The Pressor Response to the Drinking of Cold Water and Cold Carbonated Water in Healthy Younger and Older Adults.

Purpose: Water drinking has been proposed for the treatment of orthostatic hypotension because it can increase blood pressure in patients. This study aimed to investigate whether drinking water with a cold or carbonation stimulus would cause a more effective pressor response, and whether it would be greater in older than in younger adults. Methods: We assessed blood pressure and heart rate from non-invasive arterial pressure (a volume-clamp method) and type II electrocardiography in 13 healthy young adults (6 females, 7 males; mean age, 19.9 ± 1.1 years) and nine healthy older adults (all females; mean age, 71.4 ± 4.2 years) who drank 200 mL of cold, cold carbonated, and room temperature water. Results: The pressor response to the drinking of cold and cold carbonated water was greater than that to room temperature water in both younger and older participants (p < 0.05; changes in systolic blood pressure of room temperature water, cold water and cold carbonated water in young: 15.31 ± 9.66, 22.56 ± 11.51 and 32.6 ± 17.98 mmHg, respectively; changes in systolic blood pressure of room temperature water, cold water and cold carbonated water in elderly: 21.84 ± 14.31, 41.53 ± 19.82 and 48.16 ± 16.77 mmHg, respectively). In addition, the pressor response to cold and cold carbonated water was persistent during the recovery period by about 5-10 mmHg (p < 0.05). Furthermore, the pressor response during the drinking and recovery periods was greater in the older than in the younger participants (p < 0.05). Conclusion: Our data suggest that even smaller amounts of water are able to elicit a sustained pressor response, in particular if the water is cold and carbonated. We speculate that the pressor effect may render cold and carbonated water an appropriate first aid method against certain forms of acute hypotension.

Comparison of anti-inflammatory effects of rivaroxaban vs. dabigatran in patients with non-valvular atrial fibrillation (RIVAL-AF study): multicenter randomized study.

Some experimental studies have shown that direct oral anticoagulants (DOACs) have anti-inflammatory effects. However, the interval changes in inflammatory markers in patients with non-valvular atrial fibrillation (AF) who receive DOACs remain unknown. Between July 2013 and April 2014, a total of 187 AF patients randomly assigned to receive rivaroxaban (n = 91) or dabigatran (n = 96) were assessed for eligibility. The levels of the following inflammatory markers were serially evaluated: high-sensitivity C-reactive protein, pentraxin-3, interleukin (IL)-1ß, IL-6, IL-18, tumor necrosis factor-α, monocyte chemotactic protein-1, growth and differentiation factor-15, and soluble thrombomodulin (sTM). The aim in this study was to evaluate the anti-inflammatory effects of rivaroxaban and dabigatran in patients with AF, in addition to the impact of markers on bleeding events. Finally, 117 patients (rivaroxaban: n = 55, dabigatran: n = 62) were included in the analysis at 12 months. Although the interval changes in sTM levels tended to be greater in the dabigatran group [0.3 (0-0.7) vs. 0.5 (0-1.0) FU/ml, p = 0.061], there were no significant differences in the interval changes in any inflammatory marker between 2 groups. There were no significant differences in bleeding events between 2 groups. The interval changes in sTM levels were significantly greater in patients with bleeding compared with those without [0.8 (0.5-1.3) vs. 0.4 (- 0.1-0.8) FU/ml, p = 0.017]. There were no significant differences in the interval changes in any inflammatory marker between rivaroxaban and dabigatran treatments in patients with AF. The increased levels of sTM after DOACs treatment might be related to bleeding events.

Does Treatment of Impaired Glucose Tolerance Improve Cardiovascular Outcomes in Patients with Previous Myocardial Infarction?

PURPOSE: We evaluated the effects of an alpha-glucosidase inhibitor, voglibose, on cardiovascular events in patients with a previous myocardial infarction (MI) and impaired glucose tolerance (IGT). METHODS: This prospective, randomized, open, blinded-endpoint study was conducted in 112 hospitals and clinics in Japan in 3000 subjects with both previous MI and IGT receiving voglibose (0.6 mg/day, n = 424) or no drugs (n = 435) for 2 years. The Data and Safety Monitoring Board (DSMB) recommended discontinuation of the study in June 2012 after an interim analysis when the outcomes of 859 subjects were obtained. The primary endpoint was cardiovascular events including cardiovascular death, nonfatal MI, nonfatal unstable angina, nonfatal stroke, and percutaneous coronary intervention/coronary artery bypass graft. Secondary endpoints included individual components of the primary endpoint in addition to all-cause mortality and hospitalization due to heart failure. RESULTS: The age, ratio of males, and HbA1C were 65 vs. 65 years, 86 vs. 87%, and 5.6 vs. 5.5% in the groups with and without voglibose, respectively. Voglibose improved IGT; however, Kaplan-Meier analysis showed no significant between-group difference with respect to cardiovascular events [12.5% with voglibose vs. 10.1% without voglibose for the primary endpoint (95% confidence interval, 0.82-1.86)]; there were no significant differences in secondary endpoints. CONCLUSION: Although voglibose effectively treated IGT, no additional benefits for cardiovascular events in patients with previous MI and IGT were observed. Voglibose may not be a contributing therapy to the secondary prevention in patients with MI and IGT. TRIAL REGISTRATION: Clinicaltrials.gov number: NCT00212017.

Assessment of effects of differences in trunk posture during Fowler's position on hemodynamics and cardiovascular regulation in older and younger subjects.

BACKGROUND: Downward shifts in blood volume with changing position generally cause tachycardic responses. Age-related decreases in vagal nerve activity could contribute to orthostatic hypotension in older individuals. Fowler's position is a reclined position with the back between 30° and 60°, used to facilitate breathing, eating, and other routine daily activities in frail and elderly patients. OBJECTIVE: This study examined whether stroke volume (SV) was higher and heart rate (HR) lower in Fowler's position with an upright upper trunk than in Fowler's position with the whole trunk upright in both older and younger subjects, based on the assumption that lower HR would result from reduced sympathetic activation in older individuals. METHODS: We assessed hemodynamics and HR variability from electrocardiography, noninvasive arterial pressure and impedance cardiography in 11 younger male subjects (age range, 20-22 years) and 11 older male subjects (age range, 64-79 years), using three positions: supine, or Fowler's positions with either 30° of lower trunk inclination and 60° of upper trunk inclination (UT60) or 60° of whole trunk inclination (WT60). Comparisons were then made between age groups and between positions. RESULTS: Reductions in SV and tachycardic response were smaller with UT60 than with WT60, in both younger and older subjects. In addition, reduced tachycardic response with upright upper trunk appeared attributable to decreased vagal withdrawal in younger subjects and to reduced sympathetic activation in older subjects. CONCLUSION: Our findings indicate that an upright upper trunk during Fowler's position allowed maintenance of SV and inhibited tachycardic response compared to an upright whole trunk regardless of age, although the autonomic mechanisms underlying tachycardic responses differed between younger and older adults. An upright upper trunk in Fowler's position might help to reduce orthostatic stress and facilitate routine activities and conversation in frail patients.

Small proximal aortic diameter is associated with higher central pulse pressure and poor outcome in patients with congestive heart failure.

BACKGROUND: A small proximal aortic diameter (AoD) is thought to be associated with a higher characteristic impedance of the proximal aorta. However, there has been no evidence of a relationship between directly evaluated AoD and directly measured central aortic pressure or the outcome of patients with cardiovascular diseases. METHODS AND RESULTS: (a) In 135 patients without heart failure (HF), who underwent coronary catheterization, we retrospectively examined the relationship between the AoD and the central aortic pressure or aortic elastance. The AoD adjusted with covariates was inversely correlated with the central pulse pressure (cPP; coefficient=-0.75; P=0.04; model R(2)=0.575) and the effective arterial elastance index (coefficient=-0.12; P=0.001; model R(2)=0.366). (b) In 197 patients who were hospitalized due to HF, we examined the relationship between the AoD (evaluated using echocardiography) and the outcome using a Cox proportional hazard model. Fifty-three patients died from various causes during the follow-up period (2.2±1.1 years). Multivariable analysis revealed that the AoD remained an independent risk factor for all-cause death (hazard ratio for 1 s.d. increase of the AoD: 0.68, 95% confidence interval: 0.50-0.92, P=0.013) and cardiovascular death (hazard ratio for 1 s.d. increase of the AoD: 0.63, 95% confidence interval: 0.43-0.93, P=0.019). CONCLUSIONS: A small AoD was associated with a higher cPP and aortic stiffening in the patients without HF, as well as with a poor outcome for HF patients. Although it is easy to evaluate the AoD, it may offer important information regarding the pulsatile load and may be useful for risk stratification of HF patients.

Long-term effects of ezetimibe-plus-statin therapy on low-density lipoprotein cholesterol levels as compared with double-dose statin therapy in patients with coronary artery disease.

OBJECTIVE: To assess the mechanism of long-term LDL-C-lowering effect of ezetimibe-plus-statin. METHODS: Coronary artery disease patients whose LDL-C ≥ 70 mg/dL after treatment with atorvastatin 10 mg/day or rosuvastatin 2.5 mg/day were randomly assigned to receive ezetimibe 10 mg/day + statin (n = 78) or double-dose statin (n = 72) for 52 weeks. RESULTS: Greater LDL-C reduction was observed and maintained until 52 weeks in ezetimibe-plus-statin, while LDL-C levels re-increased after 12 weeks in double-dose statin. Although lathosterol/TC increased, campesterol/TC decreased more in ezetimibe-plus-statin. In contrast, lathosterol/TC unchanged and campesterol/TC increased, increasing campesterol/lathosterol ratio for 52 weeks in double-dose statin. Plasma PCSK9 levels were higher in double-dose statin than in ezetimibe-plus-statin at 12 weeks, but similar at 52 weeks. CONCLUSION: Although the difference in PCSK9 between 2 groups was transient, that in both campesterol and lathosterol persisted until 52 weeks. These results demonstrated simultaneous inhibition of cholesterol absorption and synthesis provides stable and greater decrease in LDL-C levels.

Clinical usefulness of additional treatment with ezetimibe in patients with coronary artery disease on statin therapy. - From the viewpoint of cholesterol metabolism.-.

BACKGROUND: Ezetimibe-plus-statin therapy has been reported to provide greater reduction in low-density lipoprotein cholesterol (LDL-C) level than statin monotherapy. The aim of the present study was to evaluate the relationship between LDL-C lowering effect and baseline cholesterol absorption and synthesis markers in patients with coronary artery disease (CAD). METHODS AND RESULTS: A total of 171 patients with CAD whose LDL-C level was ≥ 100 mg/dl after treatment with atorvastatin (10mg/day) or rosuvastatin (2.5 mg/day) for 4 weeks were assigned to additionally receive ezetimibe (10mg/day) plus a statin or a double dose of statin for 12 weeks. The decreases in LDL-C (-30.0 ± 15.6 mg/dl vs. -19.2 ± 14.2 mg/dl) and the ratio of campesterol, an absorption marker, to total cholesterol levels (-1.35 ± 0.90 µg/mg vs. 0.33 ± 0.74 µg/mg) were greater in the ezetimibe-plus-statin group (P<0.05, respectively). The decrease in LDL-C level in the ezetimibe-plus-statin group was greatest in patients with baseline levels of higher absorption and lower synthesis markers and smallest in patients with baseline levels of lower absorption and higher synthesis markers (-34.3 ± 15.6 mg/dl vs. -21.5 ± 16.7 mg/dl, P<0.05). The decrease in LDL-C did not differ, irrespective of baseline levels of cholesterol absorption and synthesis markers, in the double-dose statin group, and was similar to that in patients with lower absorption and higher synthesis markers in the ezetimibe-plus-statin group. CONCLUSIONS: Ezetimibe-plus-statin therapy may be useful for lowering LDL-C level, irrespective of baseline levels of cholesterol absorption and synthesis markers.

[A case of a primary gastrointestinal stromal tumor (GIST) found in the greater omentum of a 99-year-old woman].

We report the case of a primary gastrointestinal stromal tumor (GIST) found in the greater omentum of an extremely elderly woman. A 99-year-old woman with a history of heart failure and renal failure presented with dyspnea and disturbance of consciousness. A tumor located between the stomach and spleen had been detected by abdominal computed tomography three years previously. After admission, she received oxygen supplementation and diuretics. However she died of heart failure and disseminated intravascular coagulation on the 31st day of hospitalization. Autopsy was performed on the same day. A large mass measuring 12.5 x 7.0 x 7.5 cm was revealed, originating from the greater omentum. Histopathologically, it was composed of spindle cells with the nuclei showing a focal palisading pattern, however there were no mitoses. Immunohistochemically, the tumor was positive for c-kit. The tumor was diagnosed as a primary GIST of the greater omentum.

Estimation of myocardial cell damage on the basis of mean electrocardiographic voltage and anatomical left ventricular mass.

Left ventricular mass (LVM) as assessed by magnetic resonance imaging (MRI, LVM(MRI)) and electrocardiographic (ECG) voltage reflect different pathological features. We hypothesized that ECG voltage is related to the electrical potential of cardiac muscle cells (electrical LVM) and to anatomical LVM as evaluated by MRI, and that the divergence between electrical LVM and anatomical LVM reflects the degree of myocardial damage. Because adipose tissue has high electrical resistance, we previously found a very strong correlation between body-fat-corrected mean ECG voltage (Vfm) and LVM as estimated by echocardiography in patients with essential hypertension. In this study we compared LVM(MRI), Vfm, the ratio of Vfm x 10(2)/LVM(MRI), and the results of 99mTc tetrofosmin scintigraphy in patients with and without myocardial infarction (MI). We studied 33 patients without Ml and 26 patients with Ml. Vfm significantly correlated with LVM(MRI) in patients without MI (r=0.71, p<0.01). The ratio of Vfm x 10(2)/LVM(MRI) apparently reflected the relation between electrical LVM and anatomical LVM. Vfm x 10(2)/LVM(MRI) in patients with MI was smaller than that in patients without MI (0.98+/-0.28 vs. 1.42+/-0.29, p<0.01). Vfm x 10(2)/LVM(MRI) decreased as 99mTc score increased (r=-0.66, p<0.01). Our results indicate that Vfm is a useful index of electrical LVM and that Vfm x 10(2)LVM(MRI) reflects the electrical potential of the viable myocardium in total anatomical LVM.