Aim: The optimal risk assessment model (RAM) to stratify the risk of venous thromboembolism (VTE) in medical inpatients is not known. We examined and compared how well the Padua Prediction Score (PPS) and the Caprini RAM stratify VTE risk in medical inpatients.

Methods: We undertook a retrospective case-control study among medical inpatients admitted to a large general hospital in China during a 4-year period. In total, 902 cases were confirmed to have VTE during hospitalization and 902 controls were selected randomly to match cases by medical service.

Results: The VTE risk increased significantly with an increase of the cumulative PPS or Caprini RAM score. A PPS and Caprini RAM “high risk” classification was, respectively, associated with a 5.01-fold and 4.10-fold increased VTE risk. However, the Caprini RAM could identify 84.3% of the VTE cases to receive prophylaxis according to American College of Chest Physicians guidelines, whereas the PPS could only identify 49.1% of the VTE cases. In the medical inpatients studied, five risk factors seen more frequently in VTE cases than in controls in the Caprini RAM were not included in the PPS. The Caprini RAM risk levels were linked almost perfectly to in-hospital and 6-month mortality.

Conclusions: Both the PPS and Caprini RAM can be used to stratify the VTE risk in medical inpatients effectively, but the Caprini RAM may be considered as the first choice in a general hospital because of its incorporation of comprehensive risk factors, higher sensitivity to identify patients who may benefit from prophylaxis, and potential for prediction of mortality.

Aim: Neopterin is an activation marker for monocytes/macrophages. We prospectively investigated the predictive value of plasma neopterin levels on 2-year and long-term cardiovascular events in patients with stable angina pectoris (SAP) undergoing coronary stent implantation.

Methods: We studied 123 consecutive patients with SAP who underwent primary coronary stenting (44 patients with bare metal stent: BMS group and 79 with drug-eluting stent: DES group). Plasma neopterin levels were measured on admission using HPLC. Moreover, one frozen coronary artery specimen after DES and three frozen coronary specimens after BMS were obtained by autopsy or endarterectomy, followed by immunohistochemical staining for neopterin.

Results: Plasma neopterin levels were significantly higher in patients with cardiovascular events than in those without them (P＜0.001). In subgroup analyses, higher levels of plasma neopterin in patients with cardiovascular events (P＜0.001) and a positive correlation between neopterin levels and late lumen loss after stenting (P =0.008) were observed in the BMS group but not in the DES group (P=0.53 and P=0.17, respectively). In long-term cardiovascular events, multivariate Cox regression analysis identified the significance of the high-neopterin group as independent determinants of cardiovascular events (hazard ratio, 2.225; 95% CI, 1.283–3.857; P =0.004). Immunohistochemical staining showed abundant neopterin-positive macrophages in the neointima after BMS implantation but no neopterin-positive macrophages in the neointima after DES implantation.

Conclusion: These findings suggest that neopterin is associated with cardiovascular events after coronary stent implantation in patients with SAP. However, there might be a strong association between neopterin and cardiovascular events after BMS but not after DES in these patients.

Aims: The identification and appropriate management of commercial motor vehicle (CMV) drivers with unrecognized obstructive sleep apnea (OSA) is a major public health concern and priority; OSA among drivers has not been fully investigated in Japan, and a better understanding of this undiagnosed disease is warranted. Therefore, we evaluated the prevalence of OSA and the factors related to apnea–hypopnea index (AHI) in Japanese CMV drivers.

Methods: This retrospective study included 1309 Japanese CMV drivers aged 40–69 years. All the subjects received type Ⅳ portable sleep monitors (PMs) with Epworth Sleepiness Scale (ESS) and a periodic health check including anthropometrical and laboratory measurements, and a questionnaire of medical history, smoking status, and life style, following which variables related to AHI were analyzed.

Results: Of all the subjects, 23.9% had moderate to severe OSA (AHI ≥15). Age, body mass index (BMI), Log_eHbA1c and diastolic blood pressure (DBP) showed significance with AHI in 1309 subjects. The following factors were found to have significant odds ratio (OR) for AHI of ≥15 in 1309 subjects: age, ESS, DBP, and Log_eHbA1c.

Conclusion: Notably, drivers with undiagnosed OSA exist. In these subjects, AHI was related to obesity, hypertension, and diabetes. For the early diagnosis and intervention of OSA, BMI, blood pressure, and HbA1c measurements may be helpful, particularly for drivers. Furthermore, when performing an objective assessment of the suspected OSA, evaluating these parameters during routine medical check-ups may be useful and feasible in the detection of drivers with latent OSA.

Aim: Maximal hyperemic response, leading to examination of microvascular resistance in lower-limb lesions is not well understood. This study aimed to investigate the infrainguinal arterial physiological response through a hyperemic condition and the pathophysiological significance of microvascular resistance in peripheral artery disease.

Methods: Sixteen limbs with focal stenosis of the superficial femoral artery (SFA) and 16 control limbs were analyzed. We assessed the fractional flow reserve (FFR), vascular flow reserve (VFR), and hyperemic microvascular resistance (h-MR) of the SFA with a pressure/Doppler flow sensor-tipped combination guidewire before and after endovascular therapy (EVT). Skin perfusion pressure (SPP) on both the dorsal and the plantar sides of the foot was measured at baseline before and after the endovascular procedures.

Results: FFR (p＜0.05) and VFR (p＜0.05), but not h-MR, improved after EVT. There was no association between h-MR and FFR or VFR before EVT. h-MR was negatively correlated with the dorsal SPP before EVT (r=－0.589, p＜0.05). h-MR in patients with high h-MR before EVT significantly decreased after EVT (p＜0.05). Patients with high, but not those with low, h-MR before EVT exhibited a significant increase in dorsal and plantar SPP after EVT (p＜0.05, each).

Conclusion: EVT for SFA stenosis improved FFR and VFR comprehensively, with no apparent change in h-MR. However, high h-MR before EVT may play a predictive role for limb perfusion improvement associated with h-MR reduction after EVT.

Aim: Speckle-tracking imaging has been introduced for the precise assessment of vessel mechanics. However, there are no data on the role of this imaging tool in assessing the changes in vasculature with statin therapy, which is known to enhance vascular elasticity.

Methods: This study was a prospective study including 48 statin-naïve patients (age, 58.2±8.4 years; 29.2% male) with hypercholesterolemia. Circumferential carotid artery strain (CAS) and stiffness index (β₂) were measured using speckle-tracking imaging before and after 3 months of high-dose pitavastatin treatment (4 mg daily). For the comparison, we measured conventional carotid elasticity parameters and intima–media thickness using B-mode ultrasound at the same time points.

Results: Compared with baseline, there was significant improvement in circumferential CAS (2.98%±1.18% to 3.40%±1.43%, p=0.008) and β₂ (0.19±0.07 to 0.17±0.08, p=0.047) after statin therapy. Contrariwise, there were no significant changes in all conventional carotid elasticity metrics and intima–media thickness. When stratifying patients into two subgroups by 10 year atherosclerotic cardiovascular disease (ASCVD) risk, speckle-tracking-derived circumferential CAS and β₂ improved significantly only in patients with ASCVD risk ≥ 7.5%.

Conclusions: Short-term treatment with high-dose pitavastatin improved carotid artery elasticity measured by speckle-tracking method, but not conventional parameters by B-mode ultrasound. Speckle-tracking-based measurements may allow the early noninvasive assessment of statin effects on vascular function in hypercholesterolemic patients.

Aim: Osteoglycin is one of proteoglycans that are biologically active components of vascular extracellular matrix. However, the role of osteoglycin in atherosclerosis remains unclear.

Methods: We investigated plasma osteoglycin levels and the presence, severity, and lesion morphology of coronary artery disease (CAD) in 462 patients undergoing elective coronary angiography.

Results: Of 462 patients, 245 had CAD. Osteoglycin levels were higher in patients with CAD than without CAD (median 29.7 vs. 25.0 ng/mL, P＜0.05). However, osteoglycin levels did not differ among patients with one-vessel, two-vessel, or three-vessel disease (30.8, 30.6, and 29.4 ng/mL, respectively) and did not correlate with the number of stenotic segments. Among 245 CAD patients, 41 had complex coronary lesions, and 70 had total occlusion, of whom 67 had good collateralization. Between 70 patients with occlusion and 175 without occlusion, osteoglycin levels did not differ (30.4 vs. 29.5 ng/mL). Notably, osteoglycin levels were lower in 41 patients with complex lesions than in 204 without such lesions (24.2 vs. 31.6 ng/mL, P＜0.02). In multivariate analysis, osteoglycin levels were an independent factor for complex lesion but not for CAD. Odds ratio for complex lesion was 0.80 (95%CI=0.67–0.96) for each 10 ng/mL increase in osteoglycin levels (P＜0.02).

Conclusion: Although plasma osteoglycin levels were high in patients with CAD, they did not correlate with the severity of CAD and were not an independent factor for CAD. Notably, osteoglycin levels were low in patients with complex lesions and were a factor for complex lesions, suggesting that osteoglycin plays a role in coronary plaque stabilization.

Aim: Atherosclerosis is a chronic inflammatory process of the arterial wall and carotid intima-media thickness (cIMT) is regarded as its early marker. Several members of the IL-17 family are involved in pro-inflammatory functions. The specific aim of the study was to explore the relationships of common genetic variants on IL-17 genes with cIMT thickening.

Methods: In the discovery stage, 146 SNPs on 11 IL-17 genes were screened for their relationships with cIMT by a case-control study that enrolled 284 and 464 subjects who had thicker and normal cIMT, respectively. Findings were replicated by an independent case-control study that enrolled 282 subjects who had thicker cIMT and 282 age-sex-matched subjects who had normal cIMT.

Results: Among 134 eligible SNPs in the discovery study, only IL-17RC rs279545 was significantly correlated with cIMT (p=6.9×10⁻⁵). The rs279545 and 2 nearby linked SNPs rs55847610 and rs3846167 were included in the validation study. We found that the rs279545^＊G, rs55847610^＊G, and rs3846167^＊C were correlated with significantly higher likelihoods of having thicker cIMT. The corresponding multivariate-adjusted ORs were 1.462 (95% CI: 1.055–2.027), 1.481 (95% CI:1.090–2.013), and 1.589 (95% CI: 1.147–2.200), respectively. Analyses of rs279545-rs55847610 haplotypes showed that the multivariate-adjusted OR for A-A haplotype was significantly decreased (OR=0.665, 95% CI: 0.487–0.908) and for G-G haplotype was significantly increased (OR=1.539, 95% CI: 1.097–2.161).

Conclusions: We first correlated cIMT, a preclinical clinical cardiovascular marker, with IL-17RC, the key molecule in the IL-17 signaling pathway. Our results indicated that IL-17RC may play critical role in the development of atherosclerotic diseases.

Aim: In-Stent Restenosis (ISR) is the major reason for recurrent ischemia and amputation after endovascular treatment of Peripheral Artery Disease (PAD). Our previous study demonstrated that miR-140-3p is significantly down-regulated in PAD arteries. However, expression and function of miR-140-3p in ISR of human PAD are currently unclear.

The aim of this study is to determine the miR-140-3p expression and its regulative role in ISR of PAD.

Methods: The RNA level was determined by quantitative real-time polymerase chain Reaction (qRT-PCR) and in situ hybridization. Primary cultured ASMCs were isolated from human femoral arterial of the healthy donors or ISR patients. Cell proliferation was determined by Edu incorporation and CCK-8 assay. Apoptosis was determined by Annexin-Ⅴ/PI Double-Staining assay and TUNEL assay. A rat carotid artery balloon angioplasty model was used to investigate the effect of miR-140-3p on restenosis.

Results: MiR-140-3p was significantly down-regulated in PAD and ISR arteries than normal arteries. Primary cultured ISR ASMCs exhibited elevated proliferation and down-regulated miR-140-3p than normal ASMCs. Transfection of miR-140-3p mimic attenuated PDGF-BB-induced proliferation in cultured ASMCs and induced apoptosis. Luciferase reporter assay indicated that miR-140-3p transfection significantly down-regulated C-Myb and BCL-2 in ISR ASMCs by targeting to their 3'-UTRs. MiR-140-3p transfection induced anti-proliferation and apoptosis in ASMCs, which were ameliorated by over-expression of C-Myb or BCL-2. Moreover, the animal study showed that miR-140-3p can reduce restenosis following angioplasty via targeting C-Myb and BCL-2.

Conclusions: The result suggests that miR-140-3p regulates ASMC function via targeting C-Myb and BCL-2 in the process of ISR in PAD. The novel findings may offer a hopeful therapeutic target for human PAD.