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Background Elevated left atrial (LA) pressure predisposes individuals to the initiation and persistence of atrial fibrillation (AF), and LA hypertension is associated with AF recurrence after catheter ablation (CA). However, the exact frequency and factors associated with LA hypertension are unknown, and its noninvasive estimation is challenging. This study aimed to investigate the prevalence and determinants of LA hypertension in patients with AF who underwent first CA. Methods and Results We examined 183 patients with AF who underwent conventional and speckle-tracking echocardiography before CA to assess LA size, reservoir strain, and stiffness. Direct LA pressure was measured at the time of CA, and LA hypertension was defined as mean LA pressure >15 mm Hg. Thirty-three (18.0%) patients exhibited LA hypertension. Patients with LA hypertension had a significantly larger LA volume index (40.2 [28.4-52.1] versus 34.1 [26.9-42.4] mL/m 2 , P =0.025), reduced LA reservoir strain (15.1 [10.4-21.7] versus 22.7 [14.4-32.3] %, P =0.002) and increased LA stiffness (0.69 [0.34-0.99] versus 0.36 [0.24-0.54], P <0.001). Multivariable analyses showed that waist circumference, C-reactive protein level, LA reservoir strain, and LA stiffness were independently associated with LA hypertension (all P <0.05), while LA volume and E/e' ratio were not. Among echocardiographic parameters, receiver operating characteristic curve analysis identified LA stiffness as the best predictor of LA hypertension. Conclusions Approximately 20% of patients with AF who underwent CA had LA hypertension. Central obesity and inflammation might be involved in the pathophysiological mechanisms of LA hypertension, and echocardiography-derived LA stiffness may have clinical utility for the detection of LA hypertension before CA.

Primary aldosteronism (PA) is the most common cause of endocrine hypertension. Unilateral PA can be cured using unilateral adrenalectomy (Adx). PA surgery outcome (PASO) criteria, which include clinical and biochemical outcomes, have been proposed to evaluate PA cure after Adx. However, clinical outcomes are often inconsistent with biochemical outcomes. In addition, although confirmatory tests are included as endpoints of biochemical outcomes in the PASO criteria, their clinical usefulness has not yet been established. We evaluated clinical parameters and confirmatory test results before and after Adx in 16 patients with PA and assessed the usefulness of the confirmatory tests. The following were the clinical outcomes after Adx: 37.5% complete success, 62.5% partial success, and 0% absent success. The ratio of biochemical complete success was as follows: 69% aldosterone/renin ratio and basal plasma aldosterone concentration, 19% as assessed by the captopril challenge test, 47% as assessed by the saline infusion test, 30% as assessed by the furosemide upright test, and 100% urine aldosterone. Of these, biochemical complete success was judged in four cases by aldosterone/renin ratio and basal plasma aldosterone concentration, one case by captopril challenge test, five cases by saline infusion test, and one case by furosemide upright test. Although clinical outcomes and urine aldosterone levels improved after Adx, confirmatory tests failed to improve in some cases. The current criteria are not considered useful for biochemical evaluation after Adx. To determine whether additional treatment with mineralocorticoid receptor antagonists is required, more accurate biochemical criteria should be established after Adx., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2023 Shingo Murasawa et al.)

Aims: The impact of blood pressure (BP) levels on subclinical left ventricular (LV) dysfunction and possible sex-specific difference remains unclarified. This study investigated the relationship between BP categories given in the new 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline and subclinical LV dysfunction in subjects free of cardiac disease., Methods and Results: We examined antihypertensive medication-naive 858 individuals who underwent extensive cardiovascular health check-up. LV global longitudinal (LVGLS) and circumferential strain (LVGCS) were assessed by two-dimensional speckle-tracking echocardiography. Participants were categorized into four groups: normal BP, elevated BP, isolated diastolic hypertension (IDH), and systolic hypertension (SH). Among the 858 participants, 422 individuals had normal BP, 113 had elevated BP, 160 had IDH, and 163 had SH. Prevalence of abnormal LVGLS (>-18.6%) was greatest in SH (19.0%), followed by IDH (17.5%), elevated BP (14.2%), and normal BP (7.1%, P < 0.001); no significant differences were observed for LVGCS (P = 0.671). In the multivariable analyses, IDH and SH were associated with impaired LVGLS [adjusted odds ratio (OR) 2.69 and 2.66, P < 0.001], and borderline significance was observed for elevated BP (adjusted OR 1.90, P = 0.060); there was no significant association between any of the BP groups and LVGCS. In sex-stratified analysis, IDH and SH carried the significant risk of abnormal LVGLS in both sexes, while elevated BP was associated with LVGLS only in women., Conclusions: Isolated diastolic hypertension and SH redefined by ACC/AHA guideline carried significant risk for LVGLS, but not LVGCS. Elevated BP was associated with LVGLS only in women. Our findings provide information on cardiac correlates of the newly established BP categories., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

The association between changes in body weight and blood pressure (BP) in overweight people in the general population still remains unclear. We sought to clarify the effect of body weight change on BP using a community-based cohort. We studied 1,170 overweight subjects with a body mass index (BMI) ≥ 22 kg/m 2 who underwent health check-ups. Among the study subjects, 175 (15%) were categorized in the weight loss group (weight loss ≥ 5%), 869 (74%) in the weight stable group, and 126 (11%) in the weight gain group (weight gain ≥ 5%). There were no significant differences in baseline BP between the 3 groups. In the weight loss group, systolic and diastolic BP, and the rates of stage 2 (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) and stage 1 hypertension (130 mmHg≤ systolic BP < 140 mmHg or 80 mmHg≤ diastolic BP < 90 mmHg) decreased. In contrast, in the weight gain group, systolic and diastolic BP and the rate of stage 2 hypertension increased. Subgroup analysis showed that the correlation between change in body weight and BP was seen in each subgroup according to age, sex, and BMI. The results of the present study suggest the significance of body weight control for BP control in subjects with BMI ≥ 22 kg/m 2 .

American College of Cardiology/American Heart Association recently updated their guidelines for hypertension, and lowered the threshold of normal blood pressure (BP). However, the validity of the updated guidelines remains controversial. We investigated the relation between the revised BP classification and carotid intima-media thickness, using a community-based cohort. We examined 1,241 subjects who underwent health check-ups at our institute. They were divided into 3 groups based on their BP levels: normal blood pressure (sBP <130 mm Hg and dBP <80 mm Hg, n = 556); stage 1 hypertension (130 mm Hg ≤sBP <140 mm Hg or 80 mm Hg ≤ dBP <90 mm Hg, n = 236); and stage 2 hypertension (sBP ≥140 mm Hg or dBP ≥90 mm Hg, including subjects prescribed with antihypertensive medications, n = 449). With an increase in BP, increase in the mean age, proportion of males, and prevalence of CVD risk factors was seen. The prevalence of carotid plaque, defined as intima-media thickness ≥1.1 mm, also increased with increase in BP. After adjustment with covariates, higher BP was seen to be associated with carotid plaque presence. Atherosclerotic changes are present in stage 1 hypertension even in the healthy population, suggesting the importance of aggressive antihypertensive treatment based on the updated American College of Cardiology/American Heart Association guidelines., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Context: The hypothalamus-pituitary-adrenal (HPA) axis and the renin-angiotensin aldosterone system (RAAS) are well known to be associated with hypertension. However, the extent of the effects is not yet well elucidated in general conditions., Objective: To separately determine the effect of the HPA axis and the RAAS on hypertension in a general population., Design, Setting, and Participants: A population-based study of 859 Japanese individuals enrolled in the 2014 Iwaki study and without hypertension or steroid treatment (age, 50.2 ± 14.7 years)., Main Outcome Measures: Hypertension prevalence, plasma concentration of aldosterone, ACTH, cortisol, and plasma renin activity., Results: Principal component (PC) analysis using these four hormones identified two PCs (PC1 and PC2), which represent levels of these hormones as a whole, and dominance between the HPA axis (ACTH and cortisol) and the RAAS (plasma renin activity and plasma concentration of aldosterone), respectively. Association between these PCs and hypertension was significant (PC1, high vs low, odds ratio [OR], 1.48; 95% confidence interval [CI], 1.09-2.02; and PC2, HPA axis vs RAAS dominancy, OR, 2.08; and 95% CI, 1.51-2.85). However, association between the hormone levels as a whole and hypertension became insignificant after adjustment for multiple factors including these PCs together. However, association between the HPA axis dominance and hypertension remained significant even after the adjustment (the HPA axis vs the RAAS, OR, 1.73; 95% CI, 1.20-2.48)., Conclusions: The HPA axis dominance over the RAAS is significantly associated with hypertension in a Japanese population.

Background: Physical examination as an initial screening tool to diagnose abdominal aortic aneurysm (AAA) has lost favor over the past 20 years. This multicenter cohort study aimed to determine the prevalence of AAA in elderly Japanese patients with hypertension (HT) and to clarify the diagnostic accuracy of physical examination using a pocket-sized ultrasound imaging device (the "pocket-echo"). METHODS AND RESULTS: A total of 1,731 patients with HT aged >60 years from 20 collaborating institutions were enrolled in this study. Abdominal palpation was performed on physical examination, and the pocket-echo was used to confirm the diagnosis of AAA. The abdominal aorta was well visualized in 1,692 patients (98%). AAA was discovered in 69 patients (4.1%), with advanced age and male sex identified as independent risk factors. The prevalence of AAA increased according to age regardless of sex, and reached 9.2% and 5.7%, respectively, in males and females ≥80 years. Overall, 33 cases of AAA were missed on abdominal palpation (sensitivity, 52%), whereas for AAAs >40 mm, the sensitivity was 75%., Conclusions: We assessed the utility of the pocket-echo and physical examination for diagnosing AAA in Japanese patients with HT aged over 60 years. Our findings highlight the importance of AAA screening programs in high-risk Japanese populations, and confirm the ability of physical examination to detect large, but not small, AAAs.

The objective of the present study was to review previous investigations on the association of haplotypes in the G-protein β3 subunit (GNB3) gene with representative cardiovascular risk factors/phenotypes: hypertension, overweight, and variation in the systolic and diastolic blood pressures (SBP and DBP, respectively) and as well as body mass index (BMI). A comprehensive literature search was undertaken in Pubmed, Web of Science, EMBASE, Biological Abstracts, LILACS and Google Scholar to identify potentially relevant articles published up to April 2011. Six genetic association studies encompassing 16,068 participants were identified. Individual participant data were obtained for all studies. The three most investigated GNB3 polymorphisms (G-350A, C825T and C1429T) were considered. Expectation-maximization and generalized linear models were employed to estimate haplotypic effects from data with uncertain phase while adjusting for covariates. Study-specific results were combined through a random-effects multivariate meta-analysis. After carefully adjustments for relevant confounding factors, our analysis failed to support a role for GNB3 haplotypes in any of the investigated phenotypes. Sensitivity analyses excluding studies violating Hardy-Weinberg expectations, considering gender-specific effects or more extreme phenotypes (e.g. obesity only) as well as a fixed-effects "pooled" analysis also did not disclose a significant influence of GNB3 haplotypes on cardiovascular phenotypes. We conclude that the previous cumulative evidence does not support the proposal that haplotypes formed by common GNB3 polymorphisms might contribute either to the development of hypertension and obesity, or to the variation in the SBP, DBP and BMI.

To facilitate personalized health care for multifactorial diseases, risks of genetic and clinical/environmental factors should be assessed together for each individual in an integrated fashion. This approach is possible with the likelihood ratio (LR)-based risk assessment system, as this system can incorporate manifold tests. We examined the usefulness of this system for assessing type 2 diabetes (T2D). Our system employed 29 genetic susceptibility variants, body mass index (BMI), and hypertension as risk factors whose LRs can be estimated from openly available T2D association data for the Japanese population. The pretest probability was set at a sex- and age-appropriate population average of diabetes prevalence. The classification performance of our LR-based risk assessment was compared to that of a non-invasive screening test for diabetes called TOPICS (with score based on age, sex, family history, smoking, BMI, and hypertension) using receiver operating characteristic analysis with a community cohort (n = 1263). The area under the receiver operating characteristic curve (AUC) for the LR-based assessment and TOPICS was 0.707 (95% CI 0.665-0.750) and 0.719 (0.675-0.762), respectively. These AUCs were much higher than that of a genetic risk score constructed using the same genetic susceptibility variants, 0.624 (0.574-0.674). The use of ethnically matched LRs is necessary for proper personal risk assessment. In conclusion, although LR-based integrated risk assessment for T2D still requires additional tests that evaluate other factors, such as risks involved in missing heritability, our results indicate the potential usability of LR-based assessment system and stress the importance of stratified epidemiological investigations in personalized medicine.

Association of the C825T G-protein β3 subunit (GNB3) gene polymorphism with cardiovascular disease (CVD) incidence was examined in a population-based longitudinal study of the Japanese individuals. The incidence of CVD (stroke and coronary heart disease (CHD)) was assessed in a cohort population (n=1524) consisting of participants of the 2001-2005 Funagata study through March 2008. Cumulative incidences according to genotype were compared with the Kaplan-Meier product-limit method. During the follow-up, 78 subjects experienced a CVD event (stroke: n=54; CHD: n=30; both consecutively: n=6). At the end of the follow-up (longest and median follow-up periods: 81 and 68 months, respectively), the cumulative incidence of CVD for the TT genotype was significantly higher than that of the C-carriers (0.077 vs 0.042, P=0.004). Blood pressures and the prevalence of hypertension were not different between the genotypes. Cox's proportional hazard analysis showed that the TT genotype is a significant risk factor for CVD (hazard ratio (HR)=1.82 (95% confidence interval (CI) 1.14-2.89); P=0.012) and stroke (HR=1.76 (95% CI: 1.01-3.07); P=0.048) incidences after adjustment for age, sex, hypertension, hyperlipidemia, diabetes, alcohol drinking and smoking at baseline. The TT genotype of the C825T GNB3 gene polymorphism was found to be a significant risk factor for the incidence of CVD and stroke independent of hypertension and other established CVD risk factors in a Japanese population.

We evaluated the effectiveness of a home telehealth service in hypertension control. Patients with hypertension were divided into two groups based on the frequency that they measured blood pressure (BP) at home: the regular group made >3 measurements per week and the irregular group made ≤ 20 measurements per month. Both groups were provided with home monitoring equipment (the Citizen Telemedical Care Service System, CTCS) which contained a computer and video communication device. A total of 160 participants were enrolled and 156 completed the 12-month study. There were 101 participants in the regular BP measurement group and 55 in the irregular group. There was a significant reduction in the average systolic BP from baseline after 6 months in the regular group (P < 0.001) and after 1 month in the irregular group (P < 0.001). There was no difference in average diastolic BP between the two groups. For both groups, the systolic BP control was good, especially for irregular group. The results suggest that patients who used CTCS tele-monitoring achieved better BP control than those who self-measured BP at home only.

Objective: To determine whether retinal arteriolar narrowing, possibly reflecting peripheral arteriolar vasoconstriction, predicts risk of hypertension in Japanese persons., Methods: The Funagata study is a population-based cohort study of Japanese aged 35+ years. Baseline examinations were conducted in 2000-2002 among 1058 persons without hypertension. Of these, 581 persons (55%) returned for a 5-year follow-up examination, with data on 563 available for analyses. Retinal photographs taken at the baseline visits were assessed for retinal arteriolar or venular diameter and retinal vessel wall signs using standardized protocols. Hypertension was defined if systolic blood pressure > or =140 mmHg, diastolic blood pressure > or =90 mmHg or from self-reported clinical diagnosis, including the use of antihypertensive medications. Incident hypertension was defined as an absence of hypertension at baseline but presence of hypertension at the follow-up visit., Results: One hundred ninety-three subjects (34.3%) had developed hypertension at 5-year follow-up. After adjusting for age, gender, baseline blood pressure and other risk factors, narrower retinal arterioles at baseline was significantly associated with an increased risk of incident hypertension (odds ratio per standard deviation decrease in arteriolar diameter: 1.53, 95% confidence interval: 1.08-2.18)., Conclusions: Our findings support the concept that arteriolar narrowing, evident in the retina, signals an increased risk of developing hypertension in Japanese persons.

The purpose of this study is to determine whether the angiotensin-converting enzyme (ACE) gene polymorphism is associated with retinal arteriolar narrowing, a subclinical marker of chronic hypertension. The Funagata Study examined a population-based sample of Japanese aged 35+ years; 368 participants had both retinal vessel diameter measurements and ACE insertion/deletion (ACE I/D) polymorphism analyses performed. Assessment of retinal vessel diameter and retinal vessel wall signs followed the protocols used in the Blue Mountains Eye Study. ACE gene polymorphisms D/D, I/D and I/I were present in 34 (9.2%), 170 (46.2%) and 164 (44.5%) participants, respectively, distributed in Hardy-Weinberg equilibrium. After multivariable adjustment, retinal arteriolar diameter was significantly narrower in subjects with the D/D genotype compared to subjects with I/D and I/I genotypes (mean difference -6.49 microm, 95% confidence interval (CI): -12.86 microm, -0.11 microm). Our study suggests that the ACE I/D polymorphism may be associated with subclinical structural arteriolar changes related to chronic hypertension.

Antihypertensive therapy has been well established to reduce hypertension related morbidity and mortality, but the optimal therapy for Japanese patients remains unknown. The Valsartan Amlodipine Randomized Trial (VART), a prospective randomized open-label trial, was designed to determine whether treatment with an angiotensin II type 1 receptor blocker (valsartan) or a calcium channel blocker (amlodipine) lowers cardiovascular disease events in essential hypertensives in Japan. Registration, randomization and data entry were performed over the Internet. The minimization method (to control for age, gender, blood pressure level and history) was used at random assignment to ensure that the background factors were equivalent between the groups at baseline. After the registration, patients were followed-up for cardiovascular events (primary endpoints), echocardiography, (123)I-metaiodobenzylguanidine (MIBG) imaging, laboratory tests and blood pressure for 3 years. Currently, 797 patients have been enrolled and assigned to two groups: a valsartan (n=399) and an amlodipine (n=398) group. At baseline, controlled factors (age, gender, blood pressure level, and left ventricular hypertrophy) and the proportions of patients with diabetes and hyperlipidemia were equally allocated. At 12 months, both drugs evenly and significantly lowered blood pressure to the target level (valsartan: 133/79 mmHg; amlodipine: 132/79 mmHg). In conclusion, by combining the data on cardiovascular events with the results of echocardiographic, radionuclide imaging, and blood/urine studies, the VART study will provide mechanistic insights into the clinical outcomes and treatment effects of the trial.