Tachioka S, Kanda H, Yamakuchi M
… +9 more, Higashi S, Suzuki M, Maywar DN, Toyokawa K, Mukaihara K, Matsumoto K, Horiuchi H, Hashiguchi T, Soga Y
J Atheroscler Thromb
· 2026 Feb · PMID 40790819
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AIM: The preoperative to early remote postoperative von Willebrand factor (VWF) large multimer index (LMI) in patients with aortic stenosis (AS) remains unclear. Assessment of LMI changes may be better understood if othe...AIM: The preoperative to early remote postoperative von Willebrand factor (VWF) large multimer index (LMI) in patients with aortic stenosis (AS) remains unclear. Assessment of LMI changes may be better understood if other valvular diseases are integrated. However, this association requires further investigation. METHODS: A quantitative time-course assessment of the VWF, including LMI, was performed in 23 patients with AS who underwent aortic valve replacement. The proposed total valve score was used to study the correlation between the LMI and valvular diseases, including diseases other than AS. RESULTS: The postoperative VWF LMI was significantly higher; this increase was sustained across nine measurements up to one year postoperatively. The total valve score showed a moderate negative correlation with the VWF LMI (Spearman correlation coefficient r = -0.5483, p = 0.0068), demonstrating a stronger negative correlation and a lower p-value than the peak flow velocity and mean pressure gradient. CONCLUSIONS: Improved VWF LMI was maintained one year after AS surgery and correlated better with echocardiographic severity when considering other valvular diseases than AS severity alone. VWF LMI may indicate overall cardiac shear stress and treatment effectiveness in early remote stages.
Shimizu Y, Yokouchi-Konishi T, Aoki-Kamiya C
… +9 more, Temukai M, Hizuka K, Sawada M, Kakigano A, Iwanaga N, Kanagawa T, Murai K, Makino H, Yoshimatsu J
J Atheroscler Thromb
· 2025 Nov · PMID 40790812
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Although the risk of acute coronary syndrome increases during pregnancy and the postpartum period compared to the non-pregnant state, dyslipidemia-one of the key risk factors for atherosclerotic cardiovascular disease-is...Although the risk of acute coronary syndrome increases during pregnancy and the postpartum period compared to the non-pregnant state, dyslipidemia-one of the key risk factors for atherosclerotic cardiovascular disease-is often undertreated in this population. Several lipid-lowering medications, including statin, have not been used due to concerns about their impact on the fetus. Herein, we report a pregnant woman with possible familial hypercholesterolemia (FH) and coronary artery stenosis, whose low-density lipoprotein cholesterol (LDL-C) level was managed by a combination of statin and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor for the secondary prevention of coronary artery disease.A 37-year-old pregnant woman with dyslipidemia was found to have severe coronary artery stenosis. She was suspected of having FH, and her lipid control was initiated with the goal of lowering LDL-C levels to ＜100 mg/dL. Althoug ezetimibe and colestimide were administered at 14 weeks, the target LDL-C level was not achieved. Thus, treatment with pravastatin was started at 23 weeks and evolocumab at 32 weeks of gestation. With the combination of pravastatin and evolocumab, her LDL-C levels decreased to 67 mg/dL after 35 weeks of gestation. The patient delivered vaginally at 37 weeks of gestation without any cardiac events, and her baby did not present with any abnormalities. In conclusion, the combined use of statin and PCSK9 inhibitor could effectively manage LDL-C levels, and it might be a safe option during pregnancy. Nevertheless, further research is required to assess the safety and efficacy of this combination therapy during pregnancy.
Harada K, Kato M, Terashima S
… +8 more, Takeda S, Matsunaga S, Kataoka T, Harada K, Nagao T, Shinoda N, Marui N, Murohara T
J Atheroscler Thromb
· 2026 Feb · PMID 40769890
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AIMS: Although previous studies have shown that epicardial adipose tissue (EAT) volume is increased in patients with acute coronary syndrome (ACS), its correlation with left ventricular (LV) remodeling and LV ejection fr...AIMS: Although previous studies have shown that epicardial adipose tissue (EAT) volume is increased in patients with acute coronary syndrome (ACS), its correlation with left ventricular (LV) remodeling and LV ejection fraction (LVEF) after ACS remains unknown. This study evaluated the association between the EAT volume and temporal LVEF changes in patients with ACS. METHODS: This prospective cohort study included 197 patients hospitalized for ACS. Among them, 143 (86 males, 67±12 years) underwent follow-up. Echocardiography was performed for three years. The patients were divided into three groups according to their LVEF: heart failure with reduced EF (HFrEF), heart failure with mildly reduced EF (HFmrEF), and heart failure with preserved EF (HFpEF). RESULTS: There was no association between the EAT volume at the onset of ACS and the difference in LVEF during follow-up (β = -0.08, p = 0.42). Peak creatine phosphokinase levels during ACS were most strongly correlated with the chronic-phase LVEF (r = -0.51, p＜0.01). Patients with HFrEF had the highest EAT volume (HFrEF: 134±38 mL; HFmrEF: 102±35 mL; HFpEF: 120±51mL; p = 0.04). Among patients with chronic HFmrEF and HFpEF, but not HFrEF, EAT volume was positively correlated with body mass index (r = 0.37, p = 0.03, and r = 0.45, p＜0.01, respectively). CONCLUSIONS: EAT volume was not associated with LVEF changes at 3 years after ACS. However, patients with chronic HFrEF had a significantly higher EAT volume despite not being obese.
Fujita K, Kinoshita Y, Sagawa H
… +8 more, Bongguk K, Kobayashi Y, Wakabayashi H, Ishikawa M, Fujii S, Takahashi S, Hirai S, Sumita K
J Atheroscler Thromb
· 2026 Jan · PMID 40769889
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AIMS: We aimed to evaluate the effect of serum lipoprotein(a) (Lp(a)) levels on carotid artery ulceration using digital subtraction angiography (DSA), which is the gold standard for assessing atherosclerotic plaque surfa...AIMS: We aimed to evaluate the effect of serum lipoprotein(a) (Lp(a)) levels on carotid artery ulceration using digital subtraction angiography (DSA), which is the gold standard for assessing atherosclerotic plaque surface morphology. METHODS: Of the consecutive cerebrovascular patients prospectively collected serum Lp(a) levels from June 2021 to October 2024 admitted to our institution, patients with carotid artery stenosis were enrolled in this study. Blood samples were collected within three months of admission. Based on common carotid angiography and 3D rotational angiography to confirm the morphology of stenotic lesions, patients were dichotomized according to the presence or absence of carotid artery ulceration. RESULTS: Of the 439 cerebrovascular patients, 94 with carotid artery stenosis were analyzed (18 females, median 75 [interquartile range, 71-81] years) and carotid artery ulceration was confirmed in 38 (40.0 %) patients. Patients with carotid artery ulceration showed a higher proportion of dyslipidemia (94.7% versus 75.0%; p = 0.013), and higher L(a) levels (28 [11-56] vs 10 [5-25] mg/dL, p = 0.007) than those without. Multivariable logistic analysis adjusted for other atherosclerotic risk factors showed a significant association between higher Lp(a) levels and carotid artery ulceration (odds ratio per 10 mg/dL increase, 1.21; 95%CI, 1.02-1.43; p = 0.026). Receiver operating characteristic curve analysis showed that Lp(a) ≥ 26 mg/dL was the threshold to predict the presence of carotid artery ulceration (area under the curve = 0.67; sensitivity, 52.6%; specificity, 78.6%). CONCLUSIONS: In patients with carotid artery stenosis who may be considered candidates for surgical treatment, elevated Lp(a) levels were associated with carotid artery ulceration.
Miyamoto S, Kakutani Y, Morioka T
… +5 more, Yamazaki Y, Ochi A, Fukumoto S, Shoji T, Emoto M
J Atheroscler Thromb
· 2025 Dec · PMID 40721378
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AIM: Serum syndecan-1 (SDC-1) concentration is a biomarker for endothelial glycocalyx (EG) degradation, which is elevated in type 2 diabetes (T2D). EG degradation is an early step in vascular endothelial dysfunction. Thi...AIM: Serum syndecan-1 (SDC-1) concentration is a biomarker for endothelial glycocalyx (EG) degradation, which is elevated in type 2 diabetes (T2D). EG degradation is an early step in vascular endothelial dysfunction. This study investigated the association between serum SDC-1 concentration and visceral fat accumulation, which is closely related to vascular endothelial dysfunction, in people with and without T2D. METHODS: This was a cross-sectional study with two independent groups, one including 219 individuals without diabetes (ND) and the other including 203 individuals with T2D. Visceral fat accumulation was assessed as the visceral fat area (VFA) using computed tomography (CT) in ND or dual bioelectrical impedance analysis (BIA) in T2D. Multivariate analyses were performed for ND and T2D to assess the association between VFA and serum SDC-1 concentrations. RESULTS: The medians of serum SDC-1 concentration were 16.0 ng/mL and 26.5 ng/mL in ND and T2D, respectively. In the univariate analysis, both CT-VFA in the ND group and BIA-VFA in the T2D group were positively correlated with serum SDC-1 concentration. Moreover, the association between VFAs and serum SDC-1 concentration was independent of other covariates in multivariate analysis for each group. However, neither the body mass index nor subcutaneous fat area were associated with serum SDC-1 concentrations in either group. CONCLUSIONS: CT-VFA and BIA-VFA were independently associated with serum SDC-1 concentrations. Our findings suggest that visceral fat accumulation is involved in the degradation of EG irrespective of the presence of T2D.
Tanaka A, Takahara M, Suzuki K
… +4 more, Iida O, Yamaoka T, Soga Y, REAL-AI Investigators
J Atheroscler Thromb
· 2026 Jan · PMID 40721377
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AIM: The long-term clinical outcomes of endovascular therapy (EVT) for aortoiliac (AI) artery lesions remain unclear. This study aimed to investigate 10-year patency and mortality after AI stent implantation. METHODS: Th...AIM: The long-term clinical outcomes of endovascular therapy (EVT) for aortoiliac (AI) artery lesions remain unclear. This study aimed to investigate 10-year patency and mortality after AI stent implantation. METHODS: This multicenter retrospective study included 1919 patients (2375 limbs) who underwent AI stent implantation to treat symptomatic peripheral artery disease (PAD) between January 2005 and December 2010. The study outcome was primary patency, which was defined as a treated vessel without restenosis, mortality, and associated factors. RESULTS: The mean age of the study cohort was 71±9 years. Chronic limb-threatening ischemia (CLTI) accounted for 17.2% of cases, and chronic total occlusion (CTO) was found in 24.6% of cases. During a median follow-up period of 2.9 years (interquartile range: 1.0-6.0 years), 412 patients lost patency, whereas 467 patients died without experiencing loss of patency. At 1, 6, and 10 years post-EVT, respectively, the primary patency rates were estimated to be 92.8%, 79.3%, and 77.2%, and the survival rates were 94.9%, 77.0%, and 63.1%. Female sex, CTO, and the presence of outflow lesions were significantly associated with an increased risk of patency loss after stent implantation (all P＜0.05), whereas age, dialysis-dependent renal failure, heart failure, and CLTI were significantly associated with an increased risk of mortality. CONCLUSION: Stent implantation for AI lesions achieved favorable 10-year patency, with patency loss plateauing after six years. No AI lesion characteristic was associated with mortality. These results support the long-term efficacy of EVT in the clinical practice.
Wang M, Pu S, Jin A
… +13 more, Johnston SC, Bath PM, Dong Q, Xu A, Yan H, Meng X, Yuan B, Jing J, Lin J, Jiang Y, Xie X, Pan Y, Wang Y
J Atheroscler Thromb
· 2025 Dec · PMID 40707193
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AIMS: Stroke severity may affect the benefits and safety of antiplatelet therapies. We aimed to investigate whether the efficacy and safety of indobufen versus aspirin were affected by stroke severity. METHODS: We compar...AIMS: Stroke severity may affect the benefits and safety of antiplatelet therapies. We aimed to investigate whether the efficacy and safety of indobufen versus aspirin were affected by stroke severity. METHODS: We compared the efficacy and safety of indobufen versus aspirin in patients with NIHSS scores of 4-6, 7-9, and 10-18. The primary efficacy outcome was new stroke (ischemic or hemorrhagic) within 90 days, and the primary safety outcome was moderate or severe bleeding within 90 days. The non-inferiority criteria were set at 1.25 for the upper bounds of the 95% CI of the HR for indobufen versus aspirin based on the statistical analysis of the primary clinical trial. RESULTS: In total, 3921 patients presented with NIHSS scores of 4-6, 998 patients presented with NIHSS scores of 7-9, and 515 patients presented with NIHSS scores of 10-18. The risk of the primary outcome among patients with NIHSS scores of 4-6 was higher in indobufen group than that in aspirin group (HR, 1.62; 95% CI, 1.26 to 2.08). However, indobufen was non-inferior to aspirin in patients with NIHSS scores of 7-9 (HR, 0.66; 95% CI, 0.38 to 1.15; non-inferiority P = 0.01) and NIHSS scores of 10-18 (HR, 0.49; 95% CI, 0.23 to 1.05; non-inferiority P = 0.008), with a significant statistical interaction (P = 0.001). Moderate or severe bleeding risk differences between treatments did not vary with stroke severity. CONCLUSIONS: This exploratory analysis indicates that the benefit of indobufen in reducing new strokes within 3 months may vary across stroke severity. The potential non-inferiority of indobufen relative to aspirin in patients with NIHSS scores of ≥ 7, with no significant difference in safety, requires further study.
Mashima T, Oishi E, Honda T
… +7 more, Hata J, Minohara T, Ohara T, Nakao T, Kitazono T, Yamaura K, Ninomiya T
J Atheroscler Thromb
· 2025 Dec · PMID 40707192
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AIM: To investigate the association between a prolonged heart rate-corrected QT (QTc) interval on a 12-lead electrocardiogram and the risk of developing dementia and its subtypes using long-term prospective longitudinal...AIM: To investigate the association between a prolonged heart rate-corrected QT (QTc) interval on a 12-lead electrocardiogram and the risk of developing dementia and its subtypes using long-term prospective longitudinal data from a Japanese community. METHODS: A total of 1,082 residents ≥ 60 years old without dementia were followed up for 24 years. The QT interval was corrected for the heart rate using Bazett's equation. QTc prolongation was defined as QTc ≥ 440 ms, and participants with QTc ＜440 ms were divided into tertiles. Therefore, QTc interval levels at baseline were divided into 4 ranges: ≤ 401, 402-417, 418-439, and ≥ 440 ms. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) of QTc interval levels on the risk of dementia. RESULTS: During the follow-up period, 475 participants developed all-cause dementia, 146 had vascular dementia (VaD), and 295 had Alzheimer's disease (AD). Compared with the lowest QTc level (≤ 401 ms), the multivariable-adjusted HRs for VaD increased significantly with longer QTc intervals (HR [95% confidence interval] 1.80 [1.05 to 3.08] for 402-417 ms, 1.93 [1.12 to 3.34] for 418-439 ms, and 2.64 [1.49 to 4.68] for ≥ 440 ms; p for trend = 0.01). No significant association was found between QTc interval and the risk of both all-cause dementia and AD. CONCLUSION: The present findings suggest that QTc prolongation serves as a potential indicator for identifying individuals at a high risk of developing VaD. QTc measurement may assist in the primary prevention of VaD.
Omatsu T, Koseki M, Ito K
… +11 more, Saga A, Sawabe H, Tanaka K, Inui H, Okada T, Nishida M, Takahashi H, Aishima S, Kamada Y, Yoshida H, Sakata Y
J Atheroscler Thromb
· 2026 Jan · PMID 40670082
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AIM: Desmosterol, a cholesterol precursor, is converted by Δ24-dehydrocholesterol reductase. Hence, desmosterol levels are considered to reflect cholesterol metabolism. This study aimed to evaluate sterols as novel bioma...AIM: Desmosterol, a cholesterol precursor, is converted by Δ24-dehydrocholesterol reductase. Hence, desmosterol levels are considered to reflect cholesterol metabolism. This study aimed to evaluate sterols as novel biomarkers of liver condition in Asian moderate obese patients with metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: In total, 218 patients with MASLD who underwent liver biopsy were prospectively enrolled. Liver biopsy samples were evaluated by a well-versed pathologist according to the criteria. The serum sterols of biopsy-proven patients', such as desmosterol, sitosterol, and campesterol, of the patients with biopsy-proven MASLD were analyzed using liquid chromatography-mass spectrometry. RESULTS: Inflammation grade 0/1/2/3 was observed in 8/107/90/12 patients, and fibrosis stage 0/1/2/3/4 was observed in 25/48/64/63/17 patients, respectively. Serum desmosterol levels were significantly different by inflammation grade 0-3 (one-way analysis of variance [ANOVA], p = 0.004), with a beta coefficient of 0.219 (95% confidence interval [CI]: 0.088-0.350, p＜0.01). Ordinal logistic regression analysis data on inflammation grade, adjusted for other parameters, showed that desmosterol had an odds ratio of 3.727 (95% CI 1.422-9.901, p＜0.005). Although desmosterol levels are influenced by statin treatment, in non-statin-treated patients, serum desmosterol levels remained significantly different by inflammation grade (one-way ANOVA, p = 0.041), and the beta coefficient was 0.233 (95% CI: 0.066-0.400, p＜0.01). CONCLUSIONS: Serum desmosterol levels indicated the degree of hepatic inflammatory activity in patients with MASLD. Since desmosterol, a ligand of nuclear receptor LXR, reflects hepatic cholesterol metabolism, we hope that our findings will contribute to establishing a novel biomarker to screen the high-risk patients for cardiovascular diseases in MASLD.
Egawa M, Ikeda M, Tada H
… +2 more, Harada-Shiba M, Yoshida M
J Atheroscler Thromb
· 2025 Dec · PMID 40670081
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AIM: Women with familial hypercholesterolemia (FH) face specific challenges during pregnancy and childbirth, such as treatment restrictions and the absence of guidelines. This study therefore assessed the status of perin...AIM: Women with familial hypercholesterolemia (FH) face specific challenges during pregnancy and childbirth, such as treatment restrictions and the absence of guidelines. This study therefore assessed the status of perinatal management and the needs of women with FH. METHODS: We contacted 240 board-certified FH specialists, and these physicians screened eligible patients for the survey. Two internet-based surveys were conducted between August 2023 and March 2024: one for physicians and one for women with FH. RESULTS: A total of 72 physicians completed the questionnaires. Fifty-seven percent had managed pregnant women with FH, and 64% reported difficulties, including "selecting and adjusting treatment options" and "the absence of guidelines on pregnancy and childbirth for women with FH." Few physicians referred their patients to obstetricians prior to pregnancy. Eighty-three women with FH completed a questionnaire. Among those who had given birth after being diagnosed with FH, the most common problems reported were "could not be treated," "obstetricians' insufficient knowledge of FH," and "insufficient information about pregnancy and delivery for women with FH." Half of these women discontinued treatment for over one year. In addition, 78% of women indicated a need for counseling on pregnancy-related matters. CONCLUSION: Many physicians have reported challenges in managing pregnant women with FH, and some women have lost years of treatment during pregnancy-related periods. Women with FH should receive advice on planned pregnancy and breastfeeding to balance FH treatment with childbearing and parenting, and obstetricians should actively collaborate with physicians.
J Atheroscler Thromb
· 2025 Sep · PMID 40619217
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Polygenic risk scores (PRSs), constructed from numerous common single nucleotide polymorphisms (SNPs), have emerged as useful tools for predicting future atherosclerotic cardiovascular disease (ASCVD). PRSs have shown in...Polygenic risk scores (PRSs), constructed from numerous common single nucleotide polymorphisms (SNPs), have emerged as useful tools for predicting future atherosclerotic cardiovascular disease (ASCVD). PRSs have shown independent associations with ASCVD outcomes and are increasingly being considered to enhance risk stratification and guide primary prevention strategies. However, most evidence to date has been derived from populations of European ancestry, and their generalizability to other populations, including East Asians, remains uncertain. This review summarizes the current epidemiological evidence on the association between PRS and ASCVD outcomes, focusing on findings in Japanese cohorts. We discuss the potential of PRS as a clinical decision support tool, its incremental value over traditional risk factors, and its role in the early identification of high-risk individuals. We also highlight the limited number of prospective studies in the Japanese population, where validation and implementation studies are ongoing. Given the growing accessibility of genetic testing and the potential of PRS to complement conventional risk assessments, further large-scale studies are warranted to evaluate its clinical utility across diverse populations. Expanding ancestry-specific biobanks and improving PRS transferability are essential steps toward the equitable implementation of genomic risk prediction in ASCVD prevention.
Cai D, Fang ZQ, Cui NH
… +3 more, Wang B, Gao MJ, Wang XB
J Atheroscler Thromb
· 2025 Dec · PMID 40571603
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AIM: Per- and polyfluoroalkyl substances (PFASs) are widespread environmental pollutants that were previously associated with dyslipidemia and type 2 diabetes mellitus (T2DM). We therefore investigated the association be...AIM: Per- and polyfluoroalkyl substances (PFASs) are widespread environmental pollutants that were previously associated with dyslipidemia and type 2 diabetes mellitus (T2DM). We therefore investigated the association between PFAS exposure and clinical outcomes after percutaneous coronary intervention (PCI) in patients with T2DM and assessed the extent to which lipidomic alterations mediate this association. METHODS: This case-control study was nested within a prospective cohort of patients with type 2 diabetes who underwent primary PCI for obstructive coronary artery disease between September 2017 and September 2019. During the 2-year follow-up after PCI, 150 matched pairs of patients with T2DM who did not experience major adverse cardiovascular and cerebrovascular events (MACCEs) were included. Serum PFASs and lipidomes were measured at baseline using liquid chromatography-mass spectrometry and analyzed using multipollutant models and integrative approaches. RESULTS: Overall, a higher exposure to a mixture of nine PFASs was associated with an increased odds of two-year MACCEs after PCI, with perfluoroundecanoic acid and perfluorodecanoic acid contributing the most to the association. Integration with the serum lipidome generated a network of 110 PFAS-associated lipids with differential contributions to discriminating MACCEs, half of which were identified as significant mediators explaining 9.6%-56.4% of the PFAS-MACCE association. Furthermore, we estimated a cluster of patients with high probabilities of developing MACCEs after PCI, characterized by high PFAS levels; increased abundance of phosphatidylcholine, triacylglycerol, diacylglycerol, and acylcarnitine lipids; and decreased abundance of phosphatidylethanolamine and phosphatidylethanol lipids. CONCLUSION: With mediation by serum lipidomic perturbations, PFAS exposure contributes to poor outcomes after PCI in patients with T2DM.
Nitta M, Iwata K, Kaneko M
… +3 more, Fushimi K, Ueda S, Shimizu S
J Atheroscler Thromb
· 2025 Dec · PMID 40571591
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AIM: This study investigated regional disparities in the incidence, management, and in-hospital outcomes of critical limb ischemia (CLI) in Japan to inform standardized care practices. METHODS: We conducted a retrospecti...AIM: This study investigated regional disparities in the incidence, management, and in-hospital outcomes of critical limb ischemia (CLI) in Japan to inform standardized care practices. METHODS: We conducted a retrospective cohort study using the nationwide Diagnosis Procedure Combination database, including patients ≥ 18 years old who were discharged from acute-care hospitals between April 2018 and March 2020. Patients with CLI were identified using ICD-10 codes and restricted to those undergoing invasive treatments including endovascular therapy (EVT), bypass surgery, or amputation. Regional differences in patient demographics, in-hospital management, and outcomes were analyzed across seven regions in Japan. RESULTS: In total, 19,699 records were identified. CLI admissions per million population were highest in the Kyushu region (112.1) and lowest in the Kanto region (59.9). The proportion of patients with a body mass index (BMI) ＜18.5 kg/m ranged from 17.8% (Kanto) to 23.9% (Kansai), while the proportion with a BMI ≥ 30.0 kg/m ranged from 3.3% (Kyushu) to 8.2% (Okinawa). The proportion of patients requiring dialysis ranged from 33.8% in the Chugoku-Shikoku region to 38.2% in the Okinawa region (P = 0.005). Anti-platelet agents were prescribed to 82.1% of patients with CLI, whereas statins were prescribed to 36.1% of patients. The EVT rates varied from 67.6% (Hokkaido-Tohoku) to 84.8% (Kansai) (P＜0.001), while the amputation rates varied from 22.2% (Kansai) to 33.4% (Chugoku-Shikoku) (P＜0.001). The in-hospital mortality rates varied from 5.7% (Chugoku-Shikoku) to 10.9% (Okinawa) (P = 0.001). CONCLUSIONS: This study revealed significant regional disparities in CLI incidence, management, and outcomes across Japan. These findings highlight the need for standardized, evidence-based care strategies that address regional disparities to improve outcomes for patients with CLI.
Nakashima H, Shinohara R, Emoto T
… +9 more, Saito Y, Yoshida N, Hirata KI, Murakami T, Mori H, Toyoda A, Sugiyama T, Yamada T, Yamashita T
J Atheroscler Thromb
· 2025 Nov · PMID 40533160
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AIM: Arteriosclerosis is a condition that leads to coronary artery disease (CAD) and stroke. Basic and clinical studies have suggested a link between the gut microbiota and various diseases, including atherosclerosis. Th...AIM: Arteriosclerosis is a condition that leads to coronary artery disease (CAD) and stroke. Basic and clinical studies have suggested a link between the gut microbiota and various diseases, including atherosclerosis. Therefore, we focused on gut microbiota and aimed to develop a probiotic-based treatment for atherosclerosis. METHOD: From 6 to 14 weeks of age, apoE-deficient mice, a mouse model of atherosclerosis, were orally administered with Phocaeicola dorei and Phocaeicola vulgatus or saline five times/week. The diet was changed to a western diet at eight weeks of age. Finally, the mice were sacrificed at 14 weeks of age, and the atherosclerotic lesion area was evaluated. RESULT: Previous studies have shown that atherosclerosis is suppressed by the administration of live type strains (TS) of P. dorei and P. vulgatus in apoE-deficient mice. In this study, we isolated P. vulgatus AF299, which highly expresses commensal colonization factors. Oral administration of P. dorei TS and AF299 to model mice further suppressed atherosclerosis compared to the administration of P. dorei TS and P. vulgatus TS. Genetic analysis of lesion tissues showed that the expression levels of genes associated with inflammatory responses were significantly reduced in mice treated with P. dorei TS and AF299. Moreover, gene expression related to immune response and IgA secretion was increased in the ileum. CONCLUSION: Our results suggest that the bacteria-induced immune response in the gut leads to the suppression of the inflammatory response in atherosclerotic lesions. These results indicate the potential for the development of prophylactic drugs for atherosclerosis.
Sugawara H, Yoshida K, Shigematsu H
… +9 more, Mimura Y, Fujita T, Saito Y, Kato M, Yamamoto M, Ito H, Shimazu S, Ochiai M, Ogata H
J Atheroscler Thromb
· 2025 Dec · PMID 40518303
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AIMS: To present an update on undiagnosed coronary artery disease (CAD) in patients starting hemodialysis at a Japanese hospital, with a focus on CAD prevalence, risk factors, and coronary lesions' distribution in this p...AIMS: To present an update on undiagnosed coronary artery disease (CAD) in patients starting hemodialysis at a Japanese hospital, with a focus on CAD prevalence, risk factors, and coronary lesions' distribution in this population. METHODS: A cross-sectional, retrospective study of patients who began hemodialysis due to end-stage renal disease (ESRD) in a Japanese hospital between January 2009 and December 2023 and underwent coronary computed tomography (CCT) was carried out. Coronary artery disease was screened using CCT immediately after the initiation of hemodialysis and then confirmed by CCT/coronary angiography (CAG). Based on these evaluations, patients were divided into CAD and non-CAD groups, and their demographic and clinical characteristics were compared. Logistic regression analysis was performed to detect factors associated with CAD. Additionally, variations in CAD prevalence and coronary artery calcification scores (CACS) over time were assessed considering 3-year intervals. RESULTS: Data from 272 patients were included. CAD was observed in nearly half (47%) of them. Lesions were mainly observed in the left anterior descending artery (73%). The prevalence of a coronary artery calcification score of ＞65 notoriously increased from 2012-2014 to 2015-2017 and thereafter stabilized, while the proportion of patients diagnosed with CAD tended to decrease overall. Multiple regression analysis indicated that only a history of smoking, statin use, low albumin levels, and low HDL-C levels were independently and significantly associated with CAD occurrence in these ESRD patients. CONCLUSIONS: Many well-known CAD risk factors in the general population were not predictors of undiagnosed CAD in our target population.
Kitagawa K, Toi S, Yoshizawa H
… +2 more, Sato Y, Todo K
J Atheroscler Thromb
· 2025 Nov · PMID 40484683
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AIMS: The blood inflammatory marker interleukin 6 (IL-6) has been shown to predict future stroke, major adverse cardiovascular events (MACEs), and dementia. However, no study has yet examined this relationship in the sam...AIMS: The blood inflammatory marker interleukin 6 (IL-6) has been shown to predict future stroke, major adverse cardiovascular events (MACEs), and dementia. However, no study has yet examined this relationship in the same population. The present study compared the predictive utility of IL-6 levels in stroke, MACEs, and Alzheimer's disease (AD) dementia. METHODS: In this post-hoc analysis, we derived data from a Japanese observational registry in which 1011 patients with evidence of cerebral vessel disease were enrolled. After excluding patients who required assistance with daily tasks, were suspected of having dementia, and lacked IL-6 measurement, 471 patients were included. The patients were followed up until March 2023. The outcomes were incident stroke, MACEs, and AD dementia. RESULTS: During a median follow-up period of 4.6 years, stroke, MACEs, and AD dementia occurred in 24, 36, and 21 patients, respectively. Serum IL-6 levels are associated with age, sex, and vascular factors. A Cox proportional hazard analysis revealed that the highest IL-6 tertile (≥ 2.5 pg/mL) was associated with a significantly higher risk of stroke and MACEs than the lowest IL-6 tertile after adjusting for confounding factors (stroke, adjusted hazard ratio 4.84 [95% confidence interval, 1.02-23.05], P = 0.048; MACEs, adjusted hazard ratio 3.68 [95% confidence interval, 1.01-13.51], P = 0.049). However, no association was found between IL-6 tertile groups and AD dementia. CONCLUSION: Serum IL-6 levels predicted stroke and cardiovascular events but not AD dementia in patients with vascular risk factors. The involvement of low-grade systemic inflammation appears to be significantly greater in atherothrombotic events than that in AD dementia.
J Atheroscler Thromb
· 2025 Sep · PMID 40467521
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Dyslipidemia is a major risk factor for atherosclerosis and subsequent cardiovascular disease (CVD). Despite conventional treatment with statins, ezetimibe, or PCSK9 inhibitors, there are cases of familial hypercholester...Dyslipidemia is a major risk factor for atherosclerosis and subsequent cardiovascular disease (CVD). Despite conventional treatment with statins, ezetimibe, or PCSK9 inhibitors, there are cases of familial hypercholesterolemia (FH) in which LDL-C levels cannot be sufficiently lowered to the target level, resulting in failure to prevent CVD. Inhibition of Angiopoietin-like protein 3 (ANGPTL3) has emerged as a new therapeutic strategy to reduce LDL-C levels independent of the LDL receptor function. Since ANGPTL3 suppresses lipoprotein lipase (LDL) and endothelial lipase (EL) activities, its inhibition facilitates the clearance of very low-density lipoprotein cholesterol, decreasing both LDL-C and triglyceride (TG) levels. In fact, evinacumab, an anti-ANGPTL3 monoclonal antibody, has been shown to substantially reduce LDL-C and TG levels, even in FH patients with LDL receptor gene mutations who are resistant to the conventional treatments described above. Clinical trials have also shown that siRNA therapeutics, such as zodasiran and solbinsiran, improve lipid profiles in patients with dyslipidemia. Recently, we have begun developing a peptide-based anti-ANGPTL3 vaccine and confirmed in a preclinical FH mouse model that it significantly decreases LDL-C and TG levels, reduces atherosclerotic lesions and maintains long-term efficacy without adverse effects. In this review, we discuss the promising advances in ANGPTL3-targeted therapeutics that may overcome treatment-resistant dyslipidemia and reduce CVD risk in high-risk populations.