Journal of atherosclerosis and thrombosis最新文献

Aim: This study addressed the alteration and related factors of cholesterol efflux capacity (CEC) and anti-oxidative activity in patients with chronic kidney disease (CKD).

Methods: This retrospective cross-sectional observational study included 333 patients (median age: 50 [20, 81] years old, male: 46.5%) who underwent a kidney biopsy at Kitano Hospital. CEC and oxygen radical adsorption capacity (ORAC) were measured using serum obtained at the time of the kidney biopsy. Changes in CEC and ORAC in relation to the clinical and kidney injury parameters were evaluated.

Results: Mean CEC and ORAC were 0.83±0.15 and 0.86±0.14, respectively. High-density lipoprotein-cholesterol (HDL-C) levels were significantly associated with CEC (r = 0.673, p＜0.001) and ORAC (r = 0.164, p = 0.003). CEC showed a weak association with ORAC (r = 0.333, p＜0.001). Both HDL-C and CEC were negatively associated with the body mass index (r = -0.407, p＜0.001 and r = -0.248, p＜0.001, respectively) and were significantly higher in women than in men (p＜0.001). The ORAC was positively associated with the serum albumin level (r = 0.330, p＜0.001) and negatively associated with the urinary protein creatinine ratio (UPCR) (r = -0.236, p＜0.001). A multiple regression analysis showed that CEC was associated with the estimated glomerular filtration rate (eGFR), serum albumin, and ORAC. There was no significant correlation between global sclerosis and either CEC or ORAC.

Conclusions: The HDL-C level did not represent HDL functionalities in CKD patients. The decreased eGFR and reduced serum albumin levels induced by an increased UPCR might therefore be associated with impaired HDL functionalities.

Aims: Interleukin-6 (IL-6) is a cytokine involved in the development of atherosclerosis and ischemic stroke. Herein, we investigated the association between serum IL-6 levels at stroke onset and long-term outcomes in patients with ischemic stroke.

Methods: This prospective observational study enrolled 655 consecutive patients (mean age, 70 years; male, 62.1%) with ischemic stroke within one week of onset followed-up for one year. Patients were divided into 3 groups according to baseline serum IL-6 tertiles: tertile 1, ＜2.6 pg/mL (n = 216); tertile 2, 2.6-6.1 pg/mL (n = 217); and tertile 3, ＞= 6.2 pg/mL (n = 222). We evaluated the association of serum IL-6 levels with a composite of major adverse cardiovascular events (MACE; nonfatal stroke, nonfatal acute coronary syndrome, major peripheral artery disease, and vascular death) and the poor functional outcome defined as modified Rankin Scale score of ≥ 3 at one year.

Results: Higher serum IL-6 levels were associated with increased prevalence of chronic kidney disease, atrial fibrillation, chronic heart disease, active cancer, and post-stroke pneumonia. The three groups showed significant differences in the one-year MACE risk (annual rate, 11.2%, 10.8%, and 19.1% in the tertiles 1, tertile 2, and tertile 3 groups, respectively). Higher serum IL-6 levels were significantly associated with poor functional outcomes at one year after stroke (14.4%, 29.5%, and 56.8% in the tertile 1, tertile 2, and tertile 3 groups, respectively; P＜0.001), even when adjusting for baseline covariates and MACE during follow-up.

Conclusions: Higher serum IL-6 level at ischemic stroke onset was an independent predictor of poor functional prognosis at one year.

Polygenic risk scores (PRSs), constructed from numerous common single nucleotide polymorphisms (SNPs), have emerged as useful tools for predicting future atherosclerotic cardiovascular disease (ASCVD). PRSs have shown independent associations with ASCVD outcomes and are increasingly being considered to enhance risk stratification and guide primary prevention strategies. However, most evidence to date has been derived from populations of European ancestry, and their generalizability to other populations, including East Asians, remains uncertain. This review summarizes the current epidemiological evidence on the association between PRS and ASCVD outcomes, focusing on findings in Japanese cohorts. We discuss the potential of PRS as a clinical decision support tool, its incremental value over traditional risk factors, and its role in the early identification of high-risk individuals. We also highlight the limited number of prospective studies in the Japanese population, where validation and implementation studies are ongoing. Given the growing accessibility of genetic testing and the potential of PRS to complement conventional risk assessments, further large-scale studies are warranted to evaluate its clinical utility across diverse populations. Expanding ancestry-specific biobanks and improving PRS transferability are essential steps toward the equitable implementation of genomic risk prediction in ASCVD prevention.

Aim: To evaluate the risk factors, location, treatment, and outcomes of stroke due to arterial dissection, we examined these characteristics in a substantial, long-standing, nationwide stroke cohort.

Methods: The study participants were patients with acute stroke who were registered in the Japan Stroke Data Bank between January 1999 and December 2020. We focused on patients with stroke caused by extracranial or intracranial artery dissection and examined their clinical characteristics, treatments, and outcomes. In addition, we compared the results between clinical subtypes with and without dissection.

Results: Among the 218,799 registered patients with acute stroke, 1,353 (0.62%) were attributed to artery dissection. Of these, 880 patients had ischemic stroke, 16 had intracerebral hemorrhage, and 457 had subarachnoid hemorrhage (SAH). Dissection cases were most prevalent among individuals in their 40s and 50s, with intracranial vertebral artery dissection being the primary cause of ischemic stroke and SAH. Male sex, dyslipidemia, diabetes mellitus, and a history of smoking were associated with a higher likelihood of ischemic stroke than SAH. Unfavorable outcomes, defined as a modified Rankin score ≥ 4 at discharge, were observed in 18.9% of ischemic stroke cases and 42.6% of SAH cases with dissection. Neurological severity and older age at admission are associated with unfavorable outcomes in patients with ischemic stroke and SAH.

Conclusions: Ischemic stroke was the most frequent subtype of stroke in patients with arterial dissection, followed by SAH. Patients with stroke due to dissection were younger than those without. Neurological severity and older age at admission are substantial risk factors for unfavorable stroke outcomes due to artery dissection.

Aim: The American Heart Association (AHA) proposed Life's Essential 8 score (LE8) in 2022 as a new metric for cardiovascular health (CVH). This study investigated the association between the LE8 score and the development of carotid artery plaque.

Methods: Data were drawn from the Asymptomatic Polyvascular Abnormalities Community (APAC) cohort study. In 2010, 1,938 participants without carotid plaques were recruited and followed-up until 2012. LE8 scores ranging from 0 to 100 were categorized as low (0-49), moderate (50-79), and high (80-100), whereas carotid plaques were measured using color Doppler ultrasound. A logistic analysis was used to analyze the association between the LE8 score and carotid plaque.

Results: During the 2-year follow up period, 350 (18.1%) patients developed new carotid plaques. The incidence of newly developed carotid plaques decreased from 27.0% in the low-LE8 group to 13.7% in the high-LE8 group (p＜0.001). Adjusted odds ratios (ORs) for plaque development were 0.65 (95% confidence interval [CI], 0.45-0.93) in the moderate-LE8 group and 0.55 (95% CI, 0.34-0.90) in the high-LE8 group compared to the low-LE8 group. Higher LE8 scores were associated with a lower risk of stable and multiple carotid plaques.

Conclusions: An elevated LE8 score was associated with a lower risk of carotid plaque formation as well as plaque stability and quantity. Promoting adherence to optimal CVH levels may be beneficial in reducing the burden of carotid plaques and the risk of cardiovascular disease.

Aim: Cholesterol uptake capacity (CUC) is a functional assessment of high-density lipoprotein (HDL) and has drawn attention for the risk stratification of atherosclerotic cardiovascular disease (ASCVD). This study evaluated the usefulness of HDL-CUC as a predictive marker for long-term ASCVD events in patients with coronary artery disease (CAD).

Methods: This retrospective observational study included 503 patients with CAD who underwent coronary revascularization. Blood was sampled from the participants within three months before or after index revascularization. The CUC was assayed using a previously reported automated system. The study population was divided into three groups according to the tertiles of CUC levels. The primary outcome was ASCVD events, which were defined as a composite of all-cause death, acute myocardial infarction, stroke, and peripheral artery disease.

Results: A total of 29 events were observed during the follow-up (median 2.8 years). The risk of the primary outcome in the low-CUC group was significantly higher than that in the high-CUC group (3-year incidence: low CUC 8.8% vs. high CUC 4.0%; log-rank p = 0.046). After adjusting for age and sex, the risk in the low-CUC group relative to that in the high-CUC group remained significantly high (hazard ratio 3.17, 95% confidence interval 1.05-9.54, p = 0.040).

Conclusion: Low CUC in patients with CAD were associated with a higher risk of ASCVD events after coronary revascularization than high CUC levels. The assessment of HDL functionality measured by CUC would be useful for the risk prediction of ASCVD after coronary revascularization.

Aim: Adiponectin is an anti-diabetic and anti-atherogenic protein secreted primarily from adipose tissue. Adiponectin and modified LDL (mLDL) form a complex to modulate their biological activity. To elucidate the significance of the complex formation, we analyzed its effects on vascular tissue and developed and verified novel quantifying methods for adiponectin.

Methods: To study the significance of the mLDL-adiponectin complex (MAC) formation, we used the wire-myography method on rat mesenteric artery. We developed a method to measure MAC by using LOX-1 as the capture protein and anti-adiponectin antibody for detection. We compared serum MAC levels between hemodialysis patients and control subjects.

Results: Administering mLDL alone to rat mesenteric artery impaired endothelium-dependent vasorelaxation, whereas simultaneously administering adiponectin with mLDL protected rat mesenteric artery from the mLDL-induced impairment of vasorelaxation. This finding indicates MAC formation prevents endothelium from mLDL-induced dysfunction in tissue. Using our novel ELISA for MAC, we found that MAC was increasingly detectable depending on the doses of mLDL and adiponectin in vitro. In serum, hemodialysis patients showed a significantly higher ratio of MAC-high patients (higher than the median level of MAC) than did healthy controls. Furthermore, the MAC-high hemodialysis group had lower mLDL activity measured as LOX-1 ligand containing apoB.

Conclusion: Using our ELISA, we detected MAC in human serum that protected blood vessels from the deleterious effects of oxidized LDL.

Aim: The accumulation of metabolic risk factors, namely high blood pressure, hyperlipidemia, and hyperglycemia, has been associated with cardiovascular diseases. However, little evidence is available on the prognostic significance of metabolic risk factor accumulation in nonobese individuals. This study investigated this issue by analyzing prefecture-wide health checkup and health insurance data in Japan.

Methods: We analyzed data from 366,881 adults aged 40-74 years who were enrolled in the National Health Insurance, excluding those who experienced a stroke or coronary artery diseases or required long-term care. Baseline clinical information was obtained from annual health checkup data. Incidences of stroke and coronary artery diseases were obtained from insurance data.

Results: In the nonobese population, the hazard ratio for stroke increased linearly with the number of accumulated metabolic risk factors, particularly among those aged ＜65 years men (one factor: 2.21, two factors: 2.60; three factors: 3.93) and women (one factor: 1.49, two factors: 1.57; three factors: 2.27). Similar results were observed in the analysis for coronary artery diseases. After excluding participants receiving medications, the association of metabolic risk factor with stroke remained significant, although its association with coronary artery disease became less significant. In the analysis for each metabolic risk factors, high blood pressure (men: hazard ratio = 2.85; women: hazard ratio = 2.17; P＜0.001), but not hyperlipidemia and hyperglycemia, was associated with stroke in the nonobese population.

Conclusion: The accumulation of metabolic risk factors needs to be considered a risk factor for cardiovascular diseases even in individuals without obesity.

Aims: Lipoprotein(a) (Lp[a]) exhibits atherogenic and thrombogenic properties. We investigated the association between Lp(a) levels and the risk of coronary heart disease (CHD) and stroke.

Methods: We used data from 5138 people ≥ 30 years old registered in the Suita Study, a Japanese population-based prospective cohort study. All participants were initially free from CHD or stroke. Cox proportional hazard models were applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CHD and stroke among participants with elevated Lp(a) levels.

Results: At baseline, only 17.0% of participants had Lp(a) levels ≥ 30 mg/dL. Within the median follow-up period of 11.7 years, 164 CHD and 234 stroke events were detected. In the multivariable-adjusted regression model, Lp(a) ≥ 30 mg/dL was associated with an increased risk of CHD (HR, 1.52 [95% CI, 1.05-2.21]). Every 10-ml/dL increment in Lp(a) level was associated with a 7.9% increase in CHD risk. The association with CHD did not change significantly after adjusting for total cholesterol level or lipid-lowering drugs. In contrast, increased Lp(a) levels were not associated with stroke risk or any subtype.

Conclusions: Lp(a) ≥ 30 mg/dL was associated with an increased risk of CHD in the Japanese population.

Aims: This post-hoc analysis from the Behavioural Intervention by allied health professionals to promote Physical activity (BIP) trial examined the relationship between depression and step count and walking capacity over two years in people with peripheral artery disease (PAD).

Methods: BIP included participants with walking impairment due to PAD followed up at 4, 12 and 24 months to measure step count over 7 days using an accelerometer and six-minute walking distance. The relationships between depression at entry with step count and walking distance during follow-up were assessed using linear mixed effects models.

Results: At entry, 29 (14.5%) of the 200 participants had depression being treated with anti-depressant medication. Participants diagnosed with depression were more likely to be female (13 of 29, 44.8%) than those not diagnosed with depression (43 of 171, 25.1%). Over 24 months follow-up, daily step count progressively decreased in participants with depression (mean [SD] 4406 (2266) at entry to 3888 (2555) at 24 months) as compared to no change in participants without depression (mean (SD) 5271 (2526) at entry compared to 5120 (2446) at 24 months), inter-group difference p = 0.010. No significant difference in change in six-minute walking distance over 2 years was found between participants with and those without depression.

Conclusion: Depression is associated with greater decline in self-regulated walking in patients with PAD. Effective treatments for depression are needed which help promote physical activity in people with PAD.