Effects of indomethacin on patent ductus arteriosus in neonates with genetic disorders and/or congenital anomalies.

OBJECTIVES: The study aimed to evaluate the effectiveness of intravenous indomethacin (IND) therapy for patent ductus arteriosus (PDA) in neonates with genetic disorders and/or congenital anomalies soon after birth. STUDY DESIGN: A total of 301 neonates with a genetic disorder and/or congenital anomalies and with a gestational age of ≥ 35 weeks were admitted during the study period. Eighty-five neonates with 56 genetic disorders (30 cases of trisomy 21, 10 cases of trisomy 18, and 16 others) and 29 congenital anomalies, and with clinical symptoms received intravenous IND therapy. The management methods were similar to those used for PDA in low-birth-weight infants. RESULTS: IND therapy had a clinical benefit at a high rate of 79% in these patients (90% and 70% in neonates with trisomies 21 and 18, respectively), including complete closure of the PDA in 52% of the patients. Although oliguria was observed in 43 infants (51%) and slight gastrointestinal bleeding was observed in 12 (14%), no infants had severe complications such as intracranial bleeding. CONCLUSIONS: IND therapy is an effective treatment option before considering surgery for PDA in neonates with genetic disorders and/or congenital anomalies. This therapy may reduce the difficulty of treatment in the acute stage among these neonates.

Umbilical cord milking stabilizes cerebral oxygenation and perfusion in infants born before 29 weeks of gestation.

OBJECTIVE: To investigate the effects of umbilical cord milking at birth on cerebral perfusion and systemic perfusion in very low birth weight (VLBW) infants. STUDY DESIGN: Cerebral tissue oxygenation index and cerebral fractional tissue oxygen extraction were monitored in 50 stable VLBW infants (gestational age <29 weeks, birth weight <1250 g), with 26 allocated to the milked group and 24 to the control group. We used near-infrared spectroscopy 3-6, 12, 18, 24, 36, 48, and 72 hours after birth. Left ventricular end-diastolic dimension, left ventricular ejection fraction, left ventricle (LV) Tei index (measurement of left ventricular systolic and diastolic function), left ventricular cardiac output, and superior vena cava flow were measured concurrently using echocardiography. RESULTS: There were no significant differences in gestational age and birth weight between the 2 groups. Hematocrit, left ventricular end-diastolic dimension, left ventricular cardiac output, and superior vena cava flow were higher in the milked group than in the control group, with improvement in the LV Tei index despite the absence of left ventricular ejection fraction changes within 24 hours after birth. Tissue oxygenation index increased and cerebral fractional tissue oxygen extraction decreased in the milked group within 24 hours after birth. CONCLUSION: Umbilical cord milking stabilized cerebral oxygenation and perfusion in VLBW infants by improving LV diastolic function by increasing LV preload.

Differential impact of antihypertensive drugs on cardiovascular remodeling: a review of findings and perspectives for HFpEF prevention.

Heart failure (HF) is an important health problem worldwide whose stages have traditionally been classified from A to D. In addition, HF can be categorized as that with preserved ejection fraction (HFpEF) and that with reduced ejection fraction (HFrEF). Hypertension and arterial stiffness in stage A HF are major drivers of the progression to left ventricular hypertrophy (LVH), a criterion of stage B HF. Although the pathogenesis of HFpEF is heterogeneous, affected patients tend to be older than HFrEF patients and have a greater prevalence of hypertension, which is closely associated with arterial stiffness and LVH. Thus, to treat HFpEF, the optimal intervention for improving prognosis is an aggressive approach to early-stage, i.e., Stage A and B, HF. This paper reviews the findings on arterial stiffness and LVH using conventional antihypertensive drugs such as angiotensin receptor II blockers (ARBs) and a new drug class for HF, ARB/neprilysin inhibitor (ARNi). Previous studies have suggested that the combination of an ARB with an L-T-type calcium channel blocker might be recommended for the improvement of arterial stiffness and regression of LVH. More recent research has shown that ARNi also improves central BP, which leads to a reduced afterload and a significant reduction in LVH. For optimal treatment of HFpEF, drug therapy should directly address arterial stiffness as well as hypertension.

A Simple Electrostatic Precipitator for Trapping Virus Particles Spread via Droplet Transmission.

The purpose of this study was to develop a simple electrostatic apparatus to precipitate virus particles spread via droplet transmission, which is especially significant in the context of the recent coronavirus disease 2019 (COVID-19) pandemic. The bacteriophage φ6 of Pseudomonas syringae was used as a model of the COVID-19 virus because of its similar structure and safety in experiments. The apparatus consisted of a spiked, perforated stainless plate (S-PSP) linked to a direct-current voltage generator to supply negative charge to the spike tips and a vessel with water (G-water) linked to a ground line. The S-PSP and G-water surface were paralleled at a definite interval. Negative charge supplied to the spike tips positively polarised the G-water by electrostatic induction to form an electric field between them in which ionic wind and negative ions were generated. Bacteriophage-containing water was atomised with a nebuliser and introduced into the electric field. The mist particles were ionised by the negative ions and attracted to the opposite pole (G-water). This apparatus demonstrated a prominent ability to capture phage-containing mist particles of the same sizes as respiratory droplets and aerosols regardless of the phage concentration of the mist particles. The trapped phages were successfully sterilised using ozone bubbling. Thus, the present study provides an effective system for eliminating droplet transmission of viral pathogens from public spaces.

Changes in cerebral perfusion in extremely LBW infants during the first 72 h after birth.

Cerebral perfusion and its relation with systemic circulation in extremely LBW (ELBW) infants in the early neonatal period are not well understood. The cerebral tissue oxygenation index (TOI) and cerebral fractional tissue oxygen extraction (FTOE) were monitored in stable 16 ELBW infants (GA <29 wk) using near-infrared spectroscopy (NIRS) at 3-6, 12, 18, 24, 36, 48, and 72 h after birth. The left ventricular end-systolic wall stress (ESWS), left ventricular ejection fraction (LVEF), left ventricular cardiac output (LVCO), and superior vena cava (SVC) flow were also measured simultaneously using echocardiography. The ESWS increased till 18 h and then decreased; LVEF, LVCO, and SVC flow decreased till 12 h and increased thereafter. The TOI decreased till 12 h and correlated with SVC flow; FTOE increased until 12 h and then decreased. These changes in variables of NIRS and echocardiographic measurements contrasted to changes in mean arterial blood pressure (MABP), which showed trends of continuous and gradual increase after birth. We conclude that even stable ELBW infants undergo evident transitional changes in cerebral oxygenation and perfusion in the early postnatal period, which may reflect changes in cardiac function and cardiac output.

Body Water-Mediated Conductivity Actualizes the Insect-Control Functions of Electric Fields in Houseflies.

In the present study, the relationship between body water loss and conductivity was examined in adult houseflies (Musca domestica). The events an insect experiences in an electric field are caused by the conductive nature of the insect body (i.e., movement of electricity within or its release from the insect). After houseflies were dehydrated, rehydrated, refrigerated, and frozen and thawed, they were placed in static and dynamic electric fields. Untreated houseflies were deprived of their free electrons to become positively charged and then attracted to the insulated negative pole in the static electric field and were exposed to corona and arc discharge from non-insulated negative pole in the dynamic electric field. There was no current in the bodies of dehydrated and frozen flies; hence, there was no attractive force or discharge exposure. In the remaining insects, the results were identical to those in the untreated control insects. These results indicated that the reduction of body water conductivity inhibited the release of electricity from the body in the static electric field and the discharge-mediated current flow through the body in the dynamic electric field. The insect was affected by the electric fields because of its conductivity mediated by body water.

Effects of Olmesartan and Azilsartan on Albuminuria and the Intrarenal Renin-Angiotensin System.

PURPOSE: Olmesartan and azilsartan decrease blood pressure more effectively than other angiotensin receptor blockers (ARBs). ARBs additionally decrease the urinary albumin to creatinine ratio (UACR), a urinary albumin marker, and urinary angiotensinogen (u-AGT), an intrarenal renin-angiotensin system activity marker. We examined the effects of these ARBs on blood pressure, UACR, and u-AGT in patients with uncontrolled hypertension. METHODS: Patients with uncontrolled hypertension treated with conventional ARBs, excluding olmesartan and azilsartan, for over 8 weeks were enrolled. We randomly switched patients from their prior ARBs to either olmesartan or azilsartan, and followed them for 24 weeks. RESULTS: Systolic blood pressure (SBP), diastolic blood pressure (DBP), and central systolic blood pressure (cSBP) significantly decreased at 24 weeks. UACR and u-AGT also decreased at 24 weeks in both groups. There were no significant differences in SBP, DBP, cSBP, UACR, or u-AGT between the groups. Therefore, we combined both groups for further analyses. After combining, SBP (160.5 ± 16.4 to 139.6 ± 15.6 mm Hg, P < 0.0001), DBP (88.4 ± 13.7 to 80.7 ± 13.2 mm Hg, P = 0.008), cSBP (167.4 ± 20.8 to 146.6 ± 24.6 mm Hg, P < 0.0001), UACR (13.8 to 9.0 mg/g Cre, P = 0.0096), and u-AGT (4.13 to 2.32 µg/g Cre, P = 0.0074) significantly decreased at 24 weeks. Patients with microalbuminuria (UACR ≥ 30 mg/g Cre) had significantly greater ΔUACR (-39.4 vs 0.27, P = 0.0024) and Δu-AGT (-11.9 vs -0.61, P = 0.0235) than patients without microalbuminuria. The changes in u-AGT were significantly associated with changes in UACR (r = 0.411, P = 0.046); however, there was no significant relationship between the changes in u-AGT and those in SBP or DBP. CONCLUSION: Olmesartan and azilsartan decreased blood pressure, UACR, and u-AGT more than the other ARBs, and exerted depressor and renoprotective effects.

Comparison between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on the risk of stroke recurrence and longitudinal progression of white matter lesions and silent brain infarcts on MRI (CEREBRAL study): rationale, design, and methodology.

OBJECTIVES: Patients with a history of ischemic stroke are known to develop new ischemic stroke. While asymptomatic, the presence and progression of silent brain infarcts and white matter lesions on magnetic resonance imaging are associated with an increased risk of future strokes. Both angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are recommended for the primary and secondary prevention of stroke, but there are no direct comparisons of angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers regarding their cerebroprotective effects, including their effect on asymptomatic cerebral lesions detected by magnetic resonance imaging. METHODS: Elderly (65 years or older) patients with essential hypertension who underwent cerebral magnetic resonance imaging and were found to have any cerebral ischemic lesions, such as cerebral infarction, silent brain infarct, or white matter lesion, were enrolled in this CEREBRAL study. Patients who agreed to participate were enrolled in the randomized controlled trial portion. Patients who did not agree to participate in the randomized controlled trial were enrolled in the cohort study portion. After two-years of angiotensin-converting enzyme inhibitor or angiotensin II receptor blockers treatment, follow-up magnetic resonance imaging examination will be performed. The primary end-point is the composite of (1) occurrence of a fatal or nonfatal cerebrovascular event or (2) progression of cerebrovascular lesions as evaluated by magnetic resonance imaging, including white matter lesions or silent brain infarcts. After enrollment, cognitive function was evaluated, if possible, using the Mini-Mental State Examination. CONCLUSIONS: Our study will clarify whether angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers are more effective for preventing primary and recurrence of ischemic stroke, including the progression of asymptomatic cerebral lesions on magnetic resonance imaging, in elderly hypertensive patients.

Determination of enterovirus serotype inferred from sequence analysis of PCR products.

BACKGROUND: Enterovirus infections are common in neonates. Virus isolation is the only diagnostic method to confirm enterovirus serotype infections, however, is not always successful. OBJECTIVES: A new approach for the diagnosis of enterovirus infections was performed, using the reference strain inferred from sequence analysis of PCR products. STUDY DESIGN: Virus isolation, enterovirus RT-PCR and sequence analysis were performed from clinical samples or stored sera from two neonates with fever and rash. Neutralizing test (NT) antibodies against prototype reference virus were measured in paired sera. RESULTS: Virus isolation was negative in both patients but the enterovirus genome was amplified in the acute phase sera obtained from the two patients. From the results of sequence analysis of 109 nucleotides located in the 5'-noncoding of the conserved region of enteroviruses, a high homology to echovirus types 25 and 30 was found. More than a 4-fold increase in NT antibodies against reference viruses was demonstrated in the acute and convalescent phase sera. They were confirmed as echovirus type 25 and 30 infection, respectively. CONCLUSIONS: These virological examinations are practical and useful for clinical settings for a diagnosis of enterovirus infections because of an insufficient positive rate in virus isolation.

Efficacy of various antihypertensive agents as evaluated by indices of vascular stiffness in elderly hypertensive patients.

When observed in elderly hypertensive patients, increased pulse pressure (PP) and arterial stiffness are known to be independent risk factors for cardiovascular diseases. Increased systolic blood pressure (SBP) leads to left ventricular hypertrophy, while decreased diastolic blood pressure (DBP) results in decreased coronary circulation. It is known that increased arterial stiffness is the major cause of increased PP. Thus basic morbid states of cardiac failure or ischemic heart diseases are more likely to develop in elderly hypertensive patients with increased PP and arterial stiffness, and there is need of antihypertensive drugs that decrease these effects in elderly hypertensives. In this study, we compared the effects of an angiotensin-receptor blocker (ARB: valsartan), an angiotensin-converting enzyme inhibitor (ACE-I: temocapril), and long-acting Ca antagonists (L- and N-type Ca channel blocker: cilnidipine; and L-type Ca channel blocker: nifedipine CR) on PP and arterial stiffness measured by pulse wave velocity in elderly hypertensive patients for 3 months. The ARB yielded the largest reductions in PP and brachial-ankle pulse wave velocity (baPWV), followed by the ACE-I and L- and N-type Ca channel blocker, while the L-type Ca channel blocker yielded no improvement. The effects on arterial stiffness and PP thus varied among the drug characteristics. Although ARB achieved the largest reduction in baPWV, this decrease was not associated with any reductions in PP, SBP, DBP, or mean blood pressure, as were the baPWV-decreases achieved by the other drugs, suggesting that ARB may further reduce the risk of arteriosclerosis in elderly hypertensive patients by decreasing arterial stiffness in addition to its antihypertensive effect.

Enterovirus-related type 1 diabetes mellitus and antibodies to glutamic acid decarboxylase in Japan.

OBJECTIVES: In order to clarify the relationship between enteroviruses and type 1 diabetes mellitus in Japan we investigated enteroviral RNA in serum from children with type 1 diabetes mellitus. METHODS: We investigated enteroviral RNA in serum from children with type 1 diabetes mellitus by using highly sensitive RT-PCR. Additionally the sequences and viral loads were determined and compared with anti-coxsackie virus antibodies and anti-glutamic acid decarboxylase (GAD) antibodies. RESULTS: RT-PCR for enterovirus was positive in 23 (37.7%) from 61 samples. The positivity had no disparity of age, but decreased by aging after the occurrence of type 1 diabetes mellitus. The sequences of the positives were similar as those of coxsackie B4. The viral loads revealed that there was no positive patient with high titers of anti-GAD antibodies. CONCLUSION: In Japan there is some correlation with type 1 diabetes mellitus and enterovirus. The pathophysiology of type 1 diabetes mellitus seems to consist of a direct destruction by persistent coxsackie virus and the autoimmune mechanism through autoantibodies against beta-cells.

Hypothermia during kainic acid-induced seizures reduces hippocampal lesions and cerebral nitric oxide production in immature rabbits.

We investigated (1) whether cerebral hypothermia during kainic acid (KA)-induced seizures was neuroprotective; and (2) whether nitric oxide (NO) production in the brain during seizures was altered by cerebral hypothermia in immature rabbits. Twelve female rabbits, aged 2 weeks, were anesthetized, paralyzed and mechanically ventilated. We continuously measured NO production in the brain by NO-selective electrode, cortical electroencephalogram (EEG), regional cerebral blood flow (rCBF) by laser Doppler flowmetry, rectal and cerebral temperatures and mean arterial blood pressure (MABP) during KA (12 mg/kg, i.v.)-induced seizures in the hypothermic group (n = 6; rectal temperature, 33 degrees C), and in the normothermic group (n = 6; rectal temperature, 37 degrees C). The normothermic group showed a gradual increase in NO generation in the brain, which was significantly inhibited in the hypothermic group. There were no significant differences in the increases in rCBF, MABP, arterial blood gases, blood glucose, or EEG abnormalities between the two groups. Neuronal damages in the hippocampus (CA3) were significantly lower in hypothermia than in normothermia. These results suggest that hypothermia attenuates NO production during drug-induced seizures and decreases hippocampal brain lesions in the immature rabbit brain. These results may help to explain the neuroprotective effects of hypothermia.

A case of Wilson-Mikity syndrome with high serum KL-6 levels.

KL-6 and surfactant protein D (SP-D) serum concentrations are known to rise in adult patients with various types of interstitial pneumonia. We evaluated the time course of serum KL-6, SP-D, and lactate dehydrogenase (LDH) levels in an infant with Wilson-Mikity syndrome. In this case, serum KL-6 levels correlated with clinical symptoms better than serum SP-D and LDH levels. The findings of this case suggest that high serum levels of KL-6 show activity of interstitial lung disease of Wilson-Mikity syndrome.

Difference in cerebral and peripheral hemodynamics among term and preterm infants during the first three days of life.

BACKGROUND: The relationship between cerebral and peripheral hemodynamics during the early postnatal period has not been clarified. OBJECTIVES: To evaluate cerebral and peripheral oxygenation and blood volumes between term and preterm infants during the first 3 days of life. MATERIALS AND METHODS: We performed near-infrared time-resolved spectroscopy on 32 term infants (term group) and 40 preterm infants (preterm group), with an optode placed on their forehead and upper arm. The cerebral blood volume (CBV), peripheral blood volume (PBV), cerebral Hb oxygen saturation (cSO2) and peripheral Hb oxygen saturation (pSO2) were measured at 3-6, 12, 24, 48 and 72 h after birth. RESULTS: The CBV in the term group (2.45 ± 0.47 ml/100 g) was significantly higher than that in the preterm group (1.97 ± 0.33 ml/100 g). In contrast to the CBV, the PBV in the preterm group (3.63 ± 0.76 ml/100 g) was significantly higher than that in the term group (3.26 ± 0.56 ml/100 g). In the preterm group, there was a significant positive relationship between the CBVs and PBVs at each time point except at 72 h after birth. Despite the differences in blood volumes, there were no differences in the cSO2 and pSO2 between the two groups. CONCLUSIONS: The contrasting results in the CBV and PBV between the term and preterm infants might be explained by differences in the maturation of the physiological mechanism to control CBV and PBV.

Comparison of changes in cerebral and systemic perfusion between appropriate- and small-for-gestational-age infants during the first three days after birth.

PURPOSE: The aims of the current study were to compare changes in cerebral and systemic perfusion in appropriate-for-gestational-age (AGA) and small-for-gestational-age (SGA) infants immediately after birth. METHODS: Cerebral blood volume (CBV), cerebral Hb oxygen saturation (cSO2) and cerebral fractional tissue oxygen extraction (cFTOE) among 57 AGA infants and 30 SGA infants were monitored using a newly developed time-resolved spectroscopy system during the first 3days of life. The left ventricular ejection fraction (LVEF), left ventricular cardiac output (LVCO) and E/e' values were determined by three-dimensional echocardiography and tissue Doppler imaging performed simultaneously. RESULTS: There were significant differences between the body weights of both the AGA and SGA infants, but not between the gestational age and head circumferences in both groups. Although CBV showed no significant difference between the groups, cSO2 was significantly higher and cFTOE was lower in SGA infants than in AGA infants. Hematocrit (Ht) levels were significantly higher and LVEF and LVCO were lower in SGA infants than in AGA infants. Negative correlation was observed between CBV and Ht levels in AGA infants, but not in SGA infants. CONCLUSIONS: The high Ht levels and vasoreactivity in SGA infants might be a compensatory mechanism in order to maintain oxygen delivery to the brain, which reflects the condition of chronic hypoxia during the fetal period and also reflects the weak contraction and low cardiac output of the left ventricle sustaining the relatively large brain from the fetal period to after birth.

Azelnidipine plus olmesartan versus amlodipine plus olmesartan on arterial stiffness and cardiac function in hypertensive patients: a randomized trial.

PURPOSE: 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 (ß = 0.41, P < 0.001) and CBP (ß = 0.47, P = 0.01) were independently associated with the change in LVMI, the change in baPWV (ß = 0.25, P < 0.001) was independently associated with the change in E/e' ratio, and the changes in baPWV (ß = 0.21, P = 0.001) and AIx (ß = 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.

Major risk factors for the appearance of white-matter lesions on MRI in hypertensive patients with controlled blood pressure.

PURPOSE: 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 (<60 mL/minute/1.73 m(2)) tended to have higher grade WMLs. The odds ratio was 2.87 for FDWMH (P = 0.017), 1.99 for FPVH (P = 0.131), and 2.33 for SDWMH in the parietal area (P = 0.045). CONCLUSION: Presence of WMLs was associated with eGFR, but not with either the brachial SBP or cSBP in hypertensive patients with well-controlled BP.

Adding thiazide to a rennin-angiotensin blocker regimen to improve left ventricular relaxation in diabetes and nondiabetes patients with hypertension.

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 A(1c) 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.

Effects of smoking cessation on central blood pressure and arterial stiffness.

PURPOSE: 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.

Effects of Azelnidipine plus OlmesaRTAn versus amlodipine plus olmesartan on central blood pressure and left ventricular mass index: the AORTA study.

PURPOSE: 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.