Manuela Casula (Italy)
University of Milan
Department of Pharmacological and Biomolecular Sciences
Manuela Casula Researcher at Epidemiology and Preventive Pharmacology Service (SEFAP), Department of Pharmacological and Biomolecular Sciences (DiSFeB), University of Milan In 2007: Degree in Chemistry and Pharmaceutical Technology, Faculty of Pharmacy, University of Milan, Italy. In 2014: PhD in Medical, Surgical, Clinical, and Experimental Sciences (Curriculum: pharmacoepidemiology) Research on - epidemiological studies on cardiovascular disease and associated risk factors - pharmacoutilization and pharmacoepidemiology studies: analyses of administrative, clinical, of pharmacovigilance databases with record linkage procedures, or meta-analyses from published data - evaluation of appropriate medication use (drug-drug interactions, off-label use, misprescribing/overprescribing, adherence to therapy) and educative/informative interventions Coordination of activities for clinical/epidemiological studies carried out by SISA Foundation for the promotion of research on atherosclerotic diseases, including interactions with the ethics committees for the procedural aspects and relations with the participating researchers. Author of more than sixty papers in international peer reviewer journals (Citation Report - Scopus [March, 2021] Sum of the Times Cited: 2960; h-index: 14) and more than thirty papers in Italian scientific journals. Member of: Italian Society of Pharmacology (SIF), Italian Society for Clinical and Experimental Therapeutics (SITeCS), Italian Society for the Study of Atherosclerosis (SISA), European Atherosclerosis Society (EAS).

Presenter of 1 Presentation

 Conference Calendar

LDL-CHOLESTEROL LEVELS AND LDL POLYGENIC SCORE IN A COHORT OF PATIENTS WITH CLINICALLY DIAGNOSED FAMILIAL HYPERCHOLESTEROLEMIA. DATA FROM THE LIPIGEN STUDY

Session Name
0410 - Apo B containing lipoproteins (ID 8)
Session Type
Workshop - Lipids, lipoproteins
Date
Tue, 24.05.2022
Session Time
11:00 - 12:30
Room
Anitschkow - Silver Plenary hall
Presenter
Lecture Time
11:50 - 12:00

Abstract

Background and Aims

Polygenic hypercholesterolemia has been suggested to explain the significant proportion of patients with a diagnosis of familial hypercholesterolemia (FH) based on clinical and biochemical criteria, but without any disease-causing mutation.

Methods

We evaluated the distribution of a polygenic risk score proposed by Talmud et al. (Lancet, 2013), consisting of 12 LDL cholesterol (LDL-C) raising variants (LDLc-score), in a large Italian population of adult patients diagnosed with clinical FH

Results

Within the LIPIGEN study, 875 mutation-positive (FH/M+) patients (females 54.75%, mean age 42.47±15.00 years) and 644 mutation-negative (FH/M-) patients (females 54.21%, mean age 49.73±13.54 years) were evaluated. FH/M- patients had lower mean levels of pre-treatment LDL-C than FH/M+ group (217.14±55.49 vs 270.52±68.59 mg/dL, p<0.0001). The mean value (±SD) of the LDLc-score was 1.00 (±0.18) in FH/M- patients and 0.94 (±0.20) in FH/M+ group (p-value <0.0001). Higher mean LDLc-score levels were observed among FH/M- having pre-treatment LDL-C levels in the range 150-350 mg/dL (150-249 mg/dL: 1.01 vs 0.91, p-value <.0001; 250-349 mg/dL: 1.02 vs 0.95, p-value=0.0001). A positive correlation between LDLc-score and pre-treatment LDL-C levels was observed among FH patients independently of the presence of causative mutations.

Conclusions

From these data, we suggest that variants in multiple LDL-cholesterol-raising genes can play a role in determining LDL-C levels even in patients with monogenic familial hypercholesterolemia. More data is needed to investigate the association between the polygenic score and the risk of atherosclerotic disease to support its use in clinical practice.

Hide