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Pathology registers can be a useful tool to overcome obstacles in the identification and management of familial hypercholesterolemia since childhood. In 2018, the LIPIGEN pediatric group was constituted within the Italian LIPIGEN study to focus on FH subjects under 18 years. This work aimed at discussing its recent progress and early outcomes. Demographic, biochemical, and genetic baseline characteristics were collected, with an in-depth analysis of the genetic defects. The analysis was carried out on 1,602 children and adolescents (mean age at baseline 9.9 ± 4.0 years), and almost the whole cohort underwent the genetic test (93.3%). Overall, the untreated mean value of LDL-C was 220.0 ± 97.2 mg/dl, with an increasing gradient from subjects with a negative (N = 317; mean untreated LDL-C = 159.9 ± 47.7 mg/dl), inconclusive (N = 125; mean untreated LDL-C = 166.4 ± 56.5 mg/dl), or positive (N = 1,053; mean untreated LDL-C = 246.5 ± 102.1 mg/dl) genetic diagnosis of FH. In the latter group, the LDL-C values presented a great variability based on the number and the biological impact of involved causative variants. The LIPIGEN pediatric group represents one of the largest cohorts of children with FH, allowing the deepening of the characterization of their baseline and genetic features, providing the basis for further longitudinal investigations for complete details.

Background: EDU.RE.DRUG study is a prospective, multicentre, open-label, parallel-arm, controlled, pragmatic trial directed to general practitioners (GPs) and their patients. Methods: The study data were retrieved from health-related administrative databases of four local health units (LHUs) of Lombardy and four LHUs in Campania. According to the LHUs, the GPs/patients were assigned to (A) intervention on both GPs (feedback reports about appropriate prescribing among their patients and online courses) and patients (flyers and posters on proper drug use), (B) intervention on GPs, (C) intervention on patients, and (D) no intervention (control arm). A set of appropriate prescribing indicators (potential drug–drug interactions [pDDIs], potential and unnecessary therapeutic duplicates [pTDs], and inappropriate prescriptions in the elderly [ERD-list]) were measured at baseline and after the intervention phase. The effectiveness of the intervention was evaluated estimating the absolute difference in percentages of selected indicators carrying out linear random-intercept mixed-effect models. Results: A cohort of 3,586 GPs (2,567 in intervention groups and 1,019 in the control group) was evaluated. In Campania, the mean pre-intervention percentage of patients with at least one pDDI was always greater than 20% and always lower than 15% in Lombardy. The pre–post difference was quite heterogeneous among the LHUs, ranging from 1.9 to −1.4 percentage points. The mean pre-intervention percentage of patients with pTDs ranged from 0.59 to 2.1%, with slightly higher values characterizing Campania LHUs. The magnitude of the pre–post difference was very low, ranging from −0.11 to 0.20. In Campania, the mean pre-intervention percentage of patients with at least one ERD criterium was considerably higher than in Lombardy (approximately 30% in Lombardy and 50% in Campania). The pre–post difference was again quite heterogeneous. The results from the models accounting for GP geographical bel

BackgroundEvidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and ResultsAn lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score >= 1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups <0.0001); however, subjects with FH/M- and lp(a) score >= 1 had higher mean (SD) pretreatment low-density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M- and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low-density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low-density lipoprotein cholesterol level >= 190 mg/dL (or from 68% to 50%, considering a more conservative formula). ConclusionsOur study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH.

Despite the invaluable efficacy of statins, adherence to therapy is extremely poor in clinical practice. Improvement interventions should be as personalized as possible, but it is necessary to know factors that most influence adherence, and sex seems to be a key determinant. Thus, we aimed at exploring potential areas of sex-differences in statin adherence in a real-world population. For this purpose, we assessed adherence (as proportion of days covered) on a wide cohort of new statin users aged >40 years, and we evaluated its association with several covariates through sex-stratified log-binomial regression models. In addition, to compare also the benefits of optimal statin adherence in primary prevention of cardiovascular disease between men and women, we implemented sex-stratified Cox proportional hazard models. Our study showed that women are more likely to stop or be less adherent to statin treatment than men. Moreover, we observed significant sex-differences on effect size of several factors associated with adherence that should be taken into consideration for the management of patients. Finally, we observed no significant difference between men and women regarding statin efficacy in terms of reduction of incident hospitalization for ischemic heart disease and/or non-haemorrhagic cerebrovascular disease. These results invoke the responsibility of physicians to a prompt and personalized intervention. Physicians should consider routine screening for non-adherence in their clinical practice, target patients at higher risk of non-adherence, and improved motivation and communication.

Background and aims: Familial hypercholesterolemia (FH) is an inherited disorder characterized by high levels of blood cholesterol from birth and premature coronary heart disease. Thus, the identification of FH patients is crucial to prevent or delay the onset of cardiovascular events, and the availability of a tool helping with the diagnosis in the setting of general medicine is essential to improve FH patient identification. Methods: This study evaluated the performance of the Dutch Lipid Clinic Network (DLCN) score in FH patients enrolled in the LIPIGEN study, an Italian integrated network aimed at improving the identification of patients with genetic dyslipidaemias, including FH. Results: The DLCN score was applied on a sample of 1377 adults (mean age 42.9 ± 14.2 years) with genetic diagnosis of FH, resulting in 28.5% of the sample classified as probable FH and 37.9% as classified definite FH. Among these subjects, 43.4% had at least one missing data out of 8, and about 10.0% had 4 missing data or more. When analyzed based on the type of missing data, a higher percentage of subjects with at least 1 missing data in the clinical history or physical examination was classified as possible FH (DLCN score 3–5). We also found that using real or estimated pre-treatment LDL-C levels may significantly modify the DLCN score. Conclusions: Although the DLCN score is a useful tool for physicians in the diagnosis of FH, it may be limited by the complexity to retrieve all the essential information, suggesting a crucial role of the clinical judgement in the identification of FH subjects.

After more than a decade of intense investigation, Pro-protein Convertase Subtilisin-Kexin type 9 (PCSK9) remains a hot topic of research both at experimental and clinical level. Interestingly PCSK9 is expressed in different tissues suggesting the existence of additional function(s) beyond the modulation of the Low-Density Lipoprotein (LDL) receptor in the liver. Emerging data suggest that PCSK9 might play a role in the modulation of triglyceride-rich lipoprotein (TGRL) metabolism, mainly Very Low-Density Lipoproteins (VLDL) and their remnants. In vitro, PCSK9 affects TGRLs production by intestinal cells as well as the catabolism of LDL receptor homologous and non-homologous targets such as VLDL receptor, CD36 and ApoE2R. However, the in vivo relevance of these findings is still debated. This review aims at critically discussing the role of PCSK9 on TGRLs metabolism with a major focus on the impact of its genetic and pharmacological modulation on circulating lipids and lipoproteins beyond LDL.