Effects of sodium-glucose co-transporter 2 inhibitors on ultrafiltration in patients with peritoneal dialysis: a protocol for a randomized, double-blind, placebo-controlled, crossover trial (EMPOWERED).

BACKGROUND: Volume overload is common and associated with high mortality in patients on peritoneal dialysis (PD). Traditional strategies including diuretics, water/salt restriction, and icodextrin-based solutions cannot always fully correct this condition, necessitating novel alternative strategies. Recent studies confirmed the expression of sodium-glucose cotransporter 2 (SGLT2) in the human peritoneum. Experimental data suggest that SGLT2 inhibitors decrease glucose absorption from the PD solution, thereby increasing the ultrafiltration volume. This trial aims to assess whether SGLT2 inhibitors increase the ultrafiltration volume in patients on PD. METHODS: The EMPOWERED trial (trial registration: jRCTs051230081) is a multicenter, randomized, double-blind, placebo-controlled, crossover trial. Patients with clinically diagnosed chronic heart failure are eligible regardless of the presence of diabetes if they use at least 3 L/day glucose-based PD solutions. Participants will be randomly assigned (1:1) to receive empagliflozin 10 mg once daily and then placebo or vice versa. Each treatment period will last 8 weeks with a 4-week washout period. This study will recruit at least 36 randomized participants. The primary endpoint is the change in the daily ultrafiltration volume from baseline to week 8 in each intervention period. The key secondary endpoints include changes in the biomarkers of drained PD solutions, renal residual function, and anemia-related parameters. CONCLUSIONS: This trial aims to assess the benefit of SGLT2 inhibitors in fluid management with a novel mechanism of action in patients on PD. It will also provide insights into the effects of SGLT2 inhibitors on solute transport across the peritoneal membrane and residual renal function.

Exploring the link between Alport syndrome and multiple intracranial artery stenoses: a case report of COL4A5 mutation (118/120 characters).

BACKGROUND: Alport syndrome is a genetic disorder caused by mutations in the COL4A5 gene, which encodes type IV collagen α5 chain, leading to chronic nephritis, hearing loss, and ocular abnormalities. Recent reports suggest this genetic mutation may also increase the risk of cerebral aneurysms and fibromuscular dysplasia, indicating a potential association with vascular vulnerability. CASE PRESENTATION: A 66-year-old woman was admitted with recurrent transient weakness of the left hand, which had gradually worsened in duration over three months. Her medical history included chronic nephritis since childhood. Her two sons had end-stage renal disease and hearing loss since their 20s, and her mother also had chronic kidney disease and hearing loss. One son had a history of traumatic subarachnoid hemorrhage, and the other had spinal epidural hematoma. On admission, she had reduced renal function with proteinuria, acute cerebral infarction in the subcortical white matter of the right fronto-parietal and parieto-occipital lobes, and multiple intracranial arterial stenoses (ICAS), including the right middle and right posterior cerebral artery. Vessel wall imaging of the right middle cerebral artery showed a concentric stenotic pattern. Genetic tests identified a pathogenic missense mutation in exon 24 of COL4A5 (exon 24:c.G1700 >C: p.(Gly567Arg)) that was heterozygous for the patient and hemizygous for her son. She was diagnosed with Alport syndrome. CONCLUSION: It is important to consider Alport syndrome as a possible cause of ICAS in patients with a family history of renal failure or hearing loss and to conduct a genetic analysis of type IV collagen genes. (249/250 words).

Kinetics of atrial and brain natriuretic peptides during hemodialysis are regulated in association with different cardiac functional changes.

The blood levels of atrial and brain natriuretic peptides (ANP and BNP) are both increased markedly in hemodialysis patients, but the kinetics of the two are not always parallel. The present study investigated the association of changes in ANP and BNP levels before and after dialysis with changes in cardiac function in hemodialysis patients. A total of 57 patients (mean age 64 years, 47 males and 10 females) on maintenance hemodialysis with sinus rhythm were enrolled. Blood samples were taken at the beginning and end of dialysis, and plasma levels of ANP and BNP were measured. Changes in cardiac function during dialysis were examined by echocardiography performed just before and after dialysis. Both plasma ANP and BNP concentrations decreased significantly after hemodialysis, but the rate of decrease in BNP [mean ± SD, 555 ± 503 to 519 ± 477 pg/mL (- 6.4%), P = 0.011] was much smaller than that in ANP [233 ± 123 to 132 ± 83 pg/mL (- 43.4%), P < 0.001]. As for the relation to the changes in echocardiographic parameters before and after dialysis, the decrease in inferior vena cava diameter had a close correlation with the decrease in ANP (r = 0.528, P < 0.001), but not BNP. In contrast, the decrease in left ventricular end-diastolic volume index was correlated only with the decrease in BNP (r = 0.297, P = 0.035). The peak velocity ratio of early diastolic to atrial filling decreased with preload reduction by dialysis, and its decrease was more strongly correlated with the decrease in BNP (r = 0.407, P = 0.002) than that in ANP (r = 0.273, P = 0.040). These results demonstrated that in hemodialysis patients, the decrease in plasma ANP by a single dialysis was essentially caused by blood volume reduction, while BNP decrease was mainly induced by the reduction of left ventricular overload. Our findings indicate that the kinetics of both peptides during dialysis are regulated by different cardiac and hemodynamic factors.

Combined evaluation of plasma B-type natriuretic peptide and urinary liver-type fatty acid-binding protein/creatinine ratio is related to worsening renal function in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: There are few reports on the significance for the combined evaluation of blood humoral factors and urinary biomarkers in terms of worsening renal function (WRF) after coronary angiography (CAG)/percutaneous coronary arterial intervention (PCI). METHOD AND RESULTS: Urinary liver type-fatty acid-binding protein (L-FABP), neutrophil gelatinase associated lipocalin (NGAL), and adrenomedullin (AM) were measured less than 24 h before and 3 h, 6 h, 1 day, and 2 days after CAG/PCI. WRF was defined as a > 20% decrease in the estimated GFR. WRF occurred in seven of 100 patients and the increase in L-FABP/creatinine (Cr) at 1 day after CAG/PCI was significantly higher in the WRF group than in the non-WRF group. Plasma B-type natriuretic peptide (BNP) before CAG/PCI and L-FABP/Cr at 1 day after CAG/PCI were independent predictors for WRF. The areas under the receiver-operating characteristic curves were as follows: 0.760 for BNP before CAG/PCI, 0.731 for L-FABP/Cr at 1 day after CAG/PCI, and 0.892 for BNP and L-FABP/Cr. Urinary AM levels after PCI/CAG were negatively correlated only to serum potassium levels. Gene expressions of AM and AM-receptor were detectable in renal tubule epithelial cells. AM increased intracellular second messenger levels in a dose-dependent manner. CONCLUSIONS: Our results suggest that combined evaluation of plasma BNP and urinary L-FABP/Cr is useful as a predictor of renal dysfunction in CAG/PCI patients.

An Exploratory Study of Dapagliflozin for the Attenuation of Albuminuria in Patients with Heart Failure and Type 2 Diabetes Mellitus (DAPPER).

BACKGROUND AND AIMS: Sodium-dependent glucose transporter-2 (SGLT-2) inhibitors, which are anti-diabetic drugs, reportedly decrease the incidence of cardiovascular events in high-risk patients with cardiovascular diseases, and thus chronic heart failure (CHF). SGLT-2 inhibitors also decrease albuminuria in patients with type 2 diabetes mellitus (T2D). Since albuminuria is a biomarker of not only chronic kidney disease but also cardiovascular events, we hypothesized that, among T2D patients with CHF, SGLT-2 inhibitors will decrease the extent of albuminuria and also improve CHF concomitantly. METHODS: DAPPER (UMIN000025102) is a multicenter, randomized, open-labeled, parallel-group, standard treatment-controlled study, which is designed to evaluate whether dapagliflozin, one of the SGLT-2 inhibitors, decreases albuminuria in T2D patients with CHF and exerts cardioprotective effects on the failing heart. The patients are randomized to either of the dapagliflozin (5 or 10 mg, once daily orally) or control group (administration of anti-diabetic drugs administered other than SGLT 2 inhibitors). The estimated number of patients that need to be enrolled is 446 in total (223 in each group). The primary objective is the changes in the urinary albumin-to-creatinine ratio from the baseline after 2-year treatment. The key secondary objectives are (1) the safety of dapagliflozin and (2) the cardiovascular and renal efficacies of dapagliflozin. CONCLUSION AND PERSPECTIVES: DAPPER study investigates whether dapagliflozin decreases albuminuria and exerts beneficial effects on the failing heart in T2D patients. (UMIN000025102).

Impact of decreased serum albumin levels on acute kidney injury in patients with acute decompensated heart failure: a potential association of atrial natriuretic peptide.

Although hypoalbuminemia at admission is a risk for acute kidney injury (AKI) and mortality in patients with acute decompensated heart failure (ADHF), the clinical significance of decreased serum albumin levels (DAL) during ADHF therapy has not been elucidated. This study aimed to evaluate whether DAL was associated with AKI, and whether intravenous atrial natriuretic peptide (ANP) administration, which provides an effective treatment for ADHF but promotes albumin extravasation, was associated with DAL and AKI. A total of 231 consecutive patients with ADHF were enrolled. AKI was defined as ≥0.3 mg/dl absolute or 1.5-fold increase in serum creatinine levels within 48 h. AKI occurred in 73 (32%) of the 231 patients during ADHF therapy. The median value of decreases in serum albumin levels was 0.3 g/dl at 7 days after admission. When DAL was defined as ≥0.3 g/dl decrease in serum albumin levels, DAL occurred in 113 patients, and was independently associated with AKI. Of the 231 patients, 73 (32%) were treated with intravenous ANP. DAL occurred more frequently in patients receiving ANP than in those not receiving ANP (77 vs. 36%, p < 0.001), and ANP was independently associated with DAL. The incidence of AKI was higher in patients receiving ANP than in those not receiving ANP (48 vs. 24%, p < 0.001). ANP was independently associated with AKI. In conclusion, DAL is associated with AKI. Intravenous ANP administration may be one of the promoting factors of DAL, which leads to AKI, indicating a possible novel mechanism of AKI.

Impact of onset time of acute kidney injury on outcomes in patients with acute decompensated heart failure.

Since acute kidney injury (AKI) is not always related to mortality in patients with acute decompensated heart failure (ADHF), the aim of this study was to focus on onset time of AKI and its clinical importance. A total of 371 ADHF patients were included. The impact of AKI (≥ 0.3 mg/dl or 1.5-fold increase in serum creatinine level within 48 h) with early onset (≤ 4 days from admission) or late onset (≥ 5 days from admission) was assessed. AKI occurred in 99 patients, who were divided into two groups according to the median onset time of AKI: 50 with early onset of AKI and 49 with late onset of AKI. The maximum increase in serum creatinine level from admission was greater in patients with late onset of AKI than in patients with early onset of AKI (p = 0.012). Patients with late onset of AKI had a higher 12-month mortality rate than that in patients with early onset of AKI (log-rank test, p = 0.014). Late onset of AKI was an independent predictor of mortality (hazard ratio: 3.39, 95 % confidence interval: 1.84-6.18, p < 0.001). Late onset of AKI was associated with high blood urea nitrogen level at admission and intravenous administration of dobutamine. In conclusion, late onset of AKI related to high blood urea nitrogen level and intravenous administration of dobutamine, but not early onset of AKI, is linked to high mortality rate. Onset time of AKI may be useful for risk stratification of mortality in ADHF patients developing AKI.

Effects of cigarette smoking on ambulatory blood pressure, heart rate, and heart rate variability in treated hypertensive patients.

We investigated the influence of cigarette smoking on the levels and circadian patterns of blood pressure (BP), heart rate (HR), and HR variability (HRV) in hypertensive patients. Sixteen hypertensive smokers (57 ± 2 years old) receiving antihypertensive treatments participated in this study. Ambulatory monitoring of BP, HR, and electrocardiograms was performed every 30 min for 24 hours on a smoking day and nonsmoking day in a randomized crossover manner. Average 24-hour BP and daytime BP were significantly higher in the smoking period than in the nonsmoking period. No significant differences were observed in nighttime BP between the two periods. Average 24-hour and daytime HR, but not nighttime HR, were also higher in the smoking period than in the nonsmoking period. The daytime high frequency (HF) component of HRV was attenuated more in the smoking period than in the nonsmoking period. No significant differences were observed in the low frequency (LF) components of HRV or LF/HF ratio between the two periods. These results demonstrated that cigarette smoking increased the daytime and average 24-hour BP and HR, and the increases observed in daytime BP and HR were associated with the attenuation of parasympathetic nerve activity.

Risk Stratification of Acute Kidney Injury Using the Blood Urea Nitrogen/Creatinine Ratio in Patients With Acute Decompensated Heart Failure.

BACKGROUND: Risk stratification of acute kidney injury (AKI) is important for acute decompensated heart failure (ADHF). The aim of this study was to determine whether clinical markers, such as the blood urea nitrogen/creatinine ratio (BUN/Cr) or BUN or creatinine values alone, stratify the risk of AKI for mortality. METHODS AND RESULTS: In all, 371 consecutive ADHF patients were enrolled in the study. AKI was defined as serum creatinine ≥0.3 mg/dl or a 1.5-fold increase in serum creatinine levels within 48 h. During ADHF therapy, AKI occurred in 99 patients; 55 patients died during the 12-month follow-up period. Grouping patients according to AKI and a median BUN/Cr at admission of 22.1 (non-AKI+low BUN/Cr, non-AKI+high BUN/Cr, AKI+low BUN/Cr, and AKI+high BUN/Cr groups) revealed higher mortality in the AKI+high BUN/Cr group (log-rank test, P<0.001). Cox's proportional hazard analysis revealed an association between AKI+high BUN/Cr and mortality, whereas the association with AKI+low BUN/Cr did not reach statistical significance. When patients were grouped according to AKI and median BUN or creatinine values at admission, AKI was associated with mortality, regardless of BUN or creatinine. CONCLUSIONS: The combination of AKI and elevated BUN/Cr, but not BUN or creatinine individually, is linked with an increased risk of mortality in ADHF patients, suggesting that the BUN/Cr is useful for risk stratification of AKI.

Aggravated renal tubular damage and interstitial fibrosis in mice lacking guanylyl cyclase-A (GC-A), a receptor for atrial and B-type natriuretic peptides.

BACKGROUND AND AIM: The infusion of chronic angiotensin II (Ang II) has been shown to promote renal interstitial fibrosis. To evaluate the pathophysiological significance of the natriuretic peptide-GC-A system, we infused Ang II (1.0 mg/kg/day) in GC-A-deficient mice (GC-A-KO). METHODS: We used 5 groups (Wild-Saline n = 12, Wild-Ang II n = 14, GC-A-KO-Saline n = 11, GC-A-KO-Ang II n = 13, and GC-A-KO-Ang II-Hydralazine n = 10). Saline or Ang II was infused subcutaneously using an osmotic minipump for 3 weeks. Hydralazine was administered orally (0.05 g/L in drinking water). RESULTS: Systolic blood pressure was significantly higher in the GC-A-KO-Saline group (130 ± 12 mmHg) than in the Wild-Saline group (105 ± 30 mmHg), and was similar to that in the Wild-Ang II (141 ± 17 mmHg) and GC-A-KO-Ang II-Hydralazine (140 ± 20 mmHg) groups. Systolic blood pressure was significantly higher in the GC-A-KO-Ang II group (159 ± 21 mmHg) than in the 4 other groups. Renal tubular atrophy and interstitial fibrosis were significantly more severe in the GC-A-KO-Ang II group (atrophy 13.4 %, fibrosis 12.0 %) than in the Wild-Saline (0, 2.0 %), Wild-Ang II (2.9, 4.4 %), and GC-A-KO-Saline (0, 2.6 %) groups. Hydralazine could not inhibit this aggravation (GC-A-KO-Ang II-Hydralazine 13.5, 11.3 %). The expression of monocyte chemotactic protein-1 in tubular cells, and F4/80 and alpha-smooth muscle actin in the interstitium was clearly detected in the Ang II-infused wild and GC-A-KO groups and was associated with renal tubular atrophy and interstitial fibrosis. The expression of E-cadherin in tubular cells was absent in the Ang II-infused wild and GC-A-KO groups and was associated with renal tubular atrophy. CONCLUSIONS: The natriuretic peptide-GC-A system may play an inhibitory role in Ang II-induced renal tubular atrophy, interstitial fibrosis, and phenotypic transformation in renal tubular cells and fibroblasts.

Trends in the awareness of salt restriction and actual salt intake in hypertensive patients at a hypertension clinic and general clinic: A one-year follow-up study.

The aim of the present study was to investigate trends in the awareness of salt restriction and actual salt intake in hypertensive patients at a hypertension clinic and general clinic following guidance regarding salt restriction. Subjects comprised 107 patients (mean age 71 ± 12 years) who were followed at a hypertension clinic and 164 patients (mean age 68 ± 11 years) who were followed at a general clinic. Estimated salt intake using spot urine samples and awareness of salt intake using a self-description questionnaire were assessed in 2013 and one year after guidance regarding salt restriction. No significant changes were observed in office blood pressure at the two clinics. Estimated salt intake in 2013 was slightly lower at the hypertension clinic than at the general clinic (8.9 ± 2.5 vs 9.3 ± 2.5 g/day). Estimated salt intake decreased and the awareness of salt intake improved significantly after one year at both clinics; however, the reduction in estimated salt intake was larger at the general clinic than that at the hypertension clinic (-1.6 ± 3.2 vs -0.6 ± 2.9 g/day, p < 0.01). Individual guidance including data on actual salt intake appeared to be effective and important for reducing salt intake in hypertensive patients.

Effects of daily walking on office, home and 24-h blood pressure in hypertensive patients.

Aerobic exercise has been recommended in the management of hypertension. However, few studies have examined the effect of walking on ambulatory blood pressure (BP), and no studies have employed home BP monitoring. We investigated the effects of daily walking on office, home, and 24-h ambulatory BP in hypertensive patients. Sixty-five treated or untreated patients with essential hypertension (39 women and 26 men, 60 ± 9 years) were examined in a randomized cross-over design. The patients were asked to take a daily walk of 30-60 min to achieve 10 000 steps/d for 4 weeks, and to maintain usual activities for another 4 weeks. The number of steps taken and home BP were recorded everyday. Measurement of office and ambulatory BP, and sampling of blood and urine were performed at the end of each period. The average number of steps were 5349 ± 2267/d and 10 049 ± 3403/d in the control and walking period, respectively. Body weight and urinary sodium excretion did not change. Office, home, and 24-h BP in the walking period were lower compared to the control period by 2.6 ± 9.4/1.3 ± 4.9 mmHg (p < 0.05), 1.6 ± 6.8/1.5 ± 3.7 mmHg (p < 0.01), and 2.4 ± 7.6/1.8 ± 5.3 mmHg (p < 0.01), respectively. Average 24-h heart rate and serum triglyceride also decreased significantly. The changes in 24-h BP with walking significantly correlated with the average 24-h BP in the control period. In conclusion, daily walking lowered office, home, and 24-h BP, and improved 24-h heart rate and lipid metabolism in hypertensive patients. However, the small changes in BP may limit the value of walking as a non-pharmacologic therapy for hypertension.

Effects of a selective aldosterone blocker and thiazide-type diuretic on blood pressure and organ damage in hypertensive patients.

The aim of the present study was to compare the effects of the aldosterone blocker eplerenone and thiazide-like diuretic indapamide on blood pressure (BP) and target organs with reference to salt intake in hypertensive outpatients. Twenty hypertensive patients (nine women and 11 men, mean age 71 ± 13 years) with inadequate BP control despite taking calcium channel blockers (CCBs) and angiotensin II receptor blockers (ARBs) were administered eplerenone (50 mg/day) or indapamide (1 mg/day) for 3 months each in a randomized crossover manner. Salt intake, BP and indices of organ damage were assessed at baseline and at the end of each treatment period. Eplerenone and indapamide were similarly effective in lowering office and home BPs. Both the treatments significantly reduced the estimated glomerular filtration rate (eGFR) and increased serum uric acid levels. The treatment with eplerenone significantly increased serum potassium levels, whereas the treatment with indapamide significantly decreased them. The treatment with eplerenone significantly decreased pulse wave velocity and urinary 8-hydroxydeoxyguanosine levels. These changes were not significantly affected by the treatment with indapamide. In conclusion, eplerenone and indapamide were similarly effective in lowering office and home BPs in hypertensive patients treated with CCBs and ARBs. Eplerenone may exert more favorable effects on arterial stiffness and oxidative stress.

Awareness of salt restriction and actual salt intake in hypertensive patients at a hypertension clinic and general clinic.

The purpose of the present study was to investigate awareness of salt restriction and actual salt intake in hypertensive patients at a hypertension clinic and general clinic. Subjects included 330 patients, with a mean age of 69±12 years, who were followed at a hypertension clinic and 200 patients, with a mean age of 67±11 years, who were followed at a general clinic. We estimated 24-h salt excretion using spot urine samples and checked the awareness of salt intake using a self-description questionnaire. The number of antihypertensive drugs available at the hypertension clinic was significantly higher than that at the general clinic (2.2±1.1 versus 1.6±0.9, p<0.01); however, no significant difference was observed in office systolic blood pressure between the two groups. Urinary salt excretion was significantly lower at the hypertension clinic than at the general clinic (8.7±2.5 versus 9.3±2.5 g/d, p<0.01). The rate of achievement of salt intake<6 g/d was 15% at the hypertension clinic and 6% at the general clinic. In patients with excessive salt intake (≥10 g/d), 28% of patients at the hypertensive clinic and 23% at the general clinic thought that their salt intake was low. Urinary salt excretion in hypertensive patients was lower at a hypertensive clinic than at a general clinic. This may be due to the professional nutritional guidance at the hypertension clinic. However, most patients could not comply with the guidelines, and the awareness of salt restriction in patients with excessive salt intake was low.

Related factors for worsening renal function following percutaneous transluminal renal angioplasty (PTRA) in patients with atherosclerotic renal artery stenosis.

PURPOSE: To identify candidates for PTRA in terms of the preservation of renal function, we herein evaluated factors that caused worsening renal function (WRF) after PTRA. METHODS: We evaluated 92 patients with atherosclerotic renal artery stenosis (mean age 70.7 ± 8.4 years). WRF was defined as a ≥0.3 mg/dL increase in creatinine levels after PTRA compared to before PTRA. RESULTS: A total of 92 patients exhibited non-WRF 83 (90.2%), WRF 9 (9.8%). Significant differences were observed in serum creatinine levels between two groups both before (non-WRF 1.34 ± 0.49 versus WRF 1.70 ± 0.68 mg/dL, p = 0.0462) and after PTRA (non-WRF 1.31 ± 0.43 versus WRF 2.42 ± 1.12 mg/dL, p < 0.0001). Patients with WRF had higher comorbidity rate of diabetes mellitus (DM) (non-WRF 31.3% versus WRF 66.7%, p = 0.0345) and proteinuria (non-WRF 27.7% versus WRF 66.7%, p = 0.0169), and had higher systolic blood pressure (non-WRF 143.6 ± 18.7 versus WRF 157.1 ± 19.9 mmHg, p = 0.0436), higher plasma B-type natriuretic peptide (BNP) levels, and larger left atrial and left ventricular end-diastolic dimensions before PTRA. Patients with WRF had a higher rate of taking diuretics (non-WRF 27.7% versus WRF 66.7%, p = 0.0169) after PTRA. Multiple logistic regression analysis revealed that comorbidity of DM was an independent related factor for WRF (comorbidity of DM, yes: OR 31.0, 95% CI 2.44-1024.62, p = 0.0055). CONCLUSIONS: Comorbidity of DM, coexisting of proteinuria, high creatinine level, high blood pressure, high BNP levels, and large left atrial and ventricular dimensions were related to WRF after PTRA in patients with atherosclerotic renal artery stenosis.

Trend of office and home blood pressure control in treated hypertensive patients: changes in antihypertensive medication and salt intake.

Blood pressure (BP) control in hypertensives has improved in recent years; however, it remains insufficient. We investigated the trend of BP control status in hypertensive patients with antihypertensive medication and salt intake. Two hundred and eight treated hypertensive patients were prospectively followed between 2007 and 2012. During this period, average clinic BP significantly decreased from 137±12/80±9 to 133±11/76±8 mmHg, and the achievement rate of BP control defined as <140/90 mmHg increased from 58% to 71% (p<0.01). Morning home BP also significantly decreased from 132±8/80±8 to 130±8/76±7 mmHg, and the percentage of patients with sustained hypertension (CBP≥140/90 mmHg and HBP≥135/85 mmHg) decreased from 27% to 16% (p<0.05). The number of antihypertensive drugs increased significantly from 2.1±1.2 to 2.3±1.1 (p<0.01), while no differences were observed in urinary salt excretion (9.0±2.4 g/day in 2007, 9.0±2.6 g/day in 2012). Office and home BP decreased and the rate of BP control increased in treated hypertensive patients in the past 5 years. Intensive pharmacological therapy, but not a reduction in salt intake appears to have contributed to improved BP control.

Relationship between 2nd-generation angiotensin receptor blockers and the risk of hypotension in COVID-19 patients admitted to hospital.

It has not yet been established whether angiotensin II receptor blockers (ARB), statins, and multiple drugs affect the severity of COVID-19. Therefore, we herein performed an observational study on the effects of 1st- and 2nd-generation ARB, statins, and multiple drugs, on COVID-19 in patients admitted to 15 Japanese medical facilities. The results obtained showed that ARB, statins, and multiple drugs were not associated with the primary outcome (odds ratio: 1.040, 95% confidence interval: 0.688-0.571; 0.696, 0.439-1.103; 1.056, 0.941-1.185, respectively), each component of the primary outcome (in-hospital death, ventilator support, extracorporeal membrane oxygenation support, and admission to the intensive care unit), or the secondary outcomes (oxygen administration, disturbed consciousness, and hypotension, defined as systolic blood pressure ≤90 mmHg). ARB were divided into 1st- and 2nd-generations based on their approval for use (before 2000 and after 2001), with the former consisting of losartan, candesartan, and valsartan, and the latter of telmisartan, olmesartan, irbesartan, and azilsartan. The difference of ARB generation was not associated with the primary outcome (odds ratio with 2nd-generation ARB relative to 1st-generation ARB: 1.257, 95% confidence interval: 0.613-2.574). The odd ratio for a hypotension as one of the secondary outcomes with 2nd-generation ARB was 1.754 (95% confidence interval: 1.745-1.763) relative to 1st-generation ARB. These results suggest that patients taking 2nd-generation ARB may be at a higher risk of hypotension than those taking 1st-generation ARB and also that careful observations are needed. Further studies are continuously needed to support decisions to adjust medications for co-morbidities.

Improving quantum gate fidelities by using a qubit to measure microwave pulse distortions.

We present a new method for determining pulse imperfections and improving the single-gate fidelity in a superconducting qubit. By applying consecutive positive and negative π pulses, we amplify the qubit evolution due to microwave pulse distortions, which causes the qubit state to rotate around an axis perpendicular to the intended rotation axis. Measuring these rotations as a function of pulse period allows us to reconstruct the shape of the microwave pulse arriving at the sample. Using the extracted response to predistort the input signal, we are able to reduce the average error per gate by 37%, which enables us to reach an average single-qubit gate fidelity higher than 0.998.

Control of home blood pressure with an amlodipine- or losartan-based regimen and progression of carotid artery intima-media thickness in hypertensive patients: the HOSP substudy.

Carotid artery intima-media thickness (IMT) has emerged as a predictor of cardiovascular events. Home blood pressure (BP) is more closely associated with cardiovascular prognosis than clinic BP. The aim of this study was to compare the progression of carotid IMT with respect to strict and mild control of morning home systolic BP (SBP) and amlodipine- and losartan-based antihypertensive therapy in hypertensive patients. Subjects included 80 hypertensive outpatients who participated in the Hypertension Control Based on Home Systolic Pressure (HOSP) pilot study. After a 1-month drug-free period, the patients were randomly assigned to either the strict control group (target SBP <130 mm Hg) or the mild control group (130-139 mm Hg) and to either the amlodipine group or the losartan group. Additional antihypertensive drugs were added if target BP was not achieved with monotherapy. Morning SBP achieved target levels during 5 years in the strict control group and in the mild control group, while it was comparable between amlodipine and losartan groups. In all patients, mean and maximum carotid IMT increased significantly. Changes in carotid IMT did not differ between strict and mild control groups. Changes in mean carotid IMT in amlodipine group were smaller than those in losartan group at year 1, but were not different between the two groups at year 5. In conclusion, carotid IMT increased over time in hypertensive patients in spite of the strict control of home BP. Amlodipine may slow the progression of IMT more than losartan, although a difference was not obvious after 5 years.

Extremely large lamb shift in a deep-strongly coupled circuit QED system with a multimode resonator.

We report experimental and theoretical results on the extremely large Lamb shift in a multimode circuit quantum electrodynamics (QED) system in the deep-strong coupling (DSC) regime, where the qubit-resonator coupling strength is comparable to or larger than the qubit and resonator frequencies. The system comprises a superconducting flux qubit (FQ) and a quarter-wavelength coplanar waveguide resonator ([Formula: see text] CPWR) that are coupled inductively through a shared edge that contains a Josephson junction to achieve the DSC regime. Spectroscopy is performed around the frequency of the fundamental mode of the CPWR, and the spectrum is fitted by the single-mode quantum Rabi Hamiltonian to obtain the system parameters. Since the qubit is also coupled to a large number of higher modes in the resonator, the single-mode fitting does not provide the bare qubit energy but a value that incorporates the renormalization from all the other modes. We derive theoretical formulas for the Lamb shift in the multimode resonator system. As shown in previous studies, there is a cut-off frequency [Formula: see text] for the coupling between the FQ and the modes in the CPWR, where the coupling grows as [Formula: see text] for [Formula: see text] and decreases as [Formula: see text] for [Formula: see text]. Here [Formula: see text] is the frequency of the nth mode. The cut-off effect occurs because the qubit acts as an obstacle for the current in the resonator, which suppresses the current of the modes above [Formula: see text] at the location of the qubit and results in a reduced coupling strength. Using our observed spectrum and theoretical formulas, we estimate that the Lamb shift from the fundamental mode is 82.3% and the total Lamb shift from all the modes is 96.5%. This result illustrates that the coupling to the large number of modes in a CPWR yields an extremely large Lamb shift but does not suppress the qubit energy to zero, which would happen in the absence of a high-frequency cut-off.