Ren Y, Miao M, Tan R
… +3 more, Xu G, Liu Y, Yin X
J Atheroscler Thromb
· 2025 Jul · PMID 39864856
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AIMS: Evidence supporting the prescription of anticoagulant therapy for patients with atrial fibrillation (AF) with advanced chronic kidney disease (CKD) has been limited, and its clinical application in this context rem...AIMS: Evidence supporting the prescription of anticoagulant therapy for patients with atrial fibrillation (AF) with advanced chronic kidney disease (CKD) has been limited, and its clinical application in this context remains controversial. METHODS: We identified AF patients with advanced CKD (G4-G5) and a history of stroke who were admitted to the First Affiliated Hospital of Dalian Medical University between January 1, 2011, and June 30, 2023. Patients were classified into warfarin, non-vitamin K antagonist oral anticoagulant (NOAC), antiplatelet therapy, and control (no antithrombotic therapy) groups. We evaluated the benefits and safety of different antithrombotic therapies by comparing the long-term clinical outcome measures, including the incidence of subsequent ischemic stroke events, bleeding, and all-cause death. RESULTS: In total, 570 patients were included. In this cohort, 87 (15.3%) patients had no antithrombotic treatment, 252 (44.2%) received antiplatelet therapy, 105 (18.4%) received warfarin, and 126 (22.1%) received NOAC therapy. Compared with patients without treatment, we found that treatment with anticoagulant therapy significantly decreased the risk of ischemic stroke, but antiplatelet therapy did not. Treatment with anticoagulant therapy was associated with significantly lower mortality than no antithrombotic therapy or antiplatelet therapy , at least within the study period. Furthermore, compared with warfarin treatment, patients treated with NOAC therapy showed a significant decrease in the incidence of bleeding risks. CONCLUSION: Among AF patients with advanced CKD and prior stroke, receiving anticoagulants resulted in a reduced risk of recurrent ischemic stroke events than no antithrombotic treatment, and lower mortality than no antithrombotic treatment or antiplatelet therapy.
Hattori Y, Imada S, Usui R
… +3 more, Yamamoto A, Nakamura M, Ihara M
J Atheroscler Thromb
· 2025 Aug · PMID 39864855
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AIM: Branch atheromatous disease (BAD), characterized by the occlusion of perforating branches near the orifice of a parent artery, often develops early neurological deterioration because the mechanisms underlying BAD re...AIM: Branch atheromatous disease (BAD), characterized by the occlusion of perforating branches near the orifice of a parent artery, often develops early neurological deterioration because the mechanisms underlying BAD remain unclear. Abnormal wall shear stress (WSS) is strongly associated with endothelial dysfunction and plaque growth or rupture. Therefore, we hypothesized that computational fluid dynamics (CFD) modeling could detect differences in WSS between BAD and small-vessel occlusion (SVO), both of which result from perforating artery occlusion/stenosis. METHODS: This cross-sectional observational study included consecutive patients admitted to our institution within 7 days after symptom onset who met the following criteria: absence of stenosis/occlusion in the intracranial major arteries on brain magnetic resonance angiography (MRA) or extracranial carotid arteries on carotid ultrasonography. The WSS and blood flow velocity in the M1 segment of the middle cerebral artery were analyzed using CFD based on MRA. RESULTS: The number of patients with a WSS ratio (ipsilesional/contralesional) of ＞1 was significantly higher in patients with BAD (n = 27) than in those with SVO (n = 27) [20 (74.1%) vs. 11 (40.7%), p = 0.013]. Higher WSS on ipsilesional M1 than on contralesional M1 was an independent risk factor for BAD (adjusted odds ratio 4.38, 95% confidence interval 1.29-14.82, p = 0.018). Blood flow velocity in the M1 segment was not associated with BAD. CONCLUSIONS: In patients with BAD, higher M1 segment WSS on CFD can be a risk factor for the development of vulnerable plaques in branch orifices. Moreover, the use of CFD may contribute to the diagnosis of BAD.
J Atheroscler Thromb
· 2025 May · PMID 39828369
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The deposition of cholesterol containing cholesterol crystals and the infiltration of immune cells are features of atherosclerosis. Although the role of cholesterol crystals in the progression of atherosclerosis have lon...The deposition of cholesterol containing cholesterol crystals and the infiltration of immune cells are features of atherosclerosis. Although the role of cholesterol crystals in the progression of atherosclerosis have long remained unclear, recent studies have clarified the involvement of cholesterol crystals in inflammatory responses. Cholesterol crystals activate the NLRP3 inflammasome, a molecular complex involved in the innate immune system. Activation of NLRP3 inflammasomes in macrophages cause pyroptosis, which is accompanied by the release of inflammatory cytokines such as IL-1β and IL-1α. Furthermore, NLRP3 inflammasome activation drives neutrophil infiltration into atherosclerotic plaques. Cholesterol crystals trigger NETosis against infiltrated neutrophils, a form of cell death characterized by the formation of neutrophil extracellular traps (NETs), which, in turn, prime macrophages to enhance inflammasome-mediated inflammatory responses. Colchicine, an anti-inflammatory drug effective in cardiovascular disease, is expected to inhibit cholesterol crystal-induced NLRP3 inflammasome activation and neutrophil infiltration. In this review, we illustrate the reinforcing cycle of inflammation that is amplified by inflammasome activation and NETosis.
J Atheroscler Thromb
· 2025 May · PMID 39805627
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Diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), is a pervasive chronic disease that affects millions of people worldwide. It predisposes individuals to a range of severe microvascular and macrovascular c...Diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), is a pervasive chronic disease that affects millions of people worldwide. It predisposes individuals to a range of severe microvascular and macrovascular complications, which drastically impact the patient's quality of life and increase mortality rates owing to various comorbidities. This extensive review explores the intricate pathophysiology underlying diabetic complications, focusing on key mechanisms, such as atherosclerosis, insulin resistance, chronic inflammation, and endothelial dysfunction. It also highlights recent therapeutic advancements, including the introduction of SGLT2 inhibitors and GLP-1 receptor agonists, which provide benefits beyond glycemic control and offer cardiovascular and renal protection. Furthermore, the future position of SGLT2 inhibitors and GLP-1 receptor agonists in terms of the prevention of diabetes and macrovascular diseases will be discussed. Considering the differences in insulin secretion capacity between Western and Asian patients, including Japanese patients, we propose a treatment strategy for high-quality diabetes in Japan.
J Atheroscler Thromb
· 2025 Mar · PMID 39779225
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Apolipoprotein E (apoE) is a key apoprotein in lipid transport and is susceptible to genetic mutations. ApoE variants have been studied for four decades and more than a hundred of them have been reported. This paper pres...Apolipoprotein E (apoE) is a key apoprotein in lipid transport and is susceptible to genetic mutations. ApoE variants have been studied for four decades and more than a hundred of them have been reported. This paper presents an up-to-date review of the function and structure of apoE in lipid metabolism, the E2, E3, and E4 isoforms, the APOE gene, and various pathologies, such as familial type III hyperlipidemia and lipoprotein glomerulopathy, caused by apoE variants. Alzheimer's disease was barely mentioned in this paper. But this review should help researchers obtain a comprehensive overview of human apoE in lipid metabolism.
Miura M, Ikeda A, Tomooka K
… +6 more, Maruyama K, Kawamura R, Takata Y, Osawa H, Saito I, Tanigawa T
J Atheroscler Thromb
· 2025 Jun · PMID 39756984
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AIM: Previous studies have shown that higher educational levels are associated with slower progression of arterial stiffness; however, evidence from Asian countries is lacking. We aimed to examine the association between...AIM: Previous studies have shown that higher educational levels are associated with slower progression of arterial stiffness; however, evidence from Asian countries is lacking. We aimed to examine the association between educational level and arterial stiffness measured using the cardio-ankle vascular index (CAVI) over time in a sample of Japanese men and women. METHODS: A total of 1381 participants (453 men and 928 women) were included in the present study. Arterial stiffness was measured using the CAVI at baseline (2009-2012) and 5 years later (2014-2018). The educational level was divided into two groups (junior or senior high school vs. junior college, professional school, college, or higher) based on a self-administered questionnaire. A mixed-effects model was used to analyze the association between education and the CAVI at baseline and its change over 5 years. The participants were stratified by sex and age (＜65 vs. ≥ 65 years). RESULTS: The CAVI at baseline did not differ significantly according to education in any of the four subgroups accorded to age and sex. However, among women of ≥ 65 years of age, the change in the CAVI over 5 years was significantly smaller in the higher education group (p=0.04). No such association was found in women of ＜65 years of age or men. CONCLUSIONS: Education is a factor that affects arterial stiffness in women of ≥ 65 years of age. These results suggest that educational level affects arterial stiffness, depending on sex and age.
Tada H, Okada H, Yoshida S
… +16 more, Shimojima M, Nomura A, Tsuda T, Mori M, Takashima SI, Kato T, Usui S, Sakata K, Hayashi K, Fujino N, Inazu A, Nagase K, Mizukoshi E, Kawashiri MA, Takamura M, Hokuriku-plus Familial Hypercholesterolemia Registry Study Group †
J Atheroscler Thromb
· 2025 Jul · PMID 39756983
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AIM: We aimed to clarify the degree and factors associated with low-density lipoprotein (LDL)-cholesterol treatment target attainment among patients with heterozygous familial hypercholesterolemia (HeFH) using the Hokuri...AIM: We aimed to clarify the degree and factors associated with low-density lipoprotein (LDL)-cholesterol treatment target attainment among patients with heterozygous familial hypercholesterolemia (HeFH) using the Hokuriku-plus FH registry. METHODS: The Hokuriku-plus FH registry (UMIN000038210) was a prospective, observational, multicenter cohort study that enrolled consecutive patients with FH who fulfilled the clinical criteria for FH in Japan from 37 participating hospitals, mostly in the Hokuriku region, from April 2020 to March 2024. This registry collects data on clinical parameters, including lipid levels, physical findings, genetic background, and clinical events. In total, 431 patients were enrolled, and the median followup period was 3.1 years. We assessed the degree and factors associated with LDL-cholesterol treatment target attainment among patients with HeFH using the Hokuriku-plus FH registry. RESULTS: Among the 431 patients, sufficient data were collected from 386 patients. Logistic regression analysis revealed that male sex (odds ratio [OR] = 2.16, 95% confidence interval [CI]: 1.14-3.18, p＜0.001) and genetic testing (OR = 1.68, 95% CI: 1.10-2.26, p＜0.001) were significantly associated with LDL-cholesterol treatment target attainment. In fact, female patients were less likely to attain LDL-cholesterol treatment target than male patients (24.0% vs. 38.1%, p＜0.001), and patients who did not undergo genetic testing were less likely to attain LDL-cholesterol treatment target than those who underwent genetic testing (24.5% vs. 37.1%, p＜0.001). CONCLUSION: Sex bias and masked genetic status are significant barriers to the clinical management of patients with HeFH.
J Atheroscler Thromb
· 2025 Jul · PMID 39756982
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AIM: This study assessed the predictive value of pericarotid fat density (PFD) on carotid computed tomography angiography (CTA) for recurrent ischemic stroke or transient ischemic attack (TIA). METHODS: In total, 739 pat...AIM: This study assessed the predictive value of pericarotid fat density (PFD) on carotid computed tomography angiography (CTA) for recurrent ischemic stroke or transient ischemic attack (TIA). METHODS: In total, 739 patients who underwent CTA between January 2014 and December 2021 were retrospectively included in this study. The PFD was evaluated using carotid CTA. The clinical endpoint was recurrent ischemic stroke or transient ischemic attack (TIA). The association between PFD and the endpoint was examined using Kaplan-Meier and Cox analyses. The combination model was established using significant clinical imaging risk factors and PFD. The predictive performance of the model was assessed using the receiver operating characteristic curve (ROC). RESULTS: A total of 739 patients (mean age: 64.28±9.44 years old, 496 males) completed a median of 3.31 years of follow-up (interquartile range, 2.11-4.05). During the follow-up period, 166 patients reached the clinical end point. The event-free survival (EFS) rate was lower in the high-PFD group than in the low-PFD group (log-rank P＜0.001). Multivariate Cox analyses showed that the PFD was associated with recurrent stroke or TIA (all P＜0.05). The combination model demonstrated excellent performance in predicting the clinical endpoint (area under the curve = 0.89). In addition, the endpoint event prognostic value was significantly improved by adding the PFD to the baseline model (C-statistic improvement: 0.61-0.84). CONCLUSION: CTA-assessed PFD is an independent predictor of recurrent stroke or TIA.
J Atheroscler Thromb
· 2025 Mar · PMID 39756980
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Atherosclerotic cardiovascular disease (ASCVD) is a leading global cause of mortality, and recent research has underscored the critical role of lipoproteins in modulating cardiovascular (CV) risk. Elevated low-density li...Atherosclerotic cardiovascular disease (ASCVD) is a leading global cause of mortality, and recent research has underscored the critical role of lipoproteins in modulating cardiovascular (CV) risk. Elevated low-density lipoprotein cholesterol (LDL-C) levels have been linked to increased CV events, and while numerous trials have confirmed the efficacy of lipid-lowering therapies (LLT), significant gaps remain between recommended LDL-C targets and real-world clinical practice. This review addresses care gaps in LLT, emphasizing the necessity for innovative approaches that extend beyond LDL-C management. It explores combination therapy approaches such as statins combined with ezetimibe or PCSK9 inhibitors, which have shown promise in enhancing LDL-C reduction and improving outcomes in high-risk patients. Additionally, this review discusses new approaches in lipid modification strategies, including bempedoic acid, inclisiran, and drugs that lower Lp(a), highlighting their potential for CV risk reduction. Furthermore, it emphasizes the potential of polygenic risk scores to guide LLT and lifestyle changes despite challenges in implementation and genetic testing ethics. This article discusses the current guidelines and proposes innovative approaches for optimizing lipoprotein management, ultimately contributing to improved patient outcomes in ASCVD prevention.
Nagakura Y, Shoji T, Fukumoto S
… +8 more, Uedono H, Nakatani S, Mori K, Nagata Y, Imanishi Y, Morioka T, Watanabe T, Emoto M
J Atheroscler Thromb
· 2025 Jun · PMID 39721707
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AIM: Patients with type 2 diabetes mellitus (T2D) are prone to develop vascular calcification. Fetuin-A protects against vascular calcification but it increases insulin resistance. T50 calciprotein crystallization (also...AIM: Patients with type 2 diabetes mellitus (T2D) are prone to develop vascular calcification. Fetuin-A protects against vascular calcification but it increases insulin resistance. T50 calciprotein crystallization (also called serum calcification propensity) is a novel marker of calcification stress. This study examined whether T2D affects T50 and the potential role of fetuin-A in the relationship between T2D and T50. METHODS: This cross-sectional study included 101 individuals with T2D and 101 individuals without diabetes (controls). T50 and fetuin-A levels were measured using the established nephelometric method and an enzyme-linked immunosorbent assay, respectively. RESULTS: Although fetuin-A levels were higher in the T2D group, T50 was not significantly different between the T2D and control groups. In multivariable-adjusted analyses of the total population, T50 was not independently associated with the presence of T2D, fasting plasma glucose, or HbA1c, whereas T50 was significantly associated with fetuin-A, phosphate, and calcium levels. The association between T50 and fetuin-A was modified by the presence of T2D. A subgroup analysis revealed that the positive association between T50 and fetuin-A was significant but smaller in the T2D group, and that the associations of T50 with serum phosphate and calcium were more evident in the T2D group. Additional analyses showed that T50/fetuin-A ratio was lower in the T2D group and that T50/fetuin-A ratio was inversely correlated with fasting glucose and HbA1c levels. CONCLUSIONS: T2D itself was not significantly associated with T50 but T2D modified the association between T50 and fetuin-A in favor of developing vascular calcification in T2D.
Takei T, Tokuda T, Yoshioka N
… +7 more, Ogata K, Tanaka A, Kojima S, Yamaguchi K, Yanagiuchi T, Nakama T, LEADers PAD (peripheral artery disease) investigators
J Atheroscler Thromb
· 2025 Jul · PMID 39721706
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AIM: Few studies have evaluated the midterm prognosis of patients with intermittent claudication who underwent endovascular therapy (EVT) for femoropopliteal lesions. Therefore, we aimed to assess 2-year mortality and pr...AIM: Few studies have evaluated the midterm prognosis of patients with intermittent claudication who underwent endovascular therapy (EVT) for femoropopliteal lesions. Therefore, we aimed to assess 2-year mortality and prognostic factors in these patients. METHODS: We retrospectively analyzed 947 patients who underwent EVT for intermittent claudication between January 2018 and December 2021 at eight Japanese cardiovascular centers. Kaplan-Meier survival analysis was performed for mortality, and prognostic factors were analyzed using the Cox proportional hazards regression model. Patient backgrounds and medications were included in the investigation of prognostic factors. RESULTS: Notably, 79 deaths occurred during the mean follow-up period of 20.9±6.2 months. The 2-year mortality rate was 9.1%. In multivariate analysis, body mass index (BMI) ＜18.5 kg/m (p＜0.001), coronary artery disease (CAD) (p＜0.001), dialysis (p＜0.001), and ankle-brachial pressure index (ABI) ＜0.6 (p=0.012) were risk factors. Statins and cilostazol were protective factors (p=0.014 and p=0.036, respectively). When the study population was stratified based on the number of these risk factors, the mortality rate was highest (32.5% at 2 years) in patients with at least three risk factors. However, when stratified according to protective factors, the mortality rate was lowest in patients with two protective factors (2.1% at 2 years). CONCLUSIONS: Dialysis, low BMI, CAD, and low ABI were risk factors for a worse 2-year prognosis in patients with intermittent claudication who underwent EVT for femoropopliteal lesions. Statins and cilostazol may improve the 2-year prognosis of patients with lower extremity artery disease.
Goto H, Saito Y, Yaginuma H
… +5 more, Asada K, Sato T, Hashimoto O, Kitahara H, Kobayashi Y
J Atheroscler Thromb
· 2025 Jul · PMID 39721703
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AIMS: Several risk-scoring models, including the Fukuoka Stroke Risk Score, Essen Stroke Risk Score, and Stroke Prognosis Instrument II, have been developed to predict recurrent cerebrovascular events in patients with is...AIMS: Several risk-scoring models, including the Fukuoka Stroke Risk Score, Essen Stroke Risk Score, and Stroke Prognosis Instrument II, have been developed to predict recurrent cerebrovascular events in patients with ischemic stroke. As myocardial infarction (MI) and ischemic stroke are both atherosclerotic diseases, these scoring models in the field of cerebrovascular disease may be applicable and useful for risk stratification in patients with acute MI. We therefore evaluated the diagnostic ability and clinical applicability of these stroke risk scores in predicting atherosclerotic events after acute MI. METHODS: This multicenter retrospective study included 2016 patients with acute MI who underwent percutaneous coronary intervention and survived to discharge. The three risk-scoring models were calculated, and their diagnostic ability for major adverse cardiovascular events (MACE) after discharge, a composite of cardiovascular death, recurrent MI, and ischemic stroke, was evaluated. RESULTS: During the median follow-up of 523 days, 218 (10.8%) patients experienced MACE after discharge. High values for Fukuoka Stroke Risk Score, Essen Stroke Risk Score, and Stroke Prognosis Instrument II were progressively associated with an increased risk of MACE after discharge. Overall, the diagnostic abilities of the three risk scores were similar. CONCLUSIONS: Risk prediction models in the field of ischemic stroke, including the Fukuoka Stroke Risk Score, Essen Stroke Risk Score, and Stroke Prognosis Instrument II, were useful in stratifying MACE risk in patients with acute MI. Risk-scoring models for atherosclerotic cardiovascular disease may be applicable to patient populations with other cardiovascular diseases in different arterial territories.
Kikuno M, Ueno Y, Tateishi Y
… +18 more, Kuriki A, Doijiri R, Shimizu T, Takekawa H, Kanemaru K, Shimada Y, Yamaguchi E, Koga M, Kamiya Y, Ihara M, Tsujino A, Hirata K, Hasegawa Y, Aizawa H, Terashi H, Hattori N, Urabe T, CHALLENGE ESUS/CS collaborators
J Atheroscler Thromb
· 2025 Jul · PMID 39721702
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AIMS: Atherogenic dyslipidemia (AD) is regarded as a residual risk of cardiovascular diseases characterized by low high-density lipoprotein cholesterol (HDL-C) and high triglyceride (TG) levels and related to the intracr...AIMS: Atherogenic dyslipidemia (AD) is regarded as a residual risk of cardiovascular diseases characterized by low high-density lipoprotein cholesterol (HDL-C) and high triglyceride (TG) levels and related to the intracranial stenosis of atheromatous thrombotic brain infarction (ATBI). Further, atherosclerosis is possibly related to another stroke subtype, including cryptogenic stroke (CS). In particular, an aortic complicated lesion (ACL) is a notable embolic source of CS, since recurrence of aortogenic brain embolism is not rare. This study aimed to clarify the underlying association between AD and CS. METHODS: CHALLENGE ESUS/CS (Mechanisms of Embolic Stroke Clarified by Transesophageal Echocardiography for ESUS/CS) had extensive data from CS patients who underwent transesophageal echocardiography (TEE). AD was defined as HDL-C ≤ 40 mg/dl and TG ≥ 150 mg/dl. Based on these criteria, patients were divided into an AD group and a non-AD group to compare the clinical features. RESULTS: Of 664 CS patients (446 men, 68.7±12.8 years), 68 (10.2%) met the criteria of AD (AD group), and 596 (89.8%) were in the non-AD group. On multiple logistic regression analysis, body mass index (unit OR 1.11, 95%CI 1.04-1.19, p=0.002), diabetes mellitus (OR 2.23, 95%CI 1.28-3.87, p=0.004), ACL in the arch (OR 1.89, 95%CI 1.09-3.31, p=0.025), and deterioration during hospitalization (OR 3.96, 95%CI 1.32-10.68, p=0.009) were independently associated with AD. CONCLUSION: AD was not rare in the present CS population. Moreover, AD was crucially related to ACL in CS. Therefore, intensive and pleiotropic lipid-modifying therapy would be efficacious for further treatment of aortogenic brain embolism.
Tanigawa R, Nakajima A, Eguchi Y
… +7 more, Takahashi H, Loomba R, Suganami H, Tanahashi M, Saito A, Iida Y, Yamashita S
J Atheroscler Thromb
· 2025 Jul · PMID 39694503
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AIM: In the PEMA-FL study in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), pemafibrate was shown to significantly decrease low-density lipoprotein cholesterol (LDL-C) levels. We aimed to...AIM: In the PEMA-FL study in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), pemafibrate was shown to significantly decrease low-density lipoprotein cholesterol (LDL-C) levels. We aimed to investigate the mechanisms of pemafibrate-induced LDL-C reduction in patients with MASLD by conducting an additional sub-analysis of the PEMA-FL study. METHODS: The PEMA-FL study randomized 118 patients with MASLD to receive pemafibrate or placebo for 72 weeks. This sub-analysis examined the percentage change in LDL-C and related lipid markers by tertile of baseline LDL-C levels and the correlation between these changes in the pemafibrate group. RESULTS: Pemafibrate significantly decreased LDL-C levels approximately 25% (p＜0.001 at all timepoints) from baseline in the highest tertile of baseline LDL-C levels (≥ 137.5 mg/dL), with similar trends for non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (ApoB) levels. Lipoprotein (a) [Lp(a)] levels decreased only in patients with the highest baseline LDL-C levels. Regardless of the baseline LDL-C levels, pemafibrate altered the LDL particle profile (increased LDL particle size and decreased the number); reduced lathosterol, β-sitosterol, and campesterol; and increased angiopoietin-like protein 3 (ANGPTL3). The percentage change in LDL-C positively correlated with that in ApoB, non-HDL-C, Lp(a), lathosterol, β-sitosterol, and campesterol but not HDL-C and ANGPTL3. CONCLUSION: Pemafibrate reduced LDL-C, ApoB, and non-HDL-C levels in patients with MASLD, and the effect was greater in those with higher baseline LDL-C levels. Pemafibrate may clinically benefit patients with MASLD by improving LDL-C levels and the LDL particle profile.
Mizuta H, Ishii M, Ikebe S
… +4 more, Otsuka Y, Yamanouchi Y, Nakamura T, Tsujita K
J Atheroscler Thromb
· 2025 Jul · PMID 39675972
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AIMS: To investigate the association between triglyceride levels and major adverse cardiovascular events (MACE) in primary and secondary prevention cohorts. METHODS: This retrospective study was conducted with a nationwi...AIMS: To investigate the association between triglyceride levels and major adverse cardiovascular events (MACE) in primary and secondary prevention cohorts. METHODS: This retrospective study was conducted with a nationwide health insurance claims database, which included approximately 3.8 million participants with medical checkups between January 2005 and August 2020 in Japan. The participants were classified into primary prevention (n=3,415,522) and secondary prevention (n=29,806) cohorts based on cardiovascular or cerebrovascular disease history. Each participant was categorized as having very low (triglyceride ＜50 mg/dL), low normal (50-99), high normal (100-149), or hypertriglyceridemia (≥ 150). The primary prevention cohort was further stratified into low-, intermediate-, and high-risk groups according to atherosclerotic cardiovascular diseases risk. Outcome was MACE, including acute myocardial infarction (AMI), unstable angina, ischemic stroke, and cardiac death. RESULTS: Over a mean follow-up of 3.25 years, 0.3% and 2.6% MACE occurred in primary and secondary prevention, respectively. Hypertriglyceridemia was associated with high risk of MACE in the primary prevention, but not in the secondary prevention. A significant interaction was observed between prevention categories and the association of TG levels with MACE in those with TG ＜150 mg/dL and ischemic stroke in those with TG ≥ 150 mg/dL. The population-attributable fraction for hypertriglyceridemia in primary prevention was 4.1% for MACE. In primary prevention, lower risks of AMI were observed in the lower TG category compared to the current threshold. CONCLUSIONS: This study suggests distinct triglyceride thresholds for MACE risk in primary and secondary prevention cohorts, requiring further prospective validation for clinical implementation.
Liu S, Wang Y, Yang M
… +9 more, Dai X, Huang T, Liao R, Song H, Li P, Chen Y, Huang H, Zhang C, Xiao Y
J Atheroscler Thromb
· 2025 Jun · PMID 39662948
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AIMS: Plasma S-adenosylhomocysteine (SAH) level is positively associated with cardiovascular risk. However, the relationship between plasma SAH levels and the risk of all-cause and cardiovascular mortality remains unknow...AIMS: Plasma S-adenosylhomocysteine (SAH) level is positively associated with cardiovascular risk. However, the relationship between plasma SAH levels and the risk of all-cause and cardiovascular mortality remains unknown. This study aimed to explore the relationship between plasma SAH levels and the risk of all-cause and cardiovascular mortality in patients with coronary artery disease (CAD). METHODS: Plasma SAH levels were measured in 1553 patients with CAD. The association between plasma SAH level and the risk of all-cause and cardiovascular mortality was estimated using Cox Proportional hazards regression models. RESULTS: Relative to participants in the lowest quartile of plasma SAH levels, those in the highest quartile of plasma SAH levels had a higher risk of all-cause death (adjusted Hazard Ratio [HR], 2.15; 95% CI, 1.54-3.01; P＜0.001) and cardiovascular death (adjusted HR, 2.20; 95% CI, 1.49-3.25; P=0.001) in the age- and sex-adjusted model. The results of the multivariable adjusted analysis were similar (all-cause death [adjusted HR, 1.81; 95% CI, 1.27-2.58; P=0.002] and cardiovascular death [adjusted HR, 1.84; 95% CI, 1.21-2.79; P=0.031]). The age- and sex-adjusted HRs for each 1 SD increase in plasma SAH level were 1.30 (95% CI, 1.22-1.38) for all-cause mortality, and 1.34 (95% CI, 1.25-1.43) for cardiovascular mortality, respectively. A 1 SD increase in the SAH level was associated with a 25% higher risk of total death (adjusted HR, 1.25; 95% CI, 1.17-1.34) and a 29% greater risk of cardiovascular death (adjusted HR, 1.29; 95% CI, 1.20-1.39) in multivariable adjusted analysis. CONCLUSIONS: We found that the plasma SAH level is positively correlated with the risk of all-cause and cardiovascular mortality in patients with CAD in both age- and sex-adjusted and multivariable-adjusted models.
Tamaki A, Kuroda M, Yonaha K
… +15 more, Ishiki Y, Uehara M, Nakayama Y, Honma KI, Chinen R, Uema T, Okamoto S, Miyoshi J, Kirinashizawa M, Sato K, Aohara T, Yamamoto M, Maezawa Y, Yokote K, Masuzaki H
J Atheroscler Thromb
· 2025 May · PMID 39662947
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A 59-year-old Japanese woman was referred for an extremely low level of circulating high-density lipoprotein cholesterol (HDL-C). The serum HDL-C level had long been within the normal range but suddenly decreased asympto...A 59-year-old Japanese woman was referred for an extremely low level of circulating high-density lipoprotein cholesterol (HDL-C). The serum HDL-C level had long been within the normal range but suddenly decreased asymptomatically to 7 mg/dL. She had no typical symptoms associated with familial lecithin, cholesterol acyltransferase deficiency (FLD), including proteinuria, anemia, and corneal opacity. The circulating level of ApoA-1 was also markedly decreased at 48 mg/dL, and the proportion of esterified cholesterol to free cholesterol was irregularly low at 26%. Whole-genome sequencing revealed no apparent pathological mutations in the LCAT gene. Notably, anti-LCAT antibodies were detected in the serum at 146±1.7 ng/mL, resulting in her being diagnosed with acquired LCAT insufficiency (ALCATI) caused by anti-LCAT antibodies. Five years after her HDL-C levels spontaneously decreased, they increased without any identifiable cause. To our knowledge, only six cases of ALCATI caused by anti-LCAT antibodies have been reported to date. In contrast to the present case, previously reported cases of ALCATI manifested proteinuria that improved with steroid therapy. The unique clinical course in the present case highlights the heterogeneity of ALCATI, warranting further research to clarify the molecular pathophysiology of FLD and ALCATI.