Journal Of Atherosclerosis And Thrombosis[JOURNAL]
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200 papers
Perspectives on Bempedoic Acid, ATP-citrate lyase inhibitor: Targeting Lipid Metabolism and Inflammation.
Kitamoto R, Morikawa-Isogai Y, Shimano H
J Atheroscler Thromb · 2026 May · PMID 42178228 · Publisher ↗
Bempedoic acid is a novel oral low-density lipoprotein cholesterol (LDL-C)-lowering agent that selectively inhibits ATP-citrate lyase (ACL), an enzyme located upstream of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) r...
Bempedoic acid is a novel oral low-density lipoprotein cholesterol (LDL-C)-lowering agent that selectively inhibits ATP-citrate lyase (ACL), an enzyme located upstream of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase in the cholesterol biosynthesis pathway. Inhibition of ACL suppresses acetyl-CoA production, leading to reduced cholesterol synthesis and increased hepatic expression of LDL receptors, which lowers circulating LDL-C. Clinical trials have demonstrated an approximately 20% reduction in LDL-C when bempedoic acid is used in combination with statins. To offer a new perspective on the underlying mechanism, we reviewed the literature examining the LDL-C-lowering effects of bempedoic acid based on Michaelis-Menten kinetics. This framework helps explain why adding bempedoic acid to statin therapy may result in a synergistic increase in LDL-C reduction, greater than from increasing the statin dose alone. In animal studies, reductions observed in both hepatic and plasma triglyceride (TG) levels have been attributed to suppressed fatty acid synthesis due to decreased acetyl-CoA availability following ACL inhibition. Additionally, bempedoic acid has been shown to lower high-sensitivity C-reactive protein (hs-CRP) and inflammatory cytokines, suggesting potential anti-inflammatory and anti-lipotoxic effects. These findings support broader metabolic benefits of bempedoic acid, particularly in conditions such as obesity and fatty liver with hypercholesterolemia. In this review article, we outline the synergistic effects of bempedoic acid with statins, and its potential metabolic benefits based on the mechanism of action of bempedoic acid, and discuss its prospective role in future lipid management strategies.
Cross-Sectional Association of Lipoprotein(a) Levels With Vascular Complications and Related Parameters in a Japanese Type 2 Diabetes Cohort.
Hirano T, Uetani M, Nakata K … +4 more , Suzuki N, Aoki E, Hirashima T, Ito Y
J Atheroscler Thromb · 2026 May · PMID 42161533 · Publisher ↗
AIMS: To investigate the association between Lipoprotein(a) (Lp(a)) levels and vascular complications, as well as related parameters, in a cohort of Japanese patients with type 2 diabetes. METHODS: This cross-sectional a...
AIMS: To investigate the association between Lipoprotein(a) (Lp(a)) levels and vascular complications, as well as related parameters, in a cohort of Japanese patients with type 2 diabetes. METHODS: This cross-sectional analysis was conducted using data from a cohort of patients with 1465 type 2 diabetes. Lp(a) was measured by a turbidimetric immunoassay. Participants were categorized according to Lp(a) levels: GI (＜30), GII (30-49), and GIII (≥ 50 mg/dL). Small dense low-density lipoprotein (LDL)-cholesterol (sdLDL-C) and LDL-triglycerides were measured using homogeneous assays. RESULTS: The median [interquartile range] plasma Lp(a) concentration was 12.7 [6.1-24.6] mg/dL (21.8 [6-50.5] nmol/L). The prevalence rates for GI, GII, and GIII were 80, 12, and 8%, respectively, while low Lp(a) levels (＜5 mg/dL) were present in 18%. These prevalence rates were comparable to those reported in the general Japanese population. Higher Lp(a) grades were associated with the prevalence of coronary artery disease (CAD), peripheral artery disease including borderline cases, severe diabetic retinopathy, and chronic kidney disease (CKD), but not with stroke. Lp(a) levels were higher in older individuals, female, kidney dysfunction, and statin users, whereas lower levels were observed in those with higher glycemia, current drinkers, and liver dysfunction. Patients with CAD or statin users had lower levels of LDL-C, sdLDL-C, LDL-triglycerides, and apolipoprotein B but higher Lp(a) concentrations compared to the control group. CONCLUSIONS: Lp(a) levels were associated with the prevalence of diabetic complications, particularly CKD and CAD. Lp(a) remains relevant associated factor with CAD in cross-sectional studies influenced by ongoing lipid-lowering therapies.
Association Between Plasma Omega-3 and Omega-6 Fatty Acid Levels and Atrial Fibrillation: A Large-Scale, Real-World Retrospective Study in Japan.
Yanagisawa N, Fujibayashi K, Miyazaki T … +1 more , Daida H
J Atheroscler Thromb · 2026 May · PMID 42161527 · Publisher ↗
AIM: The relationship between omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) and atrial fibrillation (AF) remains unclear. This retrospective study aimed to investigate the association between plasma levels of o...
AIM: The relationship between omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) and atrial fibrillation (AF) remains unclear. This retrospective study aimed to investigate the association between plasma levels of omega-3 PUFAs (eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA]) and omega-6 PUFAs (arachidonic acid [AA] and dihomo-γ-linolenic acid [DGLA]) and the prevalence of AF. METHODS: After excluding patients who were prescribed icosapent ethyl (IPE) or were younger than 40 years, data from 9,178 patients at Juntendo University Hospital with plasma EPA, DHA, AA, and DGLA measurements obtained between April 2017 and January 2021 were analyzed. The plasma PUFA levels were divided into quartiles, with the lowest quartile used as the reference. Multivariable logistic regression and restricted cubic spline analyses were performed to assess the association between the PUFA levels and AF. RESULTS: The median age was 69 years (interquartile range [IQR], 59-77 years), and 60.6% of the participants were male. AF was diagnosed in 908 (9.9%) patients. After adjusting for age, sex, and body mass index (BMI), higher plasma levels of EPA, DHA, EPA+DHA, AA, and DGLA were significantly associated with a lower risk of AF (all P＜0.001). In contrast, no significant associations were observed between the PUFA ratios, including (EPA+DHA)/AA, EPA/AA, DHA/AA, and DGLA/AA, and AF. Restricted cubic spline analyses revealed linear inverse associations for EPA, DHA, EPA+DHA, and AA and AF, whereas a nonlinear association for DGLA and AF was observed. CONCLUSION: Within the physiological ranges, higher plasma levels of EPA, DHA, EPA+DHA, AA, and DGLA were independently and inversely associated with AF risk. However, extremely high EPA concentrations, achieved through pharmacological interventions, have been suggested to be associated with an increased risk of AF.
Hospital Course and Outcomes After Major Bleeding in Patients on Factor Xa Inhibitors in Japan: A Nationwide Observational Study.
Kohsaka S, Yasaka M, Hoshino M … +3 more , Ide R, Wada F, Morita N
J Atheroscler Thromb · 2026 May · PMID 42161526 · Publisher ↗
AIM: To evaluate the clinical characteristics, management, and in-hospital outcomes of patients hospitalized with major bleeding while receiving direct factor Xa inhibitors (FXa-I) using a large-scale, nationwide adminis...
AIM: To evaluate the clinical characteristics, management, and in-hospital outcomes of patients hospitalized with major bleeding while receiving direct factor Xa inhibitors (FXa-I) using a large-scale, nationwide administrative claims database. METHODS: This retrospective cohort study analyzed an administrative hospital claims database to identify patients hospitalized with major bleeding while receiving FXa-I between August 2011 and May 2022 (before the launch of andexanet alfa), resulting in 8011 patients (median age, 80.0 years) being eligible for the analysis. The data collected encompassed patient demographics, hospitalization details, bleeding sites, and outcomes of interest, such as in-hospital mortality and the resumption of OACs. RESULTS: The most common bleeding sites were upper gastrointestinal bleeding (GIB; 30.3%), intracranial hemorrhage (ICH; 17.6%), lower GIB (11.7%), and trauma-related bleeding (9.1%). Patients had a median hospital stay of 11.0 days (range, 1-911 days). The overall in-hospital mortality rate was 7.1% (95% CI: 6.6-7.7%). In-hospital mortality rates by bleeding site were 17.8% for ICH, 5.1% for upper GIB, 1.4% for lower GIB, 10.2% for trauma-related bleeding, and 4.1% for other bleeding sites. The most common cause of death was hemorrhage-related (70.1%). OACs were resumed in 67.9% of patients, with a median time to resumption of 3.0 days. CONCLUSION: In this nationwide study, the in-hospital mortality rate for patients hospitalized for FXa-I-related major bleeding was approximately 7%. Although most patients resumed oral anticoagulant therapy during hospitalization, the significant in-hospital mortality rates observed, especially in cases of ICH, highlight the need for strategies to further improve the outcomes in patients experiencing FXa-I-related complications.
A Literature Review on the Waist Circumference Criteria for Metabolic Syndrome in Japan: Evidence and Implications for Cardiovascular Risk Stratification.
Uchida T, Hirata A
J Atheroscler Thromb · 2026 May · PMID 42144349 · Publisher ↗
Waist circumference (WC) is widely used as a marker of central obesity in the diagnosis of metabolic syndrome (MetS) and it plays an important role in cardiovascular disease (CVD) risk screening. In Japan, the MetS diagn...
Waist circumference (WC) is widely used as a marker of central obesity in the diagnosis of metabolic syndrome (MetS) and it plays an important role in cardiovascular disease (CVD) risk screening. In Japan, the MetS diagnostic criteria established in 2005 require abdominal obesity as a mandatory component, with WC cutoff values of 85 cm for men and 90 cm for women. These criteria are also applied in the national Specific Health Checkup and Specific Health Guidance programs to identify individuals at a high risk of CVD. However, the scientific basis and clinical implications of these thresholds remain controversial.This review summarizes the epidemiological evidence on WC cutoff values in the Japanese population and their relevance to CVD risk. A literature search of PubMed and Ichushi-Web identified studies examining WC thresholds in relation to visceral fat accumulation, clustering of cardiometabolic risk factors, and incident CVD. The evidence was organized into four themes: (1) WC cutoffs based on visceral fat area, (2) prediction of cardiometabolic risk factor clustering, (3) the association between WC and incident CVD, and (4) associations between MetS definitions and CVD risk.Available evidence suggests that the WC thresholds corresponding to visceral fat accumulation and cardiometabolic risk clustering are generally lower than the current Japanese criterion for women. Prospective studies examining WC alone have reported inconsistent associations with incident CVD, particularly among women. Overall, the evidence suggests that CVD risk stratification frameworks requiring abdominal obesity based on WC thresholds may have limitations. Future screening strategies in Japan may benefit from greater emphasis on clustering and the overall burden of cardiometabolic risk factors.
A Phase 1 Study Evaluating the Pharmacokinetics, Pharmacodynamics, and Safety of Zerlasiran in Japanese Participants.
Fok H, Harada-Shiba M, Rider D … +2 more , Owada Y, Rambaran C
J Atheroscler Thromb · 2026 May · PMID 42108101 · Publisher ↗
AIM: Zerlasiran is an N-acetylgalactosamine-conjugated small interfering RNA that targets lipoprotein(a), a risk factor for atherosclerosis and calcific aortic stenosis. Zerlasiran has not been studied in Japanese partic...
AIM: Zerlasiran is an N-acetylgalactosamine-conjugated small interfering RNA that targets lipoprotein(a), a risk factor for atherosclerosis and calcific aortic stenosis. Zerlasiran has not been studied in Japanese participants previously. METHOD: This was an open-label, single-dose trial that enrolled 18 adult participants with lipoprotein(a) levels ≥ 70 nmol/L at a single site in Japan to evaluate subcutaneous doses of zerlasiran (30 mg, 100 mg, and 300 mg) in three ascending-dose cohorts. The participants were monitored for 150 days post-dose to assess the systemic pharmacokinetics, pharmacodynamics (lipoprotein (a) and lipid biomarkers), and safety. RESULTS: Following dosing, median T was reached at 5 hours with plasma concentrations gradually declining to undetectable levels by 36 hours, with t approximately 4 hours. Both C and AUC increased in a dose-dependent manner. The maximum median (interquartile range [IQR]) percent reduction in lipoprotein (a) in the 30 mg, 100 mg, and 300 mg cohorts were -72.8% (-79.7%, -67.1%), 88.8% (-89.5%, -84.7%), and -97.8% (-98.6, -96.9%), respectively, between days 30 and 60, with a sustained effect observed at 150 days at all dose levels. All adverse events were mild and self-limiting. CONCLUSION: Zerlasiran was well tolerated with no significant safety findings observed at any dose level. A typical pharmacokinetic profile expected of an N-acetylgalactosamine-conjugated small interfering RNA, coupled with a potent and sustained reduction in lipoprotein(a), was observed in Japanese participants. No adverse effects on either the liver or kidney function were observed.
It's Time to Measure Lp(a): Recognizing a Neglected Cardiovascular Risk.
Tada H, Takamura M
J Atheroscler Thromb · 2026 May · PMID 42108091 · Publisher ↗
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Lipoprotein(a) Distribution and Cardiovascular Risk in Japan: Insights from a Multi-center LEAP Study.
Yamada T, Tada H, Ogura M … +18 more , Funabashi S, Yoshida H, Hiraishi C, Ebihara T, Hadano T, Masaki T, Takeji Y, Fukatsu K, Egawa M, Kataoka Y, Michikura M, Shishikura D, Fujioka S, Sasano T, Maehara T, Ai M, Shiba-Harada M, Yoshida M
J Atheroscler Thromb · 2026 May · PMID 42091526 · Publisher ↗
AIM: Although lipoprotein(a) [Lp(a)] is recognized as an independent risk factor for cardiovascular disease (CVD), its distribution and risk thresholds in the Japanese population remain unclear. This study aimed to chara...
AIM: Although lipoprotein(a) [Lp(a)] is recognized as an independent risk factor for cardiovascular disease (CVD), its distribution and risk thresholds in the Japanese population remain unclear. This study aimed to characterize the distribution of Lp(a) in Japanese clinical settings and evaluate its association with CVD risk, including coronary artery disease (CAD), atherosclerotic cardiovascular disease (ASCVD), and familial hypercholesterolemia (FH). METHODS: The LEAP study is a multicenter retrospective cohort analysis of 6,173 patients from six Japanese institutions. The Lp(a) values were harmonized to nmol/L using kit-specific conversion equations, enabling a consistent analysis across different immunoassays. Associations with CAD, ASCVD, chronic kidney disease (CKD), diabetes mellitus (DM), and FH were assessed. The risk thresholds were defined using a receiver operating characteristic analysis. RESULTS: The median Lp(a) concentration was 20.88 nmol/L, with a right-skewed distribution. Elevated Lp(a) levels were significantly associated with CAD, ASCVD, CKD, and FH. In contrast, DM was related to lower Lp(a). An ROC analysis identified 25 nmol/L as a screening threshold and 125 nmol/L as a high-risk boundary. The CAD prevalence increased stepwise across these categories: 20.2% (≤ 25 nmol/L), 30.3% (25-125 nmol/L), and 39.9% (＞125 nmol/L). CONCLUSION: This study provides the first nmol/L-standardized Lp(a) distribution in Japanese patients and proposes provisional thresholds for clinical risk stratification.
Association between cardiovascular disease risk factors and white matter lesions: The Tohoku Medical Megabank Cohort Study.
Satake M, Chiba I, Kogure M … +14 more , Hatanaka R, Nakaya K, Takase M, Tokioka S, Nakaya N, Mori N, Koyama T, Abe Y, Taki Y, Fuse N, Kinoshita K, Izumi Y, Mugikura S, Hozawa A
J Atheroscler Thromb · 2026 Apr · PMID 42055686 · Publisher ↗
AIM: White matter lesions (WML) are associated with dementia and they are influenced by cardiovascular disease (CVD) risk factors. Managing these risk factors may prevent WML progression. However, few longitudinal studie...
AIM: White matter lesions (WML) are associated with dementia and they are influenced by cardiovascular disease (CVD) risk factors. Managing these risk factors may prevent WML progression. However, few longitudinal studies have examined the association between CVD risk factors and changes in the WML volume. This study aimed to investigate this association across a broad age range, including younger individuals. METHODS: This longitudinal study included 4,595 participants (age range, 21-90 years; women, 61.7%) who underwent brain magnetic resonance imaging. WML was defined on T1-weighted images. The associations between each CVD risk factor (hypertension, diabetes, dyslipidemia, and current smoking) and WML volume changes (per 4 years) were analyzed using a generalized linear model with estimated regression coefficients (β) and 95% confidence intervals (CI). The analyses were stratified by age group (＜50, 50-59, 60-69, and ≥ 70 years). RESULTS: Hypertension was significantly associated with increased WML volume change in those aged ＜50 and 50-59 years (β [95%CI] = 57.1 [8.0-106.2] and β [95%CI] = 77.9 [6.8-149.0], respectively). For both diabetes and dyslipidemia, the WML volume increased in those aged ＜50 years (β [95%CI] = 376.5 [209.3-543.8] and β [95%CI] = 154.0 [93.0-215.0], respectively). Current smoking showed an increase in those aged 50-59 and ≥ 60 years (β [95%CI] = 104.5 [2.1-206.8] and β [95%CI] = 305.9 [133.4-478.5], respectively). No significant associations were observed for any CVD risk factors in the other age groups. CONCLUSIONS: The WML volume changes were larger in younger age groups for most CVD risk factors, suggesting that early management of these factors may help prevent WML progression.
Association of Relative LDL-Cholesterol Reduction With Cardiovascular Outcomes After Percutaneous Coronary Intervention.
Morishita T, Uzui H, Sato Y … +4 more , Shimizu T, Kataoka T, Hasegawa K, Tada H
J Atheroscler Thromb · 2026 Apr · PMID 42021053 · Publisher ↗
AIM: Intensive low-density lipoprotein cholesterol (LDL-C) lowering is a cornerstone of secondary prevention after percutaneous coronary intervention (PCI). Although most evidence has focused on achieved LDL-C levels, th...
AIM: Intensive low-density lipoprotein cholesterol (LDL-C) lowering is a cornerstone of secondary prevention after percutaneous coronary intervention (PCI). Although most evidence has focused on achieved LDL-C levels, the prognostic significance of relative LDL-C reduction has been less well characterized. The joint influence of achieved LDL-C levels and relative reduction in real-world PCI populations remains unclear. METHODS: We retrospectively analyzed consecutive patients who underwent PCI between 2006 and 2016 at a single tertiary center. Relative LDL-C reduction was calculated from baseline and follow-up measurements. The primary outcome was three-point major adverse cardiovascular events plus any coronary revascularization. Cox proportional hazards models with restricted cubic splines were used to assess continuous dose-response relationships. Secondary analyses evaluated categorical thresholds of relative LDL-C reduction (＜30%, 30-49%, ≥50%) and achieved LDL-C ＜55 mg/dL. A thin-plate spline generalized additive model was used to visualize their joint association with cardiovascular risk. RESULTS: Among 809 patients, greater relative LDL-C reduction was associated with a significantly lower risk of the primary outcome in a nonlinear pattern (overall P = 0.0001; nonlinearity P = 0.0007). Compared with ＜30% reduction, 30-49% and ≥ 50% reductions were associated with progressively lower risk. Achieved LDL-C ＜55 mg/dL was associated with lower risk, and the most favorable outcomes were observed when low achieved LDL-C levels were accompanied by substantial relative LDL-C reduction. CONCLUSION: Relative LDL-C reduction provides clinically meaningful prognostic information after PCI, complementing achieved LDL-C levels and supporting guideline-based lipid-lowering strategies.
The Tortuosity of Middle Cerebral Artery is Associated with Ipsilateral Recurrence of Ischemic Events.
Chen Y, Wang Y, Zhu Y … +8 more , He Y, Zhao T, Lin J, Shao Y, He Y, Yang Y, Zhu Y, Yu M
J Atheroscler Thromb · 2026 Apr · PMID 42021052 · Publisher ↗
AIM: To investigate whether the tortuosity of the culprit middle cerebral artery (MCA) is correlated with the recurrence of ipsilateral ischemic events in patients with ischemic stroke caused by intracranial atherosclero...
AIM: To investigate whether the tortuosity of the culprit middle cerebral artery (MCA) is correlated with the recurrence of ipsilateral ischemic events in patients with ischemic stroke caused by intracranial atherosclerotic disease (ICAD) on M segment of MCA. METHODS: A total of 279 patients with first-ever M-ICAD-related stroke were enrolled. The morphology of the culprit M segment was measured using MR or CT angiography, including the arc and chord length. The tortuosity index was calculated as (arc length / chord length - 1) × 100%. During the follow-up, the primary endpoints included recurrent transient ischemic attack and ischemic stroke attributable to culprit M-ICAD. The participants were stratified into subgroups according to the tertiles of the tortuosity index: Q (＜9.98%), Q (9.98%-19.17%), and Q (＞19.17%). Multivariate Cox regression was performed to identify the factors associated with recurrence and the recurrence rates of subgroups was analyzed by log-rank test. RESULTS: The recurrence rates (group Q, 20.4%, group Q, 10.6%, group Q, 4.3%, p = 0.003) are statically different. The tortuosity index (HR[hazard ratios] = 0.96, 95% CI[confidence intervals] = 0.92-0.997, p = 0.037) is inversely associated with the recurrence. The Q group exhibits a higher risk of recurrence (HR = 5.39, 95% CI: 1.66-17.48, p = 0.005) than the Q3 group, with the rate difference of 16.1% (95% CI: 6.9%-25.3%, p = 0.002). CONCLUSION: In patients with M-ICAD-related stroke, lower tortuosity index of culprit MCA is associated with a higher risk of recurrent ipsilateral ischemic events.
Lipoprotein(a) Is Associated with Coronary Plaque Vulnerability and Compensatory Vascular Enlargement: An Intravascular Ultrasound Study.
Jiang Y, Lin J, Ma M … +3 more , Xu J, Yu P, Wang H
J Atheroscler Thromb · 2026 Apr · PMID 42002902 · Publisher ↗
AIMS: Lipoprotein(a) [Lp(a)] has emerged as a critical determinant of residual cardiovascular risk. However, its impact on plaque morphology remains underinvestigated. This study aimed to elucidate the relationship betwe...
AIMS: Lipoprotein(a) [Lp(a)] has emerged as a critical determinant of residual cardiovascular risk. However, its impact on plaque morphology remains underinvestigated. This study aimed to elucidate the relationship between the serum Lp(a) levels, coronary plaque vulnerability, and vascular remodeling characteristics by utilizing intravascular ultrasound (IVUS). METHODS: We retrospectively enrolled 292 consecutive patients with coronary artery disease who underwent IVUS. Target lesions were classified into vulnerable (n = 83) or stable (n = 209) plaque groups based on the IVUS criteria. Multivariate binary logistic regression was performed to identify independent predictors. The morphological parameters were further compared between the high (＞18.8 mg/dL) and low (≤ 18.8 mg/dL) Lp(a) groups. RESULTS: The vulnerable plaque group exhibited significantly higher median serum Lp(a) levels than the stable group (14.56 vs. 11.04 mg/dL, P = 0.011). After adjusting for age, sex, LDL-C, smoking, diabetes, and hypertension, Lp(a) ＞18.8 mg/dL remained an independent predictor of plaque vulnerability (OR = 1.76; 95% CI: 1.00-3.07; P = 0.049). Notably, the LDL-C levels did not predict vulnerability in this cohort. Furthermore, the high Lp(a) group demonstrated significantly larger vascular dimensions (EEM CSA: 14.67±4.95 vs. 13.22±4.20 mm, P = 0.016) and plaque area (11.07±4.61 vs. 9.71±3.79 mm, P = 0.015) than the low Lp(a) group, consistent with compensatory vascular enlargement, although the difference in the remodeling index did not reach statistical significance. CONCLUSION: Elevated serum Lp(a) levels are independent predictors of coronary plaque vulnerability. The underlying mechanism involves Lp(a) promoting compensatory vascular enlargement, accompanied by an increased plaque volume. These findings underscore the necessity of Lp(a) screening to identify any residual risk, particularly in patients with effectively controlled low-density lipoprotein cholesterol (LDL-C).
Ligand-Specific Notch Signaling in Atherosclerosis: Implications for Inflammation and Plaque Stability.
Bavuu O, Fukuda D
J Atheroscler Thromb · 2026 Jun · PMID 41987387 · Full text
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Clinical Efficacy with Evolocumab among Japanese Patients in PROFICIO: A Pooled Analysis of 1,040 Patients.
Oyama K, Yoshida M, Kiyosue A … +7 more , Osada N, Sheng F, Harada N, Miyawaki K, Shimauchi J, Fu Y, Yamashita S
J Atheroscler Thromb · 2026 Jul · PMID 41987365 · Publisher ↗
AIMS: Lowering low-density lipoprotein cholesterol (LDL-C) is essential for reducing the risk of atherosclerotic cardiovascular disease (ASCVD). This study assessed the clinical efficacy of evolocumab, a human monoclonal...
AIMS: Lowering low-density lipoprotein cholesterol (LDL-C) is essential for reducing the risk of atherosclerotic cardiovascular disease (ASCVD). This study assessed the clinical efficacy of evolocumab, a human monoclonal antibody targeting PCSK9, in Japanese patients using data from the PROFICIO program. METHODS: Data were pooled from Japanese participants enrolled in five clinical trials: YUKAWA-1, YUKAWA-2, OSLER-1, OSLER-2, and FOURIER. The primary endpoint was percent change in LDL-C from baseline to Week 12. Secondary endpoints included changes in other lipid parameters, achievement of LDL-C targets, incidence of major adverse cardiovascular events (MACE), and subgroup analyses. RESULTS: A total of 1,040 patients with high cardiovascular risk or established ASCVD were included. At Week 12, the mean percent reduction in LDL-C was 75.7% with evolocumab compared with 1.3% with placebo (least-square mean treatment difference: ‑75.0%; 95% confidence interval [CI]: -76.7 to -73.4; p＜0.001), which was consistent across subgroups. Other lipid parameters showed directionally consistent percent changes, with variable magnitudes across markers. Overall, 92.9% of patients treated with evolocumab achieved an LDL-C ＜55 mg/dL at Week 12 compared with 0.8% of patients in the placebo group. In FOURIER, over a median follow-up of 2.1 years, incidence of MACE was lower with evolocumab than placebo (5.9% vs. 12.4%; hazard ratio: 0.47; 95% CI: 0.24-0.92). Treatment effects on MACE were consistent in both primary and secondary prevention groups (pooled odds ratio: 0.42; 95% CI: 0.23-0.79). CONCLUSION: Evolocumab significantly and consistently lowered LDL-C and reduced the risk of MACE in Japanese patients.
Role of T1-weighted MRI in Identifying Coronary Intraplaque Hemorrhage: CATCH the Truly High-Risk Plaque.
Matsumoto H
J Atheroscler Thromb · 2026 Jul · PMID 41967927 · Publisher ↗
Intraplaque hemorrhage (IPH) is a key feature of plaque vulnerability that contributes to atherothrombotic events. Non-invasive coronary plaque imaging has been challenging because of the small size of the coronary arter...
Intraplaque hemorrhage (IPH) is a key feature of plaque vulnerability that contributes to atherothrombotic events. Non-invasive coronary plaque imaging has been challenging because of the small size of the coronary arteries and motion caused by cardiac contraction and respiration. Recent advances in magnetic resonance imaging (MRI) have enabled the non-invasive detection of coronary IPH. Compared with coronary computed tomography angiography and intravascular imaging modalities, MRI offers unique noninvasive tissue characterization based on intrinsic signal properties. Histopathological and intravascular imaging investigations have indicated that erythrocyte-derived materials, rather than lipid components, constitute the predominant substrate of coronary high-intensity plaques, reflecting recent IPH. This review summarizes the pathophysiological basis, imaging characteristics, and clinical implications of MRI-detected coronary IPH, in the context of other imaging modalities.
Switching from Conventional Fibrates to Pemafibrate Improves Lipid Profiles, Liver Enzymes, Renal Function, and Fibrosis Markers in Dyslipidemic Patients with MASLD: A Multicenter Real-World Study.
Sato T, Miyamoto T, Fukuoka R … +8 more , Sugimoto K, Tanimoto Y, Nakayama T, Tanimoto K, Sugimura K, Fujimoto Y, Kiyooka T, Kawamura A
J Atheroscler Thromb · 2026 Jul · PMID 41951373 · Publisher ↗
AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent worldwide. Conventional fibrates effectively lower triglycerides but may elevate liver enzymes and creatinine, limiting long-term...
AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent worldwide. Conventional fibrates effectively lower triglycerides but may elevate liver enzymes and creatinine, limiting long-term use. Pemafibrate, a selective PPARα modulator (SPPARMα), offers potent triglyceride reduction with favorable hepatic and renal safety. This study evaluated the effects of switching from conventional fibrates to pemafibrate on lipid profiles, liver enzyme, fibrosis indices(Fibrosis-4 index) with particular emphasis on renal safety in clinical practice. METHODS: We retrospectively analyzed 144 patients with dyslipidemia, including those with MASLD or chronic kidney disease, who were switched from bezafibrate 200mg (N = 24) or 400mg (N = 30), or fenofibrate 80mg (N = 51) or 160mg (N = 39), to pemafibrate (0.2mg/day). Laboratory parameters were assessed at baseline and 6 months post-switch. RESULTS: Triglycerides decreased significantly, particularly in the bezafibrate 200 mg and fenofibrate 80 mg groups, while other lipid profiles remained stable. Serum alanine aminotransferase decreased significantly with bezafibrate 200mg (29±27 to 17±13U/L, p＜0.05) and fenofibrate 80mg (26±18 to 20±10 U/L, p＜0.05), whereas treatment with bezafibrate (400mg) and fenofibrate (160mg) showed a trend toward reduction. The glutamyl transferase showed a similar trend. The Fibrosis-4 index showed reductions across all groups, reaching statistical significance in bezafibrate200mg (1.51±0.63→1.36±0.47, p = 0.02) and fenofibrate 80mg (1.17±0.37→1.07±0.33, p = 0.001). Renal function remained stable across all groups, with no clinically significant deterioration in estimated glomerular filtration rate, supporting the renal safety of pemafibrate. CONCLUSION: Switching from conventional fibrates to pemafibrate improved triglyceride levels, liver enzymes, and fibrosis indices in patients with MASLD, while maintaining a favorable renal safety profile.
Beyond Conventional Imaging: From Time-Based to Data-Driven Decision-Making in Acute Ischemic Stroke.
Deguchi I, Aoki J
J Atheroscler Thromb · 2026 Jun · PMID 41936446 · Full text
Reperfusion therapy has profoundly transformed acute ischemic stroke (AIS) care. Initially, treatment decisions relied primarily on time from symptom onset. However, growing evidence has shown that the extent of irrevers...
Reperfusion therapy has profoundly transformed acute ischemic stroke (AIS) care. Initially, treatment decisions relied primarily on time from symptom onset. However, growing evidence has shown that the extent of irreversibly injured tissue and the presence of salvageable brain tissue determine the efficacy and safety of reperfusion therapy. This caused a paradigm shift from time-based selection toward tissue-based assessment, placing neuroimaging at the center of clinical decision-making. This narrative review traces the evolution of imaging-based stroke assessment in the reperfusion era. We review the development and clinical impact of the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) and diffusion-weighted imaging (DWI)-ASPECTS, which translated the pathophysiological concept of the ischemic core into a practical, reproducible, routine clinical tool. We discuss the emergence of imaging and clinical mismatch concepts, including perfusion-based ischemic core-penumbra mismatch, as well as clinical-diffusion, MRA-diffusion, and DWI-FLAIR mismatches, which address the limitations of strict time-based criteria and expand treatment opportunities, particularly in patients with unknown onset time. Finally, we examine the growing role of artificial intelligence (AI)-driven automated imaging platforms in acute stroke care, enabling rapid, standardized, and quantitative assessment of ischemic core, penumbra, and vascular pathology. These tools support clinical decision-making under severe time constraints and reduce inter-reader and inter-institutional variability. This iterative process of trial and refinement has shaped the current framework of tissue-based, data-driven stroke care. We discuss how integrating established imaging concepts with emerging AI technologies may further advance precision reperfusion therapy and improve equity and outcomes in AIS treatment.
Impact of High-Intensity Statins and Low-Density Lipoprotein Cholesterol on the Outcomes of Coronary Intervention for Chronic Coronary Syndrome in Japan.
Yamauchi Y, Kanzaki Y, Shishikura D … +9 more , Sakaguchi K, Fujioka S, Kusumoto H, Tsuda K, Sakane K, Fujisaka T, Michikura M, Harada-Shiba M, Morita H
J Atheroscler Thromb · 2026 Jul · PMID 41905939 · Publisher ↗
AIM: The clinical effect of high-intensity statin therapy after percutaneous coronary intervention (PCI) in Japanese patients with chronic coronary syndrome (CCS) remains unclear. We investigated the association between...
AIM: The clinical effect of high-intensity statin therapy after percutaneous coronary intervention (PCI) in Japanese patients with chronic coronary syndrome (CCS) remains unclear. We investigated the association between high-intensity statin therapy and the cardiovascular outcomes following PCI in patients with CCS. METHODS: We retrospectively evaluated 716 patients with CCS who underwent PCI and categorized them into high- or non-high-intensity statin groups, according to the Japan Atherosclerosis Society guidelines. The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and revascularization, while the secondary outcome was all-cause death. The outcomes were further assessed according to the low-density lipoprotein cholesterol (LDL-C) levels (＜55 mg/dL, 55-69 mg/dL, and ≥ 70 mg/dL). The hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox model. RESULTS: Over a median follow-up of 2 years, high-intensity statin therapy reduced the incidence of the primary outcome (HR, 0.32; 95% CI, 0.17-0.61; P＜0.01) and all-cause death (HR, 0.18; 95% CI, 0.06-0.57; P＜0.01). This association with the primary composite outcome was consistently observed across the achieved LDL-C categories. CONCLUSIONS: High-intensity statin therapy was associated with a reduced risk of cardiovascular events after PCI in Japanese patients with CCS, independent of the achieved LDL-C levels.
Comparison of Clinical Characterization and Therapeutic Strategies between Homozygous Familial Hypercholesterolemia and Heterozygous Familial Hypercholesterolemia.
Shishikura D, Harada-Shiba M, Michikura M … +6 more , Sakaguchi K, Kusumoto H, Fujioka S, Fujisaka T, Kanzaki Y, Morita H
J Atheroscler Thromb · 2026 Jul · PMID 41905938 · Publisher ↗
AIMS: Homozygous Familial hypercholesterolemia (HoFH) is a rare genetic disease characterized by very high levels of low-density lipoprotein cholesterol (LDL-C). Owing to LDL receptor activity being completely or nearly...
AIMS: Homozygous Familial hypercholesterolemia (HoFH) is a rare genetic disease characterized by very high levels of low-density lipoprotein cholesterol (LDL-C). Owing to LDL receptor activity being completely or nearly all lost in HoFH, LDL-C levels greatly exceed normal levels, and are even higher than in heterozygous (HeFH), which can cause fatal cardiovascular disease even in infancy. The current study updates differences in clinical characterization, therapeutic strategies and cardiovascular outcomes between HoFH and HeFH. METHODS: A total of 157 patients who were genetically or clinically diagnosed with FH (HoFH: 15, HeFH: 142) were retrospectively analyzed. Clinical characteristics, lipid profiles and atherosclerotic prognosis were evaluated between HoFH and HeFH patients. RESULTS: Age and sex were similar between the two groups. Untreated LDL-C in HoFH was about double that in HeFH (498.4±164.3 vs. 232.0±60.5 mg/dL, p＜0.001), while on-treatment LDL-C with lipid lowering therapies did not differ significantly (83.8±59.1 vs. 127.1±59.6 mg/dL, p = 0.15). There was wide diversity in lipid lowering therapies between the two groups and a significantly higher prevalence of coronary artery and valvular disease in HoFH. Consequently, HoFH patients were more likely to receive percutaneous and surgical interventions at a younger age compared to HeFH patients. CONCLUSIONS: The findings of this observational study show the clinical relevance of FH. Although both HeFH and HoFH are inherited disorders of lipoprotein metabolism, HoFH should be treated with a different, stricter therapeutic strategy to prevent premature ASCVD.
An Improved Prognosis in Subjects With Homozygous Familial Hypercholesterolemia Associated With Advances in LDL-Lowering Therapy.
Tada H, Takamura M
J Atheroscler Thromb · 2026 Jul · PMID 41905937 · Publisher ↗
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