Manuela Casula | Università degli Studi di Milano - State University of Milan (Italy) (original) (raw)

Papers by Manuela Casula

Atherosclerosis, 2020

BACKGROUND AND AIMS Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder ch... more BACKGROUND AND AIMS Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by extremely elevated plasma levels of low density lipoprotein cholesterol (LDL-C) and high risk of premature atherosclerotic cardiovascular disease (ASCVD). HoFH is caused by pathogenic variants in several genes, such as LDLR, APOB and PCSK9, responsible for autosomal dominant hypercholesterolemia (ADH), and LDLRAP1 responsible for autosomal recessive hypercholesterolemia (ARH). Aim of this study was the review of the clinical and molecular features of patients with HoFH identified in Italy from 1989 to 2019. METHODS Data were collected from lipid clinics and laboratories, which had performed molecular diagnosis in suspected HoFH. Clinical data included baseline lipid levels and ASCVD events. RESULTS A total of 125 subjects with ADH were identified, of whom 60 were true homozygotes, 58 compound heterozygotes and 7 double heterozygotes for LDLR (likely) pathogenic variants. C...

Pharmacological Research, 2018

Atherosclerosis Supplements

Cells

For a long time, high-density lipoprotein cholesterol (HDL-C) has been regarded as a cardiovascul... more For a long time, high-density lipoprotein cholesterol (HDL-C) has been regarded as a cardiovascular disease (CVD) protective factor. Recently, several epidemiological studies, while confirming low plasma levels of HDL-C as an established predictive biomarker for atherosclerotic CVD, indicated that not only people at the lowest levels but also those with high HDL-C levels are at increased risk of cardiovascular (CV) mortality. This “U-shaped” association has further fueled the discussion on the pathophysiological role of HDL in CVD. In fact, genetic studies, Mendelian randomization approaches, and clinical trials have challenged the notion of HDL-C levels being causally linked to CVD protection, independent of the cholesterol content in low-density lipoproteins (LDL-C). These findings have prompted a reconsideration of the biological functions of HDL that can be summarized with the word “HDL functionality”, a term that embraces the many reported biological activities beyond the so-ca...

The Lancet, 2021

Background The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaborat... more 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 crit...

Frontiers in Pharmacology

Background Studies have emphasized the importance of geographical factors and general practitione... more 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.

Atherosclerosis, 2016

We aimed at describing the therapeutic approach in young adult patients diagnosed with heterozygo... more We aimed at describing the therapeutic approach in young adult patients diagnosed with heterozygous familial hypercholesterolemia (HeFH) and their adherence and persistence to treatment. From regional administrative databases, individuals aged ≤40 years, who received exemption for HeFH between January 1, 2003 and December 31, 2011, and concomitantly started statin treatment, were identified. Within the first year of treatment, we evaluated therapeutic changes, adherence as MPR (medication possession ratio), persistence as continuous drug coverage without gaps ≥60 days, and influencing factors using log binomial models. Of 1404 patients, 42.4% were initially treated with a high-efficacy statin. 23.4% of patients showed at least one treatment change. Mean MPR was 68.7% (29.9), and patients showing continued statin use were 47.0%. Therapy modification was significantly associated with a past cardiovascular event (relative risk, RR [95% confidential interval] 2.28 [1.69-3.09]) and at least one lipid test (RR 1.82 [1.31-2.53]). MPR ≥80% was significantly associated with the first statin prescribed (atorvastatin RR 1.28 [1.09-1.51] and rosuvastatin RR 1.21 [1.01-1.44], vs. simvastatin), a past cardiovascular event (RR 1.33 [1.12-1.59]), at least one therapy change (RR 1.28 [1.15-1.43]), at least a lipid test (RR 1.26 [1.07-1.49]). A similar pattern was observed for persistence. This analysis of young adult HeFH patients showed that therapy change was quite frequent, and probably reflected adjustments according to individual response. Adherence and persistence were inadequate, even in this population at high cardiovascular risk, and they need to be improved through proper patient education and shared treatment decision-making approach.

Treatment and prevention of cardiovascular disease in the general population has benefited greatl... more Treatment and prevention of cardiovascular disease in the general population has benefited greatly from the identification of cardiovascular disease risk factors. Given the particularly high risk of cardiovascular disease and total mortality among patients with chronic renal insufficiency (CRI) and end-stage renal disease (ESRD), it is important to assess the role of traditional and nontraditional risk factors for cardiovascular disease. This review discusses the foundations of risk factor epidemiology and briefly summarizes the evidence regarding cardiovascular risk factors in renal disease. Diabetes and hypertension have a very high prevalence in patients with CRI. Patients with CRI and ESRD also have a higher frequency of cardiac dysfunction and left ventricular hypertrophy, which further increase the risk of cardiovascular disease. Finally, patients with renal disease have a higher prevalence of less established risk factors, including low HDL, and high triglycerides, lipoprotein(a), and homocysteine, where prospective studies and clinical trials are needed to provide a scientific basis for reduction of cardiovascular risk among patients with renal disease.

Atherosclerosis. Supplements, 2017

Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by elevated pla... more Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by elevated plasma levels of LDL-cholesterol that confers an increased risk of premature atherosclerotic cardiovascular disease. Early identification and treatment of FH patients can improve prognosis and reduce the burden of cardiovascular mortality. Aim of this study was to perform the mutational analysis of FH patients identified through a collaboration of 20 Lipid Clinics in Italy (LIPIGEN Study). We recruited 1592 individuals with a clinical diagnosis of definite or probable FH according to the Dutch Lipid Clinic Network criteria. We performed a parallel sequencing of the major candidate genes for monogenic hypercholesterolemia (LDLR, APOB, PCSK9, APOE, LDLRAP1, STAP1). A total of 213 variants were detected in 1076 subjects. About 90% of them had a pathogenic or likely pathogenic variants. More than 94% of patients carried pathogenic variants in LDLR gene, 27 of which were novel. Pathogenic varian...

Nutrients

Background: The prevention and treatment of obesity and its cardio-metabolic complications are re... more Background: The prevention and treatment of obesity and its cardio-metabolic complications are relevant issues worldwide. Among lifestyle approaches, very low-calorie ketogenic diets (VLCKD) have been shown to lead to rapid initial weight loss, resulting in better long-term weight loss maintenance. As no information on VLCKD studies carried on in a real-world setting are available, we conducted this multi-centre study in a real-world setting, aiming at assessing the efficacy and the safety of a specific multiphasic VLCKD program in women with overweight or obesity. Methods: A multi-center, prospective, uncontrolled trial was conducted in 33 outpatient women (age range 27–60 y) with overweight or obesity (BMI: 30.9 ± 2.7 kg/m2; waist circumference: 96.0 ± 9.4 cm) who started a VLCKD dietary program (duration: 24 weeks), divided into four phases. The efficacy of VLCKD was assessed by evaluating anthropometric measures and cardiometabolic markers; liver and kidney function biomarkers w...

Journal of Internal Medicine

Primary Health Care Research & Development

Introduction: Pharmacological intervention is an important component of patient care. However, dr... more Introduction: Pharmacological intervention is an important component of patient care. However, drugs are often inappropriately used. It is necessary for countries to implement strategies to improve the rational use of drugs, including independent information for healthcare professionals and the public, which must be supported by well-trained staff. The primary objectives of the EDU.RE.DRUG (Effectiveness of informative and/or educational interventions aimed at improving the appropriate use of drugs designed for general practitioners and their patients) study are the retrospective evaluation of rates of appropriate prescribing indicators (APIs) and the assessment of the effectiveness of informative and/or educational interventions addressed to general practitioners (GPs) and their patients, aimed at improving prescribing quality and promoting proper drug use. Methods and analysis: This is a prospective, multicentre, open-label, parallel-arm, controlled, pragmatic trial directed to GP...

Russian Journal of Cardiology

Рабочая группа Европейского кардиологического общества (ESC, ЕОК) и Европейского общества по изуч... more Рабочая группа Европейского кардиологического общества (ESC, ЕОК) и Европейского общества по изучению атеросклероза (EAS, ЕОА) по лечению дислипидемий Авторы/члены Рабочей группы: François Mach* (Председатель) (Швейцария), Colin Baigent* (Председатель) (Великобритания),