Shirouzu T, Koga JI, Orkhonselenge N
… +3 more, Nagata Y, Miyamoto T, Kataoka M
J Atheroscler Thromb
· 2026 May · PMID 41621902
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AIM: Chronic kidney disease (CKD) is linked to accelerated vascular remodeling, characterized by medial thickening and fibrosis; however, the molecular mechanisms driving this process remain unclear. METHODS: We investig...AIM: Chronic kidney disease (CKD) is linked to accelerated vascular remodeling, characterized by medial thickening and fibrosis; however, the molecular mechanisms driving this process remain unclear. METHODS: We investigated the role of toll-like receptor 4 (TLR4) in CKD-associated vascular remodeling using a 5/6 nephrectomy mouse model. TLR4 signaling was selectively inhibited by the long-term administration of TAK-242, a small-molecule-specific inhibitor of TLR4. RESULTS: TLR4 blockade decreased aortic medial thickening and perivascular fibrosis independent of blood pressure. Immunostaining revealed that blockade of TLR4 decreased Mac-3-positive macrophage accumulation and Ki-67-positive proliferating cells in the aorta. The mRNA expression of IL-6 was suppressed in aortas treated with TAK-242. Disulfide HMGB1 induced the expression of IL-6 in macrophages. Serum from CKD mice induced the expression of IL-6 in RAW264.7 cells and promoted in vitro vascular smooth muscle cell growth, both of which were attenuated with serum from TAK-242-treated CKD mice. CONCLUSION: These findings suggest that TLR4-mediated sterile inflammation may contribute to vascular remodeling in CKD and that modulation of TLR4 signaling could be explored as a potential therapeutic strategy to mitigate cardiovascular complications in CKD patients.
Fujioka Y, Tanaka SI, Tsujino T
… +2 more, Ishida T, Hirata KI
J Atheroscler Thromb
· 2026 May · PMID 41621901
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AIM: Apolipoprotein CIII (ApoC-III) is a lipid-associated protein crucial for the lipid metabolism. Recent studies have shown that ApoC-III also plays a role in vascular dysfunction and the development of coronary heart...AIM: Apolipoprotein CIII (ApoC-III) is a lipid-associated protein crucial for the lipid metabolism. Recent studies have shown that ApoC-III also plays a role in vascular dysfunction and the development of coronary heart disease (CHD). This study examined the hypothesis that the serum ApoC-III concentration is associated with the future risk of CHD in a general Japanese population. METHODS: We prospectively studied 1,676 individuals (1,005 women, 671 men; mean age 57.1 years) in a rural community in Japan. In the 1993 baseline survey, anthropometric examinations, current smoking status, blood pressure, and serum concentrations of lipids and apolipoproteins were assessed. During the follow-up period of 10.9 years (interquartile range 10.8 - 11.1), 48 participants developed CHD, including 18 fatal and non-fatal myocardial infarction patients and 30 sudden death cases. RESULTS: In the age- and sex-adjusted analysis, we did not find any association between the baseline serum ApoC-III concentration and the risk of CHD and sudden death (HR 2.11, CI 0.88 - 5.03, P = 0.094). However, in a multivariable analysis adjusted for age, sex, the presence of hypertension, presence of diabetes mellitus, current smoking status, total cholesterol, high-density lipoprotein cholesterol, and triglycerides, serum ApoC-III concentration was significantly associated with the risk of CHD and sudden death (HR 3.59, CI 1.05 - 12.3, P = 0.041). CONCLUSION: Serum ApoC-III concentration was independently associated with the risk of CHD and sudden death in a general Japanese population.
Aoki S, Yamagishi K, Muraki I
… +7 more, Kihara T, Ishihara J, Iso H, Yasuda N, Inoue M, Tsugane S, Sawada N
J Atheroscler Thromb
· 2026 May · PMID 41605675
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AIM: We evaluated the association between the dietary fiber intake and the risk of dementia. METHODS: We performed a prospective study within the Japan Public Health Center-based Prospective Study involving 41,467 Japane...AIM: We evaluated the association between the dietary fiber intake and the risk of dementia. METHODS: We performed a prospective study within the Japan Public Health Center-based Prospective Study involving 41,467 Japanese individuals aged 45-74 years between 1995-1998. Information regarding food intake was collected using a food frequency questionnaire. Disabling dementia was detected using the National Long-term Insurance System between 2006 and 2016. We calculated the hazard ratios and 95% confidence intervals for disabling dementia according to quartiles of soluble, insoluble, and total fiber intake and dietary fiber intake from food groups (cereals, potatoes and starches, soybeans, vegetables, and fruits) intake by sex. RESULTS: During an average follow-up period of 9.4, 4910 cases of disabling dementia were documented. The total fiber intake was inversely associated with the risk of disabling dementia in both men and women. The multivariable hazard ratios (95% confidence intervals: CIs) of disabling dementia for the highest versus lowest quartiles of total fiber intake were 0.82 (0.73-0.91) in women (p for trend ＜0.001) and 0.86 (0.74-1.00) in men (p for trend = 0.03). Similar inverse associations between soluble and insoluble fiber intake and the risk of disabling dementia were observed. The dietary fiber intake from cereals, potatoes, starches, vegetables, and fruits, but not soybeans, was inversely associated with the risk of disabling dementia, with some variation by sex. CONCLUSIONS: The dietary intake of total, soluble, and insoluble fiber was associated with a lower risk of disabling dementia. The associations did not vary materially according to the food source of the fiber.
J Atheroscler Thromb
· 2026 May · PMID 41565295
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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 i...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.
Nagakura Y, Shoji T, Fukumoto S
… +8 more, Uedono H, Nakatani S, Mori K, Nagata Y, Imanishi Y, Morioka T, Watanabe T, Emoto M
J Atheroscler Thromb
· 2026 May · PMID 41548921
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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 second...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 m (β = -0.418, P = 0.013), whereas it was not in the subgroup with an eGFR ≥ 60 mL/min/1.73 m. 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.
Orkhonselenge N, Koga JI, Kakumori D
… +7 more, Kondo Y, Hidaka K, Shirouzu T, Ueno H, Yagita H, Nishimura Y, Kataoka M
J Atheroscler Thromb
· 2026 Jun · PMID 41526223
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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...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.
Morimoto N, Yamamoto Y, Toragai R
… +4 more, Kuroshima T, Watanabe Y, Ito Y, Ai M
J Atheroscler Thromb
· 2026 Apr · PMID 41485991
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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 betwe...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/1.73m), or those using lipid-lowering medication were excluded. The outcome was GHF, defined as ＞95 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.
Fujioka S, Shishikura D, Sakaguchi K
… +5 more, Kusumoto H, Michikura M, Kanzaki Y, Harada-Shiba M, Morita H
J Atheroscler Thromb
· 2026 May · PMID 41443833
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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, it...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.
Okuda N, Nakamura K, Watanabe M
… +10 more, Kamide K, Yoshita K, Torii S, Miura K, Higashiyama A, Tanno K, Yonekura Y, Nagahata T, Kuribayashi T, Okayama A
J Atheroscler Thromb
· 2026 May · PMID 41443831
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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) an...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/m): 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.
J Atheroscler Thromb
· 2026 Apr · PMID 41423245
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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...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.
Tanaka A, Oyama K, Yakushiji Y
… +19 more, Natsuaki M, Mizuno A, Saito Y, Matsumoto S, Yamagami H, Kunieda T, Shibata S, Nishimoto M, Ayuzawa N, Shimabukuro M, Tsuchiya K, Okazaki H, Nomura A, Kaneko H, Kohsaka S, Yoshida M, Harada-Shiba M, Shimano H, Node K
J Atheroscler Thromb
· 2026 Mar · PMID 41423223
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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 ASC...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.
Kunimura A, Tsukamoto N, Suzuki W
… +5 more, Kuno S, Naito K, Ando H, Suzuki Y, Amano T
J Atheroscler Thromb
· 2026 Apr · PMID 41423222
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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...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.
J Atheroscler Thromb
· 2026 Mar · PMID 41407356
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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, cardiovas...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.
Keremu M, Zhou ZX, Li XL
… +8 more, Li XM, Liu F, Wulamu A, Ding SY, Li X, Wang YN, Adi D, Ma YT
J Atheroscler Thromb
· 2026 Apr · PMID 41371706
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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...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 = 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.
Niwa Y, Naruse H, Kawai H
… +16 more, Sakaguchi E, Ishihara Y, Hattori H, Uehara K, Ito M, Yamada S, Yamada A, Muramatsu T, Kitagawa F, Takahashi H, Ishii J, Sarai M, Yanase M, Ozaki Y, Saito K, Izawa H
J Atheroscler Thromb
· 2026 May · PMID 41371705
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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 in...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.