Journal of clinical lipidology最新文献

{"title":"Comparison of diagnostic genetic testing and clinical scoring results for familial chylomicronemia syndrome (FCS) in the 66-patient Balance study","authors":"Philippe Moulin MD, Andrew Dibble PhD, Veronica Alexander PhD, Daniel Gaudet MD, Sotirios Tsimikas MD, Robert Hegele MD, Alan Brown MD","doi":"10.1016/j.jacl.2025.04.102","DOIUrl":"10.1016/j.jacl.2025.04.102","url":null,"abstract":"<div><h3>Funding</h3><div>This study was sponsored by Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA. The first draft was written by Mary Beth DeYoung, PhD of Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA. Editorial support was provided by Red Nucleus and funded by Ionis Pharmaceu</div></div><div><h3>Background/Synopsis</h3><div>Familial chylomicronemia syndrome (FCS), a rare, pancreatitis-associated genetic disorder, is commonly misdiagnosed. An FDA-approved treatment for FCS in the United States increases the urgency for accurate, reliable and timely diagnosis. While potentially definitive, FCS diagnosis based on genetic testing may not be accessible or conclusive. Clinical scoring systems have been devised as a diagnostic alternative. For instance, the North American (NA) FCS scoring system was devised using the RAND/UCLA modified Delphi process as a practical, rapid, validated tool to diagnose FCS (Hegele et al, J Clin Lipidol 2024). The detection sensitivity of a score ≥ 45 is 89% and the specificity is 97%.</div></div><div><h3>Objective/Purpose</h3><div>To evaluate the sensitivity of the NAFCS scoring system in the 66 genetically identified FCS patients enrolled in Balance, a phase 3 study on the efficacy and safety of olezarsen. Olezarsen is an APOC3 directed antisense oligonucleotide approved by the United States FDA as an adjunct to diet to reduce triglycerides in adults with FCS.</div></div><div><h3>Methods</h3><div>NAFCS scores were calculated individually for Balance patients using established methodology. Scoring parameters include age of severe hypertriglyceridemia (sHTG) onset; body-mass index (BMI) < 25 kg/m<sup>2</sup>; history of pancreatitis; secondary factors contributing to sHTG; and laboratory values (TG > 880 mg/dL, TG/TC > 8.00, and ApoB-100 < 1.00 g/L). A NAFCS score > 45 and ≥ 60 identified patients with “likely” or “definite” genetic FCS, respectively. Genetic testing procedures and results are described in the Balance publication (PMID: 38587247).</div></div><div><h3>Results</h3><div>The mean (SD) NAFCS score overall was 66 (14); range 33 to 93. Of 66 patients, 63 (95%) and 49 (74%) had NAFCS scores ≥ 45 and ≥ 60, respectively. Variability was found in some key attributes (Table). A high proportion (> 95%) of FCS patients had TG > 880 mg/dL and ApoB-100 < 1.00 g/L at screening, nearly 80% had no secondary risk factors for sHTG, and ∼70% had a history of acute pancreatitis. More than half of patients had BMI < 25 kg/m<sup>2</sup>. Although the sample was small, patients with NAFCS scores < 45 in Balance appeared less likely to have pathogenic LPL variants than patients with scores ≥ 45 (1/3 [33%] versus 54/63 [86%], respectively).</div></div><div><h3>Conclusions</h3><div>The NAFCS score incorporates laboratory parameters, particularly low ApoB-100, which was found in nearly all FCS patients in Balance. In Balance, the NAFCS score showed a sensitivity of 74% for the highly selective score o","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 3","pages":"Page e73"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168359","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":"Bridging the gap: enhancing lipoprotein(a) testing and education in federally qualified health centers","authors":"David Peña MPH, Kristin Colson MS, Meg Yuan MPH, Eliana Collins MPH, CarriAnne Crabill BS, Jeremy Skinner BS","doi":"10.1016/j.jacl.2025.04.028","DOIUrl":"10.1016/j.jacl.2025.04.028","url":null,"abstract":"<div><h3>Funding</h3><div>Yes, Novartis is proud to support the American Heart Association's Lp(a) Federally Qualified Health Centers Discovery Project.</div></div><div><h3>Background/Synopsis</h3><div>Lipoprotein(a) [Lp(a)] is a significant genetic risk factor for atherosclerotic cardiovascular disease (ASCVD), particularly among Black/African American and South Asian populations who have been shown to have higher levels of Lp(a) compared to other groups. These populations are served by Federally Qualified Health Centers (FQHCs), which provide critical care to under-resourced and high-risk communities.</div></div><div><h3>Objective/Purpose</h3><div>The American Heart Association's (AHA) 3-year Lp(a) FQHC Discovery Project aims to assess current practices and identify barriers to Lp(a) testing in FQHCs, establish site-specific improvement goals, enhance clinician knowledge of Lp(a) and its role in ASCVD risk management, and improve patient education to support shared decision-making between clinicians and patients.</div></div><div><h3>Methods</h3><div>The AHA selected 10 FQHCs based on their 1) capacity to implement quality improvement (QI) initiatives, 2) patient education practices, 3) patient demographics, and 4) rural-urban classification. In-person qualitative interviews were conducted with clinical and quality champions to map current clinical workflows and patient pathways, identify barriers and establish goals for Lp(a) testing. The AHA program consultants analyzed the results to identify opportunities for integrating Lp(a) testing into clinical care. Proposed Lp(a) testing strategies were incorporated into monthly virtual consultations led by an AHA QI Consultant. Quarterly learning collaboratives provide opportunities to share progress, exchange best practices, and refine strategies. Findings from another initiative, the Lp(a) Discovery Project, which gathered insights from health systems with established Lp(a) testing practices, support the development of educational resources for the FQHCs.</div></div><div><h3>Results</h3><div>The cohort collectively serves over 250,000 patients including priority populations at higher risk for elevated Lp(a) levels. Baseline assessments identified barriers such as patient and clinician engagement and education, staffing, and testing costs. Notably, no significant out-of-pocket costs for Lp(a) testing have been reported by patients. Podcasts, webinars, and an eModule were developed for clinician education on Lp(a) testing, while a health lesson, care kit, infographics, and video were developed in consultation with FQHCs for culturally relevant patient education. The in-person interviews and consultations revealed that annual visits are the best opportunity for clinicians to recommend and educate patients on Lp(a) testing.</div></div><div><h3>Conclusions</h3><div>The Lp(a) FQHC Discovery Project highlights the importance of targeted interventions to enhance clinician and patient education, boost engage","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 3","pages":"Page e21"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168568","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":"Risk of acute pancreatitis among patients with hypertriglyceridemia (HTG) or severe hypertriglyceridemia (sHTG)","authors":"Kirti Batra MBA,&nbsp;Qiana Amos PhD,&nbsp;Seth Baum MD,&nbsp;Montserrat Vera-Llonch PhD,&nbsp;Daniel Soffer MD,&nbsp;Asia Sikora Kessler PhD","doi":"10.1016/j.jacl.2025.04.093","DOIUrl":"10.1016/j.jacl.2025.04.093","url":null,"abstract":"<div><h3>Background/Synopsis</h3><div>HTG is associated with an increased risk of acute pancreatitis (AP). However, real-world evidence evaluating the risk of AP at varying levels of elevated triglycerides (TG) is limited.</div></div><div><h3>Objective/Purpose</h3><div>This study evaluates the incidence of AP event in patients with HTG and sHTG levels compared to normal TG levels.</div></div><div><h3>Methods</h3><div>This retrospective cohort study was conducted using the Optum Research Database between 01 January 2016 – 31 March 2022. Adults 18 years and older with ≥ 1 diagnostic test for serum/plasma TG were included. Patients were assigned to four cohorts: normal TG (35 ≤ TG &lt; 150 mg/dL), HTG (150 ≤ TG &lt; 500 mg/dL), and sHTG (placed into 500 ≤ TG &lt; 880 mg/dL or TG ≥ 880 mg/dL cohorts). The index date was the cohort-specific earliest TG measurement. Patients had at least 12 months of pre- and post-index continuous enrollment. The primary study outcome was AP event, defined as having one of the following: ≥ 2 AP-specific medical claims; ≥ 1 claim for AP hospitalization; ≥ 1 claim for upper abdominal pain (UAP) and serum/plasma lipase or amylase level &gt; 200 U/L within 15 days of the UAP claim. Incidence rates were calculated per 100,000 person-years (PY) at risk. Kaplan-Meier analysis and an adjusted Cox proportional hazards model were conducted to estimate the risk of AP event in the HTG cohort and sHTG cohorts compared with the normal TG cohort.</div></div><div><h3>Results</h3><div>A total of 134,316 patients were identified across the four cohorts. The mean (SD) age of patients was 56.3 (15.7) years, 54% were males, and the mean follow-up was 987 days. AP incidence rates were significantly higher for the HTG (171.8), the 500 ≤ TG &lt; 880 mg/dL (377.8), and the TG ≥ 880 mg/dL (977.6) cohorts, compared to the normal TG cohort (92.2; all p &lt; 0.001). The cumulative incidence of AP events at 3 years was 0.5% in the HTG cohort, 1.1% in the 500 ≤ TG &lt; 880 mg/dL cohort, and 2.8% in the TG ≥ 880 mg/dL cohort, compared to 0.3% in the normal TG cohort (Figure; all p &lt; 0.001). In the adjusted Cox regression model, the hazard ratio (95% CI) of AP was 1.50 (1.20–1.87) in the HTG cohort, 2.63 (2.06–3.35) in the 500 ≤ TG &lt; 880 mg/dL cohort, and 4.78 (3.45–6.61) in the TG ≥ 880 mg/dL cohort, compared to the normal TG cohort (Table).</div></div><div><h3>Conclusions</h3><div>Patients with elevated TG levels had higher risk of AP event compared to patients with normal levels, with risk of AP increasing with higher TG levels, demonstrating the need for improved therapeutic interventions focused on the clinical management of sHTG.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 3","pages":"Page e67"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144167941","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 apolipoprotein B and obesity: A cross-sectional analysis of NHANES data","authors":"Jason Holligan MD,&nbsp;Moatamn Skuk MD,&nbsp;Wael Kanjo MD,&nbsp;Walter Agyeman MD,&nbsp;Elsie Kodjoe MD","doi":"10.1016/j.jacl.2025.04.080","DOIUrl":"10.1016/j.jacl.2025.04.080","url":null,"abstract":"<div><h3>Background/Synopsis</h3><div>Apolipoprotein B (apoB) plays a critical role in the development of atherosclerosis, making it an essential biomarker for cardiovascular disease (CVD). Obesity, a significant global health concern affects 40.3% of adults in the United States of America (US) according to the Centers for Disease Control and Prevention (CDC). As rates of both obesity and CVD continue to rise globally, understanding the relationship between obesity and apoB levels is crucial for developing targeted strategies to reduce cardiovascular risks. Despite its importance, few studies have explored the effect of obesity on apoB levels in a large cohort of adults in the US.</div></div><div><h3>Objective/Purpose</h3><div>This study aims to investigate the association between obesity and apoB levels among US adults.</div></div><div><h3>Methods</h3><div>This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) 2009–2016. The sample included 10,539 adults aged 18 years and older who had apoB levels measured, representing approximately 62 million non-institutionalized US adults. Participants were classified as obese (BMI ≥ 30 kg/m²) or non-obese (BMI &lt;30 kg/m²). Apo B was analyzed as a continuous variable. Linear regression was performed to assess the association between obesity and apoB levels, adjusting for potential confounders including age, sex, race, diabetes, hypertension, and socioeconomic status. Effect modification was examined by sex and age group (&lt; 65 years vs. ≥ 65 years).</div></div><div><h3>Results</h3><div>Among the 10,539 participants, the mean age was 48 years, 51% were female, and 41% were White. The average apoB level was 90.5 mg/dL. Obese adults had higher apoB levels (94 mg/dL) compared to non-obese adults (88 mg/dL). A one-unit increase in obesity was associated with a statistically significant 6.91 mg/dL increase in apoB levels [Coefficient: 6.91; p &lt; 0.001; 95% CI: 5.90, 7.95]. After adjusting for confounders, the association remained statistically significant [Coefficient: 6.66; p &lt; 0.001; 95% CI: 5.52, 7.81]. There was no significant difference in the association by sex; however, the association was stronger among younger individuals compared to older adults.</div></div><div><h3>Conclusions</h3><div>Obesity is significantly associated with higher apoB levels, particularly in younger individuals. Addressing obesity as a key component of CVD prevention strategies may help reduce apoB levels and the associated cardiovascular risk.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 3","pages":"Page e59"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144167947","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 gamification to educate internal medicine residents on managing lipids in patients with inflammatory conditions","authors":"Jack Jnani MD,&nbsp;Ji-Cheng (Jason) Hsieh MD,&nbsp;Cassie Wang MD,&nbsp;Nadim Ammari MD,&nbsp;Yisrael Wallach MD,&nbsp;Spencer Weintraub MD,&nbsp;Lauren Block MD,&nbsp;Rahul Rege MD","doi":"10.1016/j.jacl.2025.04.016","DOIUrl":"10.1016/j.jacl.2025.04.016","url":null,"abstract":"<div><h3>Background/Synopsis</h3><div>Inflammatory conditions such as human immunodeficiency virus (HIV) and autoimmune diseases increase patients’ risk of atherosclerotic cardiovascular disease (ASCVD). Trainees in the primary care setting may not be familiar with management of ASCVD risk in the setting of these conditions. Gamification, a novel educational tool, can improve learners’ engagement and knowledge to help them better manage ASCVD risk for those living with inflammatory conditions.</div></div><div><h3>Objective/Purpose</h3><div>We studied the effectiveness of gamification in educating internal medicine residents on management of ASCVD in patients with inflammatory conditions.</div></div><div><h3>Methods</h3><div>At a single large academic internal medicine residency program, we compared a resident-led virtual gamified curriculum utilizing KAHOOT® to a traditional slide-based curriculum. All residents in the program received a 1-hour case-based session summarizing American College of Cardiology, National Lipid Association and American Heart Association guidelines on enhanced cardiovascular risk in the setting of HIV and autoimmune diseases. Pre-post-surveys included knowledge questions, 5-point Likert scales (1 to 5) assessing self-reported confidence in managing cardiovascular risk and referencing guidelines, motivation to adhere to guidelines, engagement, and format preference. Matched pre-post test data and unmatched Likert scale data were analyzed with two-tailed students’ t-tests.</div></div><div><h3>Results</h3><div>65/108 (60.2%) categorical internal medicine residents received the gamified format and 43/108 (39.8%) received the traditional format. 14/65 (21.5%) residents in the gamified group and 7/43 (16.3%) in the traditional group completed pre-post tests and were analyzed as matched pairs. There was a significant increase in test performance in the gamified (pre- 0.43 to post- 0.76, p&lt;0.01) and traditional (pre- 0.55 to post- 0.81, p = 0.02) groups. There was no difference (gamified 0.33 vs. traditional 0.26, p = 0.52) in the post-pre change in test performance between groups. There were significant increases in Likert scale ratings of confidence in counseling patients and referencing guidelines in both gamified and traditional groups. There was a trend towards greater motivation to adhere to guidelines (gamified 4.5 vs. traditional 4, p = 0.06) in the gamified group. 15/21 (71.4%) of residents preferred a gamified format.</div></div><div><h3>Conclusions</h3><div>Both gamified and traditional lectures significantly improved residents’ knowledge of management of ASCVD in the setting of inflammatory conditions. Gamification was the favored method for lectures. Further research is needed to identify if gamification education on ASCVD risk in inflammatory disease can impact clinical practice and outcomes.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 3","pages":"Pages e11-e12"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168314","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":"Racial disparities in LDL-C control, ASCVD risk reclassification by statin use, coronary artery calcium scores, and the Pooled Cohort Equation","authors":"Benjamin Hsieh MD,&nbsp;Lorenzo Cotugno MD,&nbsp;Sana Saeed MD,&nbsp;Ethan Swartz MD,&nbsp;Prit Patel DO","doi":"10.1016/j.jacl.2025.04.066","DOIUrl":"10.1016/j.jacl.2025.04.066","url":null,"abstract":"<div><h3>Background/Synopsis</h3><div>ASCVD is a leading cause of morbidity and mortality, with LDL-C control essential for prevention. Significant racial disparities exist in LDL-C control, statin adherence, and ASCVD risk assessment. The Pooled Cohort Equation (PCE) estimates risk but may lack precision for racial minorities. Adding Coronary Artery Calcium Score (CACS) can refine risk stratification, but its impact on reclassification across racial groups, combined with statin adherence, is not well understood. This study addresses these gaps to improve risk assessment and reduce disparities.</div></div><div><h3>Objective/Purpose</h3><div>This study examines the interplay between LDL-C control, statin adherence, CACS, and the PCE in refining ASCVD risk stratification across racial groups. It aims to explore how CACS and PCE contribute to risk reclassification, focusing on the role of statin therapy.</div></div><div><h3>Methods</h3><div>A retrospective cohort of adults aged 40–75 without CAD from the MESA study was analyzed. Participants with complete data on LDL-C, statin use, CACS, and PCE variables (age, gender, race, blood pressure, diabetes, smoking, and cholesterol) were included. LDL-C control, statin use, and PCE-based risk were compared by race. ASCVD risk reclassification by CACS (0, 1–99, ≥ 100 HU) was assessed alongside PCE, stratified by statin adherence. Multivariable models evaluated interactions between race, statin use, CACS, and risk reclassification.</div></div><div><h3>Results</h3><div>The study included 3,282 participants. Whites exhibited the highest LDL-C control rates (mean LDL-C: 105.3 mg/dL), followed by Asians (115.6 mg/dL), Blacks (120.2 mg/dL), and Hispanics (125.4 mg/dL). Statin adherence varied significantly, with Whites showing the highest adherence rates (65%), compared to 52% in Blacks and 48% in Hispanics. CACS and PCE-based risk estimates demonstrated racial disparities, with 31.6% of Blacks having CACS = 0 compared to 31.6% of Whites. Reclassification of ASCVD risk by combining PCE and CACS led to a reduction in predicted risk for 15% of Black participants compared to 10% of Whites. Statin therapy improved CACS- and PCE-based reclassification consistency, especially among racial minorities. Interaction models demonstrated that LDL-C control, PCE-estimated risk, and statin adherence significantly influenced reclassification outcomes, with race modifying these effects.</div></div><div><h3>Conclusions</h3><div>Racial disparities in LDL-C control, statin adherence, and CACS distribution affect PCE-based ASCVD risk estimation. Incorporating CACS and PCE improves stratification, especially for minorities. These findings underscore the importance of integrating statin adherence, PCE, and advanced imaging techniques into personalized risk assessment strategies. Further research should assess the long-term clinical impact.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 3","pages":"Page e50"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168736","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 causal association between lipid-lowering strategies and risk of intracranial aneurysms: A drug-target Mendelian randomization study","authors":"Da Zhou MD, PhD ,&nbsp;Jiahao Song MD ,&nbsp;Guangyu Han MD ,&nbsp;Xiaoming Zhang MD ,&nbsp;Xunming Ji MD, PhD ,&nbsp;Ran Meng MD, PhD","doi":"10.1016/j.jacl.2025.01.003","DOIUrl":"10.1016/j.jacl.2025.01.003","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Observational studies have suggested potential correlations between unfavorable lipid profiles and the occurrence of intracranial aneurysms (IAs), proposing that lipid-lowering therapies might curb IA progression and prevent rupture. This study aimed to explore the causal impacts of lipid-reducing strategies on the risk of IAs.</div></div><div><h3>METHODS</h3><div>We employed 3 genetic tools as proxies for our exposures and assessed causal effects using outcome genome-wide association study data from the FinnGen Biobank. Single nucleotide polymorphisms strongly associated with low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol, and triglycerides, located within ±100 kb of the region of target genes, were selected as instrumental variables for drug-target Mendelian randomization (MR). Additionally, gene expression and protein MR analyses were conducted to elucidate the causal effects of lipid levels from transcriptional and translational perspectives, using two-sample MR (TSMR) and summary-data-based MR (SMR).</div></div><div><h3>RESULTS</h3><div>Drug-target MR analysis revealed that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition-mediated LDL-C reduction was associated with an increased risk of IA development (odds ratio [OR] = 1.406, <em>P</em> = 3.28E-09). In contrast, protein MR demonstrated that higher PCSK9 expression had protective effects against IA incidence (OR_TSMR = 0.896, <em>P</em> = 1.79E-03; OR_SMR = 0.881, <em>P</em> = 1.78E-02). Subgroup analyses further suggested that PCSK9 might reduce the risk of IA rupture (OR_TSMR = 0.893, <em>P</em> = 1.08E-02; OR_SMR = 0.866, <em>P</em> = 3.39E-02).</div></div><div><h3>CONCLUSION</h3><div>Our MR analyses indicated a potential causal relationship between higher PCSK9 expression and a reduced risk of both IA formation and rupture, highlighting the dual role of PCSK9 inhibitors in cerebrovascular disease. Hence, careful consideration is warranted when prescribing PCSK9 inhibitors, particularly in patients at risk for developing IAs.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 3","pages":"Pages 670-678"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468133","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":"Atherogenic lipoproteins associate with loss of glycemic control in youth-onset type 2 diabetes: Results from the TODAY study","authors":"Lorraine E. Levitt Katz MD ,&nbsp;Samuel S. Gidding MD ,&nbsp;James D. Otvos PhD ,&nbsp;Kimberly L. Drews PhD ,&nbsp;Fida Bacha MD ,&nbsp;Steven Willi MD ,&nbsp;Santica Marcovina PhD, ScD ,&nbsp;Siripoom McKay MD ,&nbsp;Ruth S. Weinstock MD, PhD ,&nbsp;TODAY Study Group","doi":"10.1016/j.jacl.2025.01.005","DOIUrl":"10.1016/j.jacl.2025.01.005","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Type 2 diabetes (T2D) in adolescents is associated with an unfavorable lipid profile, but lipoprotein particle subspecies and branched-chain amino acid (BCAA) data are scarce.</div></div><div><h3>OBJECTIVE</h3><div>To evaluate lipoprotein particle distributions, lipoprotein insulin resistance index (LP-IR), and BCAA levels longitudinally and their relationships with sex, race/ethnicity, treatment, and loss of glycemic control in adolescents with youth-onset T2D.</div></div><div><h3>METHODS</h3><div>Participants from the TODAY study (<em>n</em> = 348) had samples analyzed yearly for glycated hemoglobin and nuclear magnetic resonance lipoprotein and BCAA assessments.</div></div><div><h3>RESULTS</h3><div>At baseline, participants with T2D were 13.7 years old with T2D, obesity, and from racial and ethnic minority groups (32.2% Non-Hispanic Black [NHB], 43.7% Hispanic). Smaller low-density lipoprotein (LDL) and larger very low-density lipoprotein (VLDL) sizes, higher high-density lipoprotein (HDL) particle number, and increased LP-IR score predicted worsening of glycemic control. LDL, HDL, and VLDL particle numbers increased over 3 years with weaker trends for decreasing LDL and HDL size. LP-IR and BCAA levels were higher longitudinally in those who lost glycemic control. Females had larger HDL size than males at baseline and throughout. NHBs had the largest LDL and HDL sizes, smaller VLDL size, and lower LP-IR and BCAA.</div></div><div><h3>CONCLUSION</h3><div>These data in youth with T2D demonstrate a progressive atherogenic lipoprotein phenotype over 3 years. Increased LP-IR and BCAA are associated with worsening glycemic control and may be contributing to the premature development of atherosclerosis in youth with T2D.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 3","pages":"Pages 628-637"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605118","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":"Safety and effectiveness of evinacumab in an infant with homozygous familial hypercholesterolemia: A new renaissance for the very young?","authors":"Elena Fornari MD ,&nbsp;Claudia Stefanutti MD, PhD ,&nbsp;Valentina Mancioppi MD ,&nbsp;Gerald F. Watts MD, PhD ,&nbsp;Livia Pisciotta MD, PhD ,&nbsp;Anita Morandi MD, PhD ,&nbsp;Claudio Maffeis MD","doi":"10.1016/j.jacl.2025.02.012","DOIUrl":"10.1016/j.jacl.2025.02.012","url":null,"abstract":"<div><div>The rare homozygous form of familial hypercholesterolemia (HoFH) is characterized by extremely high low-density lipoprotein (LDL) cholesterol levels, typically exceeding 13 mmol/L (500 mg/dL), and a variable phenotype that may include marked premature atherosclerotic cardiovascular disease. HoFH with null-null LDL receptor mutations can be highly resistant to standard pharmacological therapies. The standard of care treatment option is lipoprotein apheresis (LA). However, LA is not commonly available, is technically demanding, and is relatively invasive and arduous for very young patients. Here we report effective lowering of the LDL cholesterol in a 13-month-old child with HoFH treated with evinacumab, initially at a low dose (7.5 mg/kg), later increased to 15 mg/kg/28 days. The decision was made after the failure of standard drug therapies in a sibling with the same null-null mutation in the LDL receptor, submitted to liver transplantation, who had severe complications. The treatment with evinacumab was safe and effective; LDL cholesterol, triglycerides, and apolipoprotein B concentrations all decreased by over 80%. Our findings suggest that evinacumab is a safe and effective option for treating very young patients with HoFH who do not respond to conventional therapies.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 3","pages":"Pages 689-694"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788204","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":"Accelerating evidence generation to implementation in cardiometabolic health: Establishment of the LATTICE Consortium","authors":"Ankeet Bhatt MD,&nbsp;Leandro Boer MD,&nbsp;Gemme Campbell-Salome PhD,&nbsp;Erica Davis,&nbsp;Nihar Desai MD,&nbsp;Jyothis George MD,&nbsp;Ty Gluckman MD,&nbsp;Lisa Head PharmD,&nbsp;Francoise Marvel MD,&nbsp;Marc Penn MD,&nbsp;Eric Peterson MD,&nbsp;Nishant Shah MD,&nbsp;Katherine Wilemon,&nbsp;Bethany Kalich PharmD,&nbsp;Seth Martin MD,&nbsp;Laney Jones PharmD","doi":"10.1016/j.jacl.2025.04.008","DOIUrl":"10.1016/j.jacl.2025.04.008","url":null,"abstract":"<div><h3>Background/Synopsis</h3><div>Recent scientific advancements have led to the development of innovative therapies to reduce the risk of cardiometabolic events, offering new hope to address the world's leading cause of mortality. However, the time from evidence generation in the research-setting to implementation in the care-setting is elongated, has resulted in a high rate of cardiovascular and metabolic consequences for patients, clinicians, and health systems in the United States.</div></div><div><h3>Objective/Purpose</h3><div>Improved collaboration among patients, clinicians, health systems, payers, patient advocacy, and life science companies to translate evidence-based advancements into clinical practice is key to closing this health care gap.</div></div><div><h3>Methods</h3><div>Utilizing implementation science theories, methods, and frameworks can improve translation of evidence-based practices to improve cardiometabolic care. To close the gaps in cardiometabolic care, we will evaluate implementation tools, methodologies, and strategies. We will then measure both implementation and health outcomes.</div></div><div><h3>Results</h3><div>We describe the establishment of the LATTICE consortium, Leading Awareness to Action through Implementation of Cardiometabolic Efforts. LATTICE is a first-of-its-kind community dedicated to addressing cardiometabolic patient needs through implementation efforts (Figure). The LATTICE consortium helps unite partners contributing to the overall mission of improving cardiometabolic health by creating an inclusive platform for sharing evidence-based tools, methodologies, and strategies and collaborating to improve the effectiveness of cardiometabolic patient care at scale.</div></div><div><h3>Conclusions</h3><div>Success of LATTICE consortium will be measured by reducing time from evidence generation to implementation, improved awareness, and downstream implementation by individuals of successful, scalable, and sustainable care strategies that close cardiometabolic care gaps in meaningful ways.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 3","pages":"Pages e5-e6"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144167920","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}