"Vascular failure" is a new concept, which can be used interchangeably with "vascular dysfunction". It can be evaluated with several arterial properties, such as endothelial function, arterial stiffness, wave reflection, and intima-media thickness. The current Chinese hypertension guidelines recommend some of these vascular properties for risk assessment and stratification in the management of hypertension. However, none of these measurements are routine in the clinical setting in China, because of the lack of available devices and insufficient knowledge on the clinical efficacy of these vascular measurements. In order to improve the use of these vascular measurements in clinical practice, therapeutic research is required to prove reversibility of vascular failure by either pharmacological treatments or lifestyle modifications. Other research directions include identification of emerging risk factors, risk prediction and prevention with vascular measurements, and the development of newer, more accurate and efficient devices.

Currently, the prevalence of hypertension (HT), diabetes mellitus (DM), and hyperlipidemia (HL) is high, and these diseases are important risk factors for cardiovascular disease (CVD). Furthermore, patients with CVD often have more than one of these diseases. Generally, patients take multiple drugs for each disease. Therefore, clinicians must pay attention to drug interactions. Although HT, DM, and HL are different diseases, they share some of the same pathophysiological mechanisms and ultimately lead to the same cardiovascular events.

Currently, most patients with CVD are treated with 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins), and various beneficial pleiotropic effects of statins have been reported since the 1990s.

In this review, we evaluate the additional effects of antihyperlipidemic agents on blood pressure (BP).

Background: Irbesartan has been reported to inhibit renal uric acid reabsorption and thereby decrease serum uric acid (Sur) levels. However, its effect on uric acid metabolism in hypertensive patients has not been reported. Methods and Results: We conducted a retrospective observational study that included 40 hypertensive patients to clarify the effects of irbesartan (mean dose 87.5 mg) on blood pressure (BP) and uric acid metabolism [Sur, urinary uric acid (Uur), serum creatinine (Scr), urinary creatinine (Ucr), uric acid clearance (Cur), creatinine clearance (Ccr), urinary uric acid to urinary creatinine ratio (Uur/Ucr), and uric acid clearance to creatinine clearance ratio (Cur/Ccr) ] at baseline and after 3 months of treatment. We allocated patients into two groups, patients with Uur/Ucr <0.5 (low Uur/Ucr group) or those with Uur/Ucr ≥0.5 (normal/high Uur/Ucr group), into other two groups, patients with Cur/Ccr <5.5% (low Cur/Ccr group) or those with Cur/Ccr ≥5.5% (normal/ high Cur/Ccr group). The hypoexcretion group contained low Uur/Ucr group and low Cur/Ccr group, and the normal/ hyperexcretion group contained normal/high Uur/Ucr group and normal/ high Cur/Ccr group. Further, we allocated patients into another two groups, patients with Sur ≥7 mg/dl (hyperuricemic group) or those with Sur <7 mg/dl (normouricemic group). Irbesartan significantly decreased systolic BP without affecting heart rate, and decreased Sur without altering Uur/Ucr or Cur/Ccr. In the hypoexcretion group, irbesartan decreased Sur while increasing Uur/Ucr and Cur/Ccr. In contrast, in the normal/hyperexcretion and hyperuricemic groups, irbesartan decreased Sur without changing Uur/Ucr or Cur/Ccr. In a normouricemic group, patients showed no changes in Sur after treatment with irbesartan. Conclusions: Irbesartan improved the secretion of uric acid, and reduced Sur in the hypoexcretion group, but did not influence uric acid excretion in the normal/hyperexcretion group. In hyperuricemic patients, irbesartan did not affect uric acid excretion but may have influenced uric acid production.

Recently, inhibition of absorbed cholesterol has been reported to reduce the recurrence of vascular events in patients with acute coronary syndrome. However, the effect of absorbed cholesterol on atherosclerosis in healthy subjects remains unclear. In the present study, we investigated the relationship between cholesterol synthesis and absorption biomarkers, and vascular elasticity or morphological changes in healthy subjects. Methods: Among 580 subjects who underwent a complete medical checkup between 2012 and 2015, 256 healthy subjects (male/female: 161/95; mean age, 55±10 years) who did not receive any medication were included in the present study. We measured blood pressure, heart rate, blood glucose level, lipid parameters, lathosterol level (cholesterol synthesis marker), and campesterol level (cholesterol absorption marker). We then analyzed the relationship between these measured values and vascular elasticity (cardio-ankle vascular index [CAVI]) or carotid arterial plaque score (CAPS). Results: The CAVI and CAPS significantly correlated with the campesterol-to-lathosterol ratio (CAVI; r=-0.20, p=0.015; CAPS; r=-0.16, p=0.023). Multivariate analysis of conventional atherosclerotic factors and campesterol-to-lathosterol ratio for CAVI and CAPS as the objective variables showed that age, systolic blood pressure, low-density lipoprotein-to-high-density lipoprotein ratio, and campesterol-to-lathosterol ratio were the significant determining factors for CAVI, and age and campesterol-to-lathosterol ratio were the determining factors for CAPS. Discussion: We found that absorbed cholesterol is closely related to vascular elasticity and morphological changes, and that a higher balance of absorption could induce favorable effects on atherosclerosis in healthy subjects. These findings might propose new nutritional guidance for healthy subjects.

Background: Although there have been studies comparing percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), few comparative cost-benefit analyses using reimbursement data have been performed, especially in Japan. Data from the Diagnosis Procedure Combination/Per-Diem Payment System (DPC/PDPS), a reimbursement system in Japan, may be useful in performing a cost-benefit analysis. Methods and Results: Between July 2008 and March 2016, a total of 48,177 patients were admitted to Saga University Hospital. Using DPC/PDPS data, we identified 638 patients without a history of myocardial infarction who underwent PCI (Group PCI, n=462) or isolated CABG (Group CABG, n=176). There were no marked differences in the mortality rate, but the incidence of myocardial infarction was higher in Group PCI. A multivariate logistic regression analysis showed that performing PCI was a significant risk factor for myocardial infarction. The number of admissions was smaller in Group CABG, but the medical cost was higher and the total hospital stay was longer than in Group PCI. However, after three or more PCIs, the difference in medical cost disappeared between PCI and CABG. Conclusions: In our single-center experience, we were able to show that, while there was no marked difference in the survival rate, the incidence of myocardial infarction was higher with PCI than with CABG. PCI required multiple admissions but was less costly than CABG. The feasibility of using the DPC/PDPS data for cost-benefit analysis of procedures like PCI and CABG should be confirmed in a multi-center study.

Background: Sodium-glucose transporter-2 inhibitor (SGLT2) is reported to have anti-atherosclerotic effects in experiment. However, the effect of SGLT2 on endothelial function (ECF) in humans is not fully investigated. Method and Results: We measured ECF in 11 diabetic patients with coronary artery disease (CAD) and poor control of diabetics (HbA1c>7%; 75±8 years old) by simultaneously measuring brachial artery flow-mediated dilation (FMD) and EndoPAT2000 (measuring RHI). FMD and RHI were measured before and after mean periods of 4-week treatment of Canagliflozin (100 mg per every other day). Canagliflozin improved HbA1c along with increasing FMD and RHI (HbA1c, 9.2±1.4 vs. 8.6±1.1%, P<0.01; FMD, 6.40±1.29 vs. 8.98±1.68%, P<0.01; RHI, 1.5±0.3 vs.1.8±0.3, P<0.05). In addition, the changes of HbA1c did not tend to correlate with either FMD or RHI. Conclusions: Since the improved FMD and RHI reflect salutary effect of Canagliflozin on ECF, these results might suggest that SGLT2 could have anti-arteriosclerotic effects in diabetics with CAD.

Background and Aims: Reactive hyperemia-peripheral arterial tonometry (RH-PAT) has been developed to detect early stage vascular dysfunction. Recent studies have suggested that Reactive hyperemia index (RHI) assessed using RH-PAT could be used to predict the mortality of subjects with high risks for cardiovascular events. On the other hand, carotid intima-media thickness (IMT), pulse wave velocity (PWV), and/or cardio-ankle vascular index (CAVI) have been used as screening tools for vascular disorders. Since obesity and metabolic syndrome are the risk factors for cardiovascular events, we aimed to examine the association of RHI, CAVI, and carotid artery plaque scores with the body mass index (BMI). Methods: The participants of this study were 39 Japanese subjects who were admitted at the Department of Liver Disease of Shimane University Hospital between August and December 2016 (mean age, 62 years). RH-PAT findings, CAVI, and carotid IMT were evaluated, and their associations with BMI were analyzed. Carotid IMT and plaque score (PS) were evaluated by ultrasonography following the standard protocol. A score of less than 1.67 was defined as a low RHI. Results: The PS was associated with age (r=0.511, p<0.0001) but not with BMI. Interestingly, CAVI had a positive association with age (r=0.706, p<0.0001) and an inverse association with BMI (r=-0.511, p<0.0001). In contrast, RHI had no significant association with age and BMI. Among 14 patients with non-alcoholic steatohepatitis (NASH) or non-alcoholic fatty liver disease (NAFLD) with BMI≥25, only one patient had high CAVI (>9.0) whereas 6 patients had low RHI. Conclusions: NASH/NAFLD subjects, especially those with obesity, are good candidates for RH-PAT examination to detect early stage of vascular failure.

The renal complication of type 2 diabetes mellitus is diagnosed as the diabetic nephropathy. Its pathophysiology has not yet been fully clarified, however. Although a concept of diabetic kidney disease has recently been proposed, the background of its pathophysiology is limited to type 2 diabetes and definite pathophysiological features are difficult to indicate. Under these conditions, we propose metabolic syndrome nephropathy (combined renal microangiopathy and intrarenal arteriosclerosis), taking account of the metabolic syndrome which plays an important role in the development of type 2 diabetes. This article is a report of our early-diagnosis method established for such nephropathy.

The new diagnostic method (using vascular resistance measurement by renal ultrasound imaging and estimated renal blood flow measurement with a contrast agent for ultrasound imaging), as compared with the conventional method (using albuminuria detection and estimated glomerular filtration rate measurement), showed a marked increase of diagnostic rate (89.4% vs. 51.3%). This new method, if applicable in the early-diagnosis of renal damage, will hold promise in providing a clue for preventing the end-stage renal failure.

Background: Obstructive sleep apnea syndrome (OSAS) is a novel risk factor for cardiovascular disease (CVD) and thought to be associated with endothelial dysfunction. Although many reports have demonstrated endothelial dysfunction of large conduit artery by flow-mediated dilatation in patients with OSAS, only a few reports have assessed microvascular endothelial function in OSAS patients. In this study, we investigated microvascular endothelial function by reactive hyperemia-peripheral arterial tonometry (RH-PAT) in patients with OSAS and assessed the effects of continuous positive airway pressure (CPAP) treatment on microvascular endothelial function. Methods: Twelve male patients with OSAS (51±13 yrs, body mass index [BMI]: 27.6±7.1 kg/m², apnea hypopnea index [AHI]: 44±18/hr) and 12 male patients with CVD (54±13 yrs, BMI: 25.5±3.0 kg/m²) underwent an endothelial function test by RH-PAT using Endo-PAT 2000 before and 12 months after induction of CPAP treatment. Results: The baseline reactive hyperemia index (RHI) in patients with OSAS was similar to that in patients with CAD (1.78±0.48 vs 1.79±0.36, P=0.878). In patients with OSAS, the RHI increased 12 months after CPAP treatment (to 2.32±0.40; P=0.003). The change in RHI from baseline after CPAP treatment tended to have a negative correlation with the baseline 3% oxygen desaturation index (3% ODI) (R=-0.526, P=0.079) and was correlated negatively with the baseline AHI (R=-0.607, P=0.036). Conclusion: Microvascular endothelial function is impaired in patients with OSAS, but improves after CPAP treatment. In addition, the improvement of microvascular endothelial function through CPAP treatment was driven by mainly patients with mild to moderate OSAS at baseline.