Browsing by Author "Antunes, Marília"
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- Characterisation of the Lipid Profile of the Portuguese PopulationPublication . Mariano, Cibelle; Antunes, Marília; Bourbon, MafaldaCardiovascular disease (CVD), particularly coronary heart disease (CHD) and stroke, are the leading cause of morbidity and mortality worldwide. The common forms of CVD have a complex aetiology in which interactions between multiple genetic and environmental factors play an important roles. The incidence rates of these diseases are increasing in developing countries as a result of the modification of lifestyles and increased prevalence of cardiovascular risk factors. Many independent cardiovascular risk factors could be modifiable, in contrast to the genetic risk factors. However, the associated risk of the genetic factors can be prevented if early identified, making genetic studies a priority in cardiovascular genetics research.
- Classification Methods Applied to Familial Hypercholesterolemia Diagnosis at Pediatric Age: Comparison of Simon Broome Criteria with Modified Decision Tree ModelsPublication . Albuquerque, João; Medeiros, Ana Margarida; Alves, Ana Catarina; Antunes, Marília; Bourbon, MafaldaIntroduction: Familial Hypercholesterolemia (FH) is an inherited disorder of lipid metabolism, resulting in severe dyslipidemia and increased CVD risk. Simon Broome (SB) criteria for the diagnostic of FH are among the most frequently used in clinical setting, and are based on elevated total cholesterol (TC) and low density lipoprotein (LDLc) cholesterol levels, presence of tendinous xanthomas and family history [1]. The molecular diagnosis that confirms this diagnosis reveals, however, a high false positive rate when following these criteria, which can represent a heavy burden in terms of healthcare costs. The main purpose of this work was to develop alternative classification models for FH diagnosis, based on different decision tree (DT) algorithms, using commonly available biochemical markers as predictors.
- Classification methods applied to the diagnosis of pediatric patients with familial hypercholesterolemia: comparison of Simon Broome criteria with logistic regression and modified decision tree modelsPublication . Albuquerque, João; Antunes, Marília; Alves, Ana Catarina; Medeiros, Ana Margarida; Bourbon, MafaldaFamilial Hypercholesterolemia (FH) is a monogenic disorder of lipid metabolism, resulting in severe dyslipidemia and increased cardiovascular disease risk. Simon Broome (SB) criteria for the diagnostic of FH are among the most frequently used in clinical setting, and are based on elevated total cholesterol (TC) and low density lipoprotein (LDLc) cholesterol levels, presence of tendinous xanthomas and family history, although only genetic testing can confirm the diagnosis. According to the Portuguese Study of Familial Hypercholesterolemia (EPHF), only around 42% of the patients with clinical criteria reveal a positive diagnostic for FH, a high false positive rate that represents a heavy burden in terms of healthcare costs. The main purpose of this work was to develop alternative classification models for FH diagnosis based on two different methods, logistic regression (LR) and decision trees (DT), using several biochemical indicators as predictor variables. Both models were compared with SB clinical criteria in terms of accuracy and efficiency, through bootstrap resampling techniques.
- Comparative study between a Logistic Regression Model and Simon Broome Criteria for the Diagnosis of Pediatric Patients with Familial HypercholesterolemiaPublication . Albuquerque, João; Alves, Ana Catarina; Medeiros, Ana Margarida; Bourbon, Mafalda; Antunes, MaríliaIntroduction: Familial Hypercholesterolemia (FH) is an inherited disorder of lipid metabolism, resulting in severe dyslipidemia and increased cardiovascular disease risk. Simon Broome (SB) criteria for the diagnostic of FH are among the most frequently used in clinical setting, and are based on elevated total cholesterol (TC) and low density lipoprotein cholesterol (LDLc) levels, presence of tendinous xanthomas and family history, although only genetic testing can confirm the diagnosis [1]. According to the Portuguese FH Study, only around 42% of the patients with clinical criteria reveal a positive diagnostic for FH [2], a high false positive rate that represents a heavy burden in terms of healthcare costs. The main purpose of this work was to develop an alternative classification method for FH diagnosis based on a logistic regression (LR) model, using several biochemical indicators as predictor variables. For this purpose, different operating characteristics (OC) were compared between both models, through bootstrap resampling techniques.
- Comparative study on the performance of different classification algorithms, combined with pre- and post-processing techniques to handle imbalanced data, in the diagnosis of adult patients with familial hypercholesterolemiaPublication . Albuquerque, João; Medeiros, Ana Margarida; Alves, Ana Catarina; Bourbon, Mafalda; Antunes, MaríliaFamilial Hypercholesterolemia (FH) is an inherited disorder of cholesterol metabolism. Current criteria for FH diagnosis, like Simon Broome (SB) criteria, lead to high false positive rates. The aim of this work was to explore alternative classification procedures for FH diagnosis, based on different biological and biochemical indicators. For this purpose, logistic regression (LR), naive Bayes classifier (NB), random forest (RF) and extreme gradient boosting (XGB) algorithms were combined with Synthetic Minority Oversampling Technique (SMOTE), or threshold adjustment by maximizing Youden index (YI), and compared. Data was tested through a 10 x 10 repeated k-fold cross validation design. The LR model presented an overall better performance, as assessed by the areas under the receiver operating characteristics (AUROC) and precision-recall (AUPRC) curves, and several operating characteristics (OC), regardless of the strategy to cope with class imbalance. When adopting either data processing technique, significantly higher accuracy (Acc), G-mean and F-1 score values were found for all classification algorithms, compared to SB criteria (p < 0.01), revealing a more balanced predictive ability for both classes, and higher effectiveness in classifying FH patients. Adjustment of the cut-off values through pre or post-processing methods revealed a considerable gain in sensitivity (Sens) values (p < 0.01). Although the performance of pre and post-processing strategies was similar, SMOTE does not cause model's parameters to loose interpretability. These results suggest a LR model combined with SMOTE can be an optimal approach to be used as a widespread screening tool.
- Development and Validation of Screening Methods Applied to Familial Hypercholesterolemia DiagnosisPublication . Albuquerque, João; Antunes, Marília; Antunes, Marília; Bourbon, Mafalda; Soares, RaquelFamilial hypercholesterolemia (FH) is an inherited disorder of lipid metabolism, characterized by increased low density lipoprotein cholesterol (LDLc) levels. If untreated, the severe dyslipidemia from birth leads to the early development of atherosclerosis, representing a major risk factor for cardiovascular disease (CVD). The early diagnosis of FH is associated with a signi cant reduction in CVD risk, supporting the introduction of risk mitigation strategies, such as cascade screening of rst degree relatives, and adequate lipid lowering therapy (LLT) as precociously as possible. The importance of genetic testing is emphasized by evidence that individuals with a con rmed pathogenic variant possess a signi cant increase in the risk of CVD when compared to subjects with FH-like phenotype for whom a causative variant is not detected. Nevertheless, molecular testing is still not available as a rst line diagnosis tool, and previous selection and strati cation of subjects to undergo this procedure should be made. Currently used clinical criteria, typically based on LDLc levels, family history of hypercholesterolemia and/ or premature CVD and presence of physical signs like tendon xanthomas, present the limitation of retaining a high number of false positive cases. This may constitute a heavy burden in terms of healthcare costs, and limits the access to the genetic study of a larger universe of true FH cases. The main purpose of this work was to develop alternative classi cation methods for FH diagnosis, based on di erent biochemical and clinical indicators, with improved ability to screen for FH cases in comparison to traditional clinical criteria. The metrics used for comparison range from the areas under the receiver operating characteristics (AUROC) and precision-recall (AUPRC) curves, to several operating characteristics (OC), to agreement tests, among others
- Distribution of Chlamydia trachomatis ompA-genotypes over three decades in PortugalPublication . Lodhia, Zohra; Cordeiro, Dora; Correia, Cristina; João, Inês; Carreira, Teresa; Vieira, Luís; Nunes, Alexandra; Ferreira, Rita; Schäfer, Sandra; Aliyeva, Elzara; Portugal, Clara; Monge, Isabel; Pessanha, Maria Ana; Toscano, Cristina; Côrte-Real, Rita; Antunes, Marília; Gomes, Joao Paulo; Borges, Vítor; José Borrego, MariaObjectives: Chlamydia trachomatis is classified into 15 major genotypes, A to L3, based on the diversity of ompA gene. Here, we evaluated and characterised the distribution and diversity of ompA-genotypes over 32 years (1990-2021) in Portugal. Methods: The collection of the Portuguese National Reference Laboratory for Sexually Transmitted Infections includes 5824 C. trachomatis-positive samples that were successfully ompA-genotyped between 1990 and 2021. An in-depth analysis of ompA-genotypes distribution across the years, as well as by biological sex, age and anatomical site of infection was performed. Results: ompA-genotype E was consistently the most frequently detected across the years, with a median frequency of 34.6%, followed by D/Da (17.6%), F (14.3%) and G (10.7%). The prevalence of lymphogranuloma venereum (LGV) genotypes (mostly L2, 62.0%, followed by L2b, 32.1%) increased since 2016, reaching the highest value in 2019 (20.9%). LGV, G and Da genotypes were associated with biological sex, specifically with being male, and were the most frequent among anorectal specimens (37.7%, 19.4% and 17.7%, respectively). Notably, LGV ompA-genotypes represented 38.9% of the male anorectal specimens since 2016, and were also detected among oropharynx and urogenital samples. ompA-genotype E was the most frequently detected at the oropharynx (28.6%) and urogenital (33.9%) sites during the study period, followed by D/Da (17.4%) and F (16.0%) in the urogenital specimens, and by G (26.1%) and D/Da (25.7%) in oropharynx specimens. Our data also highlight the emergence of the recombinant L2b/D-Da strain since 2017 (representing between 2.0% and 15.5% of LGV cases per year) and the non-negligible detection of ompA-genotype B in urogenital and anorectal specimens. Conclusions: This study provides a comprehensive landscape of C. trachomatis molecular surveillance in Portugal, highlighting the continued relevance of ompA-genotyping as a complement to rapid LGV-specific detection tests. It also contributes to a deeper understanding of C. trachomatis epidemiology, diversity and pathogenicity.
- Distribution of Chlamydia trachomatis ompA-genotypes over three decades in PortugalPublication . Lodhia, Zohra; Cordeiro, Dora; Correia, Cristina; João, Inês; Carreira, Teresa; Vieira, Luís; Nunes, Alexandra; Ferreira, Rita; Schäfer, Sandra; Aliyeva, Elzara; Portugal, Clara; Monge, Isabel; Pessanha, Maria Ana; Toscano, Cristina; Côrte-Real, Rita; Antunes, Marília; Gomes, Joao Paulo; Borges, Vítor; Borrego, Maria JoséObjectives: Chlamydia trachomatis is classified into 15 major genotypes, A to L3, based on the diversity of ompA gene. Here, we evaluated and characterised the distribution and diversity of ompA-genotypes over 32 years (1990–2021) in Portugal. Methods: The collection of the Portuguese National Reference Laboratory for Sexually Transmitted Infections includes 5824 C. trachomatis-positive samples that were successfully ompA-genotyped between 1990 and 2021. An in-depth analysis of ompA-genotypes distribution across the years, as well as by biological sex, age and anatomical site of infection was performed. Results: ompA-genotype E was consistently the most frequently detected across the years, with a median frequency of 34.6%, followed by D/Da (17.6%), F (14.3%) and G (10.7%). The prevalence of lymphogranuloma venereum (LGV) genotypes (mostly L2, 62.0%, followed by L2b, 32.1%) increased since 2016, reaching the highest value in 2019 (20.9%). LGV, G and Da genotypes were associated with biological sex, specifically with being male, and were the most frequent among anorectal specimens (37.7%, 19.4% and 17.7%, respectively). Notably, LGV ompA-genotypes represented 38.9% of the male anorectal specimens since 2016, and were also detected among oropharynx and urogenital samples. ompA-genotype E was the most frequently detected at the oropharynx (28.6%) and urogenital (33.9%) sites during the study period, followed by D/Da (17.4%) and F (16.0%) in the urogenital specimens, and by G (26.1%) and D/Da (25.7%) in oropharynx specimens. Our data also highlight the emergence of the recombinant L2b/D-Da strain since 2017 (representing between 2.0% and 15.5% of LGV cases per year) and the non-negligible detection of ompA-genotype B in urogenital and anorectal specimens. Conclusions: This study provides a comprehensive landscape of C. trachomatis molecular surveillance in Portugal, highlighting the continued relevance of ompA-genotyping as a complement to rapid LGV-specific detection tests. It also contributes to a deeper understanding of C. trachomatis epidemiology, diversity and pathogenicity.
- e_LIPID–Characterization of hypercholesterolemia and association with cardiovascular disease in the Portuguese populationPublication . Chora, Joana Rita; Alves, Ana Catarina; Mariano, Cibelle; Antunes, Marília; Rato, Quitéria; Bourbon, MafaldaThe e_LIPID study aimed to characterise the lipid profile of the Portuguese population and study its association with cardiovascular disease (CV D) events. Demographic, clinical, and biochemical data derived from the e_COR Study, a cross-sectional epidemiological study with 1688 adults (18-79 years old) from five Portuguese continental regions. Population specific percentiles for lipid and lipoprotein biomarkers were esmated stratified by sex and age. All calculations were weighted by sex, age, and geographic region to be representative of the mainland Portuguese population. Odds ratio was calculated to study association of biochemical profile with CV D. Associations of total cholesterol (TC), LDL, ApoB and non-HDL were performed only on individuals under no lipid-lowering therapy. Individuals with LDL above the 9th5 percentile and fulfilling Simon-Broome criteria of Familial Hypercholesterolemia (FH) were sequenced for LDLR, APOB and PCSK9. National prevalence of individuals with TC≥190mg/dl were 52.4%, with LDL≥116mg/dl were 53.9%, with ApoB≥90mg/dl were 53.8%, with non- HDL≥146mg/dl were 38.9%, and with Lp(a)≥125nmol/L were 21.1%. The 90th percentile for lipid and lipoprotein biomarkers for the Portuguese population are TC of 244mg/dl, LDL of 169mg/dl, ApoB of 128mg/dl, non-HDL of 193mg/dl, and Lp(a) of 223nmol/L. The 10th percentile for HDL is 38mg/dl. Individuals with LDL≥116mg/dl presented 2.50 [1.13-6.07] higher odds of having had CV D events (p=0.018), with non-HDL≥146mg/dl had 2.06 [1.01-4.31] higher odds (p=0.041), and with high Lp(a)≥125nmol/L had 1.77 [1.13-2.72] higher odds (p=0.008) than their respective counterparts. From the 33 individuals sequenced 3 individuals were found to have heterozygous FH. Population age and sex specific values are important for dyslipidaemia assessment. Having LDL≥116mg/dl, non-HDL≥146mg/dl or Lp(a) ≥125nmol/L can double the odds of CV D. Our results highlight that hypercholesterolemia is a neglected cardiovascular risk factor with more than 50% of the population with TC≥190mg/dl, LDL≥116mg/dl, or ApoB≥90mg/dl. Since hypercholesterolemia is a modifiable risk factor in the majority of cases, strategies to increase adherence to changes in lifestyle habits need to be urgently discussed.
- e_LIPID: caraterização do perfil lipídico da população portuguesaPublication . Mariano, Cibelle; Antunes, Marília; Rato, Quitéria; Bourbon, MafaldaObjetivo: O estudo e_COR foi desenvolvido com o objetivo de determinar a prevalência dos principais fatores de risco cardiovascular na população portuguesa, com especial enfoque na dislipidemia e na caraterização genética do risco cardiovascular. Participaram 1688 indivíduos (848 homens e 840 mulheres, com idade entre os 18 e 79 anos) distribuídos pelas regiões Norte, Centro, Lisboa, Alentejo e Algarve. Aqui apresentam-se os resultados do estudo paralelo e_LIPID, que pretendeu determinar o perfil lipídico da população portuguesa
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