapeutic options for blood cholesterol reduction and cardiovascular risk mitigation have been explored. Finally, this document outlines the diagnostic and therapeutic pathways for the clinical management of patients with hypercholesterolaemia.

Familial hypercholesterolaemia (FH) is a common genetic cause of premature coronary heart disease (CHD). Globally, one baby is born with FH every minute. If diagnosed and treated early in childhood, individuals with FH can have normal life expectancy. This consensus paper aims to improve awareness of the need for early detection and management of FH children. Familial hypercholesterolaemia is diagnosed either on phenotypic criteria, i.e. an elevated low-density lipoprotein cholesterol (LDL-C) level plus a family history of elevated LDL-C, premature coronary artery disease and/or genetic diagnosis, or positive genetic testing. Childhood is the optimal period for discrimination between FH and non-FH using LDL-C screening. An LDL-C ≥5 mmol/L (190 mg/dL), or an LDL-C ≥4 mmol/L (160 mg/dL) with family history of premature CHD and/or high baseline cholesterol in one parent, make the phenotypic diagnosis. If a parent has a genetic defect, the LDL-C cut-off for the child is ≥3.5 mmol/L (130 mg/dL). We recommend cascade screening of families using a combined phenotypic and genotypic strategy. In children, testing is recommended from age 5 years, or earlier if homozygous FH is suspected. A healthy lifestyle and statin treatment (from age 8 to 10 years) are the cornerstones of management of heterozygous FH. Target LDL-C is <3.5 mmol/L (130 mg/dL) if >10 years, or ideally 50% reduction from baseline if 8-10 years, especially with very high LDL-C, elevated lipoprotein(a), a family history of premature CHD or other cardiovascular risk factors, balanced against the long-term risk of treatment side effects. Identifying FH early and optimally lowering LDL-C over the lifespan reduces cumulative LDL-C burden and offers health and socioeconomic benefits. To drive policy change for timely detection and management, we call for further studies in the young. Increased awareness, early identification, and optimal treatment from childhood are critical to adding decades of healthy life for children and adolescents with FH., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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 prevalences between 1/500 and 1/200, between 14 and 34 million individuals worldwide have FH. We recommend that children, adults, and families should be screened for FH if a person or family member presents with FH, a plasma cholesterol level in an adult ≥8 mmol/L(≥310 mg/dL) or a child ≥6 mmol/L(≥230 mg/dL), premature CHD, tendon xanthomas, or sudden premature cardiac death. In FH, low-density lipoprotein cholesterol targets are <3.5 mmol/L(<135 mg/dL) for children, <2.5 mmol/L(<100 mg/dL) for adults, and <1.8 mmol/L(<70 mg/dL) for adults with known CHD or diabetes. In addition to lifestyle and dietary counselling, treatment priorities are (i) in children, statins, ezetimibe, and bile acid binding resins, and (ii) in adults, maximal potent statin dose, ezetimibe, and bile acid binding resins. Lipoprotein apheresis can be offered in homozygotes and in treatment-resistant heterozygotes with CHD., Conclusion: Owing to severe underdiagnosis and undertreatment of FH, there is an urgent worldwide need for diagnostic screening together with early and aggressive treatment of this extremely high-risk condition.

Background: Lipoid proteinosis (LP), also known as Urbach-Wiethe disease, is a rare autosomal recessive disorder characterized by a hoarse voice, warty skin infiltration and scarring. Mutations within the extracellular matrix protein 1 (ECM1) gene cause LP., Objectives: We report the molecular analysis of the ECM1 gene in a Sicilian patient with LP in order to extend the mutation spectrum of this genodermatosis., Methods: We studied a 32-year-old female born from consanguineous parents who was diagnosed at the age of 11 years as having LP. She has a clinical phenotype corresponding to Urbach-Wiethe disease characterized by papules/nodules, indurated plaques and sometimes ulcerated lesions primarily involving the skin and mucous membranes, and extracutaneous features such as epilepsy, hoarseness of the voice and neuropsychiatric abnormalities. Samples of clinically affected skin obtained by biopsies were analysed after staining with haematoxylin and eosin, periodic acid-Schiff (PAS), and PAS-diastase. The whole ECM1 gene was analysed by direct sequencing., Results: We identified a homozygous nonsense mutation in exon 6 of the ECM1 gene, C589T (Q197Ter)., Conclusions: Over 60% of mutations occur in exons 6 and 7. Exon 7 is alternatively spliced and frameshift mutations in exon 7 lead to ablation of the ECM1a transcript, but not the shorter ECM1b transcript that normally lacks this exon. Homozygous nonsense or frameshift mutations in exon 6 are predicted to affect both full-length ECM1a and ECM1b transcripts, whereas ECM1b should be unaffected for similar types of mutation in exon 7. It has been suggested that individuals with mutations in exon 7 have a slightly milder phenotype than those with exon 6 mutations. This is the first report with respect to a novel mutation of the ECM1 gene responsible for recessive LP in Sicily.

Familial apolipoprotein (apo) CII deficiency is a rare autosomal recessive inborn error of metabolism clinically resembling lipoprotein lipase deficiency. A number of mutations of the apo CII gene are known to date; they are located in the promoter region, the coding exons, or in the splice junctions. We present a simple assay based on PCR and denaturing gradient gel electrophoresis, which allows scanning of the promoter, the entire coding sequence, and the splice junctions of the apo CII gene for sequence variants. All gene fragments are amplified using a common PCR protocol and are examined for mutations on a single gradient gel. Using this method and direct sequencing, we identified homozygosity for a donor splice-site mutation in the second intron, previously designated apo CII-Hamburg, as the genetic cause of apo CII deficiency in a 9-year-old boy presenting with chylomicronemia, eruptive xanthoma, and pancreatitis. In addition, the method allowed us to detect all of six different other known mutations of the apo CII gene. We conclude, therefore, that our assay is highly sensitive; in addition, it is easy to perform and may facilitate the differential diagnosis of disorders of lipoprotein metabolism at the genetic level.

The aims of this study were to evaluate plasma lipid, apoprotein and Lp(a) levels in patients with severe coronary atherosclerosis undergoing aorto-coronary bypass surgery (BP) and to relate these parameters to the involvement of one or more vessels. Seventy-seven male patients and 77 cardiovascular disease-free controls, matched for sex, age and body weight were studied. Higher triglyceride and apo B levels with lower HDL-cholesterol and apo A-I levels were found in BP patients in comparison with the controls. Lp(a) levels were slightly, but not significantly, increased. Moreover BP patients presented a significantly higher prevalence of HDL-cholesterol levels below 35 mg dl-1 (49.3% vs 22.1%) and Lp(a) levels above 70 mg dl-1 (10.4% vs 1.3%) than the controls. When patients were divided according to the number of coronary vessels involved (one, two or three), no significant difference was found, with a trend to increase in Lp(a) mean levels and in prevalence of Lp(a) levels above 30 and 70 mg dl-1 in more severely diseased patients. These results suggest that patients with severe coronary artery disease undergoing aorto-coronary bypass surgery show low HDL-cholesterol levels with high triglyceride levels. Moreover Lp(a) levels above 70 mg dl-1 are highly associated with severe coronary vessel stenosis.

The aim of the present study was to determine the prevalence of biliary lithiasis (BL) and its major associated factors in the elderly people of a small town in Sicily. All inhabitants over the age of 65 were interviewed and underwent a general physical examination, blood tests and ultrasonography of the gallbladder and biliary tracts. The final group included 328 subjects (162 men and 166 women), representing 63.1% of the population asked to participate, with a mean age of 74.3 +/- 6.8 years (range 65-95). The prevalence of BL (lithiasis in progress + subjects cholecystectomized for previous calculosis) was 18.6%. No male subject had been cholecystectomized. Prevalence was higher in women than in men, but there was no progressive increase with age. There was no significant correlation between number of pregnancies and BL and there was no statistically significant difference between subjects with and without lithiasis for total cholesterol, triglycerides, HDL-cholesterol, A-I and B apoprotein values; a significant difference was found only for body weight values (p less than 0.01). Stones were more often multiple and more radiopaque than in younger subjects; specific symptoms and positive family histories were found in 22% and 18% of the study group, respectively.

In 12 patients with arterial hypertension (stages I and II according to WHO), adrenergic stimulation was induced by the immersion of a hand in ice water for 2 min. Blood samples were withdrawn before, at the end of, and 15 min after the cold application: the experiment was repeated 2 h after the ingestion of 200 mg acebutolol, a selective betablocking agent. The following assays were performed: serum nonesterified fatty acid (NEFA), plasma beta-thromboglobulin (BTG) and PF4 with specific radioimmunoassays; thromboxane B2 (TXB2) in plasma was also estimated with radioimmunoassay, platelet sensitivity to exogenous prostacyclin; furthermore, the thrombin-induced thromboxane production before and after acebutolol ingestion as well as serum TXB2-levels were measured. The blood pressure and the heart rate were also monitored. After cold stimulation, a significant increase of NEFA, BTG, and plasma TXB2 was observed, which was still discernible 15 min after the application of cold. After acebutolol, the cold treatment led to a lower increase of blood pressure with a reduction of the heart rate, as well as to a diminished release of BTG, PF4 and TXB2 no changes in the reduced platelet sensitivity to prostacyclin were noticed.