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Abstract: Objective: Several studies have shown that periodontitis is a risk factor for cardiovascular diseases. There is an association between inflammation and endothelial dysfunction. The purpose of this study was to evaluate endothelial function in patients with coronary artery disease (CAD) who had periodontitis. Methods and results: We evaluated forearm blood flow (FBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and to sodium nitroprusside (SNP), an endothelium-independent vasodilator, in 101 CAD patients with periodontitis (37 men and 11 women, 63±12 yr) and without periodontitis (36 men and 17 women, 62±13 yr). FBF was measured by using strain-gauge plethysmography. Circulating levels of C-reactive protein and interleukin-6 were significantly higher in the periodontitis group than in the non-periodontitis group. FBF response to ACh was significantly smaller in the periodontitis group than in the non-periodontitis group. SNP-stimulated vasodilation was similar in the two groups. Periodontal therapy reduced serum concentrations of C-reactive protein from 2.7±1.9 to 1.8±0.9mg/L (P <0.05) and interleukin-6 from 2.6±3.4 to 1.6±2.6ng/L (P <0.05) and augmented ACh-induced vasodilation from 14.7±5.2 to 20.1±6.1mL/(min100mL) tissue (P <0.05) in patients with periodontitis. The SNP-stimulated vasodilation was similar before and after treatment. After administration of NG-monomethyl-l-arginine, a nitric oxide synthase inhibitor, FBF response to ACh was similar before and after treatment. Conclusion: These findings suggest that periodontitis is associated with endothelial dysfunction in patients with CAD through a decrease in nitric oxide bioavailability. Systemic inflammation may be, at least in part, a cause and predictor of progression of endothelial dysfunction. [Copyright &y& Elsevier]

The development of a comprehensive assessment tool based on the International Classification of Functioning, Disability, and Health (ICF) for elderly patients with heart failure is urgently required. In this study, we classified the ICF categories relevant to heart failure in the elderly through a Delphi survey (3-step questionnaire survey) of 108 Registered Instructors of Cardiac Rehabilitation in the Hiroshima Prefecture. Questionnaires were conducted using postal mail or a web-based platform. The survey was conducted three times, and the survey results were provided as feedback to the participants in the second and third rounds. More than 80% of the respondents selected categories according to the ICF core set methodology. Data were collected from December 2018 to March 2019, with 67, 54, and 46 participants in the first, second, and third rounds, respectively. A total of 58 ICF items were adopted based on the results: 27 body function items, 4 body structure items, 20 activity and participation items, and 7 environmental factor items. This study is characterised by the inclusion of a large number of ICF items for mental function. This result seems to be influenced by the increasing interest in cognitive dysfunction in elderly patients with heart failure. The ICF categories selected for this study allow for a comprehensive assessment of clients for occupational therapy. The findings of this study are expected to provide a basis for an outcome measure to determine the effectiveness of occupational therapy for these patients. [ABSTRACT FROM AUTHOR]

Coronary flow reserve (CFR) reflects the functional capacity of microcirculation to adapt to blood demand during increased cardiac work. We tested the hypothesis that aging had impacts on coronary flow velocities and CFR in patients with no evidence of myocardial perfusion abnormality on single photon emission computed tomography (SPECT). Seventy-six patients undergoing transthoracic Doppler echocardiography with no evidence of myocardial perfusion abnormality on SPECT were enrolled in this study. CFR was defined as the ratio of hyperemic to resting peak diastolic coronary flow velocity. Patients were divided into the three groups based on age: 17 patients aged less than 70 years (Group I), 38 patients aged 70–79 years (Group II), and 21 patients aged 80 years or more (Group III). Compared with Group I, CFR was significantly lower in Group II (p < 0.01) and Group III (p < 0.01). Multivariate linear regression analysis showed that female (β = − 0.26, p = 0.03), cigarette smoking (β = − 0.32, p = 0.004), hemoglobin level (β = − 0.40, p = 0.001) and LV mass index (β = 0.24, p = 0.03) were determinants for resting coronary flow velocity. On the other hand, age (β = -0.30, p = 0.008), hemoglobin level (β = -0.47, p < 0.001) and LV mass index (β = 0.24, p = 0.04) were determinants for hyperemic coronary flow velocity. Age was only determinant for CFR (β = -0.48, p < 0.001). Our data suggested that that aging had a decreased effect on hyperemic coronary flow velocity rather than resting coronary flow velocity, and was further associated with impaired CFR in patients with no evidence of myocardial perfusion abnormality. [ABSTRACT FROM AUTHOR]

The dipeptidyl peptidase-4 inhibitor saxagliptin is a widely used antihyperglycemic agent in patients with type 2 diabetes. The purpose of this study was to evaluate the effects of saxagliptin on endothelial function in patients with type 2 diabetes. This was a prospective, multicenter, interventional study. A total of 34 patients with type 2 diabetes were enrolled at four university hospitals in Japan. Treatment of patients was initially started with saxagliptin at a dose of 5 mg daily. Assessment of endothelial function assessed by flow-mediated vasodilation (FMD) and measurement of stromal cell-derived factor-1α (SDF-1α) were conducted at baseline and at 3 months after treatment with saxagliptin. A total of 31 patients with type 2 diabetes were included in the analysis. Saxagliptin significantly increased FMD from 3.1 ± 3.1% to 4.2 ± 2.4% (P = 0.032) and significantly decreased total cholesterol from 190 ± 24 mg/dL to 181 ± 25 mg/dL (P = 0.002), glucose from 160 ± 53 mg/dL to 133 ± 25 mg/dL (P < 0.001), HbA1c from 7.5 ± 0.6% to 7.0 ± 0.6% (P < 0.001), urine albumin-to-creatinine ratio from 63.8 ± 134.2 mg/g to 40.9 ± 83.0 mg/g (P = 0.043), and total SDF-1α from 2108 ± 243 pg/mL to 1284 ± 345 pg/mL (P < 0.001). These findings suggest that saxagliptin is effective for improving endothelial function. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate acute effects of coffee with a high content of chlorogenic acids and different hydroxyhydroquinone contents on postprandial endothelial dysfunction. Methods: This was a single-blind, randomized, placebo-controlled, crossover-within-subject clinical trial. A total of 37 patients with borderline or stage 1 hypertension were randomized to two study groups. The participants consumed a test meal with a single intake of the test coffee. Subjects in the Study 1 group were randomized to single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone or coffee with a high content of chlorogenic acids and a high content of hydroxyhydroquinone with crossover. Subjects in the Study 2 group were randomized to single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone or placebo coffee with crossover. Endothelial function assessed by flow-mediated vasodilation and plasma concentration of 8-isoprostanes were measured at baseline and at 1 and 2 h after coffee intake. Results: Compared with baseline values, single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone, but not coffee with a high content of chlorogenic acids and high content of hydroxyhydroquinone or placebo coffee, significantly improved postprandial flow-mediated vasodilation and decreased circulating 8-isoprostane levels. Conclusions: These findings suggest that a single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone is effective for improving postprandial endothelial dysfunction. Clinical Trial Registration: URL for Clinical Trial: https://upload.umin.ac.jp; Registration Number for Clinical Trial: UMIN000013283. [ABSTRACT FROM AUTHOR]

Backgrounds Nitroglycerine-induced vasodilation (NID) is usually assessed as a control test for flow-mediated vasodilation (FMD). However, NID per se is impaired in patients with high cardiovascular risk. The purpose of this study was to investigate the associations of chronic kidney disease (CKD) with NID and FMD. Methods We measured NID and FMD in a total of 1567 adult subjects without end-stage renal disease (ESRD), 28% of whom had CKD as judged by measurements of estimated glomerular filtration rate (995 men and 572 women; mean age, 59.0 ± 16.9 years; age range, 18 to 92 years). Results NID was significantly smaller in patients with CKD than in those without CKD (10.8 ± 6.0% vs. 12.7 ± 5.7%, P < 0.001). The prevalence of vascular smooth muscle dysfunction, defined as NID of less than the division point for the lowest quartile, was significantly higher in patients with CKD than in those without CKD (37.5% vs. 21.5%, P < 0.001). Multivariate analysis revealed that CKD was independently associated with vascular smooth muscle dysfunction (OR: 1.36, 95% CI: 1.02 to 1.81, P = 0.04). FMD was significantly smaller in patients with CKD than in those without CKD (3.1 ± 2.8% vs. 4.0 ± 3.0%, P < 0.001). The prevalence of endothelial dysfunction, defined as FMD of less than the division point for the lowest quartile, was significantly higher in patients with CKD than in those without CKD (31.7% vs. 23.1%, P = 0.002). However, CKD was not independently associated with endothelial dysfunction in an age- and sex-adjusted model (OR: 0.95, 95% CI: 0.71 to 1.26, P = 0.72). Conclusions Non-ESRD CKD is independently associated with vascular smooth muscle dysfunction but not with endothelial dysfunction. [ABSTRACT FROM AUTHOR]

Background: Patients with heart failure (HF) are reportedly at high risk for ‘all-cause’ re-hospitalization. A biomarker for HF, N-terminal pro-brain natriuretic peptide (NT-proBNP), enables to simply detect patients with possible HF (pHF). We examined the hospitalization and medical cost of Japanese patients detected by an elevated serum NT-proBNP, and also evaluated the effects of institutional team approaches for HF on their all-cause hospitalizations. Methods: We retrospectively extracted all adult patients with serum NT-proBNP ≥400 pg/ml measured between January and March 2012 in Hiroshima University Hospital as pHF-positive patients. We studied their all-cause hospitalization records during the past 3-year period. We also extracted all pHF-negative patients with NT-proBNP <400 pg/ml and studied as well. In the pHF-positive patients followed for 3 years after starting interprofessional team approaches to prevent the onset and exacerbation of HF in the hospital, we compared the hospitalization and medical cost between the 3-year periods before and after the start of the team approaches. Results: We enrolled 432 pHF-positive and 485 pHF-negative patients with one or more hospitalization records. Compared to the pHF-negative patients, the pHF-positive patients had longer total hospitalization days (median [interquartile range], 30 [13–58] versus. 18 [8–39], p <0.0001) and higher total medical cost for hospitalizations (2.42 [1.07–5.08] versus. 1.80 [0.79–3.65] million yen, p <0.0001). A subset of 303 pHF-positive patients was followed for 3 years after starting the team approaches, and we found that both total hospitalization days (30 [13–57] to 8 [0–31]) and medical cost for hospitalizations (2.59 [1.37–5.05] to 0.76 [0–2.38] million yen) showed marked reduction in them. Conclusions: Patients with an elevated serum NT-proBNP have longer hospitalizations and higher costs for all-cause hospitalizations than those without. Institutional team approaches for HF may reduce them. [ABSTRACT FROM AUTHOR]

Background and aims Baseline brachial artery (BBA) diameter has been reported to be a potential confounding factor of flow-mediated vasodilation (FMD). The purpose of this study was to evaluate the relationships between BBA diameter and cardiovascular risk factors and compare the diagnostic accuracy of BBA diameter in subjects without cardiovascular risk factors and patients with cardiovascular disease (CVD) with that of FMD. Methods We measured BBA diameter and FMD in 5695 male subjects. In addition, we retrospectively investigated the incidence of cardiovascular events using another population sample consisting of 440 male subjects, to compare the accuracy of BBA diameter with that of FMD in predicting cardiovascular events. Results BBA diameter and FMD significantly correlated with age, body mass index, systolic blood pressure, diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol, and glucose as well as Framingham risk score. The prevalence of cardiovascular risk factors and CVD increased with the increase in BBA diameter and FMD. Area under the curve (AUC) value of the receiver operating characteristic (ROC) curve for BBA diameter to diagnose subjects without cardiovascular risk factors (0.59 vs. 0.62, p = 0.001) or patients with CVD (0.58 vs. 0.64, p < 0.001) was significantly lower than that for FMD. In the retrospective study, the AUC value of the ROC curve for BBA diameter to predict first major cardiovascular events was significantly lower than that of FMD (0.50 vs. 0.62, p = 0.03). Conclusions In men, BBA diameter was inferior to FMD for assessment of cardiovascular risk. [ABSTRACT FROM AUTHOR]

Cardiopulmonary exercise testing (CPET) is useful for the evaluation of patients with suspected or confirmed pulmonary hypertension (PH). End-tidal carbon dioxide pressure (PETCO) during exercise is reduced with elevated pulmonary artery pressure. However, the utility of ventilatory parameters such as CPET for detecting PH remains unclear. We conducted a review in 155 patients who underwent right heart catheterization and CPET. Fifty-nine patients had PH [mean pulmonary arterial pressure (mPAP) ≥25 mmHg]. There was an inverse correlation between PETCO at the anaerobic threshold (AT) and mPAP ( r = −0.66; P < 0.01). Multiple regression analysis showed that PETCO at the AT was independently associated with an elevated mPAP ( P = 0.04). The sensitivity and specificity of CPET for PH were 80 and 86%, respectively, when the cut-off value identified by receiver operating characteristic curve analysis for PETCO at the AT was ≤34.7 mmHg. A combination of echocardiography and CPET improved the sensitivity in detecting PH without markedly reducing specificity (sensitivity 87%, specificity 85%). Evaluation of PETCO at the AT is useful for estimating pulmonary pressure. A combination of CPET and previous screening algorithms for PH may enhance the diagnostic ability of PH. [ABSTRACT FROM AUTHOR]

Background Periodontal disease is associated with endothelial dysfunction, leading to cardiovascular disease. The effect of detailed tooth brushing behavior, not only frequency but also duration of tooth brushing, on endothelial function is unclear. The purpose of this study was to evaluate the relationships of detailed methods of tooth brushing with vascular function. Methods We evaluated flow-mediated vasodilation (FMD), nitroglycerine-induced vasodilation, and frequency and duration of tooth brushing in 896 subjects. We divided the subjects into three groups according to the frequency and duration of tooth brushing: low frequency and short duration group (< twice/day and < 2 min/procedure), low frequency or short duration group (< twice/day or < 2 min/procedure), non-low frequency and non-short duration group (≥ twice/day and ≥ 2 min/procedure). Results FMD in the low frequency and short duration group was significantly lower than FMD in the low frequency or short duration group and FMD in the non-low frequency and non-short duration group [3.1 (2.7)% vs. 4.2 (3.1)% and 4.7 (3.1)%, P = 0.001 and < 0.001, respectively]. Nitroglycerine-induced vasodilation was similar in the three groups. Using the non-low frequency and non-short duration group as the reference, the low frequency and short duration of tooth brushing group was significantly associated with an increased odds ratio of a low FMD tertile after adjustment for conventional risk factors (OR: 2.25, 95% CI: 1.39–3.59; P < 0.001). Conclusions These findings suggest that low frequency and short duration of tooth brushing are associated with endothelial dysfunction. Clinical trial registration information : URL for clinical trial: http://UMIN ; registration number for clinical trial: UMIN000003409. [ABSTRACT FROM AUTHOR]

Background Endothelial dysfunction and abnormal vascular structure may be involved in the pathogenesis of chronic heart failure (HF). The purpose of this study was to evaluate simultaneously vascular function and vascular structure in patients with heart failure with preserved ejection fraction (HFpEF). Methods We measured flow-mediated vasodilatation (FMD) and nitroglycerine-induced vasodilation as indices of vascular function and intima-media thickness (IMT) as an index of vascular structure of the brachial artery in 41 patients with HFpEF (23 men and 18 women; mean age, 66 ± 12 yr) and 165 patients without HF (95 men and 70 women; mean age, 54 ± 16 yr). Results FMD was significantly smaller in patients with HFpEF than in patients without HF (2.9 ± 2.1% versus 4.6 ± 2.7%, P = 0.0002). Nitroglycerine-induced vasodilation was significantly smaller in patients with HFpEF than in patients without HF (9.3 ± 4.1% versus 12.9 ± 4.9%, P < 0.0001). Brachial artery IMT was significantly larger in patients with HFpEF than in patients without HF (0.35 ± 0.06 mm versus 0.31 ± 0.07 mm, P = 0.0002). After adjustment for age, sex, hypertension, dyslipidemia, and diabetes mellitus, the associations remained significant between HFpEF and FMD (odds ratio, 0.79; 95% confidence interval, 0.66–0.92; P = 0.0032), nitroglycerine-induced vasodilation (odds ratio, 0.88; 95% confidence interval, 0.80–0.96; P = 0.0039), and brachial artery IMT (odds ratio, 1.08; 95% confidence interval, 1.01–1.17; P = 0.033). Conclusions These findings suggest that both endothelial dysfunction and abnormal vascular structure may contribute to the pathogenesis and maintenance of HFpEF. Endothelial function and vascular structure may be potential therapeutic targets for HFpEF. [ABSTRACT FROM AUTHOR]

Background Heavy drinking should be a predictor of endothelial dysfunction. However, there is little information on the effects of light to moderate alcohol consumption on endothelial function. The purpose of this study was to estimate the effects of dose-dependent alcohol consumption on endothelial function. Methods We measured flow-mediated vasodilation (FMD) in 2734 men aged 21–81 years who provided information on alcohol intake at 3 general hospitals. The subjects were divided into 5 groups; non-drinkers (0 g/week), light drinkers (> 0 to 140 g/week), moderate drinkers (> 140 to 280 g/week), heavy drinkers (> 280 to 420 g/week), and excessive heavy drinkers (> 420 g/week). Results FMD showed a gradual decrease in accordance with alcohol consumption in the entire study population (non-drinkers, 6.6 ± 3.4%; light drinkers, 6.2 ± 3.0%; moderate drinkers, 6.0 ± 3.0%; heavy drinkers, 5.5 ± 2.9%; excessive heavy drinkers, 5.3 ± 3.0%; P < 0.001). There was a significant difference in FMD between the light alcohol drinker group and the non-drinker group ( P = 0.015). After adjustment for other risk factors, the odds of having FMD in the lowest quartile was found to be significantly increased in the 4 drinker groups than in the non-drinker group: light (OR, 1.38; 95% CI, 1.10 to 1.75), moderate (OR, 1.36; 95% CI, 1.01 to 1.82), heavy (OR, 2.05; 95% CI, 1.46 to 2.87), excessive (OR, 2.04; 95% CI, 1.43 to 2.89). Conclusion These findings suggest that FMD is impaired in relation to alcohol consumption and that FMD is significantly smaller even in light alcohol drinkers than in non-drinkers. Alcohol intake per se may be harmful for vascular function. [ABSTRACT FROM AUTHOR]

Background Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors. It is thought that PEDF plays a protective role against atherosclerosis. Clinical studies have shown that serum levels of PEDF are increased in subjects with cardiovascular risk factors. The role of PEDF in cardiovascular disease is still controversial. The purpose of this study was to evaluate the associations between serum levels of PEDF and vascular function and structure. Methods We measured serum levels of PEDF, assessed vascular function by measurements of flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation in the brachial artery, and measured brachial artery intima-media thickness (IMT) in 150 subjects who underwent health examinations. Results and conclusions Univariate regression analysis revealed that serum level of PEDF was significantly correlated with body mass index, high-density lipoprotein cholesterol, glucose, FMD, nitroglycerine-induced vasodilation, and brachial artery IMT. Multivariate analysis revealed that serum levels of PEDF remained an independent predictor of nitroglycerine-induced vasodilation (β = − 0.20, P = 0.02) and brachial artery IMT (β = 0.14, P = 0.03) after adjustment of cardiovascular risk factors, while serum level of PEDF was not associated with FMD (β = − 0.02, P = 0.79). These findings suggest that PEDF may be a factor directly associated with atherosclerosis. The serum level of PEDF may be a new biochemical marker of atherosclerosis. [ABSTRACT FROM AUTHOR]

Background Nitroglycerine-induced vasodilation, an index of endothelium-independent vasodilation, is measured for the assessment of vascular smooth muscle cell function or alterations of vascular structure. Both coronary and brachial artery responses to nitroglycerine have been demonstrated to be independent prognostic markers of cardiovascular events. The purpose of this study was to evaluate the nitroglycerine-induced vasodilation in coronary and brachial arteries in the same patients. Methods We measured nitroglycerine-induced vasodilation in coronary and brachial arteries in 30 subjects with suspected coronary artery disease who underwent coronary angiography (19 men and 11 women; mean age, 69.0 ± 8.8 years; age range, 42–85 years). Results and conclusions The mean values of nitroglycerine-induced vasodilation in the brachial artery, left anterior descending coronary artery, and left circumflex coronary artery were 12.6 ± 5.2%, 11.6 ± 10.3%, and 11.9 ± 11.0%, respectively. Nitroglycerine-induced vasodilation in the brachial artery correlated significantly with that in the left anterior descending coronary artery (r = 0.43, P = 0.02) and that in the left circumflex coronary artery (r = 0.49, P = 0.006). There was also a significant correlation between nitroglycerine-induced vasodilation in the left anterior descending coronary artery and that in the left circumflex coronary artery (r = 0.72, P < 0.001). These findings suggest that vascular smooth muscle cell dysfunction is a systemic disorder and thus impairment of endothelium-independent vasodilation in peripheral arteries and that in coronary arteries are simultaneously present. Nitroglycerine-induced vasodilation in the brachial artery could be used as a surrogate for that in a coronary artery and as a prognostic marker for cardiovascular events. [ABSTRACT FROM AUTHOR]

Electrocardiographic left ventricular hypertrophy (ECG-LVH) gradually regressed after aortic valve replacement (AVR) in patients with severe aortic stenosis. Sokolow-Lyon voltage (SV + RV) is possibly the most widely used criterion for ECG-LVH. The aim of this study was to determine whether decrease in Sokolow-Lyon voltage reflects left ventricular reverse remodeling detected by echocardiography after AVR. Of 129 consecutive patients who underwent AVR for severe aortic stenosis, 38 patients with preoperative ECG-LVH, defined by SV + RV of ≥3.5 mV, were enrolled in this study. Electrocardiography and echocardiography were performed preoperatively and 1 year postoperatively. The patients were divided into ECG-LVH regression group ( n = 19) and non-regression group ( n = 19) according to the median value of the absolute regression in SV + RV. Multivariate logistic regression analysis was performed to assess determinants of ECG-LVH regression among echocardiographic indices. ECG-LVH regression group showed significantly greater decrease in left ventricular mass index and left ventricular dimensions than Non-regression group. ECG-LVH regression was independently determined by decrease in the left ventricular mass index [odds ratio (OR) 1.28, 95 % confidence interval (CI) 1.03-1.69, p = 0.048], left ventricular end-diastolic dimension (OR 1.18, 95 % CI 1.03-1.41, p = 0.014), and left ventricular end-systolic dimension (OR 1.24, 95 % CI 1.06-1.52, p = 0.0047). ECG-LVH regression could be a marker of the effect of AVR on both reducing the left ventricular mass index and left ventricular dimensions. The effect of AVR on reverse remodeling can be estimated, at least in part, by regression of ECG-LVH. [ABSTRACT FROM AUTHOR]

Background and aims It is established that low-density lipoprotein cholesterol is an independent risk factor for cardiovascular events. Recently, circulating triglycerides level has been focused on as a risk factor for cardiovascular events. In this study, we evaluated the associations between triglycerides and endothelial function in a general population. Methods We analyzed data for 4887 subjects who were enrolled in the FMD-Japan registry. We investigated cross-sectional associations between serum triglyceride levels and endothelial function assessed by measurement of flow-mediated vasodilation (FMD). Results Serum triglyceride levels were correlated with FMD (r = −0.12, p < 0.001). Subjects were divided into six groups based on serum triglyceride levels. FMD was significantly decreased with an increase in serum triglyceride levels (≤0.71 mmol/L, 7.0 ± 3.5%; 0.72–0.94 mmol/L, 6.3 ± 3.5%; 0.95–1.19 mmol/L, 6.0 ± 3.1%; 1.20–1.48 mmol/L, 5.8 ± 3.2%; 1.49–2.02 mmol/L, 5.7 ± 3.1%; ≥2.03 mmol/L, 5.5 ± 3.0%; p for trend <0.001). After adjustment for age, sex, and cardiovascular risk factors, including high-density lipoprotein cholesterol, serum triglyceride levels of more than 1.20 mmol/L were independently associated with the low quartile of FMD (1.20–1.48 mmol/L, odds ratio (OR) 1.41, 95% confidence interval (CI) 1.09 to 1.82; 1.49–2.02 mmol/L, OR 1.31, 95% CI 1.00 to 1.70; ≥2.03 mmol/L, OR 1.48, 95% CI 1.13 to 1.95) using serum triglyceride levels of less than 0.71 mmol/L group as the reference. Conclusions These findings suggest that triglycerides are an independent predictor of endothelial function. Lowering circulating triglyceride levels may improve endothelial function, leading to a decrease in cardiovascular events. Clinical trial registration information URL for Clinical Trial: http://UMIN ; Registration Number for Clinical Trial: UMIN000003409 [ABSTRACT FROM AUTHOR]

Abstract: Background: Cardiac computed tomography angiography (CCTA) provides the simultaneous evaluation of the aortic valve, myocardium, and coronary arteries. In particular, aortic valve calcium score (AVCS) can be accurately measured on the same scanning sequence used to measure coronary artery calcification, with no additional cost or radiation exposure. We sought to evaluate the prognostic value of CCTA measures, including AVCS, in asymptomatic aortic stenosis (AS). Methods and results: Sixty-four initially asymptomatic patients with AS with a normal ejection fraction were prospectively enrolled and followed for median 29 (IQR=18–50) months. During follow-up, 27 (42%) patients experienced cardiac events, including five cardiac deaths, eleven aortic valve replacements. Multivariate Cox proportional hazards analysis identified three CCTA measures as significant predictors of cardiac events: aortic valve area (per 0.1cm2 decrease; hazard ratio [HR]: 1.19, 95% confidence interval [CI]: 1.05–1.34); multi-vessel obstructive coronary artery disease (HR: 2.84, 95% CI: 1.10–7.32); and AVCS (per 100; HR: 1.09, 95% CI: 1.04–1.15). Kaplan–Meier analysis showed that patients with AVCS greater than or equal to the median value of 723 had significantly worse outcomes than those with AVCS less than 723 (p<0.0001). The C-statistic value for cardiac events substantially increased when these CCTA measures were added to clinical characteristics plus echocardiographic peak transaortic velocity (0.913 vs. 0.702, p<0.001). Conclusions: In patients with asymptomatic AS, CCTA measures of valve area, coronary stenosis, and calcification severity provide independent and incremental prognostic value after accounting for the echocardiographic severity of stenosis. [Copyright &y& Elsevier]

Abstract: Background: The aortic valve area (AVA) is usually calculated using the continuity equation (CE) in which the left ventricular outflow tract (LVOT) area is estimated assuming circular geometry. We sought to evaluate the LVOT ellipticity with 64-multidetector computed tomography (MDCT) and to assess the impact of LVOT ellipticity on the evaluation of CE-based AVA in patients with calcified aortic valves. Methods: We prospectively studied 110 patients with calcified aortic valves including 54 aortic stenosis (AS) with both 64-MDCT and transthoracic echocardiography. Double oblique transversal images for planimetry of the aortic valve and LVOT were obtained during the midsystolic phase. The short and long-axis diameters of the planimetered LVOT were measured. Results: The MDCT planimetered LVOT area was underestimated by the diameter-derived (π× r 2) LVOT area using echocardiography (444±70mm2 versus 369±63mm2; p<0.001). The mean difference in AVA values calculated using the CE and planimetry was 0.43±0.23cm2 and mean measurement error of CE-based AVA was 18%. When the CE-based AVA was corrected using the MDCT planimetered LVOT area, the measurement error decreased from 28±5 to 5±2% in patients with severe aortic stenosis (AVA<1.0cm2), whereas from 16±5 to 3±6% in others. Conclusion: Ellipticity of LVOT is associated with underestimation of AVA measurements using the CE. CE-based AVA corrected with MDCT planimetered LVOT area is useful especially in severe AS. [Copyright &y& Elsevier]

Abstract: Background: Rho-associated kinases (ROCKs) have been shown to be involved in the pathogenesis of atherosclerosis. It is clinically important to estimate the degree of ROCK activity in humans. The purpose of this study was to confirm the validity of a leukocyte ROCK parameter as an index of ROCK activity in comparison with vascular response to a ROCK inhibitor. Methods and results: We evaluated the ratio of phospho myosin-binding subunit (p-MBS) on myosin light-chain phosphatase to total MBS in peripheral leukocytes by Western blot analysis and forearm blood flow (FBF) response to the ROCK inhibitor fasudil using strain-gauge plethysmography in 36 healthy subjects and 39 patients with cardiovascular diseases. Fasudil (3, 10, 30μg/min) was infused intra-arterially for 5min at each dose. Leukocyte p-MBS/total-MBS was higher in cardiovascular diseases than in healthy subjects (0.97±0.37 vs. 0.51±0.14; P =0.002). Fasudil increased FBF from 4.9±1.2 to 14.5±5.7mL/min/100mL tissue (P <0.0001) in patients with cardiovascular diseases, while fasudil did not alter FBF in healthy subjects. There was a significant relationship between leukocyte p-MBS/total-MBS and maximal FBF response to fasudil in all subjects (r =0.72, P <0.0001). There was also a significant correlation between p-MBS/total-MBS and maximal FBF response to fasudil in patients with cardiovascular diseases (r =0.59, P <0.0001). In healthy subjects, there was no significant correlation between the two parameters. Conclusions: These findings suggest that assessment of leukocyte ROCK activity is minimally invasive and does not require pharmacologic intervention using ROCK inhibitors. Leukocyte p-MBS/total-MBS may be useful for evaluating ROCK activity in a clinical setting. [ABSTRACT FROM AUTHOR]

Background: Recent publications suggested that epicardial adipose tissue (EAT) contributes to the pathogenesis of coronary atherosclerosis. Although some studies showed the association between EAT accumulation and left ventricular (LV) diastolic dysfunction, these associations are not fully understood. Methods: We evaluated 153 patients without coronary artery disease who underwent coronary computed tomography (CT) angiography and Doppler echocardiography. We evaluated 153 patients (mean age of 60 years and 54% men) with zero coronary artery calcium score in coronary CT. Visceral adipose tissue (VAT) area was simultaneously measured by abdominal scans, and EAT volume was also calculated. These measurements were corrected by body surface area; VAT area index (VATAI), and EAT volume index (EATVI). The early diastolic mitral annular velocity at the septal (septal E') and lateral (lateral E') were measured using tissue Doppler echocardiography. Results: The mean values of BMI, VATAI, EATVI, and LVMI were 23.7 ± 3.8 kg/m2, 52.6 ± 26.4 cm2/m2, 71.3 ± 29.8 cm3/m2, and 83.3 ± 17.7 g/m2, respectively. The mean septal E' and lateral E' velocities were 7.2 ± 2.2 cm/s and 9.8 ± 2.9 cm/s, respectively. Each E' velocity was negatively correlated with EATVI (septal, R = 0.276, p < 0.001; lateral, R = 0.342, p < 0.001) and VATAI (septal, R = 0.241, p = 0.03; lateral, R = 0.255, p = 0.002; Figure). In contrast, each E' velocity was not correlated with LVMI (septal, R = 0.161, p = 0.03; lateral, R = 0.118, p = 0.14) and BMI (septal, R = 0.182, p = 0.03; lateral, R = 0.152, p = 0.06). To determine each E' velocity, we performed stepwise multiple regression analyses where all clinical parameters were entered. Diastolic blood pressure (p = 0.014), statin use (p = 0.011), LVMI (p = 0.003), and EATVI (p = 0.004) were independently correlated with septal E' velocity, and statin use (p = 0.024), LVMI (p = 0.011), and EATVI (p < 0.001) were independently correlated with lateral E' velocity. Conclusion: An increase in EATVI was associated with the decrease of early diastolic mitral annular velocity along each side of the left ventricle in patients with coronary calcium score of zero. These findings indicate that EAT accumulation may cause LV diastolic dysfunction in the early phase of coronary artery disease. [ABSTRACT FROM AUTHOR]

The clinical ramifications of adaptive servo-ventilation (ASV) therapy have stirred debate within the medical community. Given the potential detrimental effect of elevated expiratory positive airway pressure (EPAP) on cardiac output, we hypothesized that relatively lower EPAP may be recommended for successful ASV therapy. In-hospital patients with congestive heart failure refractory to medical therapy were included in the prospective cohort study of ASV therapy on prognosis in repeatedly hospitalized patients with chronic heart failure: longitudinal observational study of effects on readmission and mortality (SAVIOR-L) study. Assignment to either the ASV treatment group or the medical management group was at the discretion of the attending physicians. For the purposes of this retrospective study, our focus remained solely on the ASV cohort. We conducted an extensive analysis to elucidate the influence of lower EPAP settings on midterm mortality. A total of 108 patients were included. The median age was 74 years, and 83 (77%) patients were male. The median EPAP setting employed was 4 cmH 2 O, with 60 patients subjected to EPAP levels below 5 cmH 2 O. There were no significant differences in the baseline characteristics between the lower and higher EPAP groups, which were divided at the EPAP cutoff of 4.5 cmH 2 O (p > 0.05 for all). A trend toward reduced mortality emerged among patients with EPAP settings below 5 cmH 2 O, exhibiting a hazard ratio of 0.48 (95% confidence interval 0.22-1.07, p = 0.072) after adjusting for potential confounding factors: 2-year mortality 26% vs. 38%; p = 0.095. Heart failure readmission rates were not significantly different between the two groups (p = 0.61). The adoption of relatively lower EPAP settings during ASV therapy may be advisable. Such an approach has the potential to ameliorate mortality rates while concurrently maintaining heart failure recurrence rates at levels commensurate with those with default EPAP settings., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Background: This study investigated whether the chronic use of adaptive servo-ventilation (ASV) reduces all-cause mortality and the rate of urgent rehospitalization in patients with heart failure (HF)., Methods and results: This multicenter prospective observational study enrolled patients hospitalized for HF in Japan between 2019 and 2020 who were treated either with or without ASV therapy. Of 845 patients, 110 (13%) received chronic ASV at hospital discharge. The primary outcome was a composite of all-cause death and urgent rehospitalization for HF, and was observed in 272 patients over a 1-year follow-up. Following 1:3 sequential propensity score matching, 384 patients were included in the subsequent analysis. The median time to the primary outcome was significantly shorter in the ASV than in non-ASV group (19.7 vs. 34.4 weeks; P=0.013). In contrast, there was no significant difference in the all-cause mortality event-free rate between the 2 groups., Conclusions: Chronic use of ASV did not impact all-cause mortality in patients experiencing recurrent admissions for HF.

Background: Although there is reportedly a usefulness of left ventricular global longitudinal strain (LV GLS) on 2D speckle-tracking echocardiography in excluding significant coronary artery disease (CAD) in suspected intermediate- or low-risk non-ST-segment elevation-acute coronary syndrome (NSTE-ACS), the efficacy of post-systolic index (PSI) in this context is yet unknown. Therefore, we explored the usefulness of PSI in facilitating stratification of risk in patients with intermediate- or low-risk NSTE-ACS., Methods and Results: We assessed 50 consecutive patients suspected of intermediate- or low-risk NSTE-ACS, and finally analyzed 43 patients whose echocardiographic images were suitable for strain analysis. All patients underwent CAG. Among the 43 analyzed patients, 26 had CAD, and 21 underwent percutaneous coronary intervention (PCI). Patients with CAD had higher PSI (25% [20.8-40.3%] vs 15% [8.0-27.5%], P = 0.007). Receiver-operator characteristic curve analysis identified that a PSI of > 20% detected performance of PCI (sensitivity 80.7%, specificity 70.6%, area under curve [AUC] 0.72, 95% confidence interval [CI] 0.57-0.88). Moreover, the AUC obtained using the GRACE risk score was 0.57 (95% CI 0.39-0.75), and increased to 0.75 (95% CI 0.60-0.90) when PSI and LV GLS were added. Thus, the addition of PSI and LV GLS improved the classification of performance of PCI (net reclassification improvement [95%CI] 0.09 [0.0024-0.18], P = 0.04)., Conclusions: Post-systolic index is a useful parameter that can facilitate stratification of risk in patients with intermediate- or low-risk NSTE-ACS. We recommend measuring PSI in routine clinical practice., (© 2023. Japanese Society of Echocardiography.)

Objective: The number of older patients with heart failure (HF) is increasing in Japan and has become a social problem. There is an urgent need to develop a comprehensive assessment methodology based on the common language of healthcare; the International Classification of Functioning, Disability and Health (ICF). The purpose of this study was to develop and confirm the appropriateness of a scoring methodology for 43 ICF categories in older people with HF., Design: Cross-sectional survey. We applied the RAND/University of California at Los Angeles (UCLA) Appropriateness Method with a modified Delphi method., Setting and Participants: We included a panel of 26 multidisciplinary experts on HF care consisting of home physicians, cardiovascular physicians, care managers, nurses, physical therapists, a pharmacist, occupational therapist, nutritionist and a social worker., Measures: We conducted a literature review of ICF linking rules and developed a questionnaire on scoring methods linked to ICF categories in older people with HF. In the Delphi rounds, we sent the expert panel a questionnaire consisting of three questions for each of the 43 ICF categories. The expert panel responded to the questionnaire items on a 1 (very inappropriate) - 9 (very appropriate) Likert scale and repeated rounds until a consensus of 'Appropriate' and 'Agreement' was reached on all items., Results: A total of 21 panel members responded to all the Delphi rounds. In the first Delphi round, six question items in four ICF categories did not reach a consensus of 'Agreement', but the result of our modifications based on panel members' suggestions reached to a consensus of 'Appropriate' and 'Agreement' on all questions in the second Delphi round., Conclusion: The ICF-based scoring method for older people with HF developed in this study was found to be appropriate. Future work is needed to clarify whether comprehensive assessment and information sharing based on ICF contributes to preventing readmissions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The effects of outpatient cardiac rehabilitation (OCR) implementation and home nursing-care services (HNS) use are not well defined in patients with heart failure (HF) with mid-range or preserved left-ventricular ejection fraction (EF) (HFmrEF or HFpEF). Through a post-hoc analysis of the HF registry in Hiroshima Prefecture of Japan (REAL-HF), we investigated the current conditions and significance of OCR and HNS in HFmrEF or HFpEF patients. The REAL-HF enrolled adult patients hospitalized with HF in eight regional core hospitals. Patients discharged home were followed for conditions of OCR and HNS and the primary endpoints (all-cause death or unscheduled readmission) for 1 year. The patients were classified into HF with reduced EF (< 40%) (HFrEF) or HFmrEF (40% ≤ EF < 50%) or HFpEF (EF ≥ 50%) group. We followed 195 HFrEF and 381 HFmrEF or HFpEF patients. OCR was generally underutilized, especially in HFmrEF or HFpEF patients (rate of completion [5-month program], 3.2%), whereas HFmrEF or HFpEF patients were more likely to use HNS after discharge home than HFrEF patients (44.1% vs. 27.2%, P < 0.0001). Patients with the use of HNS generally had lower scores of Mini-Mental State Examination and EuroQol 5 dimensions than those without. Multivariate analysis adjusted for medical and social factors showed that the completion of OCR was a strong negative predictor of the primary endpoints both in HFrEF (hazard ratio [HR] 0.10; 95% confidence interval [CI] 0.01-0.75; P = 0.025) and HFmrEF or HFpEF (HR 0.11; 95% CI 0.01-0.78; P = 0.028) patients, whereas the use of HNS was a positive predictor only in HFmrEF or HFpEF patients (HR 1.41; 95% CI 1.00-1.97; P = 0.047). In conclusion, continuous OCR, despite its inadequate implementation, was associated with favorable overall outcomes, while the necessity for HNS related to impaired cognitive function and quality of life was associated with poorer overall outcomes in HFmrEF or HFpEF patients discharged home. Further study is warranted to fully consider the factors related to OCR implementation and HNS use., (© 2021. Springer Japan KK, part of Springer Nature.)

A favorable reverberation time in concert halls is a fundamental issue for room acoustic design, and various recommendations have been suggested so far. Nevertheless, one must track back more than half a century when it comes to systematic subjective experiments on this topic. In this study, binaural room impulse responses (RIRs) measured with a dodecahedral loudspeaker in concert halls, where orchestra concerts are regularly held, are used. First, signal processing is applied to RIR to equalize the dodecahedral loudspeaker response as flat and broad as possible within the audible frequency range. Then, anechoic recordings of music by piano and violin, excerpts from cadenzas, are convoluted with the equalized RIR. Next, subjective experiments are conducted to seek favorable reverberation times. Reverberance and clarity were judged by 16 music experts. From this research, the favorable reverberation times RT M (octave band average for 500 and 1000 Hz) for piano and violin solos are from 1.2 to 2.0 s and 1.8 to 2.4 s, respectively. However, the clarity index C 80,3 (octave band average for 500, 1000, and 2000 Hz) needs to range from 0 to 2.4 dB and -1.6 to 0.7 dB, respectively, to meet the optimum reverberance for piano and violin.

Background: Establishing an information-sharing system between medical professionals and welfare/care professionals may help prevent heart failure (HF) exacerbations in community-dwelling older adults. Therefore, we aimed to identify the ICF categories necessary for care managers to develop care plans for older patients with HF., Methods: A questionnaire was administered to 695 care managers in Hiroshima, Japan, on ICF items necessary for care planning. We compared the care managers according to their specialties (medical qualifications and welfare or care qualifications). Furthermore, we created a co-occurrence network using text mining, regarding the elements necessary for collaboration between medical and care professionals., Results: There were 520 valid responses (74.8%). Forty-nine ICF items, including 18 for body functions, one for body structure, 21 for activities and participation, and nine for environmental factors, were classified as "necessary" for making care plans for older people with HF. Medical professionals more frequently answered "necessary" than care professionals regarding the 11 items for body functions and structure and three items for activities and participation (p < 0.05). Medical-welfare/care collaboration requires (1) information sharing with related organisations; (2) emergency response; (3) a system of cooperation between medical care and non-medical care; (4) consultation and support for individuals and families with life concerns, (5) management of nutrition, exercise, blood pressure and other factors, (6) guidelines for consultation and hospitalisation when physical conditions worsen., Conclusions: Our findings showed that 49 ICF categories were required by care managers for care planning, and there was a significant difference in perception between medical and welfare or care qualifications qualifications., (© 2021. The Author(s).)

Aims: This study aimed to evaluate the prevalence and distribution of pulmonary venous systolic flow reversal (PVSFR) in patients with severe mitral regurgitation (MR), and to examine the relationship between PVSFR profile and cardiac parameters., Methods and Results: A total of 125 patients with severe MR who had transoesophageal echocardiography (TOE) performed were reviewed. Of these, 121 (96.8%) patients showed all four pulmonary venous (PV) flows by TOE. They were categorized into three groups by the MR aetiology: degenerative MR (DMR) (n = 72), ventricular functional MR (V-FMR) (n = 20), and atrial functional MR (A-FMR) (n = 16). Eighteen (16.7%) patients had PVSFR in all four PVs. Twenty-nine (26.9%) had PVSFR in three PVs, 23 (21.3%) in two PVs, and 23 (21.3%) in one PV. PVSFR appeared at right PVs more frequently compared with left PVs. A high number of PVSFR was significantly correlated with higher pulmonary capillary wedge pressure (PCWP) and 3D vena contracta area (3D-VCA). With regard to MR aetiology, the number of PVSFRs was correlated with high 3D-VCA in patients with DMR and A-FMR, while it was correlated with high PCWP in patients with V-FMR. Laminar-type PVSFR appeared more frequently in FMR compared with DMR, and it had a relationship with higher PCWP and lower right ventricular fractional area change (RVFAC)., Conclusion: All four PV were detected in 96.8%, and 16.8% patients had PVSFR in all four PVs. PCWP and 3D-VCA were correlated with the number of PVSFRs in severe MR patients. Laminar-type PVSFR was related to higher PCWP and lower RVFAC., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Using three-dimensional (3D) transesophageal echocardiography (TEE) and isometric handgrip exercise (IHE), we investigated the determinants of exercise-induced mitral regurgitation (MR) according to MR etiologies. Seventy-six patients with more than moderate MR, 40 patients with functional MR (FMR) and 36 patients with degenerative MR (DMR), underwent 3D TEE combined with IHE. Mitral valve (MV) geometry and 3D vena contracta area (3D VCA) were simultaneously evaluated at baseline and during IHE. With regard to exercise-induced MR, Δ3D VCA was calculated as the difference between 3D VCA at baseline and 3D VCA during IHE. IHE caused different changes in MV geometry between etiologies and led to exacerbation of 3D VCA at baseline. Larger Δ3D VCA was observed in the FMR group compared with the DMR group (15.9 ± 10.3 mm 2 versus 7.3 ± 4.2 mm 2 ; p < 0.0001). In multivariate analyses, tenting height and 3D VCA were selected as independent factors associated with Δ3D VCA in the FMR group (p = 0.0135 and p = 0.0201, respectively), while flail width was selected as an independent factor associated with Δ3D VCA in the DMR group (p = 0.0066). In conclusion, IHE alters mitral valve geometry and causes exacerbation of MR regardless of MR etiology and the determinants of exercise-induced MR differed between MR etiologies., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background Upstroke time is the transit time from the nadir to peak of the waveform of pulse volume recording. The purpose of this study was to determine whether upstroke time at the ankle is a useful vascular marker for detecting patients with advanced atherosclerosis in combination with ankle-brachial index (ABI). Methods and Results We measured upstroke time and ABI in 2313 subjects (mean age, 61.2±15.3 years). The prevalence of coronary artery disease (CAD) was significantly higher in patients with prolonged upstroke time (≥180 ms) than in subjects with normal upstroke time (<180 ms) (29.6% versus 11.8%; P <0.001), with a significant association between prolonged upstroke time and an increased risk of CAD (odds ratio [OR], 1.61; 95% CI, 1.07-2.44; P =0.02). In 1954 subjects with normal ABI (1.00 ≤ ABI ≤ 1.40), the prevalence of CAD was significantly higher in patients with prolonged upstroke time than in subjects with normal upstroke time (29.5% versus 10.6%; P <0.001), with a significant association between prolonged upstroke time and CAD (OR, 2.33; 95% CI, 1.41-3.87; P =0.001), whereas there was no significant association between upstroke time and CAD in subjects with low ABI (<1.00) (OR, 1.24; 95% CI, 0.72-2.16; P =0.44). Conclusions Upstroke time may be a useful vascular marker for detecting patients with CAD, especially in subjects with normal ABI who are usually considered not to have advanced atherosclerosis by ABI measurement alone. More attention should be paid to upstroke time for detecting patients with advanced atherosclerosis. Registration URL: https://www.umin.ac.jp; Unique identifier: UMIN000039512.

Aims: We sought to investigate tricuspid valve (TV) geometry and right heart remodelling in atrial functional tricuspid regurgitation (AF-TR) as compared with ventricular functional TR with sinus rhythm (VF-TR)., Methods and Results: Transoesophageal 3D echocardiography datasets of the TV and right ventricle were acquired in 51 symptomatic patients with severe TR (AF-TR, n = 23; VF-TR, n = 28). Three-dimensional right ventricular (RV) endocardial surfaces were reconstructed throughout the cardiac cycle and then postprocessed using semiautomated integration and segmentation software to calculate position of papillary muscle (PM) tips. Compared with VF-TR, AF-TR had more dilated and posteriorly displaced annulus and less leaflet tethering angles with more prominent right atrium and smaller RV end-systolic volume. On the XY (annular) plane, the centre of annulus was getting closer towards the anterior and posterior PM tips and was going away from the medial PM tip caused by prominent annular dilatation in AF-TR. On the Z-axis, the position of each PM tip in AF-TR was not so much displaced apically as that in VF-TR. Multiple linear regression analyses revealed that right atrial volume and right atrial/RV end-systolic volume ratio were determinants of annular area and orientation in AF-TR, respectively (both P < 0.001). Additionally, the posteromedial-directed component of posterior PM tip position and the apically directed component of the position of all three PM tips were independently associated with TV tethering angles of each leaflet in AF-TR (all P < 0.02)., Conclusion: Right heart remodelling and its association with 3D TV geometry differ entirely between AF-TR and VF-TR, which may offer distinctive therapeutic implication., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

The percentage of people aged 80 years or older in Japan has been increasing. The purpose of this study was to investigate the association between vascular functions and aging in the elderly population and to clarify the characteristics of vascular functions in subjects aged 80 years or older. We measured flow-mediated vasodilation (FMD), nitroglycerine-induced vasodilation (NID), and brachial-ankle pulse wave velocity (baPWV) in 737 subjects aged 60 years or older who visited the outpatient clinic at Hiroshima University Hospital. FMD and NID were significantly lower in subjects aged 80 years or older than in subjects aged 60-69 years or in subjects aged 70-79 years (1.9 ± 2.0% vs. 2.9 ± 2.6% and 2.7 ± 2.6%, P = 0.008 and P = 0.03, respectively and 8.6 ± 5.1% vs. 12.1 ± 5.6% and 11.2 ± 5.5%, P < 0.001 and P < 0.001, respectively). baPWV was significantly higher in subjects aged 80 years or older than in subjects aged 60-69 years or in subjects aged 70-79 years (1978 ± 452 cm/s vs. 1724 ± 319 cm/s and 1811 ± 318 cm/s, P < 0.001 and P < 0.001, respectively). Age over 80 years was significantly associated with lower FMD (OR, 2.02; 95% CI, 1.19-3.42; P = 0.01), lower NID (OR, 3.62; 95% CI, 2.13-6.17; P < 0.001), and higher baPWV (OR, 3.48; 95% CI, 1.99-6.08; P < 0.001) after adjustment for other cardiovascular risk factors. Vascular functions, including endothelial function, vascular smooth muscle function, and arterial stiffness, were shown to be further impaired in subjects aged 80 years or older, suggesting that vascular functions continue to be impaired throughout life with aging.

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

Background: Central venous pressure (CVP) is measured to assess intravascular fluid status. Although the clinical gold standard for evaluating CVP is invasive measurement using catheterization, the use of catheterization is limited in a clinical setting because of its invasiveness. We developed novel non-invasive technique, enclosed-zone (ezCVP TM ) measurement for estimating CVP. The purpose of this study was to assess the feasibility of ezCVP and the relationship between ezCVP and CVP measured by a catheter., Methods and results: We conducted 291 measurements in 97 patients. Linear regression analysis revealed that ezCVP was significantly correlated with CVP (r=0.65, P<0.0001). The Bland-Altman analysis showed that ezCVP had an underestimation bias of -2.5 mmHg with 95% limits of agreement of -14.1 mmHg and 9.6 mmHg for CVP (P<0.0001). The areas under the curves of receiver operating curve with ezCVP to detect the CVP ≥12 cmH 2 O (8.8 mmHg) and CVP >10 mmHg were 0.81 or 0.88, respectively. The sensitivity, specificity and positive likelihood ratio of ezCVP for the CVP ≥8.8 mmHg and CVP >10 mmHg were 0.59, 0.96 and 14.8 with a cut-off value of 11.9 and 0.79, 0.97 and 26.3 with a cut-off value of 12.7., Conclusions: These findings suggest that ezCVP measurement is feasible and useful for assessing CVP.

Atrial fibrillation (AF) is a common disease that changes cardiac morphology, especially in the left atrium (LA). It is now known that certain categories of functional mitral regurgitation (MR) are associated with AF; however, the influence of AF on right cardiac morphology is not fully understood. Our aim in this study was to investigate the association between AF and right cardiac morphology. This was a retrospective cohort study of 86 patients with persistent AF without other cardiac disease who underwent catheter ablation (CA). Seventy-one patients had sustained sinus rhythm (SR) (SR Group) and 15 patients had sustained AF (AF Group) during the study period. We compared the changes in the right cardiac dimensions and tricuspid regurgitation (TR) between the groups 12 months after CA. Patients' baseline echocardiographic assessments revealed that the LA volume index was significantly smaller in the SR group than in the AF group (46.8 ± 11.9 ml/m 2 vs 59.3 ± 12.8 ml/m 2 , respectively; p < 0.01). Comparing baseline data with the 12-month follow-up data, in the SR group, right atrial area (RAA, cm 2 ), tricuspid annular diameter (mm), and tricuspid regurgitant jet area (cm 2 ) were significantly decreased compared with the AF group (19.5 ± 4.5-15.5 ± 3.6 vs 20.7 ± 3.6-19.7 ± 2.3; 30.5 ± 4.9-26.4 ± 3.9 vs 28.7 ± 4.0-28.8 ± 3.1; and 1.4 [interquartile range (IQR) 0.7-2.6]-0.6 [IQR 0.2-1.2] vs 1.2 [IQR 1.1-1.5]-0.9 [IQR 0.4-1.3], respectively). On multivariate analysis, change in RAA correlated with the reduction in tricuspid regurgitant jet area (R = 0.51, p < 0.001). In conclusion, successful CA for persistent AF led to right heart reverse remodeling, and our findings suggested that persistent AF was associated with RAA dilatation and TR.

Background: We investigated the current medical and social conditions and outcomes of heart failure (HF) patients in Hiroshima Prefecture, a local district in Japan. Methods and Results: From March 2017 to February 2018 we enrolled all adult patients with hospitalized HF in 8 regional core hospitals that provided an interprofessional team approach for HF patients. We collected patients' clinical characteristics and information regarding living circumstances, cognitive function, quality of life, and interprofessional team approach. For patients discharged home, we followed up the primary endpoint (all-cause death and all-cause unscheduled readmission), conditions of outpatient cardiac rehabilitation, and home nursing-care services over a 1-year period after discharge. Of the registered patients (n=1,218), 39.2% were super-elderly (≥85 years old); more than half of these patients had preserved ejection fraction (≥50%). In the follow-up cohort (n=632), 140 patients (22.2%) were readmitted with HF exacerbation as the primary endpoint, and almost half (n=295, 46.7%) experienced any primary endpoint. The multivariate analysis adjusted for medical and social factors showed that completion of outpatient cardiac rehabilitation (5-month program) remained a strong negative predictor of the primary endpoint (hazard ratio: 0.15; 95% confidence interval: 0.05-0.48; P=0.0013). Conclusions: Our cohort study highlighted the super-aging of current HF patients in Japan. Cardiac rehabilitation through continuous team approach appears to be associated with favorable overall outcomes in this population., Competing Interests: This study was supported by the Japan Agency for Medical Research and Development (AMED) under Grant No. JP17ek0210058. This study was also supported by a local medical program of the Hiroshima Prefecture Government in Japan (Hiroshima Heart Health Promotion Project)., (Copyright © 2020, THE JAPANESE CIRCULATION SOCIETY.)

Background Diagnostic criteria of flow-mediated vasodilation (FMD), an index of endothelial function, and nitroglycerin-induced vasodilation (NID), an index of vascular smooth muscle function, of the brachial artery have not been established. The purpose of this study was to propose diagnostic criteria of FMD and NID for normal endothelial function and normal vascular smooth muscle function. Methods and Results We investigated the cutoff values of FMD and NID in subjects with (risk group) and those without cardiovascular risk factors or cardiovascular diseases (no-risk group) in 7277 Japanese subjects (mean age 51.4±10.8 years) from the Flow-Mediated Dilation Japan study and the Flow-Mediated Dilatation Japan Registry study for analysis of the cutoff value of FMD and in 1764 Japanese subjects (62.2±16.1 years) from the registry of Hiroshima University Hospital for analysis of the cutoff value of NID. Receiver-operator characteristic curve analysis of FMD to discriminate subjects in the no-risk group from patients in the risk group showed that the optimal cutoff value of FMD to diagnose subjects in the no-risk group was 7.1%. Receiver-operator characteristic curve analysis of NID to discriminate subjects in the no-risk group from patients in the risk group showed that the optimal cutoff value of NID to diagnose subjects in the no-risk group was 15.6%. Conclusions We propose that the cutoff value for normal endothelial function assessed by FMD of the brachial artery is 7.1% and that the cutoff value for normal vascular smooth muscle function assessed by NID of the brachial artery is 15.6% in Japanese subjects. Clinical Trial Registration www.umin.ac.jp Unique identifiers: UMIN000012950, UMIN000012951, UMIN000012952, and UMIN000003409.

Background: Both the H 2 FPEF-score and nomogram-score, which consist of simple clinical parameters, can assist in diagnosing "early" heart failure with preserved ejection fraction (HFpEF) and only exertional dyspnea, but their these usefulness in Japanese remains unclear. We sought to investigate the correlation between these scores and exercise response, including the peak oxygen uptake (V̇O 2 ), the pulmonary artery systolic pressure (PASP), the ratio of early diastolic transmitral flow velocity to early diastolic mitral annular velocity (E/e') and stroke volume (SV) using exercise stress echocardiography (ESE) combined with cardiopulmonary exercise testing (CPET)., Methods and results: In this single-center, retrospective cross-sectional study the H 2 FPEF-score and nomogram-score were calculated in a total of 139 patients who underwent ESE combined with CPET. The scores correlated with peak V̇O 2 (r=-0.48, r=-0.44), PASP (r=0.23, r=0.29) and SV (r=-0.32, r=-0.19) at peak exercise. The nomogram-score correlated with E/e' (r=0.24). The prevalence of exercise intolerance (percent predicted peak V̇O 2 <75% and <50%) increased as the H 2 FPEF-score increased and reached 88.9% and 22.2% among the patients with high H 2 FPEF-score (6-9 points)., Conclusions: The H 2 FPEF-score may be useful as the initial step to diagnosing 'early' HFpEF. The nomogram-score may be more useful in Japanese because of its more universal association with exercise response than the H 2 FPEF-score.

Hypertension is associated with vascular failure, such as increased arterial stiffness, endothelial dysfunction, and vascular smooth muscle dysfunction. The purpose of this study was to investigate the relationship between out-of-office blood pressure and vascular function in patients receiving antihypertensive drugs. We assessed out-of-office blood pressure, including daytime and night-time blood pressure, by home blood pressure monitoring and performed vascular function tests, including brachial-ankle pulse wave velocity (baPWV), flow-mediated vasodilation (FMD), and nitroglycerine-induced vasodilation (NID), in 169 patients receiving antihypertensive drugs, of whom 86 (50.9%) had normotension, 23 (13.6%) had isolated nocturnal hypertension (night-time systolic blood pressure ≥120 mm Hg), 26 (15.4%) had isolated daytime hypertension (daytime systolic blood pressure ≥135 mm Hg), and 34 (20.1%) had sustained hypertension (daytime and nocturnal hypertension). baPWV was significantly higher in patients with sustained hypertension than in those without sustained hypertension (1585 ± 257 cm/s in normotension; 1687 ± 267 cm/s in isolated nocturnal hypertension; 1688 ± 313 cm/s in isolated daytime hypertension; and 1923 ± 399 cm/s in sustained hypertension; P < 0.001). baPWV above the cutoff value of 1858 cm/s, derived from receiver operating characteristic curve analysis to diagnose patients with sustained hypertension, was significantly associated with sustained hypertension after adjustment of other confounding factors (odds ratio, 5.01; 95% confidence interval, 1.94-13.41; P < 0.001). In contrast, there was no significant association of home blood pressure status with FMD or NID in these patients. In patients receiving antihypertensive drugs, baPWV was significantly associated with sustained hypertension, whereas FMD and NID were impaired regardless of the home blood pressure status.

Background: Differences between the effects of calcium channel blockers (CCBs) and other antihypertensive drugs on vascular function have not been fully investigated. The purpose of this study was to determine the confounding effect of CCBs on vascular function tests., Methods: We measured flow-mediated vasodilation (FMD), nitroglycerine-induced vasodilation (NID), and brachial-ankle pulse wave velocity (baPWV) in 1,134 subjects who underwent health-screening examinations or who visited the outpatient clinic at Hiroshima University Hospital., Results: FMD and NID were significantly lower (4.3 ± 3.2% vs. 2.3 ± 2.4% and 14.1 ± 5.8% vs. 10.6 ± 5.3%, P < 0.001, respectively) and baPWV was significantly higher (1,604 ± 412 cm/s vs. 1,715 ± 343 cm/s, P < 0.001) in subjects receiving CCB treatment than in subjects without CCB treatment. Multivariate analyses revealed that CCB treatment was significantly associated with lower FMD (β = -0.151, P < 0.001) and lower NID (β = -0.120, P < 0.001) but not with baPWV (β = 0.017, P = 0.42). Propensity score matching analyses revealed that FMD and NID were significantly lower and baseline brachial artery diameter was significantly larger in subjects receiving CCB monotherapy than in subjects without antihypertensive medication or subjects receiving non-CCB antihypertensive monotherapy., Conclusions: CCB treatment was significantly associated with lower FMD and lower NID, which might be, at least in part, due to larger baseline brachia artery diameter, whereas there was no significant association between CCB treatment and baPWV. FMD and NID may be of no use as prognostic markers of cardiovascular events in individuals who have been receiving CCB treatment., Public Trials Registry Number: Trial Number UMIN000003409., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Estimation of left ventricular filling pressure (LVFP) is the essential part of the echocardiographic workup for exercise intolerance. The ratio of the mitral early filling velocity to the left ventricular global longitudinal strain (E/LVGLS) has emerged as a novel index of LVFP. This study aimed to investigate the relationship between E/LVGLS and exercise capacity., Methods and Results: We retrospectively reviewed 90 patients with exertional dyspnea who underwent echocardiography and cardiopulmonary exercise test. Patients were classified into three groups according to their percent-predicted maximal oxygen consumption (ppVo 2 ) (G ≧ 75, ppVo 2  > 75%, n = 20; G 50-75, ppVo 2 75-50%, n = 57; G < 50, ppVo 2  < 50%, n = 13). Measurements were (a) the relationship between ppVo 2 and E/LVGLS and (b) the efficiency of integrated diastolic assessment using E/LVGLS, left ventricular volume, mitral annular early diastolic velocity (E'), and tricuspid regurgitation to identify the patient with impaired exercise capacity. Univariate linear regression analysis demonstrated that E/LVGLS had significant correlation with ppVo 2 (ρ = 0.52, P < 0.001). The area under the ROC of E/LVGLS for ppVo 2  < 50% was 0.86 (95%CI 0.75-0.97). The DeLong test showed that E/LVGLS was efficient to detect ppVo 2  < 50% than E/E' (P = 0.007). When used in the integrated assessment of LVFP as the alternative for E/E', E/LVGLS improved risk classification for impaired exercise capacity., Conclusion: E/LVGLS may be a more efficient index than E/E' to identify exercise impairment as a single index and as a part of the integrated diastolic assessment., (© 2019 Wiley Periodicals, Inc.)

Background: Information regarding current medical and social conditions and outcome of Japanese heart failure (HF) patients is needed. Methods and Results: The registry and follow-up study regarding the medical and social conditions and outcomes of hospitalized heart failure patients (REAL-HF) is maintained by 8 regional core hospitals, which provide an interprofessional team approach for HF patients, in Hiroshima Prefecture. We planned to enroll all adult patients hospitalized with symptomatic HF (congestive HF and/or low output syndrome) in 1 year from March 2017. We registered the clinical characteristics of each patient, including physical activity (able to walk independently), during the indexed hospitalization. Information regarding living circumstances, cognitive function test, questionnaire for quality of life (QOL), and interprofessional team approaches was also collected. For patients discharged home, we planned to follow all-cause death, all-cause unscheduled readmission, and the conditions of outpatient cardiac rehabilitation and home nursing-care services at 3 and 12 months after discharge. A total of 1,218 patients has been registered initially. Follow-up is ongoing, and data analysis is expected to be completed in 2019. Conclusions: The REAL-HF will provide a significant database on the current real conditions of hospitalized HF patients in a local district of Japan, elucidating medical and social risk factors of worsened QOL and prognosis., (Copyright © 2019, THE JAPANESE CIRCULATION SOCIETY.)

Background: The usefulness of vascular function tests for management of patients with a history of coronary artery disease is not fully known., Methods and Results: We measured flow-mediated vasodilation (FMD) and brachial-ankle pulse wave velocity (baPWV) in 462 patients with coronary artery disease for assessment of the predictive value of FMD and baPWV for future cardiovascular events in a prospective multicenter observational study. The first primary outcome was coronary events, and the second primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow-up period of 49.2 months, the first primary outcome occurred in 56 patients and the second primary outcome occurred in 66 patients. FMD above the cutoff value of 7.1%, derived from receiver-operator curve analyses for the first and second primary outcomes, was significantly associated with lower risk of the first (hazard ratio, 0.27; 95% confidence interval, 0.06-0.74; P =0.008) and second (hazard ratio, 0.32; 95% confidence interval, 0.09-0.79; P =0.01) primary outcomes. baPWV above the cutoff value of 1731 cm/s was significantly associated with higher risk of the first (hazard ratio, 1.86; 95% confidence interval, 1.01-3.44; P =0.04) and second (hazard ratio, 2.19; 95% confidence interval, 1.23-3.90; P =0.008) primary outcomes. Among 4 groups stratified according to the combination of cutoff values of FMD and baPWV, stepwise increases in the calculated risk ratio for the first and second primary outcomes were observed., Conclusions: In patients with coronary artery disease, both FMD and baPWV were significant predictors of cardiovascular events. The combination of FMD and baPWV provided further cardiovascular risk stratification., Clinical Trial Registration: URL: www.umin.ac.jp. Unique identifier: UMIN000012950., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Lower urinary tract symptoms (LUTS) is not only common symptoms in elderly men and women but also risk of future cardiovascular events. The purpose of this study was to evaluate the relationships of vascular function and structure with LUTS in men and women., Methods: We investigated flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) as vascular function, brachial-ankle pulse wave velocity (baPWV) as vascular structure, and LUTS assessed by International Prostate Symptom Score (IPSS) in 287 men and 147 women., Results: IPSS was significantly correlated with traditional cardiovascular risk factors, Framingham risk score, FMD, NID and baPWV. Moderate to severe LUTS was associated with the prevalence of coronary heart disease in men but not in women. In men, FMD and NID were significantly lower in the moderate to severe LUTS group than in the none to mild LUTS group (2.1 ± 2.0% vs. 4.0 ± 3.0% and 9.3 ± 6.1% vs. 12.8 ± 6.6%, P < 0.001, respectively). baPWV was significantly higher in the moderate to severe LUTS group than in the none to mild LUTS group (1722 ± 386 cm/s vs. 1509 ± 309 cm/s, P < 0.001). In multivariate analysis, FMD was independently associated with a decrease in the odds ratio of moderate to severe LUTS in men (OR: 0.83, 95% CI, 0.72-0.95; P = 0.008) but not in women. NID and baPWV were not independently associated with moderate to severe LUTS either in men or women., Conclusions: These findings suggest that endothelial dysfunction is associated with LUTS in men. LUTS in men may be useful for a predictor of cardiovascular events., Clinical Trial Registration Information: URL for Clinical Trial: http://UMIN; Registration Number for Clinical Trial: UMIN000003409., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Although reactive hyperemia-peripheral arterial tonometry (RH-PAT) is widely used for assessment of endothelial function, RH index (RHI) cannot be measured in some cases when pulse wave amplitude (PWA) is very low. Decrease in PWA is mainly caused by proper palmar digital artery (PPDA) stenosis. The purpose of this study was to evaluate the relationship between PWA measured by RH-PAT and stenosis of the PPDA measured by digital subtraction angiography and to evaluate the limitation of assessment of endothelial function measured by RHI in patients with PPDA stenosis., Methods: We measured baseline PWA in 51 fingers including the first to third fingers of both hands in 10 patients who had PPDA stenosis and in 66 fingers that were the first fingers of both hands in 33 subjects who had no PPDA stenosis. Severe stenosis was defined as over 75% by lower percent diameter stenosis between two PPDAs in a finger., Results: PWA was significantly correlated with stenosis of the digital artery (r=-0.55; P<0.0001). A PWV value of 300mV was the optimal cut-off value for severe stenosis (sensitivity, 84.0%; specificity, 88.5%). Log RHI was significantly lower in patients with PPDA stenosis than in subjects without PPDA stenosis (0.33±0.27 versus 0.73±0.27, P=0.007)., Conclusions: RH-PAT may be useful for assessment of not only endothelial function but also PPDA stenosis. RHI may be underestimated in patients with PPDA stenosis. We should pay attention to low baseline PWA when measuring RHI., Clinical Trial Registration Information: URL for clinical trial: http://UMIN; registration number for clinical trial: UMIN000003409., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Flow-mediated vasodilation (FMD) of the brachial artery has been used for the assessment of endothelial function. Considering the mechanism underlying the vasodilatory response of the brachial artery to reactive hyperemia, hyperemic shear stress (HSS), a stimulus for FMD; nitroglycerine-induced vasodilation (NID), an index of endothelium-independent vasodilation; and baseline brachial artery diameter (BAD) are also involved in vasodilatory response. The purpose of this study was to investigate the interrelationships among FMD, HSS, NID, baseline BAD, and cardiovascular risk factors., Methods and Results: We measured FMD, HSS, NID, and baseline BAD simultaneously in 1033 participants (633 men and 400 women; mean age: 58.6±17.0 years). Framingham risk score was negatively correlated with FMD, HSS, and NID and was positively correlated with baseline BAD. HSS and NID were positively correlated with FMD, and baseline BAD was negatively correlated with FMD. In participants with normal NID, FMD was correlated with HSS, NID, and baseline BAD, all of which were independent variables of FMD in multivariate analysis. In participants with impaired NID, FMD was correlated with NID and baseline BAD, both of which were independent variables of FMD in multivariate analysis, but there was no association between FMD and HSS., Conclusions: NID and baseline BAD were independent variables of FMD regardless of the status of endothelium-independent vasodilation, whereas there was a significant association between FMD and HSS in participants with normal NID but not in those with impaired NID. The influence of HSS on FMD seems to be dependent on the status of endothelium-independent vasodilation., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

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