Journal of clinical lipidology最新文献

{"title":"Multidisciplinary teams in clinical lipidology and cardiometabolic care: A National Lipid Association Expert Clinical Review.","authors":"Mary Katherine Cheeley, Carol F Kirkpatrick, Emily E Brown, Dave L Dixon, Heather Gunter, Diane S Osborn, Michael J Wilkinson","doi":"10.1016/j.jacl.2025.05.002","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.05.002","url":null,"abstract":"<p><p>This National Lipid Association Expert Clinical Review (ECR) describes the roles of multidisciplinary care team members in optimizing the management of lipid disorders and promoting cardiometabolic health, including the contributions of physicians, advanced practice providers, pharmacists, registered dietitian nutritionists, nurses, and genetic counselors. Patients benefit from a collaborative approach to the management of dyslipidemias and cardiometabolic risk through improved diagnosis and treatment, access to comprehensive and evidence-based lifestyle interventions, optimization of pharmacotherapy, and patient education and empowerment. Certain multidisciplinary team members may not be readily accessible in all practice settings. Therefore, this ECR provides suggestions for accessing community resources to expand the reach of multidisciplinary care to a greater number of patients.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to Lipoprotein particle profile in the presence of peripheral artery disease among patients with coronary heart disease: Data from the CORDIOPREV study, Journal of Clinical Lipidology 19 (2025) 256-266.","authors":"Silvia de la Cruz-Ares, María Del Pilar Coronado-Carvajal, Oriol Alberto Rangel-Zúñiga, José David Torres-Peña, Antonio Pablo Arenas-de Larriva, Alejandro López-Moreno, Niki Katsiki, José María Ordovás, Javier Delgado-Lista, Pablo Pérez-Martínez, Francisco Miguel Gutiérrez-Mariscal, José López-Miranda","doi":"10.1016/j.jacl.2025.05.001","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.05.001","url":null,"abstract":"","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triglyceride-glucose index and 28-day all-cause mortality in critically ill obese patients: A MIMIC-IV database analysis.","authors":"Wen-Qiang Wang, Mei-Zhu Chen, Yan-Hui Yang","doi":"10.1016/j.jacl.2025.05.005","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.05.005","url":null,"abstract":"<p><strong>Background: </strong>The triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, has been linked to various metabolic disorders. This study aimed to investigate the association between the TyG index and 28-day all-cause mortality in obese critically ill patients.</p><p><strong>Methods: </strong>This study utilized the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and included adult patients with body mass index ≥30 kg/m² admitted to the intensive care unit (ICU) for the first time. The TyG index was calculated as ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The relationship between the TyG index and 28-day all-cause mortality was evaluated using Cox proportional hazards models, and restricted cubic splines (RCS) were employed to explore the dose-response relationship. Subgroup analyses were used to confirm the robustness of the results.</p><p><strong>Results: </strong>During a mean ICU stay of 7.22 days, 291 patients (22.79%) experienced 28-day all-cause mortality. Kaplan-Meier analysis revealed a significantly increased mortality risk with higher TyG index quartiles (log-rank P < .001). Multivariable Cox regression showed that each 1-unit increase in the TyG index was associated with a 41% higher mortality risk (hazard ratio [HR] = 1.41, 95% CI: 1.21-1.63). Patients in quartile 4 had a 98% higher risk compared to quartile 1 (HR = 1.98, 95% CI: 1.30-3.02). RCS analysis showed that higher levels of TyG index (>9.25) were associated with an increased risk of 28-day all-cause mortality. Subgroup analyses confirmed consistent associations across age, sex, and comorbidity subgroups.</p><p><strong>Conclusion: </strong>The TyG index is significantly associated with 28-day all-cause mortality in obese critically ill patients. A higher TyG index serves as an independent predictor of short-term mortality risk in this population.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lomitapide-induced fatty liver is a reversible condition: Evidence from a case of familial chylomicronemia syndrome.","authors":"Daniele Tramontano, Michele di Martino, Francesco Baratta, Alessia Di Costanzo, Nicholas Cocomello, Daniela Commodari, Simone Bini, Ilenia Minicocci, Marcello Arca, Laura D'Erasmo","doi":"10.1016/j.jacl.2025.05.004","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.05.004","url":null,"abstract":"<p><p>Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder characterized by severe hypertriglyceridemia. It is caused by loss-of-function variants in the genes encoding the lipoprotein lipase (LPL) enzyme and its cofactors, which severely impair the hydrolysis of triglycerides (TG). Its main complication is represented by acute pancreatitis (AP), a potentially life-threatening condition. Conventional TG-lowering therapies are poorly effective in FCS, thus requiring the search of novel treatments. Lomitapide, an inhibitor of microsomal triglyceride transfer protein (MTP), has demonstrated efficacy in reducing TG levels in FCS. However, it is associated with hepatic side effects, namely liver fat accumulation. Here we present a case study of a 71-year-old female patient with genetically confirmed FCS, baseline TG level of 2300 mg/dL (25.97 mmol/L) and a history of AP, who was treated with lomitapide for almost 5 years. The treatment allowed a marked reduction of TG (about 90%) and no recurrence of AP. However, hepatic monitoring during treatment revealed a progressive worsening of liver fat accumulation as detected by magnetic resonance imaging (MRI), which was associated with pronounced increases in liver transaminases and liver stiffness (up to 15 kPa). Due to these hepatic adverse events, it was decided to discontinue therapy with lomitapide. An MRI scan repeated after 70 days of drug withdrawal revealed complete resolution of fatty liver disease associated with normalization of liver stiffness (4.1 kPa) and liver transaminases. This case demonstrates the reversibility of lomitapide-induced fatty liver and underscores the importance of regular monitoring of the liver safety during lomitapide to guide timely interventions.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real life evidence of volanesorsen for familial chylomicronemia syndrome in Colombia.","authors":"Alejandro Román-González, Alejandro Castellanos, Diego Perdomo, Christian Colón, Juan Jose Vargas, Carlos O Mendivil, Johnayro Gutierrez","doi":"10.1016/j.jacl.2025.04.203","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.04.203","url":null,"abstract":"<p><strong>Background: </strong>Familial chylomicronemia syndrome (FCS) is an ultra-rare disorder associated with pathogenic variants in genes implicated in chylomicron metabolism such as LPL, APOA5, APOC2, GPIHBP1, and LMF1. Patients with FCS have severe hypertriglyceridemia complicated with recurrent episodes of pancreatitis. Volanesorsen is a treatment option for such patients. However, this treatment is not approved or available in all countries.</p><p><strong>Objective: </strong>To present the real-life evidence of clinical response to volanesorsen in patients with FCS in Colombia.</p><p><strong>Methods: </strong>All patients treated with volanesorsen in Colombia as of June 25, 2024, were included. After informed consent, relevant clinical and laboratory data were obtained through review of clinical charts and records from the volanesorsen patient support program.</p><p><strong>Results: </strong>Ten patients with FCS and treated with volanesorsen were included. Most cases were caused by variants in LPL. A total of 90% of cases had at least 1 episode of pancreatis, the mean number of pancreatitis episodes was 5. Median follow-up was 56.5 weeks (IQR 38.3-82.3). The median highest plasma triglyceride (TG) before treatment was 3111 mg/dL (IQR 1738-3810), while the median lowest TG level after treatment was 493 mg/dL (IQR 147-812). The mean percent decreases in plasma TG at months 1, 3, 6, and 12 were 53.6%, 59.7%, 51.5%, and 40.5%, respectively. There were no new pancreatitis episodes after initiation of volanesorsen treatment. Side effects were consistent with those reported in clinical trials.</p><p><strong>Conclusion: </strong>Real-life data of volanesorsen treatment for FCS in Colombia demonstrate efficacy and safety similar to pivotal clinical trials.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical variability in cerebral tendinous xanthomatosis (CTX): Insights from 16 cases across Gulf Cooperation Council's (GCC's) high consanguineous population.","authors":"Mohammed A Almuqbil, Mashael M ALQuaimi, Al Qasim Al-Bahlani, Arif O Khan, Badr Alsaleem, Maryam Busehail, Raashda A Sulaiman, Tawfeg Ben Omran, Zahra Alsahlawi, Zuhair N Al-Hassnan, Reem AlHaddad, Saeed Bohlega","doi":"10.1016/j.jacl.2025.04.198","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.04.198","url":null,"abstract":"<p><strong>Background: </strong>Cerebrotendinous xanthomatosis (CTX) is a rare neurometabolic disorder characterized by diverse neurological and extra-neurological manifestations. In children, chronic diarrhea, neonatal cholestasis, and cataracts are characteristics and often precede neurological symptoms, while adults typically present with cognitive decline and gait disturbances. This variability contributes to frequent misdiagnosis and delays in diagnosis, leading to significant neurological deterioration.</p><p><strong>Objective: </strong>To explore the clinical and genetic diversity of CTX cases in the Gulf Cooperation Council (GCC) region, comparing the phenotypic differences between children and adults.</p><p><strong>Methods: </strong>The retrospective, multicenter, descriptive study included 16 clinically and genetically confirmed CTX cases. Data collected encompassed clinical presentations, diagnostic delays, biochemical markers such as cholestanol levels, neuroimaging findings, and genetic mutations in the CYP27A1 gene. Participants were categorized into pediatric and adult groups.</p><p><strong>Results: </strong>Common clinical features included cognitive decline (75%), learning difficulties (69%), diarrhea (56%), cataracts (56%), gait issues (50%), and behavioral changes (44%). Notably, childhood diarrhea was strongly associated with earlier diagnosis, with approximately 90% of such cases identified in this age group. Misdiagnosis occurred in 3 patients, with an average diagnostic delay of 6.1 years-shorter for children (2.7 years) compared to adults (11.6 years). Tendon xanthoma was observed in only 1 patient. Genetic testing identified 7 CYP27A1 variants, highlighting genetic heterogeneity in this population.</p><p><strong>Conclusion: </strong>This study emphasizes the need for increased physician awareness, particularly regarding pediatric presentations, to reduce diagnostic delays and prevent irreversible neurological damage. These findings support integration of targeted genetic testing and early screening programs to improve patient outcomes.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global disparities in access to lipid-lowering therapies for patients with homozygous familial hypercholesterolemia - A physician survey.","authors":"Willemijn A M Schonck, Janneke W C M Mulder, Tycho R Tromp, Laurens F Reeskamp, G Kees Hovingh, Jeanine E Roeters van Lennep, Dirk J Blom","doi":"10.1016/j.jacl.2025.05.003","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.05.003","url":null,"abstract":"<p><strong>Background: </strong>Lipid levels and atherosclerotic cardiovascular disease (ASCVD) outcomes have been shown to differ globally in patients with homozygous familial hypercholesterolemia (HoFH), which may be related to availability and accessibility of lipid-lowering therapy (LLT).</p><p><strong>Objective: </strong>In the current study, we investigated global disparities in availability and accessibility of LLTs for patients with HoFH.</p><p><strong>Methods: </strong>Physicians participating in the HoFH International Clinical Collaborators (HICC, NCT04815005) were invited to complete an online survey on registration status, reimbursement, and access to various LLTs. Responses were compared between high-income and nonhigh-income countries.</p><p><strong>Results: </strong>Responses were received from 87 physicians (64.4% from high-income countries). Physicians from high-income countries reported significantly higher registration rates for proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAbs) (96.4% vs 51.6%), lomitapide (83.6% vs 9.7%), evinacumab (69.1% vs 0.0%), colesevelam (50.0% vs 3.2%), and lipoprotein-apheresis (96.4% vs 45.2%). Public sector reimbursement was also more common in high-income countries for PCSK9 mAbs (90.9% vs 24.1%), lomitapide (74.5% vs 3.4%), evinacumab (60.0% vs 0.0%), colesevelam (40.0% vs 3.4%), and lipoprotein-apheresis (94.5% vs 37.9%). Access to LLTs was also higher in high-income countries for statins (91.1% vs 61.3%), ezetimibe (87.5% vs 38.7%), PCSK9 mAbs (53.6% vs 6.5%), lomitapide (32.% vs 0.0%), evinacumab (32.1% vs 3.2%), colesevelam (39.3% vs 3.2%), and lipoprotein-apheresis (57.1% vs 3.2%).</p><p><strong>Conclusion: </strong>Our results confirm significant global disparities in LLT registration, reimbursement, and access between high-income and nonhigh-income countries. Improving LLT availability and accessibility, particularly in nonhigh-income countries, is essential to improve outcomes in patients with HoFH.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating genetics and lifestyles for precision nutrition in hypertriglyceridemia: A UK Biobank and KoGES analysis.","authors":"Haeng Jeon Hur, Hye Jeong Yang, Min Jung Kim, Hyun-Jun Jang, Myung-Sunny Kim, Sunmin Park","doi":"10.1016/j.jacl.2025.04.202","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.04.202","url":null,"abstract":"<p><strong>Background: </strong>Hypertriglyceridemia is an independent risk factor for cardiovascular disease.</p><p><strong>Objective: </strong>This study examined the polygenic variants associated with high serum triglyceride concentration (high-TG) and their interactions with lifestyle factors using data from the UK Biobank (n = 479,300) and the Korean Genome and Epidemiology Study (KoGES; n = 57,939).</p><p><strong>Methods: </strong>High-TG group was categorized based on over 200 mg/dL fasting serum TG concentrations (Caucasians, UK Biobank, n = 100,543; Koreans, KoGES, n = 7211). Polygenic risk scores (PRS) were calculated using risk alleles from genetic variants identified through a genome-wide association study (GWAS) and generalized multifactor dimensionality reduction (GMDR) analyses.</p><p><strong>Results: </strong>Koreans showed higher frequencies of risk alleles in GCKR, APOA5, SIK3, and APOE genes compared to Caucasians. After adjusting for covariates, a PRS including lipoprotein lipase (LPL)_rs328, apolipoprotein A5 (APOA5)_rs2072560, and glucokinase regulator (GCKR)_rs780093 showed a 2.2-fold (UK Biobank) and 2.6-fold (KoGES) increased risk of high-TG among Caucasians and Koreans, respectively. In both cohorts, the PRS was positively associated with metabolic syndrome, serum low high-density lipoprotein (HDL)-cholesterol, and high low-density lipoprotein (LDL)-cholesterol concentrations, but inversely associated with high-TG. These variants were linked to the chylomicron and very low-density lipoprotein (VLDL) remodeling pathways in Multimarker Analysis of GenoMic Annotation (MAGMA) gene analysis. Significant interactions were observed between the PRS and lifestyle factors, namely plant-based diet (P = .0008), alcohol consumption (P = .0022), and smoking status (P < .001) in both cohorts. Additionally, in the KoGES cohort, vitamin D intake (P = .027) and the glycemic index (P = .045) interacted with the PRS to influence high-TG risk.</p><p><strong>Conclusion: </strong>Similar genetic variants affected high-TG risk across populations despite ethnic differences in risk allele frequencies. The identified PRS significantly interacted with plant-based diet, alcohol consumption, and smoking status in both cohorts, with additional interactions observed with vitamin D intake and glycemic index in the Korean cohort.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of lipid-lowering therapy in patients with elevated lipoprotein(a) levels.","authors":"Michael S Kelly, Ruth N Jeminiwa, Fatima Gohar, Mario Fanous, Pablo Ramirez, Dave L Dixon","doi":"10.1016/j.jacl.2025.04.200","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.04.200","url":null,"abstract":"<p><strong>Background: </strong>Elevated lipoprotein(a) (Lp(a)) is a recognized independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and other cardiovascular-related disorders. To mitigate the increased risk associated with elevated Lp(a), intensified treatment is recommended for modifiable ASCVD risk factors, such as hypertension, hyperglycemia, and dyslipidemia. However, limited evidence has assessed how clinicians are modifying lipid-lowering therapy in response to elevated Lp(a) levels.</p><p><strong>Objective: </strong>To evaluate changes to lipid-lowering therapy and assess which patient characteristics are associated with intensifying lipid-lowering medications.</p><p><strong>Methods: </strong>This retrospective, observational case-control study evaluated changes to lipid-lowering therapy in patients with elevated Lp(a) values from January 1, 2020, through May 31, 2024.</p><p><strong>Results: </strong>Of 1042 patients with an Lp(a) value of 30 mg/dL (75 nmol/L) or higher during our study period, 539 met full inclusion eligibility. Of the 539 patients, 120 (22.3%) had their lipid-lowering therapy modified within 30 days of the elevated Lp(a) result. The most common interventions were adding ezetimibe (33.3%) and intensifying statin therapy (32.5%). Elevated low-density lipoprotein cholesterol (LDL-C) was the most significant predictor of whether patients' lipid medications were modified, concordant with current recommendations for mitigating increased ASCVD risk associated with elevated Lp(a).</p><p><strong>Conclusion: </strong>Intensification of lipid-lowering medication within 30 days occurred in less than one-quarter of patients with elevated Lp(a). Future studies are needed to determine if aggressive LDL-C lowering is superior to Lp(a)-lowering to prevent ASCVD events in patients with elevated Lp(a).</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of familial chylomicronemia syndrome in a compound heterozygote for 2 APOA5 nonsense variants.","authors":"Paul A Mueller, Sara Rosario, Joshua Hay, Paige Bergstrom, Silvia Cecilia Pacheco-Velázquez, Robert A Hegele, Nathalie Pamir, Jonathan Q Purnell","doi":"10.1016/j.jacl.2025.04.196","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.04.196","url":null,"abstract":"<p><strong>Objective: </strong>A 3-year-old patient presented with severe hypertriglyceridemia and suspected familial chylomicronemia syndrome. Genetic analysis of the patient's DNA revealed the presence of 2 different heterozygous nonsense variants in the APOA5 gene encoding apolipoprotein (apo) A-V, namely p.Q275X and p.L242C fs X54. Our objective was to characterize the structural and functional consequences of the patient's co-occuring compound heterozygous variants in APOA5.</p><p><strong>Methods: </strong>Biozentrum's SWISS-MODEL was employed to predict the structure of apo A-V variants. Plasma from the patient and their family was used to determine lipid profiles, quantify apo C-II and apo C-III protein levels, and measure lipoprotein lipase (LPL) activity. High-density lipoprotein (HDL) was isolated from plasma and was used to assess sterol efflux capacity and proteome.</p><p><strong>Results: </strong>Structural characterization of the patient's APOA5 variants indicated premature truncation of the C-terminus of apo A-V that comprises the lipid binding domain. The patient's apo A-V was completely absent from the very-low density lipoprotein (VLDL) plasma fraction, associating almost exclusively with the low-density lipoprotein (LDL) and lipoprotein-free fractions. The patient's plasma also demonstrated reduced LPL activity and elevated apo C-II and C-III compared to other family members. The patient's HDL had the lowest sterol efflux capacity of all family members and a distinct proteome with reduced phospholipid transfer protein. Dietary intervention alone was effective in preventing recurring hypertriglyceridemia.</p><p><strong>Conclusions: </strong>These findings add to the current knowledge of apo A-V's role in plasma lipid homeostasis, pointing to a critical role for apo A-V binding to the lipoprotein particle in normal hydrolysis of triglyceride-rich lipoproteins.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}