Aims: Physical exercise exerts antiatherosclerotic effects through several mechanisms. One anti-inflammatory effect of exercise is directly exerted on vascular endothelial cells by β-aminoisobutyric acid (BAIBA), which is released from the skeletal muscles during physical activity. The increased expression of estrogen-related receptor α (ERRα) and peroxisome proliferator-activated receptor-gamma co-activator (PGC)-1β also plays a role in these mechanisms. However, the underlying mechanisms remain unknown, and we aimed to explore the effects of PGC-1β on the endothelial function.

Methods: We generated human umbilical vein endothelial cells (HUVECs) with PGC-1β knockdown using siRNA or by inducing the overexpression of PGC-1β using an adenovirus. We then examined the expression of inflammation-related genes induced by tumor necrosis factor α (TNFα) using qRT-PCR and the expression of endothelial nitric oxide synthase (eNOS) and its activation-related proteins using a western blot analysis.

Results: BAIBA treatment suppressed the TNFα-induced expression of inflammation-related molecules in HUVECs. However, these protective effects were diminished following PGC-1β knockdown, which correlated with decreased levels of IκBα protein. Additionally, in PGC-1β knockdown-HUVECs, the total and phosphorylated levels of eNOS decreased along with the levels of active AMP-activated protein kinase (AMPK) and protein kinase B (Akt). Conversely, the overexpression of PGC-1β in HUVECs resulted in the opposite effect.

Conclusion: These results suggest that BAIBA exerts various protective effects on vascular endothelial cells through the PGC-1β-NFκB and PGC-1β-AMPK-Akt-eNOS axes.

Aim: T50 is the time required for primary calciprotein particles (CPPs) to transform into secondary CPPs in vitro, reflecting serum calcification propensity, and used as a biomarker for calcification stress. Since secondary CPPs induce inflammation and oxidative stress, they may promote atherosclerosis. We investigated whether or not T50 was associated with carotid artery intima-media thickness (IMT).

Methods: This was a cross-sectional study of 202 health examinees. T50 was measured by the established nephelometric method. Carotid artery IMT was measured by high-resolution ultrasonography. The association between T50 and IMT was evaluated by a multivariable-adjusted linear regression analysis.

Results: In a univariate analysis, IMT was not significantly correlated with T50. A multivariable-adjusted linear regression analysis showed that IMT was independently associated with age, sex, diabetes mellitus, dyslipidemia, and fetuin-A but not with T50 in the total subjects. However, when stratified by the estimated glomerular filtration rate (eGFR), T50 was independently and inversely associated with IMT in the subgroup with an eGFR ＜60 mL/min/1.73 m² (β = −0.418, P = 0.013), whereas it was not in the subgroup with an eGFR ≥ 60 mL/min/1.73 m².

Conclusion: T50 was independently and inversely associated with IMT in health examinees with a reduced kidney function, suggesting a novel link between calcification stress and atherosclerosis, particularly in those with chronic kidney disease.

Aim: Notch signaling is a fundamental signal that regulates morphogenesis and cell differentiation during the embryonic period, and it plays a crucial role in macrophage differentiation. Macrophage-mediated inflammation promotes atherosclerosis from the initial lesion formation to acute thrombotic complications in advanced plaques. However, their role in atherosclerosis remains unclear. We herein focused on the Notch ligand Delta-like ligand 1 (Dll1), and examined its role in the pathobiology of atherosclerosis.

Methods: In Apoe^−/− mice, a blocking antibody against Dll1 (Dll1 Ab) was administered for 12 weeks from 8 weeks (early phase) or 20 weeks (late phase) of age.

Results: Dll1 blockade suppressed both initial lesion development and plaque vulnerability compared with lesions in mice treated with non-immune IgG. Dll1 Ab decreased lipid accumulation in advanced lesions and increased the collagen content. In ex vivo cultured macrophages, the blockade of Dll1-Notch signaling by Dll1 blocking antibodies suppressed the mRNA expression of Tnf and the release of activated matrix metalloproteinase 9, which increased plaque vulnerability. In contrast, the stimulation of Dll1-Notch by recombinant Dll1 induced Il1b, Il6, and Tnf expression in macrophages, as well as NF-κB activation. An exploratory transcriptome analysis of atherosclerotic arteries suggested that Dll1-Notch signaling regulates the expression of genes associated with inflammation and mitosis.

Conclusions: These results indicate that Dll1 promotes the pathobiology of atherosclerosis from the initial lesion development to plaque destabilization in advanced atherosclerotic lesions.

Aims: While glomerular hyperfiltration (GHF) emerged as a risk factor for cardiovascular disease (CVD), little is known about the association between GHF and blood lipid profile. We aimed to examine the association between GHF and blood lipid parameters in adults with few comorbidities.

Methods: A cross-sectional study was performed on adults undergoing health screening in Osaka, Japan. Adults with a history of heart disease or stroke, those with diabetes mellitus, chronic kidney disease (estimated glomerular filtration rate (eGFR) ＜60 mL/min/1.73m²), or those using lipid-lowering medication were excluded. The outcome was GHF, defined as ＞95^th percentile of eGFR after stratification by age and sex. The exposure was blood lipid parameters, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), non-HDL-C, TG/HDL-C ratio, small dense LDL-C (sdLDL-C), and sdLDL-C/LDL-C ratio. Associations between blood lipid parameters and GHF were examined by multiple logistic regression under a Bayesian framework, adjusted for established risk factors of GHF, including body mass index, blood pressure, and lifestyle factors.

Results: Of 17,288 eligible individuals (mean age 50.1±9.9 years; 45.5% women), 853 individuals (4.9%) had GHF. Multiple logistic regression analyses demonstrated an association between a higher sdLDL-C/LDL-C ratio and GHF (odds ratio (OR) = 1.51, 95% credible interval (CrI) 1.21–1.88). LDL-C showed an inverse association with GHF (OR = 0.94, 95% CrI 0.92–0.97).

Conclusion: Our findings demonstrated an independent association between a higher sdLDL-C/LDL-C ratio and GHF. The role of an sdLDL-C/LDL-C ratio in GHF development and CVD risk merits further investigation.

Aim: Achilles tendon xanthomas are a characteristic feature of familial hypercholesterolemia (FH). Achilles tendon thickness (ATT) has been associated with the severity of coronary artery disease (CAD) in FH. However, its relevance in non-FH remains unclear. Therefore, we assessed the relationship between ATT and CAD severity in patients with acute coronary syndrome (ACS) without FH.

Methods: A total of 194 patients (mean age: 69.1±11.9 years) with ACS without FH were retrospectively investigated and divided into two groups: single-vessel disease (SVD) or multivessel disease (MVD). ATT was measured using ultrasonography (US-ATT) and radiography (Xp-ATT). The association between ATT and CAD severity was evaluated.

Results: Of the total, 107 patients (55.2%) had SVD, and 87 (44.8%) had MVD. Mean US-ATT and Xp-ATT values were 5.0±0.6 mm and 6.4±1.2 mm, respectively. ATT was significantly greater in the MVD group than in the SVD group (US-ATT: 5.2 mm vs. 4.8 mm, p＜0.01; Xp-ATT: 6.6 mm vs. 6.1 mm, p = 0.01) and correlated with the SYNTAX score (US-ATT: r = 0.30, p＜0.01; Xp-ATT: r = 0.19, p = 0.02). Multivariable analysis identified US-ATT as an independent predictor of MVD (odds ratio: 2.71; 95% confidence interval: 1.46–5.01; p＜0.01).

Conclusion: In patients with ACS without FH, ATT was significantly associated with CAD severity. This suggests that ATT, particularly US-ATT, may serve as a practical, non-invasive marker for cardiovascular risk stratification.

Aim: Specific Health Checkups (SHCs) and Specific Health Guidance (SHG) were launched in 2008, but the factors related to their effectiveness have not been clarified. We examined the mean reduction in body weight (BW) and waist circumference (WC) of participants eligible for active support under SHG. Body size was considered, as well as the number of support points given during SHG, which indicates the amount of support they received.

Methods: A dataset of participants (aged 40–64) who were eligible for SHG and had SHC results collected between 2011 and 2012 was analyzed (n = 76,565). The mean changes in BW and WC between 2011 and 2012 were compared among participants based on their participation status (did not participate, dropped out, finished) and the number of support points for those who finished. Participants were also stratified by sex and BMI (kg/m²): normal weight, overweight, and obese.

Results: The mean BW change (95% CI) for those who did not participate and finished SHG was −0.45 kg (−0.47, −0.43) and −1.32 kg (−1.39, −1.25) in men, and −0.66 kg (−0.72, −0.60) and −1.68 kg (−1.87, −1.49) in women, respectively. Higher support points and larger body sizes correlated with greater reductions in BW in men (P＜0.001), but the associations were not significant in women. The reduction in WC was greater in women with normal weight than in obese women.

Conclusion: Sex differences were observed in the association between BW/WC reduction and body size or the amount of support given during SHG.

Atherosclerotic cardiovascular disease (ASCVD) is associated with a very high risk of secondary cardiovascular events. Elevated low-density lipoprotein cholesterol (LDL-C) is a major determinant in the progression of ASCVD and in the onset of associated adverse events. Consequently, rigorous control of LDL-C is a cornerstone of secondary prevention strategies, typically achieved through statin therapy, either as monotherapy or in combination with ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors. Recent large-scale clinical trials have demonstrated that intensive LDL-C lowering significantly reduces cardiovascular risk, leading to updated guidelines in the United States and Europe that advocate for more aggressive LDL-C treatment targets for secondary prevention in ASCVD. In this context, a working group established in the Japan Atherosclerosis Society performed a scoping review of LDL-C treatment targets for the secondary prevention of ASCVD. The working group systematically reviewed the available evidence for coronary artery disease (including acute and chronic coronary syndrome), atherothrombotic brain infarction, and peripheral artery disease, all of which are defined as ASCVD. The aim was to assess the evidence-based LDL-C treatment targets for the secondary prevention of defined ASCVD in Japanese patients.

Aim: The relationship between multiple modifiable risk factors (RFs) and coronary plaque development remains unclear. This study investigated the relationship between the cumulative RF burden and coronary inflammation, a key driver of atherosclerosis, and whether this relationship varies according to the status of coronary artery stenosis.

Methods: We analyzed 958 patients who underwent coronary computed tomography angiography. Modifiable RFs included hypertension, diabetes, a body mass index ≥ 30 kg/m ², and current smoking status. Risk factor burden was categorized by the number of risk factors, ranging from none to ≥ 2. Coronary inflammation was quantified by the perivascular fat attenuation index (FAI), defining a high FAI as a value above the 75th percentile (＞-70.2 HU).

Results: Among the patients, 142 had no RFs, 467 had 1 RF, and 349 had ≥ 2 RFs. The median FAI was -76.2HU, and a high FAI was observed in 239 patients. Compared to those with no RFs, the multivariable Poisson regression with robust error variance demonstrated a significant increase in the prevalence of a high FAI among patients with higher RF burdens: 1 RF (relative risk [RR] 1.56; 95% confidence interval [CI], 1.06–2.30) and ≥ 2 RFs (RR 1.71; 95% CI, 1.16–2.52). Similar associations were observed in patients with no or minimal atheroma (＜25%): one RF (RR, 1.65; 95% CI, 1.01–2.68) and ≥ 2 RFs (RR 2.25; 95% CI, 1.38–3.66).

Conclusions: A greater RF burden was associated with increased coronary inflammation in a dose-dependent manner. These findings indicate that RF clustering is associated with higher coronary inflammation even in the absence of significant coronary plaque.

Japan’s health checkup system has developed over the last four decades as a principal national strategy for preventing cerebrovascular and cardiovascular diseases (CVD). Early community-based health checkups, implemented under the Health Services for the Elderly Act of 1982, contributed to reductions in CVD mortality and the demand for inpatient care through the improved detection and management of hypertension. As lifestyle-related diseases became increasingly prominent, the government introduced Health Japan 21 and subsequently launched the Specific Health Checkups and Specific Health Guidance (SHC/SHG) program in 2008 to strengthen evidence-based population-wide prevention targeting of visceral obesity and the associated cardiometabolic risks. The SHC program provides standardized assessments, including anthropometric measurements, laboratory testing, medical history, and lifestyle questionnaires. Risk stratification is primarily based on abdominal obesity and the accumulation of metabolic risk factors, which determine individualized health guidance through motivational or intensive support. The SHG program offers structured behavioral interventions delivered by trained health professionals to promote sustainable lifestyle modifications. Growing evidence supports the effectiveness of the SHC/SHG program. Health checkup participation has been associated with lower mortality, and health guidance has demonstrated favorable improvements in obesity indicators, metabolic parameters, and pharmacotherapy initiation. Economic evaluations further suggest that the program is cost effective. However, some limitations remain, including modest long-term effects and insufficient risk identification among non-obese individuals with elevated cardiometabolic risk. Improving the participation rates and refining risk stratification beyond obesity-based criteria are ongoing priorities. Continued research and periodic revision of checkup items are essential for enhancing the program’s impact as a nationwide strategy for ASCVD prevention.

Familial hypercholesterolemia (FH) is a highly prevalent genetic disorder that occurs in approximately one in 300 people in the general population. In cases of heterozygous FH, which are encountered frequently, cardiovascular disease, the main complication, typically manifests after adulthood. However, if the diagnosis and treatment begin in childhood, the onset of such complications can be prevented. Therefore, it can be said that the diagnosis and treatment of this disease from childhood is extremely important; even more so in the case of homozygous FH. However, specific indicators for diagnosing FH physical findings such as Achilles tendon thickening and tendon xanthomas rarely manifest in childhood. It is also difficult to obtain detailed medical histories from relatives. Therefore, it is not always easy to make a clinical diagnosis. In this context, since 2022, genetic testing for FH has been covered by national health insurance in Japan, and it can be considered for children as needed. This paper presents the previous research concerning genetic testing for children, its importance and application, as well as the latest findings on universal screening that includes genetic testing. It is expected that the development of pediatric FH management in our country, which has not been particularly proactive until now, will contribute to the suppression of cardiovascular complications in this condition.

Aims: The global distribution of lipoprotein(a) [Lp(a)] levels varies due to racial and ethnic differences. However, the clinical relevance of Lp(a) levels in Japanese patients has not been fully explored.

Methods: We investigated the association of Lp(a) levels, the Suita score, and the presence of high-risk plaque (HRP) as well as that of ≥ 50% stenosis, quantitative plaque volume, and the value of coronary artery calcium score in coronary computed tomographic angiography (CCTA), among 272 Japanese patients (mean age: 65 years) in whom serum Lp(a) levels were measured due to suspected coronary artery disease. HRP was defined as positive remodeling and/or low attenuation. Plaque volume was quantified as the percent plaque volume.

Results: HRP was identified in 33 (12.1%) patients. The prevalence of HRP, ≥ 50% stenosis, and percent plaque volume progressively increased with higher Lp (a) levels and Suita scores. In multivariate analyses, Lp(a) and the Suita score independently predicted HRP when assessed as continuous (p = 0.02, p＜0.001, respectively) or categorical variables (p = 0.005, p = 0.007, respectively). Patients in the highest tertile of Lp(a) and classified as high- or intermediate-risk by the Suita score had the highest HRP risk, whereas those in the lower 2 tertiles and low-risk group had the lowest. Incorporating Lp(a) into the Suita score improved the prediction of HRP beyond the Suita score alone (p = 0.005).

Conclusions: The combinatorial value of assessing Lp(a) levels and Suita score may provide useful insight regarding Japanese patients undergoing CCTA for the prediction of HRP.

Aim: Small dense low-density lipoprotein cholesterol (sdLDL-C) is recognized as an atherogenic risk factor. This study investigated the prognostic significance of sdLDL-C levels in patients with premature acute coronary syndrome (PACS) and multivessel disease (MVD).

Methods: This retrospective study enrolled 847 hospitalized patients diagnosed with PACS and MVD between May 2022 and November 2023. Patients were stratified based on clinical outcomes and tertiles of sdLDL-C levels. Multivariate Cox proportional hazard models were applied to determine whether or not sdLDL-C was a prognostic risk factor for major adverse cardiovascular events (MACEs). Cumulative event curves were estimated using the Kaplan–Meier method. The predictive efficacy of sdLDL-C for MACEs was assessed through a time-dependent receiver operating characteristic (ROC) analysis. In addition, a restricted cubic spline (RCS) analysis was conducted to explore the relationship between sdLDL-C levels and the risk of MACEs.

Results: During a median follow-up of 12 months (interquartile range: 9–15 months), 124 MACEs (14.64%) were observed. The sdLDL-C levels in the MACEs group were significantly higher compared to the non-MACEs group (P＜0.001). A multivariate Cox hazards regression analysis revealed that the risk of MACEs in the highest sdLDL-C tertile group was 2.38 times greater than in the lowest tertile group (hazard ratio [HR]: 2.38, 95% confidence interval [CI]: 1.42–4.00; P = 0.001). Furthermore, each 1-mg/dL increase in sdLDL-C levels corresponded to a 12.2% increase in the risk of MACEs (HR: 1.12, 95% CI: 1.08–1.16; P＜0.001). A Kaplan–Meier survival analysis identified significant differences in event-free survival among sdLDL-C tertiles (log-rank test, P＜0.001). The time-dependent ROC analysis demonstrated a progressive increase in the area under the curve during the follow-up period, particularly within the first 12 months. The RCS analysis revealed a nonlinear dose-response relationship between higher sdLDL-C levels and increased cumulative risk of MACEs (P_nonlinear = 0.001).

Conclusion: sdLDL-C is a predominant predictor of a poor prognosis in patients with PACS and MVD, underscoring its clinical relevance for risk stratification and the early identification of high-risk individuals who may benefit from targeted intervention.

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.

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.

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.

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.

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.

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.

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.

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.

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 m², 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 m². 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.

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.

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.

Aims: The HELT-E₂S₂ score is a newly developed risk stratification tool for stroke in patients with atrial fibrillation. We investigated the prognostic value of the HELT-E₂S₂ 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-E₂S₂ score ＜2, n = 146) and high-risk (HELT-E₂S₂ score ≥ 2, n = 218) groups. The major criteria of the HELT-E₂S₂ 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-E₂S₂ and other AF and LEAD risk scores.

Conclusions: The HELT-E₂S₂ score was associated with an increased risk of cardiovascular events in patients with LEAD undergoing EVT.

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.

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.

Aim: Overproduction of large very low-density lipoprotein1 (VLDL1) is a central abnormality in metabolic dyslipidemia. Excess-triglycerides (Ex-TG), based on the Friedewald equation, is considered to be a marker for TG-rich VLDL, but it remains uncertain whether Ex-TG reflects large VLDL particles.

Methods: We conducted a retrospective sub-analysis of the PROUD48 study, which compared the effects of pemafibrate and omega-3 fatty acids (FAs) on apolipoprotein B48, with data available on VLDL subfractions. Hyperlipidemic patients on statins were treated with pemafibrate (n = 56) or omega-3FAs (n = 56) for 16 weeks. VLDL subfractions: large (L), middle (M), and small (S) were separated using high-performance liquid chromatography. Ex-TG was calculated as plasma TG minus 5 x calculated VLDL-cholesterol (C).Calculated VLDL=total-C minus directly measured LDL-C minus HDL-C.

Results: Pemafibrate and omega-3FAs reduced plasma TG levels by 42% and 27%, respectively; however, a marked reduction in Ex-TG was observed only with omega-3 FAs. Ex-TG was positively correlated with L-VLDL-TG, %L-VLDL-TG, (L–M+S)-VLDL-TG, and L-VLDL-TG/C, while it showed no positive correlation with smaller VLDLs and apoB48. TG exhibited stronger correlations with L-VLDL-related parameters than Ex-TG, but was also positively associated with smaller VLDLs and apoB48. These correlation patterns remained consistent even when examining the relationship between changes in Ex-TG, TG, or apoB48 and corresponding changes in VLDL subfractions using lipid-lowering agents.

Conclusions: The behavior of Ex-TG appears consistent with previous kinetic studies showing that omega-3FAs primarily suppress VLDL1 production, whereas fibrates promote TG removal, suggesting that Ex-TG serves as a surrogate marker for VLDL1 overproduction.

A 79-year-old Chinese man was referred for nephrotic syndrome (proteinuria 4.4 g/day). In blood tests, serum high-density lipoprotein (HDL) cholesterol was undetectable, and the esterified cholesterol to total cholesterol ratio was very low. Lecithin: cholesterol acyltransferase (LCAT) activity was also undetectable. Since he had neither corneal opacity nor pathological mutations in the LCAT gene and anti-LCAT antibodies were detected in serum, a diagnosis of acquired LCAT deficiency was made. Renal biopsy revealed glomerulopathy associated with LCAT deficiency and membranous nephropathy (MN). Since the patient’s proteinuria did not improve despite prescribing an angiotensin II receptor blocker (ARB), we suggested the prescription of prednisolone, but he returned to China due to the expiration of his residence visa for Japan. One year after the initial visit, his proteinuria had improved to 0.9 g/day without immunosuppressive therapy. However, his HDL cholesterol level was still low at around 3 mg/dL, indicating a discrepancy between remission of nephrotic syndrome and lack of improvement in lipid levels.

Of the 11 patients with acquired LCAT deficiency reported to date, 4 with undetectable LCAT activity and MN on renal biopsy required immunosuppressive therapy to alleviate proteinuria. The present patient was prescribed only an ARB according to his preference, which happened to be consistent with the MN treatment guideline that states, “Wait 6 months for spontaneous remission while using maximal antiproteinuric therapy.” The clinical course of acquired LCAT deficiency varies, and further case reports are needed to determine the necessity of immunosuppressive therapy.

Aims: In-stent restenosis (ISR) is a significant limitation of coronary stent implantation, but the exact mechanism of ISR remains unclear. Patients after percutaneous coronary intervention (PCI) are in a hypercoagulable state; however, there is less information on its association with chronic coronary artery disease (CAD) in patients with ISR after PCI. We aimed to clarify whether or not CAD patients with ISR after PCI are in a hypercoagulable state and whether or not PS exposure on extracellular vesicles (EVs), blood cells (BCs), and endothelial cells (ECs) is involved in the hypercoagulable state.

Methods: Phosphatidylserine (PS) exposure to EVs, BCs, and ECs was analyzed using flow cytometry. Procoagulant activity (PCA) was analyzed by clotting time (CT), purified clotting complex assays, and fibrin production assays.

Results: Compared with pre-PCI or controls, levels of exposed PS on EVs, BCs, and ECs were significantly increased from 1 day, peaked at 3 months, and gradually decreased within 1 year in CAD patients after PCI, especially in CAD patients with ISR after PCI. Furthermore, their increased levels significantly decrease CT and enhance intrinsic/extrinsic FXa, thrombin, and fibrin generation. PCA was weakened by approximately 80% when lactadherin was used.

Conclusions: Our results revealed that CAD patients after PCI, especially those patients with ISR after PCI, are associated with a hypercoagulable state in which PS exposure on EVs, BCs, and ECs plays a more important role than tissue factors. Therefore, blocking PS exposure to EVs, BCs, and ECs may provide a new target for preventing ISR in these patients.

Aim: This study addressed the alteration and related factors of cholesterol efflux capacity (CEC) and anti-oxidative activity in patients with chronic kidney disease (CKD).

Methods: This retrospective cross-sectional observational study included 333 patients (median age: 50 [20, 81] years old, male: 46.5%) who underwent a kidney biopsy at Kitano Hospital. CEC and oxygen radical adsorption capacity (ORAC) were measured using serum obtained at the time of the kidney biopsy. Changes in CEC and ORAC in relation to the clinical and kidney injury parameters were evaluated.

Results: Mean CEC and ORAC were 0.83±0.15 and 0.86±0.14, respectively. High-density lipoprotein-cholesterol (HDL-C) levels were significantly associated with CEC (r = 0.673, p＜0.001) and ORAC (r = 0.164, p = 0.003). CEC showed a weak association with ORAC (r = 0.333, p＜0.001). Both HDL-C and CEC were negatively associated with the body mass index (r = −0.407, p＜0.001 and r = −0.248, p＜0.001, respectively) and were significantly higher in women than in men (p＜0.001). The ORAC was positively associated with the serum albumin level (r = 0.330, p＜0.001) and negatively associated with the urinary protein creatinine ratio (UPCR) (r = −0.236, p＜0.001). A multiple regression analysis showed that CEC was associated with the estimated glomerular filtration rate (eGFR), serum albumin, and ORAC. There was no significant correlation between global sclerosis and either CEC or ORAC.

Conclusions: The HDL-C level did not represent HDL functionalities in CKD patients. The decreased eGFR and reduced serum albumin levels induced by an increased UPCR might therefore be associated with impaired HDL functionalities.

Aims: Interleukin-6 (IL-6) is a cytokine involved in the development of atherosclerosis and ischemic stroke. Herein, we investigated the association between serum IL-6 levels at stroke onset and long-term outcomes in patients with ischemic stroke.

Methods: This prospective observational study enrolled 655 consecutive patients (mean age, 70 years; male, 62.1%) with ischemic stroke within one week of onset followed-up for one year. Patients were divided into 3 groups according to baseline serum IL-6 tertiles: tertile 1, ＜2.6 pg/mL (n = 216); tertile 2, 2.6-6.1 pg/mL (n = 217); and tertile 3, ＞= 6.2 pg/mL (n = 222). We evaluated the association of serum IL-6 levels with a composite of major adverse cardiovascular events (MACE; nonfatal stroke, nonfatal acute coronary syndrome, major peripheral artery disease, and vascular death) and the poor functional outcome defined as modified Rankin Scale score of ≥ 3 at one year.

Results: Higher serum IL-6 levels were associated with increased prevalence of chronic kidney disease, atrial fibrillation, chronic heart disease, active cancer, and post-stroke pneumonia. The three groups showed significant differences in the one-year MACE risk (annual rate, 11.2%, 10.8%, and 19.1% in the tertiles 1, tertile 2, and tertile 3 groups, respectively). Higher serum IL-6 levels were significantly associated with poor functional outcomes at one year after stroke (14.4%, 29.5%, and 56.8% in the tertile 1, tertile 2, and tertile 3 groups, respectively; P＜0.001), even when adjusting for baseline covariates and MACE during follow-up.

Conclusions: Higher serum IL-6 level at ischemic stroke onset was an independent predictor of poor functional prognosis at one year.

Aims: This study examined whether or not the coexistence of smoking and metabolic syndrome synergistically increases the risk of cardiovascular disease (CVD) beyond their individual effects.

Methods: This prospective cohort study included 68,743 workers from the Japan Epidemiology Collaboration on Occupational Health Study. The participants were categorized into four groups based on their smoking status and metabolic syndrome. Biological interactions were evaluated using relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S).

Results: During a mean follow-up of 7.2 (range: 0.1–10.9) years, 346 participants developed CVD. Current smokers with metabolic syndrome had the highest CVD risk (hazard ratio: 6.45, 95% confidence interval [CI]: 4.73–8.80). Approximately 35% of CVD cases among individuals exposed to both factors were attributed to their biological interactions (RERI: 2.27, 95% CI: 0.56–3.98; AP: 0.35, 95% CI: 0.15–0.55; S: 1.71, 95% CI: 1.16–2.52). An analysis of CVD subtypes revealed a significant biological interaction for myocardial infarction (RERI: 5.14, 95% CI: 0.65–9.62; AP: 0.52, 95% CI: 0.26–0.78; S: 2.38, 95% CI: 1.22–4.62) but not for stroke (RERI: 1.34, 95% CI: -0.46–3.13; AP: 0.25, 95% CI: -0.03–0.53; S: 1.44, 95% CI: 0.89–2.34).

Conclusion: Smoking and metabolic syndrome interact synergistically to elevate CVD risk, particularly for myocardial infarction. Targeting both factors is essential for CVD prevention.

Aim: Intracranial artery calcification (IAC) in patients with acute ischemic stroke may cause cerebral hemodynamic injury and aggravate ischemia-reperfusion injury. However, its relationship with brain damage and clinical outcomes has not yet been fully explored.

Methods: Patients with acute anterior circulation ischemic stroke who underwent intravenous thrombolysis (IVT) were enrolled. Intracranial artery calcification (IAC) was assessed using the IAC volume and number of calcified vessels (NCV) on pre-IVT computed tomography. Outcomes included the degree of brain injury at 24 h post-IVT, measured by serum glial fibrillary acidic protein (GFAP) levels, final infarct volumes, intracranial hemorrhaging within 24 h of IVT, and a poor prognosis at 90 days (modified Rankin Scale ＞2). A multivariate regression analysis was conducted to evaluate the associations between IAC parameters and clinical outcomes.

Results: A total of 348 patients were enrolled in the study, of whom 273 (78.4%) had IAC. Patients were divided into four quartile groups (Q1, Q2, Q3, and Q4) based on the total IAC volume. The fourth quartile (Q4), which included patients with the highest IAC volume, was independently associated with elevated GFAP levels (odds ratio [OR] = 2.449, 95% confidence interval [CI], 1.057–5.673; P = 0.037). The second quartile (Q2) was independently associated with final infarct volume (β:0.483, 95% CI:0.014–0.952, P = 0.044). In addition, NCV was independently correlated with increased GFAP levels (OR = 1.265, 95% CI:1.010–1.584, P = 0.040) and a poor prognosis (OR = 1.270, 95% CI: 1.008-1.600, P = 0.043).

Conclusion: IAC was independently associated with the degree of brain injury, final infarct volume, and prognosis in patients after IVT.

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_s = -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.

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.