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Takeshi Takami,1 Yoshihiko Saito21Department of Internal Medicine, Clinic Jingumae, Kashihara, Japan; 2First Department of Internal Medicine, Nara Medical University, Kashihara, JapanPurpose: To compare the long-term effects of olmesartan combined with either azelnidipine or amlodipine on central blood pressure (CBP), left ventricular (LV) mass index (LVMI), LV diastolic function (e´ velocity, E/e´ ratio, E/A ratio) and arterial stiffness (brachial-ankle pulse wave velocity [baPWV] and augmentation index normalized for a heart rate of 75 bpm [AIx]).Patients and methods: Patients with systolic BP ≥140 mmHg and/or diastolic BP ≥ 90 mmHg received olmesartan monotherapy (20 mg/day) for 12 weeks. They were then randomly assigned to fixed-dose add-on therapy with azelnidipine (16 mg/day; n = 26) or amlodipine (5 mg/day; n = 26) for a further 2 years. CBP, LVMI, e´ velocity, E/e´ratio, E/A ratio, baPWV, and AIx were measured at baseline, 6 months, and 2 years.Results: Baseline characteristics of both groups were similar. The decrease in brachial BP over 2 years was similar in both groups. CBP, LVMI, E/e´ ratio, baPWV, and AIx decreased significantly, and the E/A ratio and e´ velocity increased significantly in both groups. The decreases in CBP (P < 0.001), AIx (P < 0.001), baPWV (P < 0.001), LVMI (P < 0.001), and E/e´ (P = 0.002) as well as the increase in E/A ratio (P = 0.03) over 2 years were significantly greater in the olmesartan/azelnidipine group than in the olmesartan/amlodipine group. Multivariate linear regression analyses showed that the changes in baPWV (β = 0.41, P < 0.001) and CBP (β = 0.47, P = 0.01) were independently associated with the change in LVMI, the change in baPWV (β = 0.25, P < 0.001) was independently associated with the change in E/e´ ratio, and the changes in baPWV (β = 0.21, P = 0.001) and AIx (β = 0.25, P = 0.03) were independently associated with the change in E/A ratio.Conclusion: Treatment with olmesartan/azelnidipine for 2 years resulted in greater improvements in CBP, LVMI, and LV diastolic function, and arterial stiffness compared with olmesartan/amlodipine. Improvements in LV diastolic function were associated with improvements in arterial stiffness.Keywords: central blood pressure, arterial stiffness, left ventricular mass index, left ventricular diastolic function, olmesartan/azelnidipine

Takeshi Takami,1 Hiroshi Ito,2 Katsuhisa Ishii,3 Kenei Shimada,4 Katsuomi Iwakura,5 Hiroyuki Watanabe,6 Shota Fukuda,7 Junichi Yoshikawa81Department of Internal Medicine, Clinic Jingumae, Kashihara, Japan; 2Department of Cardiovascular Medicine, Okayama University, Graduate School of Medicine, Okayama, Japan; 3Department of Cardiology, Kansai Electric Power Hospital, Osaka, Japan; 4Department of Internal Medicine and Cardiology, Osaka City University of Medicine, Osaka, Japan; 5Cardiovascular Center, Sakurabashi Watanabe Hospital, Osaka, Japan; 6Department of Cardiology, Sakakibara Heart Institute, Tokyo, Japan; 7Department of Medicine, Osaka Ekisaikai Hospital, Osaka, Japan; 8Nishinomiya Watanabe Cardiovascular Center, Nishinomiya, JapanAbstract: The urinary albumin to creatinine ratio (UACR) is an independent predictor of outcomes in patients with diastolic dysfunction. Thus, we investigated the relationship between diastolic dysfunction, UACR, and diabetes mellitus (DM) in the EDEN study. We investigated the effect of switching from an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) to a combination of losartan and hydrochlorothiazide on left ventricular (LV) relaxation in patients with hypertension and diastolic dysfunction. We enrolled 106 patients with and 265 patients without DM. All patients had diastolic dysfunction and had not achieved their treatment goals with an ACEi or ARB. The measurements of e′ velocity and E/e′ ratio was performed with echocardiography as markers of LV diastolic function. We switched the ACEi or ARB to losartan/hydrochlorothiazide and followed these patients for 24 weeks. UACR was decreased in patients with DM (123.4 ± 288.4 to 66.5 ± 169.2 mg/g creatinine; P = 0.0024), but not in patients without DM (51.2 ± 181.8 to 39.2 ± 247.9 mg/g creatinine; P = 0.1051). Among DM patients, there was a significant relationship between changes in UACR and changes in e′ velocity (r = –0.144; P = 0.0257) and between changes in estimated glomerular filtration rate and changes in the E/e′ ratio (r = –0.130; P = 0.0436). Among patients without DM, there was a significant relationship between changes in high-sensitivity C-reactive protein (hs-CRP) and changes in E/e′ (r = 0.205; P = 0.0010). Multivariate analysis demonstrated changes in hemoglobin A1c levels as one of the determinants of change of e′ and E/e′ in patients with DM, whereas hs-CRP was the determinant of change of e′ among patients without DM. These data suggest that improvement in LV diastolic function is associated with an improvement of DM and a concomitant reduction in UACR among DM patients, and with a reduction of hs-CRP in patients without DM when thiazide is added to a renin–angiotensin blocker treatment regimen.Keywords: diastolic dysfunction, diabetes, urinary albumin to creatinine ratio, losartan, HCTZ

Takeshi Takami1, Shigeru Yamano2, Sadanori Okada3, Mio Sakuma4, Takeshi Morimoto4, Hiroshi Hashimoto5, Satoshi Somekawa3, Yoshihiko Saito31Department of Internal Medicine, Clinic Jingumae, Kashihara, Japan; 2Department of Internal Medicine, Nara Rehabilitation Center, Nara, Japan; 3First Department of Internal Medicine, Nara Medical University, Kashihara, Japan; 4Center for General Internal Medicine and Emergency Care, Kinki University School of Medicine, Osaka, Japan; 5Department of Neurosurgery, Hashimoto Clinic, Kashihara, JapanPurpose: Blood pressure (BP), age, and reduced renal function are major risk factors for white-matter lesions (WMLs) in the general population. However, it remains unclear whether or not the BP itself or other parameters related to the BP are associated with WMLs in hypertensive patients with well-controlled BP. We investigated the relationships of the presence of WMLs with the central systolic BP (cSBP) and estimated glomerular filtration rate (eGFR) in treated hypertensive patients.Method: We studied 185 hypertensive patients with median duration of hypertension, 10.0 years, whose BP is controlled to SBP and diastolic BP (DBP) of 139 ± 17 and 79 ± 10 mmHg, respectively. We measured cSBP and brain magnetic resonance imaging (MRI) was examined within 2 weeks after last BP and biological measurements.Results: Patients with higher-grade WMLs, as assessed by the presence of Scheltens deep white-matter hyperintensity (SDWMH) in the frontal (grade 0–2 vs 3–6) and parietal areas (grade 0–2 vs 3–6) where small arteries are affected at earlier stage of hypertension, as well as that of Fazekas deep white-matter hyperintensity (FDWMH) (grade 2–3 vs 0–1) and Fazekas periventricular hyperintensity (FPVH) (grade 1–3 vs 0) were older, had higher serum creatinine levels, a longer duration of hypertension, and lower eGFR values. The grade of the WMLs was not associated with either the cSBP or the brachial SBP. In logistic regression analyses after adjustment for age, sex, cSBP, and hypertension duration, showed significant association between eGFR and WMLs. The patients with lower eGFR (

Takeshi Takami1,Yoshihiko Saito21Department of Internal Medicine, Clinic Jingumae, Kashihara, Nara, Japan; 2First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, JapanPurpose: Smoking affects arterial stiffness, thus causing an elevation in central blood pressure (CBP). The present study was designed to examine whether smoking cessation treatment improved CBP and arterial stiffness.Patients and methods: We conducted an observational study of 70 patients receiving smoking cessation treatment. Before and 60 weeks after the start of a 12-week varenicline treatment, we measured brachial blood pressure, CBP, brachial-ankle pulse wave velocity (baPWV), normalized radial augmentation index (rAIx@75), left ventricular weight, and left ventricular diastolic function of each patient. The data were compared between the patients who succeeded in quitting smoking (smoking cessation group; n = 37) and those who failed to quit smoking (smoking group; n = 33).Results: Baseline characteristics were similar in both groups. Brachial blood pressure remained unchanged in both groups. CBP, baPWV, and rAIx@75 decreased significantly in the smoking cessation group, while these parameters showed no significant change in the smoking group. Thus, CBP, baPWV, and rAIx@75 showed greater decrease in the smoking cessation group than in the smoking group (CBP, −7.1 ± 1.4 mmHg vs 1.2 ± 2.7 mmHg; P < 0.01; baPWV, −204 ± 64 cm/s vs −43 ± 72 cm/s; P < 0.01; rAIx@75, −6.4 ± 2.8% vs −1.0 ± 3.9%; P < 0.01). Left ventricular weight and left ventricular diastolic function remained unchanged in both groups.Conclusion: Patients in the smoking cessation group showed significant improvement in CBP, baPWV, and rAIx@75. These results indicate that smoking cessation can improve arterial stiffness and CBP.Keywords: central blood pressure, augmentation index, brachial-ankle pulse wave velocity, smoking cessation, varenicline

Takeshi Takami1, Yoshihiko Saito21Department of Internal Medicine, Clinic Jingumae, Kashihara, Japan; 2First Department of Internal Medicine, Nara Medical University, Kashihara, JapanPurpose: The aim of this study was to compare the effects of olmesartan combined with either azelnidipine or amlodipine on central blood pressure (CBP) and left ventricular mass index (LVMI) in hypertensive patients.Patient and methods: Patients with brachial systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg received olmesartan monotherapy (20 mg daily) for 12 weeks. The patients were then randomly assigned to fixed-dose add-on therapy with azelnidipine (16 mg daily) or amlodipine (5 mg daily) (25 patients/group) for a further 24 weeks. CBP and LVMI were measured at baseline and at the end of the study.Results: Baseline characteristics were similar in both groups. The decrease in brachial BP was similar in both groups. CBP and LVMI decreased significantly in both groups (both, P < 0.001). However, the decreases in CBP and LVMI were significantly greater with olmesartan/azelnidipine than with olmesartan/amlodipine (CBP, P < 0.001; LVMI, P = 0.002).Conclusions: These findings indicate that olmesartan/azelnidipine had greater effects on CBP and LVMI than did olmesartan/amlodipine, even though the reduction in brachial BP was similar in both groups. These differential effects on CBP and LVMI may have important implications for cardiovascular risk reduction.Keywords: central blood pressure, left ventricular mass index, augmentation index, brachial-ankle pulse wave velocity, olmesartan/azelnidipine

Abstract Understanding how symmetry-breaking processes generate order out of disorder is among the most fundamental problems of nature. The scalar Higgs mode – a massive (quasi-) particle – is a key ingredient in these processes and emerges with the spontaneous breaking of a continuous symmetry. Its related exotic and elusive axial counterpart, a Boson with vector character, can be stabilized through the simultaneous breaking of multiple continuous symmetries. Here, we employ a magnetic field to tune the recently discovered axial Higgs-type charge-density wave amplitude modes in rare-earth tritellurides. We demonstrate a proportionality between the axial Higgs component and the applied field, and a 90° phase shift upon changing the direction of the magnetic field. This indicates that the axial character is directly related to magnetic degrees of freedom. Our approach opens up an in-situ control over the axial character of emergent Higgs modes.

An experiment involving the 270 GHz millimeter wave mixing of a Ba(sub 1-x)K(sub x)BiO3 (BKBO) junction with a log-periodic antenna using a quasi-optical coupling technique. The BKBO grain boundary junction and antenna were fabricated on an MgO bicrystal substrate with an in-plane misorientation angle of 24 degrees. The first quasiparticle mixing in an oxide superconductor was demonstrated.

Abstract Fractionalization of quantum degrees of freedom holds the key to finding new phenomena in physics, e.g., the quark model in hadron physics and the spin-charge separation in strongly-correlated electron systems. A typical example of the fractionalization in quantum spin systems is the spin-1 Haldane state, whose intriguing characteristics are well described by fractionalized virtual spins, delivering two individual spin-1/2 degrees of freedom as edge states. Here we theoretically propose an exotic extension of the Haldane state to the pseudo spin-1 model consisting of the mixture of real spin and spin chirality, resulting in quasi-fractionalization of spin-1/2 magnetization, i.e., an approximately-1/4 spin. Existence of the edge state is confirmed both analytically and numerically in a triangular spin tube, combining a low-energy perturbation theory and variational matrix-product state method. Our study not only proposes an unconventional quantum spin object but paves a way to chop the elementary quantities further.

Recent advancements in pulse laser technology have facilitated the exploration of nonequilibrium spectroscopy of electronic states in the presence of strong electric fields across a broad range of photon energies. The Keldysh crossover serves as an indicator that distinguishes between excitations resulting from photon absorption triggered by near-infrared multicycle pulses and those arising from quantum tunneling induced by terahertz pulses. Using a time-dependent density-matrix renormalization group, we investigate the emergence of the Keldysh crossover in a one-dimensional (1D) Mott insulator. We find that the Drude weight is proportional to photo-doped doublon density when a pump pulse induces photon absorption. In contrast, the Drude weight is suppressed when a terahertz pulse introduces doublons and holons via quantum tunneling. The suppressed Drude weight accompanies glassy dynamics with suppressed diffusion, which is a consequence of strong correlations and exhibits finite polarization decaying slowly after pulse irradiation. In the quantum tunneling region, entanglement entropy slowly grows logarithmically. These contrasting behaviors between the photon-absorption and quantum tunneling regions are a manifestation of the Keldysh crossover in 1D Mott insulators and provide a novel methodology for designing the localization and symmetry of electronic states called subcycle-pulse engineering.