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.

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.

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.

Association between oral frailty and cystatin C-related indices-A questionnaire (OFI-8) study in general internal medicine practice.

BACKGROUND: Cystatin C-related indices such as the ratio of creatinine to cystatin C (Cr/CysC) and the ratio of estimated glomerular filtration rate by cystatin C (eGFRcys) to creatinine eGFRcre (eGFRcys/eGFRcre) levels have been shown to be associated with muscle mass and strength and can be markers of sarcopenia. Oral frailty is defined as an age-related gradual loss of oral functions, accompanied by a decline in cognitive and physical functions. It results in adverse health-related outcomes in older age, including mortality, physical frailty, functional disability, poor quality of life, and increased hospitalization and falls. Therefore, poor oral health among the elderly is an important health concern due to its association with the pathogenesis of systemic frailty, suggesting it to be a multidimensional geriatric syndrome. The Oral Frailty Index-8 (OFI-8) is a questionnaire that can be used for easy screening of oral frailty. This study aimed to investigate whether cystatin C- related indices are different between patients with low to moderate risk of oral frailty and those at high risk of oral frailty, using the OFI-8 in attending a general internal medicine outpatient clinic. MATERIALS AND METHODS: This is a cross-sectional study that included 251 patients with a mean age of 77.7±6.6 years and a median age of 77 years (128 men: mean age, 77.1±7.3 years; median age, 77 years and 123 women: mean age, 78.4±5.7 years; median age, 78 years) attending general internal medicine outpatient clinics. OFI-8 scores were tabulated by gender to determine whether there were differences between patients at low to moderate risk of oral frailty (OFI-8 score ≤3 points) and those at high risk (OFI-8 score ≥4 points) in Cr/CysC, eGFRcys/eGFRcre levels, height, weight, grip strength, etc. were examined. RESULTS: The OFI-8 score was higher in women than in men, suggesting that oral frailty is more common in women. Cr/CysC, eGFRcys/eGFRcre and grip strength were significantly lower in both men and women in the high-risk group for oral frailty (OFI-8 score ≥ 4). Height, hemoglobin level, red blood cell count, and serum albumin levels were significantly lower in men with an OFI-8 score ≥4. Receiver operating characteristic curve (ROC) analysis also showed that Cr/CysC and eGFRcys/eGFRcre were significantly associated with an OFI-8 score≥4 in both men and women. CONCLUSION: Cr/CysC and eGFRcys/eGFRcre were significantly lower in the high-risk group for oral frailty on the OFI-8in both men and women. A relationship exists among cystatin C-related indices, which can effectively screen systemic frailty. Similarly, the OFI-8 score can be used to effectively screen oral frailty. Thus, a collaboration that incorporates both systemic and oral frailty from medical and dental perspectives is required.

Blood pressure per the 2017 ACC/AHA and 2018 ESC/ESH guidelines and heart failure risk: the Suita Study.

Hypertension is a significant risk factor for heart failure (HF). Since hypertension definition varies across guidelines, identifying blood pressure (BP) categories that should be targeted to prevent HF is required. We, therefore, investigated the association between hypertension per the 2017 American College of Cardiology/American Heart Association (ACC/AHA) and 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines and HF risk. This prospective cohort study included randomly selected 2809 urban Japanese people from the Suita Study. Cox regression was used to assess HF risk, in the form of hazard ratios (HRs) and 95% confidence intervals (95% CIs), for different BP categories in both guidelines, compared to a reference category defined as systolic BP (SBP) <120 mmHg and diastolic BP (DBP) <80 mmHg. Within 8 years of median follow-up, 339 HF cases were detected. Per the 2017 ACC/AHA guidelines, hypertension I and II and isolated systolic hypertension were associated with increased HF risk: HRs (95% CIs) = 1.81 (1.33-2.47), 1.68 (1.24-2.27), and 1.64 (1.13-2.39), respectively. Per the 2018 ESC/ESH guidelines, high-normal BP, hypertension I, II, and III, and isolated systolic hypertension were associated with increased HF risk: HRs (95% CIs) = 1.88 (1.35-2.62), 1.57 (1.13-2.16), 2.10 (1.34-3.29), 2.57 (1.15-5.77), and 1.51 (1.04-2.19), respectively. In conclusion, hypertension and isolated systolic hypertension per the 2017 ACC/AHA and 2018 ESC/ESH guidelines and high-normal BP per the 2018 ESC/ESH guidelines are risk factors for HF.

DAPagliflozin for the attenuation of albuminuria in Patients with hEaRt failure and type 2 diabetes (DAPPER study): a multicentre, randomised, open-label, parallel-group, standard treatment-controlled trial.

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the urinary albumin-to-creatinine ratio (UACR) in patients with elevated levels of albuminuria in the presence or absence of heart failure (HF) or type 2 diabetes mellitus (T2D). However, these effects have not yet been reported in the presence of both HF and T2D. This lack of evidence prompted us to conduct a clinical trial on the effects of dapagliflozin on UACR in patients with HF and T2D. Methods: DAPPER is a multicentre, randomised, open-labeled, parallel-group, standard treatment-controlled trial that enrolled patients at 18 medical facilities in Japan. Eligible participants with both HF and T2D and aged between 20 and 85 years were randomly assigned to a dapagliflozin or control (anti-diabetic drugs other than SGLT 2 inhibitors) group with a 1:1 allocation. The primary outcome was changes in UACR from baseline after a two-year observation, and secondary endpoints were cardiovascular (CV) events and parameters related to HF. This trial was registered with the UMIN-CTR registry, UMIN000025102 and the Japan Registry of Clinical Trials, jRCTs051180135. Findings: Between 12 May 2017 and 31 March 2020, 294 patients were randomly assigned to the dapagliflozin group (n = 146) or control group (n = 148). The mean age of patients was 72.1 years and 29% were female. The mean glycated hemoglobin value was 6.9%, mean NT-proBNP was 429.1 pg/mL, mean estimated GFR was 65.7 mL/min/1.73 m2, and median UACR was 25.0 (8.8-74.6) mg/g Cr in the dapagliflozin group and 25.6 (8.2-95.0) mg/g Cr in the control group. Of the 146 patients in the dapagliflozin group, 122 completed the study, and 107 (87.7%) were taking 5 mg of dapagliflozin daily at the end of the observation period. The primary outcome did not significantly differ between the dapagliflozin and control groups. Among the secondary endpoints, the mean decrease in left ventricular end-diastolic dimensions as one of the echocardiographic parameters was larger in the dapagliflozin group than in the control group. The composite endpoint, defined as CV death or hospitalisation for CV events, hospitalisation for HF events, hospitalisation for all causes, and an additional change in prescriptions for heart failure in a two-year observation, was less frequent in the dapagliflozin group than in the control group. Interpretation: Although dapagliflozin at a dose of 5 mg daily did not reduce urinary albumin excretion in patients with HF and T2D from that in the controls, our findings suggest that dapagliflozin decreased CV events and suppressed left ventricular remodeling. Funding: AstraZeneca KK, Ono Pharmaceutical Co., Ltd.

Acute Calcineurin Inhibitor Nephrotoxicity Diagnosed Using Kidney Doppler Ultrasonography After Heart Transplant: A Case Report.

BACKGROUND: Acute calcineurin inhibitor (CNI) nephrotoxicity is a common complication associated with CNI exposure. However, it can be difficult to diagnose. Herein, we report a case of acute CNI nephrotoxicity after heart transplant that was visualized using kidney Doppler ultrasonography. CASE REPORT: A 38-year-old female patient underwent heart transplant 5 years after the use of left ventricular assist device support because of advanced heart failure due to ischemic cardiomyopathy. Corticosteroids, tacrolimus, and mycophenolate mofetil were administered as immunosuppressive regimens postoperatively. The patient gradually developed kidney dysfunction despite a favorable perioperative clinical course and hemodynamics. Serum creatinine increased to 1.89 mg/dL on postoperative day (POD) 9, and the kidney Doppler ultrasonography examination showed severely reduced blood flow in the renal and renal segmental arteries, indicating acute CNI nephrotoxicity due to vasoconstriction of the renal arterioles. After the cessation of tacrolimus, kidney function returned to baseline levels within 2 days, and the kidney Doppler ultrasonography examination on POD 19 revealed a significant increase in blood flow in the renal and renal segmental arteries. Basiliximab followed by everolimus were administered as alternative immunosuppressants. No organic stenosis of the renal artery was detected on the kidney magnetic resonance angiography, and the patient was discharged on POD 51, without any other adverse events, including rejection. CONCLUSIONS: Although CNIs are widely used after heart transplant, acute nephrotoxicity should always be considered. After heart transplant, a kidney Doppler ultrasonography should be performed routinely and promptly if there are any clinical manifestations related to kidney function.

Plasma Clearance of Intravenously Infused Adrenomedullin in Rats with Acute Renal Failure.

Plasma adrenomedullin concentrations are reportedly elevated in patients with renal failure; however, the underlying mechanism is unclear. In this study, we investigated the plasma clearance of synthetic human adrenomedullin (AM) in two models of rats with renal dysfunction; one was induced by subcutaneous injection of mercury chloride (RD-Ag) and the other by completely blocking bilateral renal blood flow (RD-Bl). Sixty minutes after starting intravenous AM infusion, AM levels in RD-Ag, RD-Bl, and rats with normal renal function (NF) were still increased slightly; however, plasma AM levels in RD-Ag rats were approximately three times as high as in RD-Bl and NF rats. Plasma AM disappearance after the end of treatment was similar among the three groups. Pharmacokinetic analysis revealed that elevated plasma AM in RD-Ag rats may be caused by a reduced volume of distribution. The adrenomedullin functional receptor is composed of heterodimers, including GPCR, CLR (calcitonin receptor-like receptor, CALCRL), and the single transmembrane proteins, RAMP2 or RAMP3 (receptor activity modifying protein). Calcrl expression was downregulated in the lungs and kidneys of RD-Ag rats. Furthermore, the plasma concentration of exogenous AM was elevated in mice deficient in vascular endothelium-specific Ramp2. These results suggest that decreased plasma AM clearance in RD-Ag is not due to impaired renal excretion but to a decreased volume of distribution caused by a reduction in adrenomedullin receptors.

Renin-angiotensin system blocker and the COVID-19 aggravation in patients with hypertension, diabetes, renal failure, Cerebro-cardiovascular disease, or pulmonary disease: Report by the COVID-19 Registry Japan.

BACKGROUND: The role of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) in the pandemic context of coronavirus disease 2019 (COVID-19) continues to be debated. Patients with hypertension, diabetes mellitus, chronic renal failure, cerebro-cardiovascular disease, or chronic obstructive pulmonary disease (COPD), who often use ACEi/ARB, may be at risk of severe COVID-19. However, there are no data available on the association of ACEi/ARB use with COVID-19 severity in this population. METHODS: This study is an observational study of patients with a positive severe acute respiratory syndrome coronavirus 2 test and inpatient treatment at a healthcare facility, using the registry information of COVIREGI-JP. Our primary outcomes were in-hospital death, ventilator support, extracorporeal membrane oxygenation support, and intensive care unit admission. Out of the 6055 patients, 1921 patients with preexisting hypertension, diabetes mellitus, chronic renal failure, cerebro-cardiovascular disease, or COPD were enrolled. RESULTS: Factors associated with an increased risk of the primary outcomes were aging, male sex, COPD, severe renal impairment, and diabetes mellitus. No correlations were observed with ACEi/ARB, cerebro-cardiovascular diseases, or hypertension. Associated factors in male patients were aging, renal impairment, hypertension, and diabetes. In female patients, factors associated with an increased risk were aging, ACEi/ARB, renal impairment, and diabetes, whereas hypertension was associated with a lower risk of the primary outcomes. CONCLUSIONS: Independent factors for the primary outcomes were aging, male sex, COPD, severe renal impairment, and diabetes, but not ACEi/ARB. Based on this registry data analysis, more detailed data collection and analysis is needed with the cooperation of multiple healthcare facilities.

Impact of Percutaneous Transluminal Renal Angioplasty on Autonomic Nervous System and Natriuresis in Hypertensive Patients With Renal Artery Stenosis.

Background We investigated the early postoperative effect of percutaneous transluminal renal angioplasty on ambulatory blood pressure (BP) and the circadian characteristics of natriuresis and autonomic nerve activity. Methods and Results A total of 64 patients with hypertension with hemodynamically significant renal artery stenosis (mean age, 60.0±21.0 years; 31.3% fibromuscular dysplasia) who underwent angioplasty were included, and circadian characteristics of natriuresis as well as heart rate variability indices, including 24-hour BP, low-frequency and high-frequency (HF) components, and the percentage of differences between adjacent normal R-R intervals >50 ms were evaluated using an oscillometric device, TM-2425, both at baseline and 3 days after angioplasty. In both the fibromuscular dysplasia and atherosclerotic stenosis groups, 24-hour systolic BP (fibromuscular dysplasia, -19±14; atherosclerotic renal artery stenosis, -11±9 mm Hg), percentage of differences between adjacent normal R-R intervals >50 ms, HF, brain natriuretic peptide, and nighttime urinary sodium excretion decreased (all P<0.01), and heart rate increased (both P<0.05) after angioplasty. In both groups, revascularization increased the night/day ratios of percentage of differences between adjacent normal R-R intervals >50 ms (both P<0.01) and HF, and decreased those of low frequency/HF (all P<0.05) and nighttime urinary sodium excretion (fibromuscular dysplasia, 1.17±0.15 to 0.78±0.09; atherosclerotic renal artery stenosis, 1.37±0.10 to 0.99±0.06, both P<0.01). Multiple logistic regression analysis indicated that a 1-SD increase in baseline low frequency/HF was associated with at least a 15% decrease in 24-hour systolic BP after angioplasty (odds ratio, 2.30 [95% CI, 1.03-5.67]; P<0.05). Conclusions Successful revascularization results in a significant BP decrease in the early postoperative period. Intrarenal perfusion might be a key modulator of the circadian patterns of autonomic nerve activity and natriuresis, and pretreatment heart rate variability evaluation seems to be important for treatment success.

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.

Catheter-based ultrasound renal denervation in patients with resistant hypertension: the randomized, controlled REQUIRE trial.

Renal denervation is a promising new non-pharmacological treatment for resistant hypertension. However, there is a lack of data from Asian patients. The REQUIRE trial investigated the blood pressure-lowering efficacy of renal denervation in treated patients with resistant hypertension from Japan and South Korea. Adults with resistant hypertension (seated office blood pressure ≥150/90 mmHg and 24-hour ambulatory systolic blood pressure ≥140 mmHg) with suitable renal artery anatomy were randomized to ultrasound renal denervation or a sham procedure. The primary endpoint was change from baseline in 24-hour ambulatory systolic blood pressure at 3 months. A total of 143 patients were included (72 renal denervation, 71 sham control). Reduction from baseline in 24-hour ambulatory systolic blood pressure at 3 months was not significantly different between the renal denervation (-6.6 mmHg) and sham control (-6.5 mmHg) groups (difference: -0.1, 95% confidence interval -5.5, 5.3; p = 0.971). Reductions from baseline in home and office systolic blood pressure (differences: -1.8 mmHg [p = 0.488] and -2.0 mmHg [p = 0.511], respectively), and medication load, did not differ significantly between the two groups. The procedure-/device-related major adverse events was not seen. This study did not show a significant difference in ambulatory blood pressure reductions between renal denervation and a sham procedure in treated patients with resistant hypertension. Although blood pressure reduction after renal denervation was similar to other sham-controlled studies, the sham group in this study showed much greater reduction. This unexpected blood pressure reduction in the sham control group highlights study design issues that will be addressed in a new trial. CLINICAL TRIAL REGISTRATION: NCT02918305 ( http://www.clinicaltrials.gov ).

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.

Hypocholesterolemia is a risk factor for reduced systemic vascular resistance reactivity during hemodialysis.

Intradialytic hypotension (IDH) is associated with high mortality. Peripheral vascular resistance and circulating blood volume are important factors in IDH; however, the effects of hemodialysis (HD) on vascular resistance in IDH remain unclear. We herein performed a retrospective observational cohort study to investigate changes in and factors related to vascular resistance during HD. A total of 101 HD patients were divided into two groups (Decreased blood pressure (BP) during HD group: N = 19, Nondecreased BP group: N = 82), and cardiac output was measured with electrical velocimetry (AESCLON) for 3 h. The systemic vascular resistance index (SVRI) was significantly decreased in the Decreased BP group, while the cardiac index was similar in both groups. A multivariate regression analysis identified hypocholesterolemia as a predictor of reduced vascular resistance reactivity during HD. Furthermore, a correlation was found between changes in the SVRI and cholesterol levels in patients with a higher Geriatric Nutritional Risk Index (GNRI) but not in those with a lower GNRI. The present results suggest that hypocholesterolemia contributes to reducing systematic vascular resistance reactivity during HD, which is an important predictor of a reduction in BP during HD. The relationship between hypocholesterolemia and vascular resistance may involve mechanisms other than malnutrition.

Associations Between Arterial Stiffness Indices and Chronic Kidney Disease Categories in Essential Hypertensive Patients.

BACKGROUND: This study investigated the association between arterial stiffness indices and asymptomatic chronic kidney disease (CKD) risk categories in hypertensive patients. METHODS: Arterial stiffness indices, including 24-hour brachial and aortic systolic blood pressure (SBP) and pulse wave velocity (PWV), were measured by an oscillometric Mobil-O-Graph device, brachial-ankle PWV (baPWV) by a volume-plethysmographic method, and renal resistive index (RI) by ultrasonography, in 184 essential hypertensive patients (66.0 ± 17.1 years, 47.3% male). CKD was categorized into 3 stages based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria, using a combination of estimated glomerular filtration and albuminuria. RESULTS: The 24-hour aortic PWV (aPWV), baPWV, and RI increased with worsening severity of CKD risk category (all P < 0.01 for trend). Multivariate logistic regression analysis found that a 1 SD increase of nighttime aortic SBP (odds ratio [OR] 1.52), PWV (OR 4.80), or RI (OR 1.75) was an independent predictor of high or very-high CKD stage (all P < 0.05). After adjustment for potential confounders, day-to-night change in brachial SBP as well as in aPWV differed among groups (P < 0.05, respectively). In a multivariate regression model, day-to-night changes in aortic SBP and PWV, and RI were independently associated with day-to-night brachial SBP change. CONCLUSIONS: In hypertension, circadian hemodynamics in high CKD stage are characterized by higher nighttime values of aortic SBP and PWV and disturbed intrarenal hemodynamics. Further, the blunted nocturnal BP reduction in these patients might be mediated via disturbed intrarenal hemodynamics and circadian hemodynamic variation in aortic SBP and arterial stiffness.

Impact of Percutaneous Revascularization on Left Ventricular Mass and Its Relationship to Outcome in Hypertensive Patients With Renal Artery Stenosis.

BACKGROUND: We investigated the effects of percutaneous transluminal renal angioplasty on left ventricular (LV) mass, and the impact of LV mass reduction on outcomes. METHODS: A total of 144 hypertensive patients with renal artery stenosis (RAS) (mean age 69 years; 22.2% fibromuscular dysplasia (FMD)) who underwent angioplasty were included. Echocardiography was performed at baseline and after 1 year, and patients were thereafter followed up for a median of 5.6 years for primary composite outcomes. RESULTS: In both the FMD and atherosclerotic stenosis (ARAS) groups, LV mass decreased after angioplasty, but the decrease in LV mass index (-15.4 ± 18.3% vs. -0.8 ± 27.8%, P < 0.01) as well as the regression rate of LV hypertrophy was greater in FMD. Multiple logistic regression analysis indicated that FMD (odds ratio (OR) 2.94, P < 0.01), severe RAS (≥90%) (OR 2.94, P < 0.05), and higher LV mass index at baseline (OR 2.94 for 1 SD increase, P < 0.001) were independent predictors of LV mass index decrease of at least 20%. The primary composite outcomes occurred in 45 patients (31.3%). In FMD, lower LV mass index after 1 year (hazard ratio 2.81 for 1 SD increase, P < 0.05) or regression of LV mass (hazard ratio 0.75 for 5% decrease, P = 0.054) showed a tendency to be associated with better outcomes; however, these associations were not found in ARAS. CONCLUSIONS: Hypertensive patients with ARAS have less regression of LV mass in response to angioplasty than those with FMD, and LV mass regression is less useful as a surrogate marker of outcomes especially in ARAS.

Genetic factors associated with elevation of uric acid after treatment with thiazide-like diuretic in patients with essential hypertension.

We investigated changes in blood pressure (BP) and metabolic adverse effects, especially elevation of uric acid (UA), after treatment with a thiazide-like diuretic (TD) in patients with essential hypertension. Furthermore, the role of genetic factors in the elevation of UA by TD was assessed by a 500 K SNP DNA microarray. The subjects included 126 hypertensive patients (57 women and 69 men, mean age 59 ± 12 years) who registered for the GEANE (Gene Evaluation for ANtihypertensive Effects) study. After one month of the nontreatment period, TD, indapamide, angiotensin II receptor antagonist valsartan, and Ca channel blocker amlodipine were administered to all patients for 3 months each in a randomized crossover manner. BP, renal function, serum UA level, and electrolytes were measured at baseline and at the end of each treatment period. Single nucleotide polymorphisms (SNPs) associated with UA elevation after treatment with indapamide were investigated by a genome-wide association study (GWAS). Indapamide significantly decreased both office and home BP levels. Treatment with indapamide also significantly reduced the estimated glomerular filtration rate and serum potassium and increased serum UA. Patients whose UA level increased more than 1 mg/dl showed significantly higher baseline office SBP and plasma glucose and showed greater decline in renal function compared with those who showed less UA increase (<1 mg/dl). Some SNPs strongly associated with an increase in UA after treatment with indapamide were identified. This study is the first report on SNPs associated with UA elevation after TD treatment. This information may be useful for the prevention of adverse effects after treatment with TD.

Association Between Circadian Hemodynamic Characteristics and Target Organ Damage in Patients With Essential Hypertension.

BACKGROUND: This study investigated the association between circadian hemodynamic characteristics and asymptomatic hypertensive organ damage. METHODS: Circadian hemodynamics, including 24-hour brachial and aortic systolic blood pressure (SBP), pulse wave velocity (PWV), augmentation index (AIx@75), cardiac index, and total vascular resistance (TVR), were evaluated using an oscillometric device, Mobil-O-Graph, in 284 essential hypertensive patients (67.8 ± 16.0 years, 54% female). Hypertensive target organ damage (TOD), namely carotid wall thickening, left ventricular hypertrophy, and albuminuria, was assessed in all patients. RESULTS: Office SBP and 24-hour brachial and aortic SBP all increased with increasing number of organs involved (all P < 0.01 for trend). After multivariate logistic regression analysis, 24-hour brachial SBP (odds ratio [OR] = 1.04 for 1 mm Hg increase, P < 0.001) as well as aortic SBP (OR = 1.03 for 1 mm Hg increase, P < 0.05) maintained significance. Percent decrease during nighttime in brachial SBP, PWV, and TVR, but not cardiac index, showed a significant graded relationship with the number of organs involved. In a multivariate stepwise regression model, the nighttime values of brachial SBP, PWV, and TVR emerged as independent predictors of the presence of TOD. CONCLUSION: In essential hypertension, 24-hour aortic SBP could be a marker of subclinical TOD, and further, the blunted nocturnal BP reduction in TOD patients might be mediated by disturbed circadian hemodynamic variations in aortic SBP, vascular resistance, and arterial stiffness.

Circadian hemodynamic characteristics in hypertensive patients with primary aldosteronism.

OBJECTIVE: The present study aimed to compare circadian hemodynamic characteristics in hypertensive patients with and without primary aldosteronism. METHODS: Circadian hemodynamics, including 24-h brachial and central blood pressure (BP), SBP variability indices, central pulse wave velocity (PWV), augmentation index (AIx@75), cardiac index, and total vascular resistance (TVR), were evaluated using an oscillometric device, Mobil-O-Graph, in 60 patients with primary aldosteronism (63.4±13.3 years, 47% women) and 120 age-matched and sex-matched patients with essential hypertension. RESULTS: Office SBP, PWV, AIx@75, and BP variability indices were similar between groups; however, 24-h brachial (124 ±â€Š14 vs 130 ±â€Š11 mmHg) as well as central (112 ±â€Š12 vs 120 ±â€Š10 mmHg) SBP was higher (both P < 0.01), and the difference between 24-h brachial and central SBP (11 ±â€Š5 vs 9 ±â€Š3 mmHg, P < 0.05), an index of pressure amplification, was smaller in primary aldosteronism than in essential hypertension. In both groups, cardiac index decreased from daytime to night-time (both P < 0.01), but this decrease was smaller in primary aldosteronism (P < 0.05). During daytime, TVR in primary aldosteronism was higher than that in essential hypertension (P < 0.05), and the significant increase of TVR from daytime to night-time was lost in primary aldosteronism. In a multivariate stepwise regression model, primary aldosteronism emerged as an independent predictor of 24-h central SBP as well as the difference between 24-h brachial and central SBP. CONCLUSION: Our results demonstrated that circadian hemodynamics in primary aldosteronism patients are characterized by increased central SBP, smaller disparity between brachial and central SBP, and disturbed circadian hemodynamic variation.