Journal of clinical lipidology最新文献

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.

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 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: 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.

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: 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.

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: 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: Despite guideline-directed low-density lipoprotein cholesterol (LDL-C) lowering, substantial residual vascular risk persists after stroke. Triglycerides (TG) and interleukin-6 (IL-6) have each been linked to this risk, yet their joint prognostic effect remains unclear.

Objective: To evaluate the cumulative prognostic association of baseline TG and IL-6 levels with the risk of recurrent vascular events after stroke.

Methods: We analyzed 962 consecutive patients (mean age, 71.0 years; male, 61.1%) with ischemic stroke or transient ischemic attack enrolled within 1 week of onset in a prospective observational study. TG levels were dichotomized at 150 mg/dL, and IL-6 levels at the median of 4.0 pg/mL. Patients were classified as LL (low TG/low IL-6), HL (high TG/low IL-6), LH (low TG/high IL-6), and HH (high TG/high IL-6) groups. The primary endpoint was 1-year major adverse cardiovascular events (MACE), defined as recurrent stroke, acute coronary syndrome, or vascular death.

Results: Both TG ≥ 150 mg/dL and IL-6 ≥ 4.0 pg/mL were independently associated with an increased risk of MACE. Annual MACE rates increased across the 4 categories: 8.0%, 17.5%, 15.7%, and 23.8% in the LL, HL, LH, and HH groups, respectively (log-rank P = .001). Compared with LL, both HL (hazard ratio [HR], 2.12; 95% CI 1.18-3.80) and LH (HR, 1.71; 95% CI 1.05-2.77) had significantly higher risk, with HH showing the highest risk (HR, 2.43; 95% CI 1.40-4.23). Notably, this cumulative association remained consistent in patients with atherothrombotic stroke, those receiving statin therapy, and those with LDL-C levels <100 mg/dL or <70 mg/dL.

Conclusion: Stratification by TG and IL-6 levels revealed a cumulative increase in MACE risk after stroke, with the highest risk in patients with a dual burden of hypertriglyceridemia and systemic inflammation.