Journal of clinical lipidology最新文献

{"title":"Estimate and prognosis of patients who are candidates for treatment with eicosapentaenoic acid after an acute coronary syndrome","authors":"Alberto Cordero MD, PhD, FESC ,&nbsp;José R. Gonzalez-Juanatey MD, PhD, FESC, FACC ,&nbsp;Rosa Fernandez Olmo MD ,&nbsp;Leticia Fernandez-Freira MD, PhD ,&nbsp;Sergio Manzano MD, PhD ,&nbsp;Clara Bonanad MD, PhD ,&nbsp;Belén Alvarez-Alvarez MD, PhD ,&nbsp;Gustavo Cortez MD ,&nbsp;Armando Oterino MD, PhD ,&nbsp;Pedro J. Flores Blanco MD ,&nbsp;José M. Castellano MD, PhD ,&nbsp;Deepak L. Bhatt MD, MPH, MBA","doi":"10.1016/j.jacl.2025.04.193","DOIUrl":"10.1016/j.jacl.2025.04.193","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Treatment with icosapent ethyl<span> (IPE) has been shown to reduce the incidence of major adverse cardiovascular events (MACE) in patients at high cardiovascular risk with mildly to moderately elevated triglyceride values (&gt;135 mg/dL) and well-controlled (&lt;100 mg/dL) low-density lipoprotein cholesterol (LDLc). The main objective of this study was to estimate the number of patients eligible for IPE after an acute coronary syndrome (ACS).</span></div></div><div><h3>METHODS</h3><div>Multicenter retrospective study based on ACS registries of patients from 8 hospitals in Spain. Patients with LdLc &lt;100 mg/dL and triglyceride values &gt;135 mg/dL were analyzed as candidates for IPE. The study endpoints were MACE (cardiovascular mortality, ACS, or readmission for heart failure or stroke) and all-cause mortality.</div></div><div><h3>RESULTS</h3><div>A total of 14,483 patients with ACS were included in the registry; the mean (SD) LDLc was 99.8 mg/dL (38.5), and the median value for triglycerides was 120.5 mg/dL (IQR: 90-197 mg/dL). Of this population, 3028 (20.9%) were classified as candidates for IPE. Median follow-up was 1223 days. Candidates for IPE had significantly higher rates of MACE (39.0% vs 33.6%) and mortality (18.4% vs 14.0%). Multivariate analysis identified an independently higher risk for MACE (hazard ratio [HR]: 1.14, 95% CI: 1.05-1.20) and all-cause mortality (HR: 1.10, 95% CI: 1.04-1.26) among candidates for IPE.</div></div><div><h3>CONCLUSIONS</h3><div>Approximately 20% of patients discharged after an ACS could be candidates for IPE, and this subset of patients are at higher risk of MACE or death.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 4","pages":"Pages 827-834"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248141","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":"Cholesteryl ester transfer protein activity correlates inversely with apolipoprotein A5 levels","authors":"Yi Wen PhD ,&nbsp;Hongxia Li MS ,&nbsp;Sydney Smith BS ,&nbsp;Yanzhu Lin PhD ,&nbsp;Yan Q. Chen MD ,&nbsp;Melissa Bellinger BS ,&nbsp;Eugene Y. Zhen PhD ,&nbsp;Thomas P. Beyer PhD ,&nbsp;Robert W. Siegel PhD ,&nbsp;Yuewei Qian PhD ,&nbsp;Giacomo Ruotolo MD ,&nbsp;Robert J. Konrad MD","doi":"10.1016/j.jacl.2025.06.008","DOIUrl":"10.1016/j.jacl.2025.06.008","url":null,"abstract":"<div><h3>BACKGROUND</h3><div><span>Cholesteryl ester </span>transfer protein<span> (CETP) mediates the exchange of triglycerides (TG) from apolipoprotein B (ApoB)-containing lipoproteins to high-density lipoproteins (HDL) and the reciprocal exchange of cholesterol (C) from HDL to ApoB-containing lipoproteins. CETP inhibition increases HDL-C and decreases low-density lipoprotein cholesterol (LDL-C) while modestly decreasing TG. Considering that CETP inhibitors block removal of TG from TG-rich lipoproteins (TRL), it is interesting that CETP inhibition decreases TG concentrations. TG levels are largely regulated by lipoprotein lipase (LPL), the enzyme primarily responsible for hydrolyzing TG. The angiopoietin-like 3/8 complex (ANGPTL3/8) is the most potent circulating LPL inhibitor, while the TG-lowering apolipoprotein A5 (ApoA5) acts by suppressing ANGPTL3/8-mediated LPL inhibition.</span></div></div><div><h3>METHODS</h3><div>To better understand CETP biology, we studied the effects of CETP overexpression and CETP inhibition on the levels of ANGPTL3/8 and ApoA5 in circulation using dedicated immunoassays.</div></div><div><h3>RESULTS</h3><div>CETP-overexpressing transgenic mice had increased TG and normal ANGPTL3/8 levels but manifested dramatically reduced ApoA5 concentrations. Administration of the CETP inhibitor evacetrapib had no effect on ANGPTL3/8 levels in CETP-overexpressing mice or in humans. However, evacetrapib administration increased ApoA5 concentrations in both species. In human subjects, evacetrapib treatment increased circulating ApoA5 levels in the late-stage ACCELERATE and ACCENTUATE studies by 160.1% and 204.7%, respectively.</div></div><div><h3>CONCLUSIONS</h3><div>Our results uncover a previously unrecognized link between CETP and ApoA5 by showing that CETP overexpression reduces ApoA5 levels while CETP inhibition increases ApoA5 concentrations.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 4","pages":"Pages 1073-1084"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591303","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":"Familial hypercholesterolemia in Sri Lanka: Addressing evidence gaps and paving the road ahead","authors":"Anne Thushara Matthias MBBS, MD, MRCP, FRCP","doi":"10.1016/j.jacl.2025.06.025","DOIUrl":"10.1016/j.jacl.2025.06.025","url":null,"abstract":"<div><div>In recent years, South Asia has witnessed a staggering increase in the rate of cardiovascular (CV) deaths, overburdening healthcare systems in this low- to middle-income region. Dyslipidemia is a major risk factor for cardiovascular disease (CVD). Identifying potential gaps in screening and managing dyslipidemia could help to develop a framework for CVD management in this region. Among dyslipidemias, familial hypercholesterolemia (FH) is a risk factor for premature CVD. Data on FH in Sri Lanka, a South Asian country, are sparse. This report is the first to identify and address problems associated with FH in Sri Lanka. It provides insight into the practices employed within the country and helps assess potential barriers in managing patients with FH.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 4","pages":"Pages 1145-1147"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707646","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":"Performance of the FIND-FH machine learning algorithm for the identification of individuals with suspected familial hypercholesterolemia","authors":"Spencer V. Carter MD ,&nbsp;Taylor Triana MD, MBA ,&nbsp;Mujeeb Basit MD, MMSc ,&nbsp;Ruth Schneider MSN, APRN, ANP-BC ,&nbsp;Colby R. Ayers MS ,&nbsp;Jessica Moon ,&nbsp;Tanvi Ingle BS ,&nbsp;Lakeisha Cade ,&nbsp;Diane E. MacDougall MS ,&nbsp;George Blike MD, MHCDS ,&nbsp;Zahid Ahmad MD ,&nbsp;Amit Khera MD, MSc","doi":"10.1016/j.jacl.2025.06.009","DOIUrl":"10.1016/j.jacl.2025.06.009","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Familial hypercholesterolemia (FH) is an inherited cholesterol disorder that is markedly underdiagnosed.</div></div><div><h3>OBJECTIVE</h3><div>This study evaluated the real-world performance of the Find, Identify, Network, Deliver-FH (FIND-FH) score, a novel machine learning algorithm, in identifying individuals with high likelihood of FH.</div></div><div><h3>METHODS</h3><div>The FIND-FH model was applied to electronic health record (EHR) data from UT Southwestern Medical Center. Manual chart review was performed on those deemed high probability of FH (score &gt;0.35) to assess accuracy of FH diagnosis by modified Simon-Broome and Dutch Lipid Clinic Network (DLCN) criteria. Individual characteristics were compared across quintiles of the FIND-FH score. Individuals deemed suitable for FH outreach were identified using predetermined clinical criteria denoting adequate clinical probability of FH.</div></div><div><h3>RESULTS</h3><div>Of the 93,418 individuals in the EHR dataset, the FIND-FH algorithm identified 340 with high probability of FH. These 340 individuals had a mean age of 49.8 years, were 59% male, and had a highest low-density lipoprotein cholesterol (LDL-C) of 168.4 mg/dL (±51.9). A total of 20-32% met modified Simon-Broome or DLCN criteria for at least possible FH based on available EHR data. Several variables differed significantly by FIND-FH score quintile, including Simone-Broome and DLCN probability. In the reviewed cohort, 191 (56%) had enough clinical suspicion for FH to warrant outreach. Among these, 101 (53%) had highest LDL-C &lt;190 mg/dL and would be missed by LDL-C-based FH screening strategies.</div></div><div><h3>CONCLUSION</h3><div>In a large healthcare system EHR cohort, most individuals identified as higher risk for FH by the FIND-FH algorithm were deemed appropriate for further evaluation, despite the majority not meeting FH diagnostic criteria using available EHR data.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 4","pages":"Pages 1037-1043"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768698","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":"Isolated thrombocytopenia as an atypical presentation of sitosterolemia in a school-aged child.","authors":"Gözde Uzunyayla, Fehime Erdem-Karapinar, Esra İşat, Mehmet Şerif Cansever","doi":"10.1016/j.jacl.2025.06.022","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.06.022","url":null,"abstract":"<p><p>Sitosterolemia is a rare autosomal recessive lipid metabolism disorder caused by excessive intestinal absorption and impaired hepatic excretion of plant sterols and cholesterol. The condition caused by mutations in the ATP-binding cassette subfamily G member 5 (ABCG5) gene or the ATP-binding cassette subfamily G member 8 (ABCG8) gene is typically characterized by the presence of xanthomas, early-onset atherosclerosis, and hemolytic anemia. Hematological abnormalities including thrombocytopenia have been reported in patients with sitosterolemia, and may occasionally occur in the absence of dyslipidemia or xanthomas. We present the case of a 6-year-old girl diagnosed with sitosterolemia following the detection of isolated thrombocytopenia during a routine school health screening. Laboratory investigations revealed markedly elevated plasma plant sterol levels; however, dyslipidemia, which is a common feature of this disease, was absent in this case. Although platelet abnormalities have previously been reported in patients with sitosterolemia, the distinguishing feature of this case is the presentation of thrombocytopenia that responded to ezetimibe therapy. The platelet count increased from 58,000/mm³ prior to treatment to 117,000/mm³ following therapy, and further improved to 140,000/mm³ at the most recent follow-up visit. Genetic analysis identified a homozygous pathogenic variant in ABCG5 (c.161G>A, p.Trp54Ter), confirming the diagnosis. This case highlights the significance of thrombocytopenia responsive to ezetimibe as a primary presentation of sitosterolemia, even in the absence of dyslipidemia. In conclusion, it emphasizes the importance of considering sterol metabolism disorders in the differential diagnosis of unexplained thrombocytopenia.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859186","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 the cardiometabolic index and mortality risk in US adults: Data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018.","authors":"Da Liu, Xuliang Wang, Zhuchang Tian, You-Lan Lei, Qing Zhou, Linan Duan, Jing Li, Haiping Liu, Xiangbin Meng, Jun Gao, Jun Wen, Jingjia Wang, Wenyao Wang, Mingqi Zheng, Chunli Shao","doi":"10.1016/j.jacl.2025.06.019","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.06.019","url":null,"abstract":"<p><strong>Background: </strong>Recently, studies have suggested the use of the cardiometabolic index (CMI) to reflect the risk of cardiometabolic disease. However, the association between the CMI and the risk of mortality remains unclear. The aim of the present study was to assess the associations between the CMI and the risk of mortality in the National Health and Nutrition Examination Survey (NHANES) population.</p><p><strong>Methods: </strong>This present study analyzed data from the entire 1999 to 2018 NHANES cycle and ultimately included 20,570 individuals. All individuals were classified into 3 groups based on their CMI tertile, which was calculated by multiplying the waist-to-height ratio (WHtR) by the triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio. The study endpoints included all-cause mortality, cardiovascular mortality, and diabetes-related mortality. Kaplan‒Meier survival and Cox regression analyses were performed to determine the association between the CMI and mortality risk.</p><p><strong>Results: </strong>A total of 2660 (12.9%) individuals experienced all-cause death. Kaplan‒Meier survival curves suggested significant differences in mortality risk among the 3 groups (log-rank P < .001). According to the multivariate Cox regression analysis, the CMI was significantly associated with diabetes-related mortality risk (hazard ratio: 1.75, 95% CI: 1.38-2.22, P < .001) but not all-cause mortality or cardiovascular disease (CVD) mortality after adjusting for confounding risk factors.</p><p><strong>Conclusions: </strong>A higher CMI was independently associated with an increased risk of diabetes-related mortality but not all-cause mortality or CVD mortality in the NHANES population.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764962","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":"Long-chain and very long-chain ceramide levels in subjects with impaired glucose regulation.","authors":"Rumyana Dimova, Vesela Lozanova, Nevena Chakarova, Mina Serdarova, Georgi Kirilov, Valentin Lozanov, Stefano Del Prato, Tsvetalina Tankova","doi":"10.1016/j.jacl.2025.06.021","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.06.021","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to determine the ceramide subspecies profile in people with impaired 1-hour or 2-hour postload glucose during a 75 g oral glucose tolerance test (OGTT) and their association with cardiometabolic parameters.</p><p><strong>Methods: </strong>Out of 90 subjects (age 46.7 ± 10.5 years; body mass index of 32.0 ± 6.3 kg/m²) who underwent a 2-hour OGTT, 19 had normal glucose tolerance, 22 had 1-hour plasma glucose ≥8.6 mmol/L (1hrOGTT), and 49 had 2-hour >8.6 and ≤10 mmol/L (impaired glucose tolerance). Homeostatic model assessment of insulin resistance (HOMA-IR) was determined for each group and was subdivided into 2 subgroups (HOMA-IR <2.5 or ≥2.5). Areas under the curve (AUCs) for glucose, insulin, C-peptide, and triglycerides were calculated during the OGTT. Ceramides (C) were assessed by liquid chromatography-mass spectrometry on a fasting blood sample.</p><p><strong>Results: </strong>There was no significant difference across the glucose tolerance groups, as well as the subgroups depending on HOMA-IR, for all evaluated lipid markers and ratios. The AUC_C-peptide was positively associated with C16 (r = 0.21, P = .051), while a negative relationship was apparent between the insulin secretion-sensitivity index-2 and C24 (r = -0.21, P = .051), HOMA-IR ≥2.5 and the C16/24 (r = -0.22, P = .034), C18/24 (r = -0.22, P = .037), and C24:1/C24 (r = -0.24, P = .022) ratios.</p><p><strong>Conclusion: </strong>Our results demonstrate diminished C16/C24 and C18/C24 ratios in subjects with insulin resistance, and an independent relationship between C16:0 ceramide and stimulated insulinemia, and between C16 and C18 and kidney function, highlighting the leading role of specific ceramide subspecies rather than the overall ceramide levels for the cardiometabolic profile in early stages of glucose intolerance.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955826","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":"Genetic and polygenic contributions to familial hypercholesterolemia in Thailand: Implications for diagnosis and lipid management.","authors":"Phongthana Pasookhush, Apinya Surawit, Sophida Suta, Sureeporn Pumeiam, Pichanun Mongkolsucharitkul, Bonggochpass Pinsawas, Suphawan Ophakas, Korapat Mayurasakorn","doi":"10.1016/j.jacl.2025.06.020","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.06.020","url":null,"abstract":"<p><strong>Background: </strong>Familial hypercholesterolemia (FH) is a major risk factor for cardiovascular diseases; however, the issue of underdiagnosis remains a global challenge. This study investigates the prevalence of FH-associated variants in Thailand and examines the clinical and lipid profile characteristics of variant carriers to improve diagnostic strategies.</p><p><strong>Methods: </strong>We analyzed the genetic data of 4879 participants across 2 cohorts, identifying variants in LDLR, APOB, and PCSK9. A 12-single-nucleotide polymorphism (12-SNP) polygenic risk score (PRS) for low-density lipoprotein cholesterol (LDL-C) was calculated. Longitudinal lipid profiles, including LDL-C, total cholesterol (TC), triglyceride, and high-density lipoprotein cholesterol (HDL-C) were assessed to evaluate the sustained impact of FH-associated variants.</p><p><strong>Results: </strong>FH-associated variants were identified in 0.59% of participants, with 68.96% carrying variants in LDLR and 31.04% in APOB. FH-associated variant carriers had significantly higher LDL-C (125.5 mg/dL vs 107.8 mg/dL, P =0.015) and TC levels (208.5 mg/dL vs 190.0 mg/dL, P = .004) than noncarriers, though overlap in lipid profiles was observed. PRS analysis revealed that FH-associated variants contributed more significantly to LDL-C levels than polygenic factors. Long-term follow-up showed persistent elevation of LDL-C and TC in FH-associated variant carriers.</p><p><strong>Conclusion: </strong>This study provides the first prevalence analysis of FH in Thailand, highlighting the limitations of lipid-based diagnostic criteria. Incorporating genetic screening and developing tailored diagnostic criteria are critical for addressing FH underdiagnosis and improving lipid management in Thailand.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717990","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 rheumatoid arthritis and blood lipid levels: An integrated epidemiological observational analysis and Mendelian randomization study.","authors":"Junlin Yi, Qianhua Li, Rongpeng Gong, Jieli Qin, Xinqun Hu","doi":"10.1016/j.jacl.2025.06.017","DOIUrl":"10.1016/j.jacl.2025.06.017","url":null,"abstract":"<p><strong>Background: </strong>The association between rheumatoid arthritis (RA) and blood lipids remains controversial.</p><p><strong>Objective: </strong>This study aimed to investigate the association between RA and blood lipids by integrating observational and Mendelian randomization (MR) analyses.</p><p><strong>Methods: </strong>The association between the prevalence of RA and blood lipid levels was examined using data from the National Health and Nutrition Examination Survey (NHANES) (n = 24,345). Subsequently, the causality between RA and lipid and apolipoprotein levels was inferred in a 2-sample MR framework. Genetic instruments for RA (13,261 RA cases and 43,823 controls), lipids (n = 121,577), and apolipoproteins (n = 121,577) were obtained from large-scale genome-wide association studies. The statistical significance of the MR effect estimates was determined using a false discovery rate (FDR) with a <5% threshold to adjust for multiple testing.</p><p><strong>Results: </strong>In the NHANES cohort, RA was associated with lower total cholesterol (TC) (β -0.08; 95% CI -0.15, -0.02) and low-density lipoprotein cholesterol (LDL-C) (β -0.11; 95% CI -0.18, -0.05) levels after adjusting for potential confounders. In the 2-sample MR analyses, genetic liability to RA was associated with lower levels of TC (β -0.013; 95% CI -0.022, -0.004, FDR 0.011), LDL-C (β -0.017; 95% CI -0.027, -0.008, FDR 0.003), and apolipoprotein B (Apo B) (β -0.016; 95% CI -0.028, -0.004, FDR 0.015).</p><p><strong>Conclusion: </strong>RA is causally associated with lower TC, LDL-C, and Apo B levels. Clinicians should cautiously interpret lower atherogenic lipid levels in patients with RA, as these may indicate underlying disease processes.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882951","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":"Decline in LDL-C control in patients with dyslipidemia treated with PCSK9-inhibitors: The role of obesity in LDL-C target achievement.","authors":"Elena Formisano, Andrea Vignati, Almina Bertolini, Valeria Maria Barreto Spandonari, Michele Tafuro, Andrea Pasta, Samir Giuseppe Sukkar, Livia Pisciotta","doi":"10.1016/j.jacl.2025.06.018","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.06.018","url":null,"abstract":"<p><strong>Background: </strong>Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9-Is: alirocumab and evolocumab) have improved dyslipidemia management in patients with high cardiovascular risk. However, some patients fail to reach low-density lipoprotein cholesterol (LDL-C) targets.</p><p><strong>Objective: </strong>To evaluate factors influencing PCSK9-I therapy effectiveness.</p><p><strong>Methods: </strong>A retrospective study (2018-2023) analyzed adults treated with a PCSK9-I for at least 6 months with heterozygous familial hypercholesterolemia (He-FH) in primary prevention, dyslipidemia in secondary prevention, or diabetes with associated complications. Clinical, anthropometric data and lipid profiles were collected at baseline and after 6, 12, 24, and 36 months. The primary outcome was LDL-C target achievement according to European Society of Cardiology/European Atherosclerosis Society guidelines.</p><p><strong>Results: </strong>Among 180 patients, approximately 45% achieved the LDL-C target. Patients with overweight and obesity showed significantly lower LDL-C reductions compared to normal-weight patients. Those reductions for overweight patients were 47.8%, 50.0%, and 44.0%, and for obese patients were 25.6%, 29.4%, and 28.6%, whereas normal-weight patients achieved reductions of 54.5% (P = .021), 62.5% (P = .024), and 65.4% (P = .024), respectively. Multivariate analysis confirmed these findings (odds ratio [OR]: 0.18, 95% CI, 0.06-0.53, P = .002) and highlighted that He-FH was associated with lower likelihood of achieving LDL-C targets (OR: 0.35, 95% CI, 0.15-0.82, P = .015). Conversely, patients with coronary artery disease (CAD) were more likely to reach LDL-C targets (OR: 4.54, 95% CI, 1.98-10.41, P < .0001). Concomitant oral lipid-lowering therapy was linked to a higher probability of achieving LDL-C targets compared to PCSK9-I monotherapy (OR: 14.5, 95% CI 2.26-92.9, P = .005).</p><p><strong>Conclusion: </strong>Overweight, He-FH, CAD, and concomitant oral lipid-lowering therapy could influence the achievement of LDL-C target in patients treated with PCSK9-Is.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799247","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}