Journal of clinical lipidology最新文献

{"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}

{"title":"Utilizing innovative implementation strategies for familial hypercholesterolemia: Correspondence.","authors":"Hinpetch Daungsupawong, Viroj Wiwanitkit","doi":"10.1016/j.jacl.2024.09.007","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.09.007","url":null,"abstract":"","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621438","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":"Akira Endo (1933-2024), In Memoriam.","authors":"W Virgil Brown, Ernst J Schaefer, Antonio M Gotto","doi":"10.1016/j.jacl.2024.09.004","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.09.004","url":null,"abstract":"","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142729052","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":"Rapid lipid-lowering response in two cases of autosomal recessive hypercholesterolemia.","authors":"Havva Yazıcı, Fehime Erdem, Ebru Canda, Sema Kalkan Uçar, Mahmut Çoker","doi":"10.1016/j.jacl.2024.09.003","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.09.003","url":null,"abstract":"<p><strong>Background: </strong>Autosomal recessive hypercholesterolemia (ARH) is an ultrarare dyslipidemia caused by variants in the LDLRAP1 gene. Clinically, this condition is indistinguishable from other homozygous familial hypercholesterolemia (HoFH).</p><p><strong>Case: </strong>We present the cases of two siblings diagnosed with ARH caused by LDLRAP1 gene c.617-14C>A splicing homozygous variant. Over a five-year treatment period, the older sibling experienced an 81 % reduction in low-density lipoprotein cholesterol (LDL-C) levels with the maximal dose of pitavastatin plus ezetimibe, while the younger sibling achieved a 75 % reduction. After three sessions, the older brother no longer required LDL apheresis, and the sibling never had LDL apheresis.</p><p><strong>Conclusion: </strong>Our findings demonstrate a rapid and significant response to lipid-lowering therapy (LLT) in patients with ARH caused by c.617-14C>A splicing VUS variant, a condition that mimics HoFH at diagnosis. Long-term follow-up studies in large pediatric cohorts of ARH patients treated with pitavastatin plus ezetimibe from childhood are necessary to better define the risk of cardiovascular disease (CVD) development.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621432","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":"Association between changes in high-density lipoprotein cholesterol and risk of cardiovascular disease.","authors":"Ya Wang, Tao Yan, Yuxin Yang, Lehui Li, Ziying Zhang, Xiaodong Cao, Yuan Xia, Yuan Shen, Kun Liu, Lei Xu, Chunfa Zhang, Xingguang Zhang, Nan Zhang","doi":"10.1016/j.jacl.2024.09.001","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.09.001","url":null,"abstract":"<p><strong>Background: </strong>The present study was performed to determine the association between changes in the HDL-C concentration and incident CVD.</p><p><strong>Methods: </strong>Time-dependent Cox regression models were used to evaluate the association between changes in the HDL-C concentration and the risk of incident CVD. Participants were followed up from 2015 to 2021.</p><p><strong>Results: </strong>In total, 24,123 participants with a median follow-up of 4.26 years were analyzed, and the mean age of the cohort was 56.24 years, 57.8 % were female, 24.3 % were current smokers, and 12.8 % had a history of alcohol use. Low, normal, and high HDL-C was defined as <40, 40-80, and >80 mg/dL, respectively. The average time for the two HDL-C measurements was 2.8 years,compared with participants whose HDL-C was maintained at a normal level, the risk of CVD was higher in those whose HDL-C changed to a low level, remained unchanged at a low level(HR, 1.24; 95 % CI, 1.01-1.40,P < 0.001), similarly, the risk of CVD was higher in those whose HDL-C changed from very high level to normal level(HR, 0.81; 95 % CI, 0.67-0.99,P = 0.039). Also compared with participants whose HDL-C was maintained at a normal level, the risk of CVD was lower in those whose HDL-C increased from low to normal and high(HR, 0.80; 95 % CI, 0.66-0.98,P = 0.029).</p><p><strong>Conclusions: </strong>Participants whose HDL-C changed to a low level and whose low HDL-C level was maintained had a higher risk of CVD, whereas participants whose HDL-C changed from low to high had a lower risk of CVD.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288258","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 plasma phytosterols in sitosterolemia, their kindreds and hyperlipidemia subjects.","authors":"Xuanru Ren, Jun Zhang, Luya Wang, Yuxuan Zhang, Jialu Li, Hao Yu, Zhaohai Zheng, Yiqing Zhang, Hesong Zeng, Yan Chen, Junfang Wu","doi":"10.1016/j.jacl.2024.09.002","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.09.002","url":null,"abstract":"<p><strong>Background: </strong>Patients suffering from sitosterolemia with ABCG5/8 mutation typically present with early-onset or rapidly progressive atherosclerosis. Their kindreds with partial genetic deficiencies of ABCG5/8 are often considered healthy. However, discerning sitosterolemia from its familial kindreds and hyperlipidemia subjects has remained challenging.</p><p><strong>Methods: </strong>Here we retrospectively recruited seven families including 8 individuals diagnosed with sitosterolemia subjects, and 14 kindreds carrying single gene mutations. Additionally, 17 individuals with hyperlipidemia and 130 healthy controls served as positive and negative controls, respectively. A total of 6 phytosterols combined with cholesterol absorption indices (including sitosterol, campesterol, stigmasterol, and cholestanol) and cholesterol synthesis markers (desmosterol and 7-dehydrocholesterol), was compared across the aforementioned four groups.</p><p><strong>Results: </strong>As expected, the sitosterolemia subjects with double mutations demonstrated significantly elevated levels of sitosterol and other cholesterol absorption indices. Meanwhile, sitosterolemia kindreds with single gene mutation showed a similar pattern of activated cholesterol-absorption ability to the hyperlipidemia group, but not as high as the double mutation group. Notably, the cholesterol-synthesis enzyme 7-dehydrocholesterol reductase displayed an increase in the hyperlipidemia group but a decrease in the sitosterolemia kindred group, suggesting a potential discriminative role of 7-dehydrocholesterol in distinguishing between these two groups. The combination of phytosterols was more valuable than clinical lipid index for sitosterolemia diagnosis.</p><p><strong>Conclusion: </strong>Our study revealed mild disruptions of cholesterol absorption capacities in sitosterolemia kindreds with single mutations. Furthermore, the combination of 6 phytosterols proved effective in distinguishing between sitosterolemia, its single mutation carriers, and hyperlipidemia patients.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288259","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 therapeutic effect of liver transplantation in 14 children with homozygous familial hypercholesterolemia: a prospective cohort: Liver transplant for familial hypercholesterolemia.","authors":"Dongni Lin,Yefeng Lu,Bijun Qiu,Mingxuan Feng,Yi Luo,Feng Xue,Tao Zhou,Jianjun Zhu,Jianjun Zhang,Lvya Wang,Qiang Xia,Ping Wan","doi":"10.1016/j.jacl.2024.08.008","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.08.008","url":null,"abstract":"OBJECTIVESHomozygous familial hypercholesterolemia (HoFH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) and early-onset cardiovascular disease. To assess the therapeutic effects of liver transplantation (LT) on HoFH patients, we observed and analyzed the outcomes of HoFH children after LT.STUDY DESIGNThis prospective cohort study included all LT candidates under 18 years old diagnosed with HoFH at Ren Ji Hospital between November 2017 and July 2021. The patients were followed until October 2023. They were treated according to the standard protocol at our center. We collected data on changes in lipid profiles, clinical manifestations, and cardiovascular complications at different time points, and recorded postoperative recipient and graft survival.RESULTSFourteen HoFH patients with a median age of 7 (2-12) years were included. Preoperatively, xanthomas and arcus corneas occurred in 14 and 3 patients, respectively, with 10 patients showing mild cardiovascular disease. All patients underwent LT. Recipient and graft survival rates were 100 % over a median follow-up duration of 35 (27-71) months. Median LDL-C levels dropped from 11.83 (7.99-26.14) mmol/L preoperatively to 2.3 (1.49-3.39) mmol/L postoperative at the last measurement. Thirteen patients discontinued lipid-lowering treatment after LT, while only one patient resumed statins 6 months post-operation. Xanthomas and arcus corneas significantly improved. Cardiovascular complications regressed in five patients, with no progression observed in the others.CONCLUSIONSLT is a safe and effective treatment for severe HoFH patients beyond lipid-lowering control. Early LT improves prognosis and quality of life while minimizing the risk of cardiovascular complications.","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"2013 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265636","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":"Challenges and opportunities for identifying people with Familial hypercholesterolaemia in the UK: Evidence from the National FH PASS database.","authors":"Edward Cox, Rita Faria, Pedro Saramago, Kate Haralambos, Melanie Watson, Steve E Humphries, Nadeem Qureshi, Beth Woods","doi":"10.1016/j.jacl.2024.08.007","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.08.007","url":null,"abstract":"<p><strong>Background: </strong>Familial Hypercholesterolaemia (FH) is a monogenic disorder that causes high levels of low-density lipoprotein (LDL) cholesterol. Cascade testing, where relatives of known individuals with FH ('index') are genetically tested, is effective and cost-effective, but implementation in the UK varies.</p><p><strong>Objective: </strong>This study aims to provide evidence on current UK FH cascade yields and to identify common obstacles cascade services face and individual- and service-level predictors of success.</p><p><strong>Methods: </strong>Electronic health records from 875 index families and 5,958 linked relatives in the UK's Welsh and Wessex FH services (2019) were used to explore causes for non-testing and to estimate testing rates, detection yields, and how relative characteristics and contact methods relate to the probability of relatives being tested (using logistic regression).</p><p><strong>Results: </strong>In Wales (Wessex), families included 7.35 (7.01) members on average, with 2.41 (1.66) relatives tested and 1.35 (0.96) diagnosed with FH per index. Cascade testing is limited by individualised circumstances (too young, not at-risk, etc.) and FH services' reach, with approximately one in four relatives out-of-area. In Wales, first-degree relatives (odds ratio (OR):1.55 [95 % confidence interval (CI):1.28,1.88]) and directly contacted relatives (OR:2.11 [CI:1.66,2.69]) were more likely to be tested. In Wales and Wessex, women were more likely to be tested than men (ORs:1.53 [CI:1.28,1.85] and 1.74 [CI:1.32,2.27]).</p><p><strong>Conclusion: </strong>In Wales and Wessex less than a third of relatives of an index are tested for FH. Improvements are likely possible by integrating geographically dispersed families into cascade testing, services directly contacting relatives where possible, and finding new ways to encourage participation, particularly amongst men.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347571","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":"NLA Expert Clinical Consensus on apolipoprotein B recommends expanded clinical use and improved patient access","authors":"Kevin C. Maki PhD,&nbsp;P. Barton Duell MD","doi":"10.1016/j.jacl.2024.09.006","DOIUrl":"10.1016/j.jacl.2024.09.006","url":null,"abstract":"","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 5","pages":"Pages e645-e646"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347474","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}