Journal of atherosclerosis and thrombosis最新文献

{"title":"The PREVENT Risk Equations and Cardiovascular Prevention in East Asia.","authors":"Mitsuaki Sawano, Kentaro Ejiri, Yuichiro Mori, Hokyou Lee, Aya Hirata, Kosuke Inoue, Takeshi Kitai, Shun Kohsaka, Hyeon Chang Kim, Kunihiro Matsushita","doi":"10.5551/jat.RV22056","DOIUrl":"10.5551/jat.RV22056","url":null,"abstract":"<p><p>Cardiovascular disease remains a leading cause of morbidity and mortality in East Asia, although its epidemiological profile differs substantially from that of Western populations. As East Asia experiences rapid increases in chronic kidney disease, diabetes, multimorbidity, and heart failure driven by population aging, accurate cardiovascular risk prediction has become increasingly important for the risk-stratified prevention of these diseases. Traditional risk prediction models, including the Framingham Risk Score, Pooled Cohort Equations, and SCORE, were derived largely from Western populations and often overestimated the risk in East Asian cohorts without recalibration. In 2025, the American Heart Association introduced the PREVENT equations to estimate 10-year and 30-year risks of total cardiovascular disease, atherosclerotic cardiovascular disease, and heart failure within an integrated cardiovascular-kidney-metabolic framework. Given the growing globalization of cardiovascular prevention and international clinical research, understanding whether PREVENT performs well in East Asian populations has important implications for the clinical implementation and harmonization of risk assessment frameworks. This review summarizes the evolution of cardiovascular risk prediction, key innovations of PREVENT, and emerging validation evidence from East Asia. Early studies from Korea and China suggest the reasonable transportability of these approaches. However, evidence from Japan remains limited, and further validation and recalibration are warranted. We also discuss the challenges related to heart failure prediction, add-on variables, electronic health record data infrastructure, and AI-assisted risk assessment.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":"1232-1245"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13642998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver Dysfunction Assessed by Albumin - Bilirubin (ALBI) Score is Associated with Disturbed Cholesterol Profiles and Reduced Survival in Patients with Chronic Limb-Threatening Ischemia.","authors":"Kentaro Inoue, Shinichiro Yoshino, Yutaka Matsubara, Tadashi Furuyama, Toshihiro Onohara","doi":"10.5551/jat.66098","DOIUrl":"10.5551/jat.66098","url":null,"abstract":"<p><strong>Aims: </strong>Liver dysfunction may affect chronic limb-threatening ischemia (CLTI) outcomes, but its impact on survival and lipid profiles is unclear. To assess the association of liver dysfunction using the Albumin-Bilirubin (ALBI) score, with survival, liver fibrosis, and cholesterol in CLTI patients.</p><p><strong>Methods: </strong>We retrospectively analyzed single-center data of CLTI patients with below-knee lesions between 2008-2018. ALBI scores were calculated from serum albumin and total bilirubin. Optimal cutoff for 3-year overall survival (OS) was determined by receiver operating characteristic (ROC) analysis, dividing patients into high and low ALBI groups. Patient characteristics, cholesterol, and liver fibrosis (FIB-4 index) were compared, with primary endpoint being 3-year OS.</p><p><strong>Results: </strong>Among 263 patients, high ALBI patients (≥ -2.36, n = 135) were older (80 vs. 72 years), included fewer males (55% vs. 71%), had higher prevalence of bed-ridden status (44% vs. 2%) and heart failure (25% vs. 8%; all P＜0.01). They had higher FIB-4 index (2.49 vs. 1.76), lower total cholesterol (147 vs. 173 mg/dL), HDL-C (43 vs. 56 mg/dL), LDL-C (83 vs. 108 mg/dL), and higher LDL-C/HDL-C ratio (2.57 vs. 2.20; P＜0.01). Three-year OS was lower in high ALBI group (36% vs. 57%; P＜0.01) and remained lower after propensity matching (43% vs. 55%; P = 0.04). Multivariate analysis identified low body mass index (BMI), heart failure, high ALBI score and high FIB-4 index (≥ 1.3) and low LDL-C (＜100 mg/dL) as predictors of poor OS.</p><p><strong>Conclusions: </strong>High ALBI scores in CLTI patients links to liver fibrosis, disturbed lipid profiles, and reduced survival.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":"1272-1284"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood Lipid Levels and Intraocular Pressure in a Japanese Population: the JPHC-NEXT Eye Study.","authors":"Maho Sato, Akiko Hanyuda, Kazumasa Yamagishi, Kenya Yuki, Miki Uchino, Yoko Ozawa, Mariko Sasaki, Kazuo Tsubota, Kazuno Negishi, Norie Sawada, Shoichiro Tsugane, Hiroyasu Iso","doi":"10.5551/jat.66081","DOIUrl":"10.5551/jat.66081","url":null,"abstract":"<p><strong>Aim: </strong>Although growing epidemiological evidence suggests that metabolic risk factors may influence the intraocular pressure (IOP), the specific effects of individual lipid components on IOP regulation remain unclear. In this study, we examined the associations between the serum lipid profiles, individually and in combination, and IOP among 6,786 ophthalmologically healthy adults aged ≥ 40 years residing in Chikusei City, Japan.</p><p><strong>Methods: </strong>Participants with a history of glaucoma, the use of IOP-lowering medications, or previous ocular surgery were excluded. Comprehensive systemic and ophthalmological evaluations, including blood tests and measurements of IOP and central corneal thickness, were performed. An analysis of covariance was used to assess the associations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels with IOP.</p><p><strong>Results: </strong>After adjusting for several potential confounders, higher LDL-C, HDL-C, and TG levels were significantly associated with increased IOP. Specifically, every 10 mg/dL increase in LDL-C, HDL-C, and TG corresponded to IOP increases of 0.04±0.011 mmHg, 0.13±0.026 mmHg, and 0.02±0.006 mmHg, respectively. Notably, the positive association between LDL-C and IOP was more pronounced in individuals aged ≥ 65 years than in those aged ＜65 years (P for interaction = 0.009).</p><p><strong>Conclusion: </strong>These findings suggest that lipid homeostasis may contribute to IOP regulation, particularly in older populations.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":"1261-1271"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148156718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HDL - Immune Cell Crosstalk in Autoimmune Diseases and its Role in Accelerated Atherosclerosis.","authors":"Yasuhiro Endo, Kei Sasaki, Masatsune Ogura, Katsunori Ikewaki","doi":"10.5551/jat.RV22061","DOIUrl":"https://doi.org/10.5551/jat.RV22061","url":null,"abstract":"<p><p>Despite remarkable advances in lipid-lowering therapies, atherosclerotic cardiovascular disease (ASCVD) continues to be a major cause of morbidity and mortality worldwide, and chronic inflammation has been shown to contribute to residual cardiovascular risk.Autoimmune diseases are increasingly recognized as being associated with an increased risk of ASCVD that cannot be explained by traditional cardiovascular risk factors, such as dyslipidemia and hypertension.High-density lipoprotein (HDL) is an anti-atherogenic lipoprotein involved in reverse cholesterol transport. Recent studies have demonstrated that HDL possesses anti-inflammatory and immunomodulatory properties. In autoimmune diseases, both HDL dysfunction and immune dysregulation have been reported, including an impaired cholesterol efflux capacity (CEC), reduced paraoxonase-1 activity, alterations in HDL particle composition, and serum amyloid A enrichment. These findings suggest that crosstalk between HDL and immune cells may play an important role in atherosclerosis progression.Accordingly, this review summarizes the current evidence on HDL-immune cell interactions, discusses how HDL dysfunction contributes to accelerated atherosclerosis in autoimmune diseases, and highlights the therapeutic potential of targeting the HDL function to reduce residual cardiovascular risk or ASCVD risk.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harmonization of Lipoprotein(a) Immunoassays with the IFCC- Endorsed Reference Measurement Procedure Validated in Patient Samples and Multiple Routine testing as A Second Step Towards Apolipoprotein Standardization.","authors":"Keita Yamashita, Mitsuru Wakita, Noriyasu Niizeki, Satomi Ito, Yui Ito, Asako Sato, Hitomi Miura, Hiroshi Yoshida, Takahiro Masaki, Kazuyuki Matsushita, Kenji Kawasaki, Takao Kimura, Kiyomi Nakajima, Masami Murakami, Masato Maekawa, Hubert W Vesper, Christa M Cobbaert, Takashi Miida","doi":"10.5551/jat.66345","DOIUrl":"https://doi.org/10.5551/jat.66345","url":null,"abstract":"<p><strong>Aim: </strong>Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular disease (CVD); however, the goal of resolving its measurement issues remains unachieved. Expanding on the \"first step\" by Miida et al., this study evaluated the feasibility of harmonizing Lp(a) measurements using an IFCC endorsed mass spectrometry-based reference measurement procedure (MS-RMP)-assigned serum panel across a broader range of reagents and CVD patient sample types.</p><p><strong>Methods: </strong>Eleven immunoassays were evaluated using 536 serum samples (including 416 patients with CVD). Mass-to-molar (nmol/L) conversion equations were derived using the IFCC-MS-RMP-assigned CDC serum panels. For high-concentration samples (170-600 nmol/L), the accuracy was validated through a direct comparison with isoform-insensitive MS-RMP and physiological saline test results.</p><p><strong>Results: </strong>All reagents showed a strong correlation (rs＞0.967) with the MS-RMP in the CDC panel. Inter-reagent differences in patient samples, up to 5.3-fold in mass units, were significantly reduced after molar conversion. High-concentration samples showed a good correlation (rs = 0.904) between MS-RMP and the current immunoassay (Roche), elucidating the bias characteristics relative to the isoform-independent reference method. Furthermore, the measurements were acceptable (within 5% error) up to 3-fold physiological saline, whereas reagent-specific variability increased at higher dilution ratios and in samples with extremely high analyte concentrations.</p><p><strong>Conclusion: </strong>Expanding on previous findings, the implementation of a serum panel assigned by the IFCC-MS-RMP significantly strengthens the harmonization of Lp(a) measurements. Precise validation using MS-RMP as a benchmark, even in the high-concentration range, provides a robust foundation for international standardization and the establishment of common clinical decision values.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipoprotein(a) in Japan: An Expert Consensus Statement.","authors":"Masayuki Yoshida, Masatsune Ogura, Hayato Tada, Tomoaki Yamada, Sayaka Funabashi, Yu Kataoka, Masahito Michikura, Hiroshi Yoshida, Mariko Harada-Shiba","doi":"10.5551/jat.66330","DOIUrl":"https://doi.org/10.5551/jat.66330","url":null,"abstract":"<p><p>Lipoprotein(a) [Lp(a)] is a genetically determined causal factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis (CAVS). Although international societies have issued various guidelines, Japan requires a framework that incorporates domestic epidemiology, clinical practice, and evolving laboratory standardization. Recent Japanese evidence-including the LEAP Study-confirms that while median Lp(a) levels in Japan are lower than in Western populations, individuals with elevated concentrations (particularly ≥ 125 nmol/L) face substantial incremental ASCVD and CAVS risk.This consensus provides Japan-specific recommendations for Lp(a) measurement, risk thresholds, interpretation, and management. We propose three pragmatic risk categories based on nmol/L: low (＜25 nmol/L), intermediate (≥ 25 to ＜125 nmol/L), and high (≥ 125 nmol/L). While standardized nmol/L reporting is not yet available in Japan, the clinical significance of standardization is increasingly recognized, and the adoption of International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)-aligned assays is expanding. Lp(a) should be measured at least once in adulthood, with an emphasis on high-risk groups, including familial hypercholesterolemia (FH), premature ASCVD families, and patients with recurrent cardiovascular events.Management focuses on aggressive low-density lipoprotein cholesterol (LDL-C) lowering and optimization of modifiable risk factors. Emerging Lp(a)-specific therapies, including pelacarsen, olpasiran, muvalaplin, and SLN360, demonstrate up to 80-95% reductions in Lp(a) and may redefine care once outcome trial data (e.g., HORIZON) become available.Finally, we outline the implementation priorities for Japan, emphasizing improved measurement access, laboratory harmonization, public and professional education, and the integration of Lp(a) into existing clinical pathways and research infrastructures. This consensus statement is intended to support clinicians, researchers, and policymakers in reducing the residual ASCVD risk attributable to Lp(a) in Japan.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum Lipoprotein(a) Levels in Japanese Children with Normal Low-density Lipoprotein Cholesterol.","authors":"Kazushige Dobashi, Yoshifusa Abe","doi":"10.5551/jat.66281","DOIUrl":"https://doi.org/10.5551/jat.66281","url":null,"abstract":"<p><strong>Aim: </strong>To determine the serum lipoprotein(a) (Lp(a)) levels in Japanese children with normal low-density lipoprotein cholesterol (LDL-C) levels.</p><p><strong>Methods: </strong>Data from 170 pediatric outpatients aged 0-17 years who underwent Lp(a) measurements were included. Among them, 146 children (64 boys) with LDL-C levels ＜140 mg/dL were analyzed. At the time of blood sampling, none of the participants had any physical symptoms, and routine laboratory examinations showed no abnormalities. The association between the Lp(a) levels and clinical parameters was evaluated.</p><p><strong>Results: </strong>The mean age of the children was 9.0 years, and 25 were obese. The serum Lp(a) concentrations ranged from 1 to 82.3 mg/dL and showed a right-skewed distribution. The median Lp(a) levels were 8.0 mg/dL (27.6 nmol/L), 7.5 mg/dL in boys, and 8.4 mg/dL in girls. The 95th percentile was 29.7 mg/dL (109.6 nmol/L). Lp(a) levels were not significantly correlated with age, overweight indices, thyroid hormones, or C-reactive protein. Among the lipid-related parameters, weak positive correlations were observed for total cholesterol and apolipoprotein B. Elevated Lp(a) levels were more prevalent in children with elevated LDL-C levels. However, among children with LDL-C ＜140 mg/dL, no statistically significant association was observed between LDL-C and Lp(a), and this association was further attenuated when LDL-C corrected for the contribution of Lp(a) was used. Similar findings were observed in the multivariable regression analyses.</p><p><strong>Conclusion: </strong>In children with LDL-C ＜140 mg/dL, the Lp(a) levels appear to be largely regulated independent of body size and LDL-C. The median Lp(a) was 8 mg/dL (≈30 nmol/L), and levels ≥ 30 mg/dL (≈110 nmol/L) were considered to be high.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expectations for Angiopoietin-like 3 Inhibitors Taking Broad Lipid-modifying Effects on the Comprehensive Control of Atherosclerotic Cardiovascular Disease Risk in Patients with Homozygous Familial Hypercholesterolemia.","authors":"Hiroshi Yoshida","doi":"10.5551/jat.ED314","DOIUrl":"https://doi.org/10.5551/jat.ED314","url":null,"abstract":"","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholesterol Metabolism Regulation by Native and Oxidized Low-Density Lipoprotein in a Liver Cell Line.","authors":"Nakyoung Kim, Toshihiro Sakurai, Himeno Sakuma, Akiko Sakurai, Nanao Murakami, Iku Sazaki, Shu-Ping Hui","doi":"10.5551/jat.66254","DOIUrl":"https://doi.org/10.5551/jat.66254","url":null,"abstract":"<p><strong>Aims: </strong>Metabolic dysfunction-associated steatohepatitis (MASLD) is a highly prevalent chronic liver disease. Oxidized low-density lipoprotein (oxLDL) is implicated in MASLD progression; however, its effects on the hepatic cholesterol metabolism remain unclear. Therefore, we explored the effects of native LDL (nLDL) and oxLDL on the cholesterol metabolism and lipid composition in the human liver-derived C3A cell line.</p><p><strong>Methods: </strong>Orbitrap liquid chromatography-tandem mass spectrometry was used to measure free cholesterol (FC), cholesteryl ester (CE), and CE hydroperoxide (CEOOH) levels in LDL particles and LDL-treated C3A cells. The expression of cholesterol metabolic genes was examined using real-time PCR, and proprotein convertase subtilisin kexin type 9 (PCSK9) protein expression was quantified using Western blotting and an enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>Both LDL types, particularly nLDL, increased intracellular CE levels. nLDL preferentially increased CE species containing unsaturated fatty acids, whereas oxLDL promoted the accumulation of saturated fatty acid (SFAs)-containing CEs and CEOOH, while FC levels remained unchanged. Both LDL types downregulated SREBP2 and downstream cholesterol synthesis genes and reduced LDLR expression. The PCSK9 protein levels also decreased. SOAT1 expression was reduced, indicating that CE accumulation was primarily driven by exogenous LDL-derived lipids rather than enhanced esterification. In addition, the genes involved in cholesterol efflux (ABCA1), xenobiotic metabolism, and scavenger receptor-related pathways were downregulated in C3A cells.</p><p><strong>Conclusion: </strong>Both nLDL and oxLDL particles drive CE accumulation through impaired cholesterol release rather than increased cholesterol synthesis. Furthermore, LDL oxidation increases CEOOH and saturated CEs, thus potentially enhancing hepatocellular lipotoxicity.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148919931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 1 Study Evaluating the Pharmacokinetics, Pharmacodynamics, and Safety of Zerlasiran in Japanese Participants.","authors":"Henry Fok, Mariko Harada-Shiba, David Rider, Yasuko Owada, Curtis Rambaran","doi":"10.5551/jat.66214","DOIUrl":"10.5551/jat.66214","url":null,"abstract":"<p><strong>Aim: </strong>Zerlasiran is an N-acetylgalactosamine-conjugated small interfering RNA that targets lipoprotein(a), a risk factor for atherosclerosis and calcific aortic stenosis. Zerlasiran has not been studied in Japanese participants previously.</p><p><strong>Method: </strong>This was an open-label, single-dose trial that enrolled 18 adult participants with lipoprotein(a) levels ≥ 70 nmol/L at a single site in Japan to evaluate subcutaneous doses of zerlasiran (30 mg, 100 mg, and 300 mg) in three ascending-dose cohorts. The participants were monitored for 150 days post-dose to assess the systemic pharmacokinetics, pharmacodynamics (lipoprotein (a) and lipid biomarkers), and safety.</p><p><strong>Results: </strong>Following dosing, median T_max was reached at 5 hours with plasma concentrations gradually declining to undetectable levels by 36 hours, with t_1/2 approximately 4 hours. Both C_max and AUC_0-inf increased in a dose-dependent manner. The maximum median (interquartile range [IQR]) percent reduction in lipoprotein (a) in the 30 mg, 100 mg, and 300 mg cohorts were -72.8% (-79.7%, -67.1%), 88.8% (-89.5%, -84.7%), and -97.8% (-98.6, -96.9%), respectively, between days 30 and 60, with a sustained effect observed at 150 days at all dose levels. All adverse events were mild and self-limiting.</p><p><strong>Conclusion: </strong>Zerlasiran was well tolerated with no significant safety findings observed at any dose level. A typical pharmacokinetic profile expected of an N-acetylgalactosamine-conjugated small interfering RNA, coupled with a potent and sustained reduction in lipoprotein(a), was observed in Japanese participants. No adverse effects on either the liver or kidney function were observed.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":"1148-1156"},"PeriodicalIF":3.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13547142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147868358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}