Miwa K, Koga M, Omae K
… +10 more, Kamogawa N, Uchiyama S, Hayami S, Shoji M, Hoshino H, Kimura K, Minematsu K, Yamaguchi T, Toyoda K, CSPS.com Trial Investigators
J Atheroscler Thromb
· 2026 Apr · PMID 41339010
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AIM: Cilostazol, a phosphodiesterase III inhibitor, reduces the risk of stroke recurrence among patients with noncardioembolic ischemic stroke through inhibition of the platelet function and its pleiotropic effects. Its...AIM: Cilostazol, a phosphodiesterase III inhibitor, reduces the risk of stroke recurrence among patients with noncardioembolic ischemic stroke through inhibition of the platelet function and its pleiotropic effects. Its potential mechanisms include inhibiting angiotensin II-induced endothelial cell apoptosis and promoting vasodilation, which may lower systolic blood pressure (SBP). We hypothesized that the decreased risk of stroke recurrence could be attributed to a reduction in SBP. METHODS: In a post hoc analysis of CSPS.com, we defined change in SBP as its change at the last visit compared with baseline and treated it as a time-dependent mediator. We performed causal mediation analyses to separate the overall effects of cilostazol on the first recurrence of ischemic stroke into indirect effects (mediated by change in SBP on cilostazol) and direct effects (mediated through pathways other than a change in SBP on cilostazol). The effects were summarized by cumulative hazard rate difference. RESULTS: Ischemic stroke recurred in 27 (3%) of 889 patients on dual therapy with cilostazol and aspirin or clopidogrel and 62 (6.8%) of 906 patients on monotherapy with aspirin or clopidogrel alone during a median follow-up period of 1.4 years. The mediation analysis showed that the positive effect of dual therapy was not mediated by the association between SBP change and stroke recurrence. The estimated direct and indirect effects of cilostazol on stroke recurrence during the same follow-up period were cumulative hazard rate differences of -0.043 (95% CI, -0.070 to -0.015) and -0.0008 (-0.0024 to 0.00035), respectively. CONCLUSIONS: Our results indicate that cilostazol reduced stroke recurrence without lowering SBP, likely through other pleiotropic pathways.
Masuda D, Kajinami K, Sakayoshi N
… +4 more, Yokota D, Nagamine M, Morikawa-Isogai Y, Yamashita S
J Atheroscler Thromb
· 2026 Apr · PMID 41320340
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AIMS: Bempedoic acid is an ATP citrate lyase (ACLY) inhibitor acting in the cholesterol biosynthesis pathway. This study evaluated long-term safety and efficacy of bempedoic acid 180 mg/day for 52 weeks in Japanese patie...AIMS: Bempedoic acid is an ATP citrate lyase (ACLY) inhibitor acting in the cholesterol biosynthesis pathway. This study evaluated long-term safety and efficacy of bempedoic acid 180 mg/day for 52 weeks in Japanese patients with hypercholesterolemia. METHODS: A multicenter, open-label, single-arm Phase 3 long-term study was conducted at 26 hospitals and clinics across Japan in patients aged 18 to 85 years. Newly enrolled patients had previously failed to achieve their lipid management targets because of inadequate response to statins or statin intolerance; rollover patients had completed the 12-week treatment period of a domestic Phase 3 confirmatory study (the CLEAR-J trial) and had not met the discontinuation criteria at Week 12. RESULTS: Bempedoic acid was administered to 130 patients. Treatment-emergent adverse events (TEAEs) occurred in 83.8%, treatment-related TEAEs in 14.6%, serious TEAEs in 6.2%, and AEs leading to discontinuation in 4.6%. None were severe. Between baseline and Week 52, low-density lipoprotein-cholesterol (LDL-C) decreased by 21.6% (overall population) and 25.3% (newly enrolled group), as observed in both statin response subgroups. LDL-C target levels based on risk category were achieved by 65.6% at Week 52 (overall population). Long-term efficacy was also demonstrated for non-high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein. CONCLUSIONS: Bempedoic acid 180 mg/day for 52 weeks was well tolerated in patients with hypercholesterolemia, with no major safety concerns. Serious AEs were infrequent, and no new safety signals specific to the Japanese population were observed. More than 60% of patients achieved and sustained their LDL-C target levels.
Matsumori R, Tanaka M, Sato T
… +10 more, Akiyama Y, Hosaka I, Nakata K, Kawaharata W, Aida H, Nishizawa K, Kouzu H, Yama N, Hanawa N, Furuhashi M
J Atheroscler Thromb
· 2026 Apr · PMID 41224329
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AIM: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). Although small dense low-density lipoprotein cholesterol (sdLD...AIM: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). Although small dense low-density lipoprotein cholesterol (sdLDL-C) is a highly atherogenic lipid fraction, the association of the sdLDL-C level with MASLD and other steatotic liver disease (SLD) subcategories remain unclear. We investigated the association between various SLDs and the sdLDL-C level calculated by Sampson's equation. METHODS: A total of 15,734 Japanese participants (men/women: 10,228/5,506, mean age: 49±9 years) who underwent annual health examinations including abdominal ultrasonography were recruited after the exclusion of subjects with triglycerides ≥ 800 mg/dL. RESULTS: Among SLD subcategories including MASLD, MASLD with increased alcohol consumption (MetALD) and alcohol-associated liver disease (ALD), the mean levels of sdLDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) were the highest in participants with MASLD. Triglyceride levels were significantly lower in participants with MASLD than in those with MetALD and those with ALD. After adjustment for age, sex, body mass index, current smoking and alcohol drinking habits, treatment of hypertension, diabetes and dyslipidemia, and triglyceride level, MASLD and MetALD were independently associated with sdLDL-C level, and the association was stronger in MASLD than in other SLD subcategories. The sdLDL-C level was also independently associated with each SLD subcategory after adjustment for the same covariates. The addition of sdLDL-C to traditional risk factors significantly improved the discriminatory capacity for the presence of MASLD in comparison to the addition of non-HDL-C. CONCLUSION: MASLD is independently associated with elevated estimated sdLDL-C levels in Japanese individuals, leading to an increased risk of ASCVD.
Mineo R, Fukuda S, Iioka M
… +10 more, Nishizawa H, Kawada K, Kondo Y, Obata Y, Nagao H, Fujishima Y, Fujimoto T, Yamamoto K, Matsuzawa Y, Shimomura I
J Atheroscler Thromb
· 2026 Apr · PMID 41183894
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AIMS: Visceral fat accumulation is the central feature of metabolic syndrome and subsequent atherosclerotic cardiovascular disease. Soluble T-cadherin (sT-cad) has been identified in circulation, but its clinical signifi...AIMS: Visceral fat accumulation is the central feature of metabolic syndrome and subsequent atherosclerotic cardiovascular disease. Soluble T-cadherin (sT-cad) has been identified in circulation, but its clinical significance in the general population remains unclear. We investigated the associations of circulating sT-cad levels with metabolic syndrome and its components in a population undergoing health checkups. METHODS: A total of 1321 Japanese participants (825 males and 496 females) undergoing health checkups were enrolled. Serum levels of sT-cad (130-kDa, 100-kDa, and 30-kDa), adiponectin (APN), and other clinical parameters were measured. Associations between sT-cad and metabolic risk factors were analyzed. RESULTS: Among the three sT-cad isoforms, serum 130-kDa sT-cad levels were significantly negatively correlated with waist circumference, blood pressure, Homeostatic Model Assessment for Insulin Resistance (HOMA-R), triglycerides, Alanine aminotransferase (ALT), uric acid, and high-sensitivity C-reactive protein (hsCRP), and positively correlated with high-density lipoprotein (HDL) cholesterol and APN. In multivariate analysis, high TG levels and/or HDL-C levels and hsCRP were independent negative determinants of 130-kDa sT-cad levels in both sexes. Furthermore, 130-kDa sT-cad levels decreased progressively with an increasing number of metabolic risk factors (P for trend ＜0.001). CONCLUSION: Low serum 130-kDa sT-cad levels are associated with the presence and accumulation of metabolic syndrome-related abnormalities in a Japanese population undergoing health checkups. Inflammation and lipid abnormalities of metabolic syndrome (high TG and/or low HDL-C) may influence the serum 130-kDa sT-cad levels.
Sakaguchi K, Fujioka S, Shishikura D
… +5 more, Michikura M, Kusumoto H, Kanzaki Y, Harada-Shiba M, Morita H
J Atheroscler Thromb
· 2026 Apr · PMID 41139505
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AIM: Tendon xanthomas are part of the clinical triad of diagnostic criteria for familial hypercholesterolemia (FH) in Japan. The Achilles tendon generally has a twisted structure, and we investigated the impact of torsio...AIM: Tendon xanthomas are part of the clinical triad of diagnostic criteria for familial hypercholesterolemia (FH) in Japan. The Achilles tendon generally has a twisted structure, and we investigated the impact of torsion on Achilles tendon thickness (ATT) assessment. METHODS: In this single-center retrospective study, 61 acute coronary syndrome (ACS) patients who underwent ATT assessment using radiography (ATT-Xp) and ultrasonography (ATT-US) were analyzed. Ultrasonographic ATT assessment used two axes - antero-posterior axis (ATT-US (AP)) and corrected axis according to Achilles tendon torsion (ATT-US (correct)) - and the torsion angle was measured. The association of torsion with each ATT assessment was investigated. RESULTS: The torsion angle of the Achilles tendon varied widely. Both ATT-US (AP) and ATT-US (correct) were significantly correlated with ATT-Xp, although the correlation between ATT-Xp and ATT-US (correct) was modest compared to the correlation with ATT-US (AP) (ATT-US (AP)-Right: r= 0.91, p＜0.001, Left: r= 0.91, p＜0.001; ATT-US (correct)-Right: r = 0.82, p＜0.001, Left: r = 0.76, p＜0.001, respectively). Torsion angle was well correlated with the differences in ATT between ATT-Xp and ATT-US (correct) (Right: r= 0.62, p＜0.001, Left: r= 0.66, p＜0.001). There were no independent factors associated with Achilles tendon torsion. CONCLUSION: This is the first study to quantitatively evaluate the three-dimensional twisted structure of the Achilles tendon and demonstrate that Achilles tendon torsion is associated with the difference between ATT-Xp and ATT-US (correct). Torsion of the Achilles tendon should be considered in Achilles tendon assessment, particularly radiographical assessment.
Horie T, Baba O, Nishino T
… +3 more, Yamashita Y, Tsujisaka Y, Ono K
J Atheroscler Thromb
· 2026 Jan · PMID 41139499
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MicroRNAs (miRNAs) serve as fundamental post-transcriptional regulators of gene expression, among which the miR-33 family, consisting of miR-33a and miR-33b, has emerged as a critical modulator in the pathogenesis of car...MicroRNAs (miRNAs) serve as fundamental post-transcriptional regulators of gene expression, among which the miR-33 family, consisting of miR-33a and miR-33b, has emerged as a critical modulator in the pathogenesis of cardiovascular and metabolic diseases. These miRNAs are embedded within the intronic regions of SREBF genes and play pivotal roles in cholesterol homeostasis, fatty acid metabolism, and inflammatory regulation. Notably, miR-33a is highly conserved across various species, whereas miR-33b is found primarily in primates and some other mammals, complicating the development of relevant animal models. These miRNAs inhibit their target genes involved in cholesterol metabolism, fatty acid oxidation, and insulin signaling, consequently influencing the development and progression of cardiovascular and metabolic diseases. Inhibition or genetic ablation of miR-33 has shown therapeutic potential, improving dyslipidemia, atherosclerosis, and metabolic dysfunction-associated steatotic liver disease, through altered cholesterol metabolism, attenuation of inflammation, and increased fatty acid utilization. In addition, miR-33 suppression has been shown to promote skeletal muscle regeneration. However, systemic inhibition of miR-33 requires caution due to the role of miR-33 in hunger signaling and sympathetic nerve activity in the central nervous system, which may lead to obesity. Therefore, the development of tissue-specific strategies is essential for the safe and effective therapeutic targeting of miR-33.
Oyama N, Okazaki T, Miura H
… +4 more, Doyu K, Iwamoto T, Matsuzaki J, Yagita Y
J Atheroscler Thromb
· 2026 Mar · PMID 41139495
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AIM: This study attempted to clarify the prevalence and clinical characteristics of Janus kinase 2 V617F (JAK2) gene mutations in patients with cerebrovascular diseases. METHODS: We prospectively enrolled patients who we...AIM: This study attempted to clarify the prevalence and clinical characteristics of Janus kinase 2 V617F (JAK2) gene mutations in patients with cerebrovascular diseases. METHODS: We prospectively enrolled patients who were admitted to or referred to our department with cerebrovascular disease due to suspected major cerebral artery disease or small-vessel occlusion within 30 days of onset between January 1, 2021, and April 30, 2024, and who consented to undergo a JAK2 mutation analysis. We investigated the prevalence of JAK2 mutations based on the clinical subtype of stroke and the presence or absence of major cerebral artery disease. We also examined the clinical characteristics of patients with positive JAK2 mutation. RESULTS: Among 316 consecutive inpatients (216 males; median age, 74 years old), JAK2 mutations were detected in 4 of 102 (3.9%) patients with large artery atherosclerosis, 2 of 101 patients (2.0%) with small-vessel occlusion, and 2 of 113 (1.8%) with other stroke subtypes. A multiple logistic regression analysis showed that patients with the positive JAK2 mutation had significantly higher hematocrit values (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.07-1.62; p = 0.010), platelet counts (OR, 1.19; 95% CI, 1.07-1.31; p = 0.001), and thrombomodulin levels (OR, 1.08; 95% CI 1.01-1.15; p = 0.025) at admission than patients with the negative JAK2 mutation. CONCLUSIONS: The frequency of JAK2 mutations is very low among patients with major cerebral artery diseases and small-vessel occlusion. The mechanisms underlying stroke onset in patients with the positive JAK2 mutation may involve factors beyond hematopoietic cells, such as endothelial dysfunction.
Komaba C, Komaba H, Imagawa K
… +5 more, Hida M, Suga T, Kakuta T, Fukagawa M, Akamatsu T
J Atheroscler Thromb
· 2026 Mar · PMID 41110960
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AIMS: Chronic limb-threatening ischemia (CLTI) is a serious complication in patients with kidney failure. We aimed to investigate the frequency and clinical burden of CLTI in patients undergoing hemodialysis. METHODS: We...AIMS: Chronic limb-threatening ischemia (CLTI) is a serious complication in patients with kidney failure. We aimed to investigate the frequency and clinical burden of CLTI in patients undergoing hemodialysis. METHODS: We analyzed a historical cohort of 2,292 maintenance hemodialysis patients to examine the prevalence, risk factors, and clinical outcomes of CLTI, defined as prior surgical or endovascular arterial revascularization and/or lower limb amputation. We also evaluated the incidence of new-onset CLTI during follow-up and its association with the subsequent risk of mortality. RESULTS: At baseline, 198 patients (8.6%) had prevalent CLTI. These individuals had longer dialysis duration, poorer nutritional status, and higher serum calcium and phosphorus levels, in addition to traditional risk factors. During a median follow-up of 5.8 years, 436 patients experienced cardiovascular events, 77 underwent interventions for CLTI, and 712 died. Prevalent CLTI at baseline was associated with 2.2-, 3.2-, and 9.3-fold higher risks of all-cause mortality, cardiovascular events, and CLTI-related interventions, respectively. These associations were attenuated but remained significant after comprehensive adjustment for potential confounders. Among the 2,094 patients without CLTI at baseline, 49 developed new-onset CLTI. New-onset CLTI was also associated with an increased risk of subsequent mortality, particularly in the early phase following its onset. CONCLUSIONS: CLTI is common and associated with poor clinical outcomes in patients undergoing hemodialysis. Our findings highlight the substantial and persistent burden of CLTI in this population and underscore the urgent need for effective strategies to prevent or delay the progression of lower extremity arterial disease.
Ogawa A, Shoji-Asahina A, Kawaguchi T
… +3 more, Nakayama T, Matsuda F, Tabara Y
J Atheroscler Thromb
· 2026 Apr · PMID 41083382
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AIMS: Persistent Chlamydia pneumoniae (C. pneumoniae) infection has been suggested to be a risk factor for cardiovascular events; however, only findings from studies on small populations are available so far. This study...AIMS: Persistent Chlamydia pneumoniae (C. pneumoniae) infection has been suggested to be a risk factor for cardiovascular events; however, only findings from studies on small populations are available so far. This study investigated this hypothesis in a large general population through a longitudinal analysis. METHODS: We included 9,064 community residents who participated in the Nagahama study (mean age: 52.8 years). C. pneumoniae infection (seropositivity) was determined by serum levels of immunoglobulin A and immunoglobulin G assessed by enzyme-linked immunoassay. The incidence rates of cardiovascular diseases (CVDs), including stroke and coronary artery diseases, were determined by reviewing participants' hospital records and death certificates. Basic clinical parameters were obtained using the baseline survey of the Nagahama study. RESULTS: During a mean follow-up duration of 4,390 days, we observed 323 cases of CVDs. The incidence rates of CVDs were 45.0 and 24.5 per 10,000 person-years in the seropositive and seronegative groups, respectively (log-rank test: p＜0.001). The results of the Cox proportional hazard model analysis indicated that C. pneumoniae seropositivity was remarkably associated with CVDs (1.30, 95% confidence interval: 1.04-1.64) after adjusting for established risk factors, including arterial stiffness (p = 0.023). The hazard ratio was higher in the subpopulation aged ≤ 55 years (2.62, 95% confidence interval: 1.45-4.75, p = 0.001) and reached 3.66 (95% confidence interval: 1.39-9.65, p = 0.009) in the subpopulation aged ≤ 45 years. CONCLUSION: C. pneumoniae seropositivity was significantly associated with CVDs incidence, especially in adolescents and middle-aged individuals.
Nagayama D, Watanabe Y, Ohira M
… +2 more, Shirai K, Saiki A
J Atheroscler Thromb
· 2026 Mar · PMID 41083358
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AIM: A decline in the estimated glomerular filtration rate (eGFR) is associated with vascular dysfunction, a cardiovascular disease (CVD) risk. However, since the eGFR is based on the standard body surface area (BSA) of...AIM: A decline in the estimated glomerular filtration rate (eGFR) is associated with vascular dysfunction, a cardiovascular disease (CVD) risk. However, since the eGFR is based on the standard body surface area (BSA) of 1.73 m, its reliability may be affected by body size. We aimed to clarify whether the individual's BSA adjustment of eGFR enhances the relationship with kidney and vascular functions in the general healthy Japanese population. METHODS: This cross-sectional analysis was conducted in a total of 58,837 Japanese individuals. The BSA-adjusted eGFR (mL/min) was defined as the product of the conventional eGFR and the individual's BSA divided by 1.73 m. Arterial stiffness was assessed by the cardio-ankle vascular index (CAVI), and a high CAVI was defined as CAVI ≥ 9.0. RESULTS: Compared with the eGFR, the BSA-adjusted eGFR showed higher values in males in their 20s to 50s and lower values in females of all ages. The BSA-adjusted eGFR showed a stronger negative correlation with the CAVI than the eGFR (R: -0.444 vs. -0.388 in males, -0.449 vs. -0.416 in females). In a receiver-operating characteristic curve analysis, the discriminative power for a high CAVI was stronger for the BSA-adjusted eGFR than for the eGFR (area under the curve: 0.776 vs. 0.723 in males, 0.757 vs. 0.716 in females). The upper tertile of the BSA-adjusted eGFR showed higher odds ratios for a high CAVI than that of the eGFR in both sexes, after adjusting for covariates. CONCLUSIONS: The BSA-adjusted eGFR appropriately assesses the kidney function according to differences in sex, age and body size. Furthermore, a CAVI analysis suggested that the BSA-adjusted eGFR might facilitate the achievement of more precise preventive care for CVD.
Matsuda T, Osaki Y, Matsumoto N
… +7 more, Nakajima R, Murayama Y, Sugano Y, Iwasaki H, Mathis BJ, Sekiya M, Shimano H
J Atheroscler Thromb
· 2026 Mar · PMID 41062288
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Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of early onset atherosclerosis. Evinacumab, an ang...Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of early onset atherosclerosis. Evinacumab, an angiopoietin-like protein 3 (ANGPTL3)-inhibiting monoclonal antibody, lowers LDL-C independently of LDL receptor activity. However, its effects on other lipid-related markers remain poorly investigated in real-world clinical practice. We herein report a 54-year-old Japanese woman with genetically confirmed compound heterozygous familial hypercholesterolemia (FH) treated with evinacumab in combination with other lipid-lowering agents. Lipoprotein apheresis was continued every two weeks throughout the treatment. Serum sampling before and after evinacumab administration found that, following evinacumab initiation, LDL-C decreased from 324 to 205 mg/dL (reduction of 119 mg/dL, -36.7%) and triglycerides from 155 to 51 mg/dL (reduction of 103 mg/dL, -66.8%). Notably, atherosclerosis-related markers showed substantial reductions, with remnant-like particle cholesterol (RLP-C) decreasing from 10.5 to ＜2.0 mg/dL, small dense LDL-C (sdLDL-C) from 80.2 to 22.1 mg/dL, and malondialdehyde-modified LDL (MDA-LDL) from 105 to 87 mg/dL. Apolipoproteins (ApoB, ApoC2, ApoC3, ApoE, and ApoA5) decreased as well. No significant changes were observed in lipoprotein (a), free fatty acids, interleukin-6, or high-sensitivity C-reactive protein levels. This is the first clinical report to comprehensively evaluate the lipid-modifying effects of evinacumab in a Japanese HoFH patient. In this case, evinacumab was highly efficacious against atherosclerosis-related markers and apolipoproteins, beyond simple LDL-C reduction, suggesting additional cardiovascular benefits. These findings provide mechanistic insights that may inform therapeutic strategies for the management of HoFH.
Hirano T, Hayashi T, Sugita H
… +6 more, Tamasawa A, Ohara M, Terasaki M, Ito Y, Yamagishi SI, Mori Y
J Atheroscler Thromb
· 2026 Mar · PMID 41047339
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AIMS: Angiopoietin-like proteins (ANGPTLs) are key regulators of lipid metabolism; however, their response to lipid-lowering therapies remains incompletely understood. The PRESTIGE study compared the effects of pemafibra...AIMS: Angiopoietin-like proteins (ANGPTLs) are key regulators of lipid metabolism; however, their response to lipid-lowering therapies remains incompletely understood. The PRESTIGE study compared the effects of pemafibrate add-on versus statin dose doubling on small dense low-density lipoprotein-cholesterol (sdLDL-C) in patients with type 2 diabetes and hypertriglyceridemia receiving statins. This post-hoc analysis investigated changes in circulating ANGPTL levels. METHODS: Participants were randomized to receive either pemafibrate (0.2 mg/day; n = 48) or double-dose statin therapy (n = 49). Plasma ANGPTL levels and lipid parameters were assessed at baseline and after 12 weeks. ANGPTLs were quantified using specific human ELISA kits. sdLDL-C, LDL-triglycerides (TG), and HDL3-C were measured using the homogeneous assays. RESULTS: Pemafibrate treatment significantly increased circulating ANGPTL3 (+71%) and ANGPTL4 (+143%) levels, with no change in ANGPTL8, whereas statin dose doubling had no effect on ANGPTL levels. Pemafibrate markedly reduced TGs and sdLDL-C, while increasing large buoyant LDL-C, LDL-TG, HDL2,3-C, apolipoprotein AI, and apolipoprotein AII. The increase in ANGPTL3 was not correlated with changes in LDL subspecies but was positively associated with changes in HDL2,3-C. When participants were stratified by baseline ANGPTL3 levels, those in the low ANGPTL3 group showed an increase in LDL-C and LDL-TG in response to pemafibrate. The substantial elevation in ANGPTL4 induced by pemafibrate did not show associations with lipid changes. CONCLUSIONS: Pemafibrate markedly elevated circulating ANGPTL3 and ANGPTL4 levels, but these increases were not associated with pro-atherogenic changes in lipoprotein profiles. Notably, baseline ANGPTL3 concentrations may influence the effect of fibrates on LDL-C levels.
Okina Y, Saigusa T, Ueki Y
… +20 more, Minamisawa M, Oyama Y, Hashizume N, Yokota D, Taki M, Senda K, Wakabayashi T, Fujimori K, Karube K, Sakai T, Sunohara D, Tanaka K, Nomi H, Itagaki T, Ebisawa S, Okada A, Kato T, Miura T, Kuwahara K, I-PAD investigators
J Atheroscler Thromb
· 2026 Mar · PMID 41034094
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AIMS: The HELT-ES score is a newly developed risk stratification tool for stroke in patients with atrial fibrillation. We investigated the prognostic value of the HELT-ES score in patients with lower extremity artery dis...AIMS: The HELT-ES score is a newly developed risk stratification tool for stroke in patients with atrial fibrillation. We investigated the prognostic value of the HELT-ES score in patients with lower extremity artery disease (LEAD) and compared it with other risk scores for atrial fibrillation (AF) and LEAD. METHODS: Patients undergoing endovascular therapy (EVT) for symptomatic LEAD between August 2015 and August 2016 were enrolled in the I-PAD NAGANO registry, a prospective, multicenter, observational registry. The primary endpoint was major adverse cardiovascular events (MACEs), defined as a composite of all-cause death, nonfatal myocardial infarction, and stroke at 5 years. RESULTS: A total of 366 patients were divided into low-risk (HELT-ES score ＜2, n = 146) and high-risk (HELT-ES score ≥ 2, n = 218) groups. The major criteria of the HELT-ES score were hypertension (81.9%) and elderly age (75-84 years old) (34.1%). The incidence of MACEs at 5 years was significantly higher in the high-risk group than in the low-risk group (43.7% vs. 22.8%, P＜0.001). In the COX multivariate analysis, the high-risk group emerged as a significant predictor of MACEs at 5 years (hazard ratio 1.87, 95% confidence interval 1.22-2.89, P = 0.004). The C-statistics for MACEs were comparable among the HELT-ES and other AF and LEAD risk scores. CONCLUSIONS: The HELT-ES score was associated with an increased risk of cardiovascular events in patients with LEAD undergoing EVT.
Yoshioka N, Tokuda T, Tanaka A
… +9 more, Kojima S, Yamaguchi K, Yanagiuchi T, Ogata K, Takei T, Morita Y, Nakama T, Morishima I, LEADers PAD investigators
J Atheroscler Thromb
· 2026 Mar · PMID 40976700
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AIM: Frailty, particularly chronic limb-threatening ischemia (CLTI), is a major health concern in patients with peripheral artery disease. CLTI onset can lead to increased frailty and impaired ability to perform daily ac...AIM: Frailty, particularly chronic limb-threatening ischemia (CLTI), is a major health concern in patients with peripheral artery disease. CLTI onset can lead to increased frailty and impaired ability to perform daily activities. However, its in-hospital frailty progression in these patients remain poorly defined. This study aims to address this knowledge gap. METHODS: We analyzed 841 CLTI patients (mean age, 75.8 years; 60.2% male) who underwent endovascular therapy (EVT) and were discharged alive from a multicenter registry. Frailty was assessed at admission and discharge using the Clinical Frailty Scale (CFS), categorized as non-frail (1-3), mildly frail (4-5), or advanced frail (6-9). Frailty progression was defined as a transition to a higher frailty category during hospitalization. The predictors of frailty progression during hospitalization were assessed using logistic regression analyses. RESULTS: Overall, 103 patients (12.2%) experienced frailty progression. Compared to those without progression, these patients had lower left ventricular ejection fraction (LVEF), lower hemoglobin and albumin levels, and more severe wounds. Independent predictors of frailty progression included LVEF ＜40% (odds ratio [OR], 2.02), hemoglobin ＜11 g/dL (OR 1.67), and Wound Grade 3 (OR 2.04). Within 2 years after discharge, the amputation-free survival rate was significantly lower in the progression group than in the non-progression group (42.6% vs. 56.0%; log-rank p = 0.008). The wound healing rate within 2 years after EVT was also significantly lower in the progression group than in the non-progression group (78.2% vs. 88.8%; log-rank p = 0.001). CONCLUSIONS: In-hospital frailty progression was observed in one of the eight patients with CLTI undergoing EVT. Frailty progression was linked to more severe clinical status and worse life and limb outcomes than cases without progression.
Aoki H, Kitaoka K, Suzuki Y
… +11 more, Kaneko H, Okada A, Takeda N, Morita H, Hiroi Y, Node K, Furui Y, Okamura T, Miura K, Yasunaga H, Takeda N
J Atheroscler Thromb
· 2026 Feb · PMID 40976699
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AIMS: Despite strong recommendations for medical consultation, the treatment status and low-density lipoprotein cholesterol (LDL-C) levels at 1-year follow-up of individuals with referral-level LDL-C identified in health...AIMS: Despite strong recommendations for medical consultation, the treatment status and low-density lipoprotein cholesterol (LDL-C) levels at 1-year follow-up of individuals with referral-level LDL-C identified in health checkups remain unclear. We evaluated the treatment status and 1-year LDL-C control among individuals identified in health checkups as requiring early medical consultation due to LDL-C levels of ≥ 180 mg/dL. METHODS: We conducted a nationwide cohort study including health checkup data for individuals aged 20-74 years. We identified 102,049 individuals (median age: 48 years; male: 66.8%) with uncontrolled LDL-C (≥ 180 mg/dL) at baseline, who had no prior lipid-lowering therapy. Poisson regression with robust error variance was used to assess factors associated with uncontrolled LDL-C at 1 year. RESULTS: Among individuals with LDL-C ≥ 180 mg/dL at baseline, 56,147 (55.0%) visited a medical institution within 3 months of the checkup, and 13,124 (12.9%) were prescribed lipid-lowering medications at 1 year. At 1 year follow-up, 49,260 (48.3%) still had LDL-C ≥ 180 mg/dL. Factors associated with persistent LDL-C ≥ 180 mg/dL at 1 year included obesity (RR: 1.07, [95% CI: 1.06-1.09]), 10 mg/dL increase in LDL-C at baseline (1.11 [1.10-1.11]), smoking (1.05 [1.04-1.07]), alcohol consumption (0.95 [0.94-0.97]), poor sleep quality (1.02 [1.01-1.03]), and skipping breakfast ≥ 3 times per week (1.07 [1.05-1.08]). CONCLUSIONS: Despite being classified as requiring early medical intervention, only half of individuals with LDL-C ≥ 180 mg/dL visited a physician within 3 months, and nearly half continued to have uncontrolled LDL-C at 1 year. Strategies to facilitate timely medical visits and appropriate lipid management in health checkup-identified cases are warranted.