Journal Of Atherosclerosis And Thrombosis[JOURNAL]
Sun
200 papers
Assessments of Atherosclerosis and Treatment Strategies for Heterozygous Familial Hypercholesterolemia.
Tada H, Harada-Shiba M
J Atheroscler Thromb · 2025 Oct · PMID 40451833 · Full text
Patients with familial hypercholesterolemia (FH) carry an extremely elevated cardiovascular risk because of lifelong exposure to elevated low-density lipoprotein cholesterol (LDL-C). The Japan Atherosclerosis Society (JA...
Patients with familial hypercholesterolemia (FH) carry an extremely elevated cardiovascular risk because of lifelong exposure to elevated low-density lipoprotein cholesterol (LDL-C). The Japan Atherosclerosis Society (JAS) complies with the clinical guidelines of FH stipulating diagnostic criteria as well as the treatment targets based on their cardiovascular preventive status. These guidelines are expected to improve the FH diagnosis rate and facilitate better LDL-C management, ultimately leading to improved patient outcomes. However, there are no clear instructions on how and when to assess atherosclerosis. In addition, current treatment target goals, especially for adults with heterozygous FH (HeFH) (LDL-C ＜100 mg/dL in primary prevention and LDL-C ＜70 mg/dL in secondary prevention), are sometimes insufficient to fully navigate to prevent cardiovascular events, given that many factors, such as hypertension, diabetes, smoking, lipoprotein (a), cholesterol-year score, coronary artery calcium, and pathogenic mutations are associated with a further increased risk on top of the LDL-C level assessed cross-sectionally. Accordingly, we summarized contemporary strategies for assessing systemic atherosclerosis and treatment options.
Cholesteryl Ester Transfer Protein Deficiency and Hyperalphalipoproteinemia.
Inazu A
J Atheroscler Thromb · 2025 Aug · PMID 40436797 · Full text
Cholesteryl ester transfer protein (CETP) deficiency and lipoprotein phenotypes with CETP inhibitors were compared. The effects on atherosclerotic cardiovascular disease (ASCVD) and the recently suggested retinal disease...
Cholesteryl ester transfer protein (CETP) deficiency and lipoprotein phenotypes with CETP inhibitors were compared. The effects on atherosclerotic cardiovascular disease (ASCVD) and the recently suggested retinal disease of age-related macular degeneration (ARMD) were summarized and discussed in relation to CETP deficiency and extremely increased high-density lipoprotein (HDL) cholesterol levels (＞100 mg/dL). In CETP truncated variants leading to reduced low-density lipoprotein cholesterol levels, ASCVD risk was decreased in heterozygotes. ASCVD prevalence did not increase in homozygotes with CETP deficiency. However, the association between ASCVD and ARMD risks in cases of very high HDL cholesterol level found in multifactorial hyperalphalipoproteinemia needs to be clarified on an etiological basis. The hurdles facing the development of CETP inhibitors are summarized, including a new result for obicetrapib.
Effects of Pemafibrate on Cholesterol Synthesis and Absorption: a Post-Hoc Subgroup Analysis of a Phase 2 Clinical Trial.
Yamashita S, Araki E, Arai H … +6 more , Yokote K, Tanigawa R, Saito A, Suganami H, Minamikawa S, Ishibashi S
J Atheroscler Thromb · 2025 Nov · PMID 40436796 · Full text
AIM: Recently, we reported that a pemafibrate extended-release (XR) formulation lowered low-density lipoprotein cholesterol (LDL-C) and cholesterol synthesis and absorption markers in a phase 2 clinical pharmacology stud...
AIM: Recently, we reported that a pemafibrate extended-release (XR) formulation lowered low-density lipoprotein cholesterol (LDL-C) and cholesterol synthesis and absorption markers in a phase 2 clinical pharmacology study. Here we describe our post-hoc analysis of that study, discuss the mechanism by which pemafibrate lowers LDL-C, and suggest which patients may respond favorably to pemafibrate treatment. METHODS: In the phase 2 study, patients with hypertriglyceridemia received treatment with pemafibrate immediate-release (IR) 0.2 mg/day or XR 0.4 mg/day or 0.8 mg/day. This post-hoc subgroup analysis examined the percentage change in LDL-C, apolipoprotein B (ApoB), non-HDL-C, and cholesterol synthesis and absorption markers, in subgroups by baseline LDL-C, and then determined the correlation between the percentage change in LDL-C and the percentage change in cholesterol synthesis and absorption markers. RESULTS: Our analysis included 60 patients who received two of three formulations of the drug. A total of 78.3% (47/60) were male, 16.7% (10/60) had type 2 diabetes mellitus, and 10% (6/60) received concomitant statins. The percentage of LDL-C lowering was greater in the population with high baseline LDL-C, and similar trends were noted for the ApoB, non-HDL-C, and cholesterol synthesis and absorption markers. The percentage change in LDL-C was positively correlated with the percentage change in lathosterol, β-sitosterol, and campesterol. CONCLUSIONS: In patients with hypertriglyceridemia, results suggested that pemafibrate lowered LDL-C by inhibiting cholesterol synthesis in the liver and cholesterol absorption from the intestinal tract. This lowering effect was greater in populations with higher baseline LDL-C.
Association of Social Participation with Cardiovascular Risk Factors: A Systematic Review.
Miura M, Ikeda A, Sato S … +11 more , Muraki I, Okamura T, Ohira T, Miyazaki J, Ishihara M, Okamoto K, Kamijima J, Li Q, Ikeda S, Yamagishi K, Tanigawa T
J Atheroscler Thromb · 2025 Aug · PMID 40414707 · Full text
AIM: Although social participation, defined as involvement in social activities, may be beneficial for cardiovascular health, evidence about the association remains limited. This systematic review summarized the relation...
AIM: Although social participation, defined as involvement in social activities, may be beneficial for cardiovascular health, evidence about the association remains limited. This systematic review summarized the relationship between social participation and cardiovascular risk factors. METHODS: Original articles of longitudinal observational studies published in English before January 1, 2024, were searched via PubMed, Scopus, and Cochrane Library. Two investigators selected eligible literature for four health outcomes: hypertension, diabetes, dyslipidemia, and obesity. RESULTS: Eight articles (including duplicates) covering cohort studies were included. The results indicated that social participation is associated with lower hypertension risk, but gender differences may exist in the association between social participation and hypertension. Two articles from a Japanese cohort study were found on diabetes, both of which reported significant preventive association with social participation. The only study on dyslipidemia showed a higher hyperlipidemia risk among women, but not men, with social participation. Two studies on the risk of obesity showed inconsistent results, with one reporting the association between social participation and maintenance of smaller waist circumference only among men, while the other found no association with body mass index. CONCLUSIONS: There is some evidence of the association between social participation and better cardiovascular health outcomes. However, evidence on gender differences and validation of the methodology for measuring social participation was still lacking.
Serum Total Cholesterol and Fatal Subarachnoid Hemorrhage in 120,000 Japanese: A Pooled Analysis of Data from 12 Cohorts.
Satoh A, Arima H, Tanaka-Mizuno S … +7 more , Fujiyoshi A, Kadota A, Miura K, Ueshima H, Okamura T, Murakami Y, EPOCH JAPAN Research Group
J Atheroscler Thromb · 2025 Nov · PMID 40414706 · Full text
AIM: The aim of this study was to clarify the association between serum total cholesterol and fatal subarachnoid hemorrhage in Japanese men and women. METHODS: The study involved a pooled analysis of individual data from...
AIM: The aim of this study was to clarify the association between serum total cholesterol and fatal subarachnoid hemorrhage in Japanese men and women. METHODS: The study involved a pooled analysis of individual data from 12 well-qualified cohort studies conducted in Japan. The participants were classified according to their serum total cholesterol levels: ＜4.14 mmol/L (＜160 mg/dL), 4.14-4.64 mmol/L (160-180 mg/dL), 4.65-5.16 mmol/L (180-199 mg/dL), 5.17-5.68 mmol/L (200-219 mg/dL), 5.69-6.20 mmol/L (220-239 mg/dL), and ≥ 6.21 mmol/L (≥ 240 mg/dL). The outcome of the analysis was death from subarachnoid hemorrhage. RESULTS: A total of 120,973 participants (70,947 women and 50,026 men) aged 18-96 years at baseline underwent follow-up for a median of 12.7 years, and 261 participants died from subarachnoid hemorrhage during this period. In women, both low (＜5.69 mmol/L [＜220 mg/dL]) and high (≥ 6.21 mmol/L [≥ 240 mg/dL]) serum total cholesterol levels were significantly associated with a higher risk of fatal subarachnoid hemorrhage compared with the reference group (5.69-6.20 mmol/L [220-239 mg/dL]). These associations remained significant after adjustment for confounding factors. In contrast, no associations were observed in men. CONCLUSION: Both low and high serum total cholesterol levels were associated with a higher risk of fatal subarachnoid hemorrhage in 70,947 female participants from 12 cohort studies throughout Japan.
Impact of a Physician-led Strike Early-Strike Strong Lipid-Lowering Protocol Incorporating PCSK9 Inhibitors for Patients with Acute Myocardial Infarction.
Arai R, Hotsubo Y, Nakajima Y … +10 more , Sumida R, Mizobuchi S, Migita S, Tanaka Y, Hori K, Fukumoto K, Ebuchi Y, Kojima K, Sudo M, Okumura Y
J Atheroscler Thromb · 2025 Nov · PMID 40399054 · Full text
AIMS: Intensive lipid-lowering therapy is recommended for secondary prevention of cardiovascular events after acute myocardial infarction (AMI). However, the prescription rate of PCSK9 inhibitors (PCSK9is) remains low am...
AIMS: Intensive lipid-lowering therapy is recommended for secondary prevention of cardiovascular events after acute myocardial infarction (AMI). However, the prescription rate of PCSK9 inhibitors (PCSK9is) remains low among patients not achieving low-density lipoprotein (LDL) cholesterol target levels. METHODS: A retrospective analysis was conducted on 194 patients with AMI who were discharged alive and followed up as outpatients at our institution between October 2022 and October 2024. In October 2023, we implemented the Physician-led Strike Early-Strike Strong Lipid-Lowering Protocol (Physician-led Protocol) to enhance lipid management. Patients were divided into two groups: pre-protocol (October 2022-September 2023) and post-protocol (October 2023-October 2024). Patient background characteristics, lipid-lowering therapies, and LDL cholesterol levels in the chronic phase were compared between the two groups. The outcomes included post-discharge PCSK9i initiation rates and chronic-phase LDL levels. RESULTS: While the prescription rates of strong statins and ezetimibe were similar between the groups, PCSK9i use was significantly higher in the post-protocol group than in the pre-protocol group (15.3% vs. 2.8%, p = 0.002). Furthermore, the chronic LDL levels were significantly lower in the post-protocol group than in the pre-protocol group (51.0 vs. 58.0 mg/dL, p = 0.007). Multivariate logistic regression showed that initial LDL levels and PCSK9i use were associated with achieving chronic LDL levels ＜55 mg/dL. Among eligible patients in the post-protocol group, 36.4% received PCSK9is. CONCLUSIONS: The physician-led protocol increased PCSK9i prescriptions, achieving a median chronic LDL level of 51 mg/dL.
Intravascular Imaging and Pathological Features of Drug-Coated Balloon Angioplasty in Atherosclerotic Porcine Peripheral Arteries.
Migita S, Kitano D, Li Y … +5 more , Koyama Y, Shimodai-Yamada S, Okumura Y, Hirayama A, Hao H
J Atheroscler Thromb · 2025 Oct · PMID 40383637 · Full text
AIMS: The safety and efficacy of drug-coated balloon angioplasty (DCBA), compared to plain old balloon angioplasty (POBA) for peripheral artery in-stent restenosis (ISR), have been examined in clinical trials. However, l...
AIMS: The safety and efficacy of drug-coated balloon angioplasty (DCBA), compared to plain old balloon angioplasty (POBA) for peripheral artery in-stent restenosis (ISR), have been examined in clinical trials. However, little is known about the pathological response after DCBA for ISR. We compared the intravascular imaging findings and tissue responses of in-stent neointima in iliac arteries after DCBA and POBA using atherosclerotic porcine peripheral arteries. METHODS: Bare metal stents (BMSs) were implanted in the iliac arteries of microminipigs fed high-cholesterol chow. Four weeks after BMS implantation, stented regions were assessed by optical coherence tomography (OCT), followed by either DCBA or POBA. The adherence of the drugs delivered was observed by OCT and angioscopy, performed immediately after DCBA, and then confirmed with scanning electron microscopy. Four weeks after balloon angioplasty, the stented regions were investigated by OCT followed by pathological examination. RESULTS: Neointimal volume after DCBA was significantly reduced, while that after POBA showed minimal change. Histological assessments revealed decreases in cell number and the α-smooth muscle actin (SMA)-positive area, while the aniline blue-positive area and the alcian blue-positive area in the neointima was increased, after DCBA as compared to after POBA. CONCLUSIONS: The neointima after DCBA in the BMS-implanted region showed fewer smooth muscle cells and more mature extracellular matrix than that after POBA. These results confirmed the clinical benefits of DCBA with ISR for lower extremity arterial disease.
Cross-Sectional Association between Sedentary Behavior and Physical Inactivity with Cardiometabolic Risk Factors among Japanese: The NIPPON DATA2010.
Ohashi M, Miyagawa N, Yanagita M … +12 more , Okuda N, Fujiyoshi A, Ohkubo T, Kadota A, Okami Y, Kondo K, Harada A, Okamura T, Ueshima H, Okayama A, Miura K, NIPPON DATA2010 Research Group
J Atheroscler Thromb · 2025 Oct · PMID 40368810 · Full text
AIM: Sedentary behavior and physical inactivity increase the risk of cardiometabolic diseases. It is important to evaluate physical activity in daily life and understand the influence of these factors on cardiometabolic...
AIM: Sedentary behavior and physical inactivity increase the risk of cardiometabolic diseases. It is important to evaluate physical activity in daily life and understand the influence of these factors on cardiometabolic diseases in the Japanese population, which tends to have a prolonged sitting time. We examined the association between sedentary behavior and physical inactivity, characterized by extended television (TV) viewing and low step counts, which are easily monitored and modifiable, and cardiometabolic risk factors in the Japanese population. METHODS: This cross-sectional study included 2,531 Japanese adults (1,087 men and 1,444 women) 20-91 years old, randomly selected throughout Japan. TV viewing was assessed using a self-reported questionnaire, and step counts were measured using pedometers. Cardiometabolic risk factors were determined using physical examinations or blood samples. The association between sedentary behavior and physical inactivity with each risk factor was examined using a cross-sectional analysis with multivariate-adjusted logistic regression models. RESULTS: In both sexes, longer TV viewing positively correlated with low high-density lipoprotein (HDL) cholesterol and high triglycerides (TG). In women, TV viewing time is associated with obesity and increased abdominal circumference (AC). Conversely, in men, lower step counts were positively associated with obesity and increased AC, low HDL cholesterol, and high TG levels. CONCLUSIONS: The association between prolonged TV viewing and cardiometabolic risk factors was more pronounced in women than in men, whereas the influence of lower step counts was stronger in men than in women. These findings contribute to the improvement of cardiovascular health by monitoring and managing individual screen times and step counts in daily life.
Current Status and Future Aspect of Digital Health Innovation in Stroke Prevention and Management.
Wada S, Okada T, Koga M … +1 more , Mizuno A
J Atheroscler Thromb · 2025 Jul · PMID 40350320 · Full text
Digital health innovations (DHI) in medicine have led to remarkable progress in stroke prevention and management worldwide. For example, education regarding the knowledge and awareness of stroke, risk scores for stroke i...
Digital health innovations (DHI) in medicine have led to remarkable progress in stroke prevention and management worldwide. For example, education regarding the knowledge and awareness of stroke, risk scores for stroke incidence, and wearable devices have been used for primary prevention. Automatic telemedicine and diagnostic imaging have been introduced for the treatment of acute stroke. Rehabilitation using robot-assisted training, virtual reality systems, and other applications has been attempted. Information sharing using the DHI may be expected in secondary prevention. Although these DHI technologies likely assist in stroke prevention and management, their usage remains insufficient, partly because of insufficient evidence. Here, we report the current status and problems associated with the effective and widespread use of DHI in Japan.
Hemostatic Activation Markers and Early Neurological Deterioration in Branch Atheromatous Disease-Related Stroke.
Hoshino T, Mizuno T, Arai S … +5 more , Hosoya M, Ishizuka K, Higuchi E, Toi S, Todo K
J Atheroscler Thromb · 2025 Nov · PMID 40350319 · Full text
AIMS: Branch atheromatous disease (BAD)-related stroke, caused by atherosclerotic occlusion at the origin of a deep penetrating artery, are prone to early neurological deterioration (END). This study aimed to assess the...
AIMS: Branch atheromatous disease (BAD)-related stroke, caused by atherosclerotic occlusion at the origin of a deep penetrating artery, are prone to early neurological deterioration (END). This study aimed to assess the association between hemostatic activation markers and occurrence of END in patients with BAD-related stroke. METHODS: This prospective observational study included 88 patients with BAD-related stroke within 7 days of onset. On admission, plasma beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), and D-dimer levels were measured. END was defined as an increase of ≥ 2 points in the total National Institutes of Health Stroke Scale (NIHSS) score or ≥ 1 point in the motor items of the NIHSS within 7 days of admission. RESULTS: Of the 88 patients, 34 (38.6%) experienced END. Mean beta-TG (158 ng/mL vs. 102 ng/mL; P = 0.021), PF4 (61 ng/mL vs. 35 ng/mL; P = 0.024), and D-dimer (2.0 µg/mL vs. 1.2 µg/mL; P = 0.037) levels were significantly higher in patients with END than in those without END. Multivariate analysis revealed that beta-TG and PF4 levels were independently associated with the occurrence of END, with an adjusted odds ratio per 10 ng/mL increase (95% confidence interval) of 1.09 (1.01-1.20) and 1.21 (1.02-1.49), respectively. In contrast, D-dimer levels were not independent predictors. The optimal cutoff values for predicting END were 130 and 55 ng/mL for beta-TG and PF4, respectively. CONCLUSIONS: Elevated beta-TG and PF4 levels were independent predictors of END in patients with BAD-related stroke. Hence, the measurement of these platelet activation markers helps improve the risk assessment of BAD-related stroke and may provide management implications.
Comparative Effectiveness and Safety of Moderate-Intensity Pravastatin Versus Atorvastatin in Patients with Dyslipidemia: A Retrospective Cohort Study Using a Common Data Model of Multicenter Electronic Health Records in South Korea.
Chun SW, Kim HJ, Seo JA … +12 more , Chon S, Kim SE, Jung JH, Kim SS, Lee H, Shin S, Kim SH, Choi D, Park HK, Kim SK, Bae JH, Jeong IK
J Atheroscler Thromb · 2025 Oct · PMID 40350318 · Full text
AIM: To compare the effectiveness and safety of moderate-intensity pravastatin 40 mg/day and atorvastatin 10 mg/day in patients with dyslipidemia. METHODS: We conducted a retrospective cohort study using electronic healt...
AIM: To compare the effectiveness and safety of moderate-intensity pravastatin 40 mg/day and atorvastatin 10 mg/day in patients with dyslipidemia. METHODS: We conducted a retrospective cohort study using electronic health records of 19 million patients across 14 secondary/tertiary hospitals, standardized to a Common Data Model. New users of pravastatin (40 mg/day) and atorvastatin (10 mg/day) were identified. Six distinct cohorts were used to assess the comparative effectiveness in preventing major adverse cardiovascular events (MACE) and the risks of new-onset diabetes mellitus (NODM), myalgia or rhabdomyolysis, and hepatotoxicity (measured by aspartate aminotransferase [AST]/alanine aminotransferase [ALT]). Propensity score matching (PSM) was applied to each cohort for effectiveness and safety analyses, followed by a meta-analysis of hospital-specific results. RESULTS: After PSM, patients were equally assigned to the pravastatin and atorvastatin groups for primary (n = 2,688/group) and secondary MACE prevention (n = 1,258/group) and to assess the risk of NODM (n = 2,391/group), new-onset myalgia or rhabdomyolysis (n = 11,799/group), and hepatotoxicity (AST, n = 4,034/group; ALT, n = 3,655/group). No significant differences were observed in the hazard ratios (HRs) for primary (HR = 0.84; 95% CI, 0.59-1.20) and secondary MACE prevention (HR = 0.89; 95% CI, 0.68-1.16). Similarly, no significant difference was observed in the risk of NODM (HR, 0.99; 95% CI, 0.79-1.23). The risk of new-onset myalgia/rhabdomyolysis (HR = 0.82, 95% CI, 0.69-0.96) and the incidence of abnormal elevations in AST levels (2.35% vs. 3.37%, p＜0.05) were significantly lower in the pravastatin group. CONCLUSION: Moderate-intensity pravastatin (40 mg/day) showed comparable effectiveness to moderate-intensity atorvastatin (10 mg/day) in preventing MACE with a more favorable safety profile.
L-Shaped Association of 24-Hour Urine Output with 3-Month and 1-Year All-Cause Mortality in Patients with Acute Pulmonary Embolism: A Retrospective Cohort Study.
Ding CW, Chen YH, Xu YH … +6 more , Huang SS, Ding D, Zhang JX, Mao YM, Yuan YD, Qiu JY
J Atheroscler Thromb · 2025 Oct · PMID 40335309 · Full text
AIM: To explore the prognostic value of the first 24-h urine output (UO) after admission in patients with acute pulmonary embolism (APE) in the intensive-care unit (ICU) for short- and long-term all-cause mortality risk....
AIM: To explore the prognostic value of the first 24-h urine output (UO) after admission in patients with acute pulmonary embolism (APE) in the intensive-care unit (ICU) for short- and long-term all-cause mortality risk. METHODS: This retrospective cohort study used the MIMIC-IV database. Patients with APE were divided into 4 teams (T1-T4) by their first 24-h UO after admission: T1 (UO ≤ 400 ml), T2 (400＜UO ≤ 800 ml ), T3 (800＜UO ≤ 2500 ml), and T4 (UO＞2500 ml). The primary endpoints were the three-month and one-year all-cause mortality rates. The relationship between UO and mortality was assessed using Kaplan-Meier survival curves and Cox proportional hazards models. RESULTS: This study included 2012 patients with APE, of whom 50.75% were female. Compared to the T3 group, patients in the T1 and T2 groups had higher all-cause mortality rates. Kaplan-Meier survival curves showed that patients in the T1 and T2 groups had a higher risk of death, while those in the T4 group seemed to have a lower risk of death (P＜0.001). The results remained stable in all three adjusted models and subgroup analyses. A restricted cubic spline analysis (RCS) revealed that the risk of all-cause mortality gradually decreased with an increase in UO, showing an "L"-shaped relationship. A UO of ＜1283 ml increased the risk of death in patients. Subgroup analysis indicated that the first 24-h UO was associated with 3-month and 1-year all-cause mortality rates in most subgroups of patients. CONCLUSIONS: The first 24-h UO after admission is an important indicator for the prognosis of APE patients. A lower 24-h UO is strongly related to a higher risk of short-term and long-term all-cause mortality in ICU patients with APE.
Endovascular Therapy for Non-Acute Intracranial Atherosclerotic Occlusion: A Feasible Treatment Modality, but is it Beneficial?
Kitano T, Todo K
J Atheroscler Thromb · 2025 Oct · PMID 40254423 · Full text
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The Incremental Prognostic Value of Incorporating the Triglyceride-Glucose Index into the Traditional Cardiovascular Risk Factors for the Long-term Prognosis in Ischemic Cardiomyopathy Patients with HFpEF following Coronary Artery Bypass Grafting: A Multicenter Cohort Study.
Ruan H, Duan S, He L … +7 more , Wang Y, Yao Z, Pan L, Yin W, Yang Y, Liu J, Wang J
J Atheroscler Thromb · 2025 Oct · PMID 40222904 · Full text
AIM: The triglyceride-glucose (TyG) index, a biomarker commonly used to evaluate metabolic health status, can predict unfavorable outcomes. Thus, we aimed to explore evidence regarding the prognostic value of the TyG ind...
AIM: The triglyceride-glucose (TyG) index, a biomarker commonly used to evaluate metabolic health status, can predict unfavorable outcomes. Thus, we aimed to explore evidence regarding the prognostic value of the TyG index in patients with ischemic cardiomyopathy and heart failure with preserved ejection fraction (HFpEF). METHODS: We enrolled 277 consecutive participants with new-onset ischemic cardiomyopathy and HFpEF who underwent coronary artery bypass grafting (CABG). The primary study endpoint was major adverse cardiovascular events (MACEs), defined as cardiac death, acute myocardial infarction, graft failure, and stroke. RESULTS: During a median follow-up of 43.34 months, 70 patients (25.1%) experienced MACEs. A multivariable Cox regression analysis identified the TyG index as an independent risk factor for MACEs, with a higher baseline TyG index associated with greater risk after adjusting for confounding factors. A restricted cubic spline showed that the TyG index had a linear relationship across the range. The optimal cut-off value of 9.167 for the TyG index demonstrated a sensitivity of 70% and specificity of 84.1%, with an AUC of 0.820 (p＜0.001, 95% CI: 0.762-0.878), thus effectively stratifying participants into lower TyG index (TyG ＜9.167, n = 182) and higher TyG index groups (TyG ≥ 9.167, n = 95), while subgroup analyses confirmed a robust association with MACEs across various populations. Furthermore, the time-dependent area under the curve, calibration curve, and decision curve analyses demonstrated that incorporating the TyG index into the traditional cardiovascular risk factor model significantly enhanced the prediction of MACE risk. Additionally, significant net reclassification improvement (0.335, 95% confidence interval [CI]: 0.136-0.518, p＜0.05) and integrated discrimination improvement (0.178, 95%CI: 0.089-0.270, p＜0.001) were also observed. CONCLUSION: The TyG index is a reliable prognostic indicator for MACEs after CABG in patients with ischemic cardiomyopathy and HFpEF and it serves as a valuable complement to traditional cardiovascular risk factors by providing metabolic-related insights.
Association of Obesity and Metabolic Health Status with Cerebral Small-Vessel Disease in Stroke-Free Individuals.
Ishida A, Nakanishi R, Miyagi T … +5 more , Sakima H, Nakamura K, Yamazato M, Ohya Y, Kusunose K
J Atheroscler Thromb · 2025 Oct · PMID 40204498 · Full text
AIM: We investigated the association of obesity and metabolic health status with cerebral small-vessel disease (SVD), a predictor of stroke, in stroke-free participants during brain health checkups. METHODS: An observati...
AIM: We investigated the association of obesity and metabolic health status with cerebral small-vessel disease (SVD), a predictor of stroke, in stroke-free participants during brain health checkups. METHODS: An observational cross-sectional study was conducted on 6,088 stroke-free participants who underwent brain magnetic resonance imaging (MRI). Abdominal obesity was defined as a waist circumference ≥ 90 cm for men and ≥ 80 cm for women. A metabolically healthy status was defined as having none of the three components of metabolic syndrome, except abdominal obesity. The total SVD scores were derived from four MRI markers: silent lacunar infarcts, cerebral microbleeds, moderate-to-severe white-matter hyperintensity, and enlarged perivascular spaces. RESULTS: The mean age of participants was 55±12 years old. Obesity was prevalent in 50% of the patients. The prevalence of a total SVD score ≥ 2 (moderate-to-severe SVD) was 348 (6%), which was elevated in metabolically unhealthy individuals regardless of obesity status. Compared with the metabolically healthy non-obese group, the metabolically unhealthy non-obese (odds ratio [OR] 2.08, [95% confidence interval {CI}, 1.33-3.27]) and metabolically unhealthy obese (OR 2.62, [95% CI, 1.70-4.04]) groups had a higher multivariable-adjusted risk for a total SVD score ≥ 2. Similar results were obtained for obesity defined as a body mass index ≥ 25 kg/m instead of abdominal obesity. CONCLUSIONS: Abdominal and general obesity alone were not associated with high total SVD scores in stroke-free individuals. Metabolically unhealthy status, especially high blood pressure and hyperglycemia, are significant risk factors for moderate-to-severe SVD.
Multilevel Factors Predict Medication Adherence and Efficacy within 12 Months in Patients Receiving PCSK9 Monoclonal Antibodies: The Findings from a Real-World Analysis in China.
Zheng X, Jin Y, Fan M … +2 more , Cui H, Zhu S
J Atheroscler Thromb · 2025 Nov · PMID 40189248 · Full text
AIMS: To investigate the predictors associated with inadequate adherence in patients receiving proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) in China and to assess the mean LDL-C leve...
AIMS: To investigate the predictors associated with inadequate adherence in patients receiving proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) in China and to assess the mean LDL-C levels and the percentage reduction of LDL-C. METHODS: Patients with at least one PCSK9-mAbs prescription filled between January 2021 and December 2022 were included in this study. The LDL-C levels before and after treatment initiation were assessed using medical records. Adherence to PCSK9-mAbs was assessed for up to 12 months after treatment initiation using the proportion of days covered. RESULTS: A total of 415 patients were enrolled. The medication adherence to PCSK9-mAbs after 12 months was 31.8%. A multivariate analysis revealed that better education (junior or high school adjusted OR 2.7 and college or higher adjusted OR 5.2) and LDL-C ＜1.4 mmol/L at 3 months after starting PCSK9-mAbs (adjusted OR 3.0) were consistent predictors of adherence. At 12 months, LDL-C was 1.5mmol/L in the adherence group (mean [SD] decrease, 44.5% [26.5%]) and 1.9 mmol/L in the poor adherence group (mean [SD] decrease, 31.0% [32.7%]), with a group difference of 0.42 mmol/L (group difference in decrease, 13.48%). CONCLUSIONS: A better education and LDL-C ＜1.4 mmol/L at 3 months after starting treatment with PCSK9-mAbs were consistent predictors of adherence. In addition, the treatment effect declined more significantly in the poor adherence group over time.
Sex Differences Regarding the Risk of Incident Venous Thromboembolism in Hospitalized Patients with an Acute Exacerbation of Chronic Obstructive Pulmonary Disease.
Pu J, Yi Q, Luo Y … +16 more , Wei H, Ge H, Liu H, Zhang J, Li X, Pan P, Xie X, Yi M, Cheng L, Zhou H, Zhang J, Peng L, Zeng J, Chen X, Zhou H, MAGNET AECOPD Registry Investigators
J Atheroscler Thromb · 2025 Oct · PMID 40175131 · Full text
AIMS: Sex differences in the risk of venous thromboembolism (VTE) among patients with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) have so far only been sparsely described. This study aimed to...
AIMS: Sex differences in the risk of venous thromboembolism (VTE) among patients with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) have so far only been sparsely described. This study aimed to investigate the differences in the risk of VTE events between male and female AECOPD patients and to determine whether any specific risk factors for VTE vary between the sexes. METHODS: We prospectively enrolled patients hospitalized for AECOPD from ten medical centers in China. The primary outcome was the occurrence of VTE. Univariate and multivariate logistic regression analyses were conducted to determine whether sex was an independent risk factor for VTE and also to identify any sex-specific risk factors. RESULTS: In total, 13,664 patients were included. VTE occurred in 5.5% of females and 3.3% of males (P＜0.001). A multivariate logistic regression analysis identified female sex as an independent risk factor for VTE in patients with AECOPD (odds ratio [OR] = 1.439, 95% confidence interval [CI] = 1.177-1.759, P＜0.001) after adjusting for confounding factors. Common risk factors for both sexes included age, chronic heart failure, severe lung disease, stroke, a recent surgical history, a history of VTE, and respiratory failure. Additional risk factors unique to males were sepsis (OR = 9.514, 95% CI = 4.513-20.056, P＜0.001), varicose veins (OR = 6.170, 95% CI = 3.237-11.763, P＜0.001), and rheumatological disorders (OR = 2.677, 95% CI = 1.184-6.052, P = 0.018). No sex-specific risk factors were identified for females. CONCLUSION: Female sex was found to be an independent risk factor for VTE and some sex-specific risk factors exist among inpatients with AECOPD. These findings highlight the importance of considering sex and sex-related factors when assessing the VTE risk in AECOPD patients.
Lipoprotein(a) Levels and the Risk of Coronary Heart Disease and Stroke: The Suita Study.
Arafa A, Kato Y, Kokubo Y … +5 more , Khairan P, Matsumoto C, M Nakao Y, Kataoka Y, Harada-Shiba M
J Atheroscler Thromb · 2025 Sep · PMID 40159304 · Full text
AIMS: Lipoprotein(a) (Lp[a]) exhibits atherogenic and thrombogenic properties. We investigated the association between Lp(a) levels and the risk of coronary heart disease (CHD) and stroke. METHODS: We used data from 5138...
AIMS: Lipoprotein(a) (Lp[a]) exhibits atherogenic and thrombogenic properties. We investigated the association between Lp(a) levels and the risk of coronary heart disease (CHD) and stroke. METHODS: We used data from 5138 people ≥ 30 years old registered in the Suita Study, a Japanese population-based prospective cohort study. All participants were initially free from CHD or stroke. Cox proportional hazard models were applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CHD and stroke among participants with elevated Lp(a) levels. RESULTS: At baseline, only 17.0% of participants had Lp(a) levels ≥ 30 mg/dL. Within the median follow-up period of 11.7 years, 164 CHD and 234 stroke events were detected. In the multivariable-adjusted regression model, Lp(a) ≥ 30 mg/dL was associated with an increased risk of CHD (HR, 1.52 [95% CI, 1.05-2.21]). Every 10-ml/dL increment in Lp(a) level was associated with a 7.9% increase in CHD risk. The association with CHD did not change significantly after adjusting for total cholesterol level or lipid-lowering drugs. In contrast, increased Lp(a) levels were not associated with stroke risk or any subtype. CONCLUSIONS: Lp(a) ≥ 30 mg/dL was associated with an increased risk of CHD in the Japanese population.
Cholesterol Uptake Capacity as a Prognostic Marker of Cardiovascular Events for Patients with Coronary Artery Disease.
Yoshikawa Y, Toh R, Murakami K … +9 more , Harada A, Kim J, Kobayashi Y, Miwa K, Nagao M, Ishida T, Hirata KI, Takegami M, Nishimura K
J Atheroscler Thromb · 2025 Sep · PMID 40159248 · Full text
AIM: Cholesterol uptake capacity (CUC) is a functional assessment of high-density lipoprotein (HDL) and has drawn attention for the risk stratification of atherosclerotic cardiovascular disease (ASCVD). This study evalua...
AIM: Cholesterol uptake capacity (CUC) is a functional assessment of high-density lipoprotein (HDL) and has drawn attention for the risk stratification of atherosclerotic cardiovascular disease (ASCVD). This study evaluated the usefulness of HDL-CUC as a predictive marker for long-term ASCVD events in patients with coronary artery disease (CAD). METHODS: This retrospective observational study included 503 patients with CAD who underwent coronary revascularization. Blood was sampled from the participants within three months before or after index revascularization. The CUC was assayed using a previously reported automated system. The study population was divided into three groups according to the tertiles of CUC levels. The primary outcome was ASCVD events, which were defined as a composite of all-cause death, acute myocardial infarction, stroke, and peripheral artery disease. RESULTS: A total of 29 events were observed during the follow-up (median 2.8 years). The risk of the primary outcome in the low-CUC group was significantly higher than that in the high-CUC group (3-year incidence: low CUC 8.8% vs. high CUC 4.0%; log-rank p = 0.046). After adjusting for age and sex, the risk in the low-CUC group relative to that in the high-CUC group remained significantly high (hazard ratio 3.17, 95% confidence interval 1.05-9.54, p = 0.040). CONCLUSION: Low CUC in patients with CAD were associated with a higher risk of ASCVD events after coronary revascularization than high CUC levels. The assessment of HDL functionality measured by CUC would be useful for the risk prediction of ASCVD after coronary revascularization.
Sex-Specific Association between HO-1 (GT)n Promoter Polymorphism and Large-Artery Atherosclerosis Stroke.
Li J, Chen J, Wen J … +4 more , Cheng K, Fu X, Li S, Shi Z
J Atheroscler Thromb · 2025 Sep · PMID 40159225 · Full text
AIMS: Oxidative stress is a central factor in the pathogenesis of atherosclerosis and potentially exhibits sexual dimorphism. The induction of heme oxygenase-1 (HO-1) serves as a crucial mechanism against reactive oxygen...
AIMS: Oxidative stress is a central factor in the pathogenesis of atherosclerosis and potentially exhibits sexual dimorphism. The induction of heme oxygenase-1 (HO-1) serves as a crucial mechanism against reactive oxygen species toxicity in the vascular wall, and this induction is regulated by the promoter (GT)n repeat length. We aim to investigate whether or not HO-1 gene (GT)n polymorphism is associated with the occurrence of large-artery atherosclerotic (LAA) stroke. METHODS: We consecutively recruited stroke patients, with a control group comprising age- and sex-matched non-stroke individuals. HO-1 (GT)n genotypes were determined using DNA extracted from the peripheral leukocytes. HO-1 (GT)n polymorphism was classified as short [S, ≤ 24 (GT)n], medium [M, 25 ≤ (GT)n ＜31], or long [L, 31 ≤ (GT)n]. Clinical data were collected, and stroke patients were categorized into LAA and non-LAA groups according to the TOAST classification. A multivariable logistic regression analysis was conducted to evaluate the association between HO-1 (GT)n variants and LAA occurrence stratified by sex. RESULTS: There was no significant difference in the distribution of HO-1 (GT)n genotypes between the stroke and non-stroke populations. However, the proportion of S/S genotype was significantly lower in the LAA stroke patients than in the non-LAA stroke patients (7.08% vs. 21.78%, p＜0.001). A multivariable logistic regression analysis indicated that non-SS genotypes were associated with a significantly increased risk of LAA compared to the S/S genotype patients (odds ratio [OR] 3.35, 95% confidence interval [CI] 1.98-5.67, p＜0.001). After stratification by sex, the protective effect of the HO-1 (GT)n S/S genotype was highly significant in men (OR 5.50, 95% CI 2.67-11.34, p＜0.001), whereas the association was not significant in women (OR 1.60, 95% CI 0.75-3.34, p = 0.228). CONCLUSION: Short (GT)n variants in HO-1 may confer significant protection against LAA stroke in men but not in women.
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