Journal of clinical lipidology最新文献

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: 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.

Background: 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.

Background: Chronic vascular inflammation may persist after Kawasaki disease (KD), but the long-term cardio-cerebrovascular prognosis remains unclear. This study aimed to investigate the association between childhood KD and subsequent cardio-cerebrovascular risks.

Methods: A meta-analysis was performed on observational studies from PubMed, Embase, and Web of Science that compared individuals with and without a history of KD, assessing outcomes including lipid profiles, vascular ultrasound indices, and cardio-cerebrovascular events using a random-effects model.

Results: Fifty-one articles were meta-analyzed (46 on lipid and vascular markers, 5 on cardio-cerebrovascular events). Pooled analysis revealed reduced high-density lipoprotein cholesterol (HDLC) (weighted mean difference [WMD], 95% CI: -2.54, -4.31 to -0.77), impaired flow-mediated dilation (FMD) (WMD, 95% CI: -3.98, -5.78 to -2.17), increased carotid intima-media thickness (CIMT) (WMD, 95% CI: 0.03, 0.01-0.04), elevated ankle-brachial pulse wave velocity (BaPWV) (WMD, 95% CI: 46.00, 9.21-82.79), and a 4.4-fold increased risk (relative risk, 95% CI: 4.41, 4.02- 4.85) of cardio-cerebrovascular events vs controls. Subgroup analysis demonstrated reduced HDLC levels in patients with coronary artery lesions (CAL) (WMD, 95% CI: -3.70, -6.90 to -0.50) and Asian populations (WMD, 95% CI: -4.17, -6.86 to -1.47), along with FMD (with CAL: WMD, 95% CI: -7.01, -8.99 to -5.04; Asia: WMD, 95% CI: -5.60, -7.18 to -4.01) and increased CIMT (with CAL: WMD, 95% CI: 0.01, 0.00-0.02; Asia: WMD, 95% CI: 0.02, 0.01-0.03). Notably, reductions in both HDLC (WMD, 95% CI: -1.90, -2.39 to -1.40) and FMD (WMD, 95% CI: -5.29, -8.15 to -2.44) persisted in individuals over 10 years after KD.

Conclusion: This meta-analysis highlights that prior KD, regardless of CAL status, may confer lasting impairments in vascular homeostasis and dyslipidemia, potentially increasing the lifetime risk of developing cardio-cerebrovascular diseases.

Background and objectives: Hypertriglyceridemia (HTG) may result from various etiologies, including the rare autosoma 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.

Background: The effects of evinacumab on HDL function remains unclear.

Objective: We aimed to clarify the effects of evinacumab on HDL function.

Methods: Serum cholesterol uptake capacity (CUC) levels, which represent HDL function were determined using our original cell-free assay before and after the introduction of evinacumab in patients with genetically diagnosed homozygous familial hypercholesterolemia (HoFH) (N = 5, mean age = 54 years, male = 2).

Results: Significant reductions were observed in median LDL cholesterol level by evinacumab (152 mg/dL to 88 mg/dL, 242.1%, p = 0.008), while the median HDL cholesterol level was unchanged (37 mg/dL to 30 mg/dL, -23.3%, p = 0.29). We found significant increase of the median CUC level (122 to 149 arbitrary unit [A.U.], +22.1%, p = 0.03). The percent change of CUC was positively correlated with that of HDL cholesterol (Pearson's R² = 0.07471), while there was no correlation between that of CUC and LDL cholesterol (Pearson's R² = 0.0007).

Conclusion: HDL function assessed by serum CUC level increased by evinacumab in patients with genetically diagnosed HoFH, although the change of CUC was correlated with that of HDL cholesterol level.

Background: Epicardial adipose tissue (EAT), a visceral fat depot with metabolic and inflammatory properties, has been increasingly recognized as a potential marker for coronary artery disease (CAD). However, its clinical utility and optimal cut-off values remain under investigation.

Objective: To assess the association between 2D echocardiographic EAT thickness and the presence and severity of obstructive CAD, and to determine optimal EAT thresholds for predicting significant CAD.

Methods: This cross-sectional study included 120 patients undergoing coronary angiography at a single tertiary center in Tunisia. EAT thickness was measured echocardiographically at end-systole and end-diastole in parasternal long- and short-axis views. CAD severity was evaluated using Syntax and Gensini scores. Patients were stratified into obstructive and non-obstructive CAD groups and further divided into tertiles based on EAT thickness.

Results: Obstructive CAD was identified in 66.7% of patients. EAT thickness was significantly higher in those with obstructive CAD (diastolic: 3.29 ± 0.99 mm vs 2.15 ± 1.38 mm; systolic: 5.68 ± 1.36 mm vs 4.05 ± 1.88 mm; P < .001 for both). Diastolic EAT > 2.45 mm and systolic EAT > 4.4 mm were independent predictors of obstructive CAD (odds ratio = 3.37 and 10.57, respectively), with strong diagnostic performance (area under the curve: 0.83 and 0.82). EAT thickness also correlated positively with Gensini and Syntax scores (r ≈ 0.5, P < .001), and higher tertiles were associated with multivessel disease and calcification.

Conclusion: Echocardiographic EAT thickness is a reliable, noninvasive predictor of obstructive CAD and correlates with disease complexity. Given its simplicity and predictive value, it may serve as a useful screening tool for CAD severity stratification. Further large-scale studies are warranted to validate cut-off values and standardize assessment protocols.

Background: Cardiometabolic multimorbidity (CMM) is an emerging public health challenge in China, yet no nationwide study has examined its patterns and associations with combined unhealthy behaviors using nationally representative data.

Objective: (1) to assess the prevalence, patterns, and geographical distribution of CMM among Chinese adults, (2) to investigate the association between individual and combined unhealthy behaviors and the risk of CMM, and (3) to examine the clustering role of individual cardiometabolic diseases, particularly dyslipidemia, within multimorbidity patterns.

Methods: This study used secondary data from the 2015 China National Nutrition Health Survey involving 118,489 adults aged ≥18 years. We determined the prevalence and geographical distribution of CMM, identified patterns using association rule mining (ARM), and analyzed the relationships between unhealthy behaviors and CMM using multivariable logistic regression.

Results: The prevalence of CMM was 16.2% among Chinese adults (n = 19,840). ARM revealed dyslipidemia as a key clustering component, appearing in 56.8% of multimorbid cases despite representing only 16.1% individual prevalence. The most common dyad was dyslipidemia-hypertension (9.3% of the total population), followed by hypertension-diabetes (7.3%). Dyslipidemia showed strong bidirectional associations with diabetes (lift = 2.10), while hypertension was central to 80% of multimorbidity clusters. Geographic analysis showed that CMM prevalence peaked in northeastern provinces and was lowest in southern and western regions. Unhealthy behaviors showed dose-dependent associations with CMM risk: daily alcohol use (adjusted odds ratios [aOR] = 1.44), smoking (aOR = 2.58), and poor diet (aOR = 1.29). Combined unhealthy behaviors demonstrated progressive associations with multimorbidity development.

Conclusion: This nationally representative study revealed dyslipidemia as a central clustering component in CMM, suggesting targeted lipid management could help prevent multimorbidity progression.