Central and brachial pulse pressure predicts cardiovascular and renal events in treated hypertensive patients.

PURPOSES: Central blood pressure is a stronger predictor of cardiovascular prognosis rather than brachial blood pressure. The reflection wave reaches the abdominal aorta sooner than ascending aorta. Thus, the contribution of central pulse pressure (cPP) to renal events may differ from that of cardiovascular events. METHODS: The subanalysis of the ABC-J II study was performed. Subjects were 3434 treated hypertensive patients with a mean follow-up of 4.7 years. Left ventricular hypertrophy, an index of cardiovascular risk, correlated with cPP better than central systolic blood pressure in this cohort. The contribution of brachial pulse pressure (bPP) and cPP to cardiovascular and renal events was analysed. RESULTS: Cox proportional-hazard analysis revealed that sex (p < 0.001), height (p < 0.05), history of cardiovascular diseases (p < 0.001), number of antihypertensive drugs (p < 0.05), and cPP (p < 0.05) contributed to cardiovascular events. However, Cox proportional-hazard analysis disclosed that baseline serum creatinine (p < 0.001) and bPP (p < 0.05) predicted renal events. After adjusting for the history of cardiovascular diseases, Cox regression demonstrated only sex as a significant predictor of cardiovascular events. After adjusting for baseline serum creatinine, no parameters were shown to predict renal events. CONCLUSIONS: The present findings support our previous data that the absence of cardiovascular or renal diseases is an important determinant for event-free survival, and suggest that cPP and bPP contribute to cardiovascular and renal events in treated hypertensive patients.

Reaching Task in Rats: Quantitative Evaluation and Effects of 6-OHDA into the Striatum.

In this study, we developed an evaluation method using image analysis for reaching tasks. Using this method, we studied forearm function during the reaching task in rats that received a unilateral injection of 6-OHDA into the striatum. The success ratio of the reaching task reduced to 40.5% seven days after the injection. In addition, significant changes were observed in the pronation angle of the forearm, posture control, and targeting (i.e., the distance between all fingertips and the center of the target pellet). Thus, unilateral injection of 6-OHDA reduces dopaminergic function in the brain and causes deterioration of forearm function and posture control in the reaching task.

A parsimonious laboratory system for the evaluation of rat reaching task: recovery from the massive destruction of motor areas.

The rat reaching task is one of the best paradigms from behavioral study of upper limb movements. Rats are trained to reach and grab a pellet by extending their hand through a vertical slit. A few conventional imaging systems specific for the rat reaching task are commercially available with a high installation cost. Based on image analysis of video recordings obtained during the reaching task, we, herewith, developed a new, low-cost laboratory system that can be used for the quantitative analysis of ten basic forearm movements, in contrast to subjective assessments used in previous studies. We quantified images of the pronated and supinated palm and the accuracy and speed of reaching the target. Applying this newly developed method, we compared the forearm movements during the reaching task before and after a massive anatomical lesion of the sensorimotor cortex performed by tissue aspiration. We also wanted to investigate the recovery of upper limb function possibly induced by repeating the task for a relatively short term of a few weeks. In the experiment, 7 injured groups and 3 control groups were used. We found characteristic abnormalities of the forearm movements and a significant recovery in the success rate of grasping the target pellet. The present results demonstrate that our method is straightforward for the quantitative evaluation of forearm movements during the reaching task primarily controlled by the sensorimotor cortex.

Correction to: Regional prescription surveillance of phosphate binders in the western Saitama area: the substantial role of ferric citrate hydrate in improving serum phosphorus levels and erythropoiesis.

In the Original publication, Under the table 1, the number of participants in the April has been incorrectly published as 1373. The corrected table is given below.

Predictors of long-term prognosis in acute kidney injury survivors who require continuous renal replacement therapy after cardiovascular surgery.

The long-term prognosis of patients with postoperative acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) after cardiovascular surgery is unclear. We aimed to investigate long-term renal outcomes and survival in these patients to determine the risk factors for negative outcomes. Long-term prognosis was examined in 144 hospital survivors. All patients were independent and on renal replacement therapy at hospital discharge. The median age at operation was 72.0 years, and the median pre-operative estimated glomerular filtration rate (eGFR) was 39.5 mL/min/1.73 m2. The median follow-up duration was 1075 days. The endpoints were death, chronic maintenance dialysis dependence, and a composite of death and chronic dialysis. Predictors for death and dialysis were evaluated using Fine and Gray's competing risk analysis. The cumulative incidence of death was 34.9%, and the chronic dialysis rate was 13.3% during the observation period. In the multivariate proportional hazards analysis, eGFR <30 mL/min/1.73 m2 at discharge was associated with the composite endpoint of death and dialysis [hazard ratio (HR), 2.1; 95% confidence interval (CI), 1.1-3.8; P = 0.02]. Hypertension (HR 8.7, 95% CI, 2.2-35.4; P = 0.002) and eGFR <30 mL/min/1.73 m2 at discharge (HR 26.4, 95% CI, 2.6-267.1; P = 0.006) were associated with dialysis. Advanced age (≥75 years) was predictive of death. Patients with severe CRRT-requiring AKI after cardiovascular surgery have increased risks of chronic dialysis and death. Patients with eGFR <30 mL/min/1.73 m2 at discharge should be monitored especially carefully by nephrologists due to the risk of chronic dialysis and death.

Regional prescription surveillance of phosphate binders in the western Saitama area: the substantial role of ferric citrate hydrate in improving serum phosphorus levels and erythropoiesis.

BACKGROUND: In April 2015, five types of phosphate binders (PBs) were available by prescription in Japan, namely calcium carbonate, sevelamer hydrochloride, lanthanum carbonate, bixalomer, and ferric citrate hydrate (FeC). FeC reduces serum phosphorus levels and increases the body's iron stores. However, it is unclear whether FeC lowers serum phosphorus relative to other agents in a regional practical setting. METHODS: We performed a retrospective observational cohort study of regional hemodialysis surveillance in the western Saitama area of Japan, which included 1374 hemodialysis patients enrolled from 32 satellite dialysis units. The clinical data and prescribing information were retrospectively collected and analyzed. The difference in serum phosphorus among the groups administered five types of PBs (new or additional) from April to September 2015 was the primary outcome. RESULTS: As of April 2015, the median values of serum phosphorus, corrected calcium, and intact parathyroid hormone were 5.4 mg/dL, 9.1 mg/dL, and 147 pg/dL, respectively (N = 1374). Unexpectedly, with an increase in the number of PBs administered, serum phosphorous levels increased (p < 0.001). The significant changes in the serum phosphorus and hemoglobin levels were associated with the prescription of FeC but not with that of the other PBs. CONCLUSIONS: This regional survey suggests that serum phosphorus is well managed and that FeC has the potential to reduce the serum phosphorus level relative to other PBs and to ameliorates anemia.

Inferred systolic blood pressure levels to switch from lifestyle modifications to antihypertensive medications: a success-rate oriented simulation.

Objective: This simulation study attempted to infer the systolic blood pressure (SBP) levels at which subjects with hypertension, health nurses, and primary physicians should switch their preference of their treatment policies from lifestyle modifications to antihypertensive medications in virtual Japanese sample populations. Methods: We assumed that SBP levels were normally distributed and that the incidence rate of cardiovascular disease (IRCVD, events/year) increased exponentially according to SBP. The total IRCVD was calculated by the definite integral for the product of the distribution of SBP multiplied by IRCVD at each SBP level. The success rates were calculated according to SBP and metabolic risk profiles in the two approaches, respectively. We deduced the hypothetical SBP levels by solving differential equations of ∆(IRCVD)/ ∆(SBP) = 0 using numerical analysis. Results: In the realistic situations where the subjects were not affirmative to antihypertensive medications, the inferred SBP level to switch from lifestyle modifications to antihypertensive medications should be around 150 mmHg. If the subjects are affirmative to antihypertensive medications, the SBP level should be lowered to 140 mm Hg. Conclusion: This success rate-oriented simulation proposes that the SBP level to switch from lifestyle modifications to antihypertensive medications can be modulated according to the behavioral propensity for taking antihypertensive medications.Abbreviations: The following abbreviations are used in this manuscript: CVD: cardiovascular disease; LM: lifestyle modifications; AM: antihypertensive medications; IRCVD: incidence rate of cardiovascular disease (events/year); SBP: systolic blood pressure; ∆IRCVD: the improvements in the incidence rate of cardiovascular disease by lifestyle modifications and/or by antihypertensive medications.

Gallstones were associated with the gastrointestinal adverse events of cinacalcet in hemodialysis patients with secondary hyperparathyroidism.

This study aimed to investigate the association of gastrointestinal (GI) adverse events of cinacalcet with gallstones in the hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). A total of 23 HD patients under the treatment with cinacalcet and 101 control patients were enrolled in this cross-sectional study. We investigated the prevalence of gallstones and the association of GI adverse events of cinacalcet with gallstones. The prevalence of gallstones was significantly higher in the HD patients with cinacalcet compared with the controls (47.8% vs. 15.8%). The longer time on HD, hypercalcemia, hyperphosphatemia and elevated parathyroid hormone level were observed in the HD patients with cinacalcet. Besides, GI adverse events of cinacalcet were observed more frequently in the HD patients with gallstones compared with those without gallstones (odds ratio 13.5, 95% CI: 1.80-101). Therefore, screening for gallstones before dosing cinacalcet may reduce the risk of GI adverse events in SHPT patients.

Impacts of sodium-glucose co-transporter type 2 inhibitors on central blood pressure.

AIMS: To assess the effects of sodium-glucose co-transporter type 2 inhibitors on central blood pressure, an important determinant of cardiovascular events. METHODS: Canagliflozin, Empagliflozin or Luseogliflozin was given for 102 type 2 diabetic patients with hypertension and nephropathy. Central blood pressure was evaluated by radial tonometry. Clinical parameters were followed for 6 months. RESULTS: Three differing sodium-glucose co-transporter type 2 inhibitors similarly reduced brachial and central blood pressures, casual blood sugar, haemoglobin A1c, estimated glomerular filtration rate and albuminuria without significant changes in pulse rate and lipid profiles. Central systolic blood pressure was associated with the decreases in albuminuria by sodium-glucose co-transporter type 2 inhibitors. CONCLUSION: Comparable influences of various sodium-glucose co-transporter type 2 inhibitors on central blood pressure suggest class effects.

Kidney resistive index relates to variations of home blood pressure in chronic kidney diseases.

BACKGROUND: Kidney resistive index (RI) correlates with tubulointerstitial changes and predicts renal prognosis. Most patients with chronic kidney diseases (CKDs) manifest high blood pressure and atherosclerotic cardiovascular diseases. In addition, various atherosclerotic indexes relate to variations in blood pressure. METHODS: Subjects were 70 CKD patients, who visited our office and agreed to measure home blood pressure and receive renal ultrasonography. Cross-sectional analyses were performed. RESULTS: Patient age was averaged 61 ± 15 (SD) y/o and 60% were male. Mean serum creatinine and proteinuria were 1.2 ± 0.5 mg/dl and 0.2 ± 0.5 g/gCr, respectively. Office blood pressure and kidney RI were 128 ± 17/75 ± 11 mmHg and 0.66 ± 0.08, respectively. Multivariate regression analysis revealed that age and office blood pressure independently correlated to kidney RI (p < 0.05 for each). Home blood pressure was averaged 122 ± 7/70 ± 6 mmHg. Both standard deviation and the maximal-minimal difference in home systolic blood pressure related to kidney RI (p < 0.05). CONCLUSIONS: The present results indicate that office blood pressure correlates to kidney RI, which predicts renal prognosis. In addition, our data implicate that kidney RI relates to variations in home systolic blood pressure, and suggest that kidney RI may be a good index for atherosclerosis in CKD patients.

Lifestyle Modifications Versus Antihypertensive Medications in Reducing Cardiovascular Events in an Aging Society: A Success Rate-oriented Simulation.

Objective It is difficult to compare directly the practical effects of lifestyle modifications and antihypertensive medications on reducing cardiovascular disease (CVD). The purpose of this study was to compare the hypothetical potential of lifestyle modifications with that of antihypertensive medications in reducing CVD in an aging society using a success rate-oriented simulation. Methods We constructed a simulation model for virtual Japanese subpopulations according to sex and age at 10-year intervals from 40 years of age as an example of an aging society. The fractional incidence rate of CVD was calculated as the product of the incidence rate at each systolic blood pressure (SBP) level and the proportion of the SBP frequency distribution in the fractional subpopulations of each SBP. The total incidence rate was calculated by the definite integral of the fractional incidence rate at each SBP level in the sex- and age-specific subpopulations. Results If we consider the effects of lifestyle modifications on metabolic factors and transfer them onto SBP, the reductions in the total incidence rate of CVD were competitive between lifestyle modifications and antihypertensive medications in realistic scenarios. In middle-aged women, the preventive effects of both approaches were limited due to a low incidence rate. In middle-aged men and extremely elderly subjects whose adherence to antihypertensive medications is predicted to be low, lifestyle modifications could be an alternative choice. Conclusion The success rate-oriented simulation suggests that the effectiveness of lifestyle modifications or antihypertensive medications in preventing cardiovascular events largely depends on the baseline incidence rate and sex- and age-specific behavioral factors.

Central blood pressure and chronic kidney disease.

In this review, we focused on the relationship between central blood pressure and chronic kidney diseases (CKD). Wave reflection is a major mechanism that determines central blood pressure in patients with CKD. Recent medical technology advances have enabled non-invasive central blood pressure measurements. Clinical trials have demonstrated that compared with brachial blood pressure, central blood pressure is a stronger risk factor for cardiovascular (CV) and renal diseases. CKD is characterized by a diminished renal autoregulatory ability, an augmented direct transmission of systemic blood pressure to glomeruli, and an increase in proteinuria. Any elevation in central blood pressure accelerates CKD progression. In the kidney, interstitial inflammation induces oxidative stress to handle proteinuria. Oxidative stress facilitates atherogenesis, increases arterial stiffness and central blood pressure, and worsens the CV prognosis in patients with CKD. A vicious cycle exists between CKD and central blood pressure. To stop this cycle, vasodilator antihypertensive drugs and statins can reduce central blood pressure and oxidative stress. Even in early-stage CKD, mineral and bone disorders (MBD) may develop. MBD promotes oxidative stress, arteriosclerosis, and elevated central blood pressure in patients with CKD. Early intervention or prevention seems necessary to maintain vascular health in patients with CKD.

Lifestyle modifications supported by regional health nurses lowered insulin resistance, oxidative stress and central blood pressure in subjects with metabolic syndrome.

BACKGROUND: This study was attempted to investigate whether lifestyle modifications supported by regional health nurses should improve cardio-metabolic factors--including adipocytokines, oxidative stress, and arterial stiffness--in subjects with metabolic syndrome. METHODS: Thirty-six subjects with metabolic syndrome were enrolled, 28 of whom completed the 6-month lifestyle modifications (male:female=19:9). Blood and urine test results were examined in relation to metabolic factors before and after 6-month nutritional and physical activity modifications. In addition, oral glucose tolerance tests were performed and arterial stiffness was measured by brachial-ankle pulse wave velocity and radial augmentation index before and after them. RESULTS: Six-month lifestyle modifications significantly reduced body weight, homeostasis model assessment index, and low-density lipoprotein cholesterol (LDL-C). They significantly attenuated oxidative stress measured by the urinary 8-hydroxy-2-deoxyguanosine/creatinine ratio. They also lowered brachial and central systolic blood pressure. They tended to decrease waist circumferences and the levels of C-reactive protein. However they did not significantly change the levels of adipocytokines, including tumour necrosis factor, soluble tumour necrosis factor receptors, and interleukin 6, or arterial stiffness measured by brachial-ankle pulse wave velocity and radial augmentation index. CONCLUSIONS: Six-month lifestyle modifications supported by regional health nurses lowered body weight, insulin resistance, LDL-C, oxidative stress, and peripheral and central blood pressure in subjects with metabolic syndrome.

Blood glucose levels in peritoneal dialysis are better reflected by HbA1c than by glycated albumin.

A recent study indicated that, compared with glycated hemoglobin (HbA1c), glycated albumin (GA) provides a more accurate assessment of glycemic control in diabetic patients on hemodialysis. However, the suitability of GA for this purpose in peritoneal dialysis (PD) patients is questionable. We measured blood glucose, GA, HbA1c, serum albumin, protein losses in urine and dialysate, protein catabolic rate, hemoglobin, and dose of erythropoiesis-stimulating agents in 71 PD patients [20 with diabetes (DM), 51 without DM]. In both DM and non-DM patients, blood glucose levels correlated significantly with HbA1c (r = 0.47, p < 0.001), but not with GA (r = 0.18, p = 0.19). In patients with high serum albumin (> 3.2 g/dL), blood glucose levels correlated significantly with GA (r = 0.32, p = 0.047). Further, low protein losses in urine and dialysate (< 5.9 g daily) also significantly correlated with GA (r = 0.37, p = 0.041). In PD patients, HbA1c is better than GA as an indicator of blood glucose levels. Glycated albumin can be used as an indicator of glycemic control in PD patients with normal serum albumin and low protein losses in urine and dialysate.

Home hemodialysis and conventional in-center hemodialysis in Japan: a comparison of health-related quality of life.

Health-related quality of life (HRQOL) is an important measure of how disease affects patients' daily life. Conventional in-center hemodialysis (CHD) patients have been found to have decreased HRQOL. Recent study reported that at-home hemodialysis (HHD) improved the long-term HRQOL compared with CHD; however, there have been no data from Japanese HHD patients. A sample of 80 Japanese hemodialysis patients (46 HHD and 34 CHD) was matched for age, sex, and cause of end-stage renal disease. Patient HRQOL was measured using two health surveys: Medical Outcomes Study 36 Item Short Form Health Survey-Version 2 and Kidney Disease Quality of Life-Short Form. HHD patients reported better scores on seven out of eight domains (all domains except general heath) of the Medical Outcomes Study 36 Item Short Form Health Survey-Version 2, as well as better Kidney Disease Quality of Life-Short Form scores with respect to symptoms and problems, effect of kidney disease, and work status. No significant differences were observed for burden of kidney disease, cognitive function, quality of social interaction, sexual function, or sleep. More than 65% of HHD patients stated that they were not bothered at all by limitations on food and water intake. Japanese HHD patients demonstrate significantly higher HRQOL scores. However, while their HRQOL and employment rate were high and they were able to enjoy fewer dietary restrictions, kidney disease remained a great burden.

Calcitriol supplementation improves endothelium-dependent vasodilation in rat hypertensive renal injury.

BACKGROUND/AIMS: Vitamin D increases renal expression of klotho in normotensive rats. Klotho reduces oxidative stress. METHODS: In this study, we aimed to determine if vitamin D would suppress oxidative stress using 4 groups of hypertensive rats: uninephrectomized, stroke-prone, spontaneously hypertensive rats fed a high-salt (6%) diet (controls; C); those treated with irbesartan (I); those treated with calcitriol (V); and those treated with both irbesartan and calcitriol (I+V). RESULTS: Systolic blood pressure was higher in the C group than in the I and I+V groups. Albuminuria was attenuated in groups I, V, and I+V. Renal angiotensin II (AngII) concentration was lower in groups I and I+V than in group C, and plasma AngII levels of groups I and V were higher and lower than those in group C, respectively. Compared with group C, renal klotho expression, 8-epi-prostaglandin F2α excretion, and acetylcholine-induced decrease in blood pressure improved in the V and I+V groups. CONCLUSIONS: The data indicate that irbesartan effectively decreases blood pressure and renal AngII levels, and improves albuminuria. Our findings indicate that vitamin D enhances klotho expression, suppressing oxidative stress and albuminuria without substantial changes in renal AngII levels. These results suggest that the amelioration of endothelium function by vitamin D involves free klotho.

Calcium channel blockers suppress daily variations of blood pressure in hypertensive patients with end-stage renal diseases.

Hypertension is a well-known cardiovascular risk. Patients with end-stage renal diseases frequently suffer hypertension. Furthermore, daily variations of blood pressure are relatively large in patients treated with hemodialysis, partly due to ultrafiltration. Twenty hypertensive patients with end-stage renal diseases whose blood pressure was controlled by a single antihypertensive agent, either angiotensin receptor antagonist (ARB) or calcium channel blocker (CCB), were enrolled into the study. Home blood pressure measurements were also performed. Average systolic and diastolic blood pressures were similar between two agents. However, variations of systolic blood pressure during ARB treatment were greater than those of CCB, and maximal differences in daily systolic blood pressure during treatment with ARB (19±7 mmHg) were greater than those with CCB (14±6 mmHg, p<0.01). Systolic blood pressure measured after hemodialysis under ARB therapy (110±6 mmHg) was lower than that of CCB (118±6 mmHg, p<0.05). Daily variations of diastolic blood pressure were similar between ARB and CCB periods. Our results indicate that variations of systolic blood pressure during ARB treatment are larger than CCB, and suggest that CCB is useful to obtain the better quality of blood pressure control, improving blood pressure stability by preventing substantial drops in blood pressure in hypertensive patients with end-stage renal diseases.

Disturbed tumor necrosis factor system is linked with lower eGFR and chronic inflammation in hypertension.

BACKGROUND: The relationship between tumor necrosis factor (TNF)-related parameters and cardiorenal metabolic factors is still controversial in clinical hypertension. METHODS: Normotensive men (NT, n=60) and treated stage 2 and 3 essential hypertensive men (HT, n=89) were enrolled in this study. The relationship between TNF-related parameters and cardiorenal metabolic factors was examined in NT and HT, separately. RESULTS: HT showed higher rates of insulin resistance and enhanced chronic inflammation compared with NT. The levels of soluble TNF receptor 1 and 2 were significantly higher in HT than in NT, although TNF-α levels were unexpectedly lower in HT than in NT. Regression analysis indicated that the TNF-related parameters were closely linked with mild renal dysfunction both in NT and HT, and moderately related to chronic inflammation only in HT. HT taking inhibitors of the renin-angiotensin system showed improved insulin resistance, but no difference in the TNF-related parameters. CONCLUSION: These results suggest that the disturbed TNF system is closely linked with chronic inflammation rather than with insulin resistance in HT.

Paraoxonase-1 suppresses experimental colitis via the inhibition of IFN-γ production from CD4 T cells.

Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract, where excessive Th1 cell responses are observed. We performed experiments to identify immunologically bioactive proteins in human plasma and found that paraoxonase (PON)-1, which has esterase activity and is associated with high-density lipoproteins, inhibited the IFN-γ production by both murine and human differentiating Th1 cells. Trinitrobenzene sulfonic acid-induced colitis was attenuated by the administration of PON-1. The beneficial effects of PON-1 were associated with a reduced ratio of IFN-γ-producing CD4 T cells in the mesenteric lymph nodes and decreased production of T cell-related cytokines in the colon. PON-1 inhibited the TCR-induced activation of ERK-MAPK signaling and the nuclear translocation of NF-κB in CD4 T cells. Interestingly, an excessive CD4 T cell response was observed in PON-1-deficient mice under physiological and pathological conditions. Additionally, the efficacy of PON-1 or G3C9-C284A (G3C9), which shows a higher esterase activity than PON-1, on colitis was similar to that of an anti-TNF-α mAb, which is a clinically used CD treatment. Moreover, G3C9 more effectively suppressed CD4(+)CD45RB(high) cell transfer-induced chronic colitis in mice than did PON-1, and the efficacy of G3C9 against the colitis was similar to that of the anti-TNF-α mAb. Therefore, PON-1 (or G3C9) administration may be clinically beneficial for CD patients.