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1. Longevity-associated BPIFB4 gene counteracts the inflammatory signaling

Author: Monica Cattaneo, Andrea Baragetti, Alberto Malovini, Elena Ciaglia, Valentina Lopardo, Elena Olmastroni, Manuela Casula, Carolina Ciacci, Alberico L. Catapano, and Annibale A. Puca
Subjects: Immunologic diseases. Allergy, RC581-607, Geriatrics, RC952-954.6
Abstract: Abstract Background Increased levels of pro-inflammatory proteins in plasma can be detected in older individuals and associate with the so called chronic low-grade inflammation, which contributes to a faster progression of aged-related cardiovascular (CV) diseases, including frailty, neurodegeneration, gastro-intestinal diseases and disorders reflected by alterations in the composition of gut microbiota. However, successful genetic programme of long-living individuals alters the trajectory of the ageing process, by promoting an efficient immune response that can counterbalance deleterious effects of inflammation and the CV complications. This is the case of BPIFB4 gene in which, homozygosity for a four single-nucleotide polymorphism (SNP) haplotype, the Longevity-Associated Variant (LAV) correlates with prolonged health span and reduced risk of CV complications and inflammation. The relation between LAV-BPIFB4 and inflammation has been proven in different experimental models, here we hypothesized that also human homozygous carriers of LAV-BPIFB4 gene may experience a lower inflammatory burden as detected by plasma proteomics that could explain their favourable CV risk trajectory over time. Moreover, we explored the therapeutic effects of LAV-BPIFB4 in inflammatory disease and monolayer model of intestinal barrier. Results We used high-throughput proteomic approach to explore the profiles of circulating proteins from 591 baseline participants selected from the PLIC cohort according to the BPIFB4 genotype to identify the signatures and differences of BPIFB4 genotypes useful for health and disease management. The observational analysis identified a panel of differentially expressed circulating proteins between the homozygous LAV-BPIFB4 carriers and the other alternative BPIFB4 genotypes highlighting in the latter ones a higher grade of immune-inflammatory markers. Moreover, in vitro studies performed on intestinal epithelial organs from inflammatory bowel disease (IBD) patients and monolayer model of intestinal barrier demonstrated the benefit of LAV-BPIFB4 treatment. Conclusions Homozygosity for LAV-BPIFB4 results in the attenuation of inflammation in PLIC cohort and IBD patients providing preliminary evidences for its therapeutic use in inflammatory disorders that need to be further characterized and confirmed by independent studies.
Published: 2024
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2. Apolipoprotein B compared with low-density lipoprotein cholesterol in the atherosclerotic cardiovascular diseases risk assessment

Author: Federica Galimberti, Manuela Casula, and Elena Olmastroni
Subjects: Apolipoprotein B, Low-density lipoprotein, Cholesterol content, Particle number, Atherosclerotic cardiovascular diseases risk, Therapeutics. Pharmacology, RM1-950
Abstract: The subendothelial retention of apolipoprotein B (apoB)-containing lipoproteins is a critical step in the initiation of pro-atherosclerotic processes. Recent genetic and clinical evidence strongly supports the concept that the lipid content of the particles is secondary to the number of circulating atherogenic particles that are trapped within the arterial lumen. Since each low-density lipoproteins (LDL) particle contains one apoB molecule, as do intermediate density lipoprotein (IDL) and very low-density lipoprotein (VLDL) particles, apoB level represents the total number of atherogenic lipoproteins, which is independent of particle density, and not affected by the heterogeneity of particle cholesterol content (clinically evaluated by LDL-cholesterol level). From this perspective, apoB is proposed as a better proxy to LDL-cholesterol for assessing atherosclerotic cardiovascular disease risk, especially in specific subgroups of patients, including subjects with diabetes mellitus, with multiple cardiometabolic risk factors (obesity, metabolic syndrome, insulin resistance, and hypertension) and with high triglyceride levels and very low LDL-cholesterol levels. Therefore, given the causal role of LDL-cholesterol in atherosclerotic cardiovascular disease (ASCVD) development, routine measurement of both LDL-cholesterol and apoB is of utmost importance to properly estimate global cardiovascular risk and to determine the 'residual' risk of ASCVD in patients receiving therapy, as well as to monitor therapeutic effectiveness.
Published: 2023
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3. Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia

Author: Elena Olmastroni, Marta Gazzotti, Maurizio Averna, Marcello Arca, Patrizia Tarugi, Sebastiano Calandra, Stefano Bertolini, Alberico L. Catapano, and Manuela Casula
Subjects: cardiovascular risk, clinical diagnosis, familial hypercholesterolemia, lipoprotein(a), Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background Evidence 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 Results An 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
Published: 2023
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4. Corrigendum: The role of registers in increasing knowledge and improving management of children and adolescents affected by familial hypercholesterolemia: The LIPIGEN pediatric group

Author: Marta Gazzotti, Manuela Casula, Stefano Bertolini, Maria Elena Capra, Elena Olmastroni, Alberico Luigi Catapano, Cristina Pederiva, and LIPIGEN Paediatric Group
Subjects: familial hypercholesterolemia, pediatric cohort, genetic diagnosis, pathology register, clinical diagnosis, cardiovascular genetics, Genetics, QH426-470
Published: 2023
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5. Beta-blockers in post-acute myocardial infarction patients: Drug prescription patterns from 2018 to Italy’s first wave of the COVID-19 pandemic

Author: Elena Olmastroni, Federica Galimberti, Alberico L. Catapano, Elena Tragni, and Manuela Casula
Subjects: COVID-19 pandemic, beta-blockers, acute myocardial infarction, cardiovascular diseases, appropriate drug prescription, Therapeutics. Pharmacology, RM1-950
Abstract: Background: Major guidelines recommend the initiation of a beta-blocker therapy after an acute myocardial infarction (AMI). We aimed to map the treatment pathway of beta-blockers for AMI survivors during the first wave of COVID-19 pandemic in Italy and to investigate predictors for treatment non-initiation.Methods: Healthcare utilization databases of Lombardy Region were investigated. Subjects aged ≥18 years who were hospitalised with AMI in the period February-March-April of 2018, 2019, and 2020 were included, and followed for 30 days from the discharge date, to investigate whether they presented a first prescription of beta-blockers. A multivariate logistic model was performed to evaluate the effect of several covariates on the probability of not receiving a post-AMI beta-blocker therapy.Results: The cohorts comprised 2259, 2383, and 1932 individuals who were hospitalised with AMI in the 3-month period in 2018, 2019, and 2020, respectively. Overall in 2020, about 58–60% of individuals with AMI received a prescription of beta-blockers within 1 month after the discharge. A continuous decreasing trend over time was observed. Men were 30% more likely to start the treatment than women, increasing age was associated with significant increasing probability of not receiving a post-infarction beta-blocker therapy, while having received an antihypertensive or lipid-lowering treatment, or having been hospitalized for heart failure prior to the AMI hospitalization reduced the likelihood of not being treated with beta-blockers.Conclusion: The initiation of beta-blocker treatment after AMI remains an under-prescribed practice, that does not seem to have been further affected by the first wave of the COVID-19 pandemic.
Published: 2022
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6. The Role of Registers in Increasing Knowledge and Improving Management of Children and Adolescents Affected by Familial Hypercholesterolemia: the LIPIGEN Pediatric Group

Author: Marta Gazzotti, Manuela Casula, Stefano Bertolini, Maria Elena Capra, Elena Olmastroni, Alberico Luigi Catapano, Cristina Pederiva, the LIPIGEN Paediatric Group, Massimiliano Allevi, Marcello Arca, Renata Auricchio, Maurizio Averna, Davide Baldera, Giuseppe Banderali, Andrea Bartuli, Giacomo Biasucci, Claudio Borghi, Patrizia Bruzzi, Raffaele Buganza, Paola Sabrina Buonuomo, Paolo Calabrò, Sebastiano Calandra, Francesca Carubbi, Arturo Cesaro, Francesco Cipollone, Nadia Citroni, Giuseppe Covetti, Annalaura Cremonini, Sergio D’Addato, Maria Del Ben, Maria Donata Di Taranto, Giuliana Fortunato, Roberto Franceschi, Federica Galimberti, Simonetta Genovesi, Antonina Giammanco, Liliana Grigore, Ornella Guardamagna, Arcangelo Iannuzzi, Gabriella Iannuzzo, Lorenzo Iughetti, Lidia Lascala, Fabiana Locatelli, Sara Madaghiele, Giuseppe Mandraffino, Massimo Raffaele Mannarino, Bucci Marco, Lorenzo Maroni, Ilenia Minicocci, Giuliana Mombelli, Sandro Muntoni, Fabio Nascimbeni, Gianfranco Parati, Angelina Passaro, Chiara Pavanello, Fabio Pellegatta, Francesco Massimo Perla, Matteo Pirro, Livia Pisciotta, Arturo Pujia, Francesco Purrello, Elisabetta Rinaldi, Riccardo Sarzani, Roberto Scicali, Patrizia Suppressa, Patrizia Tarugi, Sabrina Verachtert, Giovanni Battista Vigna, Josè Pablo Werba, Alberto Zambon, Sabina Zambon, and Maria Grazia Zenti
Subjects: familial hypercholesterolemia, pediatric cohort, genetic diagnosis, pathology register, clinical diagnosis, cardiovascular genetics, Genetics, QH426-470
Abstract: 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.
Published: 2022
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7. Adherence to Mediterranean Diet: A Population-Based Longitudinal Cohort Study

Author: Elisa Mattavelli, Elena Olmastroni, Manuela Casula, Liliana Grigore, Fabio Pellegatta, Andrea Baragetti, Paolo Magni, and Alberico L. Catapano
Subjects: mediterranean diet adherence, cardiovascular disease, metabolic disease, longitudinal study, Nutrition. Foods and food supply, TX341-641
Abstract: Adherence to the Mediterranean diet (MedDiet) is recommended for cardiovascular disease prevention. However, recent epidemiological studies report a shift toward lower adherence to MedDiet. We have conducted a prospective cohort study to evaluate changes in individual determinants of MedDiet adherence over time. Clinical information and MedDiet adherence score (MEDAS) were collected in 711 subjects (mean age 68 ± 10 years; 42% males), enrolled in the PLIC study (Progression of Intimal Atherosclerotic Lesions in Carotid arteries), during two visits conducted, on average, 4.5 years apart. MEDAS score worsening and improvements (absolute change, ΔMEDAS) and the variation in the proportion of subjects reporting to meet each MEDAS criteria were assessed. Overall, 34% of the subjects improved their MedDiet adherence (ΔMEDAS: +1.87 ± 1.13), by consuming more olive oil, legumes and fish and use of dishes seasoned with sofrito and 48% subjects worsened their MedDiet adherence (ΔMEDAS: −2.02 ± 1.14) by consuming less fruit, legumes, fish and nuts, with higher rates of worsening in women and subjects aged 50–65 years. Subjects who improved the score were more obese, had higher plasma glucose levels, and metabolic syndrome at the basal visit. In summary, we report an overall decrease in MedDiet adherence, evaluated during a timeframe heavily affected by the COVID-19 pandemic, underlining the need for better dietary interventions.
Published: 2023
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8. Evaluation of Factors Associated With Appropriate Drug Prescription and Effectiveness of Informative and Educational Interventions—The EDU.RE.DRUG Project

Author: Federica Galimberti, Elena Olmastroni, Manuela Casula, Ivan Merlo, Matteo Franchi, Alberico Luigi Catapano, Valentina Orlando, Enrica Menditto, Elena Tragni, and on behalf of EDU.RE.DRUG Group
Subjects: pragmatic trial design, appropriate prescription, educational intervention, drug prescribing, feedback report, Therapeutics. Pharmacology, RM1-950
Abstract: 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 belonging suggested that none of the interventions resulted in a statistically significant effect, for all the three indicators considered.Conclusion: The proposed strategy was shown to be not effective in influencing the voluntary changes in GP prescription performance. However, the use of a set of explicit indicators proved to be useful in quantifying the inappropriateness. Further efforts are needed to find more efficient strategies and design more tailored interventions.
Published: 2022
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9. Twelve Variants Polygenic Score for Low‐Density Lipoprotein Cholesterol Distribution in a Large Cohort of Patients With Clinically Diagnosed Familial Hypercholesterolemia With or Without Causative Mutations

Author: Elena Olmastroni, Marta Gazzotti, Marcello Arca, Maurizio Averna, Angela Pirillo, Alberico Luigi Catapano, and Manuela Casula
Subjects: familial hypercholesterolemia, molecular diagnosis, polygenic risk score, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background A significant proportion of individuals clinically diagnosed with familial hypercholesterolemia (FH), but without any disease‐causing mutation, are likely to have polygenic hypercholesterolemia. We evaluated the distribution of a polygenic risk score, consisting of 12 low‐density lipoprotein cholesterol (LDL‐C)‐raising variants (polygenic LDL‐C risk score), in subjects with a clinical diagnosis of FH. Methods and Results Within the Lipid Transport Disorders Italian Genetic Network (LIPIGEN) study, 875 patients who were FH‐mutation positive (women, 54.75%; mean age, 42.47±15.00 years) and 644 patients who were FH‐mutation negative (women, 54.21%; mean age, 49.73±13.54 years) were evaluated. Patients who were FH‐mutation negative had lower mean levels of pretreatment LDL‐C than patients who were FH‐mutation positive (217.14±55.49 versus 270.52±68.59 mg/dL, P
Published: 2022
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10. Antibiotic Prescription in the Community-Dwelling Elderly Population in Lombardy, Italy: A Sub-Analysis of the EDU.RE.DRUG Study

Author: Federica Galimberti, Manuela Casula, Elena Olmastroni, Alberico L Catapano, Elena Tragni, and on behalf of EDU.RE.DRUG Group
Subjects: anti-bacterial agents, antibiotic consumption, inappropriate prescribing, elderly, Therapeutics. Pharmacology, RM1-950
Abstract: Inappropriate consumption and over-prescription of antibiotics have been extensively reported. Our aim was to specifically evaluate the antibiotic prescribing patterns and appropriateness among the elderly (≥65 years) from the Lombardy region (Italy) in primary care. Antibiotic consumption (as DID: DDD/1000 inhabitants × day) and prevalence rates in 2018 were assessed, and the prescribing quality was evaluated using ESAC-based indicators and WHO-AWaRe criteria. A multivariate logistic regression analysis was performed to evaluate the association between the probability of receiving an antibiotic prescription and patients’ and physicians’ characteristics. A total of 237,004 antibiotic users were included (mean age ± SD 75.98 ± 7.63; males 42.7%). Antibacterial consumption was equal to 17.2 DID, with values increasing with age in both males and females. The study found that the proportion of patients with at least one antibiotic prescription in 2018 was around 39.1%, with different age-related trends between males and females. Consumption (as DID) of cephalosporines (65–74 years: 1.65; 75–84 years: 2.06; ≥85 years: 2.86) and quinolones (3.88, 4.61, 4.96, respectively) increased with growing age, while consumption of penicillins (6.21, 6.08, 6.04, respectively) and macrolides, lincosamides, and streptogramins (3.25, 2.91, 2.64, respectively) decreased. In 2018, antibiotics considered to have higher toxicity concerns or resistance potential, as reported by WHO-AWaRe tool, were consumed more intensively than those to be used as first choices, independent of age and sex. The probability of receiving an antibiotic prescription was greater in females, in subjects with polypharmacy, in treatment with respiratory drugs, anti-inflammatory agents or glucocorticoids, and with previous hospitalization; but increasing age was less associated with exposition to antibiotics.
Published: 2022
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11. Oral Porphyromonas gingivalis and Fusobacterium nucleatum Abundance in Subjects in Primary and Secondary Cardiovascular Prevention, with or without Heterozygous Familial Hypercholesterolemia

Author: Maria Cristina Curia, Pamela Pignatelli, Domenica Lucia D’Antonio, Damiano D’Ardes, Elena Olmastroni, Luca Scorpiglione, Francesco Cipollone, Alberico Luigi Catapano, Adriano Piattelli, Marco Bucci, and Paolo Magni
Subjects: atherosclerosis, Porphyromonas gingivalis, Fusobacterium nucleatum, cardiovascular disease, heterozygous familial hypercholesterolemia, secondary cardiovascular prevention, Biology (General), QH301-705.5
Abstract: Background: Low-grade chronic inflammation, promoted by dysbiosis of the gut and oral microbiota, has been shown to contribute to individual susceptibility to atherosclerotic cardiovascular disease (ASCVD). High oral Porphyromonas gingivalis (Pg) and lower Fusobacterium nucleatum (Fn) concentrations have been associated with clinical and experimental atherosclerosis. We assessed oral Pg and Fn abundance in very high-risk patients with previously diagnosed ASCVD, with or without heterozygous familial hypercholesterolemia (HeFH), in subjects with HeFH in primary prevention and in healthy subjects. Methods: In this cross-sectional study, 40 patients with previously diagnosed ASCVD (10 with genetically proven HeFH, and 30 without FH), 26 subjects with HeFH in primary prevention, and 31 healthy subjects were selected to quantify oral Pg and Fn abundance by qPCR and assess oral health status. Results: Compared to healthy subjects, patients with previously diagnosed ASCVD showed greater Pg abundance (1101.3 vs. 192.4, p = 0.03), but similar Fn abundance. HeFH patients with ASCVD had an even greater Pg abundance than did non-HeFH patients and healthy subjects (1770.6 vs. 758.4 vs. 192.4, respectively; p = 0.048). No differences were found in the levels of Pg and Fn abundance in HeFH subjects in primary prevention, as compared to healthy subjects. Conclusions: Greater oral Pg abundance is present in very high-risk patients with previously diagnosed ASCVD, with or without FH, suggesting a potential relationship with CV events. Future studies will assess the predictive value of Pg abundance measurement in ASCVD risk stratification.
Published: 2022
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12. Adherence to the Mediterranean Diet: Impact of Geographical Location of the Observations

Author: Elisa Mattavelli, Elena Olmastroni, Daniela Bonofiglio, Alberico L. Catapano, Andrea Baragetti, and Paolo Magni
Subjects: Mediterranean diet, adherence, awareness, health, geographical location, ethnic, Nutrition. Foods and food supply, TX341-641
Abstract: The Mediterranean diet has emerged as a comprehensive lifestyle, including specific foods and meal composition and a set of behavioural and social features. Adherence to the Mediterranean diet has been shown to promote health and reduce the prevalence of chronic diseases. The actual implementation of the Mediterranean diet is affected by several sociocultural factors as well as geographical components. Indeed, the geographical location, such as a specific country or different areas in a country and specific latitude and climate, appears to be an important factor that may strongly affect the implementation of the Mediterranean diet or some of its principles as well as the adherence to it. Another dynamic component affecting personal nutritional choices, also regarding adherence to the Mediterranean diet and its principles, is the individual life-long trajectory of food preference and nutrition habits and awareness. In this review, we discuss the current evidence on the impact of geographical location on adherence to the Mediterranean diet.
Published: 2022
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13. Geographical Variation in Medication Prescriptions: A Multiregional Drug-Utilization Study

Author: Veronica Russo, Valentina Orlando, Valeria Marina Monetti, Federica Galimberti, Manuela Casula, Elena Olmastroni, Elena Tragni, Enrica Menditto, EDU.RE.DRUG Group, Alberico L. Catapanoa, Giovanni Corrao, Sara Mucherino, Lorenza Scotti, Antonella Zambon, Marco Gambera, Rossana Piccinelli, Samanta Sonzogni, Valter Valsecchi, Eugenio Scopinaro, Sandro Raineri, Alessia Speziali, Simona Creazzola, Michele Tari, and Mariano Fusco
Subjects: drug-utilization, geographical difference, prevalence, drug use, general practitioner, pharmacy claims, Therapeutics. Pharmacology, RM1-950
Abstract: BackgroundStudies have emphasized the importance of geographical factors and general practitioner (GP) characteristics in influencing drug prescriptions.ObjectivesTo: (i) ascertain the prevalence rate (PR) of use of drugs in six therapeutic categories used for chronic conditions; (ii) assess how geographical characteristics and GP characteristics may influence drug prescribing.MethodsThis study is part of the EDU.RE.DRUG Project, a national collaborative project founded by Italian Medicine Agency (AIFA). Cross-sectional analyses were undertaken employing the pharmacy-claim databases of four local health units (LHUs) located in two Italian regions: Lombardy and Campania. Six drug categories were evaluated: proton-pump inhibitors; antibiotics; respiratory-system drugs; statins; agents acting on the renin−angiotensin system; psychoanaleptic drugs. The PR was estimated according to drug categories at the LHU level. A linear multivariate regression analysis was undertaken to evaluate the association between the PR and geographical area, age and sex of GPs, number of patients, and percentage of patients aged >65 per GP.ResultsLHUs in Campania showed a PR that was significantly higher than that in Lombardy. Antibiotics showed the highest PR in all the LHUs assessed, ranging from 32.5% in Lecco (Lombardy) to 59.7% in Naples-2 (Campania). Multivariate linear regression analysis confirmed the association of the PR with geographical area for all drug categories. Being located in Campania increased the possibility of receiving a drug prescription from the categories considered, with estimates more marked for antibiotics, proton-pump-inhibitors, and respiratory-system drugs.ConclusionsThis study provides information about the PR of medications used for treating common and costly conditions in Italy and highlighted a significant geographical variation. These insights could help to develop area-specific strategies to optimize prescribing behavior.
Published: 2020
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14. Gut Microbiota Functional Dysbiosis Relates to Individual Diet in Subclinical Carotid Atherosclerosis

Author: Andrea Baragetti, Marco Severgnini, Elena Olmastroni, Carola Conca Dioguardi, Elisa Mattavelli, Andrea Angius, Luca Rotta, Javier Cibella, Giada Caredda, Clarissa Consolandi, Liliana Grigore, Fabio Pellegatta, Flavio Giavarini, Donatella Caruso, Giuseppe Danilo Norata, Alberico Luigi Catapano, and Clelia Peano
Subjects: Atherosclerotic Cardiovascular Diseases, Gut Microbiota, next generation sequencing, Nutrition. Foods and food supply, TX341-641
Abstract: Gut Microbiota (GM) dysbiosis associates with Atherosclerotic Cardiovascular Diseases (ACVD), but whether this also holds true in subjects without clinically manifest ACVD represents a challenge of personalized prevention. We connected exposure to diet (self-reported by food diaries) and markers of Subclinical Carotid Atherosclerosis (SCA) with individual taxonomic and functional GM profiles (from fecal metagenomic DNA) of 345 subjects without previous clinically manifest ACVD. Subjects without SCA reported consuming higher amounts of cereals, starchy vegetables, milky products, yoghurts and bakery products versus those with SCA (who reported to consume more mechanically separated meats). The variety of dietary sources significantly overlapped with the separations in GM composition between subjects without SCA and those with SCA (RV coefficient between nutrients quantities and microbial relative abundances at genus level = 0.65, p-value = 0.047). Additionally, specific bacterial species (Faecalibacterium prausnitzii in the absence of SCA and Escherichia coli in the presence of SCA) are directly related to over-representation of metagenomic pathways linked to different dietary sources (sulfur oxidation and starch degradation in absence of SCA, and metabolism of amino acids, syntheses of palmitate, choline, carnitines and Trimethylamine n-oxide in presence of SCA). These findings might contribute to hypothesize future strategies of personalized dietary intervention for primary CVD prevention setting.
Published: 2021
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15. Interactions of Oxysterols with Atherosclerosis Biomarkers in Subjects with Moderate Hypercholesterolemia and Effects of a Nutraceutical Combination (Bifidobacterium longum BB536, Red Yeast Rice Extract) (Randomized, Double-Blind, Placebo-Controlled Study)

Author: Stefania Cicolari, Chiara Pavanello, Elena Olmastroni, Marina Del Puppo, Marco Bertolotti, Giuliana Mombelli, Alberico L. Catapano, Laura Calabresi, and Paolo Magni
Subjects: oxysterols, 24-OHC, 25-OHC, 27-OHC, cholesterol metabolism, probiotic, Nutrition. Foods and food supply, TX341-641
Abstract: Background: Oxysterol relationship with cardiovascular (CV) risk factors is poorly explored, especially in moderately hypercholesterolaemic subjects. Moreover, the impact of nutraceuticals controlling hypercholesterolaemia on plasma levels of 24-, 25- and 27-hydroxycholesterol (24-OHC, 25-OHC, 27-OHC) is unknown. Methods: Subjects (n = 33; 18–70 years) with moderate hypercholesterolaemia (low-density lipoprotein cholesterol (LDL-C:): 130–200 mg/dL), in primary CV prevention as well as low CV risk were studied cross-sectionally. Moreover, they were evaluated after treatment with a nutraceutical combination (Bifidobacterium longum BB536, red yeast rice extract (10 mg/dose monacolin K)), following a double-blind, randomized, placebo-controlled design. We evaluated 24-OHC, 25-OHC and 27-OHC levels by gas chromatography/mass spectrometry analysis. Results: 24-OHC and 25-OHC were significantly correlated, 24-OHC was correlated with apoB. 27-OHC and 27-OHC/total cholesterol (TC) were higher in men (median 209 ng/mL and 77 ng/mg, respectively) vs. women (median 168 ng/mL and 56 ng/mg, respectively); 27-OHC/TC was significantly correlated with abdominal circumference, visceral fat and, negatively, with high-density lipoprotein cholesterol (HDL-C). Triglycerides were significantly correlated with 24-OHC, 25-OHC and 27-OHC and with 24-OHC/TC and 25-OHC/TC. After intervention, 27-OHC levels were significantly reduced by 10.4% in the nutraceutical group Levels of 24-OHC, 24-OHC/TC, 25-OHC, 25-OHC/TC and 27-OHC/TC were unchanged. Conclusions: In this study, conducted in moderate hypercholesterolemic subjects, we observed novel relationships between 24-OHC, 25-OHC and 27-OHC and CV risk biomarkers. In addition, no adverse changes of OHC levels upon nutraceutical treatment were found.
Published: 2021
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16. Combining family history of coronary heart disease and individual genetic predisposition to predict the risk of major coronary events: Selected Abstract - SITeCS Congress 2022

Author: Elena Olmastroni, Federica Galimberti, Alberico L. Catapano, and Brian Ference
Abstract: Background: Inherited predisposition to atherosclerosis leads to higher risk for developing coronary heart disease (CHD). There are mainly two ways to conceptualize inherited risk of CHD: family history and polygenic predisposition. We aimed at assessing the impact of family history of CHD and genetic predisposition in predicting the individual lifetime risk of major coronary events (MCE). Methods: Using adjusted Cox proportional hazard models, we estimated the lifetime risk of MCE associated with parental family history of CHD and individual genetic predisposition (estimated by a polygenic risk score including 350 variants). Results: A total of 445,744 UK-Biobank participants were included in the study (mean age 57 years; 54.3% females). Having one parent with a history of CHD increased the lifetime risk of MCE by 75% (HR 1.75, 95%CI 1.70-1.82). Having both parents with a history of CHD further increased the risk (HR 2.78, 95%CI 2.64-2.92) Similarly, a dose-dependent step-wise increase in MCE risk was observed moving from the lowest to the highest decile of the polygenic score. Compared to subjects without family history of CHD and with average level of the polygenic score, having a parental history of CHD determined an increase in lifetime risk of MCE (HR 1.90, 95%CI 1.82-1.98) comparable to belonging to the highest decile of the polygenic score (HR 1.89, 95%CI 1.76-2.02). However, if subjects present both parents with family history of CHD and a very high polygenic predisposition, the risk was even higher (HR 3.54, 95%CI 3.34-3.75), suggesting an additive contribution to the characterization of the lifetime risk. Conclusions: We described the addictive impact of family history of CHD and individual polygenic predisposition in predicting lifetime risk of MCE. In order to identify subjects at higher risk of having an early event, it is essential to retrieve information about both these hereditary components.
Published: 2023

17. Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia

Author: Olmastroni, Elena, Gazzotti, Marta, Averna, Maurizio, Arca, Marcello, Tarugi, Patrizia, Calandra, Sebastiano, Bertolini, Stefano, Catapano, Alberico L, Casula, Manuela, Laura, D'Erasmo, Angelo Baldassare Cefalù, Andrea, Bartuli, Paola Sabrina Buonuomo, Andrea, Benso, Guglielmo, Beccuti, Giacomo, Biasucci, Maria Elena Capra, Gianni, Biolo, Pierandrea, Vinci, Luca, Bonanni, Claudio, Borghi, Sergio, D'Addato, Antonio Carlo Bossi, Giancarla, Meregalli, Adriana, Branchi, Paolo, Calabrò, Francesca, Carubbi, Fabio, Nascimbeni, Francesco, Cipollone, Marco, Bucci, Nadia, Citroni, Maria Del Ben, Francesco, Baratta, Massimo, Federici, Martina, Montagna, Claudio, Ferri, Serena, Notargiacomo, Anna Maria Fiorenza, Emanuela, Colombo, Giuliana, Fortunato, Maria Donata Di Taranto, Andrea, Giaccari, Simona, Moffa, Francesco, Giorgino, Sergio Di Molfetta, Ornella, Guardamagna, Luisa De Sanctis, Arcangelo, Iannuzzi, Raimondo, Cavallaro, Gabriella, Iannuzzo, Gentile, MARCO PAOLO, Lorenzo, Iughetti, Patrizia, Bruzzi, Lia, Salvatore, Alessandro, Lupi, Giuseppe, Mandraffino, Arianna, Toscano, Rossella, Marcucci, Martina, Berteotti, Lorenzo, Maroni, Fabiana, Locatelli, Tiziana, Montalcini, Giuliana, Mombelli, Sandro, Muntoni, Davide, Baldera, Gianfranco, Parati, Angelina, Passaro, Valerio, Pecchioli, Cristina, Pederiva, Giuseppe, Banderali, Antonio, Pipolo, Debora, D'Elia, Matteo, Pirro, Vanessa, Bianconi, Livia, Pisciotta, Elena, Formisano, Purrello, Francesco, Scicali, Roberto, Elena, Repetti, Elena, Cantino, Elisabetta, Rinaldi, Elena, Sani, Riccardo, Sarzani, Francesco, Spannella, Francesco, Sbrana, Beatrice Dal Pino, Patrizia, Suppressa, Veronica, Cocco, Chiara, Trenti, Emanuele Alberto Negri, Josè Pablo Werba, Alessandra, Romandini, Sabina, Zambon, Alberto, Zambon, Maria Grazia Zenti, Giulia, Fainelli, Fabio, Pellegatta, Liliana, Grigore, Katia, Bonomo, Eleonora, Capatti, Ada, Cutolo, Fabio, Fimiani, Simonetta, Genovesi, Sandro, Inchiostro, Chiara, Pavanello, Pujia, Roberta, Alon, Schaffer, Stefano, Bertolini, Sebastiano, Calandra, Alberico Luigi Catapano, Manuela, Casula, Elena, Olmastroni, Patrizia, Tarugi, Marta, Gazzotti, and Federica, Galimberti
Subjects: cardiovascular risk, clinical diagnosis, familial hypercholesterolemia, lipoprotein(a)
Published: 2023

18. Antibiotic Prescription in the Community-Dwelling Elderly Population in Lombardy, Italy: A Sub-Analysis of the EDU.RE.DRUG Study

Author: Group, Federica Galimberti, Manuela Casula, Elena Olmastroni, Alberico L Catapano, Elena Tragni, and on behalf of EDU.RE.DRUG Group on behalf of EDU.RE.DRUG
Subjects: anti-bacterial agents, antibiotic consumption, inappropriate prescribing, elderly
Abstract: Inappropriate consumption and over-prescription of antibiotics have been extensively reported. Our aim was to specifically evaluate the antibiotic prescribing patterns and appropriateness among the elderly (≥65 years) from the Lombardy region (Italy) in primary care. Antibiotic consumption (as DID: DDD/1000 inhabitants × day) and prevalence rates in 2018 were assessed, and the prescribing quality was evaluated using ESAC-based indicators and WHO-AWaRe criteria. A multivariate logistic regression analysis was performed to evaluate the association between the probability of receiving an antibiotic prescription and patients’ and physicians’ characteristics. A total of 237,004 antibiotic users were included (mean age ± SD 75.98 ± 7.63; males 42.7%). Antibacterial consumption was equal to 17.2 DID, with values increasing with age in both males and females. The study found that the proportion of patients with at least one antibiotic prescription in 2018 was around 39.1%, with different age-related trends between males and females. Consumption (as DID) of cephalosporines (65–74 years: 1.65; 75–84 years: 2.06; ≥85 years: 2.86) and quinolones (3.88, 4.61, 4.96, respectively) increased with growing age, while consumption of penicillins (6.21, 6.08, 6.04, respectively) and macrolides, lincosamides, and streptogramins (3.25, 2.91, 2.64, respectively) decreased. In 2018, antibiotics considered to have higher toxicity concerns or resistance potential, as reported by WHO-AWaRe tool, were consumed more intensively than those to be used as first choices, independent of age and sex. The probability of receiving an antibiotic prescription was greater in females, in subjects with polypharmacy, in treatment with respiratory drugs, anti-inflammatory agents or glucocorticoids, and with previous hospitalization; but increasing age was less associated with exposition to antibiotics.
Published: 2022
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19. Impact of the COVID-19 Pandemic on the Therapeutic Continuity among Outpatients with Chronic Cardiovascular Therapies

Author: Poluzzi, Manuela Casula, Federica Galimberti, Marica Iommi, Elena Olmastroni, Simona Rosa, Mattia Altini, Alberico L. Catapano, Elena Tragni, and Elisabetta
Subjects: COVID-19 pandemic, prescriptions, adherence, chronic treatments, cardiovascular diseases
Abstract: The COVID-19 pandemic poses major challenges to healthcare systems. We aimed to investigate the impact of the pandemic on prescription and adherence patterns of chronic cardiovascular therapies (lipid-lowering [LL], oral antidiabetic drugs [AD], and antihypertensives [AH]) using administrative pharmaceutical databases. For each treatment, two cohorts of prevalent cases in 2019 and 2020 were compared. We evaluated the percentage change in dispensed packages and treatment adherence as a proportion of days covered (PDC). For all therapies, an increase was observed during March–April 2020 (LL: +4.52%; AD: +2.72%; AH: +1.09%), with a sharp decrease in May–June 2020 (LL: −8.40%; AD: −12.09%; AH: −10.54%) compared to 2019. The impact of the COVID-19 pandemic on chronic cardiovascular treatments appears negligible on adherence: 533,414 patients showed high adherence to LL (PDC ≥ 80%) in January–February 2020, and 2.29% became poorly adherent (PDC < 20%) in the following four-month period (vs. 1.98% in 2019). A similar increase was also observed for AH (1.25% with poor adherence in 2020 vs. 0.93% in 2019). For AD, the increase was restrained (1.55% with poor adherence in 2020 vs. 1.37% in 2019). The rush to supply drugs at the beginning of lockdown preserved the continuity of chronic cardiovascular therapies.
Published: 2022
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20. Oral

Author: Maria Cristina, Curia, Pamela, Pignatelli, Domenica Lucia, D'Antonio, Damiano, D'Ardes, Elena, Olmastroni, Luca, Scorpiglione, Francesco, Cipollone, Alberico Luigi, Catapano, Adriano, Piattelli, Marco, Bucci, and Paolo, Magni
Abstract: Low-grade chronic inflammation, promoted by dysbiosis of the gut and oral microbiota, has been shown to contribute to individual susceptibility to atherosclerotic cardiovascular disease (ASCVD). High oralIn this cross-sectional study, 40 patients with previously diagnosed ASCVD (10 with genetically proven HeFH, and 30 without FH), 26 subjects with HeFH in primary prevention, and 31 healthy subjects were selected to quantify oralCompared to healthy subjects, patients with previously diagnosed ASCVD showed greaterGreater oral
Published: 2022

21. The Role of Registers in Increasing Knowledge and Improving Management of Children and Adolescents Affected by Familial Hypercholesterolemia: the LIPIGEN Pediatric Group

Author: Gazzotti, Marta, Casula, Manuela, Bertolini, Stefano, Capra, Maria Elena, Olmastroni, Elena, Catapano, Alberico Luigi, Pederiva, Cristina, and the LIPIGEN Pediatric Group: Massimiliano Allevi, Internal Medicine and Geriatrics, Department of Clinical and Molecular Sciences, University 'Politecnica delle Marche' and IRCCS-INRCA, Ancona, Italy, Marcello, Arca, Dipartimento di Medicina Traslazionale, e di Precisione, O Policlinico Umberto I, Sapienza Università di Roma—A. U., Rome, Italy, Renata, Auricchio, Dipartimento di Scienze Mediche Traslazionali, AOU Policlinico Federico II, Naples, Italy, Averna, Maurizio, Dipartimento di Promozione della Salute, Materno-Infantile, di Medicina Interna, e Specialistica di Eccellenza, Università degli Studi di Palermo, Palermo, Italy, Davide, Baldera, Dipartimento di Scienze Biomediche, Università degli Studi di Cagliari and Centro per le Malattie Dismetaboliche, e l’Arteriosclerosi, Onlus Cagliari, Associazione ME. DI. CO., Cagliari, Italy, Giuseppe, Banderali, Clinica Pediatrica, U. O., Servizio Clinico Dislipidemie per lo Studio, e la Prevenzione dell’Aterosclerosi in età Pediatrica, ASSTSanti Paolo, e Carlo, Milan, Italy, Andrea, Bartuli, UOC Malattie Rare, e Genetica Medica, Ospedale Pediatrico Bambino Gesù, Irccs, Rome, Italy, Stefano, Bertolini, Department of Internal Medicine, University of Genova, Genova, Italy, Giacomo, Biasucci, Centro Dislipidemie in Età Evolutiva, Pediatria e Neonatologia, U. O., Ospedale Guglielmo da Saliceto, Piacenza, Italy, Claudio, Borghi, di Medicina Interna Cardiovascolare, U. O., Centro, Aterosclerosi, Ambulatorio, Dislipidemie, Orsola-Malpighi, IRCCS S. Orsola Ospedale Policlinico S., Bologna, Italy, Patrizia, Bruzzi, Pediatria, U. O. C., Azienda Ospedaliero Universitaria di Modena, Modena, Italy, Raffaele, Buganza, Paediatric, Endocrinology, Department of Public Health and Paediatric Sciences, Turin, University, Turin, Italy, Paola Sabrina Buonuomo, Paolo, Calabrò, U. O. C. Cardiologia Clinica a Direzione Universitaria e U. T. I. C., 'Sant’Anna e San Sebastiano', A. O. R. N., Italy and Dipartimento di Scienze Mediche Traslazionali, Università degli Studi della Campania, Sebastiano, Calandra, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Maria Elena Capra, Francesca, Carubbi, Medicina interna metabolica, U. O., Centro dislipidemie, e malattie metaboliche rare, Ospedale Civile Baggiovara, AOU di Modena, Manuela, Casula, Dipartimento di Scienze Farmacologiche, e Biomolecolari, Università degli Studi di Milano, and IRCCS MultiMedica, Sesto San Giovanni (Milan), Alberico Luigi Catapano, Arturo, Cesaro, Università degli Studi della Campania 'Luigi Vanvitelli', Francesco, Cipollone, Clinica, Medica, Centro di riferimento regionale per le Dislipidemie, Annunziata, Ospedale Policlinico S. S., Chieti, Italy, Nadia, Citroni, Centro Dislipidemie, e Aterosclerosi, UOC Medicina Interna, Ospedale di Trento, Trento, Italy, Giuseppe, Covetti, Medicina Interna 2, U. O., Centro per le malattie da arteriosclerosi, Aorn, Cardarelli, Annalaura, Cremonini, IRCCS Ospedale policlinico San Martino UOSD Dietetica, e Nutrizione Clinica and Dipartimento di Medicina Interna, Università di Genova, Sergio, D’Addato, Maria Del Ben, Dipartimento Scienze Cliniche, Internistiche, Anestesiologiche e Cardiovascolari, - Sapienza Università, Policlinico Umberto I, A. O., Maria Donata Di Taranto, Dipartimento di Medicina Molecolare, e Biotecnologie Mediche, Università degli studi di Napoli Federico II and CEINGE Biotecnologie Avanzate, s. c. a. r. l., Giuliana, Fortunato, Roberto, Franceschi, Uoc, Pediatria, Federica, Galimberti, Irccs, Multimedica, Marta, Gazzotti, Fondazione SISA (Società Italiana per lo Studio dell’Aterosclerosi), Simonetta, Genovesi, IRCCS Istituto Auxologico Italiano and Dipartimento di Medicina, e Chirurgia, Università di Milano- Bicocca, Antonina, Giammanco, Liliana, Grigore, Centro per lo Studio dell’Aterosclerosi, Italy and Centro per lo Studio dell’Aterosclerosi, Bassini, Ospedale E., Cinisello, Balsamo, Ornella, Guardamagna, Arcangelo, Iannuzzi, Gabriella, Iannuzzo, Dipartimento di Medicina Clinica, e Chirurgia, Centro Coordinamento regionale per le Iperlipidemie, Lidia Lascala, AOU Mater Domini, Fabiana, Locatelli, Ambulatorio ipertensione dislipidemie rischio cardiovascolare, ASST Valle Olona, Ospedale di Gallarate, Gallarate, Italy, Ospedale di Busto Arsizio, Busto, Arsizio, Lorenzo, Iughetti, Sara, Madaghiele, Frugoni' and Centro di Assistenza e Ricerca Malattie Rare, U. O. di Medicina Interna e Geriatria 'C., Universitaria Policlinico Consorziale, A. O., Università degli Studi di Bari 'Aldo Moro', Bari, Italy, Giuseppe, Mandraffino, Martino, Department of Clinical and Experimental Medicine—Lipid Center—University Hospital G., Messina, Italy, Massimo Raffaele Mannarino, Internal, Medicine, University of Perugia, Angiology and Arteriosclerosis Diseases. Department of Medicine and Surgery., Perugia, Italy, Bucci, Marco, Lorenzo, Maroni, Ilenia, Minicocci, Giuliana, Mombelli, Centro Dislipidemie ASST Grande Ospedale Metropolitano Niguarda, Sandro, Muntoni, Fabio, Nascimbeni, Elena, Olmastroni, Servizio di Epidemiologia, e Farmacologia Preventiva (SEFAP), Dipartimento di Science Farmacologiche, e Biomolecolari, Gianfranco, Parati, Università di Milano-Bicocca, Angelina, Passaro, Department of Translational Medicine, University of Ferrara, Italy and Research and Innovation Section, University Hospital of Ferrara Arcispedale Sant’Anna, Chiara, Pavanello, Milan, Italy and Centro Grossi Paoletti, Milano, Italy, Cristina, Pederiva, ASST-Santi Paolo, e Carlo, Fabio, Pellegatta, Francesco Massimo Perla, Dipartimento Materno Infantile, e Scienze Urologiche—Sapienza Università, Medicina, Generale, Ospedale di Trecenta, Trecenta, Rovigo, Matteo, Pirro, Livia, Pisciotta, Arturo, Pujia, Mater Domini, A. O. U., UOC di Nutrizione Clinica, Purrello, Francesco, Department of Clinical and Experimental Medicine, University of Catania, Ospedale, Garibaldi, Catania, Italy, Elisabetta, Rinaldi, Endocrinologia, U. O., Diabetologia, e Malattie del Metabolismo, Universitaria Integrata di Verona, Centro regionale specializzato per la diagnosi e terapia delle dislipidemie e aferesi terapeutica and A. O., Verona, Italy, Riccardo, Sarzani, Scicali, Roberto, Patrizia, Suppressa, Patrizia, Tarugi, Department of Life Sciences, Sabrina, Verachtert, Giovanni Battista Vigna, Josè Pablo Werba, Ambulatorio Prevenzione Aterosclerosi, U. O., IRCCS Centro Cardiologico Monzino, Alberto, Zambon, Dipartimento di Medicina, Università di Padova, Padua, Italy, Sabina, Zambon, Maria Grazia Zenti, Servizio di Diabetologia, e Malattie Metaboliche, Pederzoli, Ospedale P., Peschiera del Garda, and Verona, Italy.
Subjects: genetic diagnosis, clinical diagnosis, familial hypercholesterolemia, cardiovascular genetics, pathology register, pediatric cohort, Settore BIO/14 - Farmacologia, Genetics, Molecular Medicine, Genetics (clinical)
Abstract: 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.
Published: 2022
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22. Impact of COVID-19 Pandemic on Adherence to Chronic Therapies: A Systematic Review

Author: Elena Tragni, Manuela Casula, Elena Olmastroni, Alberico Luigi Catapano, and Federica Galimberti
Subjects: Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health
Abstract: The spread of the coronavirus disease 2019 (COVID-19) pandemic caused a sudden and significant disruption in healthcare services, especially for patients suffering from chronic diseases. We aimed at evaluating the impact of the pandemic on adherence to chronic therapies through a systematic review of available studies. PubMed, EMBASE, and Web of Science were searched since inception to June 2022. Inclusion criteria were: (1) observational studies or surveys; (2) studies on patients with chronic diseases; (3) reporting the effects of COVID-19 pandemic on adherence to chronic pharmacological treatment, as a comparison of adherence during the pandemic period vs. pre-pandemic period (primary outcome) or as rate of treatment discontinuation/delay specifically due to factors linked to COVID-19 (secondary outcome). Findings from 12 (primary outcome) and 24 (secondary outcome) studies showed that many chronic treatments were interrupted or affected by a reduced adherence in the pandemic period, and that fear of infection, difficulty in reaching physicians or healthcare facilities, and unavailability of medication were often reported as reasons for discontinuation or modification of chronic therapies. For other therapies where the patient was not required to attend the clinic, continuity of treatment was sometimes ensured through the use of telemedicine, and the adherence was guaranteed with drug stockpiling. While the effects of the possible worsening of chronic disease management need to be monitored over time, positive strategies should be acknowledged, such as the implementation of e-health tools and the expanded role of community pharmacists, and may play an important role in preserving continuity of care for people with chronic diseases.
Published: 2023

23. The Effectiveness of Interventions to Evaluate and Reduce Healthcare Costs of Potentially Inappropriate Prescriptions among the Older Adults: A Systematic Review

Author: Sara, Mucherino, Manuela, Casula, Federica, Galimberti, Ilaria, Guarino, Elena, Olmastroni, Elena, Tragni, Valentina, Orlando, Enrica, Menditto, and On Behalf Of The Edu Re Drug Group
Subjects: Drug-Related Side Effects and Adverse Reactions, Health, Toxicology and Mutagenesis, Cost-Benefit Analysis, Public Health, Environmental and Occupational Health, Prevalence, Humans, Inappropriate Prescribing, Health Care Costs, Aged
Abstract: Potentially inappropriate prescribing (PIP) is associated with an increased risk of adverse drug reactions, recognized as a determinant of adherence and increased healthcare costs. The study’s aim was to explore and compare the results of interventions to reduce PIP and its impact on avoidable healthcare costs. A systematic literature review was conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement guidelines. PubMed and Embase were queried until February 2021. Inclusion criteria followed the PICO model: older patients receiving PIP; Interventions aimed at health professionals, structures, and patients; no/any intervention as a comparator; postintervention costs variations as outcomes. The search strategy produced 274 potentially relevant publications, of which 18 articles met inclusion criteria. Two subgroups were analyzed according to the study design: observational studies assessing PIP frequency and related-avoidable costs (n = 10) and trials, including specific intervention and related outcomes in terms of postintervention effectiveness and avoided costs (n = 8). PIP prevalence ranged from 21 to 79%. Few educational interventions carried out to reduce PIP prevalence and avoidable costs resulted in a slowly improving prescribing practice but not cost effective. Implementing cost-effective strategies for reducing PIP and clinical and economic implications is fundamental to reducing health systems’ PIP burden.
Published: 2022

24. Potentially Inappropriate Prescribing among Elderly Outpatients: Evaluation of Temporal Trends 2012-2018 in Piedmont, Italy

Author: Federica, Galimberti, Manuela, Casula, Lorenza, Scotti, Elena, Olmastroni, Daniela, Ferrante, Andrealuna, Ucciero, Elena, Tragni, Alberico Luigi, Catapano, and Francesco, Barone-Adesi
Subjects: Outpatients, Polypharmacy, Prevalence, Humans, Inappropriate Prescribing, Drug Prescriptions, Aged
Abstract: Pharmacological intervention is one of the cornerstones in the treatment and prevention of disease in modern healthcare. However, a large number of drugs are often prescribed and used inappropriately, especially in elderly patients. We aimed at investigating the annual prevalence of potentially inappropriate prescriptions (PIPs) among older outpatients using administrative healthcare databases of the Piedmont Region (Italy) over a seven-year period (2012-2018). We included all Piedmont outpatients aged 65 years or older with at least one drug prescription per year. Polypharmacy and the prevalence of PIPs according to the ERD list explicit tool were measured on an annual basis. A range between 976,398 (in 2012) and 1,066,389 (in 2018) elderly were evaluated. Among them, the number of subjects with at least one PIP decreased from 418,537 in 2012 to 339,764 in 2018; the prevalence significantly reduced by ~25% over the study period. The stratified analyses by age groups and sex also confirmed the downward trend and identified several differences in the most prevalent inappropriately prescribed drugs. Overall, despite a reduction in PIP prevalence, one out of three older outpatients was still exposed to inappropriateness, highlighting the extensive need for intervention to improve prescribing.
Published: 2022

25. Evaluation of Factors Associated With Appropriate Drug Prescription and Effectiveness of Informative and Educational Interventions-The EDU.RE.DRUG Project

Author: Federica, Galimberti, Elena, Olmastroni, Manuela, Casula, Ivan, Merlo, Matteo, Franchi, Alberico Luigi, Catapano, Valentina, Orlando, Enrica, Menditto, Elena, Tragni, On Behalf Of, Edu Re Drug Group, Galimberti, F, Olmastroni, E, Casula, M, Merlo, I, Franchi, M, Catapano, A, Orlando, V, Menditto, E, and Tragni, E
Subjects: pragmatic trial design, appropriate prescription, educational intervention, drug prescribing, feedback report, Settore BIO/14 - Farmacologia
Abstract: 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 belonging suggested that none of the interventions resulted in a statistically significant effect, for all the three indicators considered. Conclusion: The proposed strategy was shown to be not effective in influencing the voluntary changes in GP prescription performance. However, the use of a set of explicit indicators proved to be useful in quantifying the inappropriateness. Further efforts are needed to find more efficient strategies and design more tailored interventions.
Published: 2022

26. Lipoprotein(a) and family history for cardiovascular disease in paediatric patients: A new frontier in cardiovascular risk stratification. Data from the LIPIGEN paediatric group

Author: Cristina Pederiva, Maria Elena Capra, Giacomo Biasucci, Giuseppe Banderali, Enrico Fabrizi, Marta Gazzotti, Manuela Casula, Alberico L. Catapano, Marcello Arca, Maurizio Averna, Stefano Bertolini, Sebastiano Calandra, Alberico Luigi Catapano, Patrizia Tarugi, Fabio Pellegatta, Andrea Bartuli, Claudio Borghi, Paolo Calabrò, Francesca Carubbi, Francesco Cipollone, Nadia Citroni, Maria Del Ben, Giuliana Fortunato, Ornella Guardamagna, Arcangelo Iannuzzi, Gabriella Iannuzzo, Lorenzo Iughetti, Giuseppe Mandraffino, Lorenzo Maroni, Giuliana Mombelli, Sandro Muntoni, Gianfranco Parati, Angelina Passaro, Livia Pisciotta, Arturo Pujia, Francesco Purrello, Anna Rita Roscini, Riccardo Sarzani, Patrizia Suppressa, Josè Pablo Werba, Sabina Zambon, Maria Grazia Zenti, Massimiliano Allevi, Renata Auricchio, Davide Baldera, Patrizia Bruzzi, Marco Bucci, Paola Sabrina Buonuomo, Angelo Baldassarre Cefalù, Giuseppe Covetti, Sergio D'Addato, Maria Donata Di Taranto, Roberto Franceschi, Fabio Fimiani, Simonetta Genovesi, Liliana Grigore, Graziana Lupattelli, Sara Madaghiele, Giulia Massini, Ilenia Minicocci, Tiziana Montalcini, Fabio Nascimbeni, Chiara Pavanello, Francesco Massimo Perla, Gaia Peroni, Elena Sani, Roberto Scicali, Arianna Toscano, Giovanni Battista Vigna, Alberto Zambon, Federica Galimberti, Elena Olmastroni, and Veronica Zampoleri
Subjects: Male, Adolescent, Family history, High cardiovascular risk, Paediatric FH, Lp(a), Children/adolescents, Premature CVD, Cholesterol, LDL, Hyperlipoproteinemia Type II, Cardiovascular Diseases, Heart Disease Risk Factors, Risk Factors, Humans, Female, Cardiology and Cardiovascular Medicine, Child, Lipoprotein(a)
Abstract: Little is known about the role of Lp(a) in the assessment of cardiovascular risk in the paediatric population. Trying to clarify the clinical relevance of Lp(a) in risk stratification, the aim of the study is to evaluate the association between Lp(a) plasma levels in children with familial hypercholesterolaemia (FH) and positive family history for premature cardiovascular disease (pCVD) in first- and second-degree relatives.653 Caucasian children and adolescents (334 females and 319 males), aged 2-17 years, with diagnosis of FH from a paediatric cohort included in the LIPIGEN Network, were selected. We compared family history of pCVD, lipid and genetic profile in two groups based on Lp(a) levels below or above 30 mg/dL. To determine the independent predictors of pCVD, a multivariate logistic regression was used, with all clinical characteristics and blood measurements as predictors.Subjects with Lp(a) 30 mg/dl more frequently reported positive family history of pCVD compared to subjects with Lp(a)≤30 mg/dl (69.90% vs 36.66%, p 0.0001), while did not show differences in terms of median [interquartile range] LDL-cholesterol level (153.00 [88.00 vs 164.50 [90.25] mg/dL, p = 0.3105). In the regression analysis, Lp(a) 30 mg/dl was an independent predictor of family history of pCVD. Comparing subjects with or without family history of pCVD, we reported significant differences for Lp(a) 30 mg/dl (46.25% vs 17.65%, p 0.0001), FH genetic mutation (50.48% vs 40.75%, p = 0,0157), as well as for LDL-cholesterol (p = 0.0013) and total cholesterol (p = 0.0101).Children/adolescents with FH and Lp(a) 30 mg/dl where more likely to have a positive family history of pCVD. Lp(a) screening in children and adolescents with FH may enhance risk assessment and help identify those subjects, children and relatives, at increased pCVD risk.
Published: 2021

27. Statin use and risk of dementia or Alzheimer's disease: a systematic review and meta-analysis of observational studies

Author: Elena Olmastroni, Giulia Molari, Noemi De Beni, Ornella Colpani, Federica Galimberti, Marta Gazzotti, Alberto Zambon, Alberico L Catapano, and Manuela Casula
Subjects: Male, Epidemiology, Statins, Alzheimer’s disease, Dementia, Meta-analysis, Observational studies, Female, Humans, Odds Ratio, Alzheimer Disease, Cognitive Dysfunction, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine
Abstract: Aims As the potential impact of statins on cognitive decline and dementia is still debated, we conducted a meta-analysis of observational studies to examine the effect of statin use on the risk of Alzheimer’s disease (AD) and dementia. Methods and results PubMed, Cochrane, and EMBASE were searched since inception to January 2021. Inclusion criteria were: (i) cohort or case–control studies; (ii) statin users compared to non-users; and (iii) AD and/or dementia risk as outcome. Estimates from original studies were pooled using restricted maximum-likelihood random-effect model. Measure of effects were reported as odds ratio (OR) and 95% confidence intervals (CIs). In the pooled analyses, statins were associated with a decreased risk of dementia [36 studies, OR 0.80 (CI 0.75–0.86)] and of AD [21 studies, OR 0.68 (CI 0.56–0.81)]. In the stratified analysis by sex, no difference was observed in the risk reduction of dementia between men [OR 0.86 (CI 0.81–0.92)] and women [OR 0.86 (CI 0.81–0.92)]. Similar risks were observed for lipophilic and hydrophilic statins for both dementia and AD, while high-potency statins showed a 20% reduction of dementia risk compared with a 16% risk reduction associated with low-potency statins, suggesting a greater efficacy of the former, although a borderline statistical significance (P = 0.05) for the heterogeneity between estimates. Conclusion These results confirm the absence of a neurocognitive risk associated with statin treatment and suggest a potential favourable role of statins. Randomized clinical trials with an ad hoc design are needed to explore this potential neuroprotective effect.
Published: 2021

28. Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

Author: Jie Lin, Snejana Tisheva, Ishwar C. Verma, Francesco Cipollone, Liam R. Brunham, Florentina Predica, Perla A.C. Gonzalez, Jocelyne Inamo, André R. Miserez, Belma Pojskic, Michel Farnier, Avishay Ellis, Katia Bonomo, Ibrahim Al-Zakwani, Maria Grazia Zenti, Humberto A. Lopez, Khairul Shafiq Ibrahim, Erkin M. Mirrakhimov, Alexey Meshkov, Jose P. de Moura, Muthukkaruppan Annamalai, Raul D. Santos, F. Paillard, Maria Del Ben, Jan Lacko, Miguel T. Rico, Ximena Reyes, Laura E.G. de Leon, Noor Shafina Mohd Nor, Ulrich Julius, Mohammed A. Batais, Dieter Böhm, Ta-Chen Su, Takuya Kobayashi, Magdalena Chmara, Marco Gebauer, Marcos M. Lima-Martínez, Ravshanbek D. Kurbanov, Daisaku Masuda, Amro El-Hadidy, Melanie Schüler, Francisco Fuentes, Florian J. Mayer, Helena Vaverkova, F. Ulrich Beil, Juraj Bujdak, Mario Stoll, Isabelle Ruel, Elena Dorn, Thomas M. Stulnig, Abubaker Elfatih, Rano B. Alieva, Jiri Vesely, Valérie Carreau, Cristina M. Sibaja, Sophie Béliard, Olivier Ziegler, Adriana Branchi, Daniel Schurr, G.B. John Mancini, Tai E. Shyong, Eric L.T. Siang, Mafalda Bourbon, Zerrin Yigit, Meral Kayıkçıoğlu, Jacques Genest, Wei Yu, Michal Vrablík, Shavkat U. Hoshimov, Dan Gaita, Antonio Pipolo, Ashraf H.A. AlQudaimi, Walter Speidl, Gianfranco Parati, Zaliha Ismail, Victoria M. Zubieta, René Valéro, Tomas Salek, Hana Halamkova, Gustavs Latkovskis, Nicole Allendorf-Ostwald, Agnes Perrin, Vladimir Soska, Anastasia Garoufi, Francisco Araujo, Nacu C. Portilla, Thomas Segiet, Charalambos Koumaras, Hila Knobler, Fatih Sivri, Hani Altaradi, Ivan Pećin, Long Jiang, Alexander Dressel, Marlena Woś, Jana Franekova, D. Agapakis, Quitéria Rato, Dirk J. Blom, Marcin A. Bartlomiejczyk, Krzysztof Dyrbuś, Maurizio Averna, Phivos Symeonides, Yung A. Chua, Asim Rana, András Nagy, Juan C.G. Cuellar, Alexander Jäkel, Maya Safarova, Neama Luqman, Amalia-Despoina Koutsogianni, Patrick Tounian, Jose A. 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I., Tziomalos K., Rallidis L., Kotsis V., Doumas M., Athyros V., Skalidis E., Kolovou G., Garoufi A., Bilianou E., Koutagiar I., Agapakis D., Kiouri E., Antza C., Katsiki N., Zacharis E., Attilakos A., Sfikas G., Koumaras C., Anagnostis P., Anastasiou G., Liamis G., Koutsogianni A.-D., Karanyi Z., Harangi M., Bajnok L., Audikovszky M., Mark L., Benczur B., Reiber I., Nagy G., Nagy A., Reddy L.L., Shah S.A.V., Ponde C.K., Dalal J.J., Sawhney J.P.S., Verma I.C., Altaey M., Al-Jumaily K., Rasul D., Abdalsahib A.F., Jabbar A.A., Al-ageedi M., Agar R., Cohen H., Ellis A., Gavishv D., Harats D., Henkin Y., Knobler H., Leavit L., Leitersdorf E., Rubinstein A., Schurr D., Shpitzen S., Szalat A., Casula M., Zampoleri V., Gazzotti M., Olmastroni E., Sarzani R., Ferri C., Repetti E., Sabba C., Bossi A.C., Borghi C., Muntoni S., Cipollone F., Purrello F., Pujia A., Passaro A., Marcucci R., Pecchioli V., Pisciotta L., Mandraffino G., Pellegatta F., Mombelli G., Branchi A., Fiorenza A.M., Pederiva C., Werba J.P., Parati G., Carubbi F., Iughetti L., Iannuzzi A., Iannuzzo G., Calabro P., Averna M, Biasucci G., Zambon S., Roscini A.R., Trenti C., Arca M., Federici M., Del Ben M., Bartuli A., Giaccari A., Pipolo A., Citroni N., Guardamagna O., Bonomo K., Benso A., Biolo G., Maroni L., Lupi A., Bonanni L., Zenti M.G., Matsuki K., Hori M., Ogura M., Masuda D., Kobayashi T., Nagahama K., Al-Jarallah M., Radovic M., Lunegova O., Bektasheva E., Khodzhiboboev E., Erglis A., Gilis D., Nesterovics G., Saripo V., Meiere R., Upena-RozeMicena A., Terauda E., Jambart S., Khoury P.E., Elbitar S., Ayoub C., Ghaleb Y., Aliosaitiene U., Kutkiene S., Kasim N.A.M., Nor N.S.M., Ramli A.S., Razak S.A., Al-Khateeb A., Kadir S.H.S.A., Muid S.A., Rahman T.A., Kasim S.S., Radzi A.B.M., Ibrahim K.S., Razali S., Ismail Z., Ghani R.A., Hafidz M.I.A., Chua A.L., Rosli M.M., Annamalai M., Teh L.K., Razali R., Chua Y.A., Rosman A., Sanusi A.R., Murad N.A.A., Jamal A.R.A., Nazli S.A., Razman A.Z., Rosman N., Rahmat R., Hamzan N.S., Azzopardi C., Mehta R., Martagon A.J., Ramirez G.A.G., Villa N.E.A., Vazquez A.V., Elias-Lopez D., Retana G.G., Rodriguez B., Macias J.J.C., Zazueta A.R., Alvarado R.M., Portano J.D.M., Lopez H.A., Sauque-Reyna L., Herrera L.G.G., Mendia L.E.S., Aguilar H.G., Cooremans E.R., Aparicio B.P., Zubieta V.M., Gonzalez P.A.C., Ferreira-Hermosillo A., Portilla N.C., Dominguez G.J., Garcia A.Y.R., Cazares H.E.A., Gonzalez J.R., Valencia C.V.M., Padilla F.G., Prado R.M., De los Rios Ibarra M.O., Villicana R.D.A., Rivera K.J.A., Carrera R.A., Alvarez J.A., Martinez J.C.A., de los Reyes Barrera Bustillo M., Vargas G.C., Chacon R.C., Andrade M.H.F., Ortega A.F., Alcala H.G., de Leon L.E.G., Guzman B.G., Garcia J.J.G., Cuellar J.C.G., Cruz J.R.G., Garcia A.H., Almada J.R.H., Herrera U.J., Sobrevilla F.L., Rodriguez E.M., Sibaja C.M., Rodriguez A.B.M., Oyervides J.C.M., Vazquez D.I.P., Rodriguez E.A.R., Osorio M.L.R., Saucedo J.R., Tamayo M.T., Talavera L.A.V., Arroyo L.E.V., Carrillo E.A.Z., Isara A., Obaseki D.E., Al-Waili K., Al-Zadjali F., Al-Zakwani I., Al-Kindi M., Al-Mukhaini S., Al-Barwani H., Rana A., Shah L.S.U., Starostecka E., Konopka A., Lewek J., Bartlomiejczyk M., Gasior M., Dyrbus K., Jozwiak J., Gruchala M., Pajkowski M., Romanowska-Kocejko M., Zarczynska-Buchowiecka M., Chmara M., Wasag B., Parczewska A., Gilis-Malinowska N., Borowiec-Wolna J., Strozyk A., Wos M., Michalska-Grzonkowska A., Medeiros A.M., Alves A.C., Silva F., Lobarinhas G., Palma I., de Moura J.P., Rico M.T., Rato Q., Pais P., Correia S., Moldovan O., Virtuoso M.J., Salgado J.M., Colaco I., Dumitrescu A., Lengher C., Mosteoru S., Meshkov A., Ershova A., Rozkova T., Korneva V., Yu K.T., Zafiraki V., Voevoda M., Gurevich V., Duplyakov D., Ragino Y., Safarova M., Shaposhnik I., Alkaf F., Khudari A., Rwaili N., Al-Allaf F., Alghamdi M., Batais M.A., Almigbal T.H., Kinsara A., AlQudaimi A.H.A., Awan Z., Elamin O.A., Altaradi H., Rajkovic N., Popovic L., Singh S., Stosic L., Rasulic I., Lalic N.M., Lam C., Le T.J., Siang E.L.T., Dissanayake S., I-Shing J.T., Shyong T.E., Jin T.C.S., Balinth K., Buganova I., Fabryova L., Kadurova M., Klabnik A., Kozarova M., Sirotiakova J., Battelino T., Kovac J., Mlinaric M., Sustar U., Podkrajsek K.T., Fras Z., Jug B., Cevc M., Pilcher G.J., Blom D.J., Wolmarans K.H., Brice B.C., Muniz-Grijalvo O., Diaz-Diaz J.L., de Isla L.P., Fuentes F., Badimon L., Martin F., Lux A., Chang N.-T., Ganokroj P., Akbulut M., Alici G., Bayram F., Can L.H., Celik A., Ceyhan C., Coskun F.Y., Demir M., Demircan S., Dogan V., Durakoglugil E., Dural I.E., Gedikli O., Hacioglu A., Ildizli M., Kilic S., Kirilmaz B., Kutlu M., Oguz A., Ozdogan O., Onrat E., Ozer S., Sabuncu T., Sahin T., Sivri F., Sonmez A., Temizhan A., Topcu S., Tuncez A., Vural M., Yenercag M., Yesilbursa D., Yigit Z., Yildirim A.B., Yildirir A., Yilmaz M.B., Atallah B., Traina M., Sabbour H., Hay D.A., Luqman N., Elfatih A., Abdulrasheed A., Kwok S., Oca N.D., Reyes X., Alieva R.B., Kurbanov R.D., Hoshimov S.U., Nizamov U.I., Ziyaeva A.V., Abdullaeva G.J., Do D.L., Nguyen M.N.T., Kim N.T., Le T.T., Le H.A., Tokgozoglu L., Catapano A.L., Ray K.K., Vallejo-Vaz, A. J., Stevens, C. A. T., Lyons, A. R. M., Dharmayat, K. I., Freiberger, T., Hovingh, G. K., Mata, P., Raal, F. J., Santos, R. D., Soran, H., Watts, G. F., Abifadel, M., Aguilar-Salinas, C. A., Alhabib, K. F., Alkhnifsawi, M., Almahmeed, W., Alnouri, F., Alonso, R., Al-Rasadi, K., Al-Sarraf, A., Al-Sayed, N., Araujo, F., Ashavaid, T. F., Banach, M., Beliard, S., Benn, M., Binder, C. J., Bogsrud, M. P., Bourbon, M., Chlebus, K., Corral, P., Davletov, K., Descamps, O. S., Durst, R., Ezhov, M., Gaita, D., Genest, J., Groselj, U., Harada-Shiba, M., Holven, K. B., Kayikcioglu, M., Khovidhunkit, W., Lalic, K., Latkovskis, G., Laufs, U., Liberopoulos, E., Lima-Martinez, M. M., Lin, J., Maher, V., Marais, A. D., Marz, W., Mirrakhimov, E., Miserez, A. R., Mitchenko, O., Nawawi, H., Nordestgaard, B. G., Panayiotou, A. G., Paragh, G., Petrulioniene, Z., Pojskic, B., Postadzhiyan, A., Raslova, K., Reda, A., Sadiq, F., Sadoh, W. E., Schunkert, H., Shek, A. B., Stoll, M., Stroes, E., Su, T. -C., Subramaniam, T., Susekov, A. V., Tilney, M., Tomlinson, B., Truong, T. H., Tselepis, A. D., Tybjaerg-Hansen, A., Vazquez Cardenas, A., Viigimaa, M., Wang, L., Yamashita, S., Kastelein, J. J. P., Bruckert, E., Vohnout, B., Schreier, L., Pang, J., Ebenbichler, C., Dieplinger, H., Innerhofer, R., Winhofer-Stockl, Y., Greber-Platzer, S., Krychtiuk, K., Speidl, W., Toplak, H., Widhalm, K., Stulnig, T., Huber, K., Hollerl, F., Rega-Kaun, G., Kleemann, L., Maser, M., Scholl-Burgi, S., Saly, C., Mayer, F. J., Sablon, G., Tarantino, E., Nzeyimana, C., Pojskic, L., Sisic, I., Nalbantic, A. D., Jannes, C. E., Pereira, A. C., Krieger, J. E., Petrov, I., Goudev, A., Nikolov, F., Tisheva, S., Yotov, Y., Tzvetkov, I., Baass, A., Bergeron, J., Bernard, S., Brisson, D., Brunham, L. R., Cermakova, L., Couture, P., Francis, G. A., Gaudet, D., Hegele, R. A., Khoury, E., Mancini, G. B. J., Mccrindle, B. W., Paquette, M., Ruel, I., Cuevas, A., Asenjo, S., Wang, X., Meng, K., Song, X., Yong, Q., Jiang, T., Liu, Z., Duan, Y., Hong, J., Ye, P., Chen, Y., Qi, J., Li, Y., Zhang, C., Peng, J., Yang, Y., Yu, W., Wang, Q., Yuan, H., Cheng, S., Jiang, L., Chong, M., Jiao, J., Wu, Y., Wen, W., Xu, L., Zhang, R., Qu, Y., He, J., Fan, X., Wang, Z., Chow, E., Pecin, I., Perica, D., Symeonides, P., Vrablik, M., Ceska, R., Soska, V., Tichy, L., Adamkova, V., Franekova, J., Cifkova, R., Kraml, P., Vonaskova, K., Cepova, J., Dusejovska, M., Pavlickova, L., Blaha, V., Rosolova, H., Nussbaumerova, B., Cibulka, R., Vaverkova, H., Cibickova, L., Krejsova, Z., Rehouskova, K., Malina, P., Budikova, M., Palanova, V., Solcova, L., Lubasova, A., Podzimkova, H., Bujdak, J., Vesely, J., Jordanova, M., Salek, T., Urbanek, R., Zemek, S., Lacko, J., Halamkova, H., Machacova, S., Mala, S., Cubova, E., Valoskova, K., Burda, L., Bendary, A., Daoud, I., Emil, S., Elbahry, A., Rafla, S., Sanad, O., Kazamel, G., Ashraf, M., Sobhy, M., El-Hadidy, A., Shafy, M. A., Kamal, S., Bendary, M., Talviste, G., Angoulvant, D., Boccara, F., Cariou, B., Carreau, V., Carrie, A., Charrieres, S., Cottin, Y., Di-Fillipo, M., Ducluzeau, P. H., Dulong, S., Durlach, V., Farnier, M., Ferrari, E., Ferrieres, D., Ferrieres, J., Gallo, A., Hankard, R., Inamo, J., Lemale, J., Moulin, P., Paillard, F., Peretti, N., Perrin, A., Pradignac, A., Rabes, J. P., Rigalleau, V., Sultan, A., Schiele, F., Tounian, P., Valero, R., Verges, B., Yelnik, C., Ziegler, O., Haack, I. A., Schmidt, N., Dressel, A., Klein, I., Christmann, J., Sonntag, A., Stumpp, C., Boger, D., Biedermann, D., Usme, M. M. N., Beil, F. U., Klose, G., Konig, C., Gouni-Berthold, I., Otte, B., Boll, G., Kirschbaum, A., Merke, J., Scholl, J., Segiet, T., Gebauer, M., Predica, F., Mayer, M., Leistikow, F., Fullgraf-Horst, S., Muller, C., Schuler, M., Wiener, J., Hein, K., Baumgartner, P., Kopf, S., Busch, R., Schomig, M., Matthias, S., Allendorf-Ostwald, N., Fink, B., Bohm, D., Jakel, A., Koschker, A. -C., Schweizer, R., Vogt, A., Parhofer, K., Konig, W., Reinhard, W., Bassler, A., Stadelmann, A., Schrader, V., Katzmann, J., Tarr, A., Steinhagen-Thiessen, E., Kassner, U., Paulsen, G., Homberger, J., Zemmrich, C., Seeger, W., Biolik, K., Deiss, D., Richter, C., Pantchechnikova, E., Dorn, E., Schatz, U., Julius, U., Spens, A., Wiesner, T., Scholl, M., Rizos, C. V., Sakkas, N., Elisaf, M., Skoumas, I., Tziomalos, K., Rallidis, L., Kotsis, V., Doumas, M., Athyros, V., Skalidis, E., Kolovou, G., Garoufi, A., Bilianou, E., Koutagiar, I., Agapakis, D., Kiouri, E., Antza, C., Katsiki, N., Zacharis, E., Attilakos, A., Sfikas, G., Koumaras, C., Anagnostis, P., Anastasiou, G., Liamis, G., Koutsogianni, A. -D., Karanyi, Z., Harangi, M., Bajnok, L., Audikovszky, M., Mark, L., Benczur, B., Reiber, I., Nagy, G., Nagy, A., Reddy, L. L., Shah, S. A. V., Ponde, C. K., Dalal, J. J., Sawhney, J. P. S., Verma, I. C., Altaey, M., Al-Jumaily, K., Rasul, D., Abdalsahib, A. F., Jabbar, A. A., Al-ageedi, M., Agar, R., Cohen, H., Ellis, A., Gavishv, D., Harats, D., Henkin, Y., Knobler, H., Leavit, L., Leitersdorf, E., Rubinstein, A., Schurr, D., Shpitzen, S., Szalat, A., Casula, M., Zampoleri, V., Gazzotti, M., Olmastroni, E., Sarzani, R., Ferri, C., Repetti, E., Sabba, C., Bossi, A. C., Borghi, C., Muntoni, S., Cipollone, F., Purrello, F., Pujia, A., Passaro, A., Marcucci, R., Pecchioli, V., Pisciotta, L., Mandraffino, G., Pellegatta, F., Mombelli, G., Branchi, A., Fiorenza, A. M., Pederiva, C., Werba, J. P., Parati, G., Carubbi, F., Iughetti, L., Iannuzzi, A., Iannuzzo, G., Calabro, P., Averna, M., Biasucci, G., Zambon, S., Roscini, A. R., Trenti, C., Arca, M., Federici, M., Del Ben, M., Bartuli, A., Giaccari, A., Pipolo, A., Citroni, N., Guardamagna, O., Bonomo, K., Benso, A., Biolo, G., Maroni, L., Lupi, A., Bonanni, L., Zenti, M. G., Matsuki, K., Hori, M., Ogura, M., Masuda, D., Kobayashi, T., Nagahama, K., Al-Jarallah, M., Radovic, M., Lunegova, O., Bektasheva, E., Khodzhiboboev, E., Erglis, A., Gilis, D., Nesterovics, G., Saripo, V., Meiere, R., Upena-RozeMicena, A., Terauda, E., Jambart, S., Khoury, P. E., Elbitar, S., Ayoub, C., Ghaleb, Y., Aliosaitiene, U., Kutkiene, S., Kasim, N. A. M., Nor, N. S. M., Ramli, A. S., Razak, S. A., Al-Khateeb, A., Kadir, S. H. S. A., Muid, S. A., Rahman, T. A., Kasim, S. S., Radzi, A. B. M., Ibrahim, K. S., Razali, S., Ismail, Z., Ghani, R. A., Hafidz, M. I. A., Chua, A. L., Rosli, M. M., Annamalai, M., Teh, L. K., Razali, R., Chua, Y. A., Rosman, A., Sanusi, A. R., Murad, N. A. A., Jamal, A. R. A., Nazli, S. A., Razman, A. Z., Rosman, N., Rahmat, R., Hamzan, N. S., Azzopardi, C., Mehta, R., Martagon, A. J., Ramirez, G. A. G., Villa, N. E. A., Vazquez, A. V., Elias-Lopez, D., Retana, G. G., Rodriguez, B., Macias, J. J. C., Zazueta, A. R., Alvarado, R. M., Portano, J. D. M., Lopez, H. A., Sauque-Reyna, L., Herrera, L. G. G., Mendia, L. E. S., Aguilar, H. G., Cooremans, E. R., Aparicio, B. P., Zubieta, V. M., Gonzalez, P. A. C., Ferreira-Hermosillo, A., Portilla, N. C., Dominguez, G. J., Garcia, A. Y. R., Cazares, H. E. A., Gonzalez, J. R., Valencia, C. V. M., Padilla, F. G., Prado, R. M., De los Rios Ibarra, M. O., Villicana, R. D. A., Rivera, K. J. A., Carrera, R. A., Alvarez, J. A., Martinez, J. C. A., de los Reyes Barrera Bustillo, M., Vargas, G. C., Chacon, R. C., Andrade, M. H. F., Ortega, A. F., Alcala, H. G., de Leon, L. E. G., Guzman, B. G., Garcia, J. J. G., Cuellar, J. C. G., Cruz, J. R. G., Garcia, A. H., Almada, J. R. H., Herrera, U. J., Sobrevilla, F. L., Rodriguez, E. M., Sibaja, C. M., Rodriguez, A. B. M., Oyervides, J. C. M., Vazquez, D. I. P., Rodriguez, E. A. R., Osorio, M. L. R., Saucedo, J. R., Tamayo, M. T., Talavera, L. A. V., Arroyo, L. E. V., Carrillo, E. A. Z., Isara, A., Obaseki, D. E., Al-Waili, K., Al-Zadjali, F., Al-Zakwani, I., Al-Kindi, M., Al-Mukhaini, S., Al-Barwani, H., Rana, A., Shah, L. S. U., Starostecka, E., Konopka, A., Lewek, J., Bartlomiejczyk, M., Gasior, M., Dyrbus, K., Jozwiak, J., Gruchala, M., Pajkowski, M., Romanowska-Kocejko, M., Zarczynska-Buchowiecka, M., Chmara, M., Wasag, B., Parczewska, A., Gilis-Malinowska, N., Borowiec-Wolna, J., Strozyk, A., Wos, M., Michalska-Grzonkowska, A., Medeiros, A. M., Alves, A. C., Silva, F., Lobarinhas, G., Palma, I., de Moura, J. P., Rico, M. T., Rato, Q., Pais, P., Correia, S., Moldovan, O., Virtuoso, M. J., Salgado, J. M., Colaco, I., Dumitrescu, A., Lengher, C., Mosteoru, S., Meshkov, A., Ershova, A., Rozkova, T., Korneva, V., Yu, K. T., Zafiraki, V., Voevoda, M., Gurevich, V., Duplyakov, D., Ragino, Y., Safarova, M., Shaposhnik, I., Alkaf, F., Khudari, A., Rwaili, N., Al-Allaf, F., Alghamdi, M., Batais, M. A., Almigbal, T. H., Kinsara, A., Alqudaimi, A. H. A., Awan, Z., Elamin, O. A., Altaradi, H., Rajkovic, N., Popovic, L., Singh, S., Stosic, L., Rasulic, I., Lalic, N. M., Lam, C., Le, T. J., Siang, E. L. T., Dissanayake, S., I-Shing, J. T., Shyong, T. E., Jin, T. C. S., Balinth, K., Buganova, I., Fabryova, L., Kadurova, M., Klabnik, A., Kozarova, M., Sirotiakova, J., Battelino, T., Kovac, J., Mlinaric, M., Sustar, U., Podkrajsek, K. T., Fras, Z., Jug, B., Cevc, M., Pilcher, G. J., Blom, D. J., Wolmarans, K. H., Brice, B. C., Muniz-Grijalvo, O., Diaz-Diaz, J. L., de Isla, L. P., Fuentes, F., Badimon, L., Martin, F., Lux, A., Chang, N. -T., Ganokroj, P., Akbulut, M., Alici, G., Bayram, F., Can, L. H., Celik, A., Ceyhan, C., Coskun, F. Y., Demir, M., Demircan, S., Dogan, V., Durakoglugil, E., Dural, I. E., Gedikli, O., Hacioglu, A., Ildizli, M., Kilic, S., Kirilmaz, B., Kutlu, M., Oguz, A., Ozdogan, O., Onrat, E., Ozer, S., Sabuncu, T., Sahin, T., Sivri, F., Sonmez, A., Temizhan, A., Topcu, S., Tuncez, A., Vural, M., Yenercag, M., Yesilbursa, D., Yigit, Z., Yildirim, A. B., Yildirir, A., Yilmaz, M. B., Atallah, B., Traina, M., Sabbour, H., Hay, D. A., Luqman, N., Elfatih, A., Abdulrasheed, A., Kwok, S., Oca, N. D., Reyes, X., Alieva, R. B., Kurbanov, R. D., Hoshimov, S. U., Nizamov, U. I., Ziyaeva, A. V., Abdullaeva, G. J., Do, D. L., Nguyen, M. N. T., Kim, N. T., Le, T. T., Le, H. A., Tokgozoglu, L., Catapano, A. L., Ray, K. K., and EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC), Borghi C
Subjects: Male, Settore MED/09 - Medicina Interna, Arterial disease, Cross-sectional study, Adult population, Coronary Disease, Disease, Global Health, Medical and Health Sciences, Doenças Cardio e Cérebro-vasculares, Anticholesteremic Agent, Monoclonal, Prevalence, Registries, Familial Hypercholesterolemia, Humanized, Stroke, 11 Medical and Health Sciences, LS2_9, Studies Collaboration, Anticholesteremic Agents, General Medicine, Heart Disease Risk Factor, Middle Aged, FHSC global registry data, Europe, Treatment Outcome, Lower prevalence, Guidance, lipids (amino acids, peptides, and proteins), Female, Proprotein Convertase 9, Familial hypercholesterolaemia, Life Sciences & Biomedicine, Human, Adult, medicine.medical_specialty, Combination therapy, FHSC global registry, heterozygous familial hypercholesterolaemia, Cardiovascular risk factors, Antibodies, Monoclonal, Humanized, Insights, Antibodies, NO, Hyperlipoproteinemia Type II, Clinician, Medicine, General & Internal, Internal medicine, General & Internal Medicine, Health Sciences, medicine, Humans, EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC), Cross-Sectional Studie, Science & Technology, Global Perspective, business.industry, Cholesterol, LDL, medicine.disease, Cross-Sectional Studies, Heart Disease Risk Factors, Hydroxymethylglutaryl-CoA Reductase Inhibitor, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business
Abstract: Background The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally. Methods Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Data were assessed overall and by WHO regions, sex, and index versus non-index cases. Findings Of the 61 612 individuals in the registry, 42 167 adults (21 999 [53.6%] women) from 56 countries were included in the study. Of these, 31 798 (75.4%) were diagnosed with the Dutch Lipid Clinic Network criteria, and 35 490 (84.2%) were from the WHO region of Europe. Median age of participants at entry in the registry was 46.2 years (IQR 34.3-58.0); median age at diagnosis of familial hypercholesterolaemia was 44.4 years (32.5-56.5), with 40.2% of participants younger than 40 years when diagnosed. Prevalence of cardiovascular risk factors increased progressively with age and varied by WHO region. Prevalence of coronary disease was 17.4% (2.1% for stroke and 5.2% for peripheral artery disease), increasing with concentrations of untreated LDL cholesterol, and was about two times lower in women than in men. Among patients receiving lipid-lowering medications, 16 803 (81.1%) were receiving statins and 3691 (21.2%) were on combination therapy, with greater use of more potent lipid-lowering medication in men than in women. Median LDL cholesterol was 5.43 mmol/L (IQR 4.32-6.72) among patients not taking lipid-lowering medications and 4.23 mmol/L (3.20-5.66) among those taking them. Among patients taking lipid-lowering medications, 2.7% had LDL cholesterol lower than 1.8 mmol/L; the use of combination therapy, particularly with three drugs and with proprotein convertase subtilisin-kexin type 9 inhibitors, was associated with a higher proportion and greater odds of having LDL cholesterol lower than 1.8 mmol/L. Compared with index cases, patients who were non-index cases were younger, with lower LDL cholesterol and lower prevalence of cardiovascular risk factors and cardiovascular diseases (all p, Pfizer Independent Grant for Learning Change [16157823]; Amgen; Merck Sharp Dohme; Sanofi-Aventis; Daiichi Sankyo; Regeneron; National Institute for Health Research (NIHR) Imperial Biomedical Research Centre, UK; NIHR; Czech Ministry of Health [NU20-02-00261]; Canadian Institutes of Health Research; Austrian Heart Foundation; Tyrolean Regional Government; Gulf Heart Association, The EAS FHSC is an academic initiative that has received funding from a Pfizer Independent Grant for Learning & Change 2014 (16157823) and from investigator-initiated research grants to the European Atherosclerosis Society-Imperial College London from Amgen, Merck Sharp & Dohme, Sanofi-Aventis, Daiichi Sankyo, and Regeneron. KKR acknowledges support from the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre, UK. KID acknowledges support from a PhD Studentship from NIHR under the Applied Health Research programme for Northwest London, UK (the views expressed in this publication are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health). TF was supported by a grant from the Czech Ministry of Health (NU20-02-00261). JG receives support from the Canadian Institutes of Health Research. The Austrian Familial Hypercholesterolaemia registry has been supported by funds from the Austrian Heart Foundation and the Tyrolean Regional Government. The Gulf Familial Hypercholesterolaemia registry was done under the auspices of the Gulf Heart Association.
Published: 2021

29. Interactions of Oxysterols with Atherosclerosis Biomarkers in Subjects with Moderate Hypercholesterolemia and Effects of a Nutraceutical Combination (

Author: Stefania, Cicolari, Chiara, Pavanello, Elena, Olmastroni, Marina Del, Puppo, Marco, Bertolotti, Giuliana, Mombelli, Alberico L, Catapano, Laura, Calabresi, and Paolo, Magni
Subjects: Male, cardiovascular risk, Biological Products, 25-OHC, hypercholesterolemia, Oxysterols, Middle Aged, Atherosclerosis, Bifidobacterium longum, monacolin K, 27-OHC, Article, Placebos, Cholesterol, 24-OHC, Dietary Supplements, cholesterol metabolism, Humans, Female, sense organs, nutraceutical, Biomarkers, probiotic, Aged
Abstract: Background: Oxysterol relationship with cardiovascular (CV) risk factors is poorly explored, especially in moderately hypercholesterolaemic subjects. Moreover, the impact of nutraceuticals controlling hypercholesterolaemia on plasma levels of 24-, 25- and 27-hydroxycholesterol (24-OHC, 25-OHC, 27-OHC) is unknown. Methods: Subjects (n = 33; 18–70 years) with moderate hypercholesterolaemia (low-density lipoprotein cholesterol (LDL-C:): 130–200 mg/dL), in primary CV prevention as well as low CV risk were studied cross-sectionally. Moreover, they were evaluated after treatment with a nutraceutical combination (Bifidobacterium longum BB536, red yeast rice extract (10 mg/dose monacolin K)), following a double-blind, randomized, placebo-controlled design. We evaluated 24-OHC, 25-OHC and 27-OHC levels by gas chromatography/mass spectrometry analysis. Results: 24-OHC and 25-OHC were significantly correlated, 24-OHC was correlated with apoB. 27-OHC and 27-OHC/total cholesterol (TC) were higher in men (median 209 ng/mL and 77 ng/mg, respectively) vs. women (median 168 ng/mL and 56 ng/mg, respectively); 27-OHC/TC was significantly correlated with abdominal circumference, visceral fat and, negatively, with high-density lipoprotein cholesterol (HDL-C). Triglycerides were significantly correlated with 24-OHC, 25-OHC and 27-OHC and with 24-OHC/TC and 25-OHC/TC. After intervention, 27-OHC levels were significantly reduced by 10.4% in the nutraceutical group Levels of 24-OHC, 24-OHC/TC, 25-OHC, 25-OHC/TC and 27-OHC/TC were unchanged. Conclusions: In this study, conducted in moderate hypercholesterolemic subjects, we observed novel relationships between 24-OHC, 25-OHC and 27-OHC and CV risk biomarkers. In addition, no adverse changes of OHC levels upon nutraceutical treatment were found.
Published: 2020

30. Geographical Variation in Medication Prescriptions: A Multiregional Drug-Utilization Study

Author: Veronica Russo, Valentina Orlando, Valeria Marina Monetti, Federica Galimberti, Manuela Casula, Elena Olmastroni, Elena Tragni, Enrica Menditto, EDU.RE.DRUG Group, Alberico L. Catapanoa, Giovanni Corrao, Sara Mucherino, Lorenza Scotti, Antonella Zambon, Marco Gambera, Rossana Piccinelli, Samanta Sonzogni, Valter Valsecchi, Eugenio Scopinaro, Sandro Raineri, Alessia Speziali, Simona Creazzola, Michele Tari, Mariano Fusco, Russo, Veronica, Orlando, Valentina, Monetti, Valeria Marina, Galimberti, Federica, Casula, Manuela, Olmastroni, Elena, Tragni, Elena, and Menditto, Enrica
Subjects: 0301 basic medicine, Drug, Drug Utilization, Multivariate statistics, Cross-sectional study, media_common.quotation_subject, prevalence, Prevalence, 03 medical and health sciences, 0302 clinical medicine, Environmental health, Bayesian multivariate linear regression, Medicine, Pharmacology (medical), Medical prescription, media_common, Original Research, drug use, Pharmacology, pharmacy claims, drug-utilization, business.industry, lcsh:RM1-950, Retrospective cohort study, geographical difference, 030104 developmental biology, lcsh:Therapeutics. Pharmacology, 030220 oncology & carcinogenesis, general practitioner, business
Abstract: Background Studies have emphasized the importance of geographical factors and general practitioner (GP) characteristics in influencing drug prescriptions. Objectives To: (i) ascertain the prevalence rate (PR) of use of drugs in six therapeutic categories used for chronic conditions; (ii) assess how geographical characteristics and GP characteristics may influence drug prescribing. Methods This study is part of the EDU.RE.DRUG Project, a national collaborative project founded by Italian Medicine Agency (AIFA). Cross-sectional analyses were undertaken employing the pharmacy-claim databases of four local health units (LHUs) located in two Italian regions: Lombardy and Campania. Six drug categories were evaluated: proton-pump inhibitors; antibiotics; respiratory-system drugs; statins; agents acting on the renin-angiotensin system; psychoanaleptic drugs. The PR was estimated according to drug categories at the LHU level. A linear multivariate regression analysis was undertaken to evaluate the association between the PR and geographical area, age and sex of GPs, number of patients, and percentage of patients aged >65 per GP. Results LHUs in Campania showed a PR that was significantly higher than that in Lombardy. Antibiotics showed the highest PR in all the LHUs assessed, ranging from 32.5% in Lecco (Lombardy) to 59.7% in Naples-2 (Campania). Multivariate linear regression analysis confirmed the association of the PR with geographical area for all drug categories. Being located in Campania increased the possibility of receiving a drug prescription from the categories considered, with estimates more marked for antibiotics, proton-pump-inhibitors, and respiratory-system drugs. Conclusions This study provides information about the PR of medications used for treating common and costly conditions in Italy and highlighted a significant geographical variation. These insights could help to develop area-specific strategies to optimize prescribing behavior.
Published: 2019

31. 03 - PREVALENCE OF STATIN-ASSOCIATED MUSCLE SYMPTOMS IN ITALY: THE PROSISA STUDY

Author: Liliana Grigore, Federica Bonaiti, Elena Olmastroni, Manuela Casula, and Marta Gazzotti
Published: 2019

32. 07 - DIAGNOSIS OF FAMILIAL HYPERCHOLESTEROLEMIA IN THE CLINICAL PRACTICE: PERFORMANCE OF DUTCH LIPID CLINIC NETWORK SCORE

Author: Marcello Arca, maurizio averna, Elena Olmastroni, Manuela Casula, and Federica Bonaiti
Published: 2019

33. 02 - USE OF BISPHOSPHONATES AND RISK OF CARDIOVASCULAR EVENTS: A POPULATION-BASED RETROSPECTIVE COHORT STUDY

Author: Lorenza Scotti, Giovanni Corrao, Elena Tragni, Elena Olmastroni, Manuela Casula, and Federica Galimberti
Published: 2019

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33 results on '"Elena Olmastroni"'

1. Longevity-associated BPIFB4 gene counteracts the inflammatory signaling

2. Apolipoprotein B compared with low-density lipoprotein cholesterol in the atherosclerotic cardiovascular diseases risk assessment

3. Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia

4. Corrigendum: The role of registers in increasing knowledge and improving management of children and adolescents affected by familial hypercholesterolemia: The LIPIGEN pediatric group

5. Beta-blockers in post-acute myocardial infarction patients: Drug prescription patterns from 2018 to Italy’s first wave of the COVID-19 pandemic

6. The Role of Registers in Increasing Knowledge and Improving Management of Children and Adolescents Affected by Familial Hypercholesterolemia: the LIPIGEN Pediatric Group

7. Adherence to Mediterranean Diet: A Population-Based Longitudinal Cohort Study

8. Evaluation of Factors Associated With Appropriate Drug Prescription and Effectiveness of Informative and Educational Interventions—The EDU.RE.DRUG Project

9. Twelve Variants Polygenic Score for Low‐Density Lipoprotein Cholesterol Distribution in a Large Cohort of Patients With Clinically Diagnosed Familial Hypercholesterolemia With or Without Causative Mutations

10. Antibiotic Prescription in the Community-Dwelling Elderly Population in Lombardy, Italy: A Sub-Analysis of the EDU.RE.DRUG Study

11. Oral Porphyromonas gingivalis and Fusobacterium nucleatum Abundance in Subjects in Primary and Secondary Cardiovascular Prevention, with or without Heterozygous Familial Hypercholesterolemia

12. Adherence to the Mediterranean Diet: Impact of Geographical Location of the Observations

13. Geographical Variation in Medication Prescriptions: A Multiregional Drug-Utilization Study

14. Gut Microbiota Functional Dysbiosis Relates to Individual Diet in Subclinical Carotid Atherosclerosis

15. Interactions of Oxysterols with Atherosclerosis Biomarkers in Subjects with Moderate Hypercholesterolemia and Effects of a Nutraceutical Combination (Bifidobacterium longum BB536, Red Yeast Rice Extract) (Randomized, Double-Blind, Placebo-Controlled Study)

16. Combining family history of coronary heart disease and individual genetic predisposition to predict the risk of major coronary events: Selected Abstract - SITeCS Congress 2022

17. Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia

18. Antibiotic Prescription in the Community-Dwelling Elderly Population in Lombardy, Italy: A Sub-Analysis of the EDU.RE.DRUG Study

19. Impact of the COVID-19 Pandemic on the Therapeutic Continuity among Outpatients with Chronic Cardiovascular Therapies

20. Oral

21. The Role of Registers in Increasing Knowledge and Improving Management of Children and Adolescents Affected by Familial Hypercholesterolemia: the LIPIGEN Pediatric Group

22. Impact of COVID-19 Pandemic on Adherence to Chronic Therapies: A Systematic Review

23. The Effectiveness of Interventions to Evaluate and Reduce Healthcare Costs of Potentially Inappropriate Prescriptions among the Older Adults: A Systematic Review

24. Potentially Inappropriate Prescribing among Elderly Outpatients: Evaluation of Temporal Trends 2012-2018 in Piedmont, Italy

25. Evaluation of Factors Associated With Appropriate Drug Prescription and Effectiveness of Informative and Educational Interventions-The EDU.RE.DRUG Project

26. Lipoprotein(a) and family history for cardiovascular disease in paediatric patients: A new frontier in cardiovascular risk stratification. Data from the LIPIGEN paediatric group

27. Statin use and risk of dementia or Alzheimer's disease: a systematic review and meta-analysis of observational studies

28. Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

29. Interactions of Oxysterols with Atherosclerosis Biomarkers in Subjects with Moderate Hypercholesterolemia and Effects of a Nutraceutical Combination (

30. Geographical Variation in Medication Prescriptions: A Multiregional Drug-Utilization Study

31. 03 - PREVALENCE OF STATIN-ASSOCIATED MUSCLE SYMPTOMS IN ITALY: THE PROSISA STUDY

32. 07 - DIAGNOSIS OF FAMILIAL HYPERCHOLESTEROLEMIA IN THE CLINICAL PRACTICE: PERFORMANCE OF DUTCH LIPID CLINIC NETWORK SCORE

33. 02 - USE OF BISPHOSPHONATES AND RISK OF CARDIOVASCULAR EVENTS: A POPULATION-BASED RETROSPECTIVE COHORT STUDY

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