Chronic kidney disease (CKD), an important worldwide public health problem, is closely associated with the risk factors for cardiovascular disease (CVD). Ensuring a healthy environment by making lifestyle modifications is important for the prevention of CKD and CVD. In addition, the use of dietary supplements may be a complementary approach to preventing CKD and CVD. Several meta-analyses have demonstrated the blood pressure-lowering effect of lactotripeptides that are thought to occur via angiotensin converting enzyme inhibitory activity, at least in part, which also offers renal protection. Therefore, based on current findings, this brief review discusses the possibility of lactotripeptide supplements for renal protection.

Background：Optimal medical therapy (OMT) may play an important role in preventing secondary events in coronary artery diseases (CAD) and peripheral artery diseases (PAD). However, few practical pharmaceutical evidence-based regimens are available for patients with CAD and PAD to prevent secondary cardiovascular events due to practical reasons for performing clinical trials using the OMT regimen. Methods：To elucidate OMT for subjects with prior cardiovascular diseases in Japan, we performed a quasi-randomized clinical trial using statistically sophisticated propensity score matching and subsequent inverse probability treatment weighting methods to test which combination of medicines was most effective as OMT to prevent secondary cardiovascular events. Two hundred and sixty-one subjects who were admitted in our hospital were consecutively enrolled. We constructed the Cox models for the composite of death, myocardial infarction, stroke, admission for heart failure, and target region revascularization. Results：On multivariable inverse probability of treatment-weighted Cox modeling, the best combination was antiplatelet agents, statins, and calcium channel blockers (CCBs) to prevent major adverse cardiac events (MACE) in patients with CAD in Japan, and significant effects were found in the new OMT group for both MACE and cardiovascular death. In contrast, we could not find any significantly effective combinations in patients with PAD. Conclusions：These findings suggested that the multiple medical regimen including antiplatelet agents, statins, and CCBs, which might be prescribed as new OMT, has significant effects for the prevention of secondary events in patients with CAD in Japan.

BACKGROUND：Obesity is a predisposing factor for heart failure (HF). However, the factors contributing to the development of HF in obesity have not been fully elucidated. We analyzed potential blood biomarkers related to metabolism and neurohormonal factors in obese and non-obese patients with HF. METHOD：Various biomarkers in the blood, including amino acid profile, free fatty acid (FFA), and neurohormonal markers, were measured in patients with HF. Patients were divided into the obese and non-obese groups (body mass index ≥23 vs. <23 kg/m², respectively) and marker levels were compared between the groups. RESULT：FFA (0.7 vs. 0.4 mEq/L, p=.02), alanine (445 vs. 376 μmol/L, p=.03), valine (257 vs. 229 μmol/L, p=.03), branched-chain amino acids (BCAAs) (466 vs. 419 μmol/L, p=.03) noradrenaline (NA) (779 vs. 408 pg/mL, p=.01), and plasma aldosterone concentration (PAC) (133 vs. 80 pg/mL, p=.05) levels were significantly higher in the obese group than in the non-obese group. Plasma valine and BCAA levels were significantly positively correlated with HbA1c level as well as albumin and hemoglobin levels which are known markers of metabolic reserve against cachexia. CONCLUSION：Obesity-related HF was associated with further neurohormonal activation indicated by elevated NA and PAC levels. It was also associated with higher valine and BCAA levels, which could be markers of insulin resistance as well as metabolic reserve against cardiac cachexia.

Background：Combination therapy with a statin and ezetimibe is recognized as a useful therapeutic option for reducing the levels of low-density lipoprotein cholesterol (LDL-C). The aim of this study was to investigate the therapeutic effects of switching from statin-monotherapy to statin/ezetimibe combination therapy on lipid and metabolic profiles in patients with type 2 diabetes (T2D) and dyslipidemia. The study also assessed the clinical characteristics of patients who achieved or did not achieve their individual treatment target of low-density lipoprotein cholesterol (LDL-C) level after 12 months of combination therapy. Methods：Patients with T2D and dyslipidemia received ezetimibe 10 mg per day for 12 months as an add-on to background statin treatment. The changes in lipid and inflammatory markers after initiation of statin/ezetimibe combination therapy were evaluated. In addition, we examined the clinical characteristics of participants who achieved or not achieve their target LDL-C level. Results：A total of 15 patients (mean age 65.7 ± 8.7 yr, 6 females) were included in the analyses. The levels of total cholesterol and LDL-C were decreased significantly at 3, 6, and 12 months compared to baseline values, whereas the levels of the other laboratory parameters remained unchanged at each time point. Six patients (40.0%) achieved their target LDL-C level, while 9 patients (60.0%) did not. The subgroup of patients who did not achieve their LDL-C targets had significantly higher baseline levels of total cholesterol (TC) and LDL-C compared to the subgroup who achieved their target. Conclusions：Switching from statin-monotherapy to statin/ezetimibe combination therapy was effective for reducing LDL-C levels. However, patients with higher baseline TC and LDL-C levels may require further intensive treatment to achieve their target level of LDL-C.

Background：Vascular endothelial dysfunction plays a role on pathophysiology of heart failure (HF) and chronic kidney disease (CKD), both of which are often comorbid. However, there have been no previous reports, where the vascular endothelial function was assessed focusing on comorbid CKD in the HF, especially non-ischemic HF. Methods：We assessed vascular endothelial function using simultaneous procedure of flow-mediated dilatation (FMD) and reactive hyperemia-peripheral arterial tonometry (RH-PAT) in 33 consecutive patients with non-ischemic HF. Results：The FMD value was lower in HF patients with comorbid CKD (CKD group; n=18) than in the remaining patients without CKD (non-CKD group; n=15) (4.37±1.89 vs 6.31±3.42, P=0.048). The value of reactive hyperemia index (RHI) measured by RH-PAT was also lower in the CKD group than in the non-CKD group (1.65±0.46 vs 2.24±0.65, P=0.004). Even after adjustment for confounding factors, which showed intra-group difference, the significant differences in both values of FMD (P=0.005) and RHI (P=0.003) still remained between CKD and non-CKD groups. Conclusions：Vascular endothelial function might be impaired more strongly in non-ischemic HF patients with comorbid CKD, compared with those without CKD. The impaired endothelial function might be associated with prevalence of CKD in patients with non-ischemic HF.