Journal of atherosclerosis and thrombosis最新文献

Patients with chronic kidney disease (CKD) face a markedly elevated risk of death from cardiovascular disease (CVD); in particular, those requiring hemodialysis have a 10- to 30-fold higher risk than the general population. This extremely increased risk of CVD death reflects the coexistence of multiple traditional and nontraditional risk factors. The present narrative review considers two distinct steps: first, the occurrence of a CVD event, and second, death resulting from an inability to recover from the CVD event. Patients undergoing hemodialysis are at an increased risk for both of these steps, accounting for the dramatically higher risk of CVD death in this population. High risk for the second step-death following a CVD event-may be driven by conditions called decreased physical resilience and increased frailty. Studies of patients on hemodialysis show that predictors for death at this stage include key components of malnutrition-inflammation-atherosclerosis syndrome-also called the malnutrition-inflammation-complex-syndrome or protein-energy wasting-such as lower body mass index, lower serum albumin, and higher C-reactive protein. Other important contributors include higher age, longer dialysis duration, diabetic kidney disease, phosphate, calcium, serum calcification propensity (T50), and insulin-like growth factor 1 levels. Notably, some of these factors also predict death following infection, suggesting that the risk predictors for the second step are shared between CVD and infection. Recognizing these steps may facilitate prevention and greater preparedness for CVD, infection, and other stressful events among patients with CKD.

Aim: To explore whether the antiplatelet effects of prasugrel and clopidogrel vary according to patient background factors in the ACUTE-PRAS study.

Methods: This was a post hoc, hypothesis-generating, exploratory analysis of the multicenter, open-label, randomized controlled ACUTE-PRAS study, in which 176 patients with acute atherothrombotic stroke or high-risk TIA received prasugrel or clopidogrel within 48 h of symptom onset. High platelet reactivity (HPR; platelet reaction units [PRU] ＞208) and absolute PRU were assessed on Day 5 in subgroups stratified by ABCD-GENE score, age, body mass index (BMI), chronic kidney disease (CKD), diabetes mellitus (DM), hypertension, dyslipidemia, time from stroke onset to treatment, National Institutes of Health Stroke Scale (NIHSS) score, and prior ischemic stroke.

Results: Patients with prasugrel had numerically lower rates of HPR than those with clopidogrel in the high-risk stratum of ABCD-GENE score ≥ 10 (OR 2.73, p = 0.076), and favorable trends in prasugrel were also observed for CKD (8.06, p = 0.012), age ＞75 years (5.02, p = 0.025), BMI ＜25 kg/m² (4.61, p = 0.012), dyslipidemia (4.73, p = 0.009), DM (3.86, p = 0.038), treatment initiation ≤ 24 h (3.31, p = 0.010), and NIHSS ≤ 3 (2.77, p = 0.036) or ≥ 4 (9.00, p = 0.025). Prasugrel also reduced PRU numerically more than clopidogrel across most subgroups, except in patients with BMI ≥ 25 kg/m², treatment initiation ＞24 hours, or prior ischemic stroke, where only numerical differences were observed.

Conclusions: Prasugrel provided favorable early platelet inhibition, particularly in subgroups characterized by advanced age, CKD, low BMI, metabolic comorbidities, or very early treatment start.

Aim: Frailty, particularly chronic limb-threatening ischemia (CLTI), is a major health concern in patients with peripheral artery disease. CLTI onset can lead to increased frailty and impaired ability to perform daily activities. However, its in-hospital frailty progression in these patients remain poorly defined. This study aims to address this knowledge gap.

Methods: We analyzed 841 CLTI patients (mean age, 75.8 years; 60.2% male) who underwent endovascular therapy (EVT) and were discharged alive from a multicenter registry. Frailty was assessed at admission and discharge using the Clinical Frailty Scale (CFS), categorized as non-frail (1-3), mildly frail (4-5), or advanced frail (6-9). Frailty progression was defined as a transition to a higher frailty category during hospitalization. The predictors of frailty progression during hospitalization were assessed using logistic regression analyses.

Results: Overall, 103 patients (12.2%) experienced frailty progression. Compared to those without progression, these patients had lower left ventricular ejection fraction (LVEF), lower hemoglobin and albumin levels, and more severe wounds. Independent predictors of frailty progression included LVEF ＜40% (odds ratio [OR], 2.02), hemoglobin ＜11 g/dL (OR 1.67), and Wound Grade 3 (OR 2.04). Within 2 years after discharge, the amputation-free survival rate was significantly lower in the progression group than in the non-progression group (42.6% vs. 56.0%; log-rank p = 0.008). The wound healing rate within 2 years after EVT was also significantly lower in the progression group than in the non-progression group (78.2% vs. 88.8%; log-rank p = 0.001).

Conclusions: In-hospital frailty progression was observed in one of the eight patients with CLTI undergoing EVT. Frailty progression was linked to more severe clinical status and worse life and limb outcomes than cases without progression.

Aims: Angiopoietin-like proteins (ANGPTLs) are key regulators of lipid metabolism; however, their response to lipid-lowering therapies remains incompletely understood. The PRESTIGE study compared the effects of pemafibrate add-on versus statin dose doubling on small dense low-density lipoprotein-cholesterol (sdLDL-C) in patients with type 2 diabetes and hypertriglyceridemia receiving statins. This post-hoc analysis investigated changes in circulating ANGPTL levels.

Methods: Participants were randomized to receive either pemafibrate (0.2 mg/day; n = 48) or double-dose statin therapy (n = 49). Plasma ANGPTL levels and lipid parameters were assessed at baseline and after 12 weeks. ANGPTLs were quantified using specific human ELISA kits. sdLDL-C, LDL-triglycerides (TG), and HDL3-C were measured using the homogeneous assays.

Results: Pemafibrate treatment significantly increased circulating ANGPTL3 (+71%) and ANGPTL4 (+143%) levels, with no change in ANGPTL8, whereas statin dose doubling had no effect on ANGPTL levels. Pemafibrate markedly reduced TGs and sdLDL-C, while increasing large buoyant LDL-C, LDL-TG, HDL2,3-C, apolipoprotein AI, and apolipoprotein AII. The increase in ANGPTL3 was not correlated with changes in LDL subspecies but was positively associated with changes in HDL2,3-C. When participants were stratified by baseline ANGPTL3 levels, those in the low ANGPTL3 group showed an increase in LDL-C and LDL-TG in response to pemafibrate. The substantial elevation in ANGPTL4 induced by pemafibrate did not show associations with lipid changes.

Conclusions: Pemafibrate markedly elevated circulating ANGPTL3 and ANGPTL4 levels, but these increases were not associated with pro-atherogenic changes in lipoprotein profiles. Notably, baseline ANGPTL3 concentrations may influence the effect of fibrates on LDL-C levels.

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

Aims: The HELT-E₂S₂ score is a newly developed risk stratification tool for stroke in patients with atrial fibrillation. We investigated the prognostic value of the HELT-E₂S₂ score in patients with lower extremity artery disease (LEAD) and compared it with other risk scores for atrial fibrillation (AF) and LEAD.

Methods: Patients undergoing endovascular therapy (EVT) for symptomatic LEAD between August 2015 and August 2016 were enrolled in the I-PAD NAGANO registry, a prospective, multicenter, observational registry. The primary endpoint was major adverse cardiovascular events (MACEs), defined as a composite of all-cause death, nonfatal myocardial infarction, and stroke at 5 years.

Results: A total of 366 patients were divided into low-risk (HELT-E₂S₂ score ＜2, n = 146) and high-risk (HELT-E₂S₂ score ≥ 2, n = 218) groups. The major criteria of the HELT-E₂S₂ score were hypertension (81.9%) and elderly age (75-84 years old) (34.1%). The incidence of MACEs at 5 years was significantly higher in the high-risk group than in the low-risk group (43.7% vs. 22.8%, P＜0.001). In the COX multivariate analysis, the high-risk group emerged as a significant predictor of MACEs at 5 years (hazard ratio 1.87, 95% confidence interval 1.22-2.89, P = 0.004). The C-statistics for MACEs were comparable among the HELT-E₂S₂ and other AF and LEAD risk scores.

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

Aim: This study attempted to clarify the prevalence and clinical characteristics of Janus kinase 2 V617F (JAK2) gene mutations in patients with cerebrovascular diseases.

Methods: We prospectively enrolled patients who were admitted to or referred to our department with cerebrovascular disease due to suspected major cerebral artery disease or small-vessel occlusion within 30 days of onset between January 1, 2021, and April 30, 2024, and who consented to undergo a JAK2 mutation analysis. We investigated the prevalence of JAK2 mutations based on the clinical subtype of stroke and the presence or absence of major cerebral artery disease. We also examined the clinical characteristics of patients with positive JAK2 mutation.

Results: Among 316 consecutive inpatients (216 males; median age, 74 years old), JAK2 mutations were detected in 4 of 102 (3.9%) patients with large artery atherosclerosis, 2 of 101 patients (2.0%) with small-vessel occlusion, and 2 of 113 (1.8%) with other stroke subtypes. A multiple logistic regression analysis showed that patients with the positive JAK2 mutation had significantly higher hematocrit values (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.07-1.62; p = 0.010), platelet counts (OR, 1.19; 95% CI, 1.07-1.31; p = 0.001), and thrombomodulin levels (OR, 1.08; 95% CI 1.01-1.15; p = 0.025) at admission than patients with the negative JAK2 mutation.

Conclusions: The frequency of JAK2 mutations is very low among patients with major cerebral artery diseases and small-vessel occlusion. The mechanisms underlying stroke onset in patients with the positive JAK2 mutation may involve factors beyond hematopoietic cells, such as endothelial dysfunction.

Aim: A decline in the estimated glomerular filtration rate (eGFR) is associated with vascular dysfunction, a cardiovascular disease (CVD) risk. However, since the eGFR is based on the standard body surface area (BSA) of 1.73 m², its reliability may be affected by body size. We aimed to clarify whether the individual's BSA adjustment of eGFR enhances the relationship with kidney and vascular functions in the general healthy Japanese population.

Methods: This cross-sectional analysis was conducted in a total of 58,837 Japanese individuals. The BSA-adjusted eGFR (mL/min) was defined as the product of the conventional eGFR and the individual's BSA divided by 1.73 m². Arterial stiffness was assessed by the cardio-ankle vascular index (CAVI), and a high CAVI was defined as CAVI ≥ 9.0.

Results: Compared with the eGFR, the BSA-adjusted eGFR showed higher values in males in their 20s to 50s and lower values in females of all ages. The BSA-adjusted eGFR showed a stronger negative correlation with the CAVI than the eGFR (R: -0.444 vs. -0.388 in males, -0.449 vs. -0.416 in females). In a receiver-operating characteristic curve analysis, the discriminative power for a high CAVI was stronger for the BSA-adjusted eGFR than for the eGFR (area under the curve: 0.776 vs. 0.723 in males, 0.757 vs. 0.716 in females). The upper tertile of the BSA-adjusted eGFR showed higher odds ratios for a high CAVI than that of the eGFR in both sexes, after adjusting for covariates.

Conclusions: The BSA-adjusted eGFR appropriately assesses the kidney function according to differences in sex, age and body size. Furthermore, a CAVI analysis suggested that the BSA-adjusted eGFR might facilitate the achievement of more precise preventive care for CVD.

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.