Aims: We investigated the optimal cut-off points of nonfasting and fasting triglycerides in Japanese individuals with lower average triglyceride levels than westerners.

Methods: Residents aged 40–69 years without a history of ischemic heart disease or stroke were enrolled between 1980 and 1994 and followed. Serum triglyceride concentrations were measured from 10851 nonfasting (＜8 h after meal) and 4057 fasting (≥ 8 h) samples. As a prerequisite, we confirmed the shape of a receiver operating characteristic (ROC) curves, the area under ROC curves (AUC), and the integrated time-dependent AUC. We identified optimal cut-off points for incident ischemic heart disease based on C-statistic, Youden index, and Harrell’s concordance statistic. We used dichotomized concentrations of triglycerides via the univariate logistic regression and Cox proportional hazards regression models. We also calculated multivariable hazard ratios and population attributable fractions to evaluate the optimal cut-off points.

Results: Nonfasting and fasting optimal cut-off points were 145 mg/dL and 110 mg/dL, with C-statistic of 0.594 and 0.626, Youden index of 0.187 and 0.252, and Harrell’s concordance statistic of 0.590 and 0.630, respectively. The corresponding multivariable hazard ratios of ischemic heart disease were 1.43 (95%CI 1.09–1.88) and 1.69 (1.03–2.77), and the corresponding population attributable fractions were 16.1% (95%CI 3.3–27.2%) and 24.6 (−0.3–43.3).

Conclusion: The optimal cut-off points of nonfasting and fasting triglycerides in the Japanese general population were 145 mg/dL and 110 mg/dL, respectively, lower than the current cut-off points recommended in the US and Europe.

Aim: Cardiovascular disease (CVD) is the second largest cause of death in Japanese women. Pregnancy and childbirth are events that put a strain on the cardiovascular system. When postpartum weight retention is insufficient, weight gain due to fat deposition during pregnancy might lead to obesity. Thus, we examined the effects of body mass index (BMI) in middle and older ages and the number of children on CVD and metabolic disorders.

Methods: From the Tohoku Medical Megabank database, we used data from 32,000 women aged ≥ 50 years. This database contains obstetrical history, medical history, and laboratory data obtained once from 2013 to 2015.

Results: The mean age of participants was 64.2 years, and 47.7% of women had two children. Compared with nulliparous women, those who had a higher number of children had higher BMI and systolic blood pressure. The prevalence of CVD was highest in obese class I (30 kg/m² ≤ BMI) women with three or more children and the prevalence of hypertension was high in pre-obese (25 kg/m² ≤ BMI ＜30 kg/m²) and obese class I women with children. Conversely, the prevalence of diabetes and proportion of women whose HbA1c values were ＞6.5% was highest in obese class I women with no children.

Conclusion: In this study, we found that not only BMI but also the number of children influenced the health status of middle- and older-aged women, suggesting the importance of childbirth history in the health management of women.

Aim: Roles of fibroblast growth factor 23 (FGF23) in endothelial dysfunction remain controversial, and evidence from population-based studies is lacking. The present study aimed to explore the effects of FGF23 on endothelial dysfunction on the basis of both clinical data of patients with coronary artery disease (CAD) and the in vitro research in human umbilical vein endothelial cells (HUVECs).

Methods: A total of 321 CAD patients were enrolled after coronary angiography, brachial artery flow-mediated dilation (FMD) was assessed using ultrasound equipment. Serum FGF23, nitric oxide (NO), and endothelin-1 (ET-1) were detected via enzyme-linked immunosorbent assay. Apoptosis was determined using the annexin V-fluorescein isothiocyanate/propidium lodide apoptosis detection kit. Cell migration was evaluated by wound healing and transwell migration assays. Reactive oxide species levels were determined using fluorescent probes, and NF-κB p65 nuclear translocation was assessed via immunofluorescence.

Results: Serum FGF23 was significantly increased in CAD patients combined with severe endothelial dysfunction (FMD ＜2%) compared to those with FMD ≥ 2% (P＜0.001). Furthermore, the levels of FGF23 were negatively correlated with NO, whereas positively correlated with ET-1 both in unadjusted analysis and multivariate-adjusted analysis. In HUVECs, FGF23 interfered with the bioavailability of NO via increased oxidative stress. Moreover, FGF23 directly impaired the endothelium by promoting HUVECs apoptosis and attenuating the migration of HUVECs. Additional experiments showed that FGF23 induced endothelial injury through activation of the NF-κB signaling pathway.

Conclusions: Elevated FGF23 is clinically associated with endothelial dysfunction in CAD patients, and FGF23 impairs endothelial function through activation of the NF-κB signaling pathway.

Aim: We aimed to examine the impact of overweight and obesity on mortality from nonrheumatic aortic valve disease.

Methods: In the Japan Collaborative Cohort Study, we analyzed data of 98,378 participants aged 40–79 years, with no history of coronary heart disease, stroke, or cancer at baseline (1988–1990) and who completed a lifestyle questionnaire including height and body weight; they were followed for mortality until the end of 2009. The Cox proportional hazards model was used to calculate the multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) of nonrheumatic aortic valve disease mortality according to body mass index (BMI) after adjusting for potential confounding factors.

Results: During the median 19.2 years follow-up, 60 deaths from nonrheumatic aortic valve disease were reported. BMI was positively associated with the risk of mortality from nonrheumatic aortic valve disease; the multivariable HRs (95% CIs) were 0.90 (0.40–2.06) for persons with BMI ＜21 kg/m², 1.71 (0.81–3.58) for BMI 23–24.9 kg/m², 1.65 (0.69–3.94) for BMI 25–26.9 kg/m², and 2.83 (1.20–6.65) for BMI ≥ 27 kg/m² (p for trend=0.006), compared with persons with BMI 21–22.9 kg/m². Similar associations were observed between men and women (p for interaction=0.56). Excluding those who died during the first ten years of follow-up or a competing risk analysis with other causes of death as competing risk events did not change the association materially.

Conclusions: Overweight and obesity may be independent risk factors for nonrheumatic aortic valve disease mortality in Asian populations.

Aim: Mechanical thrombectomy (MT) has become the gold standard for the treatment of large vessel occlusion (LVO) in acute ischemic stroke. However, it remains controversial whether emergency angioplasty or stenting in patients with intracranial atherosclerotic stenosis (ICAS) should be adopted. Thus, we performed a retrospective analysis of clinical data to determine whether emergency angioplasty or stenting is necessary.

Methods: We retrospectively analyzed data from patients undergoing MT with ICAS-related LVO of the acute anterior circulation between 2017 and 2019. Eligible patients were divided into two treatment groups: those who received rescue angioplasty or stenting [Patients treated with rescue angioplasty or stenting (PTAS) group] and those who received thrombectomy alone (non-PTAS group). The primary outcomes were good prognosis at 90 days (mRS: 0–2). Mortality, symptomatic intracranial hemorrhage, and reocclusion rate were evaluated as secondary outcomes.

Results: A total of 184 patients with severe stenosis after MT were enrolled, including 64 patients receiving rescue angioplasty or stenting and 120 patients without rescue angioplasty or stenting. Compared with the non-PTAS group, a better functional outcome (mRS0-2) (51.6% vs. 35.0%, adjusted odds ratio: 2.11, 95% confidence interval [CI]: 1.22–4.29; P=0.02), lower 7-day National Institutes of Health Stroke Scale [6 (3–12.75) vs. 10 (4–16); P=0.04], lower 24-h neurological deterioration rate (7.8% vs. 21.7%, P=0.02), and lower 24-h reocclusion rate were observed in the PTAS group (6.3% vs. 17.5%, P=0.03). There were no significant differences in mortality or incidence of symptomatic intracerebral hemorrhage.

Conclusion: Emergency angioplasty or stenting could be a safe and feasible therapeutic option with better outcomes for stroke patients with ICAS-related LVO.

Aim: Perilipins (PLINs), peripheral lipid droplet (LD) proteins, play important roles in lipid accumulation and maturation in adipocytes. The relationship between PLIN family proteins and macrophage polarization in atherosclerosis has not been elucidated.

Methods: The experiments used tissues from human arteries of 65 patients who had undergone a carotid endarterectomy, and cultured macrophages generated from healthy human peripheral blood mononuclear cells.

Results: Plaque immunohistochemistry demonstrated co-expression of PLIN1 and PLIN2 in both symptomatic (n=31) and asymptomatic patients (n=34). PLIN2 mRNA expression increased 3.38-fold in the symptomatic group compared with those from asymptomatic. PLIN1 was not expressed on small LDs at a shorter incubation but was on large LDs at longer incubation with oxidized LDL and VLDL, while PLIN2 was observed after 24 h and increased with a longer incubation in cultured M1 macrophage. In M2 macrophages, PLIN1 was seen as early as 24 h following incubation with VLDL, and LD size increased with longer incubation. PLIN1 overexpression increased the size of LDs in M1 macrophages, even after a short incubation, and reduced the RNA expression of TNFA, MMP2, ABCA1, and ABCG1 versus the M1 control. Conversely, silencing of PLIN1 in M2 macrophages had the opposite effects on LD size and RNA expression.

Conclusion: There was a relationship between macrophage polarity, cytosolic LD size, and PLIN1/PLIN2 expression levels. PLIN2 was mainly expressed in arterial plaques in symptomatic stroke patients, and associated with the inflammatory phenotype of human macrophages, while PLIN1 expression is closely associated with plaque stability and the anti-inflammatory phenotype.

Aims: The basilar artery (BA) geometry and plaque characteristics may play an important role in the development of atherosclerosis. This study was performed to explore the relationship between the mid-BA angle and plaque characteristics and its effect on pontine infarction using high-resolution magnetic resonance imaging and three-dimensional time-of-flight magnetic resonance angiography.

Methods: In total, 77 patients with BA plaques were included in this study. According to the presence of acute pontine infarction on diffusion-weighted imaging, the patients were divided into a pontine infarction group and pontine non-infarction group. The mid-BA angle, plaque burden, stenosis ratio, positive remodeling, and intraplaque hemorrhage were evaluated to investigate their effects on stroke.

Results: The pontine infarction group had a greater plaque burden, stenosis ratio, positive remodeling, and mid-BA angle than the pontine non-infarction group. The correlation between the plaque burden and mid-BA angle was the highest (r=0.441, P＜0.001). Multivariate logistic regression analysis showed that the plaque burden (odds ratio, 1.164; 95% confidence interval, 1.093–1.241; P＜0.001) was an independent risk factor for pontine infarction.

Conclusion: The mid-BA angle may increase the incidence of pontine infarction by increasing the plaque burden.

Aims: This prospective observational study, which utilized repeated annual measurements performed over a 9-year period, applied mixed model analyses to examine age-related differences in longitudinal associations between alcohol intake and arterial stiffness, pressure wave reflection, and inflammation.

Methods: In 4016 middle-aged (43±9 years) healthy Japanese male employees, alcohol intake, brachial-ankle pulse wave velocity (baPWV), radial augmentation index (rAI), and serum C-reactive protein (CRP) levels were measured annually during a 9-year study period.

Results: The estimated marginal mean baPWV (non-drinkers=1306 cm/s, mild–moderate drinkers=1311 cm/s, and heavy drinkers=1337 cm/s, P＜0.01) and that of rAI showed significant stepped increases in an alcohol dose-dependent manner in the entire cohort, but an increase in rAI was not observed in subjects aged ≥ 50 years. The estimated slope of the annual increase in baPWV, but not rAI, was higher for heavy drinkers than for non-drinkers (slope difference, 1.84; P＜0.05), especially for subjects aged ＜50 years (slope difference, 2.84; P＜0.05).

Conclusion: In middle-aged male Japanese employees, alcohol intake may attenuate inflammatory activity. While alcohol intake may exacerbate the progression of arterial stiffening in a dose-dependent manner without mediating inflammation, especially in subjects under 50 years of age, it may promote pressure wave reflection abnormalities with aging at earlier ages without further exacerbation at older ages.