Journal of clinical lipidology最新文献

Background: Autosomal recessive hypercholesterolemia (ARH) is a rare form of genetic hypercholesterolemia consequent to pathogenic variants in the low-density lipoprotein receptor adaptor protein 1 (LDLRAP1) gene, coding for a protein responsible for moving LDL-receptor (LDL-R) to its site of activity. ARH is characterized by very high levels of LDL cholesterol (LDL-C), leading to aggressive and frequently premature atherosclerotic cardiovascular disease (ASCVD). Lowering of LDL-C is the main target of treatment; however, classical lipid-lowering agents, for example, statins, frequently have a modest response, in view of their selective LDL-R-raising activity.

Objective: Among newer agents with an LDL-R-independent mechanism, evinacumab has been shown to be effective in homozygous familial hypercholesterolemia, but few data are available in LDLRAP1 variant carriers.

Methods: We here report 2 cases of this extremely rare form of familial hypercholesterolemia with a surprising response to evinacumab. Evinacumab was added to maximally tolerated background therapy.

Results: In the first patient, who had severe ASCVD and a prior inadequate response to statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and lomitapide, evinacumab reduced time-averaged LDL-C by 82% (from 549 to 62 mg/dL). In the second patient, evinacumab achieved a sustained 73.8% LDL-C reduction, maintaining levels <55 mg/dL and allowing discontinuation of the PCSK9 inhibitor.

Conclusion: These cases demonstrate a marked and clinically meaningful LDL-C-lowering effect of evinacumab in ARH, supporting its use as an effective LDL-R-independent therapeutic option.

Background: Several studies have linked skeletal muscle mass with cardiovascular disease. The clinical significance of myosteatosis in subclinical atherosclerosis has not been well investigated.

Objective: The aim of this study was to explore the relationship between intermuscular adipose tissue (IMAT) and subclinical atherosclerosis, and to determine the extent to which this association is mediated by metabolic factors.

Methods: We retrospectively enrolled 1993 participants who underwent abdominal computed tomography (CT) scans in our health promotion center between April 2021 and October 2023. IMAT was assessed by abdominal quantitative CT scans. Carotid atherosclerosis (CAS) and brachial ankle pulse wave velocity (baPWV) were selected as subclinical atherosclerosis markers.

Results: Compared with participants without CAS, those with CAS showed significantly increased IMAT% (7.40 ± 3.37% vs 6.76 ± 2.66%, P < .01). According to a multiple logistic regression model, IMAT% was significantly correlated with CAS (odds ratio [OR] = 1.18, 95% CI 1.13-1.23, P < .001) and baPWV (OR = 1.25, 95% CI 1.13-1.37, P < .001). However, when the model was adjusted for age, the associations of IMAT% with CAS and baPWV were no longer significant. In stratified analyses, there was a significant relationship between IMAT% and subclinical atherosclerosis in participants <60 years old, but not in those ≥60 years old. Mediation analysis showed that body mass index (BMI), blood pressure, fasting plasma glucose, and hemoglobin A1c partially accounted for a statistical portion of the association between IMAT% and subclinical atherosclerosis.

Conclusion: IMAT% is positively correlated with subclinical atherosclerosis. Furthermore, this association may be partially mediated by BMI, blood pressure, and blood glucose levels.

Background: Dyslipidemia is a universal finding in nephrotic syndrome with relapse, but there is limited data on its prevalence in disease remission.

Objective: Primary objectives of the study were to identify dyslipidemia and analyze the profile of serum apolipoproteins and lipoprotein(a) in children with nephrotic syndrome in disease remission.

Methods: This cross-sectional study included children (2-18 years) with nephrotic syndrome. A detailed history was elicited, and an examination was performed; blood investigations included glycosylated hemoglobin, serum albumin, kidney function tests (KFT), fasting lipid profile, serum apolipoprotein A-1 (ApoA-1), apolipoprotein B (ApoB), and lipoprotein(a), and a spot urine for urine protein-to-creatinine ratio.

Results: The median age (IQR) of 92 enrolled children (M65; F27) was 8 (6-11) years. Forty-seven had steroid-sensitive nephrotic syndrome (SSNS), 29 had steroid-resistant nephrotic syndrome (SRNS) in disease remission, and 16 were in relapse and included for comparison. Dyslipidemia was seen in 39.5%, with a prevalence of 32% in SSNS, 51.7% in SRNS during remission, and 100% in children in relapse, using conventional markers. ApoB/ApoA-1 ratio ≥0.6 was seen in 14.2% and 29.6% of children with SSNS and SRNS, respectively, while a ratio ≥0.8 was seen in only 5.2% of those in remission. The median values of the ApoB/ApoA-1 ratio in remission and relapse were 0.5 (0.4-0.6) and 0.85 (0.62-1.33), respectively. ApoB, ApoA-1, and ApoB/ApoA-1 showed sensitivities of 63.3%, 40%, and 13.3%, and specificities of 82.6%, 80.4%, and 100%, respectively, for the diagnosis of dyslipidemia, and receiver operator characteristic analysis showed area under the curve of 0.704, 056, and 0.65, respectively.

Conclusion: Identification of dyslipidemia using conventional parameters may lead to overdiagnosis in nephrotic syndrome during disease remission; the ApoB/ApoA-1 ratio appears to be a better marker.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition effectively lowers low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk, but its pleiotropic effects remain insufficiently defined. This study examined whether PCSK9 inhibition influences vascular and systemic inflammation and high-density lipoprotein (HDL) antioxidant function.

Objective: To investigate the effects of PCSK9 inhibition on vascular inflammation, systemic inflammatory markers, and high-density lipoprotein (HDL) antioxidant function in a real-world patient cohort.

Material and methods: In this monocentric, prospective study, blood samples from 89 patients were collected before and 3 to 6 months after initiation of PCSK9 inhibitor therapy. Lipoprotein-associated phospholipase A2 (LpPLA2) was measured as a marker of vascular inflammation. HDL antioxidant function was assessed by HDL lipid peroxide content (HDL_ox). Systemic inflammation was evaluated via high-sensitivity C-reactive protein (hsCRP) and a predefined cytokine panel.

Results: Seventy-three patients (82.0%) received alirocumab or evolocumab, and 16 (18.0%) received inclisiran. LDL-C decreased by 46.7% (120-64.5 mg/dL, P < .0001). LpPLA2 declined significantly (443.5-265.5 IU/L, P < .0001) and correlated with LDL-C reduction (R² = 0.58, P < .0001). HDL_ox did not change (1.190-1.210, P = .3438). Interferon gamma-induced protein (IP) 10 (P = .0141) and interleukin (IL)-2 (P = .0371) decreased, whereas hsCRP and other cytokines-including IL-1β, IL-4, IL-6, IL-8, IL-10, IL-17A, tumor necrosis factor-α, monocyte chemotactic protein-1, interferon-γ, and free radicals-remained unchanged (all P > .05).

Conclusion: PCSK9 inhibition reduces LpPLA₂ and IP-10 without changing global inflammatory response or antioxidant function of HDL, which might indicate a decrease in chronic vascular inflammation without an undesired broad systemic immune alteration.

Background: The role of the apoptosis inhibitor of macrophages (AIM) in human lipid metabolism remains unclear.

Objective: This study aimed to investigate the cross-sectional associations between serum AIM and plasma metabolites and to determine if baseline AIM concentrations predict incident dyslipidemia.

Methods: This study used a community-based cohort of 3139 participants for cross-sectional metabolomic analysis. Among them, 1292 participants without dyslipidemia at baseline were followed prospectively for up to 8.5 years. Cox proportional hazards models were used to estimate hazard ratios for incident high low-density lipoprotein cholesterol and metabolic dyslipidemia (high triglycerides and/or low high-density lipoprotein cholesterol [HDL-C]) across AIM tertiles.

Results: Cross-sectionally, higher AIM concentrations were associated with elevated acylcarnitines and tricarboxylic acid cycle intermediates. Longitudinally, higher baseline AIM was associated with an increased risk of developing metabolic dyslipidemia in women (highest vs lowest tertile hazard ratio, 1.84) and showed a similar but smaller nonsignificant trend in men. The risk for high low-density lipoprotein cholesterol was significantly increased in women but not in men. These associations remained robust after multivariable adjustment.

Conclusion: Elevated baseline AIM concentrations were prospectively associated with the development of metabolic dyslipidemia in women, with a similar but nonsignificant trend in men, and with high LDL-C in women. The related metabolomic profile suggests enhanced lipolysis and altered lipid metabolism. Therefore, AIM may serve as a biomarker for future dyslipidemia, particularly for triglyceride and HDL-C dysregulation.

Background: Insulin resistance (IR) is a key contributor to poor cardiovascular outcomes following surgery but remains underrepresented in conventional cardiac risk models. The triglyceride-glucose index (TGI), a surrogate marker of IR, has emerged as a promising metabolic risk indicator.

Objective: To evaluate the prognostic value of preoperative TGI in predicting 1-year mortality among patients undergoing isolated coronary artery bypass grafting (CABG).

Methods: In this single-center retrospective cohort study, 705 adult patients who underwent isolated CABG between January 2022 and December 2023 were analyzed. TGI was calculated as ln[(fasting triglyceride × fasting glucose)/2]. Patients were stratified based on median TGI values. Multivariable logistic regression was performed to identify independent predictors of 1-year mortality, adjusting for age, gender, and diabetes mellitus.

Results: The cohort had a median age of 62 years; 21.3% were female. Diabetes and hypertension were present in 49.9% and 58.3% of patients, respectively. Higher TGI levels were observed in patients who died within 1 year (P = .016). TGI independently predicted 1-year mortality (odds ratio: 4.304; 95% CI: 1.30-14.24; P = .018). Elevated TGI was also associated with increased incidence of acute kidney injury (P = .011), longer intensive care unit stays, and prolonged intubation times (both P < .05).

Conclusion: Preoperative TGI is an independent predictor of 1-year mortality after CABG and may enhance current risk stratification tools. Integrating TGI into preoperative assessment could guide individualized perioperative management, particularly in metabolically high-risk patients. Prospective studies are warranted to validate these findings and evaluate the impact of TGI-based interventions.

We present a case of a young adult diagnosed with homozygous familial hypercholesterolemia despite a normal lipid panel (Table 1). A deeper dive into the details of the genotype resulted in recharacterization of the genetic diagnosis. The observed phenotype-genotype discordance reflects the importance of a team-based approach to guide patients and avoid misdiagnosis and optimize treatment strategies.