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Circulating CD34-positive cell count is inversely associated with height loss. It acts as an indicator of endothelial repair activity. In conjunction with CD34-positive cells, platelets contribute to endothelial repair. The presence of hypertension increases the demand for endothelial repair. Therefore, platelet count could be associated with height loss among individuals with hypertension. A retrospective study of 2,343 individuals aged 40 to 79 years was conducted. Height loss was defined as being in the highest quartile of annual height decrease (1.6 mm/year for men and 2.0 mm/year for women). A significant inverse association between platelet count and height loss was observed only among participants with hypertension. After adjusting for known cardiovascular risk factors, the odds ratio (95% confidence interval) for height loss per 1 standard deviation increment in platelet count (5.09×104/μL for men and 5.03×104/μL for women) was 0.83 (0.70, 0.98) for participants with hypertension and 1.02 (0.90, 1.16) for participants without hypertension. Independent of known cardiovascular risk factors, platelets could prevent accelerated height loss among individuals with hypertension. Unlike CD34-positive cell count, platelet count and blood pressure, which are easy to assess in daily clinical practice, influence height loss., Competing Interests: he authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright: © 2024 Shimizu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Hot spring bathing practice helps to manage hypertension. However, the details of the relationship between hot spring bathing and hypertension remain unknown. Older people are thought to be less adept than younger people at using digital devices such as mobile applications. Whether mobile application questionnaires, which have been increasing in recent years, can be used by older people is unclear. To address the knowledge gap regarding the management of older patients with hypertension, we prospectively evaluated mobile application and paper questionnaires regarding night-time hot spring bathing in respondents who had a choice of which to use. Changes in blood pressure because of hot spring bathing were evaluated. To investigate the effects of night-time hot spring bathing on blood pressure in adults, 1116 volunteers at 14 institutions in Beppu completed the study, including 562 in the mobile application questionnaire group and 556 in the paper questionnaire group. A total of 474 of 477 (99.3%) respondents aged ≥65 years used paper questionnaires. There was a significantly lower drop in both systolic and diastolic blood pressure after using hot springs in respondents aged ≥65 years than in respondents aged <65 years (p<0.001). An age ≥65 years, hypertension with medication, arrhythmia, depression, and using a chloride hot spring were independently and significantly associated with a lower drop in both systolic and diastolic blood pressure after night-time hot spring bathing (p<0.001). Night-time hot spring bathing was significantly associated with reduced blood pressure in older adults (p<0.001). Extending this research by examining how psychosocial factors in respondents aged ≥65 years influence preferences for mobile and paper questionnaires may be beneficial, and further investigation is warranted., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Yamasaki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Although artificial intelligence (AI) is considered to be a promising tool, evidence for the effectiveness of AI-supported clinical practice for lowering blood pressure (BP) in the real world is scarce. We conducted a systematic review to elucidate whether AI-supported clinical care improves BP control. We identified two randomized control trials (RCTs) in a literature search. The results revealed no significant difference between AI-supported care and usual care in a random-effects model meta-analysis of RCTs (AI vs. usual care: systolic/diastolic BP difference: -2.13 [95% confidence interval: -4.72 to 0.46] / -1.03 [-2.52 to 0.46]). In this review, we were unable to clarify whether AI-supported clinical practice improved BP control compared with usual care. Further studies will be needed to provide robust evidence for the effectiveness of AI-supported care in clinical settings., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Enlarged perivascular spaces (EPVS) of the brain may be involved in dementia, such as Alzheimer's disease and cerebral small vessel disease (CSVD). Hypertension has been reported to be a risk factor for dementia and CSVD, but the association between blood pressure (BP) and perivascular spaces is still unclear. The aim of this study was to determine the association between BP and EPVS volumes and to examine the interactions of relevant factors., Methods: A total of 9296 community-dwelling subjects aged ≥65 years participated in a brain magnetic resonance imaging and health status screening examination. Perivascular volume was measured using a software package based on deep learning that was developed in-house. The associations between BP and EPVS volumes were examined by analysis of covariance and multiple regression analysis., Results: Mean EPVS volumes increased significantly with rising systolic and diastolic BP levels ( P for trend = .003, P for trend<.001, respectively). In addition, mean EPVS volumes increased significantly for every 1-mmHg-increment in systolic and diastolic BPs (both P values <.001). These significant associations were still observed in the sensitivity analysis after excluding subjects with dementia., Conclusions: The present data suggest that higher systolic and diastolic BP levels are associated with greater EPVS volumes in cognitively normal older people., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Toshiharu Ninomiya received funds from the Japan Agency for Medical Research and Development and Suntory Holdings Limited (Osaka, Japan). The other authors assert that they have no competing interests.

The aim of this study was to clarify the relationship between fasting and nonfasting serum triglyceride (TG) levels and the incidence of hypertension in a general Japanese population. We conducted a population-based retrospective cohort study using annual health check-up data of residents of Iki City, Nagasaki Prefecture, Japan. A total of 3202 participants without hypertension at baseline were included in the present analysis. TG levels were classified as quartile 1 (<0.82 mmol/L), quartile 2 (0.83-1.13 mmol/L), quartile 3 (1.14-1.70 mmol/L) and quartile 4 (≥1.71 mmol/L) for men, and as quartile 1 (<0.70 mmol/L), quartile 2 (0.71-0.96 mmol/L), quartile 3 (0.97-1.34 mmol/L) and quartile 4 (≥1.35 mmol/L) for women. The outcome was incident hypertension. During an average follow-up of 4.4 years, 983 participants developed hypertension, according to the Cox proportional hazards model. The annual incidence of hypertension increased with an elevation in TG levels for men (5.88% in quartile 1, 8.30% in quartile 2, 7.62% in quartile 3, and 9.82% in quartile 4). This association was significant, even after adjustment for other risk factors: hazard ratio 1.41 [95% CI 1.07-1.85] for quartile 2, 1.30 [0.99-1.71] for quartile 3, and 1.59 [1.22-2.08] for quartile 4 compared with quartile 1 (p = 0.041 for trend). In contrast, there was no clear association between serum TG levels and the incidence of hypertension after adjustment for confounding factors among women (p = 0.240 for trend). High levels of serum TG were associated with the future incidence of hypertension in a general population of Japanese men but were not associated with that in women. Casual serum triglyceride levels and incidence of hypertension in a general Japanese population: ISSA-CKD study., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Hot spring bathing is practiced to help manage various diseases, including hypertension. We investigated the preventive effects on hypertension of hot spring bathing among older adults in a data analysis using responses to a previous questionnaire with the aim to identify a novel approach in the prevention and management of hypertension. Among 10,428 adults aged ≥ 65 years, we assessed the hot spring bathing habits of 4001 individuals with a history of hypertension. We calculated odds ratios (OR) with 95% confidence intervals using a multivariable logistic regression model for history of hypertension. In multivariable logistic regression, age (≥ 85 years: OR, 1.410); history of arrythmia (OR, 1.580), stroke (OR, 1.590), gout (OR, 1.880), diabetes mellitus (OR, 1.470), hyperlipidemia (OR, 1.680), renal disease (OR, 1.520), chronic hepatitis (OR, 0.648); and hot spring bathing at 19:00 or later (OR, 0.850) were independently and significantly associated with hypertension during the lifetime. We found an inverse relationship between habitual nighttime hot spring bathing and a history of depression. Prospective randomized controlled trials on nighttime hot spring bathing as a treatment for hypertension are warranted to investigate whether nighttime hot spring bathing can help in preventing hypertension among adults aged ≥ 65 years., (© 2022. The Author(s).)

Angiogenesis inhibition therapy causes hypertension by increasing peripheral vascular resistance. Vasa vasorum angiogenesis plays a crucial role in the development of atherosclerosis. Since vascular endothelial growth factor (VEGF), which contributes to the progress of angiogenesis, is reported to be inversely associated with the minor allele of polymorphism rs3025039, the minor allele of rs3025039 could be inversely associated with atherosclerosis among individuals with hypertension. A cross-sectional study of 1793 older Japanese adults aged 60-89 years with hypertension who participated in general health check-ups was conducted. Atherosclerosis was defined as carotid intima-media thickness (CIMT) ≥ 1.1 mm. The minor allele of polymorphism rs3025020 was positively associated with VEGF. Therefore, in addition to known cardiovascular risk factors, rs3025020 genotype acted as a confounding factor in the present study. Independent of known confounding factors, the minor allele of rs3025039 was inversely associated with atherosclerosis among older Japanese adults with hypertension. The fully adjusted odds ratio (OR) and 95% confidence interval (CI) for atherosclerosis with the minor allele of rs3025039 was 0.78 (0.64, 0.96). The angiogenesis-related polymorphism rs3025039 was associated with the development of atherosclerosis among older Japanese individuals. This study indicates that the development of atherosclerosis among older individuals might partly indicate a capacity for angiogenesis., (© 2022. The Author(s).)

In recent years, lifestyle-related diseases such as hypertension and diabetes have been on the rise. These conditions can cause serious conditions such as myocardial and cerebral infarctions. Therefore, proper control of blood pressure and blood glucose levels is important issues in preventive medicine. Traditional fermented foods have been shown to have various functions, and their effects on lifestyle-related diseases have attracted particular attention. In this study, we investigated the effects of fermented soybeans and rice bran (OE-1) and supplements containing OE-1 on blood glucose levels and weight changes. We identified an inhibitory effect on elevated blood glucose levels upon administration of OE-1, and this effect was thought to be due to digestive enzyme inhibition. These effects of foods containing OE-1 are expected to have a positive effect on the prevention and improvement of lifestyle-related diseases as health foods.

We aimed to investigate the association between serum uric acid (SUA) level and development of hypertension as well as the interaction effect of chronic kidney disease (CKD) on this relationship in the general Japanese population. We included 7895 participants aged ≥30 years from the ISSA-CKD study, a population-based retrospective cohort study that used annual health check-up data of residents from Iki Island, Japan. After the exclusion of 1881 with l < 1-year follow-up, 2812 with hypertension at baseline, and 165 with missing information on SUA, a total of 3037 participants were enrolled in this analysis. Participants were divided into four groups according to the quartiles of SUA level at baseline, and multivariable-adjusted hazard ratios for new-onset hypertension were calculated. Stratified analyses were performed for each subgroup (defined by sex, age, alcohol intake, and CKD) to assess the interaction effects. During a mean follow-up period of 4.4 years, 943 participants developed hypertension. The first quartile group was set as the reference group, and the multivariable-adjusted hazard ratios (95% confidence interval) for new-onset hypertension were 1.11 (0.90-1.36) in the second quartile, 1.25 (1.02-1.54) in the third quartile, and 1.35 (1.07-1.70) in the fourth quartile compared with those in the reference group (p = .007 for trend). The stratified analyses showed that the association between SUA and hypertension was significantly stronger in participants with CKD than in those without CKD (p = .035 for interaction). SUA level is an independent risk factor for new-onset hypertension. This tendency was significantly stronger in participants with CKD., (© 2021 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

The aim of this study was to determine the relationship between eating before bed and the development of hypertension in a general Japanese population. We conducted a population-based retrospective cohort study using annual health check-up data collected from the residents of Iki City, Nagasaki Prefecture, Japan. In total, 2930 participants without hypertension at baseline (mean age 57.0 years, male 42.8%) were included in the present analysis. Eating before bed was defined as eating within 2 h of bedtime. The outcome of this study was incident hypertension (blood pressure ≥140/90 mmHg or initiation of blood pressure-lowering medications). Multivariable-adjusted hazard ratios and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. During an average follow-up of 4.5 years, 909 participants developed hypertension. The incidence (per 1000 person-years) of hypertension in the group of individuals who ate before bed was 82.8, whereas that in the group of individuals who did not eat before bed was 65.8. The association was significant even after adjusting for other risk factors, including age, sex, current smoking status, current alcohol intake, regular exercise, obesity, elevated blood pressure, diabetes mellitus, and dyslipidemia, with a hazard ratio of 1.23 (95% CI: 1.05-1.44) for the group of individuals who ate before bed compared with the group of individuals who did not eat before bed (P = 0.01 for trend). Eating before bed was correlated with a future risk of developing hypertension in the general Japanese population., (© 2021. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Our recent studies indicate that thyroid cysts have clinical implications. Thyroid cysts could have a positive effect on the supply of thyroid hormones. Both hyperthyroidism and hypothyroidism cause hypertension. Hypothyroidism, but not hyperthyroidism, is a risk factor for atherosclerosis. Therefore, thyroid cysts could be associated with hypertension, and atherosclerosis might influence the association between thyroid cysts and hypertension. To evaluate the clinical significance of thyroid cysts, a cross-sectional study was conducted with 1801 Japanese aged 40-74 years. Thyroid cysts were significantly positively associated with hypertension in participants without atherosclerosis. However, there was a significant inverse association in those with atherosclerosis. The potential confounding factor adjusted odd ratios and 95% confidence intervals (95% CIs) were 1.49 (95% CI 1.17-1.90) for participants without atherosclerosis and 0.49 (95% CI 0.24-0.98) for those with atherosclerosis. The present study demonstrates that thyroid cysts have clinical implications because thyroid cysts support thyroid hormone activity. Our findings provide sufficient evidence to develop a risk assessment for hypertension for the general population, even though further research is required.

Background: A positive association between handgrip strength and blood pressure has been reported. Since these factors are linked to the condition of the endothelium, the activity of endothelial repair might influence the association between handgrip strength and hypertension., Methods: A cross-sectional study was conducted with 257 Japanese men aged 60-69 years who underwent an annual health checkup. As individuals with high level of circulating CD34-positive cells might show active endothelial repair, which plays an important role in vascular homeostasis, participants were stratified by circulating CD34-positive cell levels, using the median value of this population (0.96 cells/μL) as the cutoff., Results: Independent of known cardiovascular risk factors, for participants with a high CD34-positive cell, handgrip strength is significantly positively associated with hypertension (odds ratio and 95% confidence interval of hypertension for 1 standard deviation increment of handgrip strength were 1.85 (1.19, 2.88) but not for participants with a low CD34-positive cell (0.91 (0.61, 1.37))., Conclusion: The positive association between handgrip strength and hypertension is limited to high CD34-positive cells. This result may help clarify the role of vascular homeostasis in maintaining muscle strength.

Recent studies have revealed an inverse association between height and cardiovascular disease. However, the background mechanism of this association has not yet been clarified. Height has also been reported to be positively associated with cancer. Therefore, well-known cardiovascular risk factors, such as increased oxidative stress and chronic inflammation, are not the best explanations for this inverse association because these risk factors are also related to cancer. However, impaired blood flow is the main pathological problem in cardiovascular disease, while glowing feeding vessels (angiogenesis) are the main characteristic of cancer pathologies. Therefore, endothelial maintenance activity, especially for the productivity of hematopoietic stem cells such as CD34-positive cells, could be associated with the height of an individual because this cell contributes not only to the progression of atherosclerosis but also to the development of angiogenesis. In addition, recent studies have also revealed a close connection between bone marrow activity and endothelial maintenance; bone marrow-derived hematopoietic stem cells contribute towards endothelial maintenance. Since the absolute volume of bone marrow is positively associated with height, height could influence endothelial maintenance activity. Based on these hypotheses, we performed several studies. The aim of this review is not only to discuss the association between height and bone marrow activity, but also to describe the potential mechanism underlying endothelial maintenance. In addition, this review also aims to explain some of the reasons that implicate hypertension as a major risk factor for stroke among the Japanese population. The review also aims to clarify the anthropological reasons behind the high risk of atherosclerosis progression in Japanese individuals with acquired genetic characteristics.

Background: Recently, short stature has been revealed to be positively associated with hypertension, possibly because this indicates lower activity of vascular maintenance, such as angiogenesis. Vascular endothelial growth factor (VEGF) polymorphism (rs3025020) plays an important role in the progression of angiogenesis and may be associated with both hypertension and hypertension-associated short stature., Methods: A cross-sectional study of 1377 elderly Japanese individuals aged 60-89 years was conducted. Short stature was defined as the lowest tertile of height (< 160.8 cm for men and < 148.7 cm for women). Hypertension was defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg and/or antihypertensive medication use., Results: Independent of known cardiovascular risk factors, short stature was found to be positively associated with hypertension; the fully adjusted odds ratio (OR) and 95% confidence interval (CI) for hypertension were 1.51 (1.17, 1.96). With the reference group of carriers of the major allele of rs3025020, TT-homozygotes showed significantly lower OR for hypertension and short stature; the fully adjusted ORs (and 95% CIs) were 0.60 (0.41, 0.90) for hypertension and 0.59 (0.38, 0.91) for short stature, respectively., Conclusions: Angiogenesis-related genetic factor (rs3025020) is associated with hypertension and short stature, whereas short stature is positively associated with hypertension. Further investigation is necessary in this regard; the capacity for angiogenesis might partly explain the mechanism underlying the inverse association between height and hypertension.

Objectives: This study aimed to clarify the relationship between the white blood cell (WBC) count and hypertension in the general Japanese population., Methods: We conducted a population-based retrospective cohort study using annual health check-up data of residents of Iki City, Nagasaki Prefecture, Japan. A total of 2935 participants without hypertension at baseline were included in the present analysis. WBC counts were classified as tertile 1 (<4700/μL), tertile 2 (4700-5999/μL), and tertile 3 (≥6000/μL). The outcome was incident hypertension (blood pressure ≥140 mmHg). Multivariable-adjusted hazard ratios and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazards model., Result: During an average follow-up of 4.5 years, 908 participants developed hypertension. The incidence (per 100 person-years) of hypertension increased with an elevation in the WBC count (6.3 in tertile 1, 7.0 in tertile 2, and 7.4 in tertile 3). This association was significant, even after adjustment for other risk factors, including age, sex, current smoking habits, current alcohol intake, exercise habits, obesity, elevated blood pressure, diabetes mellitus, and dyslipidemia. The hazard ratios were 1.07 for tertile 2 (95% CI 0.90-1.26) and 1.27 for tertile 3 (95% CI 1.06-1.51) compared with the reference group of tertile 1 (p = 0.009)., Conclusion: The WBC count was associated with future development of hypertension in the general Japanese population., Competing Interests: The authors have read the journal's policy, and the authors of this study have the following competing interests to declare: HA received funding from Daiichi Sankyo and Takeda, lecture fees from Bayer, Daiichi Sankyo, Fukuda Denshi, MSD, Takeda and Teijin, and fees for consultancy from Kyowa Kirin outside of this work. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare. There are no other conflicts of interest to disclose.

Background: Human T-cell leukemia virus type 1 (HTLV-1) activates inflammatory cascades by activating the NF-κB pathway. The minor allele of single nucleotide polymorphism (SNP) in breast cancer suppressor BRCA1-associated protein (BRAP), which has a common etiology with HTLV-1 infection, has been reported to be positively associated with carotid atherosclerosis, but inversely associated with hypertension. Therefore, HTLV-1 infection may be inversely associated with hypertension by activating endothelial maintenance, including atherosclerosis. To clarify these associations, a cross-sectional study was conducted using 2989 Japanese individuals aged 60-99 years participating in a general health check-up., Methods: Logistic regression models were used to clarify the association between HTLV-1 and hypertension. Platelet levels stratified analyses were also performed since platelet production, which plays a crucial role in endothelium maintenance, can be stimulated by activating the NF-κB pathway., Results: HTLV-1 infection was found to be significantly inversely associated with hypertension, particularly in subjects with high platelet levels (≥ second tertiles of platelet levels); the fully adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 0.75 (0.62, 0.92) for total and 0.64 (0.50, 0.82) for high platelet levels, respectively. Further analysis of the non-hypertensive subjects demonstrated that HTLV-1 infection was significantly positively associated with atherosclerosis in subjects with the highest tertile of platelet levels (2.11 [1.15, 3.86]) but not in subjects with low platelet levels (first and second tertiles of platelet level) (0.89 [0.57, 1.39])., Conclusion: Asymptomatic HTLV-1 infection is inversely associated with hypertension, possibly by activating endothelial maintenance, including atherosclerosis progression.

Serum sodium concentration within the normal range could act as an indicator of age-related changes such as decrease in muscle strength and impairment of capillary function. Since endothelial injury stimulates endothelial repair by enhancing CD34-positive cell production, the level of serum sodium may be inversely associated with that of circulating CD34-positive cells, thus indicating the degree of age-related endothelial injury. We conducted a cross-sectional study of 246 elderly Japanese men aged 60-69 years. Subjects were stratified by hypertension status because hypertension should act as a strong confounding factor for the analyses performed in this study. Serum sodium concentration was positively associated with handgrip strength in non-hypertensive subjects [standardized parameter estimate (β) = 0.29; p = 0.003], but not for hypertensive subjects (β = 0.01; p = 0.878), while it was inversely associated with circulating CD34-positive cell levels in non-hypertensive subjects [simple correlation coefficient (r) = - 0.28; p = 0.002] but not for hypertensive subjects (r = - 0.07; p = 0.454). For non-hypertensive elderly subjects, serum sodium concentration within the normal range is positively associated with handgrip strength and inversely associated with CD34-positive cells, thus partly indicating the degree of age-related endothelium injury. These associations could prove to be an efficient tool for clarifying the background mechanism governing the decrease in age-related muscle strength.

Background: The change of left ventricular function deteriorated with age because of gradual increases of blood pressure may result in increased energy loss (EL) in left ventricle (LV). The present study investigated EL in LV among hypertensive elderly patients and examined factors contributing to EL., Methods: A single-center retrospective study was performed on elderly hypertensive outpatients (≥65 years) who underwent echocardiography (N = 105). EL in the LV was measured using a vector flow mapping system, and factors affecting peak EL during the early-diastolic phase (ED-EL), late-diastolic phase (LD-EL), and systolic phase (Sys-EL) were evaluated., Result: Mean age was 79.9 ± 6.4 years (male 43%). Mean ED-EL, LD-EL, and Sys-EL were 42.1 ± 46.7, 75.6 ± 60.2, and 40.4 ± 40.2 mJ/N/s. In a stepwise regression analysis, the E/e'(lateral) (unstandardized B = 0.005, 95%CI -0.03 to 0.007, standardized β = 0.434, P < .001) was identified as factors affecting ED-EL. The factors affecting LD-EL were E/A ratio (B = -0.122, 95%CI -0.176 to -0.068, β = -0.470, P < .001) and time velocity integral (TVI) in LVOT (unstandardized B = 0.002, 95%CI 0.000 to 0.004, β = 0.247, P = .021). The factors influencing Sys-EL were TVI in LVOT (B = 0.002, 95%CI 0.001 to 0.004, β = 0.390, P < .001), E/A ratio (B = -0.054, 95%CI -0.093 to -0.015, β = -0.258, P = .008), left ventricular outflow tract (LVOT) diameter (B = -0.006, 95%CI -0.010 to -0.002, β = -0.307, P = .006), and left ventricular mass index (B = 0.000, 95%CI 0.000 to 0.001, β = 0.208, P = .039)., Conclusion: Peak EL in the LV was higher during diastolic phase than systolic phase among elderly hypertensive patients. Peak EL both during late-diastolic phase and systolic phase was affected by systolic blood flow in LVOT and LV transmitral flow pattern., (© 2020 Wiley Periodicals LLC.)

Background: The absence of thyroid cysts may indicate latent thyroid damage, as demonstrated in our previous study. However, the association between the absence of thyroid cysts and latent functional damage of the thyroid is unknown. At low thyroid hormone productivity, which may be associated with latent functional damage of the thyroid, the association between thyroid-stimulating hormone (TSH) and hypertension might be enhanced. Therefore, we evaluated the association between TSH level and hypertension stratified by thyroid cyst status., Methods: We conducted a cross-sectional study of 1724 euthyroid Japanese individuals aged 40-74 years who participated in an annual health checkup in 2014., Results: In the study population, 564 and 686 participants had thyroid cysts and hypertension, respectively. A significant positive association was observed between TSH and hypertension in subjects without a thyroid cyst but not in subjects with thyroid cysts. There was a significant positive association between hypertension and TSH in subjects without a thyroid cyst (odds ratio [OR] 1.27; 95% confidence intervals [CI] 1.01, 1.61) but not in subjects with thyroid cysts (OR 0.79; CI 0.57, 1.09) in the model fully adjusted for known confounding factors. The correlation between the TSH and free triiodothyronine (fee T3) levels (simple correlation coefficient [r] = - 0.13, p < 0.01) was stronger in the subjects without thyroid cysts than in those with thyroid cysts (r = - 0.03, p = 0.525)., Conclusions: TSH is positively associated with hypertension only in individuals without thyroid cysts. The correlation between the TSH and free T3 levels was stronger in the subjects without thyroid cysts than in those with thyroid cysts. Therefore, the absence of thyroid cysts could be related to the association between TSH level and hypertension, possibly by indicating that the subjects without thyroid cysts had limited thyroid hormone reserves. Therefore, the absence of thyroid cysts could indicate the latent functional damage of the thyroid.

Hypertension frequently occurs in subclinical hypothyroidism (SCH). By bolstering thyroid inflammation, anti-peroxidase antibody (TPO-Ab) causes autoimmune thyroiditis, which is one of the most common causes of SCH. Since the absence of thyroid cysts is associated with TPO-Ab (+) based on the indication of latent thyroid damage, we explored the potential mechanism underlying the association among TPO-Ab, SCH, hypertension, and thyroid cysts. A cross-sectional study of 1,483 Japanese aged 40-74 years was conducted. Thyroid cysts were defined as those having a maximum diameter of ≥ 2.0 mm, containing no solid component. TPO-Ab (+) was positively associated with SCH with hypertension (adjusted odds ratio [OR] and 95% confidence interval [CI], 2.62 [1.40, 4.89]) but not with SCH without hypertension (0.84 [0.37, 1.89]), respectively. Moreover, among participants without thyroid cysts, SCH was positively associated with hypertension (2.15 [1.23, 3.76]) but not among participants with thyroid cysts (0.58 [0.16, 2.16]), respectively. TPO-Ab was positively associated with SCH with hypertension, but not with SCH without hypertension. In addition, status of thyroid cysts might act as a determinant factor on the association between SCH and hypertension. These findings are efficient tools to clarify the background mechanism that underlies SCH., Competing Interests: The authors have declared that no competing interests exist.

Minor allele frequency (MAF) of rs3782886 (BRAP) and rs671 (ALDH2) are reported to be inversely associated with blood pressure. Another study revealed that hematopoietic activity which is evaluated by reticulocytes could influenced on hypertension status partly by indicating activity of endothelial maintenance. Therefore, to evaluate the association between genetic factor and hypertension, influence of hematopoietic activity should be considered. A multi-faced analysis was performed in a simple general elderly population model (1,313 older Japanese aged 60-98 years). Participants were stratified by median values of reticulocytes (5.21 × 10 4 cells/μL for men and 4.65 × 10 4 cells/μL for women). Independent of known cardiovascular risk factors, MAF of rs3782886 and rs671 are significantly inversely associated with hypertension for participants with high hematopoietic activity (high reticulocytes level) (fully adjusted odds ratio (ORs) were 0.72 (0.55, 0.96) for rs3782886 and 0.72 (0.54, 0.96) for rs671) but not for low reticulocytes count (the corresponding values were 1.05 (0.79, 1.39) and 1.08 (0.81, 1.45), respectively). Hematopoietic activity evaluated by reticulocytes levels could influence on the association between single nucleotide polymorphism (rs3782886 and rs671) and hypertension. Those results were efficient tool to clarify the part of the mechanism that underlying the association between genetic factor and hypertension.

Age-related physical changes, such as low-grade inflammation and increased oxidative stress, induce endothelial repair and cause active arterial wall thickening by stimulating the production of CD34+ cells (the principal mediators of atherosclerosis). Despite this, aggressive endothelial repair (progressing atherosclerosis) might cause a wasting reduction in CD34+ cells, which could result in a lower capacity of endothelial repair and hypertension. As yet, no prospective study has clarified the association of circulating CD34+ cells with active arterial wall thickening. We conducted a prospective study of 363 men aged 60-69 years who participated in a general health check-up at least twice from 2014-2017. The circulating CD34+ cell count was significantly positively associated with active arterial wall thickening among subjects without hypertension (n = 236), but not among subjects with hypertension (n = 127). The fully adjusted odds ratios (ORs) of active arterial wall thickening for the logarithmic circulating CD34+ cell count were 1.83 (1.19, 2.84) and 0.69 (0.36, 1.32) for subjects without and with hypertension, respectively. Circulating CD34+ cells are positively associated with active arterial wall thickening in subjects without hypertension. This study demonstrates a means to clarify the mechanisms of endothelial repair in elderly subjects.

The aim of this study was to determine whether the blood pressure (BP) classification recommended in the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) hypertension guidelines is useful for the prediction of chronic kidney disease (CKD) in adults. We conducted a retrospective cohort study using annual health check data in Iki City, Nagasaki, Japan. A total of 3269 adults without CKD, who were not on BP-lowering medication, were included in the present analysis. BP was classified as: normal (systolic BP (SBP) <120 mmHg and diastolic BP (DBP) <80 mmHg), elevated BP (120 ≤ SBP < 130 and/or DBP < 80), stage 1 hypertension (130 ≤ SBP < 140 and/or 80 ≤ DBP < 90), and stage 2 hypertension (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg). The primary outcome of the study was new-onset CKD. The effects of BP on the development of CKD were evaluated using Cox's proportional hazards modelling. During a mean follow-up of 4.8 years, 472 (14.4%) participants developed CKD. The incidence (per 1000 person-years) of new-onset CKD was higher in individuals with elevated BP. After adjustment for other risk factors, there were significant associations between elevated BP and new-onset CKD: hazard ratio 1.11 (95% confidence interval 0.87-1.42) in elevated BP, 1.25 (1.01-1.54) in stage 1 hypertension, and 1.45 (1.18-1.79) in stage 2 hypertension, compared with the reference group with normal BP (P < 0.001 for trend). Thus, the findings of this study confirm the definition of hypertension (≥130/80 mmHg) recommended by the 2017 ACC/AHA guidelines for the management of hypertension to be useful for the prediction of new-onset CKD.

Background: Even though there is bidirectional association between hypertension and atherosclerosis, atherosclerosis itself is involved in the process of endothelial repair. To clarify the association of endothelial repair with hypertension, a cross-sectional study was conducted., Methods: We conducted a cross-sectional study of 562 elderly Japanese men aged 60-69. As gamma-glutamyl transpeptidase (γ-GTP) could act as a marker of oxidative stress that injures endothelial cell and higher levels of CD34-positive cell indicate a higher activity of endothelial repair, we therefore performed a CD34-positive level specific analysis of γ-GTP on atherosclerosis and hypertension., Results: In the present study population, hypertension was independently and positively associated with atherosclerosis (multivariable odds ratio (OR) = 2.09 (1.30, 3.35)). Among participants with high CD34-positive cells, γ-GTP showed significant and positive association with atherosclerosis (OR of the log-transformed value of γ-GTP (OR) = 2.26 (1.32, 3.86)) but not with hypertension (OR = 0.77 (0.51, 1.17)). Among participants with low CD34-positive cells, even γ-GTP showed no significant association with atherosclerosis (OR = 0.92 (0.51, 1.68)), but was significantly and positively associated with hypertension (OR = 1.99 (1.27, 3.12))., Conclusions: γ-GTP revealed to have ambivalent association with hypertension and atherosclerosis. Active endothelial repair that is associated with atherosclerosis might have beneficial association with hypertension.

Purpose: Age-related reduction in bone marrow activity has been shown to cause anemia, and hypertension and endothelial dysfunction (atherosclerosis) are age-related diseases. However, recent studies have revealed a close association between bone marrow activity and endothelial maintenance. This study aimed to determine the association between elevated reticulocyte levels in conjunction with vigorous bone marrow activity and hypertension and atherosclerosis among the elderly. Study population and Methods: To determine the associations between reticulocyte levels and hypertension and atherosclerosis, we conducted a cross-sectional study of 2,098 elderly Japanese individuals, aged between 60 and 89 years, who had participated in an annual health check-up in 2014. Results: Of the total study population, 1,348 individuals were diagnosed with hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg and/or having used antihypertensive medication), and 393 were diagnosed with atherosclerosis (carotid intima-media thickness ≥1.1 mm). Reticulocyte levels were found to be significantly positively associated with hypertension and inversely associated with atherosclerosis. Cardiovascular risk factor-adjusted odds ratios and 95% confidence intervals for hypertension and atherosclerosis, when raised incrementally by 1 standard deviation to determine reticulocyte levels (5.5×10 4  cells/μL for men and 5.0×10 4  cells/μL for women), were 1.12 (1.01, 1.25) and 0.83 (0.72, 0.94), respectively. Conclusion: Along with established cardiovascular risk factors, reticulocyte levels in elderly Japanese individuals were found to be positively associated with hypertension and inversely associated with atherosclerosis. This finding may help clarify the background mechanisms concerning the association between bone marrow activity and vascular remodeling., Competing Interests: The authors report no conflicts of interest in this work.

Objectives: Arterial stiffness is associated with longitudinal increases in blood pressure and hypertension development. A screened cohort was used to test whether increases in the ankle-brachial index (ABI) with age occur as a result of increasing arterial stiffness and wave reflection and is associated with hypertension incidence., Methods: We analysed the data of 1344 participants without hypertension at baseline who underwent ABI measurements at least twice with an interval of at least 36 months. Participants with abnormal ABI values were excluded., Results: The median age of participants was 51 years (55% women). The ABI was lowest for participants younger than 40 years and increased with age. At the time of the follow-up visit (median follow-up period, 47 months), 224 (17%) participants had developed hypertension. Multiple linear regression analysis revealed that baseline ABI was positively and independently associated with the yearly change in brachial SBP and hypertension incidence. Compared with participants with a normal ABI (1.00-1.19), the adjusted odds ratio for hypertension incidence was significantly higher for participants with a high-normal ABI (1.20-1.39) before and after multivariate adjustment for conventional risk factors (odds ratio, 2.17, 95% confidence interval 1.20-3.95). Addition of ABI to a model containing conventional risk factors did not improve the c-statistics but the net reclassification index of ABI was 0.17 (95% confidence index 0.01-0.37) for hypertension incidence., Conclusion: Baseline ABI was positively and independently associated with the yearly change in SBP and hypertension incidence.

Background: Hypertension and atherosclerosis are bidirectionally related, while platelet count could serve as an indicator of endothelial repair. Therefore, high platelet counts could be associated with hypertension by indicating more intense endothelial repair activity. Furthermore, short stature has been shown to constitute a risk of atherosclerosis. Since inflammation-related single-nucleotide polymorphism (SNP (rs3782886)) is reportedly associated with myocardial infarction and short stature, rs3782886 could be associated with a high platelet count and thus more intense endothelial repair activity., Methods: We conducted a cross-sectional study of 988 elderly Japanese who participated in a general health check-up. Short stature was defined as a height of at or under the 25th percentile of the study population, and high platelet count as the highest tertiles of the platelet levels., Results: High platelet counts were found to be independently and positively associated with hypertension while rs3782886 was independently associated with high platelet levels and short stature. The classical cardiovascular risk factor-adjusted odds ratio (OR) and 95% confidence interval (CI) of high platelet count for hypertension was 1.34 (1.02, 1.77). With non-minor homo of the rs3782886 as the reference group, the adjusted OR and 95% CI for high platelet count and short stature of minor home were 2.40 (1.30, 4.42) and 2.21 (1.16, 4.21), respectively., Conclusion: SNP (rs3782886) was shown to be associated with high platelet count and short stature. This result partly explains how a genetic factor can influence the impact of height on endothelial repair.

Background: Age-related low-grade inflammation causing endothelial disruption influences sarcopenia, hypertension, and atherosclerosis. We reported previously that maintenance of muscle strength in elderly hypertensive men with high platelet levels is positively associated with subclinical atherosclerosis but not in those with low platelet levels. Since reduced tongue pressure is related to sarcopenia, tongue pressure may be associated with subclinical carotid atherosclerosis in hypertensive elderly subjects, and platelet levels may function as an indicator of the association between tongue pressure and subclinical carotid atherosclerosis., Methods: We conducted a cross-sectional study of 342 hypertensive elderly Japanese men aged 60-89 who participated in an annual health check-up in 2015 and 2016. Subclinical carotid atherosclerosis was defined as a common carotid intima-media thickness (CIMT) of 1.1 mm or more., Results: In the overall study population, 171 subjects demonstrated low platelets (< 21.4 × 10 4 /μL). Tongue pressure was significantly inversely associated with subclinical carotid atherosclerosis in these subjects, but not in subjects with high platelets. The known cardiovascular risk factor adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of subclinical carotid atherosclerosis for a 1 standard deviation (SD) increment in tongue pressure (10.4 kPa) were 0.54 (0.35, 0.85) and 1.31 (0.87, 1.96), respectively., Conclusion: Tongue pressure is inversely associated with subclinical carotid atherosclerosis in hypertensive elderly men with low platelet levels, but not in those with high levels. This finding may thus constitute an efficient tool for clarifying the background mechanism of age-related diseases such as sarcopenia, hypertension, and atherosclerosis.

Aim: Hemoglobin is reported to be positively associated with hypertension. However, the underlying mechanism of this association is unknown. Recently, bone marrow-derived CD34-positive cells have been reported to play an important role in endothelial repair in conjunction with platelets. As the association between hypertension and endothelial dysfunction is bidirectional, the influence of endothelial repair also might strongly influence the association between hemoglobin and hypertension., Methods: To clarify the clinical importance of the hematological parameter on endothelial maintenance in older men, we carried out a cross-sectional study of 222 Japanese men aged 60-69 years undergoing a general health checkup., Results: For participants with a lower platelet count (≤21.0/μL), hemoglobin was significantly positively associated with hypertension, but not for participants with a higher platelet count (>21.0/μL). The classical cardiovascular risk factor adjusted odds ratio of hypertension for 1-standard deviation increment of hemoglobin (1.0 g/dL) was 2.09 (95% CI: 1.26, 3.48) for participants with a lower platelet count, and 1.07 (95% CI: 0.68, 1.67) for participants with a higher platelet count. We also found that although there was no significant correlation between hemoglobin and circulating CD34-positive cells for participants with a lower platelet count (β = -0.06, P = 0.603), a significant positive correlation was seen for participants with a higher platelet count (β = 0.29, P = 0.004)., Conclusions: The positive association between hemoglobin and hypertension was limited to participants with a lower platelet count as a result of insufficient endothelial repair. These results represent an efficient tool for clarifying the mechanism of endothelial maintenance that correlates with hypertension. Geriatr Gerontol Int 2017; 17: 2586-2592., (© 2017 Japan Geriatrics Society.)

Aim: Bone-derived circulating CD34-positive cells are reported to play an important role in vascular maintenance. Additionally, height might influence age-related hematopoietic bone marrow decline, as it positively correlates with total bone marrow volume. As hypertension should mask the beneficial effects of circulating CD34-positive cells, hypertension status should account for this correlation. The present study aimed to clarify the clinical importance of height on vascular maintenance in older Japanese men., Methods: We carried out a cross-sectional study of 343 older men aged 65-69 years who underwent a general health checkup from 2013 to 2015., Results: Independent of known cardiovascular risk factors, height was found to be slightly, but significantly, positively correlated with the log number of circulating CD34-positive cells in systolic, but not non-systolic, hypertensive men. Multilinear regression analysis showed a parameter estimate (B) and standardized parameter estimate (β) of 3.23 × 10 -2 , 0.28 (P = 0.003) for systolic hypertensive men and -0.49 × 10 -2 , -0.04 (P = 0.495) for non-systolic hypertensive men., Conclusions: Height positively correlates with circulating CD34-positive cells in systolic, but not non-systolic, hypertensive men. As the beneficial effects of circulating CD34-positive cells on endothelial repair might be masked by hypertension where the production of CD34-positive cells is stimulated by hypertension-induced vascular damage, among individuals with systolic hypertension, circulating CD34-positive cells should indicate the limits of endothelial repair. Therefore, height might indicate the capacity for adequate vascular maintenance in older men. Geriatr Gerontol Int 2017; 17: 1729-1736., (© 2016 Japan Geriatrics Society.)

Background: Although high-density lipoprotein-cholesterol (HDL) level is inversely correlated with cardiovascular events, HDL is also reported to be positively associated with hypertension, which is a known endothelial impairment factor. Since HDL mediates important protective actions on the vascular endothelium by increasing the number of circulating endothelial progenitor cells (CD34-positive cells), the level of circulating CD34-positive cells should influence the association between HDL and hypertension., Methods: To investigate the association between HDL and hypertension in relation to the level of circulating CD34-positive cells, we conducted a cross-sectional study of 477 elderly men aged 60-69 years who participated in general health checkup., Results: HDL was found to be significantly positively associated with hypertension in subjects with a high level of circulating CD34-positive cells, while no significant association was observed for subjects with low circulating CD34-positive cells. Known cardiovascular risk factors adjusted odds (ORs) and 95% confidence intervals (CIs) of hypertension for increments of one standard deviation (SD) in HDL (13.8 mg/dL) were 1.44 (1.06, 1.96) for subjects with a high level of circulating CD34-positive cells and 0.87 (0.63, 1.19) for subjects with low circulating CD34-positive cells. We also revealed a significant association between HDL level and CD34-positive cell level on hypertension, with fully adjusted p values for the effect of this interaction on hypertension at 0.022., Conclusions: Independent of known cardiovascular risk factors, HDL was found to be positively associated with hypertension in subjects with a high level of circulating CD34-positive cells but not for subjects with low circulating CD34-positive cells.

Background and Aims: The bi-directional association between hypertension and endothelial dysfunction (vicious cycle) is crucial for the development of cardiovascular disease. Since platelets and circulating CD34-positive cells have been reported to contribute to vascular repair (endothelial repair and the development of atherosclerosis), these two factors could act as an indicator for the activity of this vicious cycle., Methods: We conducted a cross-sectional study of 580 Japanese men aged 60-69 years who underwent an annual health check-up. Since aggressive endothelial repair might cause consumptive reduction of circulating CD34-positive cells, subjects were stratified by circulating CD34-positive count (<1.01 cells/μL or ≥ 1.01 cells/μL)., Results: Platelet count is positively associated with hypertension among participants with a low CD34-positive cell count (multivariable-OR (odds ratio) for hypertension of 1 standard deviation (SD) increments in platelets (5.24 × 10 4 /μL) = 1.47 (1.12, 1.91)), but not among participants with a high CD34-positive cell count (multivariable-OR = 0.91 (0.71, 1.18)). We also found that platelet count is positively associated with carotid intima-media thickness related to endothelial dysfunction among hypertensive participants with a low CD34-positive cell count (standardized parameter estimate (β) = 0.26, p = 0.008), but not with a high CD34-positive cell count (β = 0.11, p = 0.234)., Conclusions: Our results indicate that the number of platelets and circulating CD34-positive cells acts as an indicator of the activity of the vicious cycle that exists between hypertension and endothelial dysfunction in elderly Japanese men., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Handgrip strength is a simple measurement of overall muscular strength and is used to detect sarcopenia. It also predicts adverse events in later life. Many mechanisms of sarcopenia development have been reported. A hypertensive status impairs endothelial dysfunction, which might deteriorate skeletal muscle if vascular angiogenesis is not maintained., Objectives: This study investigated muscle strength and circulating CD34-positive cells as a marker of vascular angiogenesis., Design: Cross-sectional study., Participants: 262 male Japanese community dwellers aged 60 to 69 years., Measurements: The participants' handgrip strength, medical history, and blood samples were taken. We stratified the participants by hypertensive status to investigate the association between handgrip strength and circulating CD34-positive cells according to hypertensive status. Pearson correlation and linear regression analyses were used., Results: In the Pearson correlation analysis, handgrip strength and the logarithm of circulating CD34-positive cells were significantly associated in hypertensive participants (r=0.22, p=0.021), but not in non-hypertensive participants (r=-0.01, p=0.943). This relationship was only significant in hypertensive participants (ß=1.94, p=0.021) in the simple linear regression analysis, and it remained significant after adjusting for classic cardiovascular risk factors (ß=1.92, p=0.020). The relationship was not significant in non-hypertensive participants (ß=-0.09, p=0.903)., Conclusions: We found a positive association between handgrip strength and circulating CD34-positive cells in hypertensive men. Vascular maintenance attributed by circulating CD34-positive cells is thought to be a background mechanism of this association after hypertension-induced vascular injury in skeletal muscle., Competing Interests: None

Accumulation of intra-abdominal fat is related to hypertension. Despite this, a relationship between hypertension and intra-abdominal fat in young adulthood is not clear. In this study, we verify whether intra-abdominal fat accumulation increases a hypertension risk in young adult subjects.In a cross-sectional study, intra-abdominal fat area was measured using a dual bioelectrical impedance analysis instrument in 697 university students (20.3 ± 0.7 years, 425 men). Blood pressure and anthropometric factors were measured. Lifestyle variables including smoking, drinking, physical activity, and eating behavior were assessed with questionnaire. High blood pressure risk (systolic blood pressure ≥130 mm Hg and/or diastolic blood pressure ≥85 mm Hg) with increasing intra-abdominal fat area was evaluated.Participants were divided into 5 groups according to their intra-abdominal fat area (≤24.9, 25-49.9, 50-74.9, 75-99.9, and ≥100 cm). As compared with the values of the smallest intra-abdominal fat area group, the crude and lifestyle-adjusted odds ratios (ORs) were elevated in larger intra-abdominal fat area groups [OR 1.31, 95% confidence interval (CI) 0.66-2.80; OR 3.38, 95% CI 1.60-7.57; OR 7.71, 95% CI 2.75-22.22; OR 18.74, 95% CI 3.93-105.64, respectively). The risk increase was observed only in men.Intra-abdominal fat accumulation is related to high blood pressure in men around 20 years of age. These results indicate the importance of evaluation and reduction of intra-abdominal fat to prevent hypertension., Competing Interests: The authors report no conflicts of interest.

Platelets and circulating CD34-positive cells have been reported to contribute to vascular repair (endothelial repair and developing atherosclerosis). And because hypertension is known to be a strong vascular impairment factors, it should also influence the respective numbers of these factors. To clarify the clinical importance of platelets on vascular repair, we conducted a cross-sectional study of 567 Japanese men aged 60-69 who underwent an annual health check-up between 2013 and 2015. Multiple linear regression analysis of non-hypertensive subjects adjusting for classical cardiovascular risk factors showed that although platelet count did not significantly correlate with carotid intima media thickness (β = -0.05, p = 0.356), it did positively correlate significantly with the natural log of the number of circulating CD34-positive cells (β = 0.26, p < 0.001). In hypertensive subjects, a significant positive correlation was seen between platelets and intima media thickness (β = 0.19, p = 0.008), whereas no significant correlation was seen between platelet count and the natural log of the number of circulating CD34-positive cells (β = 0.11, p = 0.119). Our results indicate that platelet count is an indicator of vascular repair activity (endothelial repair and developing atherosclerosis). Additionally, hypertension might mask the beneficial effects of circulating CD34-positive cells., Competing Interests: The authors of this manuscript declare no conflict of interests.

Background: We previously reported on the positive association of hemoglobin with hypertension and atherosclerosis. On the other hand, hepatocyte growth factor (HGF) has been evaluated as a possible biochemical index of hypertension-induced vascular damage. However, no studies have reported on a correlation between hemoglobin and HGF accounting for hypertension status., Methods: A cross-sectional study of 1108 subjects (392 men and 716 women, 40-93 years old) who were undergoing a general checkup in 2014 was conducted., Results: Multiple linear regression analysis adjustment for known cardiovascular risk factors showed no significant correlation between hemoglobin and HGF in non-hypertensive subjects, but a significant positive correlation in hypertensive subjects; β (parameter estimate) = 0.3 (p = 0.975) for non-hypertensive men, β = 0.4 (p = 0.925) for non-hypertensive women, β = 32.7 (p < 0.001) for hypertensive men, and β = 18.7 (p = 0.002) for hypertensive women., Conclusion: We found a significant positive correlation between hemoglobin and HGF among hypertensive men and women. Like HGF, hemoglobin may be a useful indicator to evaluate hypertension-induced vascular damage. Since hemoglobin can easily be measured, these results support hemoglobin as an efficient tool to evaluate vascular damage induced by hypertension in daily medical practice.

Objective: Serum triglycerides have been reported to be independently associated with the development of chronic kidney disease (CKD), which is known to play a role in vascular disturbance. On the other hand, circulating CD34-positve cells, including endothelial progenitor cells, are reported to contribute to vascular repair. However, no studies have reported on the correlation between triglycerides and the number of CD34-positive cells. Since hypertension is well known factor for vascular impairment, the degree of correlation between serum triglycerides and circulating CD34-positve cells should account for hypertension status., Methods: We conducted a cross-sectional study of 274 elderly Japanese men aged ≥ 60 years (range 60-79 years) undergoing general health checkups., Results: Multiple linear regression analysis of non-hypertensive subjects adjusting for classical cardiovascular risk factors showed that although triglyceride levels (1SD increments; 64 mg/dL) did not significantly correlate with glomerular filtration rate (GFR) (β = -2.06, p = 0.163), a significant positive correlation was seen between triglycerides and the number of circulating CD34-positive cells (β = 0.50, p = 0.004). In hypertensive subjects, a significant inverse correlation between triglycerides and GFR was observed (β = -2.66, p = 0.035), whereas no significant correlation between triglycerides and the number of circulating CD34-positive cells was noted (β = -0.004, p = 0.974)., Conclusion: Since endothelial progenitor cells (CD34-positive cells) have been reported to contribute to vascular repair, our results indicate that in non-hypertensive subjects, triglycerides may stimulate an increase in circulating CD34-positive cells (vascular repair) by inducing vascular disturbance., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: The hemoglobin levels and blood pressure has been reported in a few studies, and a positive association between the hemoglobin levels and the body mass index (BMI) status has also been documented. A higher BMI may therefore affect the association between the hemoglobin levels and hypertension. However, no published studies have examined this association in relation to the BMI status. The primary purpose of this study was to assess the association between the hemoglobin levels and hypertension in relation to the BMI status., Methods: A cross-sectional study of 3,203 non-anemic subjects (1,191 men and 2,012 women, 30-79 years old) who were undergoing general health checkups was conducted., Results: A positive association between the hemoglobin levels and hypertension was established for both men and women. For a one SD (standard deviation) increment in hemoglobin, the multivariable odds ratio (ORs) and 95% confidence interval (CIs) for hypertension were 1.21 (95%CI: 1.05-1.40) for men and 1.25 (95%CI: 1.13-1.39) for women. We also found that a significant association was confined to the participants with a BMI of <25 kg/m(2). Among the participants with a BMI of <25 kg/m(2), the multivariable ORs and 95% CIs for hypertension of a one SD increment in hemoglobin were 1.34 (95%CI: 1.12-1.60) for men and 1.31 (95%CI: 1.16-1.47) for women. Meanwhile, among those with a BMI of ≥25 kg/m(2), the corresponding values were 1.01 (95%CI: 0.79-1.30) and 1.09 (95%CI: 0.87-1.37)., Conclusion: An independent positive association between the hemoglobin levels and the risk of hypertension was observed for both non-anemic Japanese men and women, confined to participants with a BMI of <25 kg/m(2).

Background: Although serum alkaline phosphatase (ALP) levels have been associated with hypertension, and ALP is known as an enzyme affected by alcohol consumption, no study has been published on the associations between ALP and the risk of hypertension in relation to drinking status., Methods: We conducted a cross-sectional study of 2,681 participants (837 men and 1,846 women) aged 30 to 89 years undergoing a general health check-up to investigate the associations between ALP and hypertension in relation to drinking status., Results: Of the 2,681 participants, 1,549 (514 men and 1,035 women) were diagnosed with hypertension. A sex difference was observed for the relationship between ALP and hypertension. While no significant association was observed for men, the association was significantly positive for women. The multivariable adjusted odds ratio and 95% coincidence interval (CI) of hypertension per increment of 1-log ALP were 0.95 (95% CI: 0.56 to 1.59) for men and 1.57 (95% CI: 1.07 to 2.33) for women. When this analysis was restricted to nondrinkers, a significantly elevated risk of hypertension was observed for men and remained significant for women; that is, 3.32 (95% CI: 1.38 to 8.02) for men and 1.68 (95% CI: 1.11 to 2.55) for women., Conclusion: ALP is associated with hypertension for both male and female nondrinkers, but not for drinkers. For analyses of associations between ALP and blood pressure, alcohol consumption should thus be considered a potential confounder.

We investigated the hypothesis that repetitive hyperthermia (RHT) attenuates the progression of cardiac hypertrophy and delays the transition from hypertensive cardiomyopathy to heart failure in Dahl salt-sensitive (DS) hypertensive rats. Six-week-old DS rats were divided into the following five groups: a normal-salt diet (0.4% NaCl) (NS group), a normal-salt diet plus RHT by daily immersion for 10 min in 40°C water (NS+RHT group), a high-salt diet (8% NaCl) (HS group), a high-salt diet (8% NaCl) plus RHT (HS+RHT group), and high-salt diet (8% NaCl) plus RHT with 17-DMAG (HSP90 inhibitor) administration (HS+RHT+17-DMAG group). All rats were killed at 10 wk. Cardiac hypertrophy and fibrosis were noted in the HS group, whereas RHT attenuated salt-induced cardiac hypertrophy, myocardial and perivascular fibrosis, and blood pressure elevation. The phosphorylated endothelial nitric oxide synthase (eNOS) and Akt were decreased in the HS group compared with the NS group, but these changes were not observed in the HS+RHT group. The levels of HSP60, 70, and 90 were elevated by RHT. Moreover, the increased levels of iNOS, nitrotyrosine, Toll-like receptor-4, BNP, PTX3, and TBARS in the HS group were inhibited by RHT. Telomeric DNA length, telomerase activity, and telomere reverse transcriptase (TERT) were reduced in the HS group; however, these changes were partially prevented by hyperthermia. In conclusion, RHT attenuates the development of cardiac hypertrophy and fibrosis and preserves telomerase, TERT activity and the length of telomere DNA in salt-induced hypertensive rats through activation of eNOS and induction of HSPs.

Although the involvement of angiotensin II (Ang II) in insulin resistance and hypertension has been established, the temporal relationships between Ang II receptor activation and changes in insulin sensitivity and blood pressure are not clear. To better understand this issue, we infused rats with Ang II (200 ng kg(-1) min(-1)) or vehicle for 4 weeks and assessed the residual effects after the discontinuation of the infusion on blood pressure, insulin sensitivity and tissue parameters of inflammation. Four weeks after the discontinuation of the Ang II infusion, the blood pressure was higher by 12.8 mm Hg, and insulin sensitivity as determined by a euglycemic hyperinsulinemic glucose clamp was reduced (glucose infusion rate: 11.1±0.7 vs. 17.6±0.5 mg kg(-1) min(-1)) in the Ang II-treated group compared with controls. The persistent hypertension and insulin resistance were associated with greater than two-fold increases in macrophage chemoattractant protein-1, tumor necrosis factor-α and thiobarbituric acid-reactive substrates in the soleus muscle. Furthermore, total and activated forms of Rac-1, a regulatory subunit of the NADPH oxidase complex, were increased by 144±14% and 277±82%, respectively, in the skeletal muscle of Ang II-treated rats. These residual effects after Ang II infusion were all attenuated by the co-administration of tempol, a free radical scavenger, or candesartan with Ang II. The effects of candesartan were not mimicked by hydralazine at an equidepressant dose. These findings suggest that Ang II receptor activation in youth triggers the upregulation of inflammatory cytokines and the production of reactive oxygen species, thereby inducing later insulin resistance and hypertension.

Objective: This study investigated the correlation between the chronological age, telomere length in peripheral blood leukocytes and blood laboratory data of female patients with mild hypertension to identify laboratory data that reflect the biological aging of individuals., Design: Cross-sectional population-based study., Setting: Outpatient clinic of the Department of Cardiovascular, Respiratory, and Geriatric Medicine Kyushu University Hospital at Beppu in Japan., Participants: Outpatients with mild hypertension treated with a low dose of amlodipine., Measurements: The laboratory data of female patients were collected and the telomere length parameters in their peripheral blood leukocytes were determined by Southern blotting. Any correlations between the laboratory data and the telomere length parameters were assessed., Results: The patients showed a positive correlation between the telomere length and the high density lipoprotein, albumin, creatinine, hemoglobin levels, red blood cell counts, and a negative correlation with the globulin level. The extent of subtelomeric methylation of long telomeres tended to correlate negatively with the telomeric attrition. Only the creatinine level correlated with subtelomeric methylation, but not with telomeric length., Conclusion: HDL and the albumin/globulin ratio were potential indicators for individual somatic genomic aging. Creatinine may therefore be a useful indicator for a predisposition for telomeric attrition.

Aim: We investigated the correlation between age, telomere length of peripheral blood leukocytes and blood laboratory data of women with mild hypertension, to identify laboratory data that may reflect the biological aging process of individuals., Methods: The subjects were women with mild hypertension who were being treated with a low dose of amlodipine and who regularly visited the outpatient clinic of the Department of Cardiovascular, Respiratory, and Geriatric Medicine at Kyushu University Hospital. The laboratory data of patients were collected and the telomere length parameters in their peripheral blood leukocytes were determined by Southern blotting. We assessed the laboratory data and the telomere length parameters to determine any correlations., Results: The telomere length of the patients correlated positively with high-density lipoprotein cholesterol, albumin, hemoglobin levels and red blood cell counts, but negatively with globulin levels., Conclusion: Among the analyzed laboratory data, the albumin/globulin rates were the best candidate indicators for individual somatic genomic aging.

Objective: To investigate the mechanism of attenuated pressor responses to several vasoconstrictors during gestation, we sought to characterize the effects of N(G)-monomethyl-L-arginine (L-NMMA) and L-arginine (L-Arg) on the pressor response to the infusion of angiotensin II in rats., Methods: L-NMMA and L-Arg were infused intraperitoneally into rats at a constant rate by means of an osmotic minipump. The L-NMMA group received an infusion of L-NMMA (3 mg/day) daily for 13 days, whereas the L-NMMA plus L-Arg group received L-NMMA (3 mg/day) daily for 4 days, followed by L-NMMA plus L-Arg (12 mg/day) daily for 9 days. Sham-operated rats served as controls. The animals were anesthetized on day 13, and catheters were placed into the femoral artery and vein. After the animals had recovered from anesthesia, the pressor response to intravenous bolus doses of angiotensin II (50, 100, 200, and 400 ng/kg) were determined after recovery from anesthesia., Results: While the baseline mean arterial blood pressure was not affected by L-NMMA, with or without L-Arg, the pressor response to angiotensin II in the L-NMMA group was significantly increased as compared with that in the control group, at doses of 50, 100, and 200 ng/kg. The response of the L-NMMA plus L-Arg group did not differ significantly from that of the control group., Conclusion: Results indicate that the infusion of a nitric oxide synthase inhibitor, at a dose insufficient to produce hypertension, increases the pressor response to angiotensin II., (Copyright 2000 S. Karger AG, Basel)

The rostral ventrolateral medulla (RVLM) is thought to serve as a final common pathway for the integration of central cardiovascular information and to be important for the mediation of central pressor responses. An association between essential hypertension and neurovascular compression of the RVLM has been reported. To confirm this relationship and to quantitatively measure the distances between the RVLM and the neighboring arteries, we performed magnetic resonance imaging using a high-resolution 512x512 matrix and magnetic resonance angiography in 49 subjects (21 patients with essential hypertension, 10 patients with secondary hypertension, and 18 normotensive subjects). One patient with essential hypertension was excluded from the evaluations because of inadequate assessment due to poor images. Neurovascular compression of the RVLM was observed in 15 of 20 (75%) patients with essential hypertension. In contrast, neurovascular compression was observed in only 1 of 10 (10%) patients with secondary hypertension and only 2 of 18 (11%) normotensive subjects. The rate of observed neurovascular compression in the essential hypertension group was significantly higher than that in the secondary hypertension group and the normotensive group (P<.01 for both). The distances between the RVLM and the nearest arteries in the essential hypertension group were significantly shorter than those in the other groups (P<.05 for all). On the other hand, the distances between the surface of the medulla oblongata and the nearest arteries did not differ among these three groups. These results suggest that neurovascular compression of the RVLM, but not of the other regions of the medulla oblongata, is particularly related to essential hypertension.

The rostral ventrolateral medulla (RVLM) has been known to be a major regulating center of sympathetic and cardiovascular activities. An association between essential hypertension and neurovascular compression of the RVLM has been reported in clinical observations, including magnetic resonance imaging (MRI) studies. To reconfirm this relationship, we performed MRI using a high-resolution 512 x 512 matrix in patients with essential and secondary hypertension and in normotensive subjects. The duration of hypertension and the degree of organ damage by hypertension were not significantly different between the two hypertension groups. Neurovascular compression of the RVLM was observed in 74% of the essential hypertension group, and the incidence of compression was significantly higher than in the secondary hypertension group (11%) or in the normotensive group (13%) (P < .01). These results from the clinical studies suggest that neurovascular compression of the RVLM is, at least in part, causally related to essential hypertension. Although blood pressure elevation by pulsatile compression of the RVLM in an experimental baboon model has already been reported, its underlying mechanism is not well known. Accordingly, we performed experiments to investigate whether pulsatile compression of the RVLM would increase arterial pressure and to elucidate the mechanism of the pressor response in rats. Sympathetic nerve activity, arterial pressure, heart rate, and plasma levels of epinephrine and norepinephrine were increased by pulsatile compression of the RVLM. The pressor response was abolished by intravenous treatment with hexamethonium or RVLM injection of kainic acid. In summary, the results from the MRI studies suggest that neurovascular compression of the RVLM is, at least in part, causally related to essential hypertension. This was supported by the results from experimental studies using rats indicating that pulsatile compression of the RVLM increases arterial pressure by enhancing sympathetic outflow.

The effects of MPC-1304, a newly developed 1,4-dihydropyridine derivative, on blood pressure and hypertensive complications in stroke-prone spontaneously hypertensive rats fed a high-salt diet (0.8% NaCl), were investigated. The antihypertensive effectiveness of nicardipine was used for the purpose of comparison. MPC-1304 and nicardipine were added to the diet, in doses of 0.01% (0.01% MPC-1304 diet), 0.03% (0.03% MPC-1304 diet) and 0.1% (0.1% nicardipine diet), respectively, throughout the experimental period (8 to 30 weeks of age). This chronic ingestion of MPC-1304 and nicardipine inhibited the development of hypertension and reduced the concentration of blood urea nitrogen, creatinine, triglyceride and total cholesterol in serum. Treatment with MPC-1304 inhibited the incidence of cerebral stroke, cardiac fibrosis, proliferative and fibrinoid arteriolitis and malignant nephrosclerosis. There was no significant difference in the antihypertensive effectiveness between 0.01% MPC-1304 and 0.1% nicardipine diets. Thus, MPC-1304 had antihypertensive effects in stroke-prone spontaneously hypertensive rats.

Sex histories and serum samples were obtained from 27 hypertensive men before and after 3 months of therapy with either 100 mg of hydrochlorothiazide or 0.25 mg of reserpine daily. Sera were analyzed for testosterone, dihydrotestosterone, estradiol, luteinizing hormone and prolactin. Both drugs effectively lowered pressure. The incidence of impaired sexual performance was low and insignificantly different in the two treatment groups. There were no significant changes in serum hormone concentrations as a result of drug therapy.