Aim: Many cohort studies have shown that increased trans fatty acid (TFA) intake increases the risk of developing coronary heart disease. However, whether TFA intake is directly associated with the development of diabetes mellitus (DM) remains unknown.
Methods: We performed the 75-g oral glucose tolerance test in two Japanese cohorts: a cohort of 454 native Japanese living in Hiroshima, Japan, and a cohort of 426 Japanese-Americans living in Los Angeles, USA, who shared identical genetic predispositions but had different lifestyles. Serum elaidic acid concentration was measured and compared, and its association with insulin resistance was assessed.
Results: Serum elaidic acid concentrations were significantly higher in the Japanese-Americans (median, 18.2 µmol/L) than in the native Japanese (median, 11.0 µmol/L). The serum elaidic acid concentrations in the native Japanese DM group (16.0 µmol/L) were significantly higher compared with those in the normal glucose tolerance (10.8 µmol/L) and impaired glucose tolerance (11.7 µmol/L) groups. Multiple linear regression analyses showed that serum elaidic acid concentrations were significantly positively associated with homeostasis model assessment for insulin resistance (HOMA-IR) values after adjusting for various factors.
Conclusions: These results suggest that excessive TFA intake worsens insulin resistance and increases the risk of developing DM even in the native Japanese, whose intakes of animal fat and simple carbohydrates were presumed to be lower than those of the Japanese-Americans.
Aim: Accelerated thrombin action is associated with insulin resistance. It is known that upon activation by binding to dermatan sulfate proteoglycans, heparin cofactor Ⅱ(HCⅡ) inactivates thrombin in tissues. Because HCⅡ may be involved in glucose metabolism, we investigated the relationship between plasma HCⅡ activity and insulin resistance.
Methods and Results: In a clinical study, statistical analysis was performed to examine the relationships between plasma HCⅡ activity, glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), and homeostasis model assessment-insulin resistance (HOMA-IR) in elderly Japanese individuals with lifestyle-related diseases. Multiple regression analysis showed significant inverse relationships between plasma HCⅡ activity and HbA1c (p=0.014), FPG (p=0.007), and HOMA-IR (p= 0.041) in elderly Japanese subjects. In an animal study, HCⅡ＋/＋ mice and HCⅡ＋/− mice were fed with a normal diet or high-fat diet (HFD) until 25 weeks of age. HFD-fed HCⅡ＋/− mice exhibited larger adipocyte size, higher FPG level, hyperinsulinemia, compared to HFD-fed HCⅡ＋/＋ mice. In addition, HFD-fed HCⅡ＋/− mice exhibited augmented expression of monocyte chemoattractant protein-1 and tumor necrosis factor, and impaired phosphorylation of the serine/threonine kinase Akt and AMP-activated protein kinase in adipose tissue compared to HFD-fed HCⅡ＋/＋ mice. The expression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase was also enhanced in the hepatic tissues of HFD-fed HCⅡ＋/− mice.
Conclusions: The present studies provide evidence to support the idea that HCⅡ plays an important role in the maintenance of glucose homeostasis by regulating insulin sensitivity in both humans and mice. Stimulators of HCⅡ production may serve as novel therapeutic tools for the treatment of type 2 diabetes.
Aim: Children exposed to parental smoking are at increased long-term risk of subclinical atherosclerosis in adulthood. However, it has not been quantified if exposure to parental smoking in childhood is associated with adult systemic inflammation. This study aimed to determine if childhood exposure to parental smoking was associated with high-sensitivity C-reactive protein (hsCRP) in adulthood.
Methods: This longitudinal analysis of 2,511 participants used data from the Cardiovascular Risk in Young Finns Study, a prospective cohort of Finnish children. In 1980 or 1983, parents self-reported their smoking status and serum hsCRP was collected up to 31 years later in adulthood.
Results: Compared with children with non-smoking parents, the relative risk of developing high hsCRP (＞3 mg/L) in adulthood increased among those with 1 or both parents who smoked [relative risk (RR), 1.3; 95%confidence interval (CI), 1.0-1.8] after adjustment for socioeconomic status, cardiovascular risk factors, and smoking status in childhood and adulthood. Moreover, children exposed to mother smoking [RR, 2.4; 95% CI, 1.3-4.2] had highest risk of developing high hsCRP in adulthood compared with those exposed to father smoking [RR, 1.6; 95% CI, 1.2-2.3] and both parents smoking [RR, 1.4; 95% CI, 0.9-2.0].
Conclusion: Our findings suggest that children exposed to parental smoking are at increased risk of having high hsCRP in adulthood. Limiting children's exposure to passive smoking may have long-term benefits on general low-grade inflammation.
Aim: A successful antegrade wire crossing for femoro-popliteal chronic total occlusion (FP-CTO) is still a technical challenge. We attempted to demonstrate the safety and feasibility of the OUTBACK® Elite reentry catheter and the bi-directional approach for failed FP-CTO cases with the antegrade approach.
Methods: Endovascular therapy for FP-CTO was performed in 219 lesions from May 2013 to December 2016 at Morinomiya Hospital. We retrospectively analyzed the data of 43 consecutive lesions which underwent endovascular therapy using the bi-directional approach with distal access and the mono-directional approach with the OUTBACK® Elite reentry catheter for FP-CTO lesions. The antegrade success using a combination of traditional and Intravascular Ultrasound (IVUS) -guided techniques was achieved in 170 lesions out of a total of 219 lesions. From May 2013 to June 2016 (phase 1), the bi-directional approach with distal access was applied to 22 lesions after failed antegrade approaches. From July 2016 to December 2016 (phase 2), the mono-directional approach with the OUTBACK® Elite reentry catheter was applied to 21 lesions.
Results: Clinical and lesion characteristics in phase 1 were not significantly different from those in phase 2. The overall initial technical success rate was 100% in both phases. The total wire number and amount of contrast media were significantly less, and the total procedure time and the total fluoroscopic time were significantly shorter in phase 2 than in phase 1 (p＜0.01).
Conclusions: Endovascular therapy for FP-CTO using the OUTBACK® Elite reentry catheter is feasible and safe after a failed antegrade approach.
Aim: The aim of this study was to investigate whether information on arterial stiffness can improve the value of single-photon emission computed tomography (SPECT) in the detection of obstructive coronary artery disease (CAD).
Methods: A total of 233 patients (age: 62.2±10.8 years, 60.3% males) with detected ischemia on SPECT undergoing invasive coronary angiography (ICA) and brachial-ankle pulse wave velocity (baPWV) measurement within a month was retrospectively reviewed.
Results: Of the 233 patients, 190 (81.5%) had obstructive CAD (≥50% luminal stenosis). The difference in baPWV according to the presence of obstructive CAD was significant in patients in the mild ischemia group [summed stress score (SSS): 4–8] (1,770±364 cm versus 1,490±328 cm, p＜0.001) but not in the moderate (SSS: 9–13) or severe (SSS: ≥14) ischemia groups (p＞0.05 for each). Receiver operating characteristic curve analyses showed that the diagnostic value of baPWV for obstructive CAD was significant only in patients in the mild ischemia group (area under curve: 0.714; p=0.001) but not in the moderate or severe ischemia groups (p＞0.05 for each). Adding information on baPWV to SPECT results and clinical parameters significantly increased diagnostic accuracy in the detection of obstructive CAD in patients with mild ischemia (integrated discrimination improvement p=0.006) but not in those with moderate or severe ischemia on SPECT (p＞0.05 for each).
Conclusions: The results of this study suggest that baPWV may have additional value to SPECT for the detection of obstructive CAD, especially in patients with mild ischemia on SPECT.
Aim: To investigatethe association of plasma epoxyeicosatrienoic acids (EETs) with early neurologic deterioration (END), and whether EETs are mediated by EPHX2 variants in patients with minor ischemic stroke (MIS).
Method: This was a prospective, multi-center observational study in patients with acute MIS in the Chinese population.Plasma EETs levels were measured on admission. Single nucleotide polymorphisms (SNPs) of EPHX2 rs751141 were genotyped using mass spectrometry. The primary outcome was END within 10 days after admission. END was defined as an increase in NIHSS of 2 or more points. The degree of disability was assessed using the modified Rankin Scale (mRS) at 3 months after admission.
Results: A total of 322 patients were enrolled, of which 85 patients (26.4%) experienced END. The mean EETs level was 64.1±7.5 nmol/L. EETs levels were significantly lower in patients with END compared to patients without END. Frequency of EPHX2 rs751141 GG was higher in patients with END than in patients without END, and EPHX2 rs751141 GG genotype was associated with lower EETs levels. Low level (＜64.4 nmol/L) of EETs was an independent predictor of END (first and second quartiles) in multivariate analyses. END was associated with a higher risk of poor outcome (mRS scores 3–6) at 3 months.
Conclusion: END is fairly common and associated with poor outcomes in acute MIS. EPHX2 variants may mediate EETs levels, and low levels of EETs may be a predictor for END in acute MIS.
Aim: Stroke is associated closely with vascular homeostasis, and several complex processes and interacting pathways, which involve various genetic and environmental factors, contribute to the risk of stroke. Although adrenomedullin (ADM) has a number of physiological and vasoprotective functions, there are few studies of the ADM receptor system in humans. The ADM receptor comprises a calcitonin-receptor-like receptor (CLR) and receptor activity-modifying proteins (RAMPs). We analyzed single nucleotide polymorphisms (SNPs) in the RAMP2 and CLR genes to determine their association with stroke in the light of gene-environment interactions.
Methods: Using cross-sectional data from the Japan Multi-Institutional Collaborative Cohort Study in the baseline surveys, 14,087 participants from 12 research areas were genotyped. We conducted a hypothesis-based association between stroke prevalence and SNPs in the RAMP2 and CLR genes based on data abstracted from two SNPs in RAMP2 and 369 SNPs in CLR. We selected five SNPs from among the CLR variants (rs77035639, rs3815524, rs75380157, rs574603859, and rs147565266) and one RAMP2 SNP (rs753152), which were associated with stroke, for analysis.
Results: Five of the SNPs (rs77035639, rs3815524, rs75380157, rs147565266, and rs753152) showed no significant association with obesity, ischemic heart disease, hypertension, dyslipidemia, and diabetes. In the logistic regression analysis, rs574603859 had a lower odds ratio (0.238; 95% confidence interval, 0.076–0.745, adjusted for age, sex, and research area) and the other SNPs had higher odds ratios for association with stroke.
Conclusions: This was the first study to investigate the relationships between ADM receptor genes (RAMP2 and CLR) and stroke in the light of gene-environment interactions in human.