Type 2 diabetes mellitus (T2DM) is highly prevalent and is a critical risk factor for cardiovascular (CV) disease, increasing both morbidity and mortality. T2DM is one of the most important classical CV risk factors that promote atherosclerosis. Therefore, it is important for both patients with T2DM and their doctors to identify vascular dysfunction at an early stage of atherosclerosis. Recently, new therapies based on the actions of the incretin hormones and blockade of sodium glucose transporter (SGLT) 2 have become widely used, because they offer advantages over conventional treatments by achieving glycemic control and/or possible reducing CV risks. Many experimental studies have suggested that glucagon-like peptide (GLP)-1 and dipeptidyl peptidase (DPP)-4 inhibitors exert cardioprotective effects on atherosclerosis and cardiac dysfunction both in vitro and in vivo. However, thus far, there is little clinical evidence supporting the efficacy of incretin therapy in patients with CV disease. In contrast, the SGLT2 inhibitor empagliflozin achieved a remarkable reduction in CV-related mortality in a large clinical study. The present review focuses on the effects of GLP-1-related therapies and SGLT2 inhibitors on clinical indices of endothelial function.

Non-invasive measures of central hemodynamics, such as augmentation index (AI), and central blood pressure (BP) have emerged as a novel and more sophisticated method than brachial BP measurements. For the evaluation of cardiovascular risks and efficacy of medications, central hemodynamics have been shown to be better parameters than peripheral BP. We have introduced these measures of central hemodynamics in our clinical trials and found that 1) patients with type 2 diabetes (DM) had lower rAI but a higher central PP compared to that in the non-diabetes patients, which suggested a proximal conduit-predominant arterial stiffening causing reduced reflection coefficients at the systemic reflection sites: 2) An increased wave reflection caused by the stiffened aorta could be a key factor in the pathophysiology of hypertensive disorders of pregnancy: 3) Central BP compared to brachial clinic BP and home BP during antihypertensive treatment is better in predicting the measures of target organ damage: 4) a very aggressive antihypertensive therapy guided by home morning BP was effective for the change in the central SBP, and was correlated with the change in urinary albumin and PWV: 5) When beta-blockers were additionally used for the treatment of hypertension, bisoprolol achieved a greater reduction in pulse rate and improved baroreflex sensitivity and vascular stiffness, whereas celiprolol reduced the central BP. In conclusion, central hemodynamics might be useful for the evaluation of intra-individual changes, such as drug efficacy or that of some interventions, reflecting the pathophysiological mechanisms of cardiovascular diseases.

Patients with chronic respiratory diseases (e.g., chronic obstructive pulmonary disease, interstitial pneumonia, and sleep apnea syndrome) have common risk factors for atherosclerosis, including advanced age, smoking, chronic inflammation, and continuous or intermittent hypoxia. Previous epidemiological studies have revealed that patients with these diseases have an increased risk of atherosclerosis and vascular events. These comorbidities are also associated with poor survival; however, the impact of the treatment for vascular diseases on the prognosis of patients with respiratory diseases remains unclear. Further investigation is required to elucidate the mechanisms and establish treatment strategies for vascular failure associated with respiratory diseases.

Fragility fracture impairs the activities of daily living and quality of life of the elderly. Accumulating evidence has shown that patients with osteoporosis have an increased all-cause mortality as well as cardiovascular mortality rates. Osteoporosis and cardiovascular diseases have common risk factors, such as diabetes mellitus. Patients with diabetes have an increased risk of osteoporosis; thus, diabetes-related bone disease is now recognized as one of the complications of diabetes. Although accumulation of advanced glycation end products and oxidative stress are associated with the formation and progression of atherosclerosis, these are reported to be involved in the pathogenesis of osteoporosis, especially in diabetic patients. Moreover, recent studies have shown that osteocalcin, which is secreted from the bone into the circulation, has an endocrine function of regulating glucose and energy metabolism. In addition, osteocalcin directly affects vascular endothelial cells and smooth muscle cells and protects against oxidative stress-induced cell dysfunction. Therefore, the bone-vascular axis attracts widespread attention. In this review, I described the association between bone and glucose metabolism and vascular failure on the basis of recent evidence.

Background: Highly purified eicosapentaenoic acid (EPA) is a promising agent for the secondary prevention of coronary artery disease. Red blood cell distribution width (RDW), a measure of red blood cell size heterogeneity, has been shown to be associated with the risk of cardiovascular events in patients with coronary artery disease. In the present study, we investigated whether EPA affects red blood cell size heterogeneity and vascular endothelial function in patients with coronary artery disease. Methods and Results: Among the 30 patients with coronary artery disease with an EPA/arachidonic acid (AA) ratio <0.4, 19 patients were administered with EPA (1800 mg/d) (EPA group); the remaining 11 patients received no intervention (control group). During a follow-up period of 36±14 mo, the EPA/AA ratio increased in the EPA group (P<0.001) but did not change in the control group. The flow-mediated dilatation (FMD) value also increased in the EPA group (P<0.05) but not in the control group. The RDW value did not change in either group. In 15 patients with a baseline RDW value greater than the median (12.8), 8 in the EPA group had a decreased RDW value (P<0.05), while 7 in the corresponding control group had an unchanged RDW value. In all patients, the change in FMD was negatively correlated with that in RDW (R=-0.39, P<0.05). Conclusions: EPA improved red blood cell size heterogeneity as well as vascular endothelial function in patients with coronary artery disease. The improvements were correlated with each other.

A 45-year-old male patient with Buerger's disease presented with intermittent claudication, sharp rest pain in his right foot, and several episodes of lower extremity superficial thrombophlebitis. He had no cardiovascular risk factors and his glucose levels were within normal ranges. However, he had a smoking history of more than 26 years; he had stopped smoking 3 years prior. Early treatment with antithrombotic and vasodilating agents as well as intravenous infusion of prostaglandin E₁ did not improve his condition. Intra-arterial infusion of prostaglandin E₁ once a day for 2 weeks slightly increased blood flow in the areas with previous low blood flow and improved his condition from Fontaine stage III to II.