AIM: Isolated low high-density lipoprotein cholesterol (HDL-C) refers to low HDL-C levels with normal levels of triglycerides and low-density lipoprotein cholesterol. However, its prognostic significance remains controve...AIM: Isolated low high-density lipoprotein cholesterol (HDL-C) refers to low HDL-C levels with normal levels of triglycerides and low-density lipoprotein cholesterol. However, its prognostic significance remains controversial. This study aimed to investigate the association between isolated low HDL-C levels and the incidence of stroke and coronary artery disease (CAD). METHOD: This study included 496,973 Japanese individuals (mean age: 66.4 years) enrolled in municipal health insurance programs. Data on baseline clinical characteristics and cardiovascular outcomes were obtained from annual health checkup and health insurance claims data, respectively. Isolated low HDL-C was defined as HDL-C ＜40 mg/dL with normal levels of triglyceride and low-density lipoprotein cholesterol (LDL-C). RESULT: The frequency of isolated low HDL-C was 1.3%. Isolated low HDL-C was independently associated with the CAD incidence (hazard ratio [HR] = 1.87, P＜0.001). This association remained significant in age- and sex-separate analyses, as well as in the analysis of participants who were not taking lipid-lowering drugs and had severe comorbidities at baseline. Conversely, isolated low HDL-C levels were not associated with the incidence of ischemic stroke (HR = 1.08, P = 0.266) or hemorrhagic stroke (HR = 1.16, P = 0.223) in all participants. However, it showed a significant association with ischemic stroke in the subgroup analysis of those aged ＜65 years (HR = 2.21, P＜0.001) and men (HR = 1.17, P = 0.035). CONCLUSION: Isolated low HDL-C was associated with the incidence of CAD and ischemic stroke despite normal plasma levels of triglyceride and low-density lipoprotein cholesterol.
Atrial fibrillation is one of the most important causes of ischemic stroke and it is strongly associated with recurrent stroke, systemic embolism, heart failure, cognitive decline, and mortality. Oral anticoagulation, pr...Atrial fibrillation is one of the most important causes of ischemic stroke and it is strongly associated with recurrent stroke, systemic embolism, heart failure, cognitive decline, and mortality. Oral anticoagulation, preferably direct oral anticoagulants, remains the cornerstone of secondary stroke prevention in patients with atrial fibrillation and a history of ischemic stroke. However, ischemic stroke may still occur despite appropriate anticoagulation therapy, a condition often referred to as breakthrough ischemic stroke. This residual risk reflects heterogeneous mechanisms, including inadequate anticoagulant exposure, atrial cardiomyopathy, left atrial appendage thrombus, large-artery atherosclerosis, small-vessel disease, cancer-associated thrombosis, and other competing etiologies. Rhythm control has re-emerged as a disease-modifying strategy after the EAST-AFNET 4 trial, and its prespecified subgroup analysis suggested a potential benefit in patients with prior stroke. However, the recently reported STABLED randomized clinical trial, which specifically evaluated catheter ablation in addition to edoxaban-based standard therapy after a recent ischemic stroke, did not demonstrate a significant reduction in recurrent ischemic stroke, systemic embolism, all-cause mortality, or hospitalization for heart failure. These findings do not negate the value of rhythm control for symptom relief, atrial fibrillation burden reduction, and selected cardiovascular outcomes; however, they challenge the assumption that the restoration of sinus rhythm alone is sufficient for secondary stroke prevention. Future strategies should integrate optimized anticoagulation and early rhythm control when appropriate, with a systematic evaluation of competing stroke mechanisms, vascular risk factor control, and selected left atrial appendage interventions. The next frontier is not rhythm control alone but rhythm control embedded within mechanism-based secondary stroke prevention.
Koseki M, Makino H, Otsubo Y
… +12 more, Kawashiri MA, Fujii N, Fujita N, Yamamoto Y, Waldron A, Pordy R, Ali S, Sankoh S, Kainth P, Tada H, Tobita K, Harada-Shiba M
AIM: This sub-group analysis evaluated the long-term efficacy and safety of evinacumab, an angiopoietin-like 3 inhibitor, in adolescent and adult Japanese patients with homozygous familial hypercholesterolemia (HoFH) who...AIM: This sub-group analysis evaluated the long-term efficacy and safety of evinacumab, an angiopoietin-like 3 inhibitor, in adolescent and adult Japanese patients with homozygous familial hypercholesterolemia (HoFH) who were enrolled in the open-label, single-arm, extension of the Phase 3 ELIPSE HoFH pivotal trial. METHODS: Patients aged ≥ 12 years with HoFH on stable lipid-lowering therapies received intravenous evinacumab 15 mg/kg every 4 weeks and weekly/biweekly lipoprotein apheresis. Final results are reported. RESULTS: Eleven patients were enrolled and received at least 1 dose of evinacumab at baseline, including 9 adults who participated in the evinacumab pivotal study (evinacumab-continue) and 2 newly enrolled adolescent patients (evinacumab-naïve). Mean (standard error) percent decrease in LDL-C from baseline to Week 24 was 42.9% (7.4) in the overall cohort (n = 9) and 37.1% (7.9) in the evinacumab-continue group (n = 7), with reductions in LDL-C observed as early as Week 8 and persisting through Week 168. Evinacumab treatment was also associated with reductions in other lipid parameters measured, including apolipoproteins A1 and B, non-high density lipoprotein cholesterol (HDL-C), HDL-C, total cholesterol, fasting triglycerides, and lipoprotein(a). Similar lipid-lowering results were seen in the evinacumab-naïve group (n = 2). Treatment-emergent adverse events (TEAEs) occurred in all 11 patients. Serious TEAEs occurred in 3 (27.3%) patients, and none were treatment related. CONCLUSIONS: Evinacumab treatment resulted in sustained reductions in LDL-C and other lipid parameters in Japanese patients ≥ 12 years with HoFH, including those undergoing lipoprotein apheresis, and was generally well tolerated.
AIM: Reducing low-density lipoprotein cholesterol (LDL-C) levels is crucial for preventing atherosclerotic cardiovascular disease (ASCVD). Recommended lipid-lowering therapy (LLT) includes both oral (e.g., statins) and i...AIM: Reducing low-density lipoprotein cholesterol (LDL-C) levels is crucial for preventing atherosclerotic cardiovascular disease (ASCVD). Recommended lipid-lowering therapy (LLT) includes both oral (e.g., statins) and injectable agents. However, patient awareness of LDL-C management and adherence to it remain uncertain. METHODS: This cross-sectional study surveyed 415 Japanese patients with ASCVD using a web-based platform. The participants reported their understanding of LDL-C target values and the effects of LLT. Medication adherence was evaluated using the Extent of Nonadherence scale, and a binomial logistic regression analysis was performed to identify the factors associated with nonadherence. RESULTS: Approximately 58.1%-60.2% of the participants reported confidence in knowing their correct lipid target values and managing dyslipidemia appropriately. However, only 22.2% reported LDL-C targets of ＜50 or ＜70 mg/dL, and 43.4% believed their targets to be ＜50, ＜70, or ＜100 mg/dL. In contrast, 56.7% either reported LDL-C targets of ＜120, ＜140, or ＜160 mg/dL or did not know their targets. Regarding LLT, 65.8% were unaware that extreme lowering of LDL-C levels with LLT had no disadvantages, and 74.2% were unaware that injectable LLTs were available. Overall, 39.0% of the participants were nonadherent. Higher out-of-pocket costs (≥ 3,001 yen; adjusted odds ratio [OR]: 1.83, p = 0.024) and experience with self-injections (adjusted odds ratio: 2.34, p = 0.027) were significantly associated with nonadherence. CONCLUSIONS: Our findings highlight a considerable gap in patient knowledge and adherence to dyslipidemia management strategies. Interventions that promote patient education and shared decision-making are essential for improving adherence and achieving optimal LDL-C targets.
AIMS: The quantitative flow ratio (QFR)-derived pullback pressure gradient (PPG) characterizes the pathophysiological patterns of coronary atherosclerosis. This study investigated the plaque morphologies associated with...AIMS: The quantitative flow ratio (QFR)-derived pullback pressure gradient (PPG) characterizes the pathophysiological patterns of coronary atherosclerosis. This study investigated the plaque morphologies associated with these disease patterns. METHODS: This study used the institutional QFR-PPG database registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000056097). Patients who underwent elective stenting with pre-procedural optical coherence tomography and near-infrared spectroscopy intravascular ultrasound were included. Offline QFR and QFR-PPG analyses were performed, and the lesions were stratified into tertiles. RESULTS: A total of 168 de novo lesions were analyzed in this study. The QFR tertiles were defined as severe (＜0.61), moderate (0.61-0.71), and mild (＞0.71); the QFR-PPG tertiles were defined as diffuse (＜0.66), intermediate (0.66-0.79), and focal (＞0.79). The Severe QFR tertiles exhibited a smaller minimum lumen area (MLA) and higher frequencies of thin-cap fibroatheroma (TCFA) and layered plaque. In contrast, across the QFR-PPG tertiles, MLA and TCFA frequencies were similar, whereas the diffuse group exhibited more layered plaques and larger calcium angles. The maximum lipid-core burden index did not vary across the QFR-PPG tertiles. A multivariable analysis identified MLA and TCFA as independent predictors of QFR, while layered plaque and calcium angle independently predicted QFR-PPG. However, the lipidic features were not independent predictors of QFR. CONCLUSION: Multimodal intracoronary imaging demonstrated that QFR reflects luminal narrowing and the features of vulnerable plaques. Conversely, QFR-PPG reflects disease diffuseness, characterized by layered plaques and calcium burden rather than lipid-rich features.
AIM: Atrial cardiomyopathy (AC) is associated with cardiovascular events, but the benefit of anticoagulation in embolic stroke of an undetermined source (ESUS) remains unclear. We aimed to prospectively evaluate the prog...AIM: Atrial cardiomyopathy (AC) is associated with cardiovascular events, but the benefit of anticoagulation in embolic stroke of an undetermined source (ESUS) remains unclear. We aimed to prospectively evaluate the prognostic value of AC in patients with ESUS. METHODS: We prospectively enrolled patients with ESUS who were hospitalized within 7 days of onset (January 2019 - December 2021). AC was defined as an N-terminal pro-B-type natriuretic peptide level ＞250 pg/ml, P-wave terminal force in lead V1 ＞5000 µV·ms, or enlarged left atrial diameter. Ischemic stroke/transient ischemic attack (TIA) recurrence was evaluated using Fine-Gray sub-distribution hazard models with death as a competing event. Cox proportional hazards models were used for supportive analyses and all-cause mortality. RESULTS: Among the 345 patients (mean age 59.22±13.19 years; 69.0% men), 42.0% met the criteria for AC. During a median follow-up of 18.1 months, 36 patients experienced ischemic stroke, 2 had TIA, and 18 died. AC was strongly associated with ischemic stroke/TIA recurrence in competing risk analyses (adjusted subdistribution hazard ratio [aSHR] 3.36, 95% CI 1.65-6.86; P＜0.001). For all-cause mortality, AC was associated with a higher risk after adjusting for age and sex (adjusted hazard ratio 3.80, 95% CI 1.19-12.08; P = 0.024). Adding AC to conventional risk models significantly improved the NRI (ischemic stroke/transient ischemic attack: 72.45%, P＜0.001; mortality: 66.16%, P = 0.002) and IDI (4.52%, P＜0.001; 3.89%, P = 0.041). CONCLUSIONS: AC independently predicts recurrent ischemic stroke/TIA in ESUS and improves risk stratification, while its association with mortality requires cautious interpretation due to limited events.
AIM: Chronic limb-threatening ischemia (CLTI), the most advanced stage of lower-extremity artery disease, is associated with high mortality and major amputation rates, even after revascularization. Thus, identifying pati...AIM: Chronic limb-threatening ischemia (CLTI), the most advanced stage of lower-extremity artery disease, is associated with high mortality and major amputation rates, even after revascularization. Thus, identifying patients with CLTI at a particularly high risk of poor outcomes is crucial for shared decision making. Recently, the C-reactive protein-to-albumin ratio (CAR) has emerged as a novel composite biomarker that reflects both the inflammatory and nutritional status. Nonetheless, the prognostic significance of CAR in patients with CLTI undergoing endovascular therapy (EVT) remains unclear. METHODS: Of 159 patients who underwent EVT for the first time between April 2010 and December 2023, 79 were included in this study. The patients were categorized into two groups using a CAR value of 0.17: the high-CAR group (CAR ≥ 0.17) and the low-CAR group (CAR ＜0.17). The primary endpoint was 1-year amputation-free survival (AFS) after EVT. RESULTS: The median follow-up period was 23 months (95% confidence interval [CI], 11-34). During the follow-up period, 56 patients (71%) died and 11 (14%) underwent major amputation. AFS was significantly reduced in the high-CAR group (log-rank P＜0.01). The CAR (hazard ratio: 1.43 per one-unit increase, 95% CI: 1.20-1.70, P＜0.01) was an independent predictor of reduced AFS following EVT. CONCLUSIONS: elevated preprocedural CAR was independently associated with reduced AFS after EVT in patients with CLTI. The CAR may serve as a valuable tool for evaluating patients with CLTI before EVT.
AIM: Familial chylomicronemia syndrome (FCS) is a rare disorder characterized by the accumulation of chylomicrons in the circulation due to genetic defects or autoantibodies affecting lipoprotein lipase (LPL), the key en...AIM: Familial chylomicronemia syndrome (FCS) is a rare disorder characterized by the accumulation of chylomicrons in the circulation due to genetic defects or autoantibodies affecting lipoprotein lipase (LPL), the key enzyme responsible for the metabolism of chylomicrons and very-low-density lipoproteins (VLDL), or its associated proteins, including apolipoprotein (apo) C-II, apoA-V, glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), and lipase maturation factor 1 (LMF1). This condition is associated with markedly elevated serum triglyceride (TG) levels and, in severe cases, recurrent episodes of pancreatitis and eruptive xanthomas. Among these etiologies, genetic deficiency of GPIHBP1 is exceedingly rare. We aimed to clarify the clinical and genetic basis and treatment strategies of a patient with GPIHBP1 deficiency. METHODS: A 47-year-old woman with a childhood diagnosis of FCS presented with severe epigastric pain and was admitted to Rinku General Medical Center for emergency management of acute pancreatitis secondary to severe chylomicronemia. She had a history of severe hypertriglyceridemia complicated by pancreatitis during her first pregnancy and extreme hypertriglyceridemia exceeding 6,000 mg/dL during her second pregnancy without the development of pancreatitis. DNA sequence analysis was performed as a clinical diagnostic test and outsourced to KUBIX Inc. (Hakusan, Ishikawa, Japan). RESULTS: Laboratory evaluation revealed marked hypertriglyceridemia (1,262 mg/dL) with a type V hyperlipoproteinemia pattern. Serum preheparin LPL mass was markedly reduced, and circulating GPIHBP1 was undetectable. Genetic analysis identified a novel homozygous frameshift mutation in the GPIHBP1 gene (NM_178172.4:c.20del [p.Val7AlafsTer73]), which has not been previously reported in public databases. No pathogenic variants were detected in other LPL-related genes. Acute pancreatitis improved rapidly with fasting and intravenous fluid therapy. Strict dietary fat restriction, followed by the addition of the selective PPARα modulator pemafibrate, successfully maintained TG levels below 500 mg/dL during follow-up. CONCLUSION: We report an extremely rare case of FCS caused by a novel homozygous mutation in the GPIHBP1 gene, in which pregnancy served as a major trigger for severe hypertriglyceridemia. Early diagnosis and strict lipid control are essential to prevent recurrent pancreatitis in patients with GPIHBP1 deficiency.
AIM: To investigate the effects of temperature exposure on the incidence of cardiovascular and cerebrovascular diseases in Zhanjiang, a subtropical coastal city in China. METHODS: We analyzed hospitalization data from 20...AIM: To investigate the effects of temperature exposure on the incidence of cardiovascular and cerebrovascular diseases in Zhanjiang, a subtropical coastal city in China. METHODS: We analyzed hospitalization data from 2009 to 2023 using generalized additive models (GAMs) and distributed lag nonlinear models (DLNMs) to examine the exposure-response relationships and lagged effects of daily maximum temperature on stroke (CVA), acute coronary syndrome (ACS), and acute aortic syndrome (AAS). RESULTS: Distinct temperature-associated risk patterns were observed for each disease type. ACS showed the strongest association, with significant risk increases at 1-day (relative risk [RR] = 1.19) and 5-day lags (RR = 1.12). The risk of CVA was moderately elevated at lower temperatures (22.7℃; RR = 1.08), whereas AAS exhibited a delayed peak at 5 days (RR = 1.29). CONCLUSIONS: These subtropical patterns differ from those reported in temperate regions. Our findings support climate-specific warnings: namely, multi-day monitoring for CVA at lower temperatures, immediate and sustained alerts for ACS, and focused surveillance approximately 5 days after exposure for AAS.
Adenosine triphosphate (ATP) is well known as the major intracellular energy carrier. It also functions as a potent extracellular signaling molecule. In atherosclerosis, both intracellular and extracellular ATP have been...Adenosine triphosphate (ATP) is well known as the major intracellular energy carrier. It also functions as a potent extracellular signaling molecule. In atherosclerosis, both intracellular and extracellular ATP have been increasingly implicated in the disease pathophysiology. The intracellular ATP levels are closely regulated by the balance among the metabolic pathways, including glycolysis and oxidative phosphorylation (OXPHOS), and they play diverse and cell type-specific roles in atherosclerotic plaques. In contrast, the extracellular ATP released from these cells binds to purinergic P2 receptors and activates downstream signaling cascades primarily in an autocrine or paracrine manner, thereby regulating various cellular functions during disease progression. These two contrasting ATP-associated pathways are involved in a wide range of atherosclerosis-related processes including inflammation, vascular tone and barrier function, cell proliferation, migration and differentiation, and calcification, some of which are shared or highly context-dependent. This review summarizes the fundamental aspects of ATP biology, discusses the current approaches for measuring ATP concentrations in atherosclerotic plaques, and highlights the functions of intra- and extracellular ATP in major atherosclerosis-related cell types, including endothelial cells, macrophages and vascular smooth muscle cells (VSMCs), to clarify these intricately intertwined pathophysiological processes. Finally, this overview provides insights into the current challenges in ATP biology research and outlines therapeutic opportunities targeting intra- or extracellular ATP in atherosclerotic disease.
AIMS: ADAMTS18 is a secreted metalloproteinase implicated in vascular homeostasis and protection against ischemic brain injury. However, its clinical relevance in acute ischemic stroke (AIS) remains unclear. METHODS: We...AIMS: ADAMTS18 is a secreted metalloproteinase implicated in vascular homeostasis and protection against ischemic brain injury. However, its clinical relevance in acute ischemic stroke (AIS) remains unclear. METHODS: We retrospectively analyzed 194 AIS patients from the Chengdu Stroke Registry. Serum ADAMTS18 levels were measured within 48 hours of admission using ELISA. Associations between ADAMTS18 levels and 3-month poor outcomes (modified Rankin Scale score 3-6) were evaluated using logistic regression. Predictive performance was assessed using area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: Among 194 patients, the median ADAMTS18 was 21.45 ng/mL (IQR 19.68-23.58 ng/mL), 79 (40.7%) had poor outcomes. Patients with poor outcomes had lower serum ADAMTS18 levels [19.84 (18.46-21.24) vs. 22.88 (21.14-24.81) ng/mL, P＜0.001]. After adjustment, lower ADAMTS18 levels were independently associated with poor outcome (OR 0.70, 95% CI 0.58-0.83, P＜0.001). Quartile analysis showed that compared with the lowest quartile, patients in Q3 (OR = 0.26; 95% CI: 0.08-0.83; P = 0.023) and Q4 (OR = 0.02; 95% CI: 0.00-0.11; P＜0.001) had progressively lower odds of poor functional outcome (P for trend ＜0.001). Restricted cubic spline analysis confirmed a negative linear association (adjusted P＜0.001). Incorporating ADAMTS18 into predictive models improved discrimination (AUC = 0.91 vs. 0.86, P = 0.011), IDI (11.14%, P＜0.001), and NRI (77.1%, P＜0.001). CONCLUSION: Lower admission ADAMTS18 levels are independently associated with poor 3-month functional outcomes after AIS and may provide additional prognostic information.
AIM: Children with elevated low-density lipoprotein cholesterol (LDL-C) levels, suspected familial hypercholesterolemia (FH), and elevated lipoprotein(a) (Lp(a)) levels are considered to have a particularly high lifetime...AIM: Children with elevated low-density lipoprotein cholesterol (LDL-C) levels, suspected familial hypercholesterolemia (FH), and elevated lipoprotein(a) (Lp(a)) levels are considered to have a particularly high lifetime risk of atherosclerotic cardiovascular disease. Nevertheless, the distribution of Lp(a) levels among children with elevated LDL-C levels remains unclear. This study aimed to clarify the distribution of Lp(a) levels and their association with pathogenic FH variants in children with elevated LDL-C levels. METHODS: A total of 97 children with LDL-C levels ≥ 140 mg/dL suspected of having FH who underwent genetic testing at Kagawa University Hospital between January 2018 and May 2025 were analyzed. Lp(a) levels were measured using the Lp(a) Latex "DAIICHI" assay and converted from mass units (mg/dL) to molar units (nmol/L) using the calibration-based conversion formula. Clinical and lipid parameters were compared according to Lp(a) levels (≥ 105 vs. ＜105 nmol/L) and the presence of pathogenic FH variants. RESULTS: Lp(a) levels exhibited a right-skewed distribution, with a median of 57.6 nmol/L (15.9 mg/dL) and an interquartile range of 24.0-93.4 nmol/L (7.0-25.4 mg/dL), and 21.6% of children had levels ≥ 105 nmol/L. Pathogenic FH variants were identified in 44 children. No significant differences were observed in either clinical or lipid parameters according to Lp(a) levels (≥ 105 vs. ＜105 nmol/L) or the presence of pathogenic FH variants (P = 0.672). CONCLUSION: Regardless of the presence of pathogenic FH variants, approximately 20% of the children had Lp(a) levels ≥ 105 nmol/L. These findings emphasize the importance of early lipid management and suggest that Lp(a) measurement may contribute to future cardiovascular risk stratification.
Intracranial arterial stenosis is a major cause of ischemic stroke worldwide, particularly in the Asian population. Although traditionally regarded as a manifestation of atherosclerotic disease, increasing evidence sugge...Intracranial arterial stenosis is a major cause of ischemic stroke worldwide, particularly in the Asian population. Although traditionally regarded as a manifestation of atherosclerotic disease, increasing evidence suggests that non-atherosclerotic arteriopathies also contribute substantially to its pathogenesis. These conditions, including arterial dissection, inflammatory vasculopathies, and moyamoya disease, often share overlapping clinical and imaging features, thus making precise differentiation challenging in routine practice.This phenotypic overlap highlights the heterogeneity of intracranial arterial stenosis and suggests that it may represent a spectrum of vascular disorders, rather than a single disease entity. Recent studies have highlighted the role of genetic susceptibility as a factor underlying this diversity. Among these, RNF213, originally identified as a susceptibility gene for moyamoya disease, has been implicated in a subset of intracranial arterial diseases beyond the classical diagnostic categories. These observations have led to the concept of RNF213-related vasculopathy, which extends beyond intracranial circulation and provides a framework for understanding diverse vascular phenotypes within a broader context. In addition, a two-hit model has been proposed in which genetic susceptibility interacts with environmental and acquired factors to influence the disease onset and progression.This narrative review summarizes the current understanding of intracranial arterial stenosis beyond the conventional atherosclerosis-centered paradigm and discusses emerging concepts integrating vascular heterogeneity, genetic susceptibility, and environmental modifiers with potential implications for disease classification and individualized therapeutic strategies.
AIM: Although growing epidemiological evidence suggests that metabolic risk factors may influence the intraocular pressure (IOP), the specific effects of individual lipid components on IOP regulation remain unclear. In t...AIM: Although growing epidemiological evidence suggests that metabolic risk factors may influence the intraocular pressure (IOP), the specific effects of individual lipid components on IOP regulation remain unclear. In this study, we examined the associations between the serum lipid profiles, individually and in combination, and IOP among 6,786 ophthalmologically healthy adults aged ≥ 40 years residing in Chikusei City, Japan. METHODS: Participants with a history of glaucoma, the use of IOP-lowering medications, or previous ocular surgery were excluded. Comprehensive systemic and ophthalmological evaluations, including blood tests and measurements of IOP and central corneal thickness, were performed. An analysis of covariance was used to assess the associations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels with IOP. RESULTS: After adjusting for several potential confounders, higher LDL-C, HDL-C, and TG levels were significantly associated with increased IOP. Specifically, every 10 mg/dL increase in LDL-C, HDL-C, and TG corresponded to IOP increases of 0.04±0.011 mmHg, 0.13±0.026 mmHg, and 0.02±0.006 mmHg, respectively. Notably, the positive association between LDL-C and IOP was more pronounced in individuals aged ≥ 65 years than in those aged ＜65 years (P for interaction = 0.009). CONCLUSION: These findings suggest that lipid homeostasis may contribute to IOP regulation, particularly in older populations.
LDL cholesterol (LDL-C) is the central causal factor for atherosclerotic cardiovascular disease (ASCVD), and its reduction is a cornerstone of both primary and secondary prevention. Since the introduction of statins more...LDL cholesterol (LDL-C) is the central causal factor for atherosclerotic cardiovascular disease (ASCVD), and its reduction is a cornerstone of both primary and secondary prevention. Since the introduction of statins more than three decades ago, LDL-C-lowering therapy has expanded substantially, now encompassing ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9)-targeting agents, bempedoic acid, and other emerging modalities. This expanding therapeutic landscape has improved the feasibility of achieving guideline-recommended LDL-C targets, but it has also increased the complexity of clinical decision making. This review provides a contemporary and practical overview of the LDL-C-lowering strategies, beginning with the initial evaluation of patients with elevated LDL-C, including differentiation between primary and secondary causes and the identification of familial hypercholesterolemia (FH). We summarize the current treatment targets for primary and secondary prevention, highlight the optimal selection and use of statins, and discuss the assessment and management of statin intolerance, including the role of the nocebo effect. Non-statin therapies, including ezetimibe, bile acid sequestrants, PCSK9 inhibitors, inclisiran, and bempedoic acid, are reviewed with an emphasis on their mechanisms, efficacy, and clinical positioning. Advanced therapies for severe dyslipidemia, such as lipoprotein apheresis, lomitapide, and evinacumab, are also discussed in this review. Finally, we outline the future directions, including oral PCSK9 inhibitors, next-generation cholesteryl ester transfer protein (CETP) inhibitors, lipoprotein(a)-lowering agents, and genome-editing approaches. Collectively, these developments offer new opportunities to address unmet clinical needs, particularly in patients with FH, statin intolerance, and residual cardiovascular risk. A comprehensive understanding of these therapies is essential for further reducing the burden of ASCVD in the coming decades.
AIMS: Liver dysfunction may affect chronic limb-threatening ischemia (CLTI) outcomes, but its impact on survival and lipid profiles is unclear. To assess the association of liver dysfunction using the Albumin-Bilirubin (...AIMS: Liver dysfunction may affect chronic limb-threatening ischemia (CLTI) outcomes, but its impact on survival and lipid profiles is unclear. To assess the association of liver dysfunction using the Albumin-Bilirubin (ALBI) score, with survival, liver fibrosis, and cholesterol in CLTI patients. METHODS: We retrospectively analyzed single-center data of CLTI patients with below-knee lesions between 2008-2018. ALBI scores were calculated from serum albumin and total bilirubin. Optimal cutoff for 3-year overall survival (OS) was determined by receiver operating characteristic (ROC) analysis, dividing patients into high and low ALBI groups. Patient characteristics, cholesterol, and liver fibrosis (FIB-4 index) were compared, with primary endpoint being 3-year OS. RESULTS: Among 263 patients, high ALBI patients (≥ -2.36, n = 135) were older (80 vs. 72 years), included fewer males (55% vs. 71%), had higher prevalence of bed-ridden status (44% vs. 2%) and heart failure (25% vs. 8%; all P＜0.01). They had higher FIB-4 index (2.49 vs. 1.76), lower total cholesterol (147 vs. 173 mg/dL), HDL-C (43 vs. 56 mg/dL), LDL-C (83 vs. 108 mg/dL), and higher LDL-C/HDL-C ratio (2.57 vs. 2.20; P＜0.01). Three-year OS was lower in high ALBI group (36% vs. 57%; P＜0.01) and remained lower after propensity matching (43% vs. 55%; P = 0.04). Multivariate analysis identified low body mass index (BMI), heart failure, high ALBI score and high FIB-4 index (≥ 1.3) and low LDL-C (＜100 mg/dL) as predictors of poor OS. CONCLUSIONS: High ALBI scores in CLTI patients links to liver fibrosis, disturbed lipid profiles, and reduced survival.