Journal of clinical lipidology最新文献

{"title":"Identification and functional analysis of novel homozygous LMF1 variants in severe hypertriglyceridemia.","authors":"Candy Bedoya, Rishi Thomas, Anna Bjarvin, Wilbur Ji, Hanien Samara, Jody Tai, Laurie Green, Philip H Frost, Mary J Malloy, Clive R Pullinger, John P Kane, Miklós Péterfy","doi":"10.1016/j.jacl.2024.10.004","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.10.004","url":null,"abstract":"<p><strong>Background: </strong>The genetic basis of hypertriglyceridemia (HTG) is complex and includes variants in Lipase Maturation Factor 1 (LMF1), an endoplasmic reticulum (ER)-chaperone involved in the post-translational activation of lipoprotein lipase (LPL).</p><p><strong>Objective: </strong>The objective of this study was to identify and functionally characterize biallelic LMF1 variants in patients with HTG.</p><p><strong>Methods: </strong>Genomic DNA sequencing was used to identify biallelic LMF1 variants in HTG patients without deleterious variants in LPL, apolipoprotein C-II (APOC2), glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) or apolipoprotein A-V (APOA5). LMF1 variants were functionally evaluated by in silico analyses and assessing their impact on LPL activity, LMF1 protein expression and specific activity in transiently transfected HEK293 cells.</p><p><strong>Results: </strong>We identified four homozygous LMF1 variants in patients with severe HTG: two novel rare variants (p.Asn147Lys and p.Pro246Arg) and two low-frequency variants (p.Arg354Trp and p.Arg364Gln) previously reported at heterozygosity. We demonstrate that all four variants reduce the secretion of enzymatically active LPL by impairing the specific activity of LMF1, whereas p.Asn147Lys also diminishes LMF1 protein expression.</p><p><strong>Conclusion: </strong>This study extends the role of LMF1 as a genetic determinant in severe HTG and demonstrates that rare and low-frequency LMF1 variants can underlie this condition through distinct molecular mechanisms. The clinical phenotype of patients affected by partial loss of LMF1 function is consistent with Multifactorial Chylomicronemia Syndrome (MCS) and suggests that secondary factors and additional genetic determinants contribute to HTG in these subjects.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621423","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":"Complex dyslipidemia induced by Lorlatinib therapy: A case study.","authors":"Julianna West, Abhimanyu Garg","doi":"10.1016/j.jacl.2024.10.003","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.10.003","url":null,"abstract":"<p><strong>Context: </strong>Lorlatinib is an anaplastic lymphoma kinase (ALK) inhibitor, which is currently used for the treatment of ALK-positive metastatic non-small cell lung cancer (NSCLC). Previous reports have noticed an association between lorlatinib and hyperlipidemia, however the specific mechanisms for this side effect remain unknown. Some investigators have reported nephrotic syndrome to be the underlying cause of lorlatinib-induced hyperlipidemia.</p><p><strong>Case report: </strong>A 59-year-old female with NSCLC presented with marked elevation of lipid levels, including total cholesterol, triglycerides, low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C), after initiation of lorlatinib therapy. Despite high dose atorvastatin and ezetimibe, lipid levels remained elevated. A 24-hour urine collection revealed only 226 mg of protein excretion.</p><p><strong>Conclusions: </strong>Lorlatinib induced a complex dyslipidemia in our patient with elevations of both LDL-C and HDL-C. The underlying mechanism of lorlatinib-induced hyperlipidemia remains unknown and is unlikely to be secondary to nephrotic syndrome in many patients.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621420","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":"Lipoprotein(a) in clinical practice: The role in long-term in-stent restenosis.","authors":"Francesco Sbrana, Beatrice Dal Pino","doi":"10.1016/j.jacl.2024.10.002","DOIUrl":"10.1016/j.jacl.2024.10.002","url":null,"abstract":"","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621427","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":"Time to benefit of intensive lipid lowering therapy in individuals with cardiovascular disease.","authors":"Linjie Li, Chuanyi Huang, Wennan Liu, Jingge Li, Geru A, Xiaozhi Chen, Shichen Jiang, Yiwen Fang, Roger Sik-Yin Foo, Mark Yan-Yee Chan, Ying Yu, Yongle Li, Qing Yang, Xin Zhou","doi":"10.1016/j.jacl.2024.09.014","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.09.014","url":null,"abstract":"<p><strong>Background: </strong>The timing of the clinical benefit of intensive lipid-lowering therapy in reducing major adverse cardiovascular events (MACE) in individuals with established cardiovascular disease (CVD), both before and after the advent of novel medications (proprotein convertase subtilisin/kexin type 9 inhibitor [PCSK9i] and ezetimibe) in 2010, is unclear.</p><p><strong>Objective: </strong>To evaluate the time to benefit (TTB) from intensive lipid-lowering therapy.</p><p><strong>Methods: </strong>The investigators systematically searched for randomized controlled trials evaluating intensive lipid-lowering therapy. The primary outcome was MACEs. Utilizing reconstructed individual participant data, Weibull survival curves were fitted to estimate the TTB for specific absolute risk reduction thresholds (0.002, 0.005, and 0.01).</p><p><strong>Results: </strong>Seven trials randomizing 92,180 adults aged between 58.2 and 63.6 years were identified. A TTB of 19.6 months (95 % confidence interval [CI]: 12.3 to 31.4) of intensive lipid-lowering was needed to prevent 1 MACE per 100 patients. Before 2010, when statin as the only option, a TTB for high-intensity statin therapy of 15.2 months (95 % CI: 6.52 to 35.5) was needed. After 2010, the TTB for PCSK9i-based, ezetimibe-based intensive lipid-lowering on a background of statin therapy was 17.7 (95 % CI: 12.2 to 25.6) and 47.3 (95 % CI: 20.4 to 110) months, respectively.</p><p><strong>Conclusions: </strong>In contemporary practice, to prevent 1 MACE in 100 individuals with established CVD, a TTB of 17.7 and 47.3 months was needed for PCSK9i-based and ezetimibe-based intensive lipid-lowering therapy on a background of statin therapy, respectively. The observed variations across different drug regimens highlight the need for a personalized approach to treatment decisions.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621437","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":"The role of nutrition-related clinical trials in informing dietary recommendations for health and treatment of diseases.","authors":"Penny M Kris-Etherton, Kristina S Petersen, Benoit Lamarche, Wahida Karmally, John R Guyton, Catherine M Champagne, Alice H Lichtenstein, George A Bray, Frank M Sacks, Kevin C Maki","doi":"10.1016/j.jacl.2024.09.010","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.09.010","url":null,"abstract":"<p><p>Dietary guidance is based on a robust evidence base that includes high-quality clinical trials, of which some have been designed to establish causal relationships between dietary interventions and ASCVD risk reduction. However, the complexity associated with conducting these trials has resulted in criticism of nutrition and dietary recommendations because the strength and quality of evidence falls short of that for some pharmaceutical interventions. In this paper, we aim to promote greater awareness of the nutrition-related clinical trials that have been conducted showing ASCVD benefits and how this evidence has contributed to dietary recommendations. Compared to clinical trials of pharmaceutical agents, nutrition-related clinical trials have several unique considerations, including complexities of intervention design, challenges related to the blinding of participants to treatment, modest effect magnitudes, variability in baseline dietary exposures, absence of objective dietary adherence biomarkers, achieving sustained participant adherence, and the significant timeline for endpoint responses. Evidence-based dietary recommendations are made based on multiple lines of evidence including that from randomized controlled trials, epidemiological studies, as well as animal and in vitro studies. This research has provided foundational evidence for the role of diet in prevention, management, and treatment of ASCVD. Based on the clinical trials that have been conducted, a strong consensus has evolved regarding the key elements of healthy dietary patterns that decrease ASCVD risk. Going forward, implementation research is needed to identify effective translation approaches to increase adherence to evidence-based dietary recommendations.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794879","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":"Associations of non-insulin-based insulin resistance indices with presence and extent of multi-territorial atherosclerosis: A cross-sectional study.","authors":"Yanli Zhang, Mengxing Wang, Xueli Cai, Aoming Jin, Jing Jing, Suying Wang, Xia Meng, Shan Li, Qi Zhou, Xuan Wang, Tiemin Wei, Yongjun Wang, Yuesong Pan","doi":"10.1016/j.jacl.2024.09.011","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.09.011","url":null,"abstract":"<p><strong>Background: </strong>Non-insulin-based insulin resistance (IR) indices, simple and reliable surrogates for IR calculated without insulin level, have been reported to be associated with cardiovascular and cerebrovascular diseases.</p><p><strong>Methods: </strong>Participants without diabetes from the cross-sectional baseline survey of the PRECISE (Poly-Vascular Evaluation for Cognitive Impairment and Vascular Events) cohort study were included in present study. Non-insulin-based IR indices, including triglyceride and glucose (TyG) index, triglyceride glucose-body mass (TyG-BMI) index, triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, and metabolic score for insulin resistance (METS-IR) index, were calculated and stratified into quartiles. Intracranial, extracranial, coronary, subclavian, aorta, renal, ilio-femoral, and peripheral arteries were also assessed at baseline.</p><p><strong>Results: </strong>Of 2759 included participants, the average age was 60.9 ( ± 6.6) years, and 1460 (52.9 %) were female. Compared with the first quartile of TyG index, the fourth quartile of TyG index was associated with an increased presence and extent of atherosclerotic plaques (OR, 3.51; 95 %CI,1.30-1.87; cOR, 2.22; 95 %CI,1.76-2.79) and presence and extent of atherosclerotic stenosis (OR, 1.60; 95 %CI,1.24-2.06; cOR, 1.66; 95 %CI,1.30-2.12). Such associations were also observed for the relationship of TyG-BMI index, TG/HDL-C ratio, and METS-IR index with the presence and extent of atherosclerotic plaques and stenosis. Addition of 4 non-insulin-based IR indices to the basic model with traditional risk factors improved the predictive performance of the presence of atherosclerotic plaque and stenosis.</p><p><strong>Conclusions: </strong>Elevated non-insulin-based IR indices levels were associated with an increased risk of presence and extent of atherosclerotic plaques and stenosis in non-diabetic, older individuals in the PRECISE study. Further, these IR surrogate markers have certain predictive performance to assess the risk of multi-territorial atherosclerosis.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621418","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":"Identification of a homozygous variant in ABCG5 by panel sequencing in a Pakistani family with sitosterolemia: Genotype-phenotype correlation and management considerations.","authors":"Wajahat Bin Naeem, Mehreen Ali Khan, Zaineb Akram, Tehseen Ullah Khan Afridi, Tariq Azam Khattak, Muhammad Asghar Khan, Muhammad Yousaf, Humayoon Shafique Satti","doi":"10.1016/j.jacl.2024.09.012","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.09.012","url":null,"abstract":"<p><p>Sitosterolemia is a rare autosomal recessive disorder characterized by impaired excretion of plant sterols, leading to their accumulation in tissues and organs. We identified a hitherto unreported homozygous variant, in ATP-binding cassette sub-family G member 5 (ABCG5) (NM_022436.3) c.274A>G p.(Lys92Glu), segregating in two affected sibs (Sit1C and Sit1F) of a consanguineous Pakistani family, during genetic workup for hereditary hemolytic anemia. Both patients had anemia, history of gum bleed and easy bruising. Peripheral film revealed stomatocytes and macrothrombocytopenia. Plasma sitosterol level was found to be significantly high (27.7 mg/dL and 25.1 mg/dL for Sit1C and F respectively), confirming diagnosis of sitosterolemia in both patients. Treatment with Ezetimibe, a sterol absorption inhibitor, resulted in significant decrease in sitosterol as well as LDL-cholesterol, in these patients. This study confirms the potential of panel sequencing as a diagnostic tool for sitosterolemia. Definitive diagnosis has significant clinical implications for genetic counseling and management strategies, such as dietary modifications and successful management with Ezetimibe.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621425","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":"Hypertriglyceridemia-induced acute pancreatitis in pregnancy associated with CREB3L3 mutation.","authors":"Chen Gurevitz, Jeffrey I Mechanick, Ron Do, Robert S Rosenson","doi":"10.1016/j.jacl.2024.10.001","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.10.001","url":null,"abstract":"<p><p>A 40-year-old woman at 35 weeks of gestation presented with abdominal pain and hypertriglyceridemia of above 5000 mg/dL. Following lab tests and imaging studies, she was diagnosed with hypertriglyceridemia-related acute pancreatitis in pregnancy. She was managed with NPO, IV insulin, and peripheral parenteral nutrition, but her condition further complicated with preeclampsia, and she was induced and delivered at 36 weeks of gestation. Genetic testing revealed a heterozygous variant in the CREB3L3 gene predisposing to severe hypertriglyceridemia. Postpartum lifestyle modifications, including a low-fat diet and routine exercise, significantly improved her lipid profile.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675953","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":"Novel pathogenic variant in the LCAT gene in a compound heterozygous patient with fish-eye disease and a mild phenotype.","authors":"Masaaki Miyata, Masayuki Kuroda, Junko Miyoshi, Mika Kirinashizawa, Rora Nagasawa, Misato Yamamoto, Yuichi Akasaki, Kensuke Utatsu, Yoshiro Maezawa, Koutaro Yokote, Mitsuru Ohishi","doi":"10.1016/j.jacl.2024.09.013","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.09.013","url":null,"abstract":"<p><strong>Background and objective: </strong>Low HDL-cholesterol and corneal opacity are associated with fish-eye disease (FED), familial LCAT deficiency (FLD), ApoAI deficiency, and Tangier disease. The differential diagnosis is made by clinical and biochemical tests. Measuring the LCAT activity is the ideal way to distinguish conditions caused by LCAT gene variants (FED and FLD) from the other two diseases. However, this is not accessible from all clinics. The CE/TC ratio, which is below the reference range in most cases with LCAT gene variants, has been proposed as an alternative. We report a case of compound heterozygous FED with a CE/TC ratio within the reference range.</p><p><strong>Methods: </strong>LCAT activity assays and genetic analyses were performed using patients' blood samples. Identified LCAT gene variants were examined by an in vitro expression assay.</p><p><strong>Results: </strong>The proband showed approximately 20 % LCAT α-activity relative to the normolipidemic controls, whereas a patient with a typical FED-causing variant (p.Thr147Ile) showed only 3 % activity. We identified compound heterozygous variants (c.101C>T/c.460A>G) resulting in a p.Pro34Leu/p.Asn154Asp amino acid residue substitution in the LCAT gene of the proband. The former variant has been reported previously, but the latter was newly identified. An in vitro expression assay demonstrated that the LCAT α-activity of the p.Asn154Asp variant significantly decreased regarding the wild type, but it was relatively well preserved compared to the typical FED-causing variants (p.Pro34Leu and p.Thr147Ile).</p><p><strong>Conclusion: </strong>These results suggest that the residual 20 % LCAT α-activity is sufficient to normalize CE/TC, but not sufficient to prevent the development of corneal opacity in FED.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621429","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":"Variance in the composition and number of VLDL and LDL particles with increasing triglyceride or increasing ApoB concentrations.","authors":"Justine Cole, Patrick Couture, André J Tremblay, Allan D Sniderman","doi":"10.1016/j.jacl.2024.09.009","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.09.009","url":null,"abstract":"<p><strong>Objective: </strong>The importance of any enhanced atherogenicity of triglyceride (TG)-rich lipoproteins (TRLs) will depend on the relative abundance of these particles compared with LDL or total apolipoprotein (apo)B. Accordingly, we determined the contribution that TRLs make to total apoB as TG or apoB concentrations increase. We also describe compositional changes in TRLs as TG or apoB increase to assess whether VLDL-C is a valid proxy for VLDL-apoB.</p><p><strong>Methods: </strong>We used sequential ultracentrifugation to separate lipoprotein fractions in plasma samples from 1940 dyslipidemic patients not on lipid-lowering medication, and measured apoB, cholesterol and TG in the plasma and in each subfraction. We analyzed this data in quartiles of TG or apoB.</p><p><strong>Results: </strong>There was wide variance in all parameters in all quartiles of both TG and apoB. Although VLDL-apoB accounted for almost all the increase in total apoB across TG quartiles, LDL-apoB still accounted for 80 % of the total in TG quartile 4. In contrast, LDL-apoB accounted for 90 % of the increase in apoB across apoB quartiles. As TG increases, the increase in VLDL-C is explained more by increased VLDL-C/apoB when TG is moderately elevated, and more by increased VLDL-apoB when TG is very high.</p><p><strong>Conclusions: </strong>In conclusion, VLDL-apoB only becomes a substantial component of total apoB with extreme hypertriglyceridemia and VLDL-C is not an appropriate proxy for VLDL-apoB.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621439","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}