BACKGROUND: Keeping lipid levels under control is key to preventing secondary cardiovascular events; however, few studies have detailed in depth the characteristics of patients with coronary artery disease according to l...BACKGROUND: Keeping lipid levels under control is key to preventing secondary cardiovascular events; however, few studies have detailed in depth the characteristics of patients with coronary artery disease according to low-density lipoprotein cholesterol (LDL-C) levels. OBJECTIVE: To characterize patients with heart failure (HF) of ischemic or nonischemic etiology according to their LDL-C levels and considering the thresholds of <70 mg/dL and <100 mg/dL for LDL-C goals. METHODS: We present the results from the third phase of the Colombian Registry of Heart Failure (RECOLFACA). Sociodemographic, clinical, and laboratory data were collected at baseline. For the LDL-C goal analysis, we conducted a logistic regression model. RESULTS: We included 1124 patients, 554 with ischemic and 570 with nonischemic HF. The cohort included 379 women (33.7%) and 745 men (66.3%). There was a difference in the prescription of statins observed for both ischemic and nonischemic HF groups. Patients with ischemic HF had a 62% probability of being at the LDL-C <70 mg/dL goal (odds ratio [OR] = 1.62) and a 43% probability of being at the <100 mg/dL goal (OR = 1.43). Rosuvastatin was more used by patients with ischemic HF in the <70 mg/dL LDL-C goal group in comparison to those on the same goal group but with nonischemic HF (40.4% vs 19.6%, respectively). Similar results were reported for the <100 mg/dL LDL-C goal. CONCLUSION: Our findings provide insights into distinct clinical profiles, treatment patterns, and LDL goal attainment in patients with ischemic and nonischemic HF, emphasizing the need for tailored management strategies based on HF etiology.
BACKGROUND: Many patients receiving maximally tolerated statins fail to achieve recommended low-density lipoprotein cholesterol (LDL-C) levels, and multiple add-on nonstatin therapies are now available or in development,...BACKGROUND: Many patients receiving maximally tolerated statins fail to achieve recommended low-density lipoprotein cholesterol (LDL-C) levels, and multiple add-on nonstatin therapies are now available or in development, including obicetrapib and bempedoic acid. However, no direct comparison between these drugs is available. OBJECTIVE: We conducted a network meta-analysis of randomized, double-blind, placebo-controlled trials evaluating obicetrapib or bempedoic acid on top of statin therapy. METHODS: We conducted a network meta-analysis of randomized, double-blind, placebo-controlled trials evaluating obicetrapib or bempedoic acid on top of statin therapy. The primary outcome was the mean percentage change in LDL-C from baseline vs placebo. The secondary outcome was the mean percentage change in non-high-density lipoprotein cholesterol (non-HDL-C), treatment safety, including adverse events, serious adverse events, and cardiovascular composite endpoint. A random-effects model was used to synthesize evidence, test consistency, and generate treatment rankings. Heterogeneity and publication bias were also assessed. RESULTS: Six trials involving 6025 participants met the inclusion criteria. Obicetrapib resulted in a pooled LDL-C reduction of -33.17% (95% CI, -36.21 to -30.13) vs placebo, whereas bempedoic acid produced a reduction of -18.02% (95% CI, -18.83 to -17.21). The comparison of treatments showed an additional 15.15% in LDL-C reduction, favoring obicetrapib (95% CI, -18.30 to -12.00). There was no evidence of heterogeneity or inconsistency across the network (τ² = 0; I² = 0). Obicetrapib also showed a greater non-HDL-C reduction of -16.1% (95% CI, -19.1 to -13.1). Both drugs showed a comparable safety profile. Findings were consistent across multiple sensitivity analyses. No evidence of publication bias was detected. CONCLUSION: Among statin-treated patients requiring further LDL-C lowering, obicetrapib may represent an additional oral option to achieve the LDL-C target. Results should be interpreted in the context of currently available cardiovascular outcomes evidence, pending dedicated outcomes and long-term safety data.
BACKGROUND: Conflicting results have been reported as to the relative importance of apolipoprotein A-1 (apoA-1) vs high-density lipoprotein cholesterol (HDL-C) as markers of atherosclerotic cardiovascular disease (ASCVD)...BACKGROUND: Conflicting results have been reported as to the relative importance of apolipoprotein A-1 (apoA-1) vs high-density lipoprotein cholesterol (HDL-C) as markers of atherosclerotic cardiovascular disease (ASCVD) risk. OBJECTIVE: To compare the apoA-1 and HDL-C as predictors of cardiovascular risk. METHODS: Residual discordance analysis with Cox proportional hazard models comparing apoA-1 and HDL-C as markers of ASCVD risk was applied to a sample of 291,995 UK Biobank participants, followed for a median of 11 years. Interaction tests for the 2 markers and estimation of the effects of partitioning HDL-C into apoA-1, log-triglyceride, and the remaining residual were also performed. RESULTS: ApoA-1 and HDL-C had similar associations with ASCVD risk (hazard ratios [HRs] of 0.85, P value <.001 for both). The residual of HDL-C added significantly to the risk associated with apoA-1, as did the residual of apoA-1 to HDL-C. There was a statistically significant interaction between apoA-1 and HDL-C (HR = 1.05, 95% CI: (1.04-1.06); P < .001). Decomposing HDL-C into the 3 components, apoA-1 accounted for the largest portion of the effect, with an HR of 0.85 (95% CI: 0.83-0.86), with smaller effects for ln triglycerides: 1.04 (95% CI: 1.02-1.06) and the residual of HDL-C: 0.98 (95% CI: 0.96-0.995). CONCLUSION: HDL-C and apoA-1 have associations of equivalent strength with ASCVD risk, with significant interaction modifying the effect of one by the other. Upon decomposition, apoA-1 retained more of the effect of HDL-C as compared with log-triglycerides. While only observational, the results are consistent with the relation of HDL to risk not being determined by the concurrent level of triglyceride.
BACKGROUND: Ischemic stroke is a life-threatening condition, with high serum cholesterol recognized as a major risk factor. Recent studies suggest that vitamin B12 (VB12) deficiency is associated with changes in lipid me...BACKGROUND: Ischemic stroke is a life-threatening condition, with high serum cholesterol recognized as a major risk factor. Recent studies suggest that vitamin B12 (VB12) deficiency is associated with changes in lipid metabolism, but its specific role remains unclear. OBJECTIVE: This study aims to explore the relationship between VB12 levels and lipid metabolism in patients diagnosed with acute ischemic stroke. METHODS: This cross-sectional study included 328 patients with acute ischemic stroke hospitalized at the First Affiliated Hospital of Chongqing Medical University or the First Branch of Chongqing Medical University in Chongqing, China, between January 2023 and December 2023. The results of laboratory assays were measured to examine the association between VB12 levels and lipid metabolism. The analysis utilized chi-square tests, Mann-Whitney U tests, 2-sample t-tests, Kruskal-Wallis H-tests, Spearman rank correlation, and binary logistic regression. RESULTS: Patients with VB12 levels below 300 pg/mL had significantly higher levels of triglycerides, low-density lipoprotein cholesterol (LDL-C), and total cholesterol compared to those with VB12 levels above 300 pg/mL. Furthermore, significant changes in LDL-C levels were observed with varying concentrations of VB12, and VB12 deficiency was significantly associated with atherosclerosis-related lipid risk factors (LDL-C above 1.8 mmol/L and high-density lipoprotein cholesterol below 1.04 mmol/L), indicating a potential link between VB12 levels and lipid metabolism in patients with ischemic stroke. CONCLUSION: This study highlights the association between VB12 and lipid metabolism in patients with ischemic stroke, suggesting the importance of considering VB12 levels in clinical practice. These findings provide new insights into the potential role of VB12 in lipid metabolism, which may inform future research on atherosclerosis.
BACKGROUND: Residual atherosclerotic cardiovascular disease (ASCVD) risk remains common among adults treated with moderate-intensity statins, necessitating nonstatin therapy. Ezetimibe is the preferred first-line oral no...BACKGROUND: Residual atherosclerotic cardiovascular disease (ASCVD) risk remains common among adults treated with moderate-intensity statins, necessitating nonstatin therapy. Ezetimibe is the preferred first-line oral nonstatin therapy. However, bempedoic acid is emerging as an alternative, particularly in patients with statin intolerance. Cardiovascular outcomes with bempedoic acid among patients receiving moderate-intensity statins in routine care are not well-established. OBJECTIVE: To compare cardiovascular outcomes associated with bempedoic acid vs ezetimibe when added to background moderate-intensity statin therapy in the real world. METHODS: This retrospective cohort study used the TriNetX global federated health research network. Adults aged 18 years or older receiving moderate-intensity statin therapy with add-on bempedoic acid or ezetimibe were included. The primary outcome was a composite of stroke, myocardial infarction, ischemic heart disease, new-onset heart failure, or peripheral artery disease. Risk ratios (RRs) with 95% CIs were calculated. RESULTS: After matching, 6706 patients were included (n = 3353 per cohort). Bempedoic acid was associated with a significantly lower risk of the composite outcome compared with ezetimibe (16.7% vs 22.8%; RR: 0.73; 95% CI: 0.63-0.84). All individual cardiovascular endpoints favored bempedoic acid. Low-density lipoprotein cholesterol (LDL-C) reduction was greater with ezetimibe. CONCLUSION: Among adults on moderate-intensity statins, bempedoic acid was associated with significantly lower cardiovascular event rates compared with ezetimibe, despite smaller LDL-C reductions. These findings complement Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes and suggest greater ASCVD risk-reducing potential for bempedoic acid than currently reflected in clinical guidelines.
Essalamani R, Evagelidis A, Roubtsova A
… +9 more, Chong M, Pathan N, Pare G, Petrochenko EV, Reimund M, Remaley AT, Chalifour L, Schweitzer M, Seidah NG
J Clin Lipidol
· 2026 May · PMID 41807234
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BACKGROUND: Familial hypobetalipoproteinemia is a rare autosomal codominant disorder, often caused by a defect in apolipoprotein B (apoB) production required for lipoprotein formation and secretion. OBJECTIVE: Characteri...BACKGROUND: Familial hypobetalipoproteinemia is a rare autosomal codominant disorder, often caused by a defect in apolipoprotein B (apoB) production required for lipoprotein formation and secretion. OBJECTIVE: Characterization of the lipid profiles of 3 family members exhibiting very low circulating cholesterol levels. METHODS: Plasma samples from the control sibling and the affected patients were analyzed. Fast protein liquid chromatography and high-performance liquid chromatography were used to characterize the lipid profiles, size, and distribution of lipoprotein particles. Exome sequencing of family members revealed a single-nucleotide deletion in APOB in the 3 affected individuals. The effect of the single-nucleotide deletion on the secretion of apoB was analyzed in immortalized human hepatocyte (IHH) cells. RESULTS: Plasma lipid profiles revealed that the affected individuals have low levels of total cholesterol and low-density lipoprotein cholesterol, with no difference in lipoprotein particle size. DNA sequencing of APOB revealed a single heterozygote deletion of an adenosine in exon 3 at the nucleotide position 1268 in all affected members. This deletion introduces a reading frame shift at glutamine 380, resulting in a stop codon at position 397. The C-terminally truncated apoB, called apoB9, is a variant spanning ∼9% of the full-length protein. Upon expression of apoB9 in IHH cells, the protein did not exit the endoplasmic reticulum/cis-Golgi and, hence, was not secreted into the media. Molecular modeling revealed that apoB9 lacks the βA- and βB-sheets that are required for lipid particle formation, which can explain the absence of apoB9 secretion. CONCLUSION: Our data suggested that the affected family members have ∼50% to 60% lower apoB levels and are likely protected against the development of atherosclerosis and cardiovascular diseases.
BACKGROUND: Inclisiran is approved to reduce low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH). Cost-related nonadherence remai...BACKGROUND: Inclisiran is approved to reduce low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH). Cost-related nonadherence remains a significant challenge underlying the use and optimization of lipid-lowering therapies. OBJECTIVE: To describe the real-world changes in LDL-C levels and the out-of-pocket (OOP) costs associated with inclisiran in patients initiating treatment in infusion centers. METHODS: This retrospective, observational study reviewed electronic medical records of patients with a history of atherosclerotic cardiovascular disease or HeFH initiating inclisiran treatment between March 1, 2022, and November 30, 2022; patients were followed up until February 2024. Study outcomes included changes in LDL-C levels from baseline, OOP cost by payer type, and adverse events (AEs), if documented. RESULTS: Among 562 patients included in this analysis, the mean (SD) age at index was 70.6 (9.6) years, and 50.9% of patients were male. Most patients (80.2%) were covered by Medicare. In 274 patients with LDL-C measurements, mean (SD) baseline LDL-C was 147.2 (59.7) mg/dL. The average percent reduction from mean baseline LDL-C to mean follow-up was 51%. The median (IQR) OOP costs for the initial dose were $0 ($0-$0) for Medicare-insured patients and $0 ($0-$95) for patients covered by commercial insurance. Of patients insured by Medicare, 96% paid $0 OOP for both doses. AEs were reported by 24 patients (4%), of whom 12 (50%) discontinued treatment. CONCLUSION: These real-world data demonstrate significant LDL-C reductions within 1 year in patients who initiated inclisiran. Nearly all patients with Medicare had no OOP costs.
BACKGROUND: Sitosterolemia is a rare autosomal recessive lipid disorder caused by mutations in the ABCG5 or ABCG8 genes, resulting in excessive intestinal absorption and impaired biliary excretion of plant sterols, which...BACKGROUND: Sitosterolemia is a rare autosomal recessive lipid disorder caused by mutations in the ABCG5 or ABCG8 genes, resulting in excessive intestinal absorption and impaired biliary excretion of plant sterols, which leads to their accumulation in plasma and tissues. Clinical manifestations include premature coronary artery disease, liver dysfunction, hepatosplenomegaly, and hematologic abnormalities. OBJECTIVE: We report the first Polish family diagnosed with sitosterolemia. METHODS: A 19-year-old male patient with severe hypercholesterolemia and resistance to statin therapy and his family members were examined, including biochemical and imaging studies, serum sterol assessment by gas chromatography-mass spectrometry, and genetic testing using next-generation sequencing of genes involved in lipid metabolism. RESULTS: The proband presented with total cholesterol of 8.0 mmol/L, low-density lipoprotein cholesterol of 5.80 mmol/L, high-density lipoprotein cholesterol of 1.24 mmol/L, and triglycerides of 2.38 mmol/L. Genetic analysis revealed 2 variants in the ABCG8 gene in the patient and his brother: a pathogenic variant c.1083G>A (p.Trp361Ter), present in the patient's father, and a variant of uncertain significance c.1534G>A (p.Gly512Arg), present in the patient's mother. Serum sterol concentrations in the patient were markedly elevated, including campesterol (139.8 µmol/L), stigmasterol (2.2 µmol/L), isofucosterol (56.9 µmol/L), and sitosterol (333.9 µmol/L). Introduction of ezetimibe therapy combined with a low-plant sterol diet resulted in improvement of the lipid profile. CONCLUSION: These findings highlight the role of genetic testing and serum sterol measurement in the differential diagnosis of inherited lipid disorders, especially in patients with statin-resistant hypercholesterolemia. Early diagnosis of sitosterolemia is important to introduce an appropriate diet and pharmacotherapy.
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 thi...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: Niemann-Pick disease (NPD) is a rare autosomal recessive lysosomal storage disorder caused by acid sphingomyelinase (ASM) deficiency, resulting in progressive lipid accumulation in multiple cell types and org...BACKGROUND: Niemann-Pick disease (NPD) is a rare autosomal recessive lysosomal storage disorder caused by acid sphingomyelinase (ASM) deficiency, resulting in progressive lipid accumulation in multiple cell types and organs. OBJECTIVE: To describe a rare case of suspected NPD type B with secondary sea-blue histiocytosis and to explore its diagnostic implications. METHODS: Comprehensive clinical and laboratory evaluations were conducted to assess the patient's condition. RESULTS: We report a rare case of Niemann-Pick disease type B accompanied with secondary sea-blue histiocytosis in a 32-year-old woman who had previously undergone splenectomy for congenital splenomegaly. She presented with abdominal distension, poor appetite and abdominal pain. Clinical evaluations revealed decompensated cirrhosis with no neurologic abnormalities. Transjugular liver biopsy demonstrated foamy cells infiltration, while bone marrow examination identified sea-blue histiocytes (approximately 4.5% of nucleated cells) and Niemann-Pick cells (approximately 2.5%). Although ASM activity testing and SMPD1 sequencing were recommended, the patient declined further evaluation for financial reasons. CONCLUSION: This case highlights the significance of considering ASM deficiency in patients with cryptogenic cirrhosis and underscores the diagnostic value of histopathology when definitive gene or enzyme testing is unavailable. It also raises the possibility that prior splenectomy may influence the clinical presentation of the disease.
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...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 low-density lipoprotein-receptor (LDL-R) to its site of activity. ARH is characterized by very high levels of low-density lipoprotein 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: Analyses of statin trials by the Cholesterol Treatment Trialists' Collaboration have suggested larger relative risk reduction (RRR) for major adverse cardiovascular events (MACE) per 1 mmol/L (38.7 mg/dL) low...BACKGROUND: Analyses of statin trials by the Cholesterol Treatment Trialists' Collaboration have suggested larger relative risk reduction (RRR) for major adverse cardiovascular events (MACE) per 1 mmol/L (38.7 mg/dL) low-density lipoprotein cholesterol (LDL-C) lowering in primary prevention than in secondary prevention. However, controversy remains about the value of LDL-C lowering in primary prevention. OBJECTIVE: This meta-analysis examined the relationship between LDL-C reduction and MACE risk in primary prevention with statin and nonstatin LDL-C-lowering therapies in cardiovascular outcomes trials (CVOTs). METHODS: PubMed and Cochrane Central Register of Controlled Trials were searched from inception through August 26, 2025. The primary endpoint was the pooled RRR vs controls for 4-point composite MACE (coronary heart disease death, nonfatal myocardial infarction, fatal and nonfatal stroke, and coronary revascularization) per 1 mmol/L LDL-C lowering. RESULTS: Eleven CVOTs of solely primary prevention participants (n = 74,466) and 3 in which >80% of participants were primary prevention (n = 24,071) were identified (11 statin, 1 bempedoic acid, 1 ezetimibe, 1 statin+ezetimibe). In 13 trials, the pooled mean difference between groups in LDL-C reduction was 1.00 mmol/L (95% CI: 0.82-1.18 mmol/L) with a pooled estimate of 30% (relative risk: 0.70; 95% CI: 0.67-0.74) RRR for 4-point MACE per 1 mmol/L LDL-C reduction vs control. CONCLUSION: In CVOTs of solely or predominantly primary prevention participants, each 1 mmol/L reduction in LDL-C was associated with a 30% RRR in 4-point MACE. These results strengthen the evidence and rationale for the benefits of LDL-C lowering in primary prevention.
BACKGROUND: Dyslipidemia is a universal finding in nephrotic syndrome with relapse, but there are limited data on its prevalence in disease remission. OBJECTIVE: Primary objectives of the study were to identify dyslipide...BACKGROUND: Dyslipidemia is a universal finding in nephrotic syndrome with relapse, but there are 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 (male 65; female 27) 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.
Ahmad Z, Agarwala A, Cuchel M
… +16 more, Barton Duell P, Hegele RA, Hudgins L, Jamison A, Kalra D, Khera A, Knowles JW, Kullo IJ, Morales A, Rothstein MA, Saseen JJ, Soffer DE, Warden BA, Weintraub WS, Williams L, Goldberg AC
Familial hypercholesterolemia (FH) is a common genetic disorder characterized by lifelong elevated low-density lipoprotein cholesterol (LDL-C), leading to a high risk of early onset atherosclerotic cardiovascular disease...Familial hypercholesterolemia (FH) is a common genetic disorder characterized by lifelong elevated low-density lipoprotein cholesterol (LDL-C), leading to a high risk of early onset atherosclerotic cardiovascular disease (ASCVD). This document provides an update to the National Lipid Association's 2011 clinical guidance, summarizing the remarkable progress in the field. With a global prevalence of approximately 1 in 311, FH remains severely underdiagnosed. This guidance reviews current diagnostic criteria, including the expanding role of genetic testing to complement diagnosis and to facilitate cascade screening, and emphasizes a thorough differential diagnosis. It provides recommendations for universal pediatric screening and systematic cascade screening in families to improve detection. Management strategies include intensified LDL-C treatment goals for both primary and secondary prevention of ASCVD. A stepwise approach to optimal therapy is outlined, beginning with lifestyle interventions and pharmacotherapy with maximally tolerated statins and ezetimibe. This update incorporates newer agents, including proprotein convertase subtilisin/kexin type 9 inhibitors and bempedoic acid. Additional therapies, such as lomitapide and evinacumab for homozygous FH and lipoprotein apheresis for heterozygous and homozygous FH, are discussed. Further topics include cardiovascular imaging for risk stratification, management in specific populations and circumstances, such as planning for and during pregnancy and in pediatrics, and recognition of health disparities. This guidance equips clinicians with evidence-based strategies to improve the identification and care of patients with FH, ultimately reducing the high morbidity and mortality associated with this condition.
BACKGROUND: Management of low-density lipoprotein cholesterol (LDL-C) in patients with statin intolerance requires treatment options beyond statins. Pemafibrate, primarily used to lower serum triglycerides in patients wi...BACKGROUND: Management of low-density lipoprotein cholesterol (LDL-C) in patients with statin intolerance requires treatment options beyond statins. Pemafibrate, primarily used to lower serum triglycerides in patients with hypertriglyceridemia, has also been reported in some clinical trials to reduce LDL-C. OBJECTIVE: To evaluate the efficacy and safety of pemafibrate in patients with statin-intolerant hypercholesterolemia. METHODS: In this phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group trial, patients with statin-intolerant hypercholesterolemia and normal triglyceride levels were enrolled. The primary endpoint was the percentage change in calculated LDL-C from baseline to week 12. RESULTS: Seventy-one patients were randomly assigned to receive placebo or the extended-release (XR) formulation of pemafibrate at 0.2 mg/d or 0.4 mg/d. LDL-C decreased significantly from baseline in the pemafibrate groups (least squares mean [95% CI]: -20.0% [-24.1 to -15.9] for XR 0.2 mg/d; -24.8% [-28.8 to -20.9] for XR 0.4 mg/d), demonstrating superiority over placebo (-0.4% [-4.2 to 3.5]). Reductions in apolipoprotein B were also greater in the pemafibrate groups than in the placebo group (least squares mean; -18.2% for XR 0.2 mg/d; -20.6% for XR 0.4 mg/d; P < .001 vs placebo). Treatment-emergent adverse events were generally similar across groups, though slightly more frequent in the pemafibrate groups (47.8% for XR 0.2 mg/d and 54.2% for XR 0.4 mg/d) than in the placebo group (37.5%). CONCLUSION: Pemafibrate effectively and safely reduces LDL-C in patients with statin-intolerant hypercholesterolemia and normal triglyceride levels, offering a potential new therapeutic option for this population.