INTRODUCTIONWe aimed to evaluate the effectiveness and safety of canagliflozin as compared to sitagliptin in a real-world setting among multiethnic patients with Type 2 diabetes mellitus (T2DM) in Singapore.

METHODSThis was a new-user, active-comparator, single-centre retrospective cohort study. Patients aged 18-69 years with T2DM and estimated glomerular filtration rate ≥ 60 mL/min/1.73 m were eligible for inclusion if they were initiated and maintained on a steady daily dose of canagliflozin 300 mg or sitagliptin 100 mg between 1 May and 31 December 2014, and followed up for 24 weeks.

RESULTSIn total, 57 patients (canagliflozin 300 mg, n = 22; sitagliptin 100 mg, n = 35) were included. The baseline patient characteristics in the two groups were similar, with overall mean glycated haemoglobin (HbA1c) of 9.4% ± 1.4%. The use of canagliflozin 300 mg was associated with greater reductions in HbA1c (least squares [LS] mean change -1.6% vs. -0.4%; p < 0.001), body weight (LS mean change -3.0 kg vs. 0.2 kg; p < 0.001) and systolic blood pressure (LS mean change: -9.7 mmHg vs. 0.4 mmHg; p < 0.001), as compared with sitagliptin 100 mg. About half of the patients on canagliflozin 300 mg reported mild osmotic diuresis-related side effects that did not lead to drug discontinuation.

CONCLUSIONOur findings suggest that canagliflozin was more effective than sitagliptin in reducing HbA1c, body weight and systolic blood pressure in patients with T2DM, although its use was associated with an increased incidence of mild osmotic diuresis-related side effects.

Adolescent ; Adult ; Aged ; Blood Glucose ; drug effects ; Blood Pressure ; Body Mass Index ; Body Weight ; Canagliflozin ; administration & dosage ; Diabetes Mellitus, Type 2 ; drug therapy ; Female ; Glomerular Filtration Rate ; Hemoglobins ; analysis ; Humans ; Hypoglycemic Agents ; administration & dosage ; Least-Squares Analysis ; Male ; Middle Aged ; Osmosis ; Retrospective Studies ; Singapore ; Sitagliptin Phosphate ; administration & dosage ; Systole ; Treatment Outcome ; Young Adult

OBJECTIVETo study the efficacy of Chinese medicine (CM) on isolated systolic hypertension.

METHODSSeven electronic databases were searched for randomized controlled trials (RCTs) published until August 2015. Subgroup analyses and meta-analysis were performed to assess the efficacy and safety of the included studies.

RESULTSA total of 24 studies, including 2,096 patients (1,058 patients in the intervention group and 1,038 in the control group), were evaluated in the final analysis. Compared with a conventional therapy used alone, CM as additional intervention was more effective on systolic blood pressure [mean difference (MD)=-0.66, 95% confidence interval (CI)=(-0.97,-0.36), P<0.00001] and significantly diminished the pulse pressure [MD=-7.49, CI=(-12.69,-2.29), P<0.00001]. However it showed no additional benefit on diastolic blood pressure [MD=1.16, CI=(0.02, 2.29), P=0.87]. Adverse events were not explicitly reported in most RCTs.

CONCLUSIONSCM might be a promising approach for the elderly with isolated systolic hypertension, while the evidence for CM employed alone was insufficient. Considering the inherent limitations of the included studies, larger high-quality RCTs with extensive follow-up should be performed to validate our findings in the future.

Aged ; Blood Pressure ; Clinical Trials as Topic ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Humans ; Hypertension ; drug therapy ; Publication Bias ; Pulse ; Systole ; Treatment Outcome

INTRODUCTIONCentral aortic systolic pressure (CASP) has been shown to be a stronger predictor of cardiovascular events than brachial blood pressure (BP). Different classes of drugs have differential effects on CASP and brachial BP. This open prospective cohort study aimed to observe changes in CASP (measured using radial tonometry) among hypertensive Asians after 12 weeks of treatment with valsartan, an angiotensin receptor blocker (ARB).

METHODSPatients with treatment-naïve hypertension or uncontrolled hypertension who were on non-ARB therapy were eligible for inclusion. Patients with uncontrolled BP (i.e. ≥ 140/90 mmHg) received valsartan for 12 weeks. The patients' brachial systolic and diastolic BP (SBP and DBP), and CASP changes were monitored using the BPro® watch.

RESULTSThe mean age of the 44 enrolled patients was 35 years. At baseline, the mean BP and CASP were 150.2/91.4 ± 10.6/9.4 mmHg and 136.3 ± 12.2 mmHg, respectively. Valsartan reduced SBP, DBP and CASP by 14.9 ± 10.7 mmHg, 10.9 ± 8.4 mmHg and 15.3 ± 10.9 mmHg, respectively (all p < 0.001). Every 1.0-mmHg reduction in brachial SBP resulted in a 0.8-mmHg reduction in CASP (p < 0.001). A CASP cut-off of 122.5 mmHg discriminated between controlled and uncontrolled BP (sensitivity 74%, specificity 88%).

CONCLUSIONUsing radial tonometry, we demonstrated good correlation between CASP and brachial SBP reductions after 12 weeks of treatment with valsartan in our study cohort. Correlation analysis between CASP and SBP reductions may be useful for demonstrating whether a drug is able to lower CASP beyond lowering SBP.

Adult ; Angiotensin Receptor Antagonists ; pharmacology ; Aorta ; drug effects ; Blood Pressure ; Blood Pressure Monitoring, Ambulatory ; Diastole ; Female ; Humans ; Hypertension ; drug therapy ; Male ; Manometry ; methods ; Middle Aged ; Prospective Studies ; Receptors, Angiotensin ; metabolism ; Systole ; drug effects ; Valsartan ; therapeutic use ; Young Adult

The purpose of the present study is to investigate the effect of isoliquiritigenin (ISL) on the cerebral basilar artery in spontaneously hypertensive rats (SHR). The change of SHR systolic pressure was measured by tail artery pressure measurement instrument before and after ISL intervention. After perfusion with 1 × 10(-5) mol/L phenylephrine (PE), 1 × 10(-5) mol/L PE + 1 × 10(-4) mol/L ISL and 1 × 10(-5) mol/L PE, the diameter of the cerebral basilar artery separated from SHR was measured by pressure myograph. The current of large-conductance calcium-activated potassium (BKCa) channel of SHR single vascular smooth muscle cell (VSMC) was recorded by whole-cell patch-clamp technique and the cGMP levels of basilar artery was evaluated by ELISA. The results showed that 1) after intervention with ISL for 14 days, the systolic pressure of SHR was decreased from (218.3 ± 1.6) mmHg to (119.2 ± 1.9) mmHg (P < 0.01), but there was no difference in systolic pressure between ISL-treated SHR and Wistar-Kyoto (WKY) rat; 2) 1 × 10(-4) mol/L ISL relaxed the SHR cerebral basilar artery (P < 0.01); 3) ISL significantly increased the outward current density of VSMC from SHR cerebral basilar artery (P < 0.01, n = 6), and the effect could be reversed by 1 × 10(-3) mol/L TEA (a BKCa channel inhibitor), but 3 × 10(-4) mol/L 4-AP (a Kv channel inhibitor) had no effect on the enhanced current density induced by ISL in VSMC; 4) 1 × 10(-5) mol/L Methylene blue (a sGC inhibitor) significantly inhibited the ISL-enhanced current density in VSMC (P < 0.05, n = 6); 5) ISL significantly increased the cGMP level of SHR basilar artery (P < 0.05, n = 6). The results suggest that the role of the ISL in relaxing the SHR cerebral basilar artery may be related to its effect in enhancing BKCa current by increasing the levels of cGMP in the VSMC.
Animals ; Basilar Artery ; drug effects ; Blood Pressure ; Cerebral Arteries ; drug effects ; Chalcones ; pharmacology ; Cyclic GMP ; physiology ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; physiology ; Patch-Clamp Techniques ; Potassium Channels, Calcium-Activated ; physiology ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Systole

OBJECTIVETo investigate the effect of Qindan capsule (QC) on collagen synthesis and the mechanism underlying the process in spontaneously hypertensive rats (SHRs).

METHODSTwentyfour SHRs were divided into three groups: the hypertension model group, the QC treatment group, and the losartan treatment group. Eight Wistar Kyoto (WKY) rats were used as the normal control group. The systolic blood pressure (SBP) of the rats was monitored, and the thoracic aorta adventitia of the rats was segregated. The expressions of transforming growth factor 1 (TGF-β1), Smad3, and collagens I and were measured by histological staining and reverse transcription polymerase chain reaction.

RESULTSThe SBP was significantly higher in the model group than in the normal control group (P<0.01). However, a significant SBP-lowering effect was observed in QC or losartan treatment groups (P<0.05 or P<0.01) after 3 weeks of treatment. QC-treated rats showed a decrease of approximately 40 mm Hg, and the losartan-treated rats showed a decrease of approximately 50 mm Hg at the end of treatment compared with the beginning of treatment. The protein and gene levels of TGF-β1, Smad3, and collagens I and in the model group were significantly increased compared with those in the normal control group (P<0.01). However, the levels were significantly decreased in the QC or losartan treatment group compared with the model group (P<0.05 or P<0.01). However, there was no significant difference between the QC and losartan treatment groups (P<0.05).

CONCLUSIONSQC could exert its antihypertensive effect through down-regulating TGF-β1-stimulated collagen expressions. The TGF-β1/Smad3 signaling pathway may be involved in this process.

Adventitia ; drug effects ; metabolism ; pathology ; Animals ; Blood Pressure ; drug effects ; Blood Vessels ; drug effects ; metabolism ; pathology ; Capsules ; Collagen ; biosynthesis ; Collagen Type I ; genetics ; metabolism ; Collagen Type III ; genetics ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Losartan ; pharmacology ; Male ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Smad3 Protein ; genetics ; metabolism ; Staining and Labeling ; Systole ; drug effects ; Transforming Growth Factor beta1 ; genetics ; metabolism

BACKGROUND/AIMS: Magnesium (Mg) is an essential element for vascular function and blood pressure regulation. Several studies have demonstrated that Mg concentration is inversely associated with blood pressure, and that Mg supplementation attenuates hypertension. The purpose of this study was to evaluate the effect of dietary Mg supplementation on the blood pressure effects of an angiotensin II receptor blocker (ARB) in hypomagnesemic rats. METHODS: Fifty male Sprague-Dawley rats were randomly divided into Mg-deficient (n = 30), normal diet plus Mg (n = 10), and control groups (n = 10). Mg-free, high-Mg, and normal-Mg diets were respectively fed to the rats. After 14 weeks, 10 of the 30 Mg-deficient rats were treated with Mg, 10 Mg-deficient rats received an ARB, and 10 Mg-deficient rats received an ARB plus Mg for 4 weeks. RESULTS: Systolic blood pressure was significantly higher in the Mg-deficient rats than in the control rats at week 14. Hypomagnesemic rats exhibited decreased systolic blood pressure after treatment with Mg, and systolic blood pressure showed a greater decrease after ARB treatment. Treatment with the ARB/Mg combination resulted in the greatest decrease in systolic blood pressure. Mg deficiency did not affect the serum angiotensin II level, but did increase the serum aldosterone concentration. Concomitant Mg/ARB supplementation significantly decreased the elevated serum aldosterone level in hypomagnesemic rats. Kidney tissues of the hypomagnesemic rats revealed mild to moderate inflammatory infiltrates. Mg and/or ARB treatment did not reverse the inflammatory reaction in the kidneys of hypomagnesemic rats. CONCLUSIONS: Concurrent dietary Mg supplementation can enhance ARB-induced blood pressure reduction in rats with hypomagnesemic hypertension.
Aldosterone/blood ; Angiotensin II/blood ; Angiotensin II Type 1 Receptor Blockers/*pharmacology ; Animals ; Antihypertensive Agents/*pharmacology ; Biological Markers/blood ; Blood Pressure/*drug effects ; *Dietary Supplements ; Disease Models, Animal ; Hypertension/blood/*drug therapy/pathology/physiopathology ; Kidney/drug effects/pathology ; Magnesium/blood/*pharmacology ; Magnesium Deficiency/blood/*drug therapy/pathology/physiopathology ; Male ; Rats ; Rats, Sprague-Dawley ; Systole ; Time Factors

BACKGROUNDEpidemiological study showed that the use of angiotensin-converting enzyme inhibitors was associated with higher bone mineral density (BMD) in older people, especially male subjects, which suggested that angiotensin II may have a detrimental effect on bone. Therefore, blocking its effect may have a beneficial effect on bone health.

METHODSSix-month-old male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were used. Animals of each model were randomly assigned to the following four groups: Group 1, SHAM operated+vehicle; Group 2, orchidectomy (ORX)+vehicle; Group 3, ORX+low-dose losartan (10 mg×kg(-1)×d(-1)); and Group 4, ORX+high-dose losartan (25 mg×kg(-1)×d(-1)). Blood pressure was recorded weekly. SHAM and ORX operations were performed, followed by daily losartan and vehicle treatment from day 4 after operation for 16 weeks. Serum and 24-hour urine samples were collected for measurement of bone turnover markers before euthanasia and then the left femur was collected for measurements of BMD and microarchitecture before mechanical test.

RESULTSUrine deoxypyridinoline/urine creatinine (DPD/Cr) ratio was significantly higher in SHR than in WKY. BMD and microarchitecture parameters also showed bone deterioration in SHR. After ORX, serum osteocalcin concentration decreased and urine DPD/Cr ratio increased significantly accompanied by a significant decrease in cortical and trabecular BMD and cortical bone thickness in both WKY and SHR. High-dose losartan significantly increased DPD in urine in both SHR and WKY. Apart from marginal favorable changes in bone architecture in WKY treated with high-dose losartan, losartan did not show significant effect on BMD, bone area, bone microarchitecture, and mechanical properties in both SHR and WKY.

CONCLUSIONAngiotensin II type I receptor blocker losartan was not able to demonstrate significant effect on ORX-induced bone deterioration in both hypertensive and normotensive rats.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Animals ; Bone Density ; drug effects ; Bone and Bones ; drug effects ; pathology ; Hypertension ; drug therapy ; pathology ; physiopathology ; Losartan ; therapeutic use ; Male ; Orchiectomy ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Systole ; drug effects

OBJECTIVE: The purpose of this study is to determine the effects of propranolol on the left ventricular (LV) volume during CT coronary angiography. MATERIALS AND METHODS: The LV volume of 252 normal Chinese subjects (126 subjects with propranolol medication and 126 age- and gender-matched Chinese subjects without medication) was estimated using 64 slices multi-detector CT (MDCT). The heart rate difference was analyzed by the logistic linear regression model with variables that included gender, age, body height, body weight, systolic blood pressure (SBP), diastolic blood pressure (DBP) and the dosage of propranolol. The following global LV functional parameters were calculated: the real-end diastolic volume (EDV), the real-end systolic volume (ESV) and the real-ejection fraction (EF). RESULTS: The female subjects had a greater decrease of heart rate after taking propranolol. The difference of heart rate was negatively correlated with the dosage of propranolol. The real-EDV, the real-ESV and the real-EF ranged from 48.1 to 109 mL/m2, 6.1 to 57.1 mL/m2 and 41% to 88%, respectively. There was no significant difference in the SBP and DBP between the groups without and with propranolol medication (123 +/- 17 and 80 +/- 10 mmHg; 120 +/- 14 and 80 +/- 11 mmHg, respectively). The real-EDV showed no significant difference between these two groups, but the real-ESV and real-EF showed significant differences between these two groups (69.4 +/- 9.3 and 70.6 +/- 8.9 mL/m2; 23.5 +/- 5.7 and 25.6 +/- 3.7 mL/m2, 66.5 +/- 5.1% and 63.5 +/- 4.6%, respectively). CONCLUSION: The difference of heart rate is significantly influenced by gender and the dosage of propranolol. Propranolol will also increase the ESV, which contributes to a decreased EF, while the SBP, DBP and EDV are not statistically changed.
Adrenergic beta-Antagonists/*administration & dosage ; Case-Control Studies ; China ; Contrast Media/diagnostic use ; *Coronary Angiography ; Diastole ; Electrocardiography ; Female ; Heart Rate/*drug effects ; Humans ; Logistic Models ; Male ; Middle Aged ; Propranolol/*administration & dosage ; Radiographic Image Interpretation, Computer-Assisted ; Systole ; *Tomography, X-Ray Computed ; Triiodobenzoic Acids/diagnostic use ; Ventricular Function, Left/*drug effects

BACKGROUND/AIMS: The aim of this study was to identify changes in left ventricular (LV) performance in patients with a myocardial bridge (MB) in the left anterior descending coronary artery during resting and in an inotropic state. METHODS: Myocardial strain measurement by speckle-tracking echocardiography and conventional LV wall-motion scoring was performed in 18 patients with MB (mean age, 48.1 +/- 1.7 years, eight female) during resting and intravenous dobutamine challenge (10 and 20 microg/kg/min). RESULTS: Conventional LV wall-motion scoring was normal in all patients during resting and in an inotropic state. Peak regional circumferential strain increased dose dependently upon dobutamine challenge. Longitudinal strains of the anterior and anteroseptal segments were, however, reduced at 20 microg/kg/min and showed a dyssynchronous pattern at 20 microg/kg/min. Although there were no significant differences in radial strain and displacement of all segments at rest compared with under 10 microg/kg/min challenge, radial strain and displacement of anterior segments at 20 microg/kg/min were significantly reduced compared with posterior segments at the papillary muscle level (44.8 +/- 14.9% vs. 78.4 +/- 20.1% and 5.3 +/- 2.3 mm vs. 8.5 +/- 1.8 mm, respectively; all p < 0.001), and showed plateau (40%) or biphasic (62%) patterns. CONCLUSIONS: Reduced LV strain of patients with MB after inotropic stimulation was identified. Speckle-tracking strain echocardiography identified a LV myocardial dyssynchrony that was not demonstrated by conventional echocardiography in patients with MB.
Adrenergic beta-1 Receptor Agonists/*diagnostic use ; Adult ; Aged ; Chest Pain ; Coronary Angiography ; Diastole ; Dobutamine/*diagnostic use ; Echocardiography, Stress/instrumentation/*methods ; Female ; Humans ; Male ; Middle Aged ; *Myocardial Contraction ; *Myocardium ; Physical Exertion ; Systole ; *Ventricular Dysfunction, Left ; Ventricular Function, Left/*drug effects

OBJECTIVETo observe the effect of Chinese medical regimen and integrative medical regimen on quality of life and early renal impairment in elderly patients with isolated systolic hypertension (EISH).

METHODSA multi-center, randomized, double-blinded controlled trail was adopted. A total of 270 cases of EISH were randomly divided into 3 groups: Chinese medicine group (CM), combination group and Western medicine group (WM). The course of treatment was 4 weeks. The clinical blood pressure, integral of quality of life (SF-36 scale), immunoglubin G (IgG), microalbumin (mALB), beta(2)-microglobulin (beta(2)-MG), transferrin (TRF) and N-acetyl-beta'-D-glucosa-minidase (NAG) in urine were determined before and after the treatment.

RESULTSAfter treatment, systolic blood pressure depressed significantly in each group (P<0.05), and the combination group was superior to CM or WM group in depressing SBP (P<0.05); in each group, integral of quality of life improved in different degree, and combination group was superior to WM group in all 8 dimensions (P<0.05). The level of mALB and beta(2)-MG in urine decreased in all groups (P<0.05), and the combination group was superior to CM group or WM group in decreasing mALB (P<0.05).

CONCLUSIONSChinese medical regimen has affirmative effect in treating EISH patients, and could lower the systolic blood pressure, improve quality of life and early renal impairment of the patients, and integrative medical regimen has superiority on account of cooperation, and deserves further study.

Aged ; Aged, 80 and over ; Antihypertensive Agents ; pharmacology ; therapeutic use ; Blood Pressure ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Humans ; Hypertension ; drug therapy ; physiopathology ; Integrative Medicine ; Kidney ; drug effects ; pathology ; physiopathology ; Male ; Quality of Life ; Systole ; drug effects ; physiology