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The major functions of the arterial system are to "efficiently deliver blood to the peripheral organs and maintain vascular homeostasis". Both the endothelial and medial layer contribute to the three major functions, namely, conversion of pulsatile to steady blood flow, appropriate distribution of blood flow to the target organs, and vascular protection and homeostasis. Vascular dysfunction contributes to the development of cardiovascular diseases through a combination of several mechanisms, including impaired coronary perfusion, cardiac systolic/diastolic dysfunction, microvascular damage, and abnormal hemodynamics in the arterial tree. The representative marker of endothelial function is flow-mediated vasodilatation and that of the medial layer function is pulse wave velocity, and that of the blood supply function of the arterial tree is the ankle-brachial pressure index. In hypertension, vascular dysfunction could also lead to the development of isolated systolic hypertension, isolated diastolic hypertension, and systolic/diastolic hypertension. Vascular dysfunction is involved in a vicious cycle with abnormal blood pressure variability. Furthermore, a vicious cycle may also exist between vascular dysfunction and hypertension. While the significances of vascular function tests to predict future cardiovascular events has been established in cases of hypertension, their usefulness in assessing the effectiveness of management of the vascular functions in hypertension on the cardiovascular outcomes has not yet been fully clarified. Thus, vascular dysfunction plays crucial roles in the pathophysiology of hypertension, and further research is warranted to establish strategies to improve vascular dysfunction in cases of hypertension. Vascular functions in the pathophysiology of hypertension. Vascular dysfunction and elevation of blood pressure are components of a vicious cycle even from their early stages, which including abnormal blood pressure variabilities. This vicious cycle is associated with hypertensive organ damage and also adverse cardiovascular outcomes. Strategies to break this vicious cycle have not yet been fully established., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background Hypertension and diabetes frequently coexist; however, it has not yet been clarified if the bidirectional longitudinal relationships between arterial stiffness and hypertension are independent of those between arterial stiffness and diabetes. Methods and Results In this 16-year prospective observational study, 3960 middle-aged employees of a Japanese company without hypertension/diabetes at the study baseline underwent annual repeated measurements of blood pressure, serum glycosylated hemoglobin A 1c levels, and brachial-ankle pulse wave velocity. By the end of the study period, 664, 779, 154, and 406 subjects developed hypertension, prehypertension, diabetes, and prediabetes, respectively. Increased brachial-ankle pulse wave velocity at the baseline was associated with a significant odds ratio (per 1 SD increase) for new onset of prehypertension/hypertension with (2.45/3.28; P <0.001) or without (2.49/2.76; P <0.001) coexisting prediabetes/diabetes, but not for new onset of prediabetes/diabetes without coexisting hypertension. Analyses using the latent growth curve model confirmed the bidirectional relationships between brachial-ankle pulse wave velocity and hypertension, but no such relationship was observed between brachial-ankle pulse wave velocity and abnormal glucose metabolism. Conclusions In middle-aged employees of a Japanese company, while bidirectional relationships were found to exist between increased arterial stiffness and hypertension, such a relationship was not found between increased arterial stiffness and diabetes. Therefore, it appears that increased arterial stiffness may be associated with the development of hypertension but not with that of diabetes.

Background: Our aims were to assess whether arterial stiffness is associated with a higher risk for kidney dysfunction among persons without chronic kidney disease (CKD)., Methods: We analyzed data from the national health checkup system in Japan; for our analyses, we selected records of individuals who completed assessments of cardio-ankle vascular index (CAVI) and kidney function from 2005 to 2016. We excluded participants who had CKD at baseline, defined as the presence of proteinuria or estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. We compared 2 groups of CAVI measurements-the highest quartile (≧8.1) and the combined lower 3 quartiles (<8.1). We used Cox proportional hazards models to assess associations between these 2 groups and subsequent CKD events, proteinuria, eGFR <60 ml/min/1.73 m2, and rapid eGFR decline (greater than or equal to -3 ml/min/1.73 m2 per year)., Results: The mean age of the 24,297 included participants was 46.2 years, and 60% were female. Over a mean follow-up of 3.1 years, 1,435 CKD events occurred. In a multivariable analysis, the hazard ratios with 95% confidence intervals (CIs) for the highest vs. combined lower quartiles of CAVI measurements were 1.3 (1.1, 1.5) for CKD events, 1.3 (0.96, 1.62) for proteinuria, 1.4 (1.1, 1.7) for eGFR <60 ml/min/1.73 m2, and the odds ratio with 95% CI was 1.3 (1.1, 1.4) for rapid eGFR decline., Conclusions: Persons with CAVI measurements ≧8.1 had a higher risk for CKD events compared with their counterparts with CAVI measurements <8.1. Greater arterial stiffness among adults without CKD may be associated with kidney dysfunction., (© The Author(s) 2020. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)

The score based on the office systolic blood pressure, age, fasting blood glucose level, and estimated glomerular filtration rate (SAGE score) has been proposed as a useful marker to identify elevated values of carotid-femoral pulse wave velocity (PWV). The present cross-sectional study was conducted to examine whether the SAGE score is also a useful marker to identify subjects with elevated brachial-ankle PWV values in Japanese subjects with hypertension. We measured the brachial-ankle PWV and calculated the SAGE score in a total of 1019 employees of a Japanese company with hypertension and 817 subjects with hypertension derived from a multicenter study cohort. The analyses in this study were based on data from these two study groups as well as on a composite population of the two (n = 1836). The receiver operating characteristic curve analysis showed that the area under the curve to identify subjects with brachial-ankle PWV values of ≥1800 cm/s was over 0.70 in each of the three study groups. Even after adjustments, a SAGE score ≥7 had a significant odds ratio for identifying subjects with brachial-ankle PWV values ≥1800 cm/s in the 1836 study subjects from the composite occupational and multicenter study cohort (odds ratio = 2.1, 95% confidence interval = 1.4-3.0, P < 0.01). Thus, in Japanese subjects with hypertension, the SAGE score may be a useful marker for identifying subjects with elevated brachial-ankle PWV values.

Objectives: This prospective study was conducted to clarify the significance of augmented pressure wave reflection without accompanying increased arterial stiffness in the development of isolated diastolic hypertension (IDHT)., Methods: A total of 3022 Japanese men without hypertension at the start of this study were included in the analyses. The blood pressure, brachial--ankle pulse wave velocity (brachial-ankle PWV), and radial augmentation index (rAI) were measured annually from year 2007 through year 2015., Results: At the end of the study period, 129 participants were diagnosed as having systolic/diastolic hypertension (SDHT), 112 as having isolated systolic hypertension (ISHT), and 74 as having IDHT. Both the brachial--ankle PWV and rAI showed significant individual odds ratios for new onset of SDHT and new onset of ISHT. However, only rAI, but not the brachial--ankle PWV, showed a significant odds ratio (1.44, P < 0.01) for new onset of IDHT. This association was significant in participants without elevated brachial--ankle PWV values at the start of the study, but not in those with elevated brachial--ankle PWV at the start of the study. Generalized estimating equation analyses demonstrated a significant longitudinal association of the rAI, but not brachial--ankle PWV, with the development of IDHT., Conclusion: Although increased arterial stiffness and augmented pressure wave reflection present concomitantly may be associated with the development of SDHT and ISHT, augmented pressure wave reflection alone, which may be related to isolated peripheral vascular damage, in the absence of accompanying increase of the arterial stiffness, may be a significant factor in the development of IDHT.

The usefulness of brachial-ankle pulse wave velocity (baPWV), an index of arterial stiffness, is not fully known for the management of treated hypertensive patients with a history of coronary artery disease (CAD) who have blood pressure less than 130/80 mmHg, a recommended blood pressure target in the updated major hypertension guidelines. We analyzed data for 447 treated hypertensive patients with CAD enrolled in FMD-J Study A for assessment of the predictive value of baPWV for future cardiovascular events. The primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow-up period of 47.6 months, the primary outcome occurred in 64 patients. Blood pressure less than 130/80 mmHg was significantly associated with a lower risk of the composite outcome independent of other cardiovascular risk factors in treated hypertensive patients with CAD (hazard ratio, 0.59; 95% confidence interval (CI), 0.35-0.99; P = 0.04). In treated hypertensive patients with CAD who had blood pressure less than 130/80 mmHg, baPWV above the cutoff value of 1731 cm/s, derived from receiver-operator characteristic curve analysis for the composite outcome was significantly associated with a higher risk of the composite outcome independent of conventional risk factors (hazard ratio, 2.83; 95% CI, 1.02-7.91; P = 0.04). baPWV was an independent predictor of cardiovascular events in treated hypertensive patients with CAD who had blood pressure less than 130/80 mmHg, for whom measurement of baPWV is recommended for cardiovascular risk assessment.

Hypertension (HTN) is an important risk factor for cardiovascular disease (CVD) but the association between HTN and CVD cannot be explained by average blood pressure (BP) alone. BP variability (BPV) is another important factor, along with the effects of HTN on the vasculature. The concept of systemic hemodynamic atherothrombotic syndrome (SHATS) has been proposed, describing an age-related and synergistic vicious cycle of hemodynamic stress and vascular disease. The importance of SHATS is based on the assumption that the assessment of BPV and arterial disease is likely to provide an effective opportunity to intervene early to reduce progression to HTN in younger patients or to CVD events and organ damage in older patients. In addition to providing an overview of current evidence for the mechanisms and clinical data related to SHATS, this article proposes a new SHATS score for use to diagnose and assess the severity of SHATS. The score includes two components - a BP score and a vascular score - which are multiplied to generate the SHATS score. This reflects the synergistic, rather than additive, effects of BP and vascular disease on target organ damage and CVD events. Although it requires refinement and validation in future studies, early detection of SHATS using tools such as the proposed score, combined with population-based stratification and technology-based anticipation medicine incorporating real-time individual data, has the potential to contribute to meaningful reductions in rates of CVD events and target organ damage., (Copyright © 2019. Published by Elsevier Inc.)

Importance: Aortic stiffness, as assessed by carotid-femoral pulse wave velocity, is an independent predictor of future events in individuals with hypertension. Recent data suggest a predictive role of estimated pulse wave velocity (ePWV) calculated by previously published equations using age and blood pressure in future events in individuals with hypertension., Objective: To investigate whether ePWV and its response to treatment predict survival in the Systolic Blood Pressure Intervention Trial (SPRINT)., Design, Setting, and Participants: This exploratory, hypothesis-generating, post hoc secondary analysis conducted from October 1, 2018, to August 31, 2019, examined data from 9361 participants in SPRINT and calculated ePWV at baseline and at 12 months. Adjusted hazard ratios (HRs) with 95% CIs of ePWV per 1 SD were estimated using Cox proportional hazards regression models. A total of 8450 patients were assigned to 4 groups according to their treatment allocation and their response in ePWV after 12 months., Interventions: Participants were assigned a systolic blood pressure target of less than 120 mm Hg (intensive treatment) or less than 140 mm Hg (standard treatment)., Main Outcomes and Measures: The primary composite cardiovascular outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes., Results: In the SPRINT population (3332 women and 6029 men; mean [SD] age, 67.9 [9.4] years), ePWV predicted the primary outcome (HR, 1.30 [95% CI, 1.17-1.43]; P < .001) and all-cause death (HR, 1.65 [95% CI, 1.46-1.86]; P < .001) independent of the Framingham Risk Score. Estimated pulse wave velocity improved the C statistic model for the primary outcome from 0.676 (95% CI, 0.65-0.70) to 0.683 (95% CI, 0.66-0.71; P = .049) and improved the C statistic model for all-cause death from 0.67 (95% CI, 0.64-0.69) to 0.69 (95% CI, 0.66-0.72; P = .03). Net reclassification index indicated improvement in risk discrimination for survival compared with the Framingham Risk Score (categorical net reclassification index = 0.111; P < .001). Regarding response to treatment, intensive treatment was superior to standard treatment only when it was accompanied with a response in ePWV at the first year, while, within the standard treatment group, individuals whose ePWV responded to antihypertensive treatment had improved all-cause mortality, with a 42% lower risk of death compared with nonresponders (HR, 0.58 [95% CI, 0.36-0.94]; P = .03); effects were independent of changes in systolic blood pressure., Conclusions and Relevance: These results suggest that, in the SPRINT trial, ePWV predicted outcomes independent of the Framingham Risk Score, indicating an incremental role of markers of aortic stiffness on cardiovascular risk. Better survival of individuals whose ePWV responded to antihypertensive treatment independently of systolic blood pressure reduction suggests a role of markers of aortic stiffness as effective treatment targets in individuals with hypertension.

Objectives: The endothelial dysfunction-arterial stiffness-atherosclerosis continuum plays an important pathophysiological role in hypertension. The aim of this study was to investigate the cross-sectional association between serum uric acid (SUA) and vascular markers related to this continuum, and to assess the longitudinal association between SUA and endothelial function that represents the initial step of the continuum., Methods: We evaluated the baseline associations between SUA levels and vascular markers that included flow-mediated vasodilatation (FMD), brachial-ankle pulse wave velocity (baPWV), and common carotid artery intima-media thickness (CCA-IMT) in 648 subjects receiving antihypertensive treatment. The longitudinal association between baseline SUA levels and FMD measured at 1.5 and 3 yr of follow-up was also investigated., Results: At baseline, modest, but significant correlations were observed between SUA and FMD in females (r = -0.171), baPWV in males with SUA >368.78 μmol/L (r = -0.122) and in females with a SUA level ≤ 362.83 μmol/L (r = 0.217), mean CCA-IMT in females with a SUA level ≤ 333.09 μmol/L (r = 0.139), and max CCA-IMT in females with SUA level ≤ 333.09 μmol/L (r = 0.138). A longitudinal association between SUA and FMD was less observed in males. In females, the baseline SUA was associated significantly with FMD values at 1.5 yr (r = -0.211), and SUA levels >237.92 μmol/L were associated significantly and independently with FMD values at 3 yr (r = -0.166)., Conclusions: Lower SUA levels were associated with better vascular markers of the continuum, especially in females. Furthermore, we observed a longitudinal association between SUA and endothelial function, suggesting SUA level may be a potential marker of the continuum in hypertension., (Copyright © 2018 Elsevier B.V. All rights reserved.)

It is not established whether central blood pressure (BP) evaluated by a radial pulse wave analysis is useful to predict cardiovascular prognoses. We tested the hypothesis that central BP predicts future cardiovascular events in treated hypertensive subjects. We conducted a multicenter, observational cohort study of 3566 hypertensives being treated with antihypertensive medications at 27 institutions in Japan. We performed the radial pulse wave analyses using applanation tonometry in all subjects. The primary outcome was the incidence of any of the following: stroke, myocardial infarction (MI), sudden cardiac death, and acute aortic dissection. The mean age of the subjects was 66.0 ± 10.9 years, and 50.6% were male. The mean brachial SBP and central SBP were 138 ± 18 mm Hg and 128 ± 19 mm Hg, respectively. When the central SBP was divided into quintiles, the number of events was least in the 2nd quintile, and we set it as the reference. In the Cox regression analysis adjusting for age, sex, body mass index, creatinine, diabetes, use of β-blocker, and history of MI/stroke, the patients in the 3rd (hazard ratio (HR) 3.55, 95% confidence interval 1.29-9.78, p = 0.014), 4th (HR 4.12, 95% CI 1.53-11.10, p = 0.005), and 5th quintiles (HR 2.87, 95% CI 1.01-8.18, p = 0.048) had a significantly higher incidence of cardiovascular events compared to the 2nd quintile. The results were essentially unchanged when brachial DBP was additionally adjusted. In conclusion, in treated hypertensives, high central SBP was associated with worse cardiovascular outcomes.

This study analyzed repeated measurement data to clarify the longitudinal associations between hyperuricemia and the risk factors for the development of hypertension (ie, increased arterial stiffness, renal dysfunction, and inflammation), and then examined whether these risk factors show longitudinal associations with the development of hypertension. In 3274 Japanese men without hypertension, the brachial-ankle pulse wave velocity, blood pressure, estimated glomerular filtration rate, and serum uric acid and CRP (C-reactive protein) levels were measured annually over an 8-year period. Of these, 474 subjects developed hypertension by the end of the study period. Mixed model linear regression analysis revealed a significant longitudinal association of hyperuricemia with increase of the brachial-ankle pulse wave velocity (estimate=5.50, P=0.04), decrease of the estimated glomerular filtration rate (estimate=-2.02, P<0.01), and elevation of the CRP (estimate=0.08×10 -1 , P=0.02). Hyperuricemia at the study baseline was associated with a significant odds ratio for the development of hypertension by the end of the study period. After adjustments for covariates, the brachial-ankle pulse wave velocity (estimate=0.51×10 -2 , P<0.01) and CRP (estimate=1.91, P=0.03), but not estimated glomerular filtration rate, were found to show independent longitudinal associations with the new onset of hypertension. In Japanese men without hypertension, hyperuricemia may have a longitudinal association with the development of hypertension, and increased arterials stiffness and inflammation may be involved in the risk of development of hypertension associated with hyperuricemia.

We conducted individual participant data meta-analysis to examine the validity of interarm blood pressure difference in simultaneous measurement as a marker to identify subjects with ankle-brachial pressure index <0.90 and to predict future cardiovascular events. We collected individual participant data on 13 317 Japanese subjects from 10 cohorts (general population-based cohorts, cohorts of patients with past history of cardiovascular events, and those with cardiovascular risk factors). Binary logistic regression analysis with adjustments identified interarm blood pressure difference >5 mm Hg as being associated with a significant odds ratio for the presence of ankle-brachial pressure index <0.90 (odds ratio, 2.19; 95% confidence interval, 1.60-3.03; P <0.01). Among 11 726 subjects without a past history of cardiovascular disease, 249 developed stroke during the average follow-up period of 7.4 years. Interarm blood pressure difference >15 mm Hg was associated with a significant Cox stratified adjusted hazard ratio for subsequent stroke (hazard ratio, 2.42; 95% confidence interval, 1.27-4.60; P <0.01). Therefore, interarm blood pressure differences, measured simultaneously in both arms, may be associated with vascular damage in the systemic arterial tree. These differences may be useful for identifying subjects with an ankle-brachial pressure index of <0.90 in the overall study population, and also a reliable predictor of future stroke in subjects without a past history of cardiovascular disease. These findings support the recommendation to measure blood pressure in both arms at the first visit., (© 2018 American Heart Association, Inc.)

Background: We conducted analyses of repeated-measures data to examine whether pressure wave reflection acts additively or synergistically with arterial stiffness in the pathogenesis of hypertension., Methods and Results: In 3172 middle-aged (42±9 years) healthy Japanese men without hypertension at the study baseline, systolic and diastolic blood pressures, brachial-ankle pulse wave velocity, and radial augmentation index were measured annually during a 9-year study period. Of these, 474 participants (15%) developed hypertension by the end of the study period. Binary logistic regression analysis demonstrated significant individual odds ratios for both baseline brachial-ankle pulse wave velocity and radial augmentation index for the development of hypertension. The rate of onset of hypertension during the study period was highest in the participant group with high values for both brachial-ankle pulse wave velocity and radial augmentation index at study baseline (262 of 965 participants: 27%). The generalized estimating equation analysis revealed that both radial augmentation index (estimate=0.06, SE=0.03, P =0.05) and brachial-ankle pulse wave velocity (estimate=0.07×10 -1 , SE=0.02×10 -1 , P <0.01) showed significant longitudinal association with new onset of hypertension, with no significant interaction., Conclusions: In Japanese men, abnormal wave reflection and increased arterial stiffness may be additively associated with the risk of new onset of hypertension. Abnormal wave reflection and elevated central blood pressure may be longitudinally associated with increase in arterial stiffness, and this longitudinal association may be a mechanism underlying the additive effect of these 2 variables on the risk of new onset of hypertension., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Objectives: To examine the longitudinal mutual association between endothelial dysfunction and arterial stiffness, and also to determine which of the two variables was more closely associated with the progression of subclinical organ damage., Methods: The brachial-ankle pulse wave velocity (baPWV), carotid intima-media thickness (CIMT), estimated glomerular filtration rate, microalbuminuria and flow-mediated vasodilatation of the brachial artery (FMD) were measured three times at 1.5-year intervals in 674 Japanese patients receiving antihypertensive treatment., Results: The change of the baPWV during the study period was larger in the subjects with baseline FMD values in the lowest tertile as compared to those with baseline FMD values in the highest tertile. The change of the CIMT was smaller in the subjects with baseline baPWV values in the lowest tertile than in those with baseline baPWV values in the highest tertile. After the adjustment, the FMD value at the baseline was inversely associated with the baPWV at the end of the study period (beta=-0.07, p=0.01), although, the reverse association was not significant. The baPWV, but not the FMD value, at the baseline was associated with the CIMT (beta=0.06, p=0.04) measured at the end of the study period., Conclusions: In hypertension, endothelial dysfunction was associated with the progression of arterial stiffness, although the reverse association was not confirmed. The increased arterial stiffness rather than endothelial dysfunction may be more closely associated with the progression of atherosclerotic vascular damage, and the endothelial dysfunction-arterial stiffness-atherosclerosis continuum may be important in hypertension., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Hypertension is associated with endothelial dysfunction. Blood pressure significantly correlates with endothelial function in antihypertensive drug-naive subjects. The purpose of this study was to determine whether treatment status affects the relationship between blood pressure and endothelial function. We measured flow-mediated vasodilation (FMD) in 2297 subjects, including 1822 antihypertensive drug-naive subjects and 475 treated hypertensive patients. FMD significantly decreased in relation to increase in systolic blood pressure (8.2±3.1% in subjects with systolic blood pressure of <120 mm Hg, 7.5±2.8% for 120-129 mm Hg, 7.1±2.8% for 130-139 mm Hg, and 6.7±2.6% for ≥140 mm Hg; P <0.001). Systolic blood pressure was independently associated with FMD in untreated subjects. In contrast, there was no significant relationship between systolic blood pressure and FMD in treated hypertensive patients (4.6±3.1% in treated hypertensives with systolic blood pressure of <120 mm Hg, 4.8±2.7% for 120-129 mm Hg, 4.9±2.8% for 130-139 mm Hg, and 4.5±2.3% for ≥140 mm Hg; P =0.77). Propensity score matching analysis revealed that the prevalence of endothelial dysfunction defined as FMD of less than the division point for the lowest tertile, and the middle tertile of FMD was significantly higher in treated hypertensive patients than in untreated subjects in all systolic blood pressure categories. Endothelial function assessed by FMD was impaired regardless of the level of blood pressure achieved by antihypertensive drug treatment in hypertensive patients., (© 2017 American Heart Association, Inc.)

Background: The optimal cutoff values of the brachial-ankle pulse wave velocity (baPWV) for predicting cardiovascular disease (CVD) were examined in patients with hypertension.Methods and Results:A total of 7,656 participants were followed prospectively. The hazard ratio for the development of CVD increased significantly as the baPWV increased, independent of conventional risk factors. The receiver-operating characteristic curve analysis showed that the optimal cutoff values for predicting CVD was 18.3 m/s. This cutoff value significantly predicted THE incidence of CVD., Conclusions: The present analysis suggests that the optimal cutoff value for CVD in patients with hypertension is 18.3 m/s.

Background: The mechanisms underlying the possible contribution of chronic inflammation to the development of hypertension remain unclear. We examined the longitudinal association of inflammation with the progression of vascular and/or renal abnormalities in the development of hypertension., Methods and Results: In 3274 middle-aged Japanese men without hypertension at the study baseline, brachial-ankle pulse wave velocity, blood pressure, estimated glomerular filtration rate, and serum CRP (C reactive protein) levels were measured annually during a 9-year period. During this study period, 474 participants (14.5%) developed hypertension. Analysis of the repeated-measures data revealed that sustained elevation of serum CRP levels was associated with a longitudinal increase of the brachial-ankle pulse wave velocity. A linear mixed model analysis revealed that higher log-transformed serum CRP values (log CRP) at each measurement were associated with a higher annual increase of the brachial-ankle pulse wave velocity (estimate=32.553±11.635 cm/s per log CRP, P =0.018), and that higher values of the brachial-ankle pulse wave velocity at each measurement were associated with a higher annual elevation of blood pressure (estimate=0.025±0.002 mm Hg per log CRP, P <0.001)., Conclusions: In middle-aged Japanese men without hypertension at study baseline, long-term active inflammation appears to be associated with a longitudinal increase of arterial stiffness. In turn, this longitudinal increase of arterial stiffness appears to be associated with longitudinal elevation of blood pressure to the hypertensive range. Thus, systemic inflammation may play a role in the pathogenesis of hypertension by the progression of arterial stiffness., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Endothelial dysfunction is thought to have pivotal roles for the development of hypertension, initiation/progression of hypertensive organ damages, and prognosis. In clinical setting, flow-mediated vasodilatation (FMD) of brachial artery is used as a marker of endothelial function. However, well-trained sonographer is needed to conduct FMD measurement, and therefore, FMD has not been fully standardized (i.e., the reference value of FMD has not been established). Even so, FMD predicts future cardiovascular events. Lifestyle modifications (i.e., smoking cessation, exercise, or weight loss) and antihypertensive medication provide beneficial effects on endothelial function. Thus, FMD have a potential as a useful surrogate marker for the management of hypertension.

Background: The effect of age on the augmentation index (AI) differs between young adults and the elderly, and the AI reaches a plateau after the age of 60 years. We examined whether the effects of age and an elevation in blood pressure on the AI differ between young adults and the elderly, between subjects with and without high blood pressure, or between subjects with and without a high AI., Methods: The radial AI was measured in 10,190 subjects who were either healthy or had hypertension (n = 5,477 men and 4,743 women)., Results: In both sexes, a phased increase in the radial AI with age could only be confirmed up to an age of 60 years. A phased increase in the radial AI with the systolic blood pressure (SBP) could be confirmed up to an SBP of >170 mm Hg. Among subjects categorized within the highest age tertile, the highest SBP tertile, or the highest radial AI tertile, stepwise multivariable analyses demonstrated that SBP, but not age, was a significant independent factor influencing the radial AI., Conclusions: The effect of age and blood pressure on AI differ not only between young adults and the elderly but also between those with and those without high blood pressure or between those with and those without a high AI. The effect of an elevation in blood pressure, but not aging, on the AI is significant in the elderly, in subjects with high blood pressure, or in those with a high AI., (© American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Flow-mediated vasodilatation of the brachial artery (FMD) and reactive hyperemia index (RHI) measured by peripheral arterial tonometry are known to be weakly associated with one another, but the mechanisms underlying this weak association remain to be clarified. We examined whether the autonomic nervous activation induced by the 5 min forearm clamping used to induce reactive hyperemia might exert any influence on the FMD and RHI in subjects with hypertension. In 115 subjects with hypertension (age 61±1 years), the FMD and RHI were measured simultaneously, and the heart rate variability (HRV) parameters (low-frequency component (LF), high-frequency component (HF), and the ratio (LF/HF) between the two) were calculated from the electrocardiographic recordings obtained before and after the start of forearm clamping. A multivariate linear regression analysis with adjustments for confounding variables demonstrated that the RHI, but not the FMD, was significantly associated with the percent change of the LF/HF associated with forearm clamping (beta=-0.204, P=0.043). In conclusion, autonomic nervous system activation, especially sympathetic activation, induced by 5-min forearm clamping utilized to provoke reactive hyperemia may significantly affect the RHI rather than FMD in subjects with hypertension.

Objectives: We examined the following: whether the estimated glomerular filtration rate calculated from the serum cystatin C levels (eGFRcys) and the brachial-ankle pulse wave velocity (baPWV) might be independent predictors of the development of hypertension over the short term, without any interaction; whether the baPWV may be directly associated with the development of hypertension without the mediation of the arterial stiffness-related acceleration of renal functional decline; whether the second peak of the radial pressure waveform (SP2) might also be a significant independent predictor of the development of hypertension., Methods: In 1229 middle-aged normotensive Japanese men with preserved renal function, the baPWV, SP2 and eGFRcys were measured at the baseline and at the end of the 3-year study period., Results: Hypertension was detected at the end of the 3-year study period in 127 men. The logistic regression analysis with adjustments demonstrated significant independent odds ratios of the baPWV and eGFRcys for the presence of hypertension at the end of the 3-year study period, without any interaction. When entered simultaneously in this model, the SP2 also showed a significant odds ratio. General linear model analysis revealed that none of the baPWV or SP2 measured at the baseline was related to the renal function assessed at the end of the 3-year study period., Conclusions: The mechanisms underlying the association between arterial stiffness/central hemodynamics and the short-term development of hypertension appear to differ from those underlying the association between kidney function and the short-term development of hypertension.

Background: We examined which pathophysiological abnormalities of vascular function might be closely associated with abnormal baroreflex regulation in subjects with hypertension., Methods and Results: In the cross-sectional assessment, 280 subjects with hypertension were enrolled for measurement of brachial-ankle pulse wave velocity (baPWV), radial augmentation index (rAI), flow-mediated vasodilatation (FMD) of the brachial artery and baroreceptor sensitivity (BRS). These parameters were measured again as prospective assessment in some of these subjects. In the cross-sectional assessment, after adjustment for confounding variables including anti-hypertensive medication, the baPWV, but not the rAI or FMD, was found to have a significant independent relationship with BRS (standardization coefficient, -0.149, P<0.043). In the subjects who were newly started on anti-hypertensive medication (n=40), regression of baPWV before and 1 year after the start of medication was significantly associated with change in BRS during the same period. In subjects already on anti-hypertensive medication (n=92) also, the evolutional change of baPWV over a follow-up period >1.5 years was significantly associated with change in BRS during the same period., Conclusions: Increased stiffness of the large- to middle-sized arteries, rather than abnormal central hemodynamics or endothelial dysfunction, appears to contribute to abnormal baroreflex regulation in patients with hypertension.

We examined whether the central aortic systolic blood pressure, a marker of the function of the systemic arterial tree, might be a more powerful predictor of the development of hypertension than the brachial-ankle pulse wave velocity, a marker of the stiffness of the large- to middle-sized arteries, independent of the conventional risk factors for the development of hypertension. In 1268 Japanese men without hypertension (43±8 years old), the relationships between three variables (the second peak of the radial pressure waveform (SP2), brachial-ankle pulse wave velocity and conventional risk factors measured at the first examination) with the presence of hypertension at the second examination (after 3 years' follow-up) were examined. Hypertension was detected at the second examination in 154 men. The best cutoff points of the brachial-ankle pulse wave velocity and SP2, for predicting the development of hypertension, were 12.7 m/s and 109 mm Hg, respectively. The results of a logistic regression analysis confirmed that an SP2 of ≥109 mm Hg (odds ratio=8.493, P<0.001) was a more powerful predictor of the development of hypertension than a brachial-ankle pulse wave velocity of ≥12.7 m/s, independent of the conventional risk factors. The net reclassification index of SP2 (at the best cutoff point) to brachial-ankle pulse wave velocity was 0.211 (P<0.001), indicating that SP2 is a better predictor of the development of hypertension than brachial-ankle pulse wave velocity. In middle-aged Japanese men without hypertension, SP2 may be a more powerful predictor of the development of hypertension than the assessment of stiffness in large to middle-sized arteries independent of the conventional risk factors.

Objective: Brachial-ankle pulse wave velocity (baPWV) is a measure of arterial stiffness. However, precisely how aging, hypertension and other factors influence this in progressively stiffening large arteries, especially in older adults, remains uncertain. We examined changes in arterial stiffness in a population of active older Japanese adults using a five-year follow-up cohort study., Methods: Comprehensive geriatric assessments were performed in socially active adults over the age of 70 years at The Life Planning Center Clinic in Tokyo. Clinically acceptable baPWV measurements at baseline and at the end of the study were obtained in 257 individuals (115 men, baseline mean age of 78±4 years; 142 women, baseline mean age of 77±4 years) classified into four groups based on the use of antihypertensive interventions at the end of the study: Group 1 (112 normotensives), Group 2 (49 hypertensives without medication use), Group 3 (39 hypertensives with medication use initiated during the follow-up period) and Group 4 (57 hypertensives receiving medications throughout the follow-up period)., Results: During the follow-up period, Group 1 exhibited no changes in blood pressure with increases in baPWV. Group 2 exhibited increases in blood pressure and baPWV. Both Groups 3 and 4 exhibited decreases in blood pressure without any changes in baPWV. Other factors such as age, gender and the hemoglobin level could also have influenced baPWV., Conclusion: Arterial stiffness increases with aging; however, antihypertensive medications were found to provide protective effects against the development of arterial stiffness during a five-year follow-up period. Other factors that modify baPWV were also identified.

The chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) have been recently much focused as independent risks for cardiovascular disease. Furthermore, the complication of both has a worse prognosis compared with patients with only one of these diseases. However, the details of the underlying mechanisms of this worsened prognosis have not been clear. The cross-sectional study was conducted to examine whether the overlap of COPD augment the increase in arterial stiffness in subjects with OSA. If so, we examined the exaggeration of nocturnal hypoxemia and its related inflammation are related to this augmentation of increased arterial stiffness. In 524 male subjects with OSA diagnosed by polysomnography (apnea-hypopnea index >5/h) (52 ± 14 years old), the forced expiratory volume at 1 s/the forced vital capacity (FEV(1)/FVC) ratio, brachial-ankle pulse wave velocity (baPWV), blood C-reactive protein (CRP) and B-natriuretic peptide (BNP) levels were measured. The prevalence rate of COPD was 12% in this study subjects. Plasma BNP levels and the crude (median value, 17.2 vs. 14.1 m/s, p < 0.01) and adjusted value of baPWV were significantly higher in subjects with overlap syndrome than in those with OSA alone. However, parameters of nocturnal hypoxemia and serum CRP levels were similar between both groups. Thus, the overlap of COPD in patients with OSA augments increase in arterial stiffness without the exaggeration of nocturnal hypoxemia and inflammation. Even so, this augmentation may partially contribute to the increased cardiovascular risk in the overlap syndrome., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Although insulin resistance (IR) is thought to be related to vascular dysfunction, the difference in the relationship of IR to microvasculature and macrovasculature reactivity has not yet been clarified. The present study was conducted to clarify whether the IR is more closely related to the macrovasculature reactivity (flow-mediated vasodilatation of the brachial artery induced by reactive hyperemia: FMD) or microvasculature reactivity (skin reactive hyperemia as assessed by laser Doppler flowmetry: SRH) in patients with hypertension., Methods: In 75 consecutive hypertensive patients (61 +/- 11 years of age) without obvious cardiovascular (CV) disease and/or risk factors for CV disease other than hypertension, FMD, SRH, and homeostasis model assessment index of IR (HOMA(IR)) were measured., Results: No significant relationship was observed between FMD with the parameters of SRH. In the univariate linear regression analysis, HOMA(IR) showed a significant correlation with the FMD (R(2) = 0.05, P < 0.05), but not with the parameters of SRH. Multivariate linear regression analysis demonstrated a significant association between HOMA(IR) and FMD, even after adjustments for covariates, including the use of medication for hypertension. (R(2) = 0.32, beta = -0.29, P = 0.02)., Conclusions: The complication of IR in hypertensive patients without obvious CV disease/risk factors may be related to impaired macrovasculature rather than microvasculature reactivity, apart from the influence of antihypertensive medication on the reactivity of the vasculature and insulin sensitivity.

Background: Arterial stiffness is an important risk factor for cardiovascular disease. Carotid-femoral pulse wave velocity (cfPWV) is the most recognized and established index of arterial stiffness. An emerging automatic measure of PWV primarily used in the Asian countries is brachial-ankle PWV (baPWV)., Method: To systematically compare these two methodologies, we conducted a multicenter study involving a total of 2287 patients., Results: There was a significant positive relation between baPWV and cfPWV (r = 0.73). Average baPWV was approximately 20% higher than cfPWV. Both cfPWV and baPWV were significantly and positively associated with age (r = 0.56 and 0.64), systolic blood pressure (r = 0.49 and 0.61), and the Framingham risk score (r = 0.48 and 0.63). The areas under the receiver operating curves (ROCs) of PWV to predict the presence of both stroke and coronary artery disease were comparable between cfPWV and baPWV., Conclusion: Collectively, these results indicate that cfPWV and baPWV are indices of arterial stiffness that exhibit similar extent of associations with cardiovascular disease risk factors and clinical events.

Background: This 3-year prospective study in middle-aged Japanese men with prehypertension examined the usefulness of the plasma levels of C-reactive protein (CRP) and the brachial-ankle pulse wave velocity (baPWV) as predictors of the development to hypertension as compared with other previously proposed markers, such as the age, initial blood pressure, heart rate, obesity, smoking, and alcohol intake., Methods and Results: Among 777 men with prehypertension (42 +/- 8 years old), hypertension developed in 58 men during the observation period. Significant elevation of blood pressure during this 3-year follow-up was not observed in some, but not all, subjects. Univariate linear regression analysis demonstrated that baPWV, body mass index (BMI), age, and alcohol intake, but not plasma levels of CRP, heart rate, and smoking, on the first examination were significant variables related to the changes in systolic blood pressure from the first examination to the second examination. Multivariate linear regression analysis confirmed that baPWV and BMI were weak but significant independent variables related to the changes in systolic blood pressure (R(2) = 0.03). The logistic regression analysis demonstrated that baPWV >13.5 m/s (adjusted odds ratio = 3.32 (1.79-6.15)) and BMI >25.0 (adjusted odds ratio = 2.27 (1.25 - 4.13)) were significant predictors of future hypertension independent of blood pressure on the first examination., Conclusion: This 3-year prospective study suggested that the baPWV and BMI, but not plasma CRP levels, are not powerful but significant independent markers to identify middle-aged Japanese men with prehypertension at high risk for hypertension.

Objective: This study was conducted to clarify whether the brachial-ankle pulse wave velocity (baPWV) might serve as a marker of target organ damage in middle-aged hypertensive subjects., Methods and Results: Multivariate linear regression analysis demonstrated that while the baPWV showed a significant relationship to the intima-media thickness of the carotid artery (IMT), no such relationship was observed between the baPWV and the left ventricular mass index as assessed by echocardiography or the estimated glomerular filtration rate in either the 162 hypertensive patients who had never previously received antihypertensive medication or the 269 hypertensive patients who were under antihypertensive medication for at least 1 year. Receiver-operator characteristic (ROC) curve analysis suggested that a baPWV=18m/s was the best cutoff value to identify increased IMT in hypertensive patients who had never previously received antihypertensive medication (area under curve=0.77). Binary logistic regression analysis demonstrated that the odds ratio (OR) of a baPWV of ≥18m/s for identifying increased IMT {OR=7.38 (1.94-28.05)} was significant, even after adjustments. In hypertensive patients who had been under antihypertensive medication for at least 1 year, however, the area under the curve and OR were only modest., Conclusion: The baPWV may be a marker of carotid atherosclerosis, rather than of left ventricular hypertrophy or renal insufficiency, especially in middle-aged hypertensive subjects (subjects in their 30s to 60s), not only in those who have never previously received antihypertensive medication, but also in those who are under antihypertensive medication.

Background: The present study was conducted to clarify whether azelnidipine might have beneficial effects on autonomic functions, and whether such beneficial effects might affect the vascular functions (i.e., arterial stiffness and endothelial function)., Methods and Results: This study with a cross-over design was conducted in 21 hypertensive patients (65 +/- 9 years old) being treated with calcium channel blockers (CCBs) other than azelnidipine or benidipine (i.e., during the study period, the CCB was switched to either azelnidipine 16 mg/day or benidipine 4 mg/day, administered alternately for 8 weeks each). Blood examinations were conducted and the heart rate variability, baro-receptor sensitivity (BRS), brachial-ankle pulse wave velocity (baPWV) and flow-mediated vasodilatation (FMD) in the brachial artery were measured after treatment with each of the two drugs. While the blood pressure levels decreased to a similar degree after both treatments, the BRS (8.8 +/- 5.5 ms/mmHg vs. 6.4 +/- 2.9 ms/mmHg, p < 0.01) and high-frequency power component (HF: 139 +/- 152 ms2/Hz vs. 88 +/- 97 ms2/Hz) were higher after treatment with azelnidipine than after treatment with benidipine (p < 0.05). However, the baPWV, FMD and plasma levels of malonyldialdehyde low-density lipoprotein cholesterol and nitric oxides were similar after treatment with both drugs., Conclusion: Azelnidipine has greater beneficial effects on the autonomic functions than benidipine although the degree of reduction of blood pressure induced by the two drugs was similar. However, this greater beneficial effect of azelnidipine on the autonomic functions did not produce any distinguishable differences in effects of azelnidipine and benidipine on the arterial stiffness and endothelial functions.

Background: Although telmisartan may be more beneficial for glucose metabolism than other angiotensin II receptor blockers (ARBs), it has not been determined whether telmisartan exerts more favorable effects on biological and functional parameters related to endothelial function than other ARBs., Methods: A study with a crossover design was conducted in 40 hypertensive patients (61 +/- 10 years old, mean +/- SD) who had previously been treated with ARBs other than telmisartan or valsartan (ie, ARBs were switched to either telmisartan 40 mg/day or valsartan 80 mg/day, administered alternately for 12 weeks each). Blood examinations were conducted, and the mean reactive hyperemia ratio (mRHR) was measured by plethysmography for each treatment regimen., Results: There were no significant differences in either blood pressure or plasma levels of monocyte chemoattractant protein-1, C-reactive protein, 3-nitrotyrosine, or vascular cell adhesion molecule-1 between the two treatment regimens. The mRHR (2.7 +/- 1.0 v 2.4 +/- 1.0, mean +/- SD) was larger (P < .05), and the plasma levels of asymmetric dimethylarginine (ADMA) (0.45 +/- 0.08 v 0.50 +/- 0.17 micromol/L, mean +/- SD) and the homeostasis model assessment index of insulin resistance (HOMA-IR) (2.3 +/- 1.6 v 2.8 +/- 2.1, mean +/- SD) were lower (P < .05) in telmisartan-treated patients than in valsartan treated patients. The percent change in ADMA, but not in HOMA-IR, correlated significantly with that in the mRHR (beta = -0.33, t value = -2.00, P = .04)., Conclusions: At doses producing equivalent hypotensive effects, telmisartan apparently had a more favorable effect on functional parameters related to endothelial function than did valsartan. The reduction in plasma ADMA levels may contribute to this more favorable effect of telmisartan.

Objectives: This observational study was conducted to compare the significance of the relationship between arterial stiffness and progression to higher blood pressure categories among middle-aged Japanese men with high normal blood pressure (HNP), normal blood pressure (NRP) and optimal blood pressure (OPP)., Methods and Results: During the 3-year observational period, 100 subjects with HNP developed hypertension (n=475; 42 +/- 9 years), and 175 of those with normal NRP (n=581; 41 +/- 8 years) and 249 of those with OPP (n=702; 39 +/- 8 years) showed progression to higher blood pressure categories. A binary logistic regression analysis adjusted for known risk factors revealed that values of the brachial-ankle pulse wave velocity, a surrogate marker of arterial stiffness, in the highest quartile, as compared with those in the lowest quartile, obtained at the start of the study were significantly predictive of the progression to hypertension [adjusted odds ratio = 9.4 (95% confidence interval, 3.0-29.8), P < 0.01]. The predictive value of this parameter for progression to higher blood pressure categories in subjects with HNP was more significant than that in those with NRP or OPP., Conclusions: Increased arterial stiffness and elevated blood pressure may be mutually causally related, and it appears that the significance of this relationship may increase with increasing blood pressure, even in subjects without hypertension. Assessment of arterial stiffness may be more reliable for predicting the progression to hypertension in cases of HNP than in cases with NRP or OPP.

Background: Recent studies have suggested that angiotensin-converting enzyme inhibitors (ACEi) have a more pronounced effect on endothelial function (END) than angiotensin II receptor blocker (ARB); however, whether this pronounced effect is more beneficial to patients with insulin sensitivity (IS) remains uncertain. The present study compared the effects of ACEi and ARB on END and IS in patients with hypertension., Methods: A total of 23 patients with hypertension were given either ACEi or ARB alternatively in a cross-over manner for 8-week intervals. Both END and IS were examined after each treatment period; END was assessed by the response of forearm blood flow to reactive hyperemia and IS by an insulin tolerance test. The plasma levels of bradykinin (BK), NOx, tumor necrosis factor (TNF-alpha), and adiponectin (Adi) were also measured after each treatment., Results: We found that END, BK, and NOx were higher after the ACEi treatment than after the ARB treatment. Although the IS and the Adi levels were similar after both treatments, the TNF-alpha level was lower after the ARB treatment than after the ACEi., Conclusions: We conclude that ACEi and ARB may have similar effects on insulin sensitivity, irrespective of the more pronounced effects of ACEi on endothelial function. The BK-NO pathway might contribute, at least in part, to the pronounced effect of ACEi. On the other hand, the underlying mechanisms affecting insulin sensitivity might differ for both treatments. These results suggest that endothelial function is not a major determinant of insulin sensitivity under physiologic conditions.

Although blood pressure and age are major determinants of arterial stiffness, it is still unclear whether age-related changes in arterial stiffness are similar among subjects with different degrees of severity of hypertension. The present study examined the association between age and pulse wave velocity in subjects with different degrees of hypertension stratified according to the JNC-7 classification (Normal, Prehypertensive, and Stage I or II Hypertensive subjects). A number of 5,312 subjects (age range, 30-79 years) with no atherosclerotic risk factors other than high blood pressure were selected from two cohorts who regularly underwent annual health checkups, including the measurement of brachial-ankle pulse wave velocity (baPWV). baPWV was increased according to the severity of hypertension in all age groups. The association between age and baPWV formed a quadratic curve in each stage in both genders. The steepness of the slope of the quadratic curve increased according to the severity of hypertension. In each stage of hypertension, age and the baPWV were divided into tertiles. After adjustment for systolic and diastolic blood pressure, the odds ratio of having an increased baPWV in the 3rd age tertile (the highest-age group) was found to increase according to the severity of hypertension. In conclusion, the age-related increase of baPWV was shown to be augmented in phases according to the severity of hypertension, and this augmentation occurred even between the Normal and Prehypertensive stages. These results support the JNC-7 recommendations for a strict control of blood pressure even in the elderly.

The present study was conducted to make a nomogram of the relation of brachial-ankle pulse wave velocity (baPWV) with blood pressure. In 11,375 subjects (age range: 30 to 79 years) in whom we measured baPWV, multivariate linear regression analysis demonstrated that age, systolic blood pressure, and gender were significant determinants of baPWV. Of them, we selected 5,302 subjects (2,630 men and 2,672 women, age 46 +/- 11 years) with either normal blood pressure or with high blood pressure without other atherosclerotic risk factors. Using data from these subjects, we tried to make an age-derived nomogram and a systolic blood pressure-derived nomogram for in both genders. The regression curve analysis demonstrated significant quadratic curves for both associations. The obtained nomograms were applied to 297subjects with coronary heart disease. Their measured baPWV (1,569 +/- 344 cm/s) was significantly higher than the values calculated from the age-derived nomogram (1,502 +/- 241 cm/s) and the systolic blood pressure-derived nomogram (1,418 +/- 236 cm/s) (p < 0.01). Thus, a nomogram of the relation of baPWV with blood pressure was obtained. The comparison of the measured baPWV with the values calculated from the nomograms may be useful to not to underestimate the real risk for atherosclerotic cardiovascular diseases, including the severity of atherosclerotic vascular damage, reflected by measured baPWV in subjects with different blood pressure levels.

The measurement of brachial-ankle pulse wave velocity (baPWV) is simple and applicable for general population studies. The present study was conducted to evaluate the applicability of baPWV for screening cardiovascular risk as well as for use as a marker of the severity of atherosclerotic vascular damage in a general population. baPWV was measured in a cross-sectional study involving two cohorts constituting a total of 10,828 subjects who underwent annual health screening check up examinations (6,716 males and 4,112 females; age 30 to 74 years). The Framingham risk score and Pocock's score were obtained. Multivariate analysis demonstrated that baPWV was associated with both scores, independently from conventional atherosclerotic risk factors. The receiver-operator characteristic curve demonstrated that a baPWV of 14.0 m/s is useful for risk stratification by Framingham score and to discriminate patients with either stroke or coronary heart disease (n=143), but the likelihood ratios were less than 5.0. Logistic regression analysis demonstrated that a baPWV>14.0 m/s is an independent variable for the risk stratification by Framingham score and for the discrimination of patients with atherosclerotic cardiovascular disease. Thus, baPWV has potential as a new marker of cardiovascular risk and may be more useful than other conventional markers; in addition, baPWV is easy to obtain and serves as an indicator of either atherosclerotic cardiovascular risk or severity of atherosclerotic vascular damage; thus it is useful to screen the general population. While the discriminating powers are not sufficiently high, a cutoff value of 14.0 m/s serves to screen subjects, especially in middle-aged ones, of either gender.

The effect of oxidative stress on endothelial function, platelet function, and fibrinolysis in hypertension with or without glucose intolerance was examined. The endothelium, platelets and fibrinolysis play important roles in the progression of atherosclerosis and interact with each other. We have previously demonstrated that glucose intolerance impairs endothelial function in hypertension, but its precise mechanisms have not been clarified. Hypertensive patients were divided by the results of 75-g oral glucose tolerance test into a normal glucose metabolism group (n = 65) and a glucose intolerance group (n = 47). The plasma level of thiobarbituric acid-reactive substances (TBARS) was assessed as a marker of oxidative stress. Endothelial function was assessed by flow-mediated dilatation (FMD), platelet function by the concentration of ADP dose inducing half-maximal aggregation (EC50), and fibrinolytic parameters by radioimmunoassay. These functions were assessed before and after acute administration of vitamin C. FMD was reduced while TBARS and fibrinolytic parameters were higher in patients with glucose intolerance than in those with a normal glucose metabolism. Vitamin C increased FMD and reduced fibrinolytic parameters significantly in the glucose intolerance group, but not in the group with normal glucose metabolism. On the other hand, the EC50 was similar in both groups. In conclusion, glucose intolerance aggravates oxidative stress, thereby contributing to the impairment of endothelial function in patients with hypertension. These abnormalities affect fibrinolysis but not platelet function.

BackgroundWe examined whether in addition to producing a greater degree of improvement of the arterial stiffness, long-term angiotensin II receptor blocker (ARB) treatment might also have a more beneficial effect on the cardiac diastolic dysfunction than long-term calcium-channel blocker (CCB) treatment; we also evaluated the association between the improvements of the two variables brought about by ARB treatment in subjects with stage I or II hypertension.MethodsOne hundred and thirteen patients were randomly allocated to treatment with an ARB (candesartan) or a CCB (amlodipine). Echocardiography and measurement of the brachial-ankle pulse wave velocity (PWV) were conducted in both groups at the start of the treatment and at the end of 2-3-years' treatment.ResultsAfter adjustments for covariates, the extent of reduction of the brachial-ankle PWV (−200 ± 18 cm/s vs. −141 ± 18 cm/s, P = 0.03) and that of the increase of the E/A ratio (0.08 ± 0.03 vs. 0.01 ± 0.03, P = 0.04) were significantly greater in the candesartan group than in the amlodipine group. A significant relationship was identified between the delta changes of the brachial-ankle PWV and delta changes of the E/A ratio observed following long-term candesartan treatment.ConclusionLong-term candesartan treatment may have a more beneficial effect on the stiffness of the large- to- middle-sized arteries than long-term amlodipine treatment, and this treatment may also concomitantly improve the cardiac diastolic dysfunction; a significant association appeared to exist between the improvements of the two variables observed following long-term candesartan treatment.American Journal of Hypertension (2011). doi:10.1038/ajh.2011.109 [ABSTRACT FROM AUTHOR]