Efficacy and safety of sacubitril/valsartan after switching from azilsartan in hemodialysis patients with hypertension.

This study assessed the efficacy and safety of sacubitril/valsartan in 23 hemodialysis patients with hypertension (mean age 70 years; male 69.6%) after switching from azilsartan, an angiotensin receptor blocker. Both at baseline and 3 months after the start of sacubitril/valsartan treatment, home blood pressure (BP), BP values during hemodialysis, and N-terminal pro-brain natriuretic peptide (NT-proBNP) level were measured. The mean dosage of azilsartan was 30 ± 10 mg/day at baseline and that of sacubitril/valsartan after 3 months of treatment was 204 ± 64 mg/day. After 3 months, significant reductions in mean morning home BP (155 ± 17/80 ± 12 to 147 ± 16/76 ± 11 mmHg), mean nighttime home systolic BP (153 ± 19 to 144 ± 16 mmHg), and median (IQRs) NT-proBNP level [8124 (2620-13 394) to 6271 (1570-9591) pg/mL] were observed (all P < .05), whereas BP values during hemodialysis did not change significantly. In hemodialysis patients, except for hypotension, sacubitril/valsartan was generally well tolerated, effectively controlled out-of-office BP, and improved NT-proBNP.

Blood pressure, arterial waveform, and arterial stiffness during hemodialysis and their clinical implications in intradialytic hypotension.

This study included 152 hemodialysis patients (mean age, 69 years; 34.2% female) and investigated serial changes in blood pressure (BP) and arterial stiffness indices during hemodialysis using an oscillometric device, SphygmoCor XCEL, and examined whether assessment of the arterial waveform has clinical implications for the management of intradialytic hypotension (IDH). Measurement was performed every 30 min during hemodialysis, and the threshold defining IDH was systolic BP (SBP) decrease ≥40 mmHg or a requirement for antihypotensive medication in all patients and ≥ the 75th percentile of maximum SBP decrease during hemodialysis (≥34 mmHg) in the subgroup without antihypotensive medication (n = 98). In all patients, a 1-standard deviation (SD) increase in the baseline subendocardial viability ratio (SEVR), an index of myocardial perfusion, was an independent predictor of IDH (odds ratio [OR] 0.43, p < 0.001). In the subgroup analysis, a serial change in SBP and all arterial waveform indices, including the augmentation index, augmented pressure (AP), and SEVR, during hemodialysis were greater for IDH than for non-IDH patients (all p < 0.01 by 2-way repeated-measures ANOVA), with the exception of heart rate (p = 0.40) and diastolic pressure time index (p = 0.21). Diabetes (OR 4.08), a 1-SD increase in ultrafiltration rate (OR 2.07), fractional shortening (OR 0.45), baseline SEVR (OR 0.36) and the first 1-h percent change in AP (OR 0.52) were independent predictors of IDH (all p < 0.05). In conclusion, impaired myocardial perfusion and increased arterial stiffness, particularly poor arteriolar responsiveness to acute dialysis-related changes, are associated with IDH, and predialysis SEVR evaluation can complement screening for IDH.

Renoprotective effect of chronic treatment with sodium-glucose cotransporter 2 inhibitors and its associated factors in Japanese patients with chronic heart failure and diabetes.

Background: Recent clinical trials have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors have beneficial effects on renal function in heart failure patients. This study confirmed the renoprotective effect of treatment with SGLT2 inhibitors in Japanese patients with chronic heart failure and diabetes and further investigated what cardiac/hemodynamic and noncardiac factors are involved in its effect. Methods: Eligible 50 outpatients with chronic heart failure and type-2 diabetes mellitus chronically taking SGLT2 inhibitors were enrolled. Annual changing rates of estimated glomerular filtration rate (eGFR) were compered before and after treatment with SGLT2 inhibitors and the associations of the change in eGFR slope after SGLT2 inhibitor administration with changes in various clinical and echocardiographic parameters were evaluated. Results: The mean follow-up periods before and after SGLT2 inhibitor administration were 2.6 and 1.9 years, respectively. Changing rates of eGFR per year were significantly improved after treatment with SGLT2 inhibitors (-5.78 ± 7.67 to -0.43 ± 10.81 mL/min/1.73 m2/year, p = 0.006). The daily doses of loop diuretics were not altered after SGLT2 inhibitor administration. Neither decreased body weight nor increased hematocrit was associated with the change in eGFR slope before and after SGLT2 inhibitor administration. While, the decrease in inferior vena cava diameter and the increase in its respiratory collapsibility were significantly correlated with the improvement of eGFR decline slope after SGLT2 inhibitor administration. Conclusions: Our findings indicated that chronic treatment with SGLT2 inhibitors ameliorated annual decline in eGFR in Japanese patients with chronic heart failure, suggesting the possibility that the improvement of venous congestion was involved in its renoprotective effect.

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.

The European/International Fibromuscular Dysplasia Registry and Initiative (FEIRI)-clinical phenotypes and their predictors based on a cohort of 1000 patients.

AIMS: Since December 2015, the European/International Fibromuscular Dysplasia (FMD) Registry enrolled 1022 patients from 22 countries. We present their characteristics according to disease subtype, age and gender, as well as predictors of widespread disease, aneurysms and dissections. METHODS AND RESULTS: All patients diagnosed with FMD (string-of-beads or focal stenosis in at least one vascular bed) based on computed tomography angiography, magnetic resonance angiography, and/or catheter-based angiography were eligible. Patients were predominantly women (82%) and Caucasians (88%). Age at diagnosis was 46 ± 16 years (12% ≥65 years old), 86% were hypertensive, 72% had multifocal, and 57% multivessel FMD. Compared to patients with multifocal FMD, patients with focal FMD were younger, more often men, had less often multivessel FMD but more revascularizations. Compared to women with FMD, men were younger, had more often focal FMD and arterial dissections. Compared to younger patients with FMD, patients ≥65 years old had more often multifocal FMD, lower estimated glomerular filtration rate and more atherosclerotic lesions. Independent predictors of multivessel FMD were age at FMD diagnosis, stroke, multifocal subtype, presence of aneurysm or dissection, and family history of FMD. Predictors of aneurysms were multivessel and multifocal FMD. Predictors of dissections were age at FMD diagnosis, male gender, stroke, and multivessel FMD. CONCLUSIONS: The European/International FMD Registry allowed large-scale characterization of distinct profiles of patients with FMD and, more importantly, identification of a unique set of independent predictors of widespread disease, aneurysms and dissections, paving the way for targeted screening, management, and follow-up of FMD.

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.

How should we define appropriate patients for percutaneous transluminal renal angioplasty treatment?

Renovascular hypertension (RVH) is one of the most common causes of secondary hypertension and can result in resistant hypertension. RVH is associated with an increased risk for progressive decline in renal function, cardiac destabilization syndromes including "flash" pulmonary edema, recurrent congestive heart failure, and cerebrocardiovascular disease. The most common cause of renal artery stenosis (RAS) is atherosclerotic lesions, followed by fibromuscular dysplasia. The endovascular technique of percutaneous transluminal renal angioplasty (PTRA) with or without stenting is one of the standard treatments for RAS. Randomized controlled trials comparing medical therapy with PTRA to medical therapy alone have failed to show a benefit of PTRA; however, the subjects of these randomized clinical trials were limited to atherosclerotic RAS patients, and patients with the most severe RAS, who would be more likely to benefit from PTRA, might not have been enrolled in these trials. This review compares international guidelines related to PTRA, reevaluates the effects of PTRA treatment on blood pressure and renal and cardiac function, discusses strategies for the management of RVH patients, and identifies factors that may predict which patients are most likely to benefit from PTRA.

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.

Gene and environmental interactions according to the components of lifestyle modifications in hypertension guidelines.

Risk factors for hypertension consist of lifestyle and genetic factors. Family history and twin studies have yielded heritability estimates of BP in the range of 34-67%. The most recent paper of BP GWAS has explained about 20% of the population variation of BP. An overestimation of heritability may have occurred in twin studies due to violations of shared environment assumptions, poor phenotyping practices in control cohorts, failure to account for epistasis, gene-gene and gene-environment interactions, and other non-genetic sources of phenotype modulation that are suspected to lead to underestimations of heritability in GWAS. The recommendations of hypertension guidelines in major countries consist of the following elements: weight reduction, a healthy diet, dietary sodium reduction, increasing physical activity, quitting smoking, and moderate alcohol consumption. The hypertension guidelines are mostly the same for each country or region, beyond race and culture. In this review, we summarize gene-environmental interactions associated with hypertension by describing lifestyle modifications according to the hypertension guidelines. In the era of precision medicine, clinicians who are responsible for hypertension management should consider the gene-environment interactions along with the appropriate lifestyle components toward the prevention and treatment of hypertension. We briefly reviewed the interaction of genetic and environmental factors along the constituent elements of hypertension guidelines, but a sufficient amount of evidence has not yet accumulated, and the results of genetic factors often differed in each study.

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.

Factors Associated with Outcomes of Percutaneous Transluminal Renal Angioplasty in Patients with Renal Artery Stenosis: A Retrospective Analysis of 50 Consecutive Cases.

BACKGROUND: The results of recent trials have brought some confusion to the treatment strategy for renal artery stenosis (RAS). To evaluate the applicability of percutaneous transluminal renal angioplasty (PTRA) for RAS, we extracted the factors that may affect the effectiveness of PTRA from cases experienced at a hypertension center. METHODS AND RESULTS: We retrospectively assessed the blood pressure (BP) lowering effects and renoprotective effects in 50 consecutive patients that had hemodynamically significant RAS and had undergone PTRA and stenting during 2001-2005. Subjects were diagnosed with atherosclerotic RAS (42), fibromuscular dysplasia (6), or Takayasu disease (2). After PTRA, BP significantly lowered from 152.3/80.3 mmHg to 132.6/73.2 mmHg (p < 0.05), but the estimated glomerular filtration rate (eGFR) did not change significantly. There were no factors associated with the BP lowering effects of PTRA. The baseline resistive index (RI) was negatively correlated with the change in eGFR (p < 0.05). After correction for age, sex, BMI, and the dose of contrast medium, the association of RI with change in eGFR remained significant. CONCLUSION: In cases with hemodynamically significant RAS, PTRA lowered BP but was not effective in improving renal function. Higher baseline RI may be a factor for predicting poor clinical course of renal function after PTRA.

Association between renal function and outcomes after percutaneous transluminal renal angioplasty in hypertensive patients with renal artery stenosis.

OBJECTIVE: We investigated the impact of renal function on outcomes after percutaneous transluminal angioplasty. METHODS: A total of 139 hypertensive patients with atherosclerotic renal artery stenosis (mean age, 70 years, 80.6% men) who underwent renal percutaneous transluminal angioplasty were included. Renal function was evaluated on the basis of estimated glomerular filtration rate (eGFR) and albuminuria/proteinuria, and classified into three categories according to eGFR (≥45, 30-44, and <30 ml/min/1.73 m) and albuminuria/proteinuria [normal-to-mild: albumin/creatinine ratio (ACR) less than 3.0, protein/creatinine ratio (PCR) less than 15; moderate: ACR 3.0-30.0, PCR 15-50; severe: ACR > 30.0, PCR > 50 mg/mmol]. RESULTS: During a median follow-up of 5.4 years, 36.0% of patients developed the primary composite end point, including cardiovascular and renal outcomes. In multivariate Cox regression analysis, eGFR less than 30 (hazard ratio 3.47, P < 0.01) as well as severe albuminuria/proteinuria (hazard ratio 2.63, P < 0.05) was an independent predictor of worse outcome. In the subgroup without events within 1 year after angioplasty (n = 117), the outcome differed among the three renal functional categories at 1 year based on eGFR (log-rank χ = 16.28, P < 0.001) as well as on albuminuria/proteinuria (log-rank χ = 8.30, P < 0.05). At 1 year, 24 patients (20.1%) showed at least 20% decrease in eGFR, and their outcome was worse than that in those with at least 20% increase (n = 23) (hazard ratio 3.50, P < 0.05). Multiple logistic regression analysis indicated that pretreatment moderate-to-severe albuminuria/proteinuria was an independent predictor of at least 20% eGFR decrease (odds ratio 2.82, P < 0.05). CONCLUSION: Impaired renal function, and in particular, a poor response of eGFR to angioplasty, is associated with worse outcome. Therapeutic effectiveness of renal angioplasty seems to be limited in patients with albuminuria/proteinuria.

Effective uric acid-lowering treatment for hypertensive patients with hyperuricemia.

Uric acid (UA) has been associated with hypertension, renal disease and cardiovascular disease. The aim of the present study was to compare the UA-lowering effects of a standard dose of the UA synthesis inhibitor febuxostat to a standard dose of the uricosuric agent benzbromarone, and to investigate the effects of a low-dose combination of both agents in hypertensive patients with hyperuricemia. Twenty hypertensive patients with inadequate UA control were administered febuxostat 40 mg (Feb), benzbromarone 50 mg (Ben) and febuxostat 20 mg and benzbromarone 25 mg (feb/ben) for 3 months each in a randomized modified crossover manner. UA metabolism, blood pressure (BP) and the indices of organ damage were assessed at baseline and the end of each treatment period. No significant changes were observed in BP or estimated glomerular filtration rate (eGFR) after the treatment with each UA-lowering regimen. The change in UA was significantly greater with feb/ben than with Feb. The excretion of UA and clearance of UA were higher with Ben than with Feb and feb/ben. Urinary 8-hydroxydeoxyguanosine and liver-type fatty-acid-binding protein levels were slightly lower with Ben, whereas flow-mediated dilation was slightly higher with feb/ben and Ben. The UA-lowering effects of the low-dose combination of the UA synthesis inhibitor and uricosuric agent were greater than those of the standard dose of each agent alone. The uricosuric agent may be more effective at improving vascular function than the UA synthesis inhibitor. Thus, the appropriate management of hyperuricemia with uricosuric drugs appears to be useful for hypertensive patients with hyperuricemia.

Effects of Percutaneous Transluminal Renal Angioplasty on Office and Home Blood Pressure and Home Blood Pressure Variability in Hypertensive Patients With Renal Artery Stenosis.

This study included 126 hypertensive patients with renal artery stenosis (mean age, 63 years; 22.2% fibromuscular dysplasia [FMD]) and investigated the effects of percutaneous transluminal renal angioplasty on office and home blood pressure (BP), and BP variability estimates derived from home BP, both at baseline and up to 12 months after angioplasty. Home BP was measured for 7 consecutive days, and the threshold defining uncontrolled home BP was ≥135/85 mm Hg. In both the FMD and atherosclerotic stenosis (ARAS) groups, office and home BP decreased significantly after angioplasty (all P<0.01), but the decrease in morning home (-22±19 versus -10±20 mm Hg; P<0.01) but not in office (-32±24 versus -23±28 mm Hg; P=0.11) systolic BP at 12 months was significantly greater in FMD. In both groups, all morning BP variability indices except the coefficient of variation in ARAS decreased significantly after revascularization (all P<0.05 by repeated-measures ANOVA). The decrease in all morning systolic BP variability estimates was greater for FMD than for ARAS (all P<0.05 by 2-way repeated-measures ANOVA), with the exception of variability independent of the mean (P=0.11). The prevalence of uncontrolled home BP was 77.0% at baseline and 38.9% after revascularization. Duration of hypertension (odds ratio, 1.48), ARAS (odds ratio, 3.18), and the presence of proteinuria (odds ratio, 2.10) were independent predictors of uncontrolled home BP after revascularization (all P<0.05). In conclusion, renal angioplasty produced a greater decrease of morning home systolic BP in FMD; however, in both groups, it decreased BP variability irrespective of BP response. Measurement of home BP seems to be important for treatment success, especially in ARAS.

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.