AIM:Low-density lipoprotein cholesterol (LDL-C) is a major contributor to atherosclerotic cardiovascular disease (CVD). The waist-to-height ratio (WHtR) has been proposed as a practical marker of central obesity; however, evidence linking WHtR with incident high LDL-C levels in Japanese populations remains limited. This study investigated the association between WHtR and future LDL-C elevation in a community-based cohort in Japan. METHODS:This retrospective cohort study included 3,934 adults aged 30-74 years without dyslipidemia at baseline from the Iki Epidemiological Study of Atherosclerosis and Chronic Kidney Disease. The participants were followed between 2008 and 2019. WHtR was categorized into sex-specific quartiles. Incident high LDL-C was defined as LDL-C ≥ 3.62 mmol/L or initiation of lipid-lowering therapy. Cox proportional hazards models were used to estimate the hazard ratios (HRs), after adjusting for demographic, lifestyle, and clinical factors. RESULTS:During a mean follow-up period of 5.02 years, 466 females and 424 males developed high LDL-C levels. Among females, the adjusted hazard ratio (HR) (95% confidence interval [CI]) for quartile 4 versus quartile 1 was 1.95 (1.41-2.71; p for trend ＜0.0001). Among males, the corresponding adjusted HR (95% CI) was 1.61 (1.18-2.21; p for trend = 0.001). A higher WHtR was associated with an increased risk of incident high LDL-C in both sexes (trend p＜0.01). A WHtR threshold of approximately 0.5 corresponded to a notable increase in risk. CONCLUSION:A Higher WHtR was associated with an increased risk of incident high LDL-C. These findings suggest that WHtR may be a useful anthropometric indicator for identifying individuals at risk, although further studies are required.
Although the mortality rate from cardiovascular disease (CVD) in Japan remains lower than that in Western countries, the need for the prevention of atherosclerotic diseases still merits emphasis. Cardiovascular disease develops due to the accumulation of risk factors such as visceral obesity, impaired glucose tolerance and diabetes, dyslipidemia, metabolic dysfunction associated with steatotic liver disease, hypertension, and chronic kidney disease. Dietary therapy must comprehensively improve these factors through the intake of nutrients and food components. This narrative review aims to confirm the effects of well-known nutrients that influence atherosclerotic risk factors and foods providing each nutrient in the Japanese diet. Furthermore, the actual dietary intake of the Japanese population is described.Target foods and dietary habits to modify patients' diets should be determined through nutrition assessment. Reducing carbohydrate intake requires limiting confectioneries, sweet beverages, and sweet fruits while avoiding the consumption of a lot of refined grains at once. The consumption of foods rich in saturated fatty acids, such as lard, beef tallow, butter, fatty red meat, fresh cream, and trans fatty acids contained in shortening, margarine, oily processed and fried foods, should be reduced. To meet the dietary fiber intake requirement, more unpolished grains, vegetables, citrus or whole fruits, seaweed, mushrooms, and konjac should be consumed. Fish intake is higher in Japan than in Western countries but it has been decreasing in younger generations, indicating the need for education and environments that encourage fish consumption for EPA and DHA intake and limit excess oil intake. Japanese people have higher candidate gene polymorphisms responsible for salt-sensitive hypertension than Caucasians; therefore, strict salt reduction is desirable. Sodium is included in salt, seasonings, and sodium salt additives in take-away, prepared, and ultra-processed foods, the cumulative impact of which cannot be ignored. The Japan Atherosclerosis Society (JAS) recommends a dietary pattern called "The Japan Diet," featuring higher consumption of fish, soybeans and soy products, vegetables, citrus fruits, low-fat milk and dairy products, seaweed/mushrooms/konjak, and unrefined cereals with reduced consumption of animal fat, fatty meat and poultry, sweets including desserts and snacks, and alcoholic drinks, along with reduced salt intake. "The Japan Diet", a reasonable and useful strategy for nutrition therapy, improves multiple atherosclerotic risk factors comprehensively by providing prescribed nutrients.Nutrition education for "The Japan Diet" intake improved serum lipid and metabolic parameters in patients with dyslipidemia. However, clinical intervention studies on patients with atherosclerotic risk factors remain limited. Further studies on the effect of "The Japan Diet" on CVD prevention are needed.
AIM:Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis; however, its patency is limited, particularly in patients with diabetes mellitus (DM). This study aimed to obtain exploratory data on whether changes in the venous transcriptome are present at the time of AVF creation in patients with DM and whether these changes are related to the graft prognosis. METHODS:We conducted prospective transcriptome analyses using venous samples obtained during AVF creation from 22 patients (12 with DM and 10 without DM). RNA sequencing was performed, and clinical outcomes, including primary patency, were tracked for one year. RESULTS:AVF patency was significantly lower in the DM group (median patency: 134 vs. 365 days, p＜0.05). Transcriptome profiling identified 285 differentially expressed genes, including those related to extracellular matrix organization, mitochondrial electron transport, TGF-β signaling, and the unfolded protein response. A network analysis highlighted hub genes, including MRPL27, MRPL23, and MRPL1, as potential biomarkers. A Cox regression analysis identified genes associated with the AVF prognosis, including PER3, SERINC2, COMMD10, TTC4, FKBP2, FN3KRP, KIF24, SNX32, MOB3C, SUV39H1, and TIGD6. Notably, a high COMMD10 expression, a core component of the commander complex, was associated with a shortened patency in patients with DM. CONCLUSIONS:Our findings demonstrate that DM is associated with distinct transcriptomic alterations in the access veins at the time of AVF creation. This integrative approach provides novel insights into the molecular basis of DM-related AVF failure and the potential to identify novel therapeutic targets.
AIM:To investigate whether the presence of common health education (HE) and a healthcare administrator (HA) at a worksite would be associated with a lower prevalence of current smoking, current daily alcohol consumption, and obesity among employees at real-world, small-to-medium worksites. METHODS:The present cross-sectional study included 72,704 employees aged 35-59 years at 5,910 small-to-medium companies in Okinawa, Japan. Odds ratios were calculated by sex for each factor for HE (information provision alone, lecture classes alone, or both services) presence and HA presence, using a multilevel logistic regression model, with HE absence (neither) and HA absence, respectively, serving as the reference. RESULTS:The odds ratios (95% confidence intervals) for current smoking among men and women in the combined HE services group were 0.80 (0.68-0.93) and 0.68 (0.52-0.88), respectively, after adjusting for age, HA status, medication status, and basic worksite characteristics. The adjusted odds ratios for current daily alcohol consumption among men and women in the combined HE services group were 0.81 (0.69-0.95) and 0.84 (0.69-1.02), respectively. However, the four HE groups had similar odds of obesity in both men and women. The HA-present and HA-absent groups had similar odds of all outcomes in both men and women, except that men in the HA-present group had lower odds of current daily alcohol consumption: 0.92 (0.86-0.98). CONCLUSIONS:The combined HE services presence was associated with lower odds of current smoking and daily alcohol consumption among employees, whereas HA presence was associated with lower odds of daily alcohol consumption among men.
AIMS:Ischemic stroke (IS) is a leading global cause of death and disability. The lactate-to-hematocrit ratio (LHR), which potentially reflects the oxygen metabolism and tissue perfusion, has not yet been sufficiently studied for IS prognosis prediction. To investigate the association between LHR and the 28-day all-cause mortality in patients with IS. METHODS:This MIMIC-IV database-based study included 866 patients with IS. Kaplan-Meier curves were used to compare survival between the log (LHR) subgroups. Multivariate Cox regression was performed with adjustment for the Glasgow Coma Scale (GCS) score, and robustness verification was further implemented by controlling for the SOFA score. An RCS analysis was used to explore the underlying nonlinear associations, followed by subgroup and mediation analyses. RESULTS:A survival analysis demonstrated a significantly higher 28-day mortality in log (LHR)≥ 2.32 than in the log (LHR) ＜2.32 groups (log-rank P = 0.017). In the Cox regression analysis with full adjustment for confounding factors, for every unit increase in log (LHR), the 28-day mortality risk increased by 38.1% (HR = 1.381, 95% CI: 1.111-1.718). The mortality risk of patients with log (LHR) ≥ 2.32 increased by 47.8% compared to those with log (LHR) ＜2.32 (HR = 1.478, 95% CI: 1.075-2.031). The RCS analysis showed no significant non-linear relationship between log (LHR) and the 28-day mortality rate (P-non-linear = 0.859). No significant interaction was observed in the subgroup analyses, and the relevant associations remained statistically significant within the severe stroke subgroup. After adjusting for the GCS and SOFA scores, the independent prognostic value of log (LHR) remained consistent. A mediation analysis showed that white blood cell count (mediation ratio, 33.54%) and blood urea nitrogen (mediation ratio, 18.69%) partially mediated the relationship between log (LHR) and mortality risk. The original LHR was also independently correlated with the mortality rate (HR = 1.018, 95% CI: 1.006-1.030). CONCLUSIONS:LHR was positively correlated with 28-day mortality in patients with IS, independent of stroke severity, sepsis, and systemic organ failure, and inflammation, and renal dysfunction may jointly mediate this association. As an easily accessible composite indicator, LHR has potential clinical application value in early risk stratification.
AIMS:Non-fasting triglyceride measurements have become increasingly common in screening for atherosclerotic cardiovascular disease. However, evidence of its predictive value for diabetes mellitus is limited to only a few studies. METHODS:This prospective cohort study included two groups of individuals aged 40-74 years without diabetes mellitus: 7,673 who provided non-fasting blood samples and 4,055 who provided fasting samples. We used annual health checkup data to identify new cases of diabetes mellitus, employed Cox proportional hazard models to estimate hazard ratios, and conducted decision curve analyses to assess clinical utility. RESULTS:During a median follow-up of 13 years, 727 and 444 participants were diagnosed with diabetes mellitus in the non-fasting and fasting groups, respectively. After adjusting for the glucose levels and other potential confounders measured at baseline, both non-fasting and fasting triglyceride levels were positively associated with the hazard of diabetes mellitus; the hazard ratios (95% confidence intervals) for the highest versus lowest quartiles were 1.99 (1.50-2.64) and 1.58 (1.11-2.26), respectively. Adding non-fasting or fasting triglyceride levels to a model based on traditional predictors can slightly improve the net benefit for 15-year risk prediction, corresponding to an approximate gain of 1 to 2 additional individuals per 1,000 screened. The improvement was slightly greater under non-fasting conditions than under fasting conditions. CONCLUSION:Both the non-fasting and fasting triglyceride levels were associated with an increased hazard of diabetes mellitus. Adding the triglyceride levels can therefore provide modest but potentially useful supplementary information for diabetes prediction, particularly under non-fasting conditions.
Atrial fibrillation is one of the most important causes of ischemic stroke and it is strongly associated with recurrent stroke, systemic embolism, heart failure, cognitive decline, and mortality. Oral anticoagulation, preferably direct oral anticoagulants, remains the cornerstone of secondary stroke prevention in patients with atrial fibrillation and a history of ischemic stroke. However, ischemic stroke may still occur despite appropriate anticoagulation therapy, a condition often referred to as breakthrough ischemic stroke. This residual risk reflects heterogeneous mechanisms, including inadequate anticoagulant exposure, atrial cardiomyopathy, left atrial appendage thrombus, large-artery atherosclerosis, small-vessel disease, cancer-associated thrombosis, and other competing etiologies. Rhythm control has re-emerged as a disease-modifying strategy after the EAST-AFNET 4 trial, and its prespecified subgroup analysis suggested a potential benefit in patients with prior stroke. However, the recently reported STABLED randomized clinical trial, which specifically evaluated catheter ablation in addition to edoxaban-based standard therapy after a recent ischemic stroke, did not demonstrate a significant reduction in recurrent ischemic stroke, systemic embolism, all-cause mortality, or hospitalization for heart failure. These findings do not negate the value of rhythm control for symptom relief, atrial fibrillation burden reduction, and selected cardiovascular outcomes; however, they challenge the assumption that the restoration of sinus rhythm alone is sufficient for secondary stroke prevention. Future strategies should integrate optimized anticoagulation and early rhythm control when appropriate, with a systematic evaluation of competing stroke mechanisms, vascular risk factor control, and selected left atrial appendage interventions. The next frontier is not rhythm control alone but rhythm control embedded within mechanism-based secondary stroke prevention.
AIM:Reducing low-density lipoprotein cholesterol (LDL-C) levels is crucial for preventing atherosclerotic cardiovascular disease (ASCVD). Recommended lipid-lowering therapy (LLT) includes both oral (e.g., statins) and injectable agents. However, patient awareness of LDL-C management and adherence to it remain uncertain. METHODS:This cross-sectional study surveyed 415 Japanese patients with ASCVD using a web-based platform. The participants reported their understanding of LDL-C target values and the effects of LLT. Medication adherence was evaluated using the Extent of Nonadherence scale, and a binomial logistic regression analysis was performed to identify the factors associated with nonadherence. RESULTS:Approximately 58.1%-60.2% of the participants reported confidence in knowing their correct lipid target values and managing dyslipidemia appropriately. However, only 22.2% reported LDL-C targets of ＜50 or ＜70 mg/dL, and 43.4% believed their targets to be ＜50, ＜70, or ＜100 mg/dL. In contrast, 56.7% either reported LDL-C targets of ＜120, ＜140, or ＜160 mg/dL or did not know their targets. Regarding LLT, 65.8% were unaware that extreme lowering of LDL-C levels with LLT had no disadvantages, and 74.2% were unaware that injectable LLTs were available. Overall, 39.0% of the participants were nonadherent. Higher out-of-pocket costs (≥ 3,001 yen; adjusted odds ratio [OR]: 1.83, p = 0.024) and experience with self-injections (adjusted odds ratio: 2.34, p = 0.027) were significantly associated with nonadherence. CONCLUSIONS:Our findings highlight a considerable gap in patient knowledge and adherence to dyslipidemia management strategies. Interventions that promote patient education and shared decision-making are essential for improving adherence and achieving optimal LDL-C targets.
AIM:This sub-group analysis evaluated the long-term efficacy and safety of evinacumab, an angiopoietin-like 3 inhibitor, in adolescent and adult Japanese patients with homozygous familial hypercholesterolemia (HoFH) who were enrolled in the open-label, single-arm, extension of the Phase 3 ELIPSE HoFH pivotal trial. METHODS:Patients aged ≥ 12 years with HoFH on stable lipid-lowering therapies received intravenous evinacumab 15 mg/kg every 4 weeks and weekly/biweekly lipoprotein apheresis. Final results are reported. RESULTS:Eleven patients were enrolled and received at least 1 dose of evinacumab at baseline, including 9 adults who participated in the evinacumab pivotal study (evinacumab-continue) and 2 newly enrolled adolescent patients (evinacumab-naïve). Mean (standard error) percent decrease in LDL-C from baseline to Week 24 was 42.9% (7.4) in the overall cohort (n = 9) and 37.1% (7.9) in the evinacumab-continue group (n = 7), with reductions in LDL-C observed as early as Week 8 and persisting through Week 168. Evinacumab treatment was also associated with reductions in other lipid parameters measured, including apolipoproteins A1 and B, non-high density lipoprotein cholesterol (HDL-C), HDL-C, total cholesterol, fasting triglycerides, and lipoprotein(a). Similar lipid-lowering results were seen in the evinacumab-naïve group (n = 2). Treatment-emergent adverse events (TEAEs) occurred in all 11 patients. Serious TEAEs occurred in 3 (27.3%) patients, and none were treatment related. CONCLUSIONS:Evinacumab treatment resulted in sustained reductions in LDL-C and other lipid parameters in Japanese patients ≥ 12 years with HoFH, including those undergoing lipoprotein apheresis, and was generally well tolerated.
AIMS:The quantitative flow ratio (QFR)-derived pullback pressure gradient (PPG) characterizes the pathophysiological patterns of coronary atherosclerosis. This study investigated the plaque morphologies associated with these disease patterns. METHODS:This study used the institutional QFR-PPG database registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000056097). Patients who underwent elective stenting with pre-procedural optical coherence tomography and near-infrared spectroscopy intravascular ultrasound were included. Offline QFR and QFR-PPG analyses were performed, and the lesions were stratified into tertiles. RESULTS:A total of 168 de novo lesions were analyzed in this study. The QFR tertiles were defined as severe (＜0.61), moderate (0.61-0.71), and mild (＞0.71); the QFR-PPG tertiles were defined as diffuse (＜0.66), intermediate (0.66-0.79), and focal (＞0.79). The Severe QFR tertiles exhibited a smaller minimum lumen area (MLA) and higher frequencies of thin-cap fibroatheroma (TCFA) and layered plaque. In contrast, across the QFR-PPG tertiles, MLA and TCFA frequencies were similar, whereas the diffuse group exhibited more layered plaques and larger calcium angles. The maximum lipid-core burden index did not vary across the QFR-PPG tertiles. A multivariable analysis identified MLA and TCFA as independent predictors of QFR, while layered plaque and calcium angle independently predicted QFR-PPG. However, the lipidic features were not independent predictors of QFR. CONCLUSION:Multimodal intracoronary imaging demonstrated that QFR reflects luminal narrowing and the features of vulnerable plaques. Conversely, QFR-PPG reflects disease diffuseness, characterized by layered plaques and calcium burden rather than lipid-rich features.
AIM:Atrial cardiomyopathy (AC) is associated with cardiovascular events, but the benefit of anticoagulation in embolic stroke of an undetermined source (ESUS) remains unclear. We aimed to prospectively evaluate the prognostic value of AC in patients with ESUS. METHODS:We prospectively enrolled patients with ESUS who were hospitalized within 7 days of onset (January 2019 - December 2021). AC was defined as an N-terminal pro-B-type natriuretic peptide level ＞250 pg/ml, P-wave terminal force in lead V1 ＞5000 µV·ms, or enlarged left atrial diameter. Ischemic stroke/transient ischemic attack (TIA) recurrence was evaluated using Fine-Gray sub-distribution hazard models with death as a competing event. Cox proportional hazards models were used for supportive analyses and all-cause mortality. RESULTS:Among the 345 patients (mean age 59.22±13.19 years; 69.0% men), 42.0% met the criteria for AC. During a median follow-up of 18.1 months, 36 patients experienced ischemic stroke, 2 had TIA, and 18 died. AC was strongly associated with ischemic stroke/TIA recurrence in competing risk analyses (adjusted subdistribution hazard ratio [aSHR] 3.36, 95% CI 1.65-6.86; P＜0.001). For all-cause mortality, AC was associated with a higher risk after adjusting for age and sex (adjusted hazard ratio 3.80, 95% CI 1.19-12.08; P = 0.024). Adding AC to conventional risk models significantly improved the NRI (ischemic stroke/transient ischemic attack: 72.45%, P＜0.001; mortality: 66.16%, P = 0.002) and IDI (4.52%, P＜0.001; 3.89%, P = 0.041). CONCLUSIONS:AC independently predicts recurrent ischemic stroke/TIA in ESUS and improves risk stratification, while its association with mortality requires cautious interpretation due to limited events.
AIM:Chronic limb-threatening ischemia (CLTI), the most advanced stage of lower-extremity artery disease, is associated with high mortality and major amputation rates, even after revascularization. Thus, identifying patients with CLTI at a particularly high risk of poor outcomes is crucial for shared decision making. Recently, the C-reactive protein-to-albumin ratio (CAR) has emerged as a novel composite biomarker that reflects both the inflammatory and nutritional status. Nonetheless, the prognostic significance of CAR in patients with CLTI undergoing endovascular therapy (EVT) remains unclear. METHODS:Of 159 patients who underwent EVT for the first time between April 2010 and December 2023, 79 were included in this study. The patients were categorized into two groups using a CAR value of 0.17: the high-CAR group (CAR ≥ 0.17) and the low-CAR group (CAR ＜0.17). The primary endpoint was 1-year amputation-free survival (AFS) after EVT. RESULTS:The median follow-up period was 23 months (95% confidence interval [CI], 11-34). During the follow-up period, 56 patients (71%) died and 11 (14%) underwent major amputation. AFS was significantly reduced in the high-CAR group (log-rank P＜0.01). The CAR (hazard ratio: 1.43 per one-unit increase, 95% CI: 1.20-1.70, P＜0.01) was an independent predictor of reduced AFS following EVT. CONCLUSIONS:elevated preprocedural CAR was independently associated with reduced AFS after EVT in patients with CLTI. The CAR may serve as a valuable tool for evaluating patients with CLTI before EVT.
AIM:Familial chylomicronemia syndrome (FCS) is a rare disorder characterized by the accumulation of chylomicrons in the circulation due to genetic defects or autoantibodies affecting lipoprotein lipase (LPL), the key enzyme responsible for the metabolism of chylomicrons and very-low-density lipoproteins (VLDL), or its associated proteins, including apolipoprotein (apo) C-II, apoA-V, glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), and lipase maturation factor 1 (LMF1). This condition is associated with markedly elevated serum triglyceride (TG) levels and, in severe cases, recurrent episodes of pancreatitis and eruptive xanthomas. Among these etiologies, genetic deficiency of GPIHBP1 is exceedingly rare. We aimed to clarify the clinical and genetic basis and treatment strategies of a patient with GPIHBP1 deficiency. METHODS:A 47-year-old woman with a childhood diagnosis of FCS presented with severe epigastric pain and was admitted to Rinku General Medical Center for emergency management of acute pancreatitis secondary to severe chylomicronemia. She had a history of severe hypertriglyceridemia complicated by pancreatitis during her first pregnancy and extreme hypertriglyceridemia exceeding 6,000 mg/dL during her second pregnancy without the development of pancreatitis. DNA sequence analysis was performed as a clinical diagnostic test and outsourced to KUBIX Inc. (Hakusan, Ishikawa, Japan). RESULTS:Laboratory evaluation revealed marked hypertriglyceridemia (1,262 mg/dL) with a type V hyperlipoproteinemia pattern. Serum preheparin LPL mass was markedly reduced, and circulating GPIHBP1 was undetectable. Genetic analysis identified a novel homozygous frameshift mutation in the GPIHBP1 gene (NM_178172.4:c.20del [p.Val7AlafsTer73]), which has not been previously reported in public databases. No pathogenic variants were detected in other LPL-related genes. Acute pancreatitis improved rapidly with fasting and intravenous fluid therapy. Strict dietary fat restriction, followed by the addition of the selective PPARα modulator pemafibrate, successfully maintained TG levels below 500 mg/dL during follow-up. CONCLUSION:We report an extremely rare case of FCS caused by a novel homozygous mutation in the GPIHBP1 gene, in which pregnancy served as a major trigger for severe hypertriglyceridemia. Early diagnosis and strict lipid control are essential to prevent recurrent pancreatitis in patients with GPIHBP1 deficiency.
AIM:To investigate the effects of temperature exposure on the incidence of cardiovascular and cerebrovascular diseases in Zhanjiang, a subtropical coastal city in China. METHODS:We analyzed hospitalization data from 2009 to 2023 using generalized additive models (GAMs) and distributed lag nonlinear models (DLNMs) to examine the exposure-response relationships and lagged effects of daily maximum temperature on stroke (CVA), acute coronary syndrome (ACS), and acute aortic syndrome (AAS). RESULTS:Distinct temperature-associated risk patterns were observed for each disease type. ACS showed the strongest association, with significant risk increases at 1-day (relative risk [RR] = 1.19) and 5-day lags (RR = 1.12). The risk of CVA was moderately elevated at lower temperatures (22.7℃; RR = 1.08), whereas AAS exhibited a delayed peak at 5 days (RR = 1.29). CONCLUSIONS:These subtropical patterns differ from those reported in temperate regions. Our findings support climate-specific warnings: namely, multi-day monitoring for CVA at lower temperatures, immediate and sustained alerts for ACS, and focused surveillance approximately 5 days after exposure for AAS.
Adenosine triphosphate (ATP) is well known as the major intracellular energy carrier. It also functions as a potent extracellular signaling molecule. In atherosclerosis, both intracellular and extracellular ATP have been increasingly implicated in the disease pathophysiology. The intracellular ATP levels are closely regulated by the balance among the metabolic pathways, including glycolysis and oxidative phosphorylation (OXPHOS), and they play diverse and cell type-specific roles in atherosclerotic plaques. In contrast, the extracellular ATP released from these cells binds to purinergic P2 receptors and activates downstream signaling cascades primarily in an autocrine or paracrine manner, thereby regulating various cellular functions during disease progression. These two contrasting ATP-associated pathways are involved in a wide range of atherosclerosis-related processes including inflammation, vascular tone and barrier function, cell proliferation, migration and differentiation, and calcification, some of which are shared or highly context-dependent. This review summarizes the fundamental aspects of ATP biology, discusses the current approaches for measuring ATP concentrations in atherosclerotic plaques, and highlights the functions of intra- and extracellular ATP in major atherosclerosis-related cell types, including endothelial cells, macrophages and vascular smooth muscle cells (VSMCs), to clarify these intricately intertwined pathophysiological processes. Finally, this overview provides insights into the current challenges in ATP biology research and outlines therapeutic opportunities targeting intra- or extracellular ATP in atherosclerotic disease.
AIMS:ADAMTS18 is a secreted metalloproteinase implicated in vascular homeostasis and protection against ischemic brain injury. However, its clinical relevance in acute ischemic stroke (AIS) remains unclear. METHODS:We retrospectively analyzed 194 AIS patients from the Chengdu Stroke Registry. Serum ADAMTS18 levels were measured within 48 hours of admission using ELISA. Associations between ADAMTS18 levels and 3-month poor outcomes (modified Rankin Scale score 3-6) were evaluated using logistic regression. Predictive performance was assessed using area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS:Among 194 patients, the median ADAMTS18 was 21.45 ng/mL (IQR 19.68-23.58 ng/mL), 79 (40.7%) had poor outcomes. Patients with poor outcomes had lower serum ADAMTS18 levels [19.84 (18.46-21.24) vs. 22.88 (21.14-24.81) ng/mL, P＜0.001]. After adjustment, lower ADAMTS18 levels were independently associated with poor outcome (OR 0.70, 95% CI 0.58-0.83, P＜0.001). Quartile analysis showed that compared with the lowest quartile, patients in Q3 (OR = 0.26; 95% CI: 0.08-0.83; P = 0.023) and Q4 (OR = 0.02; 95% CI: 0.00-0.11; P＜0.001) had progressively lower odds of poor functional outcome (P for trend ＜0.001). Restricted cubic spline analysis confirmed a negative linear association (adjusted Poverall＜0.001). Incorporating ADAMTS18 into predictive models improved discrimination (AUC = 0.91 vs. 0.86, P = 0.011), IDI (11.14%, P＜0.001), and NRI (77.1%, P＜0.001). CONCLUSION:Lower admission ADAMTS18 levels are independently associated with poor 3-month functional outcomes after AIS and may provide additional prognostic information.
AIM:Children with elevated low-density lipoprotein cholesterol (LDL-C) levels, suspected familial hypercholesterolemia (FH), and elevated lipoprotein(a) (Lp(a)) levels are considered to have a particularly high lifetime risk of atherosclerotic cardiovascular disease. Nevertheless, the distribution of Lp(a) levels among children with elevated LDL-C levels remains unclear. This study aimed to clarify the distribution of Lp(a) levels and their association with pathogenic FH variants in children with elevated LDL-C levels. METHODS:A total of 97 children with LDL-C levels ≥ 140 mg/dL suspected of having FH who underwent genetic testing at Kagawa University Hospital between January 2018 and May 2025 were analyzed. Lp(a) levels were measured using the Lp(a) Latex "DAIICHI" assay and converted from mass units (mg/dL) to molar units (nmol/L) using the calibration-based conversion formula. Clinical and lipid parameters were compared according to Lp(a) levels (≥ 105 vs. ＜105 nmol/L) and the presence of pathogenic FH variants. RESULTS:Lp(a) levels exhibited a right-skewed distribution, with a median of 57.6 nmol/L (15.9 mg/dL) and an interquartile range of 24.0-93.4 nmol/L (7.0-25.4 mg/dL), and 21.6% of children had levels ≥ 105 nmol/L. Pathogenic FH variants were identified in 44 children. No significant differences were observed in either clinical or lipid parameters according to Lp(a) levels (≥ 105 vs. ＜105 nmol/L) or the presence of pathogenic FH variants (P = 0.672). CONCLUSION:Regardless of the presence of pathogenic FH variants, approximately 20% of the children had Lp(a) levels ≥ 105 nmol/L. These findings emphasize the importance of early lipid management and suggest that Lp(a) measurement may contribute to future cardiovascular risk stratification.
