Pub Date : 2026-02-01Epub Date: 2025-11-25DOI: 10.1016/j.jacl.2025.11.014
Fabiana C. Juliani PhD , Fátima R. Freitas PhD , Márcio H. Miname MD, PhD , Viviane Z. Rocha MD, PhD , Josefa M. da Hora Silva Lima BSc , Rosana A.M.S. Freitas MSc, PhD , Nágila R.T. Damasceno MSc, PhD , José E. Krieger MD, PhD , Raul C. Maranhão MD, PhD , Raul D. Santos MD, MSc, PhD
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 PhD , Fátima R. Freitas PhD , Márcio H. Miname MD, PhD , Viviane Z. Rocha MD, PhD , Josefa M. da Hora Silva Lima BSc , Rosana A.M.S. Freitas MSc, PhD , Nágila R.T. Damasceno MSc, PhD , José E. Krieger MD, PhD , Raul C. Maranhão MD, PhD , Raul D. Santos MD, MSc, PhD","doi":"10.1016/j.jacl.2025.11.014","DOIUrl":"10.1016/j.jacl.2025.11.014","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Objective</h3><div>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).</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>Family history of premature CAD (<em>P</em> < .028) and tendinous xanthomas (<em>P</em> = .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 (<em>P</em> < .008). However, only family history of early CAD (odds ratio [OR]: 4.12, 95% CI, 1.23-13.80, <em>P</em> = .022) and xanthomas (OR: 3.65, 95% CI, 1.06-12.60, <em>P</em> = .040) were independently associated with plaques.</div></div><div><h3>Conclusion</h3><div>Among patients with HeFH, no HDL-related parameter was independently associated with subclinical CAD.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 2","pages":"Pages 378-388"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","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}
Pub Date : 2026-02-01Epub Date: 2025-11-01DOI: 10.1016/j.jacl.2025.10.069
Amer M. Johri MD, MSc, FRCPC, FASE , Braeden Hill BSc , Nicholas Grubic MSc , Barkha Sirwani MPH , Matt Fraser BSc , Marie-France Hétu MSc, PhD , Pamela S. Douglas MD , Valentin Fuster MD, PhD , Borja Ibanez MD, PhD , Henning Bundgaard MD, DMSc , Henrik Sillesen MD, DMSc
BACKGROUD
As the burden of atherosclerotic cardiovascular disease (ASCVD) continues to rise, knowing the prevalence of its subclinical form is essential for early risk stratification and prevention. This review investigated the prevalence of carotid subclinical atherosclerosis, defined by the presence of plaque detected by ultrasound of the carotid arteries, as it varies with age in the asymptomatic young to middle-aged general population.
SOURCES OF MATERIAL
We searched MEDLINE, EMBASE, PubMed, and CENTRAL (2005-2023) databases for observational and experimental studies assessing a population of asymptomatic (ie, no known cardiovascular disease), individuals (aged 18-65 years) who underwent carotid artery ultrasound imaging. Prevalence of plaque was calculated from each included study, as well as based on age and sex subgroups, and Freeman-Tukey double-arcsine-transformed prevalence measures were computed for each study. Pooled measures were generated with a random-effects meta-analysis model.
ABSTRACT OF FINDINGS
A total of 92 studies comprising 204,997 subjects were included in this review (median sample size: 859). The median age of the study sample was 49.5 years (range: 26.6-64 years). The overall pooled prevalence of carotid atherosclerosis across all studies was 23% (95% CI: 19.1%-27.1%). The prevalence of carotid plaque increased according to age, ranging from a pooled prevalence of 5.2% (95% CI: 2.4%-8.9%) in adults aged 18 to 45 years to 30.3% (95% CI: 21.8%-39.4%) in those aged 50 to 65 years.
CONCLUSION
Subclinical carotid atherosclerosis is prevalent among young to middle-aged healthy adults, free of known CVD, from the general population. The findings suggest that a significant proportion of low-risk individuals may have undetected plaque, justifying reconsideration of early screening strategies.
{"title":"The prevalence of carotid subclinical atherosclerosis according to age: A systematic review and meta-analysis of the young to middle-age","authors":"Amer M. Johri MD, MSc, FRCPC, FASE , Braeden Hill BSc , Nicholas Grubic MSc , Barkha Sirwani MPH , Matt Fraser BSc , Marie-France Hétu MSc, PhD , Pamela S. Douglas MD , Valentin Fuster MD, PhD , Borja Ibanez MD, PhD , Henning Bundgaard MD, DMSc , Henrik Sillesen MD, DMSc","doi":"10.1016/j.jacl.2025.10.069","DOIUrl":"10.1016/j.jacl.2025.10.069","url":null,"abstract":"<div><h3>BACKGROUD</h3><div>As the burden of atherosclerotic cardiovascular disease (ASCVD) continues to rise, knowing the prevalence of its subclinical form is essential for early risk stratification and prevention. This review investigated the prevalence of carotid subclinical atherosclerosis, defined by the presence of plaque detected by ultrasound of the carotid arteries, as it varies with age in the asymptomatic young to middle-aged general population.</div></div><div><h3>SOURCES OF MATERIAL</h3><div>We searched MEDLINE, EMBASE, PubMed, and CENTRAL (2005-2023) databases for observational and experimental studies assessing a population of asymptomatic (ie, no known cardiovascular disease), individuals (aged 18-65 years) who underwent carotid artery ultrasound imaging. Prevalence of plaque was calculated from each included study, as well as based on age and sex subgroups, and Freeman-Tukey double-arcsine-transformed prevalence measures were computed for each study. Pooled measures were generated with a random-effects meta-analysis model.</div></div><div><h3>ABSTRACT OF FINDINGS</h3><div>A total of 92 studies comprising 204,997 subjects were included in this review (median sample size: 859). The median age of the study sample was 49.5 years (range: 26.6-64 years). The overall pooled prevalence of carotid atherosclerosis across all studies was 23% (95% CI: 19.1%-27.1%). The prevalence of carotid plaque increased according to age, ranging from a pooled prevalence of 5.2% (95% CI: 2.4%-8.9%) in adults aged 18 to 45 years to 30.3% (95% CI: 21.8%-39.4%) in those aged 50 to 65 years.</div></div><div><h3>CONCLUSION</h3><div>Subclinical carotid atherosclerosis is prevalent among young to middle-aged healthy adults, free of known CVD, from the general population. The findings suggest that a significant proportion of low-risk individuals may have undetected plaque, justifying reconsideration of early screening strategies.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 2","pages":"Pages 250-261"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834054","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}
While cholesterol-lowering trials have consistently demonstrated cardiovascular disease (CVD) benefits, some observational studies showed an elevated mortality risk from all-cause, CVD, and cancer in those with low total cholesterol (TC). This inconsistency is likely due to confounding.
OBJECTIVE
We explored potential confounders through various analytical approaches such as exclusion and adjustment.
METHODS
Using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study, we analyzed all-cause, CVD, and cancer mortality in individuals aged 35 to 69, not on cholesterol-lowering medication at baseline. We applied cohort-stratified Cox proportional hazards models to estimate the hazard ratio (HR) and 95% CI of the lowest TC group (<160 mg/dL) in reference to 160 to <200 mg/dL, after excluding self-reported CVD and cancer at baseline.
RESULTS
A total of 55,677 participants were followed over 10.1 years. Initially, the lowest TC group, compared to the reference group, had significantly elevated risks for all-cause and cancer mortality. Excluding liver diseases and adjusting for serum albumin at baseline attenuated the association to non-significant; HR (95% CI) of all-cause, cancer mortality in men: 1.37 (0.99-1.87), 1.06 (0.66-1.71), respectively. The corresponding values for women were 0.96 (0.46-2.02), 1.39 (0.58-3.34). For CVD mortality, the HR in men with low TC remained elevated, while women were nonsignificant regardless of liver diseases exclusion and albumin-adjustment.
CONCLUSION
Elevated all-cause and cancer mortality in low TC individuals was likely confounded by baseline liver diseases and serum albumin. Further research is needed to identify additional confounders.
{"title":"Liver diseases and low serum albumin as potential confounders in the association between low total cholesterol and elevated all-cause and cancer mortality: The Japan Multi-Institutional Collaborative Cohort (J-MICC) study","authors":"Maggy Audrey Murielle Bassole Epse Brou MD , Akira Fujiyoshi MD, PhD, MPH , Aya Higashiyama MD, PhD , Yukiko Okami PhD , Yoshikuni Kita PhD , Katsuyuki Miura MD, PhD , Hiroaki Ikezaki MD, PhD , Takuma Furukawa PhD , Takashi Tamura PhD , Daisaku Nishimoto PhD , Takeshi Nishiyama MD, DPH, PhD , Naoyuki Takashima MD, PhD , Kiyonori Kuriki PhD , Masashi Ishizu PhD , Yingsong Lin PhD , Yumiko Kasugai PhD , Yuriko N. Koyanagi MD, PhD , Isao Oze MD, PhD , Keitaro Matsuo MD, PhD, MSc , J-MICC Study Group","doi":"10.1016/j.jacl.2025.11.009","DOIUrl":"10.1016/j.jacl.2025.11.009","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>While cholesterol-lowering trials have consistently demonstrated cardiovascular disease (CVD) benefits, some observational studies showed an elevated mortality risk from all-cause, CVD, and cancer in those with low total cholesterol (TC). This inconsistency is likely due to confounding.</div></div><div><h3>OBJECTIVE</h3><div>We explored potential confounders through various analytical approaches such as exclusion and adjustment.</div></div><div><h3>METHODS</h3><div>Using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study, we analyzed all-cause, CVD, and cancer mortality in individuals aged 35 to 69, not on cholesterol-lowering medication at baseline. We applied cohort-stratified Cox proportional hazards models to estimate the hazard ratio (HR) and 95% CI of the lowest TC group (<160 mg/dL) in reference to 160 to <200 mg/dL, after excluding self-reported CVD and cancer at baseline.</div></div><div><h3>RESULTS</h3><div>A total of 55,677 participants were followed over 10.1 years. Initially, the lowest TC group, compared to the reference group, had significantly elevated risks for all-cause and cancer mortality. Excluding liver diseases and adjusting for serum albumin at baseline attenuated the association to non-significant; HR (95% CI) of all-cause, cancer mortality in men: 1.37 (0.99-1.87), 1.06 (0.66-1.71), respectively. The corresponding values for women were 0.96 (0.46-2.02), 1.39 (0.58-3.34). For CVD mortality, the HR in men with low TC remained elevated, while women were nonsignificant regardless of liver diseases exclusion and albumin-adjustment.</div></div><div><h3>CONCLUSION</h3><div>Elevated all-cause and cancer mortality in low TC individuals was likely confounded by baseline liver diseases and serum albumin. Further research is needed to identify additional confounders.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 2","pages":"Pages 357-367"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896308","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}
Desmosterolosis is a ultra-rare autosomal recessive disorder caused by biallelic variants in the DHCR24 gene, which encodes 3-beta-hydroxysterol delta-24-reductase—an enzyme involved in the final step of cholesterol biosynthesis. Here, we report a 3.5-year-old female with previously unreported compound heterozygous DHCR24 variants: c.1412A>G (p.Tyr471Cys), and c.275C>T (p.Thr92Met).
CASE PRESENTATION
The patient presented with agenesis of the corpus callosum, hypotonia, developmental delay, and dysmorphic facial features.
METHOD AND RESULTS
Trio-clinical exome sequencing confirmed the trans configuration of the variants. Plasma desmosterol levels were elevated >50-fold (134 ng/L; reference ≤2.5 ng/L), supporting the diagnosis. In silico 3D protein modeling demonstrated structural alterations associated with both variants.
CONCLUSION
A review of reported cases revealed consistent findings of corpus callosum agenesis, developmental delay, and ocular abnormalities. Our case contributes to the limited body of literature on DHCR24-related desmosterolosis and expands the variant spectrum, emphasizing the importance of integrating clinical, biochemical, and computational approaches in diagnosing rare metabolic disorders.
{"title":"DHCR24-related desmosterolosis in the first reported Turkish patient: Expanding the genotypic and phenotypic spectrum","authors":"Canan Ceylan Kose MD , Fehime Erdem MD , Mehmet Berkay Akcan MD , Havva Yazıcı MD , Turgay Cokyaman MD , Ebru Canda MD , Fatma Sılan MD","doi":"10.1016/j.jacl.2025.10.078","DOIUrl":"10.1016/j.jacl.2025.10.078","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Desmosterolosis is a ultra-rare autosomal recessive disorder caused by biallelic variants in the <em>DHCR24</em> gene, which encodes 3-beta-hydroxysterol delta-24-reductase—an enzyme involved in the final step of cholesterol biosynthesis. Here, we report a 3.5-year-old female with previously unreported compound heterozygous <em>DHCR24</em> variants: c.1412A>G (p.Tyr471Cys), and c.275C>T (p.Thr92Met).</div></div><div><h3>CASE PRESENTATION</h3><div>The patient presented with agenesis of the corpus callosum, hypotonia, developmental delay, and dysmorphic facial features.</div></div><div><h3>METHOD AND RESULTS</h3><div>Trio-clinical exome sequencing confirmed the trans configuration of the variants. Plasma desmosterol levels were elevated >50-fold (134 ng/L; reference ≤2.5 ng/L), supporting the diagnosis. In silico 3D protein modeling demonstrated structural alterations associated with both variants.</div></div><div><h3>CONCLUSION</h3><div>A review of reported cases revealed consistent findings of corpus callosum agenesis, developmental delay, and ocular abnormalities. Our case contributes to the limited body of literature on <em>DHCR24</em>-related desmosterolosis and expands the variant spectrum, emphasizing the importance of integrating clinical, biochemical, and computational approaches in diagnosing rare metabolic disorders.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 2","pages":"Pages 451-456"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917795","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 : 2026-02-01Epub Date: 2026-03-01DOI: 10.1016/j.jacl.2025.10.061
Francis de Zegher MD, PhD , Lourdes Ibáñez MD, PhD
{"title":"Variation in gluteofemoral adipogenesis and the phenotype of adolescent PCOS","authors":"Francis de Zegher MD, PhD , Lourdes Ibáñez MD, PhD","doi":"10.1016/j.jacl.2025.10.061","DOIUrl":"10.1016/j.jacl.2025.10.061","url":null,"abstract":"","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 2","pages":"Pages 462-464"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348357","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 : 2026-02-01Epub Date: 2025-12-04DOI: 10.1016/j.jacl.2025.12.002
Shoshana H. Bardach PhD , Skye Chernichky-Karcher PhD , Allison Hawke BS , Diane MacDougall MS , Katherine Wilemon BS , Laurence S. Sperling MD, FACC, FAHA, FACP, MASPC
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 PhD , Skye Chernichky-Karcher PhD , Allison Hawke BS , Diane MacDougall MS , Katherine Wilemon BS , Laurence S. Sperling MD, FACC, FAHA, FACP, MASPC","doi":"10.1016/j.jacl.2025.12.002","DOIUrl":"10.1016/j.jacl.2025.12.002","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Lipoprotein(a) (Lp[a]), is a significant risk factor for cardiovascular disease, yet is infrequently measured.</div></div><div><h3>OBJECTIVE</h3><div>A qualitative investigation was designed to better understand the barriers and facilitators to Lp(a) testing.</div></div><div><h3>METHODS</h3><div>Focus groups were held with clinicians (<em>n</em> = 26) and at-risk individuals (<em>n</em> = 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.</div></div><div><h3>RESULTS</h3><div>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.</div></div><div><h3>CONCLUSIONS</h3><div>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.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 2","pages":"Pages 317-325"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","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 : 2026-02-01Epub Date: 2026-03-01DOI: 10.1016/j.jacl.2025.10.071
Savitha Subramanian MD , Dinesh K. Kalra MD, FNLA , Nathan D. Wong PhD, FNLA
{"title":"The 2025 AACE Dyslipidemia Guidelines – Cost concerns over evidence and missing the target?","authors":"Savitha Subramanian MD , Dinesh K. Kalra MD, FNLA , Nathan D. Wong PhD, FNLA","doi":"10.1016/j.jacl.2025.10.071","DOIUrl":"10.1016/j.jacl.2025.10.071","url":null,"abstract":"","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 2","pages":"Pages 237-242"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348366","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 : 2026-02-01Epub Date: 2025-11-08DOI: 10.1016/j.jacl.2025.11.005
Ilgin Yıldırım Sımsır MD , Oben Belen MD , Pinar Cıftcı MD , Utku Erdem Soyaltın MD , Su Ozgur PhD , Ayca Aykut MD , Haluk Akın MD , Robert A. Hegele MD, PhD
BACKGROUND AND OBJECTIVES
Hypertriglyceridemia (HTG) may result from various etiologies, including the rare autosomal recessive disorder of chylomicron metabolism known as Familial Chylomicronemia Syndrome (FCS). Due to the risk of recurrent acute pancreatitis and subsequent pancreatic insufficiency, early and accurate diagnosis of FCS is clinically critical. Although genetic testing is considered the gold standard for diagnosis, access remains limited in many settings. To address this gap, the North American Familial Chylomicronemia Syndrome score (NAFCS Score) has been developed as a clinical tool incorporating readily available clinical and biochemical parameters. This study aimed to evaluate the performance of the NAFCS score in a cohort of genetically confirmed FCS patients.
METHODS
A total of 38 patients with genetically confirmed biallelic mutations causing FCS were evaluated retrospectively. Data on demographics, comorbidities, laboratory values, and pancreatitis history were collected. NAFCS was applied to each patient, and concordance between the score categories and the genetic diagnosis was assessed descriptively.
RESULTS
Among 38 genetically confirmed FCS patients, 52.6% were female. The median age was 35 years (IQR: 27-48 years). Acute pancreatitis had occurred in 86.8% of cases. The median triglyceride level was 3523 mg/dL (IQR: 2553-4470 mg/dL), and the median NAFCS was 65 (IQR: 52-81); 65.8% scored ≥60, 18.4% scored 45 to 59, and 15.8% scored <45.
CONCLUSION
The use of the NAFCS may serve as a useful tool in the differential diagnosis of patients with limited access to genetic testing. In this cohort, 84.2% of patients scored ≥45, the proposed threshold suggestive of a likely or definite diagnosis of FCS. This highlights the clinical utility of the scoring system in cases with HTG.
{"title":"Application of the North American Familial Chylomicronemia Syndrome Score (NAFCS Score) in monogenic hypertriglyceridemia patients: A single-center Turkish cohort study","authors":"Ilgin Yıldırım Sımsır MD , Oben Belen MD , Pinar Cıftcı MD , Utku Erdem Soyaltın MD , Su Ozgur PhD , Ayca Aykut MD , Haluk Akın MD , Robert A. Hegele MD, PhD","doi":"10.1016/j.jacl.2025.11.005","DOIUrl":"10.1016/j.jacl.2025.11.005","url":null,"abstract":"<div><h3>BACKGROUND AND OBJECTIVES</h3><div>Hypertriglyceridemia (HTG) may result from various etiologies, including the rare autosomal recessive disorder of chylomicron metabolism known as Familial Chylomicronemia Syndrome (FCS). Due to the risk of recurrent acute pancreatitis and subsequent pancreatic insufficiency, early and accurate diagnosis of FCS is clinically critical. Although genetic testing is considered the gold standard for diagnosis, access remains limited in many settings. To address this gap, the North American Familial Chylomicronemia Syndrome score (NAFCS Score) has been developed as a clinical tool incorporating readily available clinical and biochemical parameters. This study aimed to evaluate the performance of the NAFCS score in a cohort of genetically confirmed FCS patients.</div></div><div><h3>METHODS</h3><div>A total of 38 patients with genetically confirmed biallelic mutations causing FCS were evaluated retrospectively. Data on demographics, comorbidities, laboratory values, and pancreatitis history were collected. NAFCS was applied to each patient, and concordance between the score categories and the genetic diagnosis was assessed descriptively.</div></div><div><h3>RESULTS</h3><div>Among 38 genetically confirmed FCS patients, 52.6% were female. The median age was 35 years (IQR: 27-48 years). Acute pancreatitis had occurred in 86.8% of cases. The median triglyceride level was 3523 mg/dL (IQR: 2553-4470 mg/dL), and the median NAFCS was 65 (IQR: 52-81); 65.8% scored ≥60, 18.4% scored 45 to 59, and 15.8% scored <45.</div></div><div><h3>CONCLUSION</h3><div>The use of the NAFCS may serve as a useful tool in the differential diagnosis of patients with limited access to genetic testing. In this cohort, 84.2% of patients scored ≥45, the proposed threshold suggestive of a likely or definite diagnosis of FCS. This highlights the clinical utility of the scoring system in cases with HTG.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 2","pages":"Pages 310-316"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917764","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 : 2026-02-01Epub Date: 2025-12-15DOI: 10.1016/j.jacl.2025.12.010
Madeeha Khan MS , Quratul Ain MPhil , Jaka Sikonja MD , Barbara Cugalj Kern PhD , Hijab Batool FCPS , Sabeen Abid Khan FCPS , Muhammad Qasim Hayat PhD , Mohammad Iqbal Khan FRCS , Urh Groselj PhD , Fouzia Sadiq PhD
BACKGROUND
Homozygous familial hypercholesterolemia (HoFH) is a leading cause of premature atherosclerotic cardiovascular disease (ASCVD) and early mortality if left untreated or inadequately treated.
OBJECTIVE
This study presents 2 pediatric cases of early death from Pakistan due to familial hypercholesterolemia (FH) and provides a systematic review of similar cases reported globally.
METHODS
Genetic analysis was conducted using next-generation sequencing to confirm pathogenic variants. For the systematic review, published reports of individuals with FH who died before the age of 18 years were identified. Data were extracted on demographic features, personal and family history, genetic variants, treatment given, and cause of death.
RESULTS
Both patients, born to consanguineous families, presented with markedly elevated low-density lipoprotein cholesterol (LDL-C) levels (792 mg/dL [20.48 mmol/L] and 896 mg/dL [23 mmol/L], respectively), multiple xanthomas, and early-onset myocardial infarction, and died at the ages of 5 and 7 years, respectively. Their genetic analysis revealed a pathogenic frameshift variant in the LDLR gene: NM_000527.5: c.2416dupG (p.Val806GlyfsTer11). The systematic review included 12 studies reporting pediatric FH-related mortality. Common clinical features included tendon xanthomas, elevated LDL-C levels, family history, and early-onset ASCVD. Genetic testing was performed in a few cases, which revealed pathogenic variations in the LDLR gene. Most of the patients received inadequate lipid-lowering therapy. The most common causes of death were severe coronary artery disease, myocardial infarction, and sudden cardiac arrest.
CONCLUSION
Our 2 cases and the accompanying systematic review identified additional cases of premature mortality. Collectively, these findings highlight diagnostic delays and inadequate treatment as common factors among patients who died prematurely.
{"title":"Early mortality in children with homozygous familial hypercholesterolemia: Case reports of deaths at ages 5 and 7 and a systematic review of global evidence","authors":"Madeeha Khan MS , Quratul Ain MPhil , Jaka Sikonja MD , Barbara Cugalj Kern PhD , Hijab Batool FCPS , Sabeen Abid Khan FCPS , Muhammad Qasim Hayat PhD , Mohammad Iqbal Khan FRCS , Urh Groselj PhD , Fouzia Sadiq PhD","doi":"10.1016/j.jacl.2025.12.010","DOIUrl":"10.1016/j.jacl.2025.12.010","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Homozygous familial hypercholesterolemia (HoFH) is a leading cause of premature atherosclerotic cardiovascular disease (ASCVD) and early mortality if left untreated or inadequately treated.</div></div><div><h3>OBJECTIVE</h3><div>This study presents 2 pediatric cases of early death from Pakistan due to familial hypercholesterolemia (FH) and provides a systematic review of similar cases reported globally.</div></div><div><h3>METHODS</h3><div>Genetic analysis was conducted using next-generation sequencing to confirm pathogenic variants. For the systematic review, published reports of individuals with FH who died before the age of 18 years were identified. Data were extracted on demographic features, personal and family history, genetic variants, treatment given, and cause of death.</div></div><div><h3>RESULTS</h3><div>Both patients, born to consanguineous families, presented with markedly elevated low-density lipoprotein cholesterol (LDL-C) levels (792 mg/dL [20.48 mmol/L] and 896 mg/dL [23 mmol/L], respectively), multiple xanthomas, and early-onset myocardial infarction, and died at the ages of 5 and 7 years, respectively. Their genetic analysis revealed a pathogenic frameshift variant in the <em>LDLR</em> gene: <span><span>NM_000527.5</span><svg><path></path></svg></span>: c.2416dupG (p.Val806GlyfsTer11). The systematic review included 12 studies reporting pediatric FH-related mortality. Common clinical features included tendon xanthomas, elevated LDL-C levels, family history, and early-onset ASCVD. Genetic testing was performed in a few cases, which revealed pathogenic variations in the <em>LDLR</em> gene. Most of the patients received inadequate lipid-lowering therapy. The most common causes of death were severe coronary artery disease, myocardial infarction, and sudden cardiac arrest.</div></div><div><h3>CONCLUSION</h3><div>Our 2 cases and the accompanying systematic review identified additional cases of premature mortality. Collectively, these findings highlight diagnostic delays and inadequate treatment as common factors among patients who died prematurely.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 2","pages":"Pages 402-410"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933558","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 : 2026-02-01Epub Date: 2025-12-19DOI: 10.1016/j.jacl.2025.12.018
Asia Sikora Kessler PhD , Montserrat Vera-Llonch MSc , Ewa Karwatowska-Prokopczuk MD, PhD , Veronica J. Alexander PhD , Quratul Ann MSc , Catalina Mejia Herrera MS , Spyros Paparrodopoulos MSc , Shuting Xia MS , Erik S.G. Stroes MD, PhD , Seth J. Baum MD , Sotirios Tsimikas MD , Balance Investigators
BACKGROUND
Familial chylomicronemia syndrome (FCS) is a rare genetic disorder associated with extreme hypertriglyceridemia and high risk of acute pancreatitis. Olezarsen—an antisense oligonucleotide targeting hepatic apolipoprotein C3 (APOC3) messenger RNA—reduces triglycerides and may decrease pancreatitis risk. Olezarsen 80 mg once monthly is approved in the United States as an adjunct to diet to reduce triglycerides in adults with FCS.
OBJECTIVE
To assess the effect of olezarsen on all-cause healthcare resource utilization (HCRU) and overall experience of patients with genetically identified FCS enrolled in the Balance trial (NCT04568434).
METHODS
Prespecified exploratory endpoints included yearly all-cause hospitalization, total inpatient days, and emergency room visits for patients treated with olezarsen (80 or 50 mg) vs placebo, as well as Patient Global Impression of Change (PGIC). Ad hoc outcomes included length of hospital stay, intensive care unit (ICU) admissions, reasons for HCRU, and all-cause HCRU according to patients’ history of acute pancreatitis and for individual olezarsen doses vs placebo.
RESULTS
Treatment with olezarsen vs placebo for 1 year was associated with an 84% reduction in all-cause hospitalizations (mean rate ratio [95% CI], 0.16 [0.05, 0.50]), 6.3 fewer total inpatient days (95% CI, −11.09, −1.53), better PGIC scores, shorter length of stay, and numerically fewer ICU admissions. Acute pancreatitis was the most frequent cause of hospitalization. Reduction in all-cause inpatient service utilization was consistent for individual dose groups and in patients with a history of acute pancreatitis.
CONCLUSION
In the Balance study, olezarsen reduced all-cause inpatient service utilization and improved the experience of patients with FCS.
{"title":"Olezarsen reduces all-cause health services utilization and improves the treatment experience of patients with familial chylomicronemia syndrome","authors":"Asia Sikora Kessler PhD , Montserrat Vera-Llonch MSc , Ewa Karwatowska-Prokopczuk MD, PhD , Veronica J. Alexander PhD , Quratul Ann MSc , Catalina Mejia Herrera MS , Spyros Paparrodopoulos MSc , Shuting Xia MS , Erik S.G. Stroes MD, PhD , Seth J. Baum MD , Sotirios Tsimikas MD , Balance Investigators","doi":"10.1016/j.jacl.2025.12.018","DOIUrl":"10.1016/j.jacl.2025.12.018","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Familial chylomicronemia syndrome (FCS) is a rare genetic disorder associated with extreme hypertriglyceridemia and high risk of acute pancreatitis. Olezarsen—an antisense oligonucleotide targeting hepatic apolipoprotein C3 (<em>APOC3</em>) messenger RNA—reduces triglycerides and may decrease pancreatitis risk. Olezarsen 80 mg once monthly is approved in the United States as an adjunct to diet to reduce triglycerides in adults with FCS.</div></div><div><h3>OBJECTIVE</h3><div>To assess the effect of olezarsen on all-cause healthcare resource utilization (HCRU) and overall experience of patients with genetically identified FCS enrolled in the Balance trial (NCT04568434).</div></div><div><h3>METHODS</h3><div>Prespecified exploratory endpoints included yearly all-cause hospitalization, total inpatient days, and emergency room visits for patients treated with olezarsen (80 or 50 mg) vs placebo, as well as Patient Global Impression of Change (PGIC). Ad hoc outcomes included length of hospital stay, intensive care unit (ICU) admissions, reasons for HCRU, and all-cause HCRU according to patients’ history of acute pancreatitis and for individual olezarsen doses vs placebo.</div></div><div><h3>RESULTS</h3><div>Treatment with olezarsen vs placebo for 1 year was associated with an 84% reduction in all-cause hospitalizations (mean rate ratio [95% CI], 0.16 [0.05, 0.50]), 6.3 fewer total inpatient days (95% CI, −11.09, −1.53), better PGIC scores, shorter length of stay, and numerically fewer ICU admissions. Acute pancreatitis was the most frequent cause of hospitalization. Reduction in all-cause inpatient service utilization was consistent for individual dose groups and in patients with a history of acute pancreatitis.</div></div><div><h3>CONCLUSION</h3><div>In the Balance study, olezarsen reduced all-cause inpatient service utilization and improved the experience of patients with FCS.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 2","pages":"Pages 299-309"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989444","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}
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