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Objective: This simulation study attempted to infer the systolic blood pressure (SBP) levels at which subjects with hypertension, health nurses, and primary physicians should switch their preference of their treatment policies from lifestyle modifications to antihypertensive medications in virtual Japanese sample populations. Methods: We assumed that SBP levels were normally distributed and that the incidence rate of cardiovascular disease (IR CVD , events/year) increased exponentially according to SBP. The total IR CVD was calculated by the definite integral for the product of the distribution of SBP multiplied by IR CVD at each SBP level. The success rates were calculated according to SBP and metabolic risk profiles in the two approaches, respectively. We deduced the hypothetical SBP levels by solving differential equations of ∆(IR CVD )/ ∆(SBP) = 0 using numerical analysis. Results: In the realistic situations where the subjects were not affirmative to antihypertensive medications, the inferred SBP level to switch from lifestyle modifications to antihypertensive medications should be around 150 mmHg. If the subjects are affirmative to antihypertensive medications, the SBP level should be lowered to 140 mm Hg. Conclusion: This success rate-oriented simulation proposes that the SBP level to switch from lifestyle modifications to antihypertensive medications can be modulated according to the behavioral propensity for taking antihypertensive medications. Abbreviations: The following abbreviations are used in this manuscript: CVD: cardiovascular disease; LM: lifestyle modifications; AM: antihypertensive medications; IR CVD : incidence rate of cardiovascular disease (events/year); SBP: systolic blood pressure; ∆IR CVD : the improvements in the incidence rate of cardiovascular disease by lifestyle modifications and/or by antihypertensive medications.

This study aimed to investigate the association of gastrointestinal (GI) adverse events of cinacalcet with gallstones in the hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). A total of 23 HD patients under the treatment with cinacalcet and 101 control patients were enrolled in this cross-sectional study. We investigated the prevalence of gallstones and the association of GI adverse events of cinacalcet with gallstones. The prevalence of gallstones was significantly higher in the HD patients with cinacalcet compared with the controls (47.8% vs. 15.8%). The longer time on HD, hypercalcemia, hyperphosphatemia and elevated parathyroid hormone level were observed in the HD patients with cinacalcet. Besides, GI adverse events of cinacalcet were observed more frequently in the HD patients with gallstones compared with those without gallstones (odds ratio 13.5, 95% CI: 1.80-101). Therefore, screening for gallstones before dosing cinacalcet may reduce the risk of GI adverse events in SHPT patients.

Background: Kidney resistive index (RI) correlates with tubulointerstitial changes and predicts renal prognosis. Most patients with chronic kidney diseases (CKDs) manifest high blood pressure and atherosclerotic cardiovascular diseases. In addition, various atherosclerotic indexes relate to variations in blood pressure., Methods: Subjects were 70 CKD patients, who visited our office and agreed to measure home blood pressure and receive renal ultrasonography. Cross-sectional analyses were performed., Results: Patient age was averaged 61 ± 15 (SD) y/o and 60% were male. Mean serum creatinine and proteinuria were 1.2 ± 0.5 mg/dl and 0.2 ± 0.5 g/gCr, respectively. Office blood pressure and kidney RI were 128 ± 17/75 ± 11 mmHg and 0.66 ± 0.08, respectively. Multivariate regression analysis revealed that age and office blood pressure independently correlated to kidney RI (p < 0.05 for each). Home blood pressure was averaged 122 ± 7/70 ± 6 mmHg. Both standard deviation and the maximal-minimal difference in home systolic blood pressure related to kidney RI (p < 0.05)., Conclusions: The present results indicate that office blood pressure correlates to kidney RI, which predicts renal prognosis. In addition, our data implicate that kidney RI relates to variations in home systolic blood pressure, and suggest that kidney RI may be a good index for atherosclerosis in CKD patients.

Hypertension is a well-known cardiovascular risk. Patients with end-stage renal diseases frequently suffer hypertension. Furthermore, daily variations of blood pressure are relatively large in patients treated with hemodialysis, partly due to ultrafiltration. Twenty hypertensive patients with end-stage renal diseases whose blood pressure was controlled by a single antihypertensive agent, either angiotensin receptor antagonist (ARB) or calcium channel blocker (CCB), were enrolled into the study. Home blood pressure measurements were also performed. Average systolic and diastolic blood pressures were similar between two agents. However, variations of systolic blood pressure during ARB treatment were greater than those of CCB, and maximal differences in daily systolic blood pressure during treatment with ARB (19±7 mmHg) were greater than those with CCB (14±6 mmHg, p<0.01). Systolic blood pressure measured after hemodialysis under ARB therapy (110±6 mmHg) was lower than that of CCB (118±6 mmHg, p<0.05). Daily variations of diastolic blood pressure were similar between ARB and CCB periods. Our results indicate that variations of systolic blood pressure during ARB treatment are larger than CCB, and suggest that CCB is useful to obtain the better quality of blood pressure control, improving blood pressure stability by preventing substantial drops in blood pressure in hypertensive patients with end-stage renal diseases.

Telmisartan is an angiotensin type 1 receptor blocker (ARB), which also partially activates liganding peroxisome proliferator-activated receptor gamma. However, the relationship between the effects of telmisartan on hemodynamics and metabolism has not sufficiently been elucidated in clinical settings. We examined the long-term effects of telmisartan on hemodynamics including home blood pressure (BP) and on insulin resistance representing as homeostasis model assessment (HOMA-R). Twenty-seven hypertensive patients were consecutively enrolled at our outpatient department. At entry, all of the participants were previously prescribed another ARB for more than 3 months and then the former ARB were replaced by telmisartan. Hemodynamic and metabolic parameters were measured before treatment and at points 1 and 3 months after treatment with telmisartan. Telmisartan significantly lowered home systolic blood pressure (SBP) and diastolic blood pressure (DBP) (DBP) and improved HOMA-R during the treatment period. However, the changes in home SBP and DBP were not correlated with that of HOMA-R. In conclusion, telmisartan lowers home BP and improves insulin resistance without correlation between their changes.

Renoprotective effects of renin-angiotensin system inhibitors are well known. However, hypertension with chronic kidney diseases (CKDs) is usually hard to manage with a single agent, and requires the addition of either a calcium antagonist or diuretics to achieve the goal of blood pressure (BP) lowering. Retrospective study was performed among the patients who regularly visited our office, and whose BP had not reached the goal of BP despite of treatment with an angiotensin receptor blocker. Clinical parameters were observed for 6 months. Comparisons of home BP and proteinuria were made between 16 patients prescribed additional calcium antagonists and 15 patients with diuretics. Patient background including age, sex BP, augmentation index, and renal function were similar between the two groups. Both calcium antagonists and diuretics considerably decreased BP. An addition of either agent resulted in similar control of home BP. While both agents reduced augmentation index (AI), calcium antagonist exerted greater improvements in AI (-7 ± 5 vs. -4 ± 3%, p < 0.01). Although urinary protein excretion in both groups was decreased, the degree of these decreases was greater among the patients treated with a calcium antagonist (-28 ± 15 vs. -11 ± 15%, p < 0.01). During observation periods, eGFR in both groups did not show any significant changes from the base line. Under the inhibition of a renin-angiotensin system, calcium antagonists elicited a greater decrease in urinary protein excretion than diuretics when BP similarly controlled. Calcium antagonists also improved AI more strongly than diuretics. Calcium antagonists appear suited for adding on renin angiotensin system inhibitors to treat hypertension with CKDs.

Although the patients with diabetic nephropathy suffered high cardiovascular risk, augmentation index (AI) in diabetic nephropathy has been poorly characterized. Cross-sectional studies were performed on 26 diabetic and 27 nondiabetic nephropathic patients. Home blood pressure was examined. In addition, blood pressure, pulse rate, and AI were measured in both supine and sitting positions. Patient backgrounds such as age, sex, sitting blood pressure, and pulse rate were similar between two groups. Circadian variations of home blood pressure were preserved in nondiabetic patients, but disappeared in diabetes. Changing from supine to sitting position induced greater decrements of systolic blood pressure (DeltaSBP -9 +/- 8 mmHg) and AI (DeltaAI -7 +/- 10) in the diabetic group than in nondiabetic patients (DeltaSBP -4 +/- 12 mmHg, DeltaAI -2 +/- 9). Multivariate regression analysis revealed that AI in a sitting position correlated positively to SBP and inversely to pulse rate. Of interest, AI in supine position related positively to age, the presence of diabetes and SBP, and inversely to pulse rate. The present data indicate autonomic dysfunction in patients with diabetic nephropathy. Furthermore, our findings provide the evidence that autonomic dysfunction elicits an inadequate physiological arterial contraction in response to postural change, thereby reducing AI that results in the fall of SBP. Finally, the present results suggest that AI in supine, but not sitting position, is suited for detecting cardiovascular risk in diabetes.

Our previous data indicated that both home blood pressure and arterial stiffness predicted the progression of renal dysfunction in the patients with chronic kidney diseases. In the present study, we examined both home blood pressure and the parameters of arterial stiffness as the indicator to the progression of chronic kidney diseases. Forty-two nondiabetic chronic kidney disease patients were enrolled and followed for 1 year. Anti-hypertensive therapy was adjusted to achieve office blood pressure below 130/80 mmHg. Home blood pressure was examined twice a day in the morning and evening. Pulse wave velocity (PWV) and augmentation index (AI) were measured as the index of arterial stiffness. The time for reflection (TR) was also determined. The relationship of annual changes in serum creatinine (Scr) with the above parameters was assessed. Multivariate regression analysis revealed that TR inversely correlated to annual increase in Scr (beta = -0.03, p < 0.05). Home blood pressure did not correlate to annual changes in Scr in the present study. The present data indicated that arterial stiffness is elevated despite good blood pressure control in chronic kidney disease, especially among the dippings. In addition, our data suggest that PWV and AI correlated to each other, while they were influenced differently by hemodynamic factors. Finally, the present findings provide the evidence that the arterial stiffness parameter is more sensitive than home blood pressure as an indicator to the progression of chronic kidney disease.

Aim: Cardiovascular disease constitutes a major cause of death in patients with chronic kidney diseases and is related to enhanced arterial stiffness. It has been reported that daytime hemodialysis patients show better prognosis than evening hemodialysis patients., Methods: Aortic augmentation index (AI) and radial AI were measured in 20 non-diabetic hemodialysis patients, using SphygmoCor (PWV Medical) and HEM-9010AI (Omron Healthcare) as markers of arterial stiffness. Cardiovascular prognosis was followed for two years., Results: Mean age, blood pressure, pulse rate, and aortic and radial AI were 52 +/- 4 y/o, 142 +/- 6/74 +/- 4 mmHg, 78 +/- 4 bpm, 21 +/- 2, and 71 +/- 4%, respectively, in 10 daytime hemodialysis patients, and they averaged 52 +/- 3 y/o, 146 +/- 6/76 +/- 4 mmHg, 74 +/- 3 bpm, 26 +/- 2, and 73 +/- 3% in 10 evening hemodialysis patients, respectively. Thus, aortic AI was higher in evening hemodialysis patients (p < 0.05). In all, one patient was hospitalized due to cardiovascular complications in daytime hemodialysis patients, as well as three patients from those dialyzed in the evening., Conclusion: Although a larger scale study is required to draw a definite conclusion, our findings suggest that a better prognosis in daytime hemodialysis non-diabetic patients is related to the lower AI.

Objectives: Insulin resistance is associated with chronic renal failure, which may amplify its cardiovascular pathologic manifestations. We previously showed the presence of insulin resistance in mild renal insufficiency due to chronic glomerulonephritis. These observations may be explained by a decrease in insulin sensitivity due to renal dysfunction. The aim of the present study was to evaluate the effects of unilateral and subtotal nephrectomy on insulin sensitivity., Methods: Unilateral heminephrectomy and five-sixths nephrectomy (5/6Nx) were performed in male Sprague-Dawley rats, measuring steady-state plasma glucose (SSPG) during the insulin suppression test., Results: The glomerular filtration rate (GFR) decreased significantly from sham-operated rats, to unilateral heminephrectomy group, to 5/6Nx rats. SSPG was unexpectedly lower in the unilateral heminephrectomy group than in controls, suggesting that unilateral heminephrectomy increased the sensitivity to insulin despite a mild decrease in renal function. However, when the analysis was limited to the 5/6Nx group, SSPG was inversely correlated with GFR (r = -0.65, p < 0.05). When renal failure caused by 5/6Nx had reached end stage, the rats became insulin resistant, despite a profound reduction in renal mass., Conclusion: It is suggested that unilateral heminephrectomy reduced GFR and increased the sensitivity to insulin. When rats became uremic, insulin sensitivity decreased, even, in 5/6Nx.