BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) is a common autosomal dominant disorder, and adults with HeFH can have other cardiometabolic risk factors that increase the risk of events. Recent studies hav...BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) is a common autosomal dominant disorder, and adults with HeFH can have other cardiometabolic risk factors that increase the risk of events. Recent studies have reported relatively low rates of these risk factors among children with HeFH. OBJECTIVE: Compare cardiometabolic risk factors among children with and without HeFH presenting to a pediatric lipid clinic. METHODS: We conducted a retrospective chart review study of subjects who presented to the pediatric lipid clinic in a single institution between January 1, 2011, and October 31, 2024. RESULTS: Among subjects with HeFH, 31.6% had body mass index percentile in the obese range, 4.1% had diabetes, and 6.7% had hypertension compared with 56.5% with obesity, 4.7% with diabetes, and 10.6% with hypertension among subjects without HeFH. CONCLUSION: In this US-based cohort, children with HeFH had a higher prevalence of cardiometabolic comorbidities compared with other populations. Health care providers should screen for and treat these conditions among children at high risk for premature atherosclerotic cardiovascular disease.
J Clin Lipidol
· 2026 Mar · PMID 41692657
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BACKGROUND: Elevated lipoprotein(a) [Lp(a)] is an independent and causal risk factor for atherosclerotic cardiovascular disease. Increasingly, prevention societies recommend testing Lp(a) at least once for all adults. OB...BACKGROUND: Elevated lipoprotein(a) [Lp(a)] is an independent and causal risk factor for atherosclerotic cardiovascular disease. Increasingly, prevention societies recommend testing Lp(a) at least once for all adults. OBJECTIVE: A quality improvement (QI) initiative aimed to increase the rates of Lp(a) ordering for patients was piloted in the general cardiology fellows' clinic at an urban academic medical center. METHODS: QI project interventions focused on provider education and inclusion of electronic health record-based tools. RESULTS: Over a period of 10 months, the proportion of patients with an Lp(a) order increased from 10.1% to 20.9%, and the proportion of patients with an Lp(a) result increased from 7.0% to 11.2%. CONCLUSION: Ahead of results from ongoing clinical trials testing Lp(a)-targeted therapies, health systems can use QI methods to assess current Lp(a) ordering practices, identify patients who may benefit from future Lp(a)-targeted therapy, and plan for rapid expansion of Lp(a) testing.
BACKGROUND: Lipoprotein(a) [Lp(a)] is an independent cardiovascular risk factor, with a growing recognized role in stroke. OBJECTIVE: To investigate the association between Lp(a) levels, large artery atherosclerosis (LAA...BACKGROUND: Lipoprotein(a) [Lp(a)] is an independent cardiovascular risk factor, with a growing recognized role in stroke. OBJECTIVE: To investigate the association between Lp(a) levels, large artery atherosclerosis (LAA) TOAST (Trial of ORG 10172 in Acute Stroke Treatment) category, and stroke-related atherosclerosis distribution (extracranial/intracranial) in a single-center retrospective cohort of patients with ischemic stroke. METHODS: We included all patients with ischemic stroke admitted between March and December 2021 with Lp(a) levels and computed tomography angiography. Multivariable regression assessed the relationship between Lp(a) and LAA, extracranial carotid stenosis, or intracranial atherosclerotic stenosis (ICAS). Predicted probabilities of atherosclerosis location per Lp(a) increment were estimated from a multinomial logistic regression model. RESULTS: We screened 523 patients and included 397 with complete data. The median age was 78 years, and 47% were female. Median Lp(a) was significantly higher in patients with stroke-related atherosclerosis, particularly those with intracranial involvement. Statin use (adjusted β = 15.01, 95% CI: 3.32-26.70, P = .012) and low-density lipoprotein levels (adjusted β = 0.236, 95% CI: 0.09-0.38, P = .002) were independently associated with Lp(a). Lp(a) was significantly associated with LAA (per 10 mg/dL increment: adjusted odds ratio [OR]: 1.08, 95% CI: 1.03-1.14, P = .003; for Lp(a) ≥50 mg/dL vs <50 mg/dL, LAA prevalence was 27% vs 15%, P = .007; adjusted OR: 2.71, 95% CI: 1.47-5.91, P = .001). Lp(a) ≥50 mg/dL was significantly associated with ICAS (adjusted OR: 4.49, 95% CI: 2.41-8.38, P < .001), but not with extracranial carotid stenosis (P = .065). With increasing Lp(a) levels, ICAS showed the steepest increase in predicted probability. CONCLUSION: Higher Lp(a) values are associated with LAA stroke, particularly ICAS. Lp(a) levels should be included in the stroke workup.
Ariza MJ, Rioja J, Seidel VA
… +17 more, Tolín-Hernani M, González-Estrada A, Salazar-Quero JC, Muñiz-Grijalvo O, Mangas A, Benavides-Román MR, Mora-Sitja M, Blasco-Alonso J, Yahyaoui R, de Las Heras J, Unceta-Suárez M, Jiménez-Navarro MF, Ordóñez-Simón RM, Espíldora-Hernández J, Benítez-Toledo MJ, Coca-Prieto I, Sánchez-Chaparro MÁ
BACKGROUND: Severe hypertriglyceridemia (fasting triglycerides >500 mg/dL) is an uncommon and heterogeneous condition in children. OBJECTIVE: The aim of this work was to assess the etiology of severe hypertriglyceridemia...BACKGROUND: Severe hypertriglyceridemia (fasting triglycerides >500 mg/dL) is an uncommon and heterogeneous condition in children. OBJECTIVE: The aim of this work was to assess the etiology of severe hypertriglyceridemia seen in 8 pediatric patients. METHODS: Eight pediatric cases with severe hypertriglyceridemia underwent clinical, biochemical, and genetic evaluations. The laboratory tests performed included lipoprotein separation by ultracentrifugation and measurement of their lipid content, measurement of apolipoproteins, analyses of post-heparin plasma lipoprotein lipase (LPL) activity and mass, detection of autoantibodies against GPIHBP1, and targeted next-generation sequencing. RESULTS: All children (3-16 years) had recorded fasting serum triglyceride levels >800 mg/dL (9 mmol/L) at least once. Five cases with pathogenic or likely pathogenic biallelic variants in GPIHBP1 (2 cases), APOA5 (1 case), APOC2 (1 case), and LPL (1 case) were diagnosed with familial chylomicronemia syndrome based on their clinical, biochemical, and genetic features. Additionally, 1 child had autoimmune chylomicronemia due to the presence of autoantibodies against GPIHBP1. Finally, 2 patients had severe hypertriglyceridemia due to secondary causes: 1 girl with the onset of type 1 diabetes in the context of diabetic ketoacidosis, and the other patient due to total parenteral nutrition and low-molecular-weight heparin. CONCLUSION: The etiology of severe hypertriglyceridemia in children is heterogeneous. A multidisciplinary approach helps to reach a definitive diagnosis and, therefore, to recommend specific therapy.
BACKGROUND: The genetic and phenotypic spectrum of homozygous familial hypercholesterolemia (HoFH) in Han Chinese populations remains insufficiently defined. OBJECTIVE: To delineate the nationwide genetic and clinical fe...BACKGROUND: The genetic and phenotypic spectrum of homozygous familial hypercholesterolemia (HoFH) in Han Chinese populations remains insufficiently defined. OBJECTIVE: To delineate the nationwide genetic and clinical features of HoFH in Taiwan, including true HoFH, double heterozygous FH (HeFH), and compound HeFH. METHODS: Patients with clinically diagnosed probable or definite FH enrolled in the Taiwan FH Registry who underwent genetic testing between 2006 and 2025 were analyzed. A comprehensive workflow integrating microarray assay, mass spectrometry, targeted next-generation sequencing, and multiplex ligation-dependent probe amplification was implemented. Variants were classified using American College of Medical Genetics and Genomics guidelines. RESULTS: Of 1479 screened individuals, 63 were genetically confirmed to have HoFH (mean age, 32.8 ± 22.7 years), including 28.6% with atherosclerotic vascular disease. The cohort comprised 14 true HoFH (including homozygous APOB variants), 6 double HeFH, and 43 compound HeFH. The highest documented low-density lipoprotein cholesterol (LDL-C) levels were 357.3 ± 123.5 mg/dL in true HoFH, 347.3 ± 39.2 mg/dL in double HeFH, and 443.5 ± 170.9 mg/dL in compound HeFH. The most frequent genotypes were LDLR [IVS2+4A>T];[IVS2+4A>T] in true HoFH, [APOB p.R3527W];[LDLR IVS2+4A>T] and [APOB p.R3527W];[LDLR p.D90N] in double HeFH, and LDLR [p.D90N];[p.C329Y] in compound HeFH. Patients with double HeFH had lower LDL-C levels and fewer xanthomas than those with LDLR homozygosity or compound mutations, while individuals with homozygous LDLR exon deletions/duplications had the highest LDL-C levels. CONCLUSION: This nationwide study provides the first comprehensive genetic and clinical characterization of HoFH in Taiwan. Our findings highlight the importance of precise genetic diagnosis and early detection strategies in improving outcomes for this high-risk population.
BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder caused by mutations in genes regulating lipoprotein lipase activity, typically manifesting early in life. CASE PRESENTATION: We d...BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder caused by mutations in genes regulating lipoprotein lipase activity, typically manifesting early in life. CASE PRESENTATION: We describe a 70-year-old man with severe refractory hypertriglyceridemia, chronic hyperCKemia, and protein-energy malnutrition, ultimately diagnosed with FCS due to a homozygous pathogenic LPL variant (c.844G>T; p.Glu282*). Despite long-standing disease and comorbidities, treatment with volanesorsen, an antisense oligonucleotide targeting apolipoprotein C-III mRNA, produced a 74% reduction in triglyceride levels and marked clinical improvement. This case underscores that FCS may remain undetected until late adulthood, particularly when confounded by diabetes or chronic kidney disease. CONCLUSION: Recognition of characteristic biochemical profiles and family history is essential to avoid diagnostic delay and prevent irreversible pancreatic damage and malnutrition. Even in elderly patients, targeted therapy can substantially improve metabolic control and quality of life.
Uddin M, Shah A, Hemida MF
… +12 more, Afridi MJ, Bacha Z, Iftikhar H, Khan S, Saif H, Jamal A, Syed A, Khalid AA, Al Badri SG, Waqas M, Irfan S, Kamil KA
BACKGROUND: Ongericimab, a novel proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody, has recently been approved in China for hypercholesterolemia management but remains unapproved by major global r...BACKGROUND: Ongericimab, a novel proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody, has recently been approved in China for hypercholesterolemia management but remains unapproved by major global regulatory agencies. This systematic review and meta-analysis provides the first pooled evidence on its efficacy and safety in participants with high cholesterol level. OBJECTIVE: To evaluate the efficacy of ongericimab to reduce lipid levels compared with placebo, assess its effects on other atherogenic and antiatherogenic lipid parameters, and determine its safety profile in randomized controlled trials (RCTs). METHODS: A comprehensive search of databases such as PubMed, Embase, and Cochrane Library from start to July 2025 identified RCTs comparing ongericimab with placebo. Primary outcome was percentage change in low-density lipoprotein cholesterol (LDL-C). Secondary outcomes included changes in other lipid parameters and safety endpoints. Data were pooled using a random-effects model, with heterogeneity assessed via the I² statistic. RESULTS: Four double-blind, placebo-controlled RCTs (n = 736) conducted in China were included. Ongericimab produced a profound reduction in LDL-C (mean difference: -68.74%; 95% CI, -72.22% to -65.26; I² = 0%) and significantly lowered total cholesterol, apolipoprotein (Apo) B, non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides, and lipoprotein(a), with the latter showing a robust -54.66% reduction after sensitivity analysis. HDL-C (+10.87%) and ApoA1 (+8.12%) were modestly increased. Safety analyses showed no significant differences in rates of upper respiratory tract infections, urinary tract infections, hyperuricemia, hepatic enzyme elevations, cardiovascular events, or severe adverse events compared with placebo. Only injection site erythema was significantly higher (odds ratios: 5.57; P = .02), though events were mild and transient. CONCLUSION: Ongericimab is a potent lipid-lowering agent with a favorable short-term safety profile, offering potential for patients requiring intensive LDL-C reduction. While findings are consistent and clinically compelling, they are derived solely from short-duration trials in Chinese populations and are limited to surrogate endpoints. Large, multiethnic cardiovascular outcomes trials are essential to confirm long-term benefits, assess rare adverse events, and establish its position among global lipid-lowering strategies.
BACKGROUND: While lipids are known prognostic markers in coronary heart disease (CHD), the long-term impact of cumulative low-density lipoprotein cholesterol (cum-LDL-C) and the duration of high LDL-C exposure remains un...BACKGROUND: While lipids are known prognostic markers in coronary heart disease (CHD), the long-term impact of cumulative low-density lipoprotein cholesterol (cum-LDL-C) and the duration of high LDL-C exposure remains unclear. OBJECTIVE: This study aimed to evaluate their association with major adverse cardiovascular events (MACE) in patients with CHD. METHODS: We included 1271 patients initially diagnosed with CHD between 2018 and 2023, each with at least 2 follow-up records. Time-weighted cum-LDL-C was calculated and categorized by quartiles (Q1-Q4). Duration of high LDL-C exposure was grouped as 0, 0-2, >2 years. Cox models were used to estimate hazard ratios (HRs) and 95% CIs for MACE, all-cause mortality, and other cardiovascular outcomes. A nomogram was developed for clinical risk scoring. RESULTS: Over a median follow-up of 1293 days, 196 patients experienced MACE. After multivariable adjustment, the highest cum-LDL-C quartile (Q4) showed significantly increased risks of MACE (HR: 3.50, 95% CI: 2.24-5.47), percutaneous coronary intervention (HR: 3.08, 1.41-6.71), and ischemic stroke (HR: 4.32, 2.25-8.30). Exposure to high LDL-C for >2 years was associated with a 1.68-fold higher MACE risk (95% CI: 1.18-2.40) and a 2.09-fold higher ischemic stroke risk (95% CI: 1.34-3.27). No significant associations were found with all-cause mortality or myocardial infarction. CONCLUSION: Both elevated cum-LDL-C and prolonged exposure to high LDL-C are associated with increased risks of MACE in patients with CHD. Extending lipid monitoring periods may help clarify cumulative risk and improve clinical management.
BACKGROUND: Statins are the cornerstone pharmacotherapy for lowering low-density lipoprotein cholesterol (LDL-C) and reducing risk of atherosclerotic cardiovascular disease (ASCVD). However, statin initiation and adheren...BACKGROUND: Statins are the cornerstone pharmacotherapy for lowering low-density lipoprotein cholesterol (LDL-C) and reducing risk of atherosclerotic cardiovascular disease (ASCVD). However, statin initiation and adherence are limited by statin-associated muscle symptoms (SAMS). Mobile health (mHealth) tools offer novel ways to assess real-time symptom data and facilitate shared decision-making. OBJECTIVE: To assess the feasibility and usability of an automated, text-message-based SAMS symptom-tracking platform to longitudinally track SAMS in patients who previously experienced muscle symptoms while on statin therapy. METHODS: We enrolled 19 patients and recorded baseline demographics, statin history, and technology use via an online survey. Quantitative SAMS scores were gathered via daily text messages, and qualitative symptom data were collected in weekly text messages. Upon study completion, participants reported study perceptions via an online exit survey. RESULTS: A total of 18 patients collected data, and 15 patients completed the 90-day study protocol. The response rate to text messages was 91.5% (92.2% for daily SAMS messages, 86.0% for weekly muscle symptom prompts). Overall reported statin adherence was 70%. Nine patients reported intolerable muscle symptoms at least once during the study, and intolerable symptom scores represented 3% of all reported symptom scores. Patients reported overall satisfaction with the study and found the SAMS scores helpful. CONCLUSIONS: Patients with previously reported SAMS successfully engaged with a text-message-based symptom-tracking platform with high interactivity and acceptability. This study demonstrates the feasibility and usability of an automated mHealth platform for longitudinally tracking SAMS in patients on statin therapy, and may provide a means for improving shared decision making to tailor statin therapy and improve adherence.
BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder characterized by extreme hypertriglyceridemia (>1000 mg/dL), recurrent pancreatitis, and lipoprotein lipase (LPL) deficiency. FCS...BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder characterized by extreme hypertriglyceridemia (>1000 mg/dL), recurrent pancreatitis, and lipoprotein lipase (LPL) deficiency. FCS is caused by biallelic loss-of-function variants in LPL or in 4 other genes encoding its cofactors and regulators, including LMF1 (lipase maturation factor 1). Variants in LMF1 are rare and present only in 1% to 2% of the FCS cases. OBJECTIVE: To assess in 3 patients with severe hypertriglyceridemia and recurrent pancreatitis and in whom a homozygous LMF1 duplication, initially classified as a variant of uncertain significance (VUS) was identified, post-heparin LPL activity. METHODS: We collected demographics, fasting lipid profiles, and body mass index, and performed next-generation sequencing using a targeted panel that included canonical FCS genes. A homozygous in-frame duplication in LMF1 (c.914_928dup; p.Ser309_Phe310dup) was identified. Variants were classified according to American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines and cross-referenced with public archive of reports of the relationships among human variations and phenotypes (ClinVar), The Human Gene Mutation Database at the Institute of Medical Genetics in Cardiff (HGMD), Leiden Open Variation Database (LOVD), The Single Nucleotide Polymorphism database (dbSNP), The Genome Aggregation Database (gnomAD), and in-house databases. LPL activity was assessed in post-heparin plasma using a radiometric assay. RESULTS: All 3 patients were homozygous for c.914_928dup (this variant was classified as a VUS) and exhibited markedly reduced LPL activity (<20% of normal). Clinical manifestations were consistent with FCS, including extreme triglyceride elevations and recurrent pancreatitis. One patient died from fulminant pancreatitis. CONCLUSION: The combined clinical, biochemical, and genetic evidence supports the reclassification of LMF1 c.914_928dup (p.Ser309_Phe310dup) as likely pathogenic according to ACMG/AMP guidelines and indicates its association with severe pancreatitis.
BACKGROUND: The size, composition, and functionality of high-density lipoprotein cholesterol (HDL-C) are potential biomarkers for predicting atherosclerosis, representing a major advance in the prevention and treatment o...BACKGROUND: The size, composition, and functionality of high-density lipoprotein cholesterol (HDL-C) are potential biomarkers for predicting atherosclerosis, representing a major advance in the prevention and treatment of cardiovascular diseases. OBJECTIVE: This study aims to explore HDL-C concentrations and a derived HDL functionality score (HFS), and to investigate suggestive genetic associations in a representative Brazilian population. METHODS: This is an observational cross-sectional study. Plasma lipid profiles were analyzed using an automated system. The Lipoprint System determined HDL particle sizes. HFS was calculated using a composite based on the large HDL particle concentration combined with relevant cardiovascular data from demographic and clinical parameters. After DNA extraction, genotyping, and quality control, information on 330,656 single-nucleotide polymorphisms (SNPs) was available for genome-wide association studies (GWAS) of HFS. RESULTS: Among 345 participants, HDL functionality was impaired in 38%. Those with low functionality exhibited higher average waist circumference, systolic blood pressure, and glucose, as well as lower HDL-C concentrations, compared with those with high HDL functionality (P < .05). GWAS revealed suggestive associations for 5 SNPs and HFS, including rs11730709, rs78565063, and rs11786395 (P < 1 × 10), as well as rs12734338 and rs36019094 (P < 1 ×10). Additional regression analyses showed that SNPs rs12734338 and rs36019094 were positively associated with HFS, while rs11730709 showed an inverse association. Furthermore, rs12734338 increased the prevalence of low HFS by 41%, whereas rs11730709 reduced it by 34%. CONCLUSION: These findings suggest potential genetic loci associated with the HFS, creating an opportunity for further investigations. Replication in larger and independent cohorts is warranted to confirm and extend these observations.
BACKGROUND: Metabolic syndrome is a cluster of increased waist circumference, high blood pressure, dyslipidemia, and impaired glucose tolerance, with a rising prevalence in Saudi Arabia. The triglyceride-glucose index (T...BACKGROUND: Metabolic syndrome is a cluster of increased waist circumference, high blood pressure, dyslipidemia, and impaired glucose tolerance, with a rising prevalence in Saudi Arabia. The triglyceride-glucose index (TyG) has gained popularity as a surrogate marker for insulin resistance. OBJECTIVE: To evaluate the diagnostic performance of the TyG index and TyG-related markers in identifying metabolic syndrome in Saudi nationals. METHODS: This cross-sectional study included 645 Saudi nationals aged 18 to 65 years. The performance of the TyG index and TyG-related markers (TyG-body mass index [TyG-BMI], TyG-waist circumference [TyG-WC], and TyG-waist-to-height ratio [TyG-WHtR]) was evaluated for identifying metabolic syndrome. RESULTS: The prevalence of metabolic syndrome was 18.6%. TyG index cutoff of 8.77 yielded 90.0% sensitivity, 80.0% specificity, and an area under the curve of 0.907 (95% CI: 0.88-0.93). Sex-specific analysis showed optimal cutoffs of 8.83 for males and 8.77 for females. The multivariable-adjusted odds ratio for the highest TyG quartile was 3.95 (95% CI: 1.55-10.1). Overall, TyG demonstrated excellent diagnostic performance. However, TyG-BMI and TyG-WHtR outperformed TyG in lean individuals, supporting the "personal fat threshold" hypothesis. CONCLUSION: Despite the cross-sectional, single-center design, these findings support the use of the TyG index as a practical screening tool for metabolic syndrome in Saudi nationals.
BACKGROUND: In heterozygous familial hypercholesterolemia (HeFH), low-density lipoprotein cholesterol (LDL-C) remains the primary treatment target, yet emerging evidence suggests apolipoprotein B (ApoB) may offer superio...BACKGROUND: In heterozygous familial hypercholesterolemia (HeFH), low-density lipoprotein cholesterol (LDL-C) remains the primary treatment target, yet emerging evidence suggests apolipoprotein B (ApoB) may offer superior cardiovascular risk stratification. ApoB/LDL-C discordance occurs when ApoB and LDL-C provide conflicting risk information, potentially identifying patients at heightened atherosclerotic cardiovascular disease (ASCVD) risk despite apparently controlled LDL-C levels. However, evidence in genetically confirmed HeFH cohorts is sparse. OBJECTIVE: To examine whether ApoB/LDL-C discordance associates with ASCVD events in a genetically confirmed HeFH cohort and to generate hypotheses for future validation studies. METHODS: This retrospective cohort study included 424 genetically confirmed HeFH patients (median age 51 years, 54.5% female) followed for a median of 9.1 years. Patients were classified as concordant (both ApoB and LDL-C above or below sex-specific thresholds) or discordant. Cox proportional hazards models evaluated associations with ASCVD events (myocardial infarction, stroke, coronary revascularization), adjusting for age, sex, diabetes, hypertension, smoking, statin therapy, and baseline lipid parameters. RESULTS: Among 424 patients, 61 ASCVD events occurred (41 prevalent, 20 incident). ApoB/LDL-C ratio ≥0.31 g/mmol associated with higher event rates (27.6% vs 11.8%, P = .0022). Adjusted hazard ratio was 38.55 (95% CI 3.72-399.36), though marked by extreme instability from sparse data stratification and small event counts. Additional exploratory analyses using R software revealed linear correlation patterns and threshold-based associations supporting the discordance hypothesis. CONCLUSION: These preliminary findings suggest ApoB/LDL-C discordance may identify residual ASCVD risk in HeFH patients, warranting prospective validation in larger, independent cohorts before clinical application.
BACKGROUND: Observational and genetic evidence show associations of high remnant cholesterol levels with atherosclerotic cardiovascular disease (ASCVD). New drugs have been developed that substantially lower remnant chol...BACKGROUND: Observational and genetic evidence show associations of high remnant cholesterol levels with atherosclerotic cardiovascular disease (ASCVD). New drugs have been developed that substantially lower remnant cholesterol; however, the corresponding absolute risk reduction of ASCVD remains unclear. Remnant cholesterol can be measured directly or calculated, but few studies have analyzed the effects of directly measured remnant cholesterol. OBJECTIVE: To estimate the 10-year absolute risk reductions of ASCVD according to proportional reduction of individual very low-density lipoprotein (VLDL) cholesterol levels among individuals with levels above 1 mmol/L (39 mg/dL). METHODS: We used VLDL cholesterol measured by nuclear magnetic resonance spectroscopy to quantify directly measured remnant cholesterol. We estimated the reduction in the average 10-year ASCVD risk associated with an intervention targeting the 2021 individuals in the Copenhagen General Population Study with VLDL cholesterol levels above 1 mmol/L (39 mg/dL), assuming a proportional reduction in their individual VLDL cholesterol levels. RESULTS: We found that a 50% or 80% proportional reduction in VLDL cholesterol was associated with a 10-year absolute risk reduction of ASCVD of 3.0% (95% CI: 2.6%-3.4%) and 4.5% (3.9%-5.1%), respectively. CONCLUSION: This suggests a clinically meaningful benefit from lowering of VLDL cholesterol in primary prevention.
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 infarc...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.
BACKGROUND: Although the association between sleep duration and lipid profiles and/or cardiovascular disease has been extensively studied, evidence regarding sleep quality remains limited. OBJECTIVE: This study aimed to...BACKGROUND: Although the association between sleep duration and lipid profiles and/or cardiovascular disease has been extensively studied, evidence regarding sleep quality remains limited. OBJECTIVE: This study aimed to investigate the association of sleep duration and quality with lipid parameters, including serum concentration of small dense low-density lipoprotein cholesterol (sdLDL-C) in a Japanese population. METHODS: A total of 24,984 Japanese men and women who had a medical checkup between April 2018 and March 2019 were included in this study. Data on sleep duration and sleep quality were obtained using self-reported questionnaires. Participants were classified into 3 groups based on sleep duration (<6 hours, 6-8 hours, and ≥8 hours). Sleep quality was categorized as either good or poor. Blood samples were used to measure serum lipid profiles, including sdLDL-C. Group comparison and multivariate analyses were performed to assess the association between sleep and these lipid parameters. RESULTS: In the <6-hour group, poor sleepers had significantly higher serum levels of median sdLDL-C than good sleepers in both genders (34.1 vs 31.7 mg/dL in men, 26.9 vs 24.0 mg/dL in women, respectively). A similar trend was observed in the 6-8-hour group, whereas no significant difference was found in the ≥8-hour group. Multivariable log-linear regression showed that poor sleep quality was associated with higher sdLDL-C levels independent of confounders. CONCLUSION: Poor sleep quality is associated with unfavorable lipid profiles, especially elevated sdLDL-C levels. Recognizing sleep quality as a modifiable lifestyle factor could contribute to reducing lipid abnormalities and preventing cardiovascular disease.
BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia, with an increasing incidence due to population aging. Approximately two-thirds of the people affected are women, possibly due to biological and hormo...BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia, with an increasing incidence due to population aging. Approximately two-thirds of the people affected are women, possibly due to biological and hormonal factors. Also, lipids could play an important role in AD and show associations with cognitive impairment. Apolipoprotein E allele 4 (ApoE ε4) genotype and cardiovascular (CV) risk lipid ratios could be relevant in lipidomic studies. OBJECTIVE: This work aims to identify specific alterations in plasma lipid profiles associated with AD in women and to explore these alterations related to ApoE and 2 CV risk lipid ratios. METHODS: A lipidomic mass spectrometry-based method was applied to plasma samples from a clinical cohort of women. The patients were accurately classified into AD (n = 76) and non-AD (n = 74) groups by cerebrospinal fluid amyloid beta (Aβ)42/Aβ40 levels. The identified lipid species were evaluated and grouped into families and subfamilies. The lipids with significant differences between groups were examined in relation to ApoE genotype and 2 CV risk ratios (total cholesterol/high-density lipoprotein [HDL], triglycerides/HDL). RESULTS: Fatty acyls and monoacylglycerols showed higher levels in AD compared with non-AD, while diacylglycerols showed lower levels in AD. Also, specific subfamilies correlated with aging, CV risk, AD biomarkers, and cognitive status. Of the 627 lipid species detected, 45 showed statistically significant differences between groups, and some of them [lysophosphatidylcholine (24:1), diacylglycerol (18:0/18:1), and triacylglycerol (50:3)] showed significant associations with ApoE genotype and CV risk. CONCLUSION: This study identified associations between lipid profiles in women and AD pathology, ApoE ε4 genotype, and high CV risk ratios.