Norihisa Ito

Osaka City University, Ōsaka, Ōsaka, Japan

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Publications (26)62.93 Total impact

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    ABSTRACT: Primary aldosteronism (PA) is common in young or middle-aged hypertensive patients, but PA among the elderly has recently become more common. As salt sensitivity increases with age, plasma renin activity (PRA) tends to decrease, whereas the aldosterone-to-renin ratio (ARR) tends to increase in the elderly. The aim of this study was to clarify the influence of aging on the diagnosis of PA. We retrospectively evaluated 155 consecutively admitted patients who were not taking antihypertensive medications or calcium channel blockers and α blockers that underwent PRA and plasma aldosterone concentration (PAC) measurements. The study subjects included 13 PA and 69 essential hypertensive (EHT) patients aged over 65 years, and 32 PA and 41 EHT patients under aged 65 years. Our study clarified the influence of aging through screening and confirmatory tests for the diagnosis of PA. Our results showed the ARR cutoff value for a screening test to be 556 (area under the curve: AUC=0.906), its sensitivity and specificity to be 84.6% and 89.9%, respectively, and the likelihood ratio to be 8.34 in the elderly, whereas the ARR cutoff value was 272 in the non-elderly. In the saline infusion test, the mean PAC was 86.6±41.8 pg ml(-1) in the elderly and 158.1±116.5 pg ml(-1) in the non-elderly (P=0.04). There was no influence from age in both the captopril challenge test and the furosemide upright test. Aging may influence PA screening and saline infusion tests; thus, we should consider the influence of aging in the diagnosis of elderly subjects with PA.Hypertension Research advance online publication, 28 August 2014; doi:10.1038/hr.2014.129.
    Hypertension research : official journal of the Japanese Society of Hypertension. 08/2014;
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    ABSTRACT: Many reports have shown that brachial-ankle pulse wave velocity (baPWV) and carotid-femoral PWV are prognostic factors for cardiovascular diseases. We evaluated heart-carotid PWV, heart-femoral PWV (hfPWV), and femoral-ankle PWV (faPWV) using carotid and femoral sensors. Our objectives were to reveal correlations among PWVs and to determine the clinical importance of the respective PWVs in predicting the cardiovascular events. This prospective cohort study included 338 patients with essential hypertension (mean age 61.3 ± 0.7, mean follow-up period 6.5 ± 0.1 years) whose regional PWVs were measured. Primary end points were stroke, cardiovascular diseases (CVD), and death. Kaplan-Meier analysis showed that subjects with higher faPWV and baPWV had a significantly higher incidence of stroke (p = 0.0288 and 0.0277, respectively), subjects with higher hfPWV had a significantly higher incidence of CVD (p = 0.0212), subjects with higher baPWV and hfPWV had a significantly higher incidence of stroke + CVD (p = 0.0070 and 0.0463, respectively), and subjects with higher baPWV had a significantly higher mortality rate (p = 0.0367). Cox proportional hazard model revealed that baPWV was a significant risk factor for stroke + CVD after adjustment for traditional risk factors (relative risk: 14.50, p = 0.0288). Higher baPWV may be a risk factor for stroke and CVD, but the prognostic impact of regional PWVs is still unclear in patients with hypertension.
    Heart and Vessels 02/2014; · 2.13 Impact Factor
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    ABSTRACT: The mean intima media thickness (IMT) and plaque score from carotid ultrasonography are both widely used to evaluate macrovascular atherosclerotic change. The present study sought to examine which parameter more effectively predicts patient prognosis. This hospital-based cohort study included 356 patients with essential hypertension (mean age: 62.4±0.6). We investigated how the mean IMT and plaque score correlated with various parameters, including pulse wave velocity (PWV), and we assessed the ability of the mean IMT and plaque score to predict cardiovascular events and total mortality. The mean IMT and plaque score significantly correlated with systemic atherosclerotic change, target organ damage, age and PWV. Subjects with a higher mean IMT and subjects with higher plaque scores showed higher frequencies of stroke and total mortality. In addition, subjects with marginal thickening of the intima media (mean0.7) showed a significantly higher frequency of stroke than subjects with a mean IMT of <0.7. After adjustment for traditional risk factors, plaque score was significantly and independently predictive of stroke, and the predictive ability of the plaque score for the onset of stroke was equivalent to that of PWV. The mean IMT and plaque score showed a nonsignificant trend of higher risk of mortality after adjustment for traditional risk factors. The mean IMT and plaque score were significantly correlated with systemic atherosclerotic change. We revealed that plaque score predicted the onset of stroke more accurately than the mean IMT, and the accuracy of this prediction was equivalent to that from PWV in hypertensive patients. We also showed that marginal thickening of the intima media (as measured by mean IMT) may be a predictor of stroke.Hypertension Research advance online publication, 4 July 2013; doi:10.1038/hr.2013.61.
    Hypertension Research 07/2013; · 2.79 Impact Factor
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    ABSTRACT: To assess how visit-to-visit variability of SBP correlates with systemic atherosclerotic change and various prognoses. Visit-to-visit SBP variability correlates with cardiovascular events. However, the mechanisms underlying the impact of visit-to-visit SBP variability on prognoses are poorly understood. A total of 485 patients with essential hypertension from the Non-Invasive Atherosclerotic Evaluation in Hypertension (NOAH) study cohort were included. We analyzed the correlation between visit-to-visit SBP variability and multiple clinical parameters. Next, we prospectively examined the correlation of SBP variability and frequency of cardiovascular disease (CVD) and total mortality. Patients with higher SBP variability exhibited significantly higher rates of statin use, as well as higher pulse wave velocity (PWV), left-ventricular mass index (LVMI), plaque score, and resistive index of the common carotid artery; these patients also exhibited lower estimated glomerular filtration rate. Kaplan-Meier analysis demonstrated that patients with higher SBP variability have a significantly higher incidence of CVD and mortality rate. The hazard ratio of SBP variability for incidence of CVD was greatly diminished after adjustment for intima-media thickness, plaque score, and resistive index, and was slightly diminished after adjustment for PWV and LVMI. Visit-to-visit SBP variability remained an independent risk factor for mortality after adjustment. Visit-to-visit SBP variability correlates significantly with systemic atherosclerotic change, incidence of CVD, and mortality rate. Altered arterial functions, such as macrovascular atherosclerosis and vascular resistance, are responsible for the correlations between visit-to-visit SBP variability and incidence of CVD.
    Journal of Hypertension 07/2013; 31(7):1387-95; discussion 1395. · 4.22 Impact Factor
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    ABSTRACT: Aim: Arterial stiffness has been reported to correlate with cardiovascular disease (CVD). Brachial-ankle pulse wave velocity (baPWV) is easy to measure and has been used as a marker to evaluate arterial stiffness. The objective of the present study was to determine the cut-off value of baPWV for predicting cardiovascular prognosis in a prospective cohort study.Methods: Four hundred forty patients with essential hypertension were analyzed in study 1 with a mean follow-up of 6.3±0.1 years. Four hundred patients from study 1 who did not have a past history of CVD and/or stroke were analyzed in study 2 with a mean follow-up of 6.4±0.1 years. Stroke, CVD, and death were the primary endpoints.Results: Receiver operating characteristic (ROC) curve analysis revealed that 1750.0 cm/sec is an appropriate cut-off value for baPWV to predict the onset of stroke, CVD, stroke+CVD, and total mortality (area under curve: 0.576-0.719). A baPWV higher than 1750.0 may also be a significant and independent risk factor for the onset of CVD+stroke (relative risk: 2.048 (1.176-3.616), p= 0.0113 in study 1; relative risk: 1.920 (1.028-3.634), p=0.0408 in study 2).Conclusions: The present study indicates that 1750.0 cm/sec could be a useful cut-off value for baPWV to predict cardiovascular prognosis.
    Journal of atherosclerosis and thrombosis 12/2012; · 2.93 Impact Factor
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    ABSTRACT: Recently, new parameters related to hypertension, such as variability in blood pressure and ambulatory arterial stiffness index (AASI), were demonstrated to correlate with arteriosclerotic change. In this study, we investigated the correlation between circadian variability in blood pressure/AASI and renal function. We also investigated differences in the clinical impact of 24 h, daytime and nighttime blood pressure variability on renal and systemic atherosclerotic changes. We analyzed data from 120 patients who underwent renal Doppler ultrasonography (RDU) and ambulatory blood pressure monitoring (ABPM) at our hospital ward, and investigated the correlation between circadian variability in blood pressure/AASI and renal function, including resistive index (RI) evaluated with RDU, which is thought to be a good indicator of renal vascular resistance. Subjects with higher circadian variability in systolic blood pressure (SBP) had significantly higher RI. Daytime variability in SBP correlated more strongly with RI than nighttime variability. Meanwhile, only nighttime variability, but not daytime variability, in SBP was related to carotid atherosclerosis. Similarly, AASI was significantly correlated with RI. Circadian variability in SBP and AASI were both significantly correlated with renal function. Daytime SBP s.d. was especially more strongly correlated with renal vascular resistance, and nighttime SBP s.d. was significantly correlated with intima-media thickness (IMT) and plaque score. These results indicate that evaluating both daytime and nighttime blood pressure variability enables an assessment of pathological conditions in hypertensive patients to prevent cardiovascular diseases.Hypertension Research advance online publication, 18 October 2012; doi:10.1038/hr.2012.162.
    Hypertension Research 10/2012; · 2.79 Impact Factor
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    ABSTRACT: Aim: Adiponectin is a key molecule involved in metabolic syndrome. Single nucleotide polymorphisms (SNPs) in the ADIPOQ gene encoding adiponectin correlate with various diseases, such as diabetes mellitus; however, there is insufficient information about ADIPOQ SNPs and the onset of cardiovascular events.Methods: This hospital-based cohort study included 353 patients with essential hypertension (mean age, 62.9±0.6; mean follow-up period. 7.9±0.2 years) in whom ADIPOQ SNPs encoding G276T, I164T, A349G, and/or G967A amino acid changes were detected. We analyzed the correlation between ADIPOQ SNPs and various parameters, including pulse wave velocity (PWV), and assessed whether these SNPs could be risk factors for the onset of stroke, cardiovascular disease, and mortality.Results: Subjects with the T allele of G276T showed significantly lower HDL cholesterol, and significantly higher HbA1c and brachial-ankle PWV (baPWV). Kaplan-Meier analysis revealed that subjects with the T allele of G276T had a significantly higher frequency of stroke (p= 0.0489). The Cox proportional hazard model showed that the T allele of G276T was an independent and significant risk factor for stroke after adjusting for traditional risk factors (relative risk: 1.879, p= 0.0479); however, when adjusted for traditional risk factors and baPWV, the relative risk was significantly diminished (relative risk: 0.710, p= 0.4937). G276T was significantly correlated with dyslipidemia and glucose metabolism.Conclusion: The T allele of G276T was a significant and independent risk for the onset of stroke, and mediated the incidence of stroke through increased arterial stiffness.
    Journal of atherosclerosis and thrombosis 10/2012; · 2.93 Impact Factor
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    ABSTRACT: Receptor of advanced glycation end products (RAGE) is reportedly linked with chronic inflammatory diseases due to aging or diabetes. The aim of this study was to show how -374 T/A RAGE has an impact on systemic vascular damage and renal function. The study subjects were a total of 468 essential hypertension patients from the Non-Invasive Atherosclerotic Evaluation in Hypertension (NOAH) study cohort. We prospectively examined the association of -374 T/A RAGE with their prognoses and investigated the correlation between -374 T/A RAGE and multiple clinical parameters. Kaplan-Meier analysis did not show a significant association of -374 T/A RAGE with total mortality or the prevalence of cardiovascular events. Carriers of the A allele showed a significantly higher prevalence of diabetes mellitus (DM) and lower estimated glomerular filtration rate (eGFR) than subjects without this allele. In subjects with DM, carriers of the A allele showed a significantly lower eGFR. These significant correlations were only seen in male subjects. Carriers of the A allele of -374 T/A RAGE show an independent risk of atherosclerosis and reduced renal function in male hypertensive patients with DM.
    Clinical and Experimental Hypertension 09/2012; · 1.28 Impact Factor
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    ABSTRACT: Background Visit-to-visit blood pressure (BP) variability has been reported to be a major risk for cardiovascular events. Renin angiotensin system (RAS) gene polymorphisms are reportedly genetic risk factors for cardiovascular diseases and arterial stiffness. In this study, we aimed to reveal the relationship between visit-to-visit BP variability and RAS gene polymorphisms.Methods Study subjects included 427 essential hypertension patients from the Non-Invasive Atherosclerotic Evaluation in Hypertension study cohort, whose BP was measured during at least six outpatient visits. We analyzed the correlation between visit-to-visit variability in systolic BP (SBP) and RAS gene polymorphisms.ResultsWe identified angiotensinogen M235T, angiotensin II type 1 receptor A1166C, and angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphisms. Only ACE I/D polymorphisms were correlated with variability in diastolic BP; no gene polymorphisms were correlated with variability in SBP.ConclusionsRAS gene polymorphisms, especially ACE I/D polymorphisms, might genetically influence the visit-to-visit BP variability in hypertensive patients.American Journal of Hypertension, 2012; doi:10.1038/ajh.2012.118American Journal of Hypertension (2012); doi:10.1038/ajh.2012.118.
    American Journal of Hypertension 08/2012; · 3.67 Impact Factor
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    ABSTRACT: The purpose of the study was to investigate the association of serum uric acid (UA) levels in hypertensive patients with the prognosis for cardiovascular disease (CVD) and mortality. This hospital-based cohort study included 669 patients with essential hypertension. A questionnaire was used to identify patients in whom hypertensive complications had occurred, as well as causes of death. The primary end point of this study was new onset of stroke or CVD (new onset of angina pectoris, myocardial infarction or heart failure). We evaluated the baseline characteristics of patients, including UA levels, and assessed whether UA levels could be used to predict stroke and CVD. We also classified subjects into four groups according to the serum UA levels. During a mean follow-up period of 7.1±0.1 years, 71 strokes, 58 cases of CVD and 64 deaths were recorded. Kaplan-Meier analysis revealed that subjects in the high UA group had a higher frequency of stroke and CVD (P=0.0120) and total mortality (P=0.0021). A Cox proportional hazard model determined that, after adjusting for traditional risk factors, serum UA levels were predictive of CVD (relative risk=1.30; P=0.0073), stroke and CVD (relative risk=1.19; P=0.0141), mortality (relative risk=1.23; P=0.0353) and stroke CVD and mortality (relative risk=1.19; P=0.0083), but not stroke (P=0.4268). The significant correlations were particularly marked in women. Serum UA levels may be an independent risk factor for stroke and CVD in patients with essential hypertension, particularly women.Hypertension Research advance online publication, 28 June 2012; doi:10.1038/hr.2012.99.
    Hypertension Research 06/2012; · 2.79 Impact Factor
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    ABSTRACT: To clarify the clinical utility of pulse wave velocity (PWV) and chronic kidney disease (CKD) in hypertension, we analyzed the prognostic impact of PWV and CKD on cerebrocardiovascular disease in hypertensive patients. This study consisted of 531 patients with essential hypertension (male/female=292/239, mean age=61.7±12.3, mean follow-up=7.0±3.0 years) and was performed between January 1998 and June 2004. We used questionnaires to assess stroke (n=57), cardiovascular diseases (CVDs; myocardial infarction, angina and congestive heart failure; n=44) and death (n=53) as primary end points. At baseline, we evaluated the carotid-femoral PWV (9.1±1.8 m s(-1)), the glomerular filtration rate and urinary protein excretions. We divided these subjects into those in the highest quartile of PWV and other subjects and into CKD (n=149) and non-CKD (n=458). We evaluated the prognostic influences of PWV and CKD with Kaplan-Meier analysis and Cox's proportional hazard model. PWV in CKD (9.6±1.9 m s(-1)) was higher than in non-CKD (8.8±1.6 m s(-1); P<0.0001), and creatinine was slightly decreased in the highest PWV group (1.09±0.35 mg dl(-1), P<0.0001). On the basis of Kaplan-Meier analysis, the highest PWV group (PWV>10.1 m s(-1); P=0.0003) and the CKD group (P=0.0005) showed significantly higher proportions of stroke and CVD events. In addition, the highest PWV group showed the highest percentage of stroke (P=0.0007), and the CKD group showed the highest proportion of CVD (P<00001). High PWV and CKD were independent predictors for stroke and CVD (P=0.0332) by Cox's proportional hazard model. These data suggest that increased aortic stiffness and CKD may be predictors for stroke and cardiovascular events in hypertensive patients.
    Hypertension Research 08/2011; 34(11):1209-15. · 2.79 Impact Factor
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    ABSTRACT: Increased arterial stiffness and impaired vasodilator response have been associated with cardiovascular events in high-risk patients. However, whether arterial changes predict the occurrence of hypertensive complications is still unclear. Therefore, we designed a hospital-based cohort study to examine the prognostic impact of arterial functional changes on stroke and cardiovascular diseases in hypertensive patients. The study employed 676 patients with essential hypertension. At baseline, we evaluated second-derived photoplethysmography, carotid-femoral pulse wave velocity (PWV), and forearm reactive hyperemia. We classified subjects into quartile groups according to the baseline measurements of these evaluations and assessed the ability of each measure to predict stroke and cardiovascular diseases (CVD). During a mean follow-up period of 57 months, 52 strokes, 40 CVD, and 22 deaths were recorded. Kaplan-Meier analysis revealed that patients in the highest quartile of PWV showed a higher frequency of stroke and CVD (p<0.0001) and total mortality (p=0.0016), and those in the highest quartile of reactive hyperemia showed a lower frequency of stroke and CVD (p=0.0415). A Cox hazard model identified that classification in the highest quartile of PWV (relative risk=2.717) and reactive hyperemia (0.416) were predictive of stroke and CVD after adjustment for other risk factors. In subjects who did not experience stroke or CVD before the study period (n=558), only PWV was related with the occurrence of stroke and CVD based on the Cox hazard model. In conclusion, increased aortic stiffness evaluated by PWV is more prognostic of cardiovascular events in hypertensive patients than several non-invasive atherosclerotic evaluations.
    Hypertension Research 07/2008; 31(6):1135-45. · 2.79 Impact Factor
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    ABSTRACT: Angiotensin receptor blockers (ARBs) are the recommended first-line antihypertensive treatment for managing chronic kidney disease, and strict blood pressure (BP) regulation is crucial for the reduction of proteinuria. Valsartan and candesartan are commonly used ARBs in Japan, with maximum permissible doses of 160 mg/day and 12 mg/day, respectively. We evaluated BP and proteinuria after changeover from the maximum dose of candesartan to the maximum dose of valsartan, in 55 poorly controlled hypertensive patients undergoing candesartan treatment who were unable to achieve optimal BP according to the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2004). We measured BP and pulse rate and assessed urinary protein excretion (UPE) before and after changeover. Changeover was associated with decreases in systolic BP and diastolic BP from 158/89 mmHg to 150/86 mmHg (p<0.01). Changeover was also associated with a reduction in UPE adjusted to urinary creatinine from 0.35+/-0.19 g/g creatinine to 0.19+/-0.37 g/g creatinine (p=0.0271) in patients who had high urinary protein levels prior to changeover without significant decreases in BP (p=0.0184). According to multiple regression analysis, higher UPE (p<0.0001) and a lower glomerular filtration rate (GFR) (p=0.0011) prior to changeover were independently correlated with reduction in UPE. Our results suggest that the maximum dose of valsartan is more effective than the maximum dose of candesartan for reducing BP and proteinuria.
    Hypertension Research 01/2008; 30(12):1187-92. · 2.79 Impact Factor
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    ABSTRACT: Both strict blood pressure control and efferent artery dilatation are critical in reducing proteinuria, which in turn helps to regulate blood pressure. Benidipine, an L- and T-type calcium channel blocker, has the potential for increased effectiveness compared with L-type-dominant calcium channel blockers such as amlodipine. Therefore, we evaluated blood pressure and proteinuria after changeover from amlodipine to benidipine in poorly controlled hypertensive patients. Fifty-eight hypertensive outpatients undergoing amlodipine treatment and unable to achieve optimal blood pressure as determined by Japanese Society of Hypertension Guidelines for the Management of Hypertention (JSH 2004) were changed over to benidipine treatment. We measured blood pressure and pulse rate and assessed urinary protein excretion before and after changeover. Systolic and diastolic blood pressure dropped from 151/90 mmHg to 140/81 mmHg (p<0.0001). Mean blood pressure (p<0.0001) and pulse pressure (p=0.0069) were also reduced, but pulse rate increased from 75 bpm to 78 bpm (p=0.0047). Urinary protein excretion adjusted for urinary creatinine was reduced from 0.35 +/- 0.82 to 0.22 +/- 0.55 g/g creatinine (p=0.0119). The urinary protein reduction was observed only in patients with renin-angiotensin inhibition (p=0.0216). By switching from amlodipine to benidipine treatment, more than 80% of patients reduced their blood pressure, and more than 40% achieved optimal blood pressure. Higher urinary protein excretion (p<0.0001), lower glomerular filtration rate (p=0.0011) and presence of diabetes (p=0.0284) were correlated with reduction of urinary proteins during changeover. Taken together, our results suggest that benidipine may have greater efficacy than amlodipine in reducing blood pressure and proteinuria.
    Hypertension Research 09/2007; 30(9):797-806. · 2.79 Impact Factor
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    ABSTRACT: Many experiments using young hypertensive animal models support the evidence that angiotensin-converting enzyme inhibitor or angiotensin receptor type 1 blocker attenuates the progression of cardiac hypertrophy. However, it is still unclear whether inhibiting the renin-angiotensin system can reverse age-related cardiac hypertrophy. To clarify the role of renin-angiotensin system inhibition in naturally advanced myocardial hypertrophy we treated spontaneously hypertensive, aging rats with an angiotensin-converting enzyme inhibitor or an angiotensin receptor type 1 blocker. We used osmotic pumps to deliver the blood-pressure reducers temocaprilat, olmesartan, hydralazine, or saline for 4 weeks. Heart and body weights were significantly reduced in animals treated with temocaprilat or olmesartan compared with animals treated with hydralazine or saline. Histologic myocyte size and cardiac fibrosis were significantly attenuated by temocaprilat or olmesartan. Real-time polymerase chain reaction (PCR) revealed that temocaprilat or olmesartan suppressed expression of cardiac transforming growth factor-beta1 and fibroblast growth factor-2 mRNA, a marker of cardiac fibrosis. Cardiac and systemic oxidative stress assessed by 8-isoprostane levels was significantly reduced in animals treated with temocaprilat or olmesartan compared with hydralazine-treated or saline-treated rats. Renin-angiotensin system inhibition reduced cardiac expression of NAD(P)H oxidative components p22phox, p47phox, and gp91phox. Renin-angiotensin system inhibition can reverse age-related, advanced cardiac hypertrophy. The mechanism of reversal is partly due to suppression of cardiac oxidative stress.
    American Journal of Hypertension 08/2007; 20(7):792-9. · 3.67 Impact Factor
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    ABSTRACT: Objective: Arterial stiffness is a risk factor for cardiovascular diseases, and is altered by age and blood pressure. Lifestyle-related diseases are also major risk factors for cardiovascular events and influence arterial stiffness. The goal of this study was to clarify the clinical influence of aging on pulse wave velocity in patients with hypertension, diabetes and/or dyslipidemia.Methods: Eight hundred and forty-seven outpatients (480 males, 367 females, mean age 61.5 years) at the Division of Geriatric Medicine and Hypertension in Osaka University Hospital who had lifestyle-related diseases such as hypertension (n = 720), diabetes (n = 228) and dyslipidemia (n = 613) were enrolled. We evaluated arterial stiffness as measured by carotid-femoral pulse wave velocity.Results: After age and systolic blood pressure adjustment, pulse wave velocity was higher in hypertensive patients (P = 0.0048), but not in patients with diabetes or dyslipidemia. By single linear regression analysis, pulse wave velocity and age were positively correlated in patients with (r = 0.359, P < 0.0001) and without (r = 0.377, P < 0.0001) hypertension, and the regression coefficients of these two groups were similar. Moreover, these variables were positively correlated with pulse wave velocity in hypertensive patients receiving medication (r = 0.324, P < 0.0001) and without medication (r = 0.425, P < 0.0001), and the regression coefficient with medication (0.033) was lower than that without medication (0.045).Conclusion These data suggest that the presence of hypertension worsened the age-related increase in arterial stiffness in patients with lifestyle-related diseases.
    Geriatrics & Gerontology International 03/2007; 7(1):54 - 60.
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    ABSTRACT: The goal of this study was to clarify the clinical usefulness and limitations of brachial-ankle pulse wave velocity (PWV) to evaluate hypertensive complications, in comparison with carotid-femoral PWV. Patients with essential hypertension (n=296, male/female=161/135; age=61.1+/-0.7 years) were enrolled. We measured brachial-ankle PWV, femoral-ankle PWV and carotid-femoral PWV simultaneously, and evaluated target organ damage and associated clinical conditions (cerebrovascular and cardiovascular disease) using the World Health Organization classification modified in 1999. Carotid-femoral PWV (p<0.0001; r=0.521) and brachial-ankle PWV (p<0.0001; r=0.478) but not femoral-ankle PWV were significantly correlated with age. Carotid-femoral PWV was significantly higher in patients with associated clinical conditions compared with that in patients with target organ damage (p<0.05) and those with no complications (p<0.0001). Brachial-ankle PWV was significantly higher in patients with associated clinical conditions (p<0.05) and target organ damage (p<0.05) compared to those with no complications, but there was no significant difference in brachial-ankle PWV between these two groups. Moreover, femoral-ankle PWV was significantly lower in patients with associated clinical conditions compared with that in patients with target organ damage (p<0.05). These data suggest that brachial-ankle PWV could underestimate arterial stiffness in hypertensive patients with a history of cardiovascular events.
    Hypertension Research 01/2007; 29(12):989-95. · 2.79 Impact Factor
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    ABSTRACT: To evaluate morning autonomic nervous activity and blood pressure profiles in hypertensive patients by analyzing heart rate variability and ambulatory blood pressure. Data from 82 patients with untreated essential hypertension were analyzed. We evaluated the 24-h profile of blood pressure and that of indices of autonomic nervous activity, i.e., the high frequency component (HF) and low frequency component/HF (LF/HF), which were obtained by wavelet transform of heart rate variability. Patients were classified by dipping status (nondippers, n=28; dippers, n=32; extreme-dippers, n=8; and risers, n=14) and morning blood pressure profile (large, n=9; small, n=60; and inverted, n=13). Nocturnal systolic blood pressure in extreme-dippers was significantly lower than that in the other groups; that in the risers was significantly higher (p<0.05). There were no significant group differences in daytime systolic blood pressure. Daytime and 24-h HF levels were significantly higher in the dipper vs. the riser group (p<0.05). Morning blood pressure elevation negatively correlated to preawake (p<0.01) and nocturnal blood pressure (p<0.05), but not to daytime and post-awake blood pressure. The preawake/postawake ratio of systolic blood pressure positively correlated to that of LF/HF (p<0.01) and negatively correlated to preawake HF levels (p<0.05). Multivariate regression analysis revealed that preawake HF levels (p=0.037) and preawake/postawake ratio of LF/HF (p=0.033) were independently correlated with morning blood pressure elevation ratio. Our results suggest that activation of HF before waking and LF/HF during waking might play an important role in the development of morning blood pressure elevation.
    Hypertension Research 01/2007; 29(12):977-87. · 2.79 Impact Factor
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    ABSTRACT: Three subtypes of beta-adrenoceptor, beta1, beta2 and beta3, are involved in the sympathetic nervous system, which plays an important role in the development of hypertension and hypertensive complications. These complications can include left ventricular hypertrophy and arterial stiffness, which are reported risk factors for cardiovascular diseases. We designed clinical trials to clarify the association between hypertensive complications and beta-adrenoceptor single nucleotide polymorphisms in essential hypertension. Using Taqman PCR methods, we detected five polymorphisms of three beta-adrenoceptors: Ser49Gly and Arg389Gly for the beta1-adrenoceptor; Gly16Arg and Glu27Gln for the beta2-adrenoceptor; and Trp64Arg for the beta3-adrenoceptor. We included 300 subjects and measured pulse wave velocity, vasodilator response to hyperemia, left ventricular hypertrophy (by electrocardiogram and echocardiography), and cardiac enlargement (by chest X-ray). We found that pulse wave velocity and nitroglycerin-induced hyperemia were both closely associated with the Ser49Gly polymorphism (p<0.05), and Glu27Gln was found by both electrocardiogram and echocardiography to be significantly associated with left ventricular hypertrophy (p<0.05). These data suggested that two polymorphisms of different beta-adrenoreceptor subtypes are the genetic influences on the development of arterial stiffness and left ventricular hypertrophy in essential hypertension.
    Hypertension Research 11/2006; 29(11):875-81. · 2.79 Impact Factor
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    ABSTRACT: Angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase that cleaves angiotensin II to angiotensin 1-7. Recently, it was reported that mice lacking ACE2 (ACE2(-/y) mice) exhibited reduced cardiac contractility. Because mechanical pressure overload activates the cardiac renin-angiotensin system, we used ACE2(-/y) mice to analyze the role of ACE2 in the response to pressure overload. Twelve-week-old ACE2(-/y) mice and wild-type (WT) mice received transverse aortic constriction (TAC) or sham operation. Sham-operated ACE2(-/y) mice exhibited normal cardiac function and had morphologically normal hearts. In response to TAC, ACE2(-/y) mice developed cardiac hypertrophy and dilatation. Furthermore, their hearts displayed decreased cardiac contractility and increased fetal cardiac gene induction, compared with WT mice. In response to chronic pressure overload, ACE2(-/y) mice developed pulmonary congestion and increased incidence of cardiac death compared with WT mice. On a biochemical level, cardiac angiotensin II concentration and activity of mitogen-activated protein (MAP) kinases were markedly increased in ACE2(-/y) mice in response to TAC. Administration of candesartan, an AT1 subtype angiotensin receptor blocker, attenuated the hypertrophic response and suppressed the activation of MAP kinases in ACE2(-/y) mice. Activation of MAP kinases in response to angiotensin II was greater in cardiomyocytes isolated from ACE2(-/y) mice than in those isolated from WT mice. ACE2 plays an important role in dampening the hypertrophic response to pressure overload mediated by angiotensin II. Disruption of this regulatory function may accelerate cardiac hypertrophy and shorten the transition period from compensated hypertrophy to cardiac failure.
    Hypertension 05/2006; 47(4):718-26. · 6.87 Impact Factor