Percorrer por autor "Cuchel, Marina"
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- Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert PanelPublication . Sturm, Amy C.; Knowles, Joshua W.; Gidding, Samuel S.; Ahmad, Zahid S.; Ahmed, Catherine D.; Ballantyne, Christie M.; Baum, Seth J.; Bourbon, Mafalda; Carrié, Alain; Cuchel, Marina; de Ferranti, Sarah D.; Defesche, Joep C.; Freiberger, Tomas; Hershberger, Ray E.; Hovingh, G. Kees; Karayan, Lala; Kastelein, Johannes Jacob Pieter; Kindt, Iris; Lane, Stacey R.; Leigh, Sarah E.; Linton, MacRae F.; Mata, Pedro; Neal, William A.; Nordestgaard, Børge G.; Santos, Raul D.; Harada-Shiba, Mariko; Sijbrands, Eric J.; Stitziel, Nathan O.; Yamashita, Shizuya; Wilemon, Katherine A.; Ledbetter, David H.; Rader, Daniel J.; convened by the Familial Hypercholesterolemia FoundationAlthough awareness of familial hypercholesterolemia (FH) is increasing, this common, potentially fatal, treatable condition remains underdiagnosed. Despite FH being a genetic disorder, genetic testing is rarely used. The Familial Hypercholesterolemia Foundation convened an international expert panel to assess the utility of FH genetic testing. The rationale includes the following: 1) facilitation of definitive diagnosis; 2) pathogenic variants indicate higher cardiovascular risk, which indicates the potential need for more aggressive lipid lowering; 3) increase in initiation of and adherence to therapy; and 4) cascade testing of at-risk relatives. The Expert Consensus Panel recommends that FH genetic testing become the standard of care for patients with definite or probable FH, as well as for their at-risk relatives. Testing should include the genes encoding the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9); other genes may also need to be considered for analysis based on patient phenotype. Expected outcomes include greater diagnoses, more effective cascade testing, initiation of therapies at earlier ages, and more accurate risk stratification.
- Contemporary Homozygous Familial Hypercholesterolemia in the United States: Insights From the CASCADE FH RegistryPublication . Cuchel, Marina; Lee, Paul C.; Hudgins, Lisa C.; Duell, P. Barton; Ahmad, Zahid; Baum, Seth J.; Linton, MacRae F.; de Ferranti, Sarah D.; Ballantyne, Christie M.; Larry, John A.; Hemphill, Linda C.; Kindt, Iris; Gidding, Samuel S.; Martin, Seth S.; Moriarty, Patrick M.; Thompson, Paul P.; Underberg, James A.; Guyton, John R.; Andersen, Rolf L.; Whellan, David J.; Benuck, Irwin; Kane, John P.; Myers, Kelly; Howard, William; Staszak, David; Jamison, Allison; Card, Mary C.; Bourbon, Mafalda; Chora, Joana R.; Rader, Daniel J.; Knowles, Joshua W.; Wilemon, Katherine; McGowan, Mary P.Background: Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment-resistant disorder characterized by earlyonset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking, and the extent of underdiagnosis and undertreatment is uncertain. Methods and Results: Data were analyzed from 67 children and adults with clinically diagnosed HoFH from the CASCADE (Cascade Screening for Awareness and Detection) FH Registry. Genetic diagnosis was confirmed in 43 patients. We used the clinical characteristics of genetically confirmed patients with HoFH to query the Family Heart Database, a US anonymized payer health database, to estimate the number of patients with similar lipid profiles in a “real-world” setting. Untreated lowdensity lipoprotein cholesterol levels were lower in adults than children (533 versus 776mg/dL; P=0.001). At enrollment, atherosclerotic cardiovascular disease and supravalvular and aortic valve stenosis were present in 78.4% and 43.8% and 25.5% and 18.8% of adults and children, respectively. At most recent follow-up, despite multiple lipid-lowering treatment, low-density lipoprotein cholesterol goals were achieved in only a minority of adults and children. Query of the Family Heart Database identified 277 individuals with profiles similar to patients with genetically confirmed HoFH. Advanced lipid-lowering treatments were prescribed for 18%; 40% were on no lipid-lowering treatment; atherosclerotic cardiovascular disease was reported in 20%; familial hypercholesterolemia diagnosis was uncommon. Conclusions: Only patients with the most severe HoFH phenotypes are diagnosed early. HoFH remains challenging to treat. Results from the Family Heart Database indicate HoFH is systemically underdiagnosed and undertreated. Earlier screening, aggressive lipid-lowering treatments, and guideline implementation are required to reduce disease burden in HoFH.
- Sex Differences in Diagnosis, Treatment, and Cardiovascular Outcomes in Homozygous Familial HypercholesterolemiaPublication . Mulder, Janneke W.C.M.; Tromp, Tycho R.; Al-Khnifsawi, Mutaz; Blom, Dirk J.; Chlebus, Krysztof; Cuchel, Marina; D'Erasmo, Laura; Gallo, Antonio; Hovingh, G. Kees; Kim, Ngoc Thanh; Long, Jiang; Raal, Frederick J.; Schonck, Willemijn A.M.; Soran, Handrean; Truong, Thanh-Huong; Boersma, Eric; Roeters van Lennep, Jeanine E.; Homozygous Familial Hypercholesterolemia International Clinical CollaboratorsHomozygous familial hypercholesterolemia (HoFH) is a rare genetic condition characterized by extremely increased low-density lipoprotein (LDL) cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Heterozygous familial hypercholesterolemia (HeFH) is more common than HoFH, and women with HeFH are diagnosed later and undertreated compared to men; it is unknown whether these sex differences also apply to HoFH. Objective: To investigate sex differences in age at diagnosis, risk factors, lipid-lowering treatment, and ASCVD morbidity and mortality in patients with HoFH. Design, setting, and participants: Sex-specific analyses for this retrospective cohort study were performed using data from the HoFH International Clinical Collaborators (HICC) registry, the largest global dataset of patients with HoFH, spanning 88 institutions across 38 countries. Patients with HoFH who were alive during or after 2010 were eligible for inclusion. Data entry occurred between February 2016 and December 2020. Data were analyzed from June 2022 to June 2023. Main outcomes and measures: Comparison between women and men with HoFH regarding age at diagnosis, presence of risk factors, lipid-lowering treatment, prevalence, and onset and incidence of ASCVD morbidity (myocardial infarction [MI], aortic stenosis, and combined ASCVD outcomes) and mortality. Results: Data from 389 women and 362 men with HoFH from 38 countries were included. Women and men had similar age at diagnosis (median [IQR], 13 [6-26] years vs 11 [5-27] years, respectively), untreated LDL cholesterol levels (mean [SD], 579 [203] vs 596 [186] mg/dL, respectively), and cardiovascular risk factor prevalence, except smoking (38 of 266 women [14.3%] vs 59 of 217 men [27.2%], respectively). Prevalence of MI was lower in women (31 of 389 [8.0%]) than men (59 of 362 [16.3%]), but age at first MI was similar (mean [SD], 39 [13] years in women vs 38 [13] years in men). Treated LDL cholesterol levels and lipid-lowering therapy were similar in both sexes, in particular statins (248 of 276 women [89.9%] vs 235 of 258 men [91.1%]) and lipoprotein apheresis (115 of 317 women [36.3%] vs 118 of 304 men [38.8%]). Sixteen years after HoFH diagnosis, women had statistically significant lower cumulative incidence of MI (5.0% in women vs 13.7% in men; subdistribution hazard ratio [SHR], 0.37; 95% CI, 0.21-0.66) and nonsignificantly lower all-cause mortality (3.0% in women vs 4.1% in men; HR, 0.76; 95% CI, 0.40-1.45) and cardiovascular mortality (2.6% in women vs 4.1% in men; SHR, 0.87; 95% CI, 0.44-1.75). Conclusions and relevance: In this cohort study of individuals with known HoFH, MI was higher in men compared with women yet age at diagnosis and at first ASCVD event were similar. These findings suggest that early diagnosis and treatment are important in attenuating the excessive cardiovascular risk in both sexes.
- Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort studyPublication . Tromp, Tycho R.; Hartgers, Merel L.; Hovingh, G Kees; Vallejo-Vaz, Antonio J.; Ray, Kausik K.; Soran, Handrean; Freiberger, Tomas; Bertolini, Stefano; Harada-Shiba, Mariko; Blom, Dirk J.; Raal, Frederick J.; Cuchel, Marina; Tromp, Tycho R.; Hartgers, Merel L.; Hovingh, G. Kees; Vallejo-Vaz, Antonio J.; Ray, Kausik K.; Soran, Handrean; Freiberger, Tomas; Bertolini, Stefano A.; Harada-Shiba, Mariko; Pang, Jing; Watts, Gerald F.; Greber-Platzer, Susanne; Mäser, Martin; Stulnig, Thomas M.; Ebenbichler, Christoph F.; Bin Thani, Khalid; Cassiman, David; Descamps, Olivier S.; Rymen, Daisy; Witters, Peter; Santos, Raul D.; Brunham, Liam R.; Francis, Gordon A.; Genest, Jacques; Hegele, Robert A.; Kennedy, Brooke A.; Ruel, Isabelle; Sherman, Mark H.; Jiang, Long; Wang, Luya; Reiner, Željko; Blaha, Vladimir; Ceska, Richard; Dvorakova, Jana; Dlouhy, Lubomir; Horak, Pavel; Soska, Vladimir; Tichy, Lukas; Urbanek, Robin; Vaverkova, Helena; Vrablik, Michal; Zemek, Stanislav; Zlatohlavek, Lukas; Emil, Sameh; Naguib, Tarek; Reda, Ashraf; Béliard, Sophie; Bruckert, Eric; Gallo, Antonio; Elisaf, Moses S.; Kolovou, Genovefa; Cohen, Hofit; Durst, Ronen; Dann, Eldad J.; Elis, Avishay; Hussein, Osama; Leitersdorf, Eran; Schurr, Daniel; Setia, Nitika; Verma, Ishwar C.; Alareedh, Mohammed D.; Al-Khnifsawi, Mutaz; Abdalsahib Al-Zamili, Ali F.; Rhadi, Sabah H.; Shaghee, Foaad K.; Arca, Marcello; Averna, Maurizio; Bartuli, Andrea; Bucci, Marco; Buonuomo, Paola S.; Calabrò, Paolo; Calandra, Sebastiano; Casula, Manuela; Catapano, Alberico L.; Cefalù, Angelo B.; Cicero, Arrigo F.G.; D'Addato, Sergio; D'Erasmo, Laura; Di Costanzo, Alessia; Fasano, Tommaso; Gazzotti, Marta; Giammanco, Antonina; Iannuzzo, Gabriella; Ibba, Anastasia; Negri, Emanuele A.; Pasta, Andrea; Pavanello, Chiara; Pisciotta, Livia; Rabacchi, Claudio; Ripoli, Carlo; Sampietro, Tiziana; Sbrana, Francesco; Sileo, Fulvio; Suppressa, Patrizia; Tarugi, Patrizia; Trenti, Chiara; Zenti, Maria G.; Hori, Mika; Ayesh, Mahmoud H.; Azar, Sami T.; Bitar, Fadi F.; Fahed, Akl C.; Moubarak, Elie M.; Nemer, Georges; Nawawi, Hapizah M.; Madriz, Ramón; Mehta, Roopa; Cupido, Arjen J.; Defesche, Joep C.; Reijman, M. Doortje; Roeters-van Lennep, Jeanine E.; Stroes, Erik S.G.; Wiegman, Albert; Zuurbier, Linda; Al-Waili, Khalid; Sadiq, Fouzia; Chlebus, Krzysztof; Bourbon, Mafalda; Gaspar, Isabel M.; Lalic, Katarina S.; Ezhov, Marat V.; Susekov, Andrey V.; Groselj, Urh; Charng, Min-Ji; Khovidhunkit, Weerapan; Aktan, Melih; Altunkeser, Bulent B.; Demircioglu, Sinan; Kose, Melis; Gokce, Cumali; Ilhan, Osman; Kayikcioglu, Meral; Kaynar, Leyla G.; Kuku, Irfan; Kurtoglu, Erdal; Okutan, Harika; Ozcebe, Osman I.; Pekkolay, Zafer; Sag, Saim; Salcioglu, Osman Z.; Temizhan, Ahmet; Yenercag, Mustafa; Yilmaz, Mehmet; Yilmaz Yasar, Hamiyet; Mitchenko, Olena; Lyons, Alexander R.M.; Stevens, Christophe A.T.; Brothers, Julie A.; Hudgins, Lisa C.; Nguyen, Christina; Alieva, Rano; Shek, Aleksandr; Do, Doan-Loi; Kim, Ngoc-Thanh; Le, Hong-An; Le, Thanh-Tung; Nguyen, Mai-Ngoc T.; Truong, Thanh-Huong; Blom, Dirk J.; Raal, Frederick J.; Cuchel, MarinaBackground: Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder resulting in extremely elevated low-density lipoprotein cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Current guidance about its management and prognosis stems from small studies, mostly from high-income countries. The objective of this study was to assess the clinical and genetic characteristics, as well as the impact, of current practice on health outcomes of HoFH patients globally. Methods: The HoFH International Clinical Collaborators registry collected data on patients with a clinical, or genetic, or both, diagnosis of HoFH using a retrospective cohort study design. This trial is registered with ClinicalTrials.gov, NCT04815005. Findings: Overall, 751 patients from 38 countries were included, with 565 (75%) reporting biallelic pathogenic variants. The median age of diagnosis was 12·0 years (IQR 5·5-27·0) years. Of the 751 patients, 389 (52%) were female and 362 (48%) were male. Race was reported for 527 patients; 338 (64%) patients were White, 121 (23%) were Asian, and 68 (13%) were Black or mixed race. The major manifestations of ASCVD or aortic stenosis were already present in 65 (9%) of patients at diagnosis of HoFH. Globally, pretreatment LDL cholesterol levels were 14·7 mmol/L (IQR 11·6-18·4). Among patients with detailed therapeutic information, 491 (92%) of 534 received statins, 342 (64%) of 534 received ezetimibe, and 243 (39%) of 621 received lipoprotein apheresis. On-treatment LDL cholesterol levels were lower in high-income countries (3·93 mmol/L, IQR 2·6-5·8) versus non-high-income countries (9·3 mmol/L, 6·7-12·7), with greater use of three or more lipid-lowering therapies (LLT; high-income 66% vs non-high-income 24%) and consequently more patients attaining guideline-recommended LDL cholesterol goals (high-income 21% vs non-high-income 3%). A first major adverse cardiovascular event occurred a decade earlier in non-high-income countries, at a median age of 24·5 years (IQR 17·0-34·5) versus 37·0 years (29·0-49·0) in high-income countries (adjusted hazard ratio 1·64, 95% CI 1·13-2·38). Interpretation: Worldwide, patients with HoFH are diagnosed too late, undertreated, and at high premature ASCVD risk. Greater use of multi-LLT regimens is associated with lower LDL cholesterol levels and better outcomes. Significant global disparities exist in treatment regimens, control of LDL cholesterol levels, and cardiovascular event-free survival, which demands a critical re-evaluation of global health policy to reduce inequalities and improve outcomes for all patients with HoFH.