Aim: One-hour post-load plasma glucose (1h-PG) during an oral glucose tolerance test and smoking are associated with arterial stiffness. However, it remains unknown whether there are synergistic effects of these two factors on arterial stiffness. This study aimed to investigate the interaction between 1h-PG and smoking in relation to brachial–ankle pulse wave velocity (baPWV) in young men with normal glucose tolerance (NGT).

Methods: The study included 25-, 30-, 35-, 40-, and 45-year-old non-industrial male workers (n=2189) who underwent a detailed health check-up. Normotensive participants with NGT and taking no medication were included.

Results: A univariate linear regression analysis showed that 1h-PG correlated with baPWV (r=0.13, p＜0.001), but the correlation was not significant in the multivariate analysis (β=0.02, p=0.24). However, we found a significant interaction between 1h-PG levels and smoking status in relation to baPWV (p=0.048). Therefore, further analyses were conducted in nonsmokers and smokers. A multivariate linear regression analysis revealed that 1h-PG significantly correlated with baPWV in smokers (β=0.11, p=0.02), but not in nonsmokers (β=0.01, p=0.79). The correlation remained significant even after adjustment for the number of cigarettes smoked per day (β=0.096, p=0.048) or the Brinkman index (β=0.097, p=0.043).

Conclusion: A significant interaction between 1h-PG and smoking in relation to baPWV was found in apparently healthy men younger than 50 years old.

Aim: Although a lower level of non-high-density lipoprotein cholesterol (HDL-C) was reported to be inversely associated with spontaneous intracranial hemorrhage (ICH), no enough evidence has verified whether lipid profiles modify hemorrhagic transformation and functional outcomes in patients with acute ischemic treated with thrombolysis.

Methods: This multicenter cohort study included 2373 patients with acute ischemic stroke treated with intravenous thrombolysis between December 2004 and December 2016. Of these, 1845 patients were categorized into either the hyperlipidemia or non-hyperlipidemia group. Symptomatic ICH (SICH) rates within 24-36 h of thrombolytic onset and functional outcomes at 30 and 90 days were longitudinally surveyed. Models of predicting hemorrhagic transformation were used to validate our findings.

Results: For enrolled 1845 patients, SICH rates were ≥2-fold reduced for the hyperlipidemia group by the NINDS (adjusted RR: 0.488 [0.281–0.846], p=0.0106), the ECASS II (adjusted RR: 0.318 [0.130-0.776], p=0.0119), and SITS-MOST standards (adjusted RR: 0.214 [0.048-0.957], p=0.0437). The favorable functional rates between the two groups were not significantly different. Lower levels of LDL-C were showed in robust association with SICH. With a cut-off LDL-C value of ＜130 mg/dL, new models are more robust and significant in predicting hemorrhagic transformation within 24-36 h.

Conclusions: This study supports the strong association between reduced LDL-C and increased SICH, but not for functional outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis. LDL-C level of ＜130 mg/dL is supposed to a candidate marker for predicting SICH within 24-36 h.

Aim: To evaluate the effect of prestroke aspirin (PA) use on initial stroke severity, early neurologic deterioration (END), stroke recurrence, hemorrhagic transformation (HT), and functional outcome in patients with ischemic stroke (IS).

Methods: This was a prospective, observational, multicenter cohort study. The acute IS patients with atherothrombosis (AT), small artery disease (SAD), or cardioembolic (CE) stroke within 24 hours of symptom onset were identified. National Institutes of Health Stroke Scale (NIHSS) scores on admission, clinical outcomes (END, recurrent ischemic stroke [RIS], myocardial infarction [MI], death, and hemorrhagic episodes), and functional outcome (modified Rankin Scale [mRS] scores) at three months after admission were compared between PA users and nonusers.

Results: Among the 1,862 patients, 401 (21.5%) reported PA use. The PA users had a significantly lower initial NIHSS score than the non-PA users. The effect was evident in AT stroke, but not in other subtypes. PA use was independently associated with the decreased risk of END. PA use increased the risk of HT; however, it was only associated with increased risk for asymptomatic HT, not for symptomatic HT. PA use was associated with better functional outcomes (mRS scores ≤2 points) irrespective of stroke subtypes at three months after admission, despite the increased risk of HT.

Conclusions: PA use may reduce initial stroke severity in AT stroke and the risk of END, and can improve functional outcome at three months irrespective of stroke subtypes.

Aim: Idiopathic membranous nephropathy (IMN) is an immune-mediated inflammatory disease characterized by a high risk of thromboembolic complications. Microparticles (MPs), a type of extracellular vesicles, have procoagulant properties, especially when they display tissue factor (TF). This study aimed to investigate whether circulating TF-positive MPs contributed to the hypercoagulable state in patients with IMN.

Methods: Twenty adult IMN patients and fourteen healthy subjects were included in the study. The basic indexes of a routine biochemical examination and coagulative function were determined. The plasma levels of MPs were detected by flow cytometry, and TF activity of MPs was examined using an assay kit. The plasma levels of lipopolysaccharide (LPS) were measured by an enzyme-linked immunosorbent assay.

Results: Total circulating MPs were not increased in patients with IMN compared with healthy controls. Circulating CD14^＋/TF^＋MPs were significantly increased in IMN patients, but this achieved significance was not observed in CD41^＋/TF^＋MPs between the two groups. Interestingly, the circulating TF-positive MPs were increased significantly. Plasma MPs TF assays revealed high procoagulant activity, which was positively associated with the D-dimer level in IMN. In addition, circulating LPS in IMN patients were significantly higher than those in the controls. Furthermore, after two hours' incubation with healthy whole blood, LPS enhanced the release of circulating TF-positive MPs and the TF activity of MPs.

Conclusion: Increased circulating LPS may mediate the release of monocyte-derived TF-positive MPs, which further contributes to the hypercoagulable state in IMN patients. These findings provide an additional mechanism by which patients with IMN have a higher risk of thromboembolic complication.

Aim: This study was designed to analyze microparticles (MPs) from endothelial cells (EMPs) and immune cells from healthy individuals and paitents with Takayasu arteritis (TA), and any possible relationships between MPs and TA acitivity.

Methods: MPs derived from the plasma of 51 subjects were analyzed, including 32 patients with TA and 19 healthy individuals. Flow cytometry was performed with Annexin (Anx)-V and antibodies against surface markers of endothelial cells (CD144), T cells (CD3), B cells (CD19), and monocytes (CD14).

Results: The concentrations of total EMPs, AnxV＋ EMPs and AnxV- EMPs were significantly increased when comparing patients with TA and healthy controls (54×10³ vs. 32×10³ MPs /ml, P=0.0004; 22×10³ vs. 12×10³ MPs /ml, P=0.0006; and 31×10³ vs. 19×10³ MPs /ml, P=0.0005), and comparing active TA patients with remission ones (85×10³ vs. 45×10³ MPs /ml, P=0.016; 39×10³ vs. 14×10³ MPs /ml, P=0.0092; and 47×10³ vs.29×10³ MPs /ml, P=0.0371). In addition, the concentrations of total EMPs (odds ratio [OR]=1.024, 95% confidence interval [CI]: 1.001 to 1.048, P=0.037), AnxV＋(OR=1.089, 95%CI: 1.011 to 1.172, P=0.024), and AnxV- EMPs (OR=1.029, 95% CI: 1.002 to 1.056, P=0.034) were positively related to TA activity. With multiple linear regression analysis, platelet was associated with both total and AnxV- EMP concentrations independently, while erythrocyte sedimentation rate was independently correlated with AnxV＋EMPs.

Conclusion: Concentrations of endothelial microparticles are correlated with inflammation in Takayasu arteritis and may be useful markers to assess disease activity.

Aims: The EXPLORE-J study aimed to assess lipid management in patients hospitalized for acute coronary syndrome (ACS) and their cardiovascular risk despite undergoing standard therapy. Here, we focused on background characteristics of patients in the EXPLORE-J study to elucidate the current lipid-lowering therapy and its issues in Japan.

Methods: In this multicenter, prospective, observational study (UMIN000018946), consecutive Japanese ACS patients who required hospitalization were registered between April 2015 and August 2016. Background and lipid profile data collected within 14 days of hospitalization were analyzed according to risk factors such as diabetes mellitus status.

Results: In total, 1944 patients were analyzed (80.3% male). The mean and standard deviation (SD) age and body mass index of all patients were 66.0 years (SD: 12.2) and 24.24 kg/m² (SD: 3.59), respectively. The most common lipid-modifying medication used at the time of ACS was statins (27.3%). The low-density lipoprotein cholesterol (LDL-C) level (first measurement after hospitalization) of patients overall was 121.2 mg/dL (SD: 39.7); 30.3% had an LDL-C level ＜100 mg/dL (current target level for secondary prevention of cardiovascular events in Japan), compared with 52.1% of patients with a previous history of coronary artery disease (CAD), and 57.2% of patients with a history of CAD and diabetes.

Conclusions: Many patients were not meeting Japanese LDL-C target levels at the time of ACS, and a large proportion of patients meeting target levels developed ACS; therefore, more stringent management and further evaluation of the target LDL-C levels is warranted in high-risk patients and those with previous history of CAD.

Aim: Betatrophin, a recently identified circulating adipokine, affects lipid and glucose metabolism. However, association between plasma betatrophin levels and atherosclerotic diseases, such as coronary artery disease (CAD) and peripheral artery disease (PAD), has not been elucidated.

Methods: We investigated plasma betatrophin levels in 457 patients undergoing elective coronary angiography who also had ankle-brachial index (ABI) test for PAD screening.

Results: Of the 457 study patients, CAD was present in 241 patients (53%) (1-vessel [1-VD], n=99; 2-vessel [2-VD], n=71; 3-vessel disease [3-VD], n=71). Compared to 216 patients without CAD, 241 with CAD had higher betatrophin levels (median 1120 vs. 909 pg/mL, p＜0.001). A stepwise increase in betatrophin levels was found depending on the number of ＞50% stenotic coronary vessels: 909 in CAD(-), 962 in 1-VD, 1097 in 2-VD, and 1393 pg/ml in 3-VD (p＜0.001). Betatrophin levels correlated with the number of ＞25% stenotic segments (r=0.24, p＜0.001). PAD (ABI＜0.9) was found in 41 patients (9%). Plasma betatrophin levels were also significantly higher in 41 patients with PAD than in 416 without PAD (1354 vs. 981 pg/mL, p＜0.001). In the multivariate analysis, betatrophin levels were not a factor for CAD, but they were a significant factor for 3-VD and PAD independent of atherosclerotic risk factors. The odds ratios for 3-VD and PAD were 1.06 (95%CI=1.01-1.11) and 1.07 (95%CI=1.01-1.13) for a 100-pg/mL increase in betatrophin levels, respectively (p＜0.05).

Conclusion: Plasma betatrophin levels were associated with the presence and severity of CAD and PAD, suggesting betatrophin has a role in atherosclerosis.