In recent years, direct oral anticoagulants (DOACs) of dabigatran, rivaroxaban, apixaban, edoxaban, which are all alternatives to warfarin, have been released. The use of DOACs is becoming more widespread in the clinical management of thrombotic stroke risk in patients with atrial fibrillation (AF). In large-scale clinical trials of each drug, DOACs were reported to inhibit intracranial hemorrhage, stroke, and death compared to warfarin. Warfarin is an endogenous vitamin K antagonist; therefore, patients who are taking warfarin must be prohibited from taking vitamin K. Vitamin K is an essential cofactor required for the ɤ-carboxylation of vitamin K-dependent proteins including coagulation factors, osteocalcin (OC), matrix Gla protein (MGP), and the growth arrest-specific 6 (GAS6). OC is a key factor for bone matrix formation. MGP is a local inhibitor of soft tissue calcification in the vessel wall. GAS6 prevents the apoptosis of vascular smooth muscle cells. Therefore, decrease of blood vitamin K levels may cause osteoporosis, vascular calcification, and the inhibition of vessels angiogenesis. This study aimed to evaluate the effects of changing from warfarin to rivaroxaban on bone mineral metabolism, vascular calcification, and vascular endothelial dysfunction. We studied 21 consecutive patients with persistent or chronic AF, who were treated with warfarin at least for 12 months. Warfarin administration was changed to rivaroxaban (10 or 15 mg/day) in all patients. Osteopontin (OPN), bone alkaline phosphatase (BAP), and under-carboxylated osteocalcin (ucOC) were measured. Pulse wave velocity (PWV) and augmentation index (AI) were also measured as atherosclerosis assessments. All measurements were done before and six months after the rivaroxaban treatment. There was a significant increase in serum level of BAP compared to baseline (12.5 ± 4.6 to 13.4 ± 4.1 U/L, P < 0.01). In contrast, there was a significant decrease in the serum level of ucOC (9.5 ± 5.0 to 2.7 ± 1.3 ng/ml, P < 0.01). Also, in the ucOC levels, there was a significant negative correlation between baseline values and baseline to 6-months changes in high ucOC group (r = -0.97, P < 0.01). The atherosclerosis- and osteoporosis-related biomarker, serum level of OPN were significantly decreased compared to baseline (268.3 ± 46.8 to 253.4 ± 47.1 ng/ml, P < 0.01). AI and PWV were significantly decreased after 6 months of treatment with rivaroxaban (33.9 ± 18.4 to 24.7 ± 18.4%, P = 0.04; 1638.8 ± 223.0 to 1613.0 ± 250.1 m/s, P = 0.03, respectively). Switching to rivaroxaban from warfarin in patients with atrial fibrillation was associated with an increase of bone formation markers and a decrease of bone resorption markers, and also improvements of PWV and AI.

Incretin hormones have been reported to have cytoprotective actions in addition to their glucose-lowering effects. We evaluated whether teneligliptin, a novel dipeptidyl peptidase-4 (DPP-4) inhibitor, affects left ventricular (LV) function in patients with type 2 diabetes mellitus (T2DM). Twenty-nine T2DM patients not receiving any incretin-based drugs were enrolled and prescribed with teneligliptin for 3 months. Compared to baseline levels, hemoglobin A1c levels decreased (7.6 ± 1.0 % to 6.9 ± 0.7 %, p < 0.01) and 1,5-anhydro-D-glucitol levels increased (9.6 ± 7.2 μg/mL to 13.5 ± 8.7 μg/mL, p < 0.01) after treatment. Clinical parameters, including body mass index and blood pressure, did not show any difference before and after treatment. Three months after treatment, there were improvements in LV systolic and diastolic function [LV ejection fraction, 62.0 ± 6.5 % to 64.5 ± 5.0 %, p = 0.01; peak early diastolic velocity/basal septal diastolic velocity (E/e') ratio, 13.3 ± 4.1 to 11.9 ± 3.3, p = 0.01]. Moreover, there was an improvement in endothelial function (reactive hyperemia peripheral arterial tonometry [RH-PAT] index; 1.58 ± 0.47 to 2.01 ± 0.72, p < 0.01). There was a significant negative correlation between changes in the E/e' ratio and RH-PAT values. Furthermore, circulating adiponectin levels increased (27.0 ± 38.5 pg/mL to 42.7 ± 33.2 pg/mL, p < 0.01) without changes in patient body weight. Teneligliptin treatment was associated with improvements in LV function and endothelial functions, and an increase in serum adiponectin levels. These results support the cardio-protective effects of teneligliptin in T2DM patients and increase in serum adiponectin levels.

Background High lipoprotein (a) [Lp(a)] levels are an independent factor for worse prognosis in patients with coronary artery disease (CAD). However, the association between serum Lp(a) level and coronary plaque vulnerability remains to be determined. Methods A total of 255 consecutive patients with CAD who underwent optical coherence tomography imaging of culprit lesions were included. Patients were divided into 2 groups according to their Lp(a) levels (the higher Lp(a) group [≥25 mg/dL], n = 87; or the lower Lp(a) group [<25 mg/dL], n = 168). Results The prevalence of thin-cap fibroatheroma (TCFA) was significantly higher in the higher Lp(a) group than in the lower Lp(a) group (23% [ n = 20] vs. 11% [ n = 19], p = 0.014). Although the prevalence of TCFA was comparable between the 2 groups among patients with a lower LDL cholesterol (LDL-C) level (<100 mg/dL), TCFA was significantly more prevalent in the higher Lp(a) group than in the lower Lp(a) group (39% [14/36] vs. 10% [5/50], p = 0.001) among patients with a higher LDL-C level (≥100 mg/dL). Conclusions A higher Lp(a) level was associated with a higher frequency of TCFA, particularly in patients with a higher LDL-C level.

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Subjects This was an observational study conducted at a single center with Japanese patients. A total of 1,021 culprit lesions in 1,021 patients who underwent optical coherence tomography (OCT) and percutaneous coronary intervention (PCI) between February 2013 and March 2019 at Kitasato University Hospital (Sagamihara, Japan) were identified. Of these, a total of 860 patients with 860 de novo lesions (171 female and 689 male) were enrolled in the present study after excluding cases of restenosis (n=132) and poor OCT of culprit lesions (n=29; Supplementary Figure 1). Because the median age in this cohort was 69 years (IQR, 60-78 years), "younger" and "elderly" were defined as <70 years old and ≥70 years old, respectively. All patients provided written informed consent for the procedure, and this study was conducted in compliance with the Declaration of Helsinki and approved by the institutional ethics committee.

The aim of this single-arm pilot study was to determine the effects of whole-body vibration training (WBVT) on endothelial function in elderly patients with cardiovascular diseases, as well as its safety. A total of 20 elderly patients with stable cardiovascular diseases underwent WBVT, which consisted of five static resistance training exercises (squats, wide stance squats, toe-stands, squats + band, and front lunges). The parameters of WBVT included vertical vibrations, 30 Hz frequency, and a 3-mm peak-to-peak amplitude. Each vibration session lasted 30 seconds, with 120 seconds of rest between sessions. Before and after WBVT, the reactive hyperemia peripheral arterial tonometry index (RH-PAT index) and transcutaneous oxygen pressure (tcPO2) were recorded as a measure of endothelial function and peripheral blood circulation. Systolic blood pressure, diastolic blood pressure, heart rate, and arterial oxygen saturation of pulse oximetry (SpO2) were measured at each rest interval as well as before and after WBVT. All patients completed our WBVT protocol without adverse events. The RH-PAT index significantly increased following WBVT (1.42 to 2.06, P < 0.001). There were no significant changes in heart rate (P = 0.777), systolic blood pressure (P = 0.183), diastolic blood pressure (P = 0.925), or SpO2 (P = 0.248) during WBVT. In conclusion, we demonstrated the acute effects of WBVT on endothelial function, with no reports of adverse events. These findings support the need for further randomized controlled studies to investigate the long-term effects of WBVT.

Cognitive impairment is frequently represented in elderly patients with cardiovascular disease (CVD); yet, the mechanism is uncertain. Recent studies have suggested the association between the vascular endothelial dysfunction and cognitive impairment. The aim of this study was to clarify the association between endothelial dysfunction and cognitive impairment in elderly patients with CVD.A total of 80 elderly patients (> 70 years old) with CVD were included. Patients who had already pharmacologically intervened for cognitive impairment were excluded. The endothelial dysfunction was assessed by the reactive hyperemia-peripheral arterial tonometry (RH-PAT). Cognitive impairment was diagnosed by the Mini-mental state examination.The RH-PAT index was significantly lower in cognitive impairment (median 1.60 [interquartile range (IQR) 1.34 to 1.89], n = 51) as compared with non-cognitive impairment (median 1.75 [IQR 1.55 to 2.30], n = 29, P = 0.005). By a multivariate analysis, the RH-PAT index was independently associated with cognitive impairment (odds ratio: 0.89; 95% confidence interval: 0.81 to 0.97; per 0.1, P = 0.044). In the receiver-operating characteristic analysis, the best cut-off of the RH-PAT index to identify cognitive impairment was 1.65 (area under the curve 0.67; P = 0.011) with limited the sensitivity (63%) and specificity (66%).A lower RH-PAT index was significantly associated with the presence of cognitive impairment in elderly CVD patients. Further studies are required to clarify the mechanism and the causal relationship between the endothelial dysfunction and cognitive impairment in patients with CVD.