Journal of atherosclerosis and thrombosis最新文献

Aims: We report that small dense low-density lipoprotein cholesterol (sdLDL-C) levels are sensitive biomarkers of metabolic dysfunction-associated steatotic liver disease (MASLD). Since triglyceride (TG)-rich very low-density lipoprotein (VLDL) is a precursor of sdLDL and is overproduced by MASLD, the composition of VLDL may be more directly associated with MAFLD than sdLDL-C or plasma TG. To identify TG-rich VLDL, this author proposed "Excess TG" and examined its association with MASLD.

Methods: Patients with type 2 diabetes (n=1295), excluding fasting hypertriglyceridemia (TG ≥ 400 mg/dL) and heavy drinkers were examined. Liver steatosis and visceral fat area (VFA) were evaluated using CT. VLDL-C was calculated as the total C minus direct LDL-C minus HDL-C. The average VLDL-TG level can be estimated using VLDL-C×5, according to the principle of the Friedewald equation for LDL-C. Thus, VLDL-TG was estimated as VLDL-C×5, and Excess TG was calculated as plasma TG minus VLDL-C×5.

Results: Patients with MASLD were younger, more likely to be men and drinkers, and had higher VFA, TG, sdLDL-C, and excess TG, while VLDL-C was comparable. Excess TG was found to be the most sensitive lipid parameter for identifying MASLD, independent of sdLDL-C, TG, TG/VLDL-C, and VFA. The odds ratios for MASLD were 2.4-, 3.7-, and 3.9-fold higher for Excess TG ranges of 0-24, 25-49, and ≥ 50 mg/dL, respectively, relative to ＜0 mg, and a close relationship remained significant after adjustment for lipid- and adiposity-related parameters.

Conclusions: Excess TG in VLDL was strongly associated with MASLD beyond TG and sdLDL-C levels, which may reflect the presence of TG-rich VLDL.

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality worldwide, including in Japan, where the aging population intensifies its impact. This review evaluated the potential impact of digital healthcare on the prevention and management of ASCVD, covering both primary and secondary prevention strategies. Digital health tools, such as risk assessment applications remote monitoring, lifestyle modification support, and remote rehabilitation, have shown promise in improving patient engagement, adherence, and outcomes. However, while digital health interventions demonstrate significant benefits, challenges persist, including interoperability issues, privacy concerns, low digital literacy among older adults, and limited health insurance coverage for digital interventions. Through an analysis of recent advancements and case studies, this review demonstrates the need for user-centered design, enhanced regulatory frameworks, and expanded insurance support to facilitate the effective integration of digital health in ASCVD care. Furthermore, emerging technologies such as personalized healthcare modules offer promising directions for tailored and impactful care. Addressing these barriers is critical to unleashing the full potential of digital healthcare to reduce the burden of ASCVD and enhance patient outcomes.

Aims: Long-term exposure to fine particulate matter (PM_2.5) is causally associated with mortality and cardiovascular disease. However, in terms of cardiovascular cause-specific outcomes, there are fewer studies about stroke than about coronary heart disease, particularly in Asia. Furthermore, there remains uncertainty regarding the PM_2.5-respiratory disease association. We examined whether long-term exposure to PM_2.5 is associated with all-cause, cardiovascular and respiratory disease mortality in Japan.

Methods: We used data of 46,974 participants (19,707 men; 27,267 women), who were enrolled in 2009 and followed up until 2019, in a community-based prospective cohort study (the second cohort of the Ibaraki Prefectural Health Study). We estimated PM_2.5 concentrations using the inverse distance weighing methods based on ambient air monitoring data, and assigned each participant to administrative area level concentrations. A Cox proportional hazard model was applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of mortality.

Results: During the average follow-up of 10 years, we confirmed 2,789 all-cause deaths. All outcomes including stroke mortality did not significantly increase as the PM_2.5 concentration increased. For non-malignant respiratory disease mortality, the multivariable adjusted HR per 1 µg/m³ increase in the PM_2.5 concentration was 1.09 (95% CI = 0.97-1.23).

Conclusions: In this population exposed to PM_2.5 at concentrations of 8.3-13.1 µg/m³, there was no evidence that long-term exposure to PM_2.5 had adverse effects on mortality. Weak evidence of positive association observed for non-malignant respiratory disease mortality needs further studies in other populations.

Aims: Evidence supporting the prescription of anticoagulant therapy for patients with atrial fibrillation (AF) with advanced chronic kidney disease (CKD) has been limited, and its clinical application in this context remains controversial.

Methods: We identified AF patients with advanced CKD (G4-G5) and a history of stroke who were admitted to the First Affiliated Hospital of Dalian Medical University between January 1, 2011, and June 30, 2023. Patients were classified into warfarin, non-vitamin K antagonist oral anticoagulant (NOAC), antiplatelet therapy, and control (no antithrombotic therapy) groups. We evaluated the benefits and safety of different antithrombotic therapies by comparing the long-term clinical outcome measures, including the incidence of subsequent ischemic stroke events, bleeding, and all-cause death.

Results: In total, 570 patients were included. In this cohort, 87 (15.3%) patients had no antithrombotic treatment, 252 (44.2%) received antiplatelet therapy, 105 (18.4%) received warfarin, and 126 (22.1%) received NOAC therapy. Compared with patients without treatment, we found that treatment with anticoagulant therapy significantly decreased the risk of ischemic stroke, but antiplatelet therapy did not. Treatment with anticoagulant therapy was associated with significantly lower mortality than no antithrombotic therapy or antiplatelet therapy , at least within the study period. Furthermore, compared with warfarin treatment, patients treated with NOAC therapy showed a significant decrease in the incidence of bleeding risks.

Conclusion: Among AF patients with advanced CKD and prior stroke, receiving anticoagulants resulted in a reduced risk of recurrent ischemic stroke events than no antithrombotic treatment, and lower mortality than no antithrombotic treatment or antiplatelet therapy.

Aim: Branch atheromatous disease (BAD), characterized by the occlusion of perforating branches near the orifice of a parent artery, often develops early neurological deterioration because the mechanisms underlying BAD remain unclear. Abnormal wall shear stress (WSS) is strongly associated with endothelial dysfunction and plaque growth or rupture. Therefore, we hypothesized that computational fluid dynamics (CFD) modeling could detect differences in WSS between BAD and small-vessel occlusion (SVO), both of which result from perforating artery occlusion/stenosis.

Methods: This cross-sectional observational study included consecutive patients admitted to our institution within 7 days after symptom onset who met the following criteria: absence of stenosis/occlusion in the intracranial major arteries on brain magnetic resonance angiography (MRA) or extracranial carotid arteries on carotid ultrasonography. The WSS and blood flow velocity in the M1 segment of the middle cerebral artery were analyzed using CFD based on MRA.

Results: The number of patients with a WSS ratio (ipsilesional/contralesional) of ＞1 was significantly higher in patients with BAD (n = 27) than in those with SVO (n = 27) [20 (74.1%) vs. 11 (40.7%), p = 0.013]. Higher WSS on ipsilesional M1 than on contralesional M1 was an independent risk factor for BAD (adjusted odds ratio 4.38, 95% confidence interval 1.29-14.82, p = 0.018). Blood flow velocity in the M1 segment was not associated with BAD.

Conclusions: In patients with BAD, higher M1 segment WSS on CFD can be a risk factor for the development of vulnerable plaques in branch orifices. Moreover, the use of CFD may contribute to the diagnosis of BAD.

The deposition of cholesterol containing cholesterol crystals and the infiltration of immune cells are features of atherosclerosis. Although the role of cholesterol crystals in the progression of atherosclerosis have long remained unclear, recent studies have clarified the involvement of cholesterol crystals in inflammatory responses. Cholesterol crystals activate the NLRP3 inflammasome, a molecular complex involved in the innate immune system. Activation of NLRP3 inflammasomes in macrophages cause pyroptosis, which is accompanied by the release of inflammatory cytokines such as IL-1β and IL-1α. Furthermore, NLRP3 inflammasome activation drives neutrophil infiltration into atherosclerotic plaques. Cholesterol crystals trigger NETosis against infiltrated neutrophils, a form of cell death characterized by the formation of neutrophil extracellular traps (NETs), which, in turn, prime macrophages to enhance inflammasome-mediated inflammatory responses. Colchicine, an anti-inflammatory drug effective in cardiovascular disease, is expected to inhibit cholesterol crystal-induced NLRP3 inflammasome activation and neutrophil infiltration. In this review, we illustrate the reinforcing cycle of inflammation that is amplified by inflammasome activation and NETosis.

Diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), is a pervasive chronic disease that affects millions of people worldwide. It predisposes individuals to a range of severe microvascular and macrovascular complications, which drastically impact the patient's quality of life and increase mortality rates owing to various comorbidities. This extensive review explores the intricate pathophysiology underlying diabetic complications, focusing on key mechanisms, such as atherosclerosis, insulin resistance, chronic inflammation, and endothelial dysfunction. It also highlights recent therapeutic advancements, including the introduction of SGLT2 inhibitors and GLP-1 receptor agonists, which provide benefits beyond glycemic control and offer cardiovascular and renal protection. Furthermore, the future position of SGLT2 inhibitors and GLP-1 receptor agonists in terms of the prevention of diabetes and macrovascular diseases will be discussed. Considering the differences in insulin secretion capacity between Western and Asian patients, including Japanese patients, we propose a treatment strategy for high-quality diabetes in Japan.

Apolipoprotein E (apoE) is a key apoprotein in lipid transport and is susceptible to genetic mutations. ApoE variants have been studied for four decades and more than a hundred of them have been reported. This paper presents an up-to-date review of the function and structure of apoE in lipid metabolism, the E2, E3, and E4 isoforms, the APOE gene, and various pathologies, such as familial type III hyperlipidemia and lipoprotein glomerulopathy, caused by apoE variants. Alzheimer's disease was barely mentioned in this paper. But this review should help researchers obtain a comprehensive overview of human apoE in lipid metabolism.