Journal of clinical lipidology最新文献

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: 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, to 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: 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: 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^-5), as well as rs12734338 and rs36019094 (P < 1 ×10^-8). 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 (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: 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: The effects of lipid traits on colorectal cancer (CRC) risk and the extent to which obesity may modify these effects remain unclear.

Objective: To examine the associations between lipid traits and CRC risk using an observational study and Mendelian randomization (MR) analyses, and the role of weight status in the potential associations.

Methods: In the Guangzhou Biobank Cohort Study (GBCS), lipid profiles were measured during 2003-2008, and CRC events were identified through record linkage with the cancer registry. MR analyses assessed the causal effects of lipid traits on CRC using a genome-wide association study meta-analysis of 185,616 Europeans.

Results: Among 28,576 GBCS participants followed until 2020, 599 CRC events occurred. Participants in the highest quartile of apolipoprotein B (apoB) had a higher CRC risk (hazard ratio [HR] 1.43, 95% CI 1.02-2.01). This association remained in those with overweight/obesity (HR 2.21, 95% CI 1.28-3.83). MR analyses supported a detrimental effect of apoB on CRC (odds ratio 1.12 per 1 SD, 95% CI 1.02-1.22). MR analyses also showed positive associations for total cholesterol and the apoB/apolipoprotein A-I ratio, which were not significant in the observational study.

Conclusion: Higher apoB levels were associated with an increased CRC risk in both observational and MR analyses, suggesting a potential role of apoB in CRC prevention, especially among participants with overweight/obesity. However, the limitations of single-time lipid measurements and the use of different ancestries across study designs indicate the need for further research to confirm the robustness and generalizability of the findings.