Pub Date : 2025-12-07DOI: 10.1016/j.jacl.2025.12.006
Soroush Masrouri, Navid Ebrahimi, Diar Zooravar, Michael D Shapiro, Fereidoun Azizi, Farzad Hadaegh
Background: To examine associations between metabolic syndrome (MetS), its components, and MetS subgroups based on the absence or presence of hypertension (HTN) and diabetes mellitus (DM), with incident myocardial infarction (MI).
Methods: Among 7824 Tehran Lipid and Glucose Study participants (mean age 46.9 years; 44.9% men) without baseline cardiovascular disease, multivariable Cox models and restricted cubic spline analyses assessed the associations of MetS, its subgroups, and components with incident MI.
Results: Of the 7824 participants included, 4092 (52.3%) were free of MetS. Among participants with MetS, 1847 (49.5%) had neither DM nor HTN, 1217 (32.6%) had HTN only (DM-/HTN+), 330 (8.8%) had DM only (DM+/HTN-), and 338 (9.1%) had both DM and HTN (DM+/HTN+). During a median follow-up of 19.9 years, 252 MI events occurred. Compared with MetS-free individuals, the adjusted hazard ratio (HR) of MetS for incident MI was 2.04 (95% CI: 1.54-2.70). HRs were 1.41 (1.00-1.99) for MetS (DM-/HTN-), 2.06 (1.44-2.95) for MetS (DM-/HTN+), 3.40 (2.15-5.38) for MetS (DM+/HTN-), and 5.09 (3.33-7.81) for MetS (DM+/HTN+) subgroups. Individuals with MetS but without the elevated glucose component or HTN were still at increased risk of MI. Using the American College of Cardiology/American Heart Association definition of HTN did not alter the findings. All MetS components showed significant associations with MI. After adjustment for the other MetS components, elevated waist circumference (HR: 1.47, 95% CI: 1.09-1.98) and elevated blood pressure (1.50; 1.14-1.98) components were associated with higher risk of MI.
Conclusion: MetS in the absence of HTN and DM conferred a greater risk of MI.
{"title":"Myocardial infarction risk and the clinical significance of metabolic syndrome in the absence of hypertension and diabetes: Insights from a large cohort screening population.","authors":"Soroush Masrouri, Navid Ebrahimi, Diar Zooravar, Michael D Shapiro, Fereidoun Azizi, Farzad Hadaegh","doi":"10.1016/j.jacl.2025.12.006","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.12.006","url":null,"abstract":"<p><strong>Background: </strong>To examine associations between metabolic syndrome (MetS), its components, and MetS subgroups based on the absence or presence of hypertension (HTN) and diabetes mellitus (DM), with incident myocardial infarction (MI).</p><p><strong>Methods: </strong>Among 7824 Tehran Lipid and Glucose Study participants (mean age 46.9 years; 44.9% men) without baseline cardiovascular disease, multivariable Cox models and restricted cubic spline analyses assessed the associations of MetS, its subgroups, and components with incident MI.</p><p><strong>Results: </strong>Of the 7824 participants included, 4092 (52.3%) were free of MetS. Among participants with MetS, 1847 (49.5%) had neither DM nor HTN, 1217 (32.6%) had HTN only (DM-/HTN+), 330 (8.8%) had DM only (DM+/HTN-), and 338 (9.1%) had both DM and HTN (DM+/HTN+). During a median follow-up of 19.9 years, 252 MI events occurred. Compared with MetS-free individuals, the adjusted hazard ratio (HR) of MetS for incident MI was 2.04 (95% CI: 1.54-2.70). HRs were 1.41 (1.00-1.99) for MetS (DM-/HTN-), 2.06 (1.44-2.95) for MetS (DM-/HTN+), 3.40 (2.15-5.38) for MetS (DM+/HTN-), and 5.09 (3.33-7.81) for MetS (DM+/HTN+) subgroups. Individuals with MetS but without the elevated glucose component or HTN were still at increased risk of MI. Using the American College of Cardiology/American Heart Association definition of HTN did not alter the findings. All MetS components showed significant associations with MI. After adjustment for the other MetS components, elevated waist circumference (HR: 1.47, 95% CI: 1.09-1.98) and elevated blood pressure (1.50; 1.14-1.98) components were associated with higher risk of MI.</p><p><strong>Conclusion: </strong>MetS in the absence of HTN and DM conferred a greater risk of MI.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146085909","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}
Background: A large evidence base supports lipid lowering to reduce atherosclerotic cardiovascular disease (ASCVD) morbidity and mortality. Despite guideline-recommended lipid-lowering therapies (LLT), gender-based disparities in lipid management persist, with women less likely to be treated aggressively and achieve optimal low-density lipoprotein cholesterol (LDL-C) levels.
Objective: We aimed to investigate whether provider gender impacted lipid treatment gaps.
Methods: We conducted a retrospective chart review of 364,021 adults within a large health system who underwent lipid testing between 2022 and 2023. Demographic, clinical, and prescribing data were abstracted from electronic health records. Optimal LDL-C was defined based on ASCVD risk.
Results: Women had higher mean LDL-C (108 vs 102 mg/dL, P < .0001) and were less likely to achieve an LDL-C of <100 mg/dL (41% vs 47%, P < .0001) compared to men. Among those with ASCVD, only 31% of women vs 47% of men achieved an LDL-C <70 mg/dL (P < .0001). Women were less likely to be prescribed statins (26% vs 33%, P < .0001) in the overall population and high-intensity statins (23% vs 31%, P < .0001) in the ASCVD population than men. No prescribing difference was noted between male and female providers across specialties.
Conclusion: Women with or at risk for ASCVD experience lower rates of LLT prescription and LDL-C goal attainment compared to men. These disparities underscore the need for targeted interventions to improve LDL-C goal attainment in women.
背景:大量证据支持降脂可降低动脉粥样硬化性心血管疾病(ASCVD)的发病率和死亡率。尽管指南推荐了降脂疗法(LLT),但基于性别的脂质管理差异仍然存在,女性不太可能接受积极治疗并达到最佳低密度脂蛋白胆固醇(LDL-C)水平。目的:我们旨在调查提供者性别是否影响脂质治疗间隙。方法:我们对一个大型卫生系统中364,021名成年人进行了回顾性图表回顾,这些成年人在2022年至2023年间进行了脂质检测。人口统计、临床和处方数据从电子健康记录中提取。最优LDL-C是根据ASCVD风险来定义的。结果:女性的平均LDL-C较高(108mg /dL vs 102mg /dL, P < 0.0001),并且达到以下LDL-C的可能性较低:结论:与男性相比,患有或有ASCVD风险的女性的LLT处方率和LDL-C目标达到率较低。这些差异强调需要有针对性的干预措施,以提高妇女低密度脂蛋白目标的实现。
{"title":"Gender differences in lipid management, LDL-C goal attainment, and prescribing practices.","authors":"Natasha Vartak, Caroline Ong, Xueqi Huang, Spencer Weintraub, Nisha Parikh, Stacey Rosen, Eugenia Gianos","doi":"10.1016/j.jacl.2025.12.008","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.12.008","url":null,"abstract":"<p><strong>Background: </strong>A large evidence base supports lipid lowering to reduce atherosclerotic cardiovascular disease (ASCVD) morbidity and mortality. Despite guideline-recommended lipid-lowering therapies (LLT), gender-based disparities in lipid management persist, with women less likely to be treated aggressively and achieve optimal low-density lipoprotein cholesterol (LDL-C) levels.</p><p><strong>Objective: </strong>We aimed to investigate whether provider gender impacted lipid treatment gaps.</p><p><strong>Methods: </strong>We conducted a retrospective chart review of 364,021 adults within a large health system who underwent lipid testing between 2022 and 2023. Demographic, clinical, and prescribing data were abstracted from electronic health records. Optimal LDL-C was defined based on ASCVD risk.</p><p><strong>Results: </strong>Women had higher mean LDL-C (108 vs 102 mg/dL, P < .0001) and were less likely to achieve an LDL-C of <100 mg/dL (41% vs 47%, P < .0001) compared to men. Among those with ASCVD, only 31% of women vs 47% of men achieved an LDL-C <70 mg/dL (P < .0001). Women were less likely to be prescribed statins (26% vs 33%, P < .0001) in the overall population and high-intensity statins (23% vs 31%, P < .0001) in the ASCVD population than men. No prescribing difference was noted between male and female providers across specialties.</p><p><strong>Conclusion: </strong>Women with or at risk for ASCVD experience lower rates of LLT prescription and LDL-C goal attainment compared to men. These disparities underscore the need for targeted interventions to improve LDL-C goal attainment in women.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911819","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}
Pub Date : 2025-12-05DOI: 10.1016/j.jacl.2025.12.004
Havva Yazıcı, Ebru Canda, Fehime Erdem, Ayşe Yüksel Yanbolu, Sakina Mammadova, Sedef Alpdoğan, Yasemin Atik Altınok, Ayça Aykut, Haluk Akın, Deniz Yılmaz Karapınar, Sema Kalkan Uçar, Robert A Hegele, Mahmut Çoker
Background: Familial hypercholesterolemia (FH) is a genetic disorder characterized by impaired clearance of low-density lipoprotein cholesterol (LDL-C), leading to severe hypercholesterolemia and increased risk of premature cardiovascular disease (CVD). Our study aims to describe and compare the clinical, biochemical, and genetic profiles of pediatric patients diagnosed with FH based on LDL-C levels exceeding 400 mg/dL (10.4 mmol/L) and confirmed by biallelic pathogenic variants in low-density lipoprotein receptor (LDLR) or low-density lipoprotein receptor adapter protein-1 (LDLRAP1) genes.
Methods: This retrospective cohort study included 39 pediatric patients diagnosed with FH at a tertiary care center. Clinical data were analyzed, including age at diagnosis, family history, lipid profile, presence of xanthomas, and cardiovascular complications. Molecular analysis was conducted using next-generation sequencing (NGS) and Sanger sequencing to confirm pathogenic variants. Statistical comparisons were performed between the LDLR and LDLRAP1 variant groups regarding lipid profiles, treatment response, and cardiovascular outcomes.
Results: Among 39 patients, 32 and 7 had pathogenic variants in LDLR and LDLRAP1 genes, respectively. Genetic analysis identified 27 unique pathogenic variants in LDLR (including 5 novel mutations) and 4 in LDLRAP1 causal for autosomal recessive hypercholesterolemia (ARH), highlighting the molecular diversity of FH. Compared to the LDLR variant group, LDLRAP1 variant patients had significantly lower untreated LDL-C levels (640.0 ± 155.6 mg/dL [16.6 ± 4.0 mmol/L] vs 506.9 ± 130.1 mg/dL [13.1 ± 3.4 mmol/L], P = .026] and showed a superior response to lipid-lowering therapy (LLT), with a greater percentage (70.6% ± 12.0%) reduction in LDL-C levels (P = .015). While xanthomas were present in 62.5% of LDLR variant patients, they were less frequent (42.9%) in the LDLRAP1 group (P = .107). Cardiovascular complications were observed exclusively in LDLR variant patients. Fourteen patients required lipoprotein apheresis (LA), and one underwent liver transplantation due to severe aortic stenosis.
Conclusion: This study highlights the importance of genetic testing in differentiating classical semidominant homozygous FH from ARH, given their phenotypic overlap but distinct treatment responses. LDLRAP1 variant patients with ARH exhibit better LDL-C reductions with conventional LLT, suggesting a milder phenotype. Early diagnosis, aggressive LLT, and novel treatments are essential to mitigate cardiovascular risk. Future studies with larger cohorts and long-term follow-ups are needed to refine treatment strategies for pediatric FH.
背景:家族性高胆固醇血症(FH)是一种以低密度脂蛋白胆固醇(LDL-C)清除受损为特征的遗传性疾病,可导致严重的高胆固醇血症和过早心血管疾病(CVD)的风险增加。我们的研究旨在描述和比较基于LDL-C水平超过400 mg/dL (10.4 mmol/L)并通过低密度脂蛋白受体(LDLR)或低密度脂蛋白受体适配器蛋白-1 (LDLRAP1)基因双等位致病变异确诊为FH的儿科患者的临床、生化和遗传谱。方法:本回顾性队列研究纳入39例在三级保健中心诊断为FH的儿童患者。分析临床资料,包括诊断年龄、家族史、血脂、黄瘤的存在和心血管并发症。采用新一代测序(NGS)和Sanger测序进行分子分析,以确定致病变异。在LDLR和LDLRAP1变异组之间进行脂质谱、治疗反应和心血管结局的统计比较。结果:39例患者中,LDLR和LDLRAP1基因分别有32例和7例致病性变异。遗传分析确定了LDLR中27个独特的致病变异(包括5个新突变)和LDLRAP1中4个常染色体隐性高胆固醇血症(ARH)的致病变异,突出了FH的分子多样性。与LDLR变异组相比,LDLRAP1变异患者的LDL-C水平显著低于未治疗组(640.0±155.6 mg/dL[16.6±4.0 mmol/L] vs 506.9±130.1 mg/dL[13.1±3.4 mmol/L], P = 0.026),并且对降脂治疗(LLT)表现出更好的反应,LDL-C水平降低的百分比(70.6%±12.0%)更高(P = 0.015)。62.5%的LDLR变异患者存在黄瘤,而LDLRAP1组的黄瘤发生率较低(42.9%)(P = 0.107)。心血管并发症仅在LDLR变异患者中观察到。14例患者需要脂蛋白分离(LA), 1例患者因严重主动脉瓣狭窄接受肝移植。结论:本研究强调了基因检测在区分经典半显性纯合子FH和ARH方面的重要性,因为它们的表型重叠,但治疗反应不同。LDLRAP1变异的ARH患者在常规LLT中表现出更好的LDL-C降低,表明表型较轻。早期诊断、积极的LLT和新的治疗方法对于降低心血管风险至关重要。未来的研究需要更大的队列和长期随访,以完善儿童FH的治疗策略。
{"title":"Severe hypercholesterolemia in a pediatric cohort: Familial homozygous and autosomal recessive hypercholesterolemia.","authors":"Havva Yazıcı, Ebru Canda, Fehime Erdem, Ayşe Yüksel Yanbolu, Sakina Mammadova, Sedef Alpdoğan, Yasemin Atik Altınok, Ayça Aykut, Haluk Akın, Deniz Yılmaz Karapınar, Sema Kalkan Uçar, Robert A Hegele, Mahmut Çoker","doi":"10.1016/j.jacl.2025.12.004","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.12.004","url":null,"abstract":"<p><strong>Background: </strong>Familial hypercholesterolemia (FH) is a genetic disorder characterized by impaired clearance of low-density lipoprotein cholesterol (LDL-C), leading to severe hypercholesterolemia and increased risk of premature cardiovascular disease (CVD). Our study aims to describe and compare the clinical, biochemical, and genetic profiles of pediatric patients diagnosed with FH based on LDL-C levels exceeding 400 mg/dL (10.4 mmol/L) and confirmed by biallelic pathogenic variants in low-density lipoprotein receptor (LDLR) or low-density lipoprotein receptor adapter protein-1 (LDLRAP1) genes.</p><p><strong>Methods: </strong>This retrospective cohort study included 39 pediatric patients diagnosed with FH at a tertiary care center. Clinical data were analyzed, including age at diagnosis, family history, lipid profile, presence of xanthomas, and cardiovascular complications. Molecular analysis was conducted using next-generation sequencing (NGS) and Sanger sequencing to confirm pathogenic variants. Statistical comparisons were performed between the LDLR and LDLRAP1 variant groups regarding lipid profiles, treatment response, and cardiovascular outcomes.</p><p><strong>Results: </strong>Among 39 patients, 32 and 7 had pathogenic variants in LDLR and LDLRAP1 genes, respectively. Genetic analysis identified 27 unique pathogenic variants in LDLR (including 5 novel mutations) and 4 in LDLRAP1 causal for autosomal recessive hypercholesterolemia (ARH), highlighting the molecular diversity of FH. Compared to the LDLR variant group, LDLRAP1 variant patients had significantly lower untreated LDL-C levels (640.0 ± 155.6 mg/dL [16.6 ± 4.0 mmol/L] vs 506.9 ± 130.1 mg/dL [13.1 ± 3.4 mmol/L], P = .026] and showed a superior response to lipid-lowering therapy (LLT), with a greater percentage (70.6% ± 12.0%) reduction in LDL-C levels (P = .015). While xanthomas were present in 62.5% of LDLR variant patients, they were less frequent (42.9%) in the LDLRAP1 group (P = .107). Cardiovascular complications were observed exclusively in LDLR variant patients. Fourteen patients required lipoprotein apheresis (LA), and one underwent liver transplantation due to severe aortic stenosis.</p><p><strong>Conclusion: </strong>This study highlights the importance of genetic testing in differentiating classical semidominant homozygous FH from ARH, given their phenotypic overlap but distinct treatment responses. LDLRAP1 variant patients with ARH exhibit better LDL-C reductions with conventional LLT, suggesting a milder phenotype. Early diagnosis, aggressive LLT, and novel treatments are essential to mitigate cardiovascular risk. Future studies with larger cohorts and long-term follow-ups are needed to refine treatment strategies for pediatric FH.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010655","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}
Pub Date : 2025-12-04DOI: 10.1016/j.jacl.2025.12.003
Yuliasih Yuliasih, Betty Rachma, Henry Sutanto
Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease associated with a markedly increased risk of cardiovascular disease (CVD) that is not fully explained by traditional risk factors. Lipoprotein(a) [Lp(a)], a genetically determined lipoprotein with proatherogenic, prothrombotic, and proinflammatory properties, has emerged as a potential contributor to this excess cardiovascular burden. Growing evidence suggests that Lp(a) may represent a mechanistic link between chronic inflammation, immune dysregulation, and accelerated atherosclerosis in RA.
Sources of material: This narrative review synthesizes evidence from observational studies, mechanistic research, genetic analyses, biomarker investigations, and emerging therapeutic trials examining Lp(a) in RA. Relevant literature was identified through comprehensive searches of major biomedical databases, with emphasis on studies addressing pathophysiology, cardiovascular outcomes, disease activity, and treatment effects on Lp(a).
Abstract of findings: RA patients frequently exhibit elevated Lp(a) levels, particularly in the presence of active systemic inflammation. Lp(a) contributes to vascular injury through enhanced arterial wall retention, carriage of oxidized phospholipids, endothelial activation, and impaired fibrinolysis. Clinical studies associate elevated Lp(a) with subclinical atherosclerosis, arterial stiffness, and increased cardiovascular events in RA, independent of conventional lipid parameters. Inflammatory cytokines, particularly interleukin-6 (IL-6), appear to modulate Lp(a) metabolism, providing a biological rationale for the Lp(a)-lowering effects observed with IL-6 receptor blockade. Advances in standardized assays, genetic insights into LPA polymorphisms, and novel RNA-based therapies have revitalized interest in Lp(a) as both a biomarker and therapeutic target in RA.
Conclusion: Lp(a) occupies a critical intersection between inflammation and atherosclerosis in RA. Incorporating Lp(a) into cardiovascular risk stratification and exploring targeted therapies may enable more precise, integrated management of cardiovascular risk in RA patients, warranting dedicated prospective studies.
{"title":"Lipoprotein(a) at the crossroads of inflammation and atherosclerosis in rheumatoid arthritis: A narrative review.","authors":"Yuliasih Yuliasih, Betty Rachma, Henry Sutanto","doi":"10.1016/j.jacl.2025.12.003","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.12.003","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is a systemic autoimmune disease associated with a markedly increased risk of cardiovascular disease (CVD) that is not fully explained by traditional risk factors. Lipoprotein(a) [Lp(a)], a genetically determined lipoprotein with proatherogenic, prothrombotic, and proinflammatory properties, has emerged as a potential contributor to this excess cardiovascular burden. Growing evidence suggests that Lp(a) may represent a mechanistic link between chronic inflammation, immune dysregulation, and accelerated atherosclerosis in RA.</p><p><strong>Sources of material: </strong>This narrative review synthesizes evidence from observational studies, mechanistic research, genetic analyses, biomarker investigations, and emerging therapeutic trials examining Lp(a) in RA. Relevant literature was identified through comprehensive searches of major biomedical databases, with emphasis on studies addressing pathophysiology, cardiovascular outcomes, disease activity, and treatment effects on Lp(a).</p><p><strong>Abstract of findings: </strong>RA patients frequently exhibit elevated Lp(a) levels, particularly in the presence of active systemic inflammation. Lp(a) contributes to vascular injury through enhanced arterial wall retention, carriage of oxidized phospholipids, endothelial activation, and impaired fibrinolysis. Clinical studies associate elevated Lp(a) with subclinical atherosclerosis, arterial stiffness, and increased cardiovascular events in RA, independent of conventional lipid parameters. Inflammatory cytokines, particularly interleukin-6 (IL-6), appear to modulate Lp(a) metabolism, providing a biological rationale for the Lp(a)-lowering effects observed with IL-6 receptor blockade. Advances in standardized assays, genetic insights into LPA polymorphisms, and novel RNA-based therapies have revitalized interest in Lp(a) as both a biomarker and therapeutic target in RA.</p><p><strong>Conclusion: </strong>Lp(a) occupies a critical intersection between inflammation and atherosclerosis in RA. Incorporating Lp(a) into cardiovascular risk stratification and exploring targeted therapies may enable more precise, integrated management of cardiovascular risk in RA patients, warranting dedicated prospective studies.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911974","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}
Pub Date : 2025-12-04DOI: 10.1016/j.jacl.2025.12.002
Shoshana H Bardach, Skye Chernichky-Karcher, Allison Hawke, Diane MacDougall, Katherine Wilemon, Laurence S Sperling
Background: Lipoprotein(a) (Lp[a]), is a significant risk factor for cardiovascular disease, yet is infrequently measured.
Objective: A qualitative investigation was designed to better understand the barriers and facilitators to Lp(a) testing.
Methods: Focus groups were held with clinicians (n = 26) and at-risk individuals (n = 24). Transcripts were thematically analyzed, guided by the Integrated Screening Action Model (I-SAM). Consistent with the I-SAM, barriers and facilitators of Lp(a) measurement were categorized as motivational, capability, and opportunity factors.
Results: Facilitators identified included perceived clinical utility, emotional reassurance associated with a newfound understanding of prior events, the ability to use Lp(a) knowledge to better prepare for the future, as well as active requests for testing. Barriers identified included a lack of perceived clinical utility and the potential to cause emotional distress with results, uncertainty and knowledge limitations around Lp(a), cost-related concerns, low expectations for testing, and clinician reluctance to test.
Conclusions: This analysis highlights that Lp(a) testing decisions are multifactorial, providing multiple opportunities for intervention and improvement. Strategies to convey how Lp(a) measurement can inform risk assessment and treatment approaches may be foundational to encouraging more widespread testing.
{"title":"Examining barriers and facilitators to testing lipoprotein(a): Understanding at-risk individual and clinician perspectives.","authors":"Shoshana H Bardach, Skye Chernichky-Karcher, Allison Hawke, Diane MacDougall, Katherine Wilemon, Laurence S Sperling","doi":"10.1016/j.jacl.2025.12.002","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.12.002","url":null,"abstract":"<p><strong>Background: </strong>Lipoprotein(a) (Lp[a]), is a significant risk factor for cardiovascular disease, yet is infrequently measured.</p><p><strong>Objective: </strong>A qualitative investigation was designed to better understand the barriers and facilitators to Lp(a) testing.</p><p><strong>Methods: </strong>Focus groups were held with clinicians (n = 26) and at-risk individuals (n = 24). Transcripts were thematically analyzed, guided by the Integrated Screening Action Model (I-SAM). Consistent with the I-SAM, barriers and facilitators of Lp(a) measurement were categorized as motivational, capability, and opportunity factors.</p><p><strong>Results: </strong>Facilitators identified included perceived clinical utility, emotional reassurance associated with a newfound understanding of prior events, the ability to use Lp(a) knowledge to better prepare for the future, as well as active requests for testing. Barriers identified included a lack of perceived clinical utility and the potential to cause emotional distress with results, uncertainty and knowledge limitations around Lp(a), cost-related concerns, low expectations for testing, and clinician reluctance to test.</p><p><strong>Conclusions: </strong>This analysis highlights that Lp(a) testing decisions are multifactorial, providing multiple opportunities for intervention and improvement. Strategies to convey how Lp(a) measurement can inform risk assessment and treatment approaches may be foundational to encouraging more widespread testing.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911874","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}
Pub Date : 2025-12-04DOI: 10.1016/j.jacl.2025.12.001
Taha Mansoor, Mahmoud Ismayl, Salim S Virani, Vijay Nambi, Arunima Misra, Xiaoming Jia, Marat Fudim, Stephen J Greene, Laurence Sperling, Sachin Parikh, Mahmoud Al Rifai, Santhosh Kg Koshy, Dmitry Abramov, Abdul Mannan Khan Minhas
Background: Heart transplantation represents an increasingly utilized procedure for end-stage heart failure patients.
Current evidence: Cardiac allograft vasculopathy (CAV) is a post-transplant complication of pathological vasculature remodeling and remains an important cause for long-term graft failure and mortality. Current preventive strategies for CAV include optimization of vascular risk factors and pharmacotherapy with statins and immunosuppressants.
Conclusion: Despite demonstrated post-transplant mortality benefit and reduction in CAV with statins, the role of other pharmacotherapies on CAV reduction through LDL-C lowering remains less established. This review explores established evidence as well as evolving pathways for LDL-C lowering strategies to prevent CAV.
{"title":"Lipid-lowering therapies to target cardiac allograft vasculopathy after heart transplantation: Current evidence and future directions.","authors":"Taha Mansoor, Mahmoud Ismayl, Salim S Virani, Vijay Nambi, Arunima Misra, Xiaoming Jia, Marat Fudim, Stephen J Greene, Laurence Sperling, Sachin Parikh, Mahmoud Al Rifai, Santhosh Kg Koshy, Dmitry Abramov, Abdul Mannan Khan Minhas","doi":"10.1016/j.jacl.2025.12.001","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.12.001","url":null,"abstract":"<p><strong>Background: </strong>Heart transplantation represents an increasingly utilized procedure for end-stage heart failure patients.</p><p><strong>Current evidence: </strong>Cardiac allograft vasculopathy (CAV) is a post-transplant complication of pathological vasculature remodeling and remains an important cause for long-term graft failure and mortality. Current preventive strategies for CAV include optimization of vascular risk factors and pharmacotherapy with statins and immunosuppressants.</p><p><strong>Conclusion: </strong>Despite demonstrated post-transplant mortality benefit and reduction in CAV with statins, the role of other pharmacotherapies on CAV reduction through LDL-C lowering remains less established. This review explores established evidence as well as evolving pathways for LDL-C lowering strategies to prevent CAV.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911867","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}
Pub Date : 2025-12-01DOI: 10.1016/j.jacl.2025.11.016
Pavla Jadrníčková, Lukáš Tichý, Martina Kašpráková, Jan Václavík, Tomáš Freiberger
Lipodystrophic syndromes are a heterogeneous group of disorders characterized by a lack of fatty tissue or abnormal fat accumulation outside of the body's typical fat distribution areas. Partial lipodystrophy most commonly manifests in childhood or young adulthood, and is classified into 6 primary subtypes, along with other rare categories. Lipodystrophy subtype 4 is associated with severe insulin resistance and unique traits, including severe hyperlipidemia, progressive liver disease, and arterial hypertension. Here we present the case of a 30-year-old woman with alarming hypertriglyceridemia, newly diagnosed diabetes mellitus, and severe hypertension. A complex differential diagnostic procedure yielded the diagnosis of familial partial lipodystrophy subtype 4. Initial treatment with plasmapheresis effectively reduced her triglyceride values but failed due to lack of intravenous access. Recurrent severe hypertriglyceridemia and normal leptin levels prompted the use of volanesorsen therapy, which is primarily indicated for treatment of hypertriglyceridemia in familial chylomicronemia syndrome. Volanesorsen proved very effective in this case.
{"title":"Improvement of severe hypertriglyceridemia in atypical subtype 4 partial lipodystrophy with volanesorsen.","authors":"Pavla Jadrníčková, Lukáš Tichý, Martina Kašpráková, Jan Václavík, Tomáš Freiberger","doi":"10.1016/j.jacl.2025.11.016","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.11.016","url":null,"abstract":"<p><p>Lipodystrophic syndromes are a heterogeneous group of disorders characterized by a lack of fatty tissue or abnormal fat accumulation outside of the body's typical fat distribution areas. Partial lipodystrophy most commonly manifests in childhood or young adulthood, and is classified into 6 primary subtypes, along with other rare categories. Lipodystrophy subtype 4 is associated with severe insulin resistance and unique traits, including severe hyperlipidemia, progressive liver disease, and arterial hypertension. Here we present the case of a 30-year-old woman with alarming hypertriglyceridemia, newly diagnosed diabetes mellitus, and severe hypertension. A complex differential diagnostic procedure yielded the diagnosis of familial partial lipodystrophy subtype 4. Initial treatment with plasmapheresis effectively reduced her triglyceride values but failed due to lack of intravenous access. Recurrent severe hypertriglyceridemia and normal leptin levels prompted the use of volanesorsen therapy, which is primarily indicated for treatment of hypertriglyceridemia in familial chylomicronemia syndrome. Volanesorsen proved very effective in this case.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145944212","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}
Pub Date : 2025-12-01DOI: 10.1016/j.jacl.2025.11.017
Irene Gracia-Rubio, Asier Benito-Vicente, Itziar Lamiquiz-Moneo, Ana María Bea, Victoria Marco-Benedí, Endika Cabrera-Antón, César Martín, Fernando Civeira, Ana Cenarro
Background: Rare variants in SCARB1, which encodes the high-density lipoprotein (HDL) receptor scavenger receptor class B type 1 (SR-B1), are hypothesized to drive unexplained extreme levels of plasma HDL cholesterol (HDL-C).
Objective: We sequenced and phenotypically correlated SCARB1 by analyzing individuals with extreme HDL-C levels and characterizing the functional consequences of rare identified variants.
Methods: SCARB1 was Sanger-sequenced in 96 unrelated participants with extreme HDL-C levels. Clinical, biochemical, and anthropometric data were compared between groups. Bioinformatic tools were used to predict the functional impact of all detected variants. Familial analyses of predicted damaging in silico or not previously described variants was assessed, and HDL uptake was quantified by flow cytometry in HEK293 cells expressing rare SCARB1 variants showing a suggestive pattern of familial segregation.
Results: Compared with the high-HDL-C group, low-HDL-C subjects exhibited lower low-density lipoprotein cholesterol and total cholesterol but higher triglycerides, higher body mass index, and a greater frequency of atherosclerotic cardiovascular disease events. Twenty-five SCARB1 variants were identified; 4 of them, c.-177G>T, p.(Thr118Ser), c.843-982G>A and p.(Thr378Met), were predicted to be deleterious. The missense changes p.(Thr118Ser) and p.(Thr378Met) showed a suggestive pattern of segregation with high HDL-C in available pedigrees. Cells expressing p.(Thr378Met) SCARB1 variant showed a reduction in HDL uptake vs wild-type.
Conclusion: Rare predicted damaging in silico variant in SCARB1, p.(Thr378Met), impairs SR-B1-mediated HDL uptake and associates with high HDL-C levels, highlighting SCARB1 as a candidate gene for genetic screening in dyslipidemic patients.
{"title":"Sequencing and functional characterization of SCARB1 variants in subjects with extreme HDL cholesterol levels.","authors":"Irene Gracia-Rubio, Asier Benito-Vicente, Itziar Lamiquiz-Moneo, Ana María Bea, Victoria Marco-Benedí, Endika Cabrera-Antón, César Martín, Fernando Civeira, Ana Cenarro","doi":"10.1016/j.jacl.2025.11.017","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.11.017","url":null,"abstract":"<p><strong>Background: </strong>Rare variants in SCARB1, which encodes the high-density lipoprotein (HDL) receptor scavenger receptor class B type 1 (SR-B1), are hypothesized to drive unexplained extreme levels of plasma HDL cholesterol (HDL-C).</p><p><strong>Objective: </strong>We sequenced and phenotypically correlated SCARB1 by analyzing individuals with extreme HDL-C levels and characterizing the functional consequences of rare identified variants.</p><p><strong>Methods: </strong>SCARB1 was Sanger-sequenced in 96 unrelated participants with extreme HDL-C levels. Clinical, biochemical, and anthropometric data were compared between groups. Bioinformatic tools were used to predict the functional impact of all detected variants. Familial analyses of predicted damaging in silico or not previously described variants was assessed, and HDL uptake was quantified by flow cytometry in HEK293 cells expressing rare SCARB1 variants showing a suggestive pattern of familial segregation.</p><p><strong>Results: </strong>Compared with the high-HDL-C group, low-HDL-C subjects exhibited lower low-density lipoprotein cholesterol and total cholesterol but higher triglycerides, higher body mass index, and a greater frequency of atherosclerotic cardiovascular disease events. Twenty-five SCARB1 variants were identified; 4 of them, c.-177G>T, p.(Thr118Ser), c.843-982G>A and p.(Thr378Met), were predicted to be deleterious. The missense changes p.(Thr118Ser) and p.(Thr378Met) showed a suggestive pattern of segregation with high HDL-C in available pedigrees. Cells expressing p.(Thr378Met) SCARB1 variant showed a reduction in HDL uptake vs wild-type.</p><p><strong>Conclusion: </strong>Rare predicted damaging in silico variant in SCARB1, p.(Thr378Met), impairs SR-B1-mediated HDL uptake and associates with high HDL-C levels, highlighting SCARB1 as a candidate gene for genetic screening in dyslipidemic patients.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900615","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}
Pub Date : 2025-11-28DOI: 10.1016/j.jacl.2025.11.015
Xingdi Hu, Anthony Lozama, Barnabie Agatep, Seth Kuranz, Iman Mohammadi, Donna McMorrow, Scott B Robinson, Lonny Reisman, Nathan D Wong
Background: Patients experiencing premature cardiovascular events (males: <55 years; females: <65 years) represent a high-risk subgroup within the atherosclerotic cardiovascular disease (ASCVD) population. Elevated lipoprotein(a) (Lp[a]) is an independent, genetic, causal risk factor for ASCVD. Lp(a) distribution among patients with premature ASCVD is poorly characterized.
Objective: This study aimed to describe Lp(a) distribution and baseline characteristics in a large real-world sample of patients with premature ASCVD.
Methods: We identified 17,594 patients with premature ASCVD who had Lp(a) values from US Medicare, Medicaid, and commercial plans between January 2016-September 2022.
Results: Mean age (SD) was 50.9 (10.1) years, most patients were female (68.9%), and half (52.2%) were not prescribed lipid-lowering therapy. Lp(a) levels ≥125, ≥175, and ≥225 nmol/L occurred in 26.8%, 18.8%, and 11.5%, respectively. Black patients had higher median (Q1-Q3) Lp(a) levels (111.0 [51.1-206.0] nmol/L) than Asian (35.0 [14.4-100.0] nmol/L), Hispanic (31.0 [10.9-95.0] nmol/L), or White patients (31.0 [10.7-110] nmol/L).
Conclusion: In one of the largest studies in the US investigating Lp(a) distribution in premature ASCVD, we found over a quarter of patients had elevated Lp(a) (≥125 nmol/L).
{"title":"Elevated lipoprotein(a) in patients with premature atherosclerotic cardiovascular disease: Insights from a large US real-world cohort.","authors":"Xingdi Hu, Anthony Lozama, Barnabie Agatep, Seth Kuranz, Iman Mohammadi, Donna McMorrow, Scott B Robinson, Lonny Reisman, Nathan D Wong","doi":"10.1016/j.jacl.2025.11.015","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.11.015","url":null,"abstract":"<p><strong>Background: </strong>Patients experiencing premature cardiovascular events (males: <55 years; females: <65 years) represent a high-risk subgroup within the atherosclerotic cardiovascular disease (ASCVD) population. Elevated lipoprotein(a) (Lp[a]) is an independent, genetic, causal risk factor for ASCVD. Lp(a) distribution among patients with premature ASCVD is poorly characterized.</p><p><strong>Objective: </strong>This study aimed to describe Lp(a) distribution and baseline characteristics in a large real-world sample of patients with premature ASCVD.</p><p><strong>Methods: </strong>We identified 17,594 patients with premature ASCVD who had Lp(a) values from US Medicare, Medicaid, and commercial plans between January 2016-September 2022.</p><p><strong>Results: </strong>Mean age (SD) was 50.9 (10.1) years, most patients were female (68.9%), and half (52.2%) were not prescribed lipid-lowering therapy. Lp(a) levels ≥125, ≥175, and ≥225 nmol/L occurred in 26.8%, 18.8%, and 11.5%, respectively. Black patients had higher median (Q1-Q3) Lp(a) levels (111.0 [51.1-206.0] nmol/L) than Asian (35.0 [14.4-100.0] nmol/L), Hispanic (31.0 [10.9-95.0] nmol/L), or White patients (31.0 [10.7-110] nmol/L).</p><p><strong>Conclusion: </strong>In one of the largest studies in the US investigating Lp(a) distribution in premature ASCVD, we found over a quarter of patients had elevated Lp(a) (≥125 nmol/L).</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878426","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}
Pub Date : 2025-11-25DOI: 10.1016/j.jacl.2025.11.014
Fabiana C Juliani, Fátima R Freitas, Márcio H Miname, Viviane Z Rocha, Josefa M da Hora Silva Lima, Rosana A M S Freitas, Nágila R T Damasceno, José E Krieger, Raul C Maranhão, Raul D Santos
Background: Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) and increased risk of premature coronary atherosclerosis. Functional aspects of high-density lipoprotein (HDL), including cholesterol transfer capacity, may contribute to cardiovascular risk heterogeneity in FH.
Objective: To investigate whether cholesterol transfer to HDL and other HDL-related parameters are associated with coronary artery disease (CAD) in patients with heterozygous FH (HeFH).
Methods: Fifty-three genetically confirmed FH patients (mean age: 49.2 years; 73.6% female) were included. Twenty-seven had plaques, while 26 had no vessel abnormalities as determined by coronary computed tomography angiography. The transfer of both unesterified and esterified cholesterol (UC and EC) to HDL, as well as HDL antioxidant capacity, particle size, and subfractions, plasma concentrations of cholesteryl ester transfer protein (CETP) and lecithin-cholesterol acyltransferase (LCAT), and paraoxonase-1 (PON-1) activity were assessed.
Results: Family history of premature CAD (P < .028) and tendinous xanthomas (P = .014) were more frequent in those with plaques. No differences were found in apolipoprotein (apo) B, LDL-C, LDL-C year score, lipoprotein(a), non-HDL-C, apo A-I, HDL-C, HDL subfractions, or triglycerides. Transfer of lipids to HDL and antioxidant capacity did not differ between the groups. LCAT concentrations and PON-1 activity were also similar. In contrast, CETP concentration was higher in those with plaques (P < .008). However, only family history of early CAD (odds ratio [OR]: 4.12, 95% CI, 1.23-13.80, P = .022) and xanthomas (OR: 3.65, 95% CI, 1.06-12.60, P = .040) were independently associated with plaques.
Conclusion: Among patients with HeFH, no HDL-related parameter was independently associated with subclinical CAD.
{"title":"Metabolic and functional aspects of high-density lipoproteins (HDL) in familial hypercholesterolemia with or without subclinical coronary atherosclerosis.","authors":"Fabiana C Juliani, Fátima R Freitas, Márcio H Miname, Viviane Z Rocha, Josefa M da Hora Silva Lima, Rosana A M S Freitas, Nágila R T Damasceno, José E Krieger, Raul C Maranhão, Raul D Santos","doi":"10.1016/j.jacl.2025.11.014","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.11.014","url":null,"abstract":"<p><strong>Background: </strong>Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) and increased risk of premature coronary atherosclerosis. Functional aspects of high-density lipoprotein (HDL), including cholesterol transfer capacity, may contribute to cardiovascular risk heterogeneity in FH.</p><p><strong>Objective: </strong>To investigate whether cholesterol transfer to HDL and other HDL-related parameters are associated with coronary artery disease (CAD) in patients with heterozygous FH (HeFH).</p><p><strong>Methods: </strong>Fifty-three genetically confirmed FH patients (mean age: 49.2 years; 73.6% female) were included. Twenty-seven had plaques, while 26 had no vessel abnormalities as determined by coronary computed tomography angiography. The transfer of both unesterified and esterified cholesterol (UC and EC) to HDL, as well as HDL antioxidant capacity, particle size, and subfractions, plasma concentrations of cholesteryl ester transfer protein (CETP) and lecithin-cholesterol acyltransferase (LCAT), and paraoxonase-1 (PON-1) activity were assessed.</p><p><strong>Results: </strong>Family history of premature CAD (P < .028) and tendinous xanthomas (P = .014) were more frequent in those with plaques. No differences were found in apolipoprotein (apo) B, LDL-C, LDL-C year score, lipoprotein(a), non-HDL-C, apo A-I, HDL-C, HDL subfractions, or triglycerides. Transfer of lipids to HDL and antioxidant capacity did not differ between the groups. LCAT concentrations and PON-1 activity were also similar. In contrast, CETP concentration was higher in those with plaques (P < .008). However, only family history of early CAD (odds ratio [OR]: 4.12, 95% CI, 1.23-13.80, P = .022) and xanthomas (OR: 3.65, 95% CI, 1.06-12.60, P = .040) were independently associated with plaques.</p><p><strong>Conclusion: </strong>Among patients with HeFH, no HDL-related parameter was independently associated with subclinical CAD.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794078","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}