Clinical Benefit of Sacubitril/Valsartan for Hypertensive Patients in Daily Practice and Predictors of Its Antihypertensive Effect.

Background: The blood pressure (BP)-lowering effect of sacubitril/valsartan (Sac/Val) is greater than that of angiotensin II receptor blockers (ARBs) but in in real-world clinical practice, Sac/Val is used in a variety of patterns other than switching from ARBs. In the present study we investigated the effects of Sac/Val on BP and biochemical parameters when switching from or adding it to various antihypertensive drugs and examined what factors could be predictors of the antihypertensive effect of Sac/Val. Methods and Results: In 108 hypertensive patients treated with antihypertensive agents (including 4 naïve cases), clinic BP and various biochemical parameters were assessed before and after switching to/adding Sac/Val (200 mg/day). Systolic and diastolic BPs significantly decreased after treatment with Sac/Val (P<0.0001, respectively). As for biochemical parameters, alanine aminotransferase, triglycerides, C-reactive protein, and uric acid significantly decreased after administration of Sac/Val, but renal function, B-type natriuretic peptide, and plasma renin activity (PRA) did not change before or after treatment with Sac/Val. Multiple regression analysis revealed that low PRA and high baseline systolic BP were independent determinants of systolic BP reduction after Sac/Val treatment. Conclusions: Sac/Val is beneficial for poorly controlled hypertension in daily clinical practice and low PRA may be a predictor of the antihypertensive effect of switching to/adding Sac/Val.

Predictive value of early-phase heart rate reduction for subsequent recovery of left ventricular systolic function in heart failure with reduced ejection fraction.

INTRODUCTION: Predictors of heart failure with recovered ejection fraction (HFrecEF) remain to be fully elucidated. This study investigated the impact of heart rate and its change on the recovery of left ventricular ejection fraction (LVEF) in heart failure with reduced ejection fraction (HFrEF). MATERIAL AND METHODS: From 398 outpatients who had a history of hospitalisation for heart failure, 138 subjects diagnosed as HFrEF (LVEF < 40%) on heart failure hospitalisation were enrolled and longitudinally surveyed. During follow-up periods more than one year, 64 and 46 patients were identified as HFrecEF (improved LVEF to ≥ 40% and its increase of ≥ 10 points) and persistent HFrEF, respectively. RESULTS: In the overall subjects, the reduction of heart rate through the observation periods was closely correlated with the improvement of LVEF (r = -0.508, p < 0.001). Heart rate on hospital admission for heart failure was markedly higher in patients with HFrecEF (112 ± 26 bpm) than in those with persistent HFrEF (90±18 bpm). Whereas heart rate at the first outpatient visit after discharge was already lower in the HFrecEF group (80 ± 13 vs. 85 ± 13 bpm in the persistent HFrEF group). A multivariate logistic regression analysis revealed that the decrease in heart rate from admission to the first visit after discharge was a significant determinant of HFrecEF (p < 0.001), independently of confounding factors such as ischemic heart disease and baseline LVEF and left ventricular dimension. CONCLUSIONS: Our findings suggest that heart rate reduction in the early phase after heart failure onset is a powerful independent predictor of the subsequent recovery of LVEF in HFrEF patients.

Evaluation of novel indices of walking performance taking oxygen desaturation into account during six-minute walk test in cardiovascular disease patients.

In pulmonary disease patients since oxygen desaturation during 6-min walk test (6MWT) affects walk distance (6MWD), some novel indices such as desaturation/distance ratio [DDR, oxygen desaturation area (DAO2)/6MWD] and distance-saturation product [DSP, 6MWD × minimum peripheral oxygen saturation (SpO2)] are evaluated. However, there has been no study examining these indices that consider exercise-induced desaturation (EID) in patients with cardiovascular disease. In 94 cardiovascular disease patients without pulmonary complications, 6MWT and echocardiography were performed at the entry of cardiac rehabilitation. SpO2 was measured during 6MWT using a continuously monitorable pulse oximeter, and DSP and DDR were calculated using minimum SpO2 and DAO2 [sum of (100-SpO2) per second during 6MWT], respectively. EID was defined as SpO2 decrease of ≥ 4% or minimum SpO2 of < 90% during 6MWT. DSP was slightly lower and DDR was markedly higher in patients with EID than in those without. When examining correlations of DSP and DDR with their components, DSP was correlated with 6MWD much closely than minimum SpO2, while DDR was correlated as closely with DAO2 as 6MWD. Furthermore, DAO2, but not minimum SpO2, had a direct correlation with 6MWD. As for associations with cardiac function, DSP was correlated with several cardiac parameters, but DDR was not correlated with any of these parameters. Our findings suggest that oxygen desaturation during 6MWT affects walking distance in cardiovascular disease patients even without pulmonary complications and that DDR is more appropriate than DSP as an index of walking performance that takes EID into consideration, independently of cardiac function.

Differential effects on renal function and glucose metabolism of renal dependent bezafibrate and non-renal dependent pemafibrate in patients with hypertriglyceridemia.

OBJECTIVE: Among fibrates as triglyceride-lowering agents, bezafibrate and fenofibrate are predominantly renally excreted, while pemafibrate is mainly hepatically metabolized and biliary excreted. To elucidate possible different properties among fibrates, this retrospective observational study examined the changes in clinical laboratory parameters, including indices of renal function and glucose metabolism, in cases of switching from bezafibrate to pemafibrate. MATERIALS AND METHODS: In 93 patients with hypertriglyceridemia, the average values of laboratory parameters including serum creatinine, estimated glomerular filtration rate (eGFR), plasma glucose, and hemoglobin A1c on respective two occasions before and after switching from bezafibrate to pemafibrate were evaluated. RESULTS: Triglycerides, low-density and high-density lipoprotein cholesterol, creatine kinase, and uric acid did not change before and after switching from bezafibrate to pemafibrate. Serum creatinine significantly decreased and eGFR significantly increased after switching from bezafibrate to pemafibrate (p < 0.001, respectively). Plasma glucose tended to increase (p = 0.070) and hemoglobin A1c significantly increased (p < 0.001) after switching to pemafibrate. The degrees of changes in creatinine, eGFR, glucose, and hemoglobin A1c before and after drug switching were not affected by the presence or absence of coexisting disease, and with or without drug treatment including statin and renin-angiotensin system inhibitor. CONCLUSION: Our findings indicate that switching from bezafibrate to pemafibrate produces a significant decrease in serum creatinine and increases in eGFR and hemoglobin A1c in patients with hypertriglyceridemia, suggesting that the effects on renal function and glucose metabolism differ among fibrates.

The E/e' ratio on echocardiography as an independent predictor of the improvement of left ventricular contraction in patients with heart failure with reduced ejection fraction.

OBJECTIVE: Clinical feature of heart failure with improved ejection fraction (HFimpEF) remains to be fully elucidated. The present study investigated the association of clinical and echocardiographic parameters with the subsequent improvement of left ventricular ejection fraction (LVEF) in heart failure with reduced ejection fraction (HFrEF). METHODS: From outpatients with a history of hospitalized for heart failure, 128 subjects diagnosed as HFrEF (LVEF <40%) on heart failure hospitalization were enrolled and longitudinally surveyed. During follow-up periods more than 1 year, 58 and 42 patients were identified as HFimpEF (improved LVEF to ≥40% and its increase of ≥10 points) and persistent HFrEF, respectively. RESULTS: There was no difference in age or sex between the two groups with HFimpEF and persistent HFrEF. The rate of ischemic heart disease was lower and that of tachyarrhythmia was higher in the HFimpEF group than in the persistent HFrEF group. At baseline (i.e., on heart failure hospitalization), LVEF did not differ between the two groups, but left ventricular systolic and diastolic diameters were already smaller and the ratio of early diastolic transmitral velocity to early diastolic tissue velocity (E/e') was lower in the HFimpEF group. A multiple logistic regression analysis revealed that lower baseline E/e' was a significant determinant of HFimpEF, independently of confounding factors such as ischemic heart disease, tachyarrhythmia, and baseline left ventricular dimension. CONCLUSION: Our findings indicate that the lower ratio of E/e' in the acute phase of heart failure onset is an independent predictor of the subsequent improvement of LVEF in HFrEF patients.

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.

Cardiac metastasis of lung cancer presented as mimicking ST-elevation myocardial infarction with reciprocal electrocardiographic changes.

We report the case of a patient with metastatic cardiac tumor who presented with chest pain and electrocardiographic changes mimicking acute inferior myocardial infarction. An 84-year-old man who had undergone lung cancer surgery one year earlier was referred to emergency outpatient visit because of chest pain. His 12-lead electrocardiography (ECG) showed ST-segment elevation in the inferior leads with reciprocal ST-segment depression in the precordial and lateral leads, which was initially interpreted as inferior acute myocardial infarction. By emergency coronary angiography, however, there was no significant stenosis or occlusion in the right coronary artery or the left circumflex artery. In echocardiographic examinations after admission, a large mass was found in the area corresponding to the infero-posterior wall of the left ventricle, which had been detected only by positron emission tomography with computed tomography six months earlier. He died one month after admission. Pathological autopsy revealed a tumor of 8 × 5 cm size in the myocardium of the posterior to inferior wall of the left ventricle, and diagnosed as cardiac metastasis from lung cancer. ECG changes with ST-segment elevation, in particular persistent ST-elevation in the absence of Q waves, can be a sign for tumor invasion of the heart. Learning objective: It is necessary to consider the possibility of myocardial metastasis when a patient with malignancy presents with acute myocardial infarction-like electrocardiography findings. Besides, in this case, positron emission tomography with computed tomography (PET-CT) had detected an abnormal accumulation in the left ventricle earlier than when the tumor was pointed out by echocardiography. Multimodality imaging including PET-CT could help physicians to make the early and accurate diagnosis of metastatic cardiac tumor.

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.

Achilles tendon thickness is associated with coronary lesion severity in acute coronary syndrome patients without familial hypercholesterolemia.

BACKGROUND: Thickening of Achilles tendon (≥9 mm on radiography) is one of the diagnostic criteria for familial hypercholesterolemia (FH). Since FH is associated with premature coronary artery disease (CAD) including acute coronary syndrome (ACS), measurement of Achilles tendon thickness (ATT) is important for early diagnosis of FH. However, clinical significance of mild thickening of Achilles tendon in non-FH patients with CAD is unclear. The present study investigated the association of ATT with coronary lesion severity in early-onset ACS without clinically diagnosed FH. METHODS: From outpatients who had a history of ACS under 60 years old, 76 clinically non-FH subjects (71 men and 5 women; mean age at the onset of ACS, 50.5 years) with maximum ATT of <9 mm were enrolled in this study. The severity of coronary lesions was assessed by SYNTAX score derived from coronary angiography at the onset of ACS. RESULTS: ATT levels were not significantly different among patients with ST-elevation myocardial infarction (STEMI, n=47), non-STEMI (n=12), and unstable angina (n=17). Whereas, both average and maximum ATT were significantly larger in patients with multivessel lesions (n=25) than in those with single-vessel disease (n=51). Furthermore, SYNTAX score was positively correlated with average ATT (r=0.368, p=0.0011) and maximum ATT (r=0.388, p=0.0005). As for the relation to clinical parameters, maximum ATT had positive correlations with body mass index and C-reactive protein. A multiple regression analysis revealed that average and maximum ATT were significantly associated with SYNTAX score, independently of various confounding factors. CONCLUSIONS: Our findings demonstrated that ATT, even though its level was <9 mm, was associated with coronary lesion severity in clinically non-FH patients with early-onset ACS. Apart from diagnosing FH, ATT may be a predictor of the progression of CAD.

Long-term administration of tolvaptan ameliorates annual decline in estimated glomerular filtration rate in outpatients with chronic heart failure.

Protective effects of tolvaptan against worsening renal function in acute heart failure have been shown. However, long-term effects of its agent on renal function remain to be elucidated. The present study investigated retrospectively whether long-term treatment with tolvaptan exerts renoprotective effects in patients with chronic heart failure, by comparing serial changes in estimated glomerular filtration rate (eGFR) for years before and after tolvaptan administration. From 63 outpatients with chronic heart failure taking diuretics including tolvaptan, 34 patients whose eGFR levels were continuously measured for more than 6 months both before and after administration of tolvaptan (average dose, 7.8 mg/day at the end of the follow-up period) were selected as eligible for the present analyses. All eGFR values were separately plotted before and after the initiation of treatment with tolvaptan (except hospitalization periods) along the time course axis and the slope of the linear regression curve was calculated as an annual change in eGFR. The mean follow-up periods before and after tolvaptan administration were 1197 and 784 days (3.3 and 2.1 years), respectively. Changing rates of eGFR per year were significantly ameliorated after treatment with tolvaptan (mean ± SD, - 8.02 ± 9.35 to - 1.62 ± 5.09 mL/min/1.73m2 /year, P = 0.001). In echocardiographic parameters, inferior vena cava (IVC) diameter significantly decreased after tolvaptan administration, and the decrease in IVC diameter was correlated with the improvement of eGFR decline slope after administration of tolvaptan (P = 0.0075). This longitudinal observational study indicated that long-term treatment with tolvaptan ameliorated annual decline in eGFR in outpatients with chronic heart failure. Our findings suggest that tolvaptan has a protective effect against chronically worsening renal function in heart failure patients.

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.

Behavior of isoprothiolane and fipronil in paddy water, soil, and rice plants after nursery-box or submerged applications.

We investigated the behavior of isoprothiolane and fipronil after nursery-box application and that of isoprothiolane after submerged application in an experimental paddy field. The concentrations of the pesticides and their metabolites were monitored in paddy water, soil, and rice plants. The distribution profile for isoprothiolane mass in the field differed greatly between the nursery-box and submerged applications. The nursery-box-applied pesticides were mostly distributed in soil near the transplanted rice seedlings (root zone), versus little distribution in paddy water and rice plants (<1.1 and <0.3% of the applied mass, respectively). The residual levels in rice plants were similar to those in the root-zone soil. To estimate the soil pesticide mass, we defined a key parameter: the ratio of the root-zone area to the total area of the paddy field estimated to be 0.1 to 0.15. This parameter is important when evaluating the concentrations of nursery-box-applied pesticides in soil and rice plants.