Journal of clinical lipidology最新文献

{"title":"Effectiveness, safety, and treatment persistence of bempedoic acid in a Spanish real-world cohort","authors":"David León-Jiménez MD,&nbsp;Sergio Martínez-Hervás MD, PhD,&nbsp;Nagore Lois-Martínez MD,&nbsp;Carlos Jericó-Alba MD,&nbsp;María Jesús Martínez-Soriano MD,&nbsp;Meritxell Royuela-Juncadella MD,&nbsp;Anabel Franco-Moreno MD,&nbsp;Gemma Rodríguez-Carnero MD,&nbsp;José F. Varona MD, PhD,&nbsp;Alberto Muela-Molinero MD, PhD,&nbsp;Rocío García-Alonso MD,&nbsp;Jesús Castiella-Herrero MD,&nbsp;Miguel Cainzos-Achirica MD, PhD,&nbsp;Analía Ramos MD,&nbsp;Gema Gutiérrez-Lara MD,&nbsp;José Pablo Miramontes-González MD, PhD,&nbsp;Paula Luque-Linero MD,&nbsp;Miguel Ángel Vázquez-Ronda MD,&nbsp;Ana Torres-Do-Rego MD,&nbsp;Pablo González-Bustos MD,&nbsp;Carlos Puig-Jové MD, PhD","doi":"10.1016/j.jacl.2026.07.033","DOIUrl":"10.1016/j.jacl.2026.07.033","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Bempedoic acid (BA) is an oral adenosine triphosphate-citrate lyase inhibitor that reduces low-density lipoprotein cholesterol (LDL-C) and is particularly relevant in patients with statin intolerance. However, real-world evidence on its effectiveness and safety remains limited.</div></div><div><h3>OBJECTIVE</h3><div>To assess the effectiveness, safety, and treatment persistence of BA in a multicenter Spanish real-world cohort.</div></div><div><h3>METHODS</h3><div>This retrospective observational study included 814 patients treated with BA across 21 vascular risk units in Spain. Lipid and laboratory parameters were evaluated at baseline and after 3 months. Generalized mixed models were used to estimate adjusted marginal means and treatment effects.</div></div><div><h3>RESULTS</h3><div>BA significantly reduced total cholesterol (207.4-167.8 mg/dL; −19.1%) and LDL-C (121.3-86.5 mg/dL; −28.8%) (both <em>P</em> &lt; 0.001). Smaller reductions were observed for high-density lipoprotein cholesterol (−3.9%) and triglycerides (−2.4%), while high-sensitivity C-reactive protein decreased nonsignificantly (−13.7%; <em>P</em> = 0.102). Uric acid increased (+11.4%; <em>P</em> &lt; 0.001). LDL-C reduction was consistent across subgroups, with greater absolute reductions in patients with statin intolerance (−43.2 vs −26.7 mg/dL; <em>P</em> for interaction = 0.046). Concomitant ezetimibe use was associated with numerically greater LDL-C reduction without significant interaction. Patients receiving proprotein convertase subtilisin/kexin type 9 inhibitors or inclisiran achieved lower LDL-C levels and greater reductions. The discontinuation rate was 4.18%, mainly because of gastrointestinal symptoms and myalgias.</div></div><div><h3>CONCLUSION</h3><div>In routine clinical practice, BA is an effective and generally well-tolerated lipid-lowering therapy, particularly in patients with statin intolerance or requiring combination treatment. These findings support its use as an effective lipid-lowering option in patients with statin intolerance or requiring combination therapy.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 9","pages":"Pages 1933-1945"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712650","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 of lipoprotein(a) with renal and cardiac outcomes in chronic kidney disease: a nationwide cohort study","authors":"Fan Luo MD,&nbsp;Xian Shao MD,&nbsp;Yuxin Lin MD,&nbsp;Mingzhen Pang MD,&nbsp;Shiyu Zhou MS,&nbsp;Ruixuan Chen MD,&nbsp;Caoxiang She MD,&nbsp;Bianxiang Hu MD, PhD,&nbsp;Xin Xu MD, PhD,&nbsp;Sheng Nie MD, PhD","doi":"10.1016/j.jacl.2026.06.027","DOIUrl":"10.1016/j.jacl.2026.06.027","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>The role of lipoprotein(a) [Lp(a)] in chronic kidney disease (CKD) remains incompletely defined.</div></div><div><h3>OBJECTIVE</h3><div>This study aimed to investigate the association of Lp(a) with renal and cardiac outcomes in CKD.</div></div><div><h3>METHODS</h3><div>Patients with CKD were identified from the China Renal Data System, a joint initiative of the National Clinical Research Center for Kidney Disease and the China Center for Disease Control and Prevention. The primary outcome was a composite of CKD progression (kidney failure, &gt;40% estimated glomerular filtration rate [eGFR] decline, or kidney replacement therapy). The secondary outcome was cardiovascular (CV) mortality.</div></div><div><h3>RESULTS</h3><div>Among 27,037 and 52,895 participants assessed for renal and cardiac outcomes, 4608 (12.4%) and 4768 (9.0%) experienced the renal and cardiac outcome, respectively, over a median follow-up of 24 and 47 months. Positive and linear relationships were observed between log-Lp(a) and CKD progression and between Lp(a) and CV mortality. Lp(a) ≥30 mg/dL was associated with an elevated risk of CKD progression (adjusted hazard ratio [aHR], 1.13, 95%CI, 1.06, 1.21) and CV mortality (aHR, 1.14, 95%CI, 1.08, 1.22); these associations persisted after adjusting for time-varying covariates and were evident in individuals with low LDL-C levels. High Lp(a) levels were associated with both increased risk of end-stage kidney disease and faster decline in eGFR. Incorporating Lp(a) into the established prediction models enhances predictive performance and risk stratification capability for renal and cardiac outcomes.</div></div><div><h3>CONCLUSION</h3><div>Elevated Lp(a) may potentially serve as a target for kidney and CV protection. It is recommended that future interventional studies be conducted in this high-risk population.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 9","pages":"Pages 1954-1964"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549374","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":"Evaluating elevated lipoprotein(a) clinical care impact in an academic health center","authors":"Aida Roman MD, MS,&nbsp;Shane J. Sacco PhD,&nbsp;John G. Tiu MD","doi":"10.1016/j.jacl.2026.06.023","DOIUrl":"10.1016/j.jacl.2026.06.023","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Elevated lipoprotein(a) [Lp(a)] is associated with atherosclerotic cardiovascular disease (ASCVD). Nevertheless, Lp(a) is a poorly addressed ASCVD risk factor.</div></div><div><h3>OBJECTIVE</h3><div>Evaluate the impact of elevated Lp(a) on clinical decision-making of known ASCVD risk factors and consideration of aspirin for primary prevention of cardiovascular disease.</div></div><div><h3>METHODS</h3><div>We extracted data of patients who underwent Lp(a) testing from January 1, 2019, to December 31, 2023. We obtained patient and provider characteristics. Multivariable logistic regression was used to evaluate the association between elevated Lp(a) levels and therapy intensification, defined as intensification of statin or initiation of new lipid-lowering therapy, antihypertensive, antiplatelet, or antihyperglycemic agents.</div></div><div><h3>RESULTS</h3><div>A total of 530 patients had at least 1 Lp(a) measurement. Most were women (54.5%) with a mean age of 54 (41-67) and a mean body mass index (BMI) of 30 (24-36). The most common races were White (72.6%), Asian (9.2%), and Black (8.1%), while the most common ethnicity was Hispanic (10.8%). The most common comorbidities were hyperlipidemia (78.9%), hypertension (53.0%), obesity (40.4%), ASCVD (28.5%), and family history of ASCVD (22.6%). Cardiology (43.6%) and primary care (39.4%) were the most common specialties ordering Lp(a). Those with elevated Lp(a) were 3.5 times more likely to have therapy intensification (95% CI: 2.34-5.41; <em>P</em> &lt; 0.001). In multivariable models, patients with intensified treatment were more likely to have a higher BMI (adjusted odds ratio [aOR] = 1.07 [&lt;1.01-1.14]), and those with public insurance were less likely to receive therapy intensification (aOR = 0.29 [0.10-0.82]).</div></div><div><h3>CONCLUSION</h3><div>Our study shows that elevated Lp(a) was associated with therapy intensification. Greater efforts to increase awareness about this risk factor are needed.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 9","pages":"Pages 1946-1953"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipoprotein(a) and atrial fibrillation: Meta-analysis of observational and mendelian randomization studies shows no clinically meaningful association","authors":"Md Fahim MD, MPH,&nbsp;Daoud Eldawud MBBS,&nbsp;Roy Wang MD,&nbsp;Asher Gorantla MD,&nbsp;Peter Khouri MS,&nbsp;Cristina A. Mitre MD,&nbsp;Adam S. Budzikowski MD, PhD, FHRS","doi":"10.1016/j.jacl.2026.07.006","DOIUrl":"10.1016/j.jacl.2026.07.006","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Elevated lipoprotein(a) [Lp(a)] is an established risk factor for atherosclerotic cardiovascular disease, but its relationship with atrial fibrillation (AF) remains uncertain. We conducted a meta-analysis of observational studies and Mendelian randomization (MR) analyses to clarify whether Lp(a) is associated with AF.</div></div><div><h3>OBJECTIVE</h3><div>To clarify the relationship between Lp(a) and AF.</div></div><div><h3>METHODS</h3><div>We systematically pooled 16 observational studies analyzing odds ratios (ORs) and hazard ratios (HRs) for AF across higher vs lower Lp(a) exposure, as defined within each study, in 2 separate random-effects models. In parallel, we pooled 7 MR studies that used genetic instruments for Lp(a) to estimate the causal effect on AF. Subgroup analyses were performed by ancestry (European and East Asian).</div></div><div><h3>RESULTS</h3><div>Observational studies showed no association between Lp(a) and AF (OR 0.980 [0.901, 1.070], <em>P</em> = 0.581; HR 1.058 [0.998, 1.110], <em>P</em> = 0.057). Stratification by ancestry showed no association either (European, OR 1.079 [0.759, 1.533], <em>P</em> = 0.673; East Asian, OR 0.978 [0.896, 1.068], <em>P</em> = 0.621). In MR studies accounting for sample overlap, we observed no association between Lp(a) and AF (OR 0.976 [0.940, 1.013], <em>P</em> = 0.208). All MR studies pooled with substantial sample overlap showed statistically significant but very small positive effects (OR 1.023 [1.002, 1.044], <em>P</em> &lt; 0.001).</div></div><div><h3>CONCLUSION</h3><div>Lp(a) is not associated with AF in observational or MR meta-analysis. MR analyses do not demonstrate a significant association when restricted to independent datasets, indicating that any true causal relationship is unlikely to be clinically meaningful.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 9","pages":"Pages 1965-1977"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603482","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 determinants of chylomicronemia in Taiwan: Predominance of LPL rare variants and APOA5 p.G185C","authors":"Eric Bo-Ru Chao MD,&nbsp;Siao-Jyuan Jhan MS,&nbsp;Po-Chih Lin MD,&nbsp;Yuh-Tsyr Chou MS,&nbsp;Wen-Chi Chang MS,&nbsp;Allen Chilun Luo MS,&nbsp;Mao-Jan Lin MS,&nbsp;Ching-Hua Kuo PhD,&nbsp;Yu-An Chen PhD,&nbsp;Pei-Lung Chen MD, PhD,&nbsp;Ta-Chen Su MD, PhD","doi":"10.1016/j.jacl.2026.07.005","DOIUrl":"10.1016/j.jacl.2026.07.005","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Chylomicronemia is a genetically heterogeneous condition with both genetic and environmental determinants. Genetic studies have largely focused on European populations, with limited data from East Asians, particularly Han Chinese. We characterized the genetic profiles of chylomicronemia patients of mainly Han Chinese ancestry in Taiwan.</div></div><div><h3>OBJECTIVE</h3><div>To identify and classify disease-causing variants in chylomicronemia patients.</div></div><div><h3>METHODS</h3><div>Capture-based targeted next-generation sequencing was performed for 108 chylomicronemia patients to assess hypertriglyceridemia-related genes, including those harboring large- and moderate-effect rare variants, and small-effect single-nucleotide variants.</div></div><div><h3>RESULTS</h3><div>Twenty-seven patients (25%) carried large-effect, disease-causing rare variants, the majority in <em>LPL</em> (86%), with additional variants identified in <em>APOA5, LMF1</em>, and <em>APOA1.</em> The most prevalent variant, NM_000237.3(<em>LPL</em>):c.835C&gt;G(p.L279V), was detected in all homozygous and compound heterozygous cases. Comparison with the Taiwan Biobank revealed significant differences in <em>APOE</em> allele and genotype distributions (<em>P</em> = 0.003492 and <em>P</em> = 0.009, respectively). Additionally, NM_001371904.1(<em>APOA5</em>): c.553G&gt;T(p.G185C) was identified in 43.5% of patients, showing a high prevalence despite not being classified as a large-effect variant, and frequently found without additional large-effect rare variants.</div></div><div><h3>CONCLUSION</h3><div>As one of the most comprehensive characterizations to date of chylomicronemia in an East Asian cohort, the predominance of large-effect <em>LPL</em> rare variants, together with the high prevalence of the <em>APOA5</em> p.G185C variant and distinct <em>APOE</em> allele distributions, highlights population-specific genetic architecture.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 9","pages":"Pages 1850-1862"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603490","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":"Predicting genetically defined familial hypercholesterolemia with the FAMCAT algorithm in an Australian tertiary clinic","authors":"Ralph K. Akyea MBChB, MPH, PhD,&nbsp;Dick C. Chan PhD,&nbsp;Jing Pang PhD,&nbsp;Seyed Saeed Tamehri Zadeh MD,&nbsp;Barbara Iyen MBBS, MPH, PhD, MRCGP,&nbsp;Nadeem Qureshi DM,&nbsp;Gerald Watts DSc, PhD, DM, FRACP, FRCP","doi":"10.1016/j.jacl.2026.07.009","DOIUrl":"10.1016/j.jacl.2026.07.009","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Familial hypercholesterolemia (FH) is a monogenic disorder associated with premature coronary artery disease. The Dutch Lipid Clinic Network (DLCN) and Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT) are tools used to identify individuals with possible FH. Although FAMCAT performs well in primary care, its accuracy for genetically confirmed FH in tertiary care settings remains unclear. This study assessed the performance of FAMCAT in an Australian tertiary lipid clinic.</div></div><div><h3>OBJECTIVE</h3><div>This study assessed the performance of FAMCAT in identifying patients with genetically confirmed FH in an Australian tertiary lipid clinic.</div></div><div><h3>METHODS</h3><div>This cross-sectional study included unrelated adult patients referred for FH genetic testing. FAMCAT and DLCN scores were calculated, and their discriminatory ability was evaluated using area under the receiver operating characteristic curve (AUROC) analysis.</div></div><div><h3>RESULTS</h3><div>Of 885 patients, 267 (30%) had genetically confirmed heterozygous FH. In univariate regression analysis, FAMCAT and DLCN scores were significant predictors of an FH-causing variant with an odds ratio of 1.13 (95% CI 1.09-1.17; <em>P</em> &lt; 0.001) and 1.49 (95% CI 1.41-1.58; <em>P</em> &lt; 0.001), respectively. These associations remained significant after adjusting for smoking, hypertension, and obesity. The AUROC for FAMCAT (0.748; 95% CI, 0.712-0.784) was significantly lower than that of DLCN (0.816; 95% CI, 0.784-0.847; <em>P</em> &lt; 0.01). Although FAMCAT and DLCN definite FH category had comparable sensitivity (67.0% vs 65.2%), FAMCAT had a lower specificity (73.3% vs 83.5%), positive predictive value (52.0% vs 63.0%), and Youden index (0.402 vs 0.487).</div></div><div><h3>CONCLUSIONS</h3><div>The DLCN criteria performed better in identifying FH genetic variants in this Australian lipid clinic. The FAMCAT algorithm showed good discriminatory accuracy and could help prioritize patients referred for specialist review and/or genetic testing. Improved family history documentation may further enhance the diagnostic accuracy of both tools.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 9","pages":"Pages 1863-1869"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"It’s time to test all adults for lipoprotein(a)","authors":"Michael J. Wilkinson MD, FACC, FNLA,&nbsp;Marlys L. Koschinsky PhD, FACC, FAHA, CAHS, FNLA","doi":"10.1016/j.jacl.2026.04.022","DOIUrl":"10.1016/j.jacl.2026.04.022","url":null,"abstract":"<div><div>The recent 2026 American College of Cardiology/American Heart Association Multisociety Guideline on the Management of Dyslipidemia joins the growing international consensus that lipoprotein(a) [Lp(a)] should be tested at least once in all adults. Despite the estimation that approximately 1 in 5 individuals have Lp(a) levels at or above those that are clearly associated with an increased risk for atherosclerotic cardiovascular disease and calcific aortic valve stenosis (≥50 mg/dL or ≥125 nmol/L), data from recent studies reveal very low testing rates across the general population. Thus, expanded Lp(a) testing is urgently needed. Along with guidance to test all adults for Lp(a), solutions are needed to help address remaining knowledge gaps, barriers to testing, and nuances in the clinical use of Lp(a). Studies designed to address these unmet needs should be prioritized as we enter the era of universal Lp(a) testing in adults.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 9","pages":"Pages 7-10"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting the paradoxical effects of artichoke leaf extract in severe obesity","authors":"Wei Chen MD,&nbsp;Jiayuan Yang MD,&nbsp;Kexin Ye MD,&nbsp;Jun Ma MD","doi":"10.1016/j.jacl.2026.05.005","DOIUrl":"10.1016/j.jacl.2026.05.005","url":null,"abstract":"","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 9","pages":"Pages 2091-2092"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148030820","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 of remnant cholesterol with prognosis in atherosclerotic cardiovascular disease: A systematic review and meta-analysis","authors":"Yanyu Pei MM,&nbsp;Bo Liu MM,&nbsp;Ying Gu BSc","doi":"10.1016/j.jacl.2026.07.018","DOIUrl":"10.1016/j.jacl.2026.07.018","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Elevated remnant cholesterol (RC) is implicated in the pathogenesis of atherosclerosis.</div></div><div><h3>OBJECTIVE</h3><div>To assess the prognostic role of RC in atherosclerotic cardiovascular disease.</div></div><div><h3>METHODS</h3><div>We systematically searched PubMed, Embase, the Cochrane Library, and Web of Science from inception to January 18, 2026, for eligible studies. The primary outcome was a composite of major adverse cardiovascular events (MACE). Pooled hazard ratios (HRs) with 95% CIs were calculated using a random-effects model.</div></div><div><h3>RESULTS</h3><div>Twenty-one studies involving 114,592 participants were included. Higher RC levels were significantly associated with an increased risk of MACE (HR: 1.44, <em>P</em> &lt; 0.001), all-cause mortality (HR: 1.40; <em>P</em> &lt; 0.001), myocardial infarction (MI) (HR: 1.35; <em>P</em> &lt; 0.001), stroke (HR: 1.21; <em>P</em> = 0.004), cardiac death (HR: 1.41; <em>P</em> &lt; 0.001), and unplanned repeat revascularization (HR: 1.56; <em>P</em> &lt; 0.001). Furthermore, each 1-SD increment in RC level was associated with an elevated risk of MACE (HR: 1.22; <em>P</em> &lt; 0.001), all-cause mortality (HR: 1.16; <em>P</em> = 0.010), MI (HR: 1.11; <em>P</em> &lt; 0.001), and unplanned repeat revascularization (HR: 1.31; <em>P</em> = 0.007). The association between RC levels and MACE risk was potentially modified by geographic region, body mass index, current smoking status, adjustment for traditional lipid parameters, and study quality.</div></div><div><h3>CONCLUSION</h3><div>Elevated RC is associated with a worse prognosis in patients with established coronary artery disease. This association persisted after adjustment for traditional cardiovascular risk factors in the included studies, although residual confounding cannot be excluded. These findings suggest that RC assessment may have potential value within secondary prevention strategies for coronary artery disease.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 9","pages":"Pages 1799-1815"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond sitosterol: A multivariable sterol model improves diagnosis of pediatric sitosterolemia in the gray zone","authors":"Mengyuan Wu MSc,&nbsp;Hongjiang Wu BSc,&nbsp;Weihua Sun MSc,&nbsp;Yan Sun MD,&nbsp;Bingbing Wu MD,&nbsp;Feihong Luo MD,&nbsp;Zhou Pei MD,&nbsp;Wei Lu MD","doi":"10.1016/j.jacl.2026.07.030","DOIUrl":"10.1016/j.jacl.2026.07.030","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Patients with sitosterolemia (ST) are often misdiagnosed as familial hypercholesterolemia (FH) because of overlapping lipid phenotypes. Sitosterol is considered a disease-specific biomarker; however, its diagnostic utility in highly heterogeneous populations—particularly among children—remains unclear.</div></div><div><h3>OBJECTIVE</h3><div>To evaluate the diagnostic value of phytosterol biomarkers and develop a multivariate model to improve the diagnostic accuracy of ST.</div></div><div><h3>METHODS</h3><div>We conducted a cross-sectional study of 379 children with suspected lipid disorders: ST (n = 38), <em>ABCG5/8</em> heterozygous carriers (n = 12), genetically confirmed FH (n = 54), individuals with FH-like (n = 50), and healthy controls (n = 225). Clinical characteristics, lipid profiles, phytosterols, liver enzymes, and genetic data were collected. The diagnostic performance of single biomarkers and a multivariate model was evaluated. A clinical gray zone based on sitosterol levels was defined to assess the models’ ability.</div></div><div><h3>RESULTS</h3><div>Sitosterol demonstrated near-perfect discrimination for ST in the overall population area under the curve ([AUC] 0.994; 95% CI, 0.988-1.000), outperforming conventional lipid markers. However, substantial overlap in phytosterol distributions was observed among ST, heterozygotes, and FH-related phenotypes. Within the gray zone (sitosterol: 17.7-50 μg/mL), the diagnostic performance of sitosterol declined markedly (AUC 0.653). The multivariable model demonstrated comparable overall performance (AUC 0.983) but significantly improved discrimination in the gray zone (AUC 0.806), with good calibration and greater net clinical benefit.</div></div><div><h3>CONCLUSION</h3><div>Although sitosterol is highly effective for identifying ST, its diagnostic performance declines significantly in clinically significant gray zone cases. A combined sterol-based model improves diagnostic discrimination in these challenging scenarios and supports a stepwise diagnostic strategy for children with suspected ST.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 9","pages":"Pages 1898-1908"},"PeriodicalIF":6.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}