In view of the consolidating evidence on the causal role of Lp(a) in cardiovascular disease, the Italian Society for the Study of Atherosclerosis (SISA) has assembled a consensus on Lp(a) genetics and epidemiology, together with recommendations for its measurement and current and emerging therapeutic approaches to reduce its plasma levels. Data on the Italian population are also provided. Lp(a) is constituted by one apo(a) molecule and a lipoprotein closely resembling to a low-density lipoprotein (LDL). Its similarity with an LDL, together with its ability to carry oxidized phospholipids are considered the two main features making Lp(a) harmful for cardiovascular health. Plasma Lp(a) concentrations vary over about 1000 folds in humans and are genetically determined, thus they are quite stable in any individual. Mendelian Randomization studies have suggested a causal role of Lp(a) in atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis and observational studies indicate a linear direct correlation between cardiovascular disease and Lp(a) plasma levels. Lp(a) measurement is strongly recommended once in a patient's lifetime, particularly in FH subjects, but also as part of the initial lipid screening to assess cardiovascular risk. The apo(a) size polymorphism represents a challenge for Lp(a) measurement in plasma, but new strategies are overcoming these difficulties. A reduction of Lp(a) levels can be currently attained only by plasma apheresis and, moderately, with PCSK9 inhibitor treatment. Awaiting the approval of selective Lp(a)-lowering drugs, an intensive management of the other risk factors for individuals with elevated Lp(a) levels is strongly recommended.

Purpose Inclisiran is a long-acting small interfering RNA (siRNA) which prevents the synthesis of PCSK9 in hepatocytes, reducing LDL-C concentration. Only limited data are available in the literature regarding its use in real-world settings. Methods In this observational multicenter registry, we included high cardiovascular risk patients from 12 lipid clinics in the Veneto region of Italy who started inclisiran therapy between October 2022 and February 2024. Primary endpoint was changes in LDL-C concentrations at 3 months of follow-up after inclisiran administration. Secondary endpoints were changes in LDL-C concentrations at 9 months of follow-up, safety, percentage of patients reaching LDL-C targets and efficacy of inclisiran according to background therapy and clinical characteristics of the population. Results Mean LDL-C levels at baseline (n = 240) were 118.7 ± 48.7 mg/dl, then they significantly fell to 56.7 ± 40.4 mg/dl (-52.3 ± 24.3%; p < 0.001) at 3 months (n = 238) and to 60.5 ± 40.1 mg/dl (-50.0 ± 22.7%; p < 0.001) at 9 months (n = 138). Three (1.3%) patients reported mild injection-site side effects. LDL-C target achievement according to ESC/EAS 2019 guidelines was 64.7% at 3 months and 62.3% at 9 months. Patients on statin therapy had a greater LDL-C reduction compared to patients with statin intolerance. At 3 months across we observed greater LDL-C reduction in patients with diabetes (59.9 ± 23.2% vs 49.7 ± 24.1%; p = 0.004). In the multivariable analysis diabetes mellitus (p = 0.006) and background statin therapy (p = 0.034) were independent predictors for greater LDL-C reduction. Conclusion This real-world multicenter registry supports inclisiran as an effective, well-tolerated option for managing hypercholesterolemia in high cardiovascular risk patients. Graphical Abstract Key findings and basal characteristics of the population studied (LDL-C, low-density lipoprotein cholesterol; LLT, lipid-lowering therapy; CV, cardiovascular; ASCVD, atherosclerotic cardiovascular disease; DM, diabetes mellitus; FH, familial hypercholesterolemia).

Detection and treatment of patients with familial hypercholesterolemia (FH) starting from childhood is fundamental to reduce morbidity and mortality. The activity of National realities such as the LIPIGEN (LIpid transPort disorders Italian GEnetic Network) Paediatric Group, founded in 2018, is a milestone in this context. The aim of this exploratory survey, conducted in October 2021 among Italian lipid clinics included in the LIPIGEN Paediatric Group, was to investigate the current clinical approach in the management and treatment of paediatric patients with suspected FH. A digital questionnaire composed of 20 questions investigating nutritional treatment and nutraceutical and pharmacological therapy for children and adolescents with FH was proposed to the principal investigators of 30 LIPIGEN centres. Twenty-four centres responded to the section referring to children aged < 10 years and 30 to that referring to adolescents. Overall, 66.7% of children and 73.3% of adolescents were given lipid-lowering nutritional treatment as the first intervention level for at least 3–4 months (29.2% and 23.3%) or 6–12 months (58.3% and 53.3%). Nutraceuticals were considered in 41.7% (regarding children) and 50.0% (regarding adolescents) of the centres as a supplementary approach to diet. Lipid-lowering drug therapy initiation was mainly recommended (91.7% and 80.0%). In 83.3% of children and 96.7% of adolescents, statins were the most frequently prescribed drug. We highlighted several differences in the treatment of paediatric patients with suspected FH among Italian centres; however, the overall approach is in line with the European Atherosclerosis Society (EAS) recommendations for FH children and adolescents. We consider this survey as a starting point to reinforce collaboration between LIPIGEN centres and to elaborate in the near future a consensus document on the management of paediatric patients with suspected FH so as to improve and uniform detection, management, and treatment of these patients in our country.