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Among the components of renin-angiotensin-aldosterone system, aldosterone facilitates the progression of cardiovascular organ injuries not only by promoting renal tubular Na reabsorption but also by causing oxidative stress, inflammation and cardiovascular tissue hypertrophy and fibrosis. Therefore, mineral corticoid receptor blockers (MRB) supposedly exhibit protective effects against cardiovascular organ injuries in hypertensive patients. In this study, the therapeutic effects of MRB in the combination antihypertensive treatment were examined in hypertensive patients. Fifty mg eplerenone (EPL) was added to 24 hypertensive patients under antihypertensive drug therapy who had not achieved the target blood pressure. The combination was continued for 3 to 4 months and the effects on blood pressure (BP) and laboratory data including renal function and cardiovascular endocrine system were evaluated. After 3-4 months, office BP was lowered from 148/91 to 135/86 mmHg (p

高血圧治療ガイドラインでは，診察室血圧（OBP）は1-2分間隔で測定を繰り返し，安定した2回の測定値の平均で評価することとされているが，数多い高血圧患者の実地診療において測定を繰り返すことは難しく，1回の測定で評価される場合も多い．本研究では診察室血圧が高値を呈する高血圧患者において，深呼吸後に測定を繰り返すことによる血圧の変化を検討した． 外来を受診した高血圧患者で，診察室の収縮期血圧（SBP）140 mmHg 以上を呈した160名を対象とした．1回目の測定の後，深呼吸を繰り返し1-2分後に2回目の測定を行い，血圧の変化に関係する因子を検討した． 1回目のOBP は147/84 mmHg であったが，2 回目は136/82 mmHg と平均11/2 mmHg低下し，69％が非高血圧となった．SBPが10 mmHg以上低下したR群（91 名）と10 mmHg 未満のN群（69 名）の比較では，R群の方が血清クレアチニン（sCr）が低く（1.03 vs 1.36 mg/dL, p＝0.018）血中ヘモグロビン（Hb）が高値（13.9 vs 13.1 g/dL, p＝0.012）で，SBP の低下とHb の間には負の相関が認められた（r＝－0.157, p＝0.046）． SBP が140 未満に低下した110例ではしなかった50例に比べ，家庭血圧で夜のSBPが低く，HbやeGFR（62.3 vs 52.1 mL/分/1.73 m2, p＝0.021）が高値で，sCr やアルブミン尿（124 vs 425 mg/gCr, p＝0.025）が低値であった． 外来加療中の高血圧患者で診察室血圧が高値である場合，特に腎機能低下や蛋白尿がなければ，多くは深呼吸を繰り返すことにより正常化するため，治療方針を決める際に考慮するべきであると思われる．, Hypertension treatment guidelines state that office blood pressure should be measured repeatedly at intervals of 1 to 2 minutes and evaluated as the average of two stable measurements. In this study, we examined changes in blood pressure in hypertensive patients with elevated office blood pressure by repeating measurements after deep breathing. One hundred and sixty hypertensive patients who were being treated in the outpatient clinic and presented a systolic blood pressure（SBP）of 140 mmHg or higher in the examination room were included in the study. After the first measurement, a second measurement was taken one to two minutes after repeated deep breathing to examine factors related to blood pressure changes. The first OBP was 147/84 mmHg, but the second was 136/82 mmHg, an average decrease of 11/2 mmHg, and 69％ were non-hypertensive. In a comparison between the group with SBP decrease more than 10 mmHg（91 patients） and the group with SBP decrease less than 10 mmHg（69 patients）, serum creatinine was lower（1.03 vs 1.36 mg/dL, p＝0.018）and blood hemoglobin（Hb）was higher（13.9 vs 13.1 g/dL, p＝0.012）in the decreased group, with a negative correlation between the SBP change and Hb（r＝－0.157, p＝0.046）. Compared to the 50 patients whose SBP were 140 or higher after deep breathing, the 110 patients whose SBP fell below 140 had lower SBP in the evening on home blood pressure, higher Hb, higher estimated glomerular filtration rate（62.3 vs 52.1 mL/min/1.73 m2, p＝ 0.021）, lower serum creatine and lower albuminuria（124 vs 425 mg/gCr, p＝0.025）. In hypertensive outpatients, high office blood pressure is often normalized by repeating deep breath especially in the absence of chronic kidney disease, which should be considered when determining the antihypertensive treatment strategy.

Patients with chronic kidney disease（CKD）are at high risk for developing cardiovascular diseases, and hyperuricemia is associated with the progression of renal dysfunction and the incidence of cardiovascular events. Allopurinol（Alp）, a xanthine oxidase inhibitor（XOi）, has been shown to improve the prognosis of CKD patients by inhibiting renal dysfunction and cardiovascular events. However, Alp possibly causes some serious side effects especially in patients with impaired renal function. Newer XOi such as febuxostat and topiroxostat（Tpx）can be safely used in CKD patients, while it has been reported that the incidence of cardiovascular death was rather higher in gout patients with cardiovascular diseases given febuxostat than those given Alp. In this study, we compared the effects of Alp and Tpx on cardiovascular risk profile in CKD patients. Thirty-five CKD patients were given Alp（50, 100, 200 mg/day）or Tpx（40, 80, 160 mg/day）for 3-6 months in a random crossover manner, and the indices of cardiovascular risk were evaluated at the end of each treatment period. Hypouricemic effect was more prominent in Tpx than Alp（5.8 vs 6.4 mg/dL, p＝0.001）. There were significant differences in systolic blood pressure（Tpx 122 vs Alp 127 mmHg, p＝0.004）, serum creatinine（1.72 vs 1.93 mg/dL, p＝0.002）, plasma brain natriuretic peptide（43 vs 63 pg/mL, p＝0.022）, and the parameter of oxidative stress（reactive oxygen metabolite：314 vs 342 U.CARR, p＝0.010）. However, serum LDL-cholesterol（113 vs 102 mg/dL, p＝0.008）were significantly higher in Tpx than in Alp. Although attention should be paid to the effects on serum lipid profile, Tpx is supposedly more effective in inhibiting cardiovascular disorders and slowing the progression of renal dysfunction in hyperuricemic CKD patients.

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.

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.

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 CTA, MRA and/or catheter-based angiography were eligible.Patients were predominantly women (82%) and Caucasians (88%). Age at diagnosis was 46±16 years (12% ≥65yo), 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 ≥65yo had more often multifocal FMD, lower eGFR 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. TRANSLATIONAL PERSPECTIVE: Fibromuscular dysplasia (FMD) is nowadays considered as a systemic arterial disease, warranting brain-to-pelvis vascular imaging in all patients. However, most current evidence is derived from a limited number of expert centres. Furthermore, one size may not fit all. Based on analysis of the first thousand patients enrolled in the European/International FMD registry (46 centres; 22 countries) we characterized distinct patient profiles according to FMD subtype, age and gender and identified predictors of widespread disease, aneurysms and dissections, paving the way for individualized management and follow-up. Further studies will allow refining patient characterization according to ethnicity, genetic profile and imaging biomarkers.

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.

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.

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 (

It is still controversial whether treatment with renin-angiotensin system (RAS) inhibitors reduces the risk of incident atrial fibrillation (AF). This longitudinal observational study was performed to investigate the confounder-independent effects of RAS inhibitors on new-onset AF in hypertensive patients. Among 1263 consecutive hypertensive patients who underwent echocardiography, 964 eligible patients (mean age, 63 years) were enrolled as the study population. Forty-nine patients developed new-onset AF during the follow-up period (mean: 4.6 years). Kaplan-Meier analysis showed that the cumulative AF event rate was lower in patients receiving RAS inhibitors than in patients without these drugs, but the difference between these two groups was not significant (P=0.057). Since the use of RAS inhibitors was influenced by concomitant diabetes, chronic kidney disease and left ventricular hypertrophy, propensity score matching (1:1) was employed to minimize the influence of selection bias for RAS inhibitors. Clinical and echocardiographic parameters showed no significant differences between the propensity score-matched groups with and without RAS inhibitor therapy (both n=326), but the cumulative AF event rate was significantly lower in the group receiving RAS inhibitors (P=0.013). Univariate and multivariate Cox regression analyses also revealed that RAS inhibitor therapy was associated with a significantly lower risk of new-onset AF during the follow-up period. In conclusion, this propensity score matching study demonstrated that the incidence of new-onset AF was lower in hypertensive patients receiving RAS inhibitor therapy.

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.

Percutaneous transluminal renal angioplasty (PTA) is one of the standard treatments for renal artery stenosis (RAS). We investigated the frequency and risk factors for restenosis, and its impact on blood pressure (BP) control.A total of 175 hypertensive patients with RAS [mean age 60 years; 34% women; 30.3% fibromuscular dysplasia (FMD)] with 207 treated renal arteries were included and followed for more than 1 year without reangioplasty. Diagnosis of restenosis was based on duplex ultrasonographic findings, and data including BP and antihypertensive medication were collected consecutively.During follow-up (mean, 5.1 years), 56 patients (32.0%) developed restenosis. In multivariate Cox regression analysis, FMD was an independent predictor of restenosis (hazard ratio 2.65, P 0.05). When divided into two groups based on FMD or atherosclerotic RAS (ARAS), the presence of previous cardiovascular disease (hazard ratio 2.84) as well as severe RAS (≥90%) (hazard ratio 3.95) in ARAS were independent predictors of restenosis (P 0.05, respectively). At 1 year after PTA, 35 patients (20.0%) had developed restenosis. When divided into four groups on the basis of FMD or ARAS, and the absence/presence of restenosis at 1 year, the number of antihypertensive drugs was significantly lower in both FMD and ARAS patients without restenosis (P 0.01, respectively); however, a significant difference in decrease in SBP (-31 ± 19 vs. -12 ± 25 mmHg, P 0.05) as well as cure of hypertension (36.4 vs. 5.0%, P 0.01) between the absence/presence of restenosis was found only in FMD patients.The frequency of restenosis after renal PTA is significant, and the presence of restenosis diminishes the benefit of its treatment, especially for FMD.

Salt restriction is important for the prevention and treatment of hypertension; however, salt consumption is still high in Japan. Improvements in dietary habits, including salt reduction in childhood, may contribute to the prevention of hypertension. The aim of the present study was to investigate the salt intake of school-aged children and the relationship between their diet diary and actual salt intake. The subjects comprised 580 schoolchildren (471 elementary school pupils and 109 junior high school pupils) who wanted to evaluate their salt intake in Kuji, a northeast coastal area in Japan. We estimated salt intake using spot urine samples and a formula. Lifestyle was assessed using a questionnaire. We also evaluated the salt intake and the lifestyles of 440 parents. The estimated salt intakes of elementary school pupils, junior high school pupils and their parents were 7.1±1.5, 7.6±1.5 and 8.0±1.7 g per day, respectively. The proportion of lower-grade children who achieved the recommended salt intake was low. In the multivariate analysis, the estimated salt intake of school-aged children correlated with their age, estimated salt intake of their parents and the menu priorities of the household. The estimated salt intake of the parents was associated with female gender, obesity, age and the habitual consumption of bread and noodles. In conclusion, the estimated salt intake of school-aged children positively correlated with the estimated salt intake of their parents, and the proportion of lower-grade children who achieved the recommended salt intake was low. Guidance on salt restriction for children and their parents may reduce the salt intake of school-aged children.

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 ± 14 vs 130 ± 11 mmHg) as well as central (112 ± 12 vs 120 ± 10 mmHg) SBP was higher (both P

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.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.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).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.

Mechanical circulatory support by a left ventricular assist device (LVAD) is used to bridge patients with advanced heart failure to transplant or as a definitive treatment. We retrospectively sought predictors of long-term outcome in a cohort of 83 patients who had undergone LVAD treatment. We subjected perioperative clinical data of patients to statistical analysis to establish parameters associated with all-cause mortality, and the cutoff values, sensitivity, and specificity of those that had a statistically significant relation with survival. Mean follow-up was 717 days (standard deviation, 334 days; range, 17-1,592 days). Fourteen patients (16.8%) died, but nine (10.8%) were weaned from support. Serum brain natriuretic peptide (BNP) concentration measured 60 days after implantation was significantly associated with all-cause mortality. The optimal BNP cutoff value to predict death during LVAD support was 322 pg/ml, with a sensitivity of 71.4% and specificity of 79.8%. Two-year survival was 92.0% in those with 60 days serum BNP concentration

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.

Objective: Atherosclerotic renal artery stenosis (ARAS) is associated with secondary hypertension. Renal dysfunction is often present in ARAS patients; however, evidence for the impact of pretreatment renal function on outcomes after percutaneous transluminal renal angioplasty (PTA) is limited. Methods: A total of 139 hypertensive patients with ARAS (mean age, 69.5±8.9 years, 112 male) who underwent renal PTA were included. Renal function was evaluated based on estimated glomerular filtration rate (eGFR) and albuminuria/proteinuria, and classified into three categories according to eGFR (≥45, 30-44, 2 ) and albuminuria/proteinuria [normal-to-mild: albumin/creatinine ratio (ACR) 30.0, PCR >50 mg/mmol]. The primary end point of this study was first occurrence of the composite of cardiovascular and renal events including all-cause death, myocardial infarction, stroke, adverse aortic events, or end-stage renal failure requiring regular hemodialysis. Results: During a median follow up of 5.4 years, 36.0% (50 of 139) of patients developed the primary composite end point including cardiovascular and renal outcomes. In multivariate Cox regression analysis, eGFR 2 =16.28, p 2 =8.30, p Conclusion: Impaired renal function, and in particular, a poor response of eGFR to PTA, is associated with worse outcome. Therapeutic effectiveness of renal angioplasty seems to be limited in patients with albuminuria/proteinuria.

We investigated the impact of renal function on outcomes after percutaneous transluminal angioplasty.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, and30 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].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).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.

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, p0.01); 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, p0.01). The rate of achievement of salt intake6 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.

Endothelin-1 (ET-1) is a potential marker of the endothelial dysfunction, which has been shown to be elevated in hypertensive subjects. No previous study has investigated the circulatory level of ET-1 and hypertension in a South Asian country. The present study assessed the circulating levels of ET-1 in subjects with or without hypertension and further examined the association of ET-1 with clinical and metabolic parameters. A total of 2543 rural Bangladeshi women with a mean age of 44.5 years were studied using a cross-sectional survey. Multiple regressions were used to examine the association between the circulatory ET-1 levels and hypertension. The prevalence of hypertension was 29.3%. The ET-1 levels were significantly higher in the hypertensive (mean 3.08 pg ml(-1), s.e. (0.19)) than in the non-hypertensive subjects (mean 2.01 pg ml(-1), s.e. (0.03)) (P = 0.001). After adjusting for age, the ET-1 level had significant positive associations with the diastolic blood pressure (P = 0.002), systolic blood pressure (P = 0.001), mean arterial pressure (P = 0.002) and fasting blood glucose (P = 0.002). In a tertile analysis, we found that hypertension in the subjects was significantly increased as the levels of ET-1 increased (P for the trend = 0.001). In a stepwise multiple regression analysis, after adjusting for age and all other potential variables, we found that the mean arterial pressure and the fasting plasma levels have significant associations with the ET-1 level. The present study demonstrates that there is a higher concentration of ET-1 among the hypertensive subjects in an apparently healthy population of Bangladeshi rural women. The relationship between ET-1 and hypertension requires further investigation to define the clinical utility and predictive value of serum ET-1 levels for hypertension for a South Asian population.

BACKGROUND This study assessed the relationship between different oral health markers-periodontitis, gingival bleeding, tooth number, and occlusal status-and hypertension in a Japanese urban population. METHODS A total of 1,643 participants with no prior cardiovascular disease (mean age = 66.6 years; 43.4% women) underwent comprehensive health checkups, including a lifestyle questionnaire and dental examination in the Suita Study. RESULTS In the multivariable-adjusted logistic model, none of the individual oral health markers, namely severe periodontitis, gingival bleeding, lowest quartile of tooth number, and malocclusion, were significantly associated with increased odds of hypertension. The additive effects of oral health markers on hypertension were examined and showed that, compared with subjects with no component of the oral health markers, the multivariale-adjusted odds ratio of hypertension in those with ≥3 components was 1.82 (95% confidence interval (CI) = 1.23-2.72; P = 0.003). In the subpopulation without antihypertensive medication (n = 1,148; 59.8% women), a significant graded relationship between multivariable-adjusted systolic blood pressure and the number of components was found (P trend = 0.03), and, compared with subjects with no component of the oral health markers, having ≥3 components was related to a higher systolic blood pressure (β = 5.41; 95% CI = 1.16-9.66; P = 0.01). CONCLUSIONS There is an additive relationship between oral health disorders and risk of hypertension. Our results suggest that the existence of moderate or severe oral health disorders-that is, several concomitant oral health disorders-is associated with risk of hypertension.

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

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 P 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 P 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

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.

Increased renal restive index (RI) measured using Doppler ultrasonography has been shown to correlate with the degree of renal impairment in hypertensive patients. We investigated the prognostic role of RI in cardiovascular and renal outcomes. A total of 426 essential hypertensive subjects (mean age, 63 years; 50% female) with no previous cardiovascular disease were included in this study. Renal segmental arterial RI was measured by duplex Doppler ultrasonography. During follow-up (mean, 3.1 years), 57 participants developed the primary composite end points including cardiovascular and renal outcomes. In multivariate Cox regression analysis, RI was an independent predictor of worse outcome in total subjects (hazard ratio, 1.71 for 1 SD increase), as well as in patients with estimated glomerular filtration rate (eGFR) 2 (hazard ratio, 2.11 for 1 SD increase; P 2 groups, the group with eGFR 2 =126.4; P P

Left ventricular assist system (LVAS) implantation is an established treatment for patients with advanced heart failure. We investigated the clinical implication of serial changes in renal function after LVAS implantation.This study included 110 patients who underwent pulsatile LVAS implantation intended as a bridge to transplantation and were alive more than 2 weeks after implantation. Data collection of demographic and hematologic values was performed 1 day before (baseline) and 2 weeks after implantation. All patients were monitored for 2 years or until death.The 2-year postimplantation mortality rate was 31.8%. Multivariate Cox regression analysis showed the baseline estimated glomerular filtration rate (eGFR) was an independent predictor of death (hazard ratio, 0.90 for each 10 mL/min increase, p0.05). The eGFR significantly increased at 2 weeks after LVAS implantation (70.5±37.8 to 121.0±78.8 mL/min, p0.01). Kaplan-Meier curves with log-rank tests showed significantly poorer event-free survival rates in the group with an inframedian value of change in eGFR at 2 weeks after implantation (ΔeGFR; p=0.03) as well as in the group with the lowest tertile of eGFR at 2 weeks after implantation (2w-eGFR; p0.01). Multivariate Cox regression analysis showed that ΔeGFR (hazard ratio, 0.89 for each 10 mL/min increase) and 2w-eGFR (hazard ratio, 0.92 for each 10 mL/min increase) were independent predictors of death (p0.01, respectively).Impaired renal function, and in particular, a poor response of eGFR to LVAS implantation, may have a strong association with worse outcome.

The effects of left ventricular assist system (LVAS) implantation on renal hemodynamics remains to be fully elucidated. We evaluated renal function and intrarenal blood flow in five advanced heart failure patients who had been supported with a Toyobo LVAS for bridge to heart transplantation. Renal function expressed as estimated glomerular filtration rate (eGFR) was calculated using the modified formula of Modification of Diet in Renal Disease. Mean blood velocities in the bilateral segmental arteries during systolic and diastolic perfusion were measured using duplex Doppler sonography, and renal vascular resistance (resistive index [RI]) of the segmental arteries was defined as (peak systolic velocity [PSV]-end-diastolic velocity [EDV])/PSV. All studies were performed before and after implantation (mean duration of support, 15.6±10.9 months). LVAS implantation significantly improved eGFR (42.7±7.9 to 64.1±16.3mL/min, P

Molecular mechanisms of sepsis-associated acute lung injury (ALI) are poorly defined. Since vascular endothelial growth factor (VEGF) is a potent vascular permeability and mitogenic factor, it might contribute to the development of ALI in sepsis. Thus, using lipopolysaccharide (LPS)-induced (15 mg/kg, intraperitoneal) endotoxemic rat model, we studied the timeline (1, 3, 6, and 10 h) of pulmonary VEGF expression and its signaling machinery. Levels of pulmonary VEGF and its angiogenic-mediating receptor, Flk-1, were downregulated by LPS in a time-dependent manner; levels of plasma VEGF and its permeability-mediating receptor, Flt-1, in contrast, was upregulated with time. In addition, blockade of Flt-1 could improve the downregulated pulmonary VEGF level and attenuate the elevated plasma and pulmonary levels of TNF-α, followed by improvement of arterial oxygenation and wet-to-dry weight ratio of the lung. Expression of signaling, pro- and or apoptotic factors after LPS administration were as follows: phosphorylated Akt, a downstream molecule was downregulated time dependently; endothelial nitric oxide synthase levels were significantly reduced; pro-apoptotic markers caspase 3 and Bax were upregulated whereas levels of Bcl-2 were downregulated. The present findings show that VEGF may play a role through the expression of Flt-1 in LPS-induced ALI. Moreover, downregulation of VEGF signaling cascade may account for LPS-induced apoptosis and impaired physiological angiogenesis in lung tissues, which in turn may contribute to the development of ALI induced by LPS.

Regulator of G-protein signaling 2 (RGS2) is a key molecule in signal pathways of vasoactive peptides, such as angiotensin II and endothelin 1, and is believed to have an important role in the pathophysiology of atherosclerosis. We have previously reported that common polymorphisms of RGS2 are associated with hypertension in Japanese. In this study, we studied whether the three previously identified common polymorphisms of RGS2 (−638A>G, 1026T>A and 1891–1892delTC) could be implicated in carotid atherosclerosis in Japanese patients with hypertension (459 men and 382 woman) and in a Japanese general population (814 men and 956 woman). We assessed two criteria for carotid atherosclerosis: maximal intima-media thickness (M-IMT) and mean-IMT. When subjects with atherosclerotic lesions were defined as having mean-IMT≥1.0 mm, multivariate logistic regression analysis performed after adjusting for confounding factors showed a significant association of the three common polymorphisms, −638A>G (AA versus AG+GG: odds ratio (OR), 1.55; 95% confidence interval (CI), 1.105–2.185; P=0.0113 only for the general population), 1026T>A (TT versus TA+AA: OR, 1.42; 95% CI, 1.027–1.972; P=0.034 for hypertensive subjects and OR, 1.56; 95% CI, 1.129–2.151; P=0.0071 for the general population), and 1891–1892delTC (II versus ID+DD: OR, 1.44; 95% CI, 1.043–2.008; P=0.028 for hypertensive subjects, OR, 1.32; 95% CI 1.002–1.742; P=0.048 for the total general population and OR 1.59; 95% CI 1.155–2.207; P=0.0047 for the general population), with carotid atherosclerosis. When atherosclerosis was defined as M-IMT ⩾1.0 mm, the values of M-IMT were also significantly different between the three genotypes in the three common polymorphisms. Taken together, these data suggest that genetic polymorphisms in RGS2 are associated with intima-media thickening of carotid artery in humans.

Endothelin (ET)-1 is a potent vasoconstrictor that has been implicated in the pathogenesis of a number of diseases, and some studies suggest that circulating ET-1 is elevated in sepsis. The present study investigated whether ET plays a role in sepsis-mediated acute lung injury and whether its expression could be down regulated by blockade of TNF-α in septic lung. Male Wistar rats at 8 weeks of age were administered with either saline or lipopolysaccharide (LPS) at different time points (1, 3, 6 and 10 h) and various tests were then performed. The features of acute lung injury were observed at 1 h after LPS administration, which gradually became severe with time. Systolic and diastolic pressures were reduced just about one hour after LPS administration, whereas pulmonary TNF-α levels were significantly increased at various time points after LPS administration. LPS induced a time-dependent expression of ET-1 and ET(A) receptor in the lungs compared to control, peaking and increasing by 3 fold at 6 h after induction of endotoxemia, whereas levels of ET(B) receptor, which has vasodilating effects, were remarkably down regulated time-dependently. We conclude that time-dependent increase of ET-1 and ET(A) receptor with the down regulation of ET(B) receptor may play a role in the pathogenesis of acute lung injury in endotoxemia. Finally, treatment of LPS-administered rats with TNF-α blocking peptide for three hours significantly suppressed levels of pulmonary ET-1. These data taken together, led us to conclude that differential alteration in ET expression and its receptors may be mediated by TNF-α and may, in part, account for the pathogenesis of acute lung injury in endotoxemia.