Search

The Gemini-AALA (Australia, Asia, Latin America, Africa/Middle East) study evaluated the efficacy and safety of single-pill amlodipine/atorvastatin (Caduet) for the treatment of patients of diverse ethnicity with concomitant hypertension and dyslipidaemia. This was a 14-week, open-label study including patients from 27 countries across the Middle East, Asia-Pacific, Africa and Latin America. Eight dosage strengths of single-pill amlodipine/atorvastatin (5/10, 10/10, 5/20, 10/20, 5/40, 10/40, 5/80 and 10/80 mg) were titrated to improve blood pressure and lipid control. Blood pressure and lipid goals were determined according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) and National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP ATP III) guidelines, respectively (blood pressure,140/90 or130/80 mm Hg; low-density lipoprotein cholesterol (LDL-C),4.1 to2.6 mmol l(-1) (160 to100 mgdl(-1))). Overall, 1649 patients received study medication. Most patients (91.4%) hador=1 cardiovascular risk factor (as defined by NCEP ATP III guidelines) in addition to hypertension/dyslipidaemia, and 61.7% had coronary heart disease/risk equivalent. At baseline, mean blood pressure was 146.6/88.3 mm Hg and LDL-C was 3.4 mmol l(-1) (130.2 mgdl(-1)). At week 14, 55.2% of patients reached both blood pressure and lipid goals, 61.3% reached blood pressure goal and 87.1% reached lipid goal (34.0% were at lipid goal at baseline). Mean blood pressure reduction was 20.2/11.4 mm Hg. For patients who were lipid-lowering drug naive at baseline, mean reduction in LDL-C was 41.0%. Treatment-related adverse events led to the discontinuation of 3.6% of patients. Single-pill amlodipine/atorvastatin therapy was well tolerated and effective for the reduction of blood pressure and lipids to recommended goals in patients from diverse ethnic backgrounds.

To examine the effects of dietary isoflavone supplementation with an extract from red clover on cognitive function in postmenopausal women.Thirty postmenopausal women aged greater than 60 years received either two tablets of an extract of aglycone isoflavones from red clover (each containing formononetin 25 mg, biochanin 2.5 mg and less than 1 mg of daidzein and genistein) for 6 months in a randomized, controlled clinical trial. Cognitive function tests were performed at baseline and at the end of isoflavone or placebo therapy.Isoflavone supplementation was associated with an apparent improvement in block design (a test of visual-spatial intelligence) compared to placebo (isoflavone +12%, placebo -3%; p = 0.03), no improvement in verbal memory compared to an improvement on placebo (isoflavone +1%, placebo +29%; p = 0.023) and a deterioration in digit recall compared to placebo (isoflavone -6%, placebo +12%; p = 0.029). However, these findings were not statistically significant when corrections were made for potential chance findings due to multiple comparisons.Isoflavone supplementation does not appear to have major short-term effects on cognitive function in postmenopausal women. However, further clinical trials are required to determine whether small effects or long-term effects on cognitive function occur during isoflavone supplementation.

The aim of this study was to determine whether dietary supplementation with isoflavones from red clover affected ambulatory blood pressure and forearm vascular endothelial function in postmenopausal type 2 diabetic women.Sixteen postmenopausal type 2 diabetics treated with diet or oral hypoglycaemic therapy completed a randomized double-blind crossover trial of dietary supplementation with isoflavones from red clover (approximately 50 mg/day) for 4 weeks compared to placebo. Twenty-four-hour ambulatory blood pressure recordings and forearm vascular responses to acetylcholine, nitroprusside and L-nitromonomethylarginine (L-NMMA) were measured at the end of each treatment period.Mean daytime systolic and diastolic blood pressures were significantly lower during isoflavone therapy compared to placebo (-8.0 +/- 3.4 and -4.3 +/- 1.9 mmHg respectively, p0.05). The increase in forearm vascular resistance following L-NMMA was significantly greater during isoflavone supplementation (20.9 +/- 6.5) than placebo (3.7 +/- 2.9 arbitrary units, p0.05), suggesting an improvement in basal endothelial function. Plasma lipoproteins, glycated haemoglobin and forearm vascular responses to acetylcholine and nitroprusside did not differ significantly between isoflavone and placebo therapy.Isoflavone supplementation from red clover may favourably influence blood pressure and endothelial function in postmenopausal type 2 diabetic women.

To assess the acceptability of the delivery of an isoflavone supplementation in the form of a powdered drink, and whether the supplementation of dietary isoflavones in this manner decreased the incidence of menopausal flushes. The secondary aims included assessment of other symptoms or parameters of estrogen deficiency and responses to isoflavones.A randomized, double-blind, placebo-controlled, parallel-group trial comprising 24 postmenopausal women with symptoms of estrogen deficiency was performed over a 12-week period. The women were randomized to receive a dietary beverage containing isoflavones or an isoflavone-free, isocaloric placebo preparation.Although there was a high compliance rate among individual patients, there was a 25% withdrawal rate from the study in the active group. The incidence of complaints of bad taste tended to be higher in the active group (p = 0.07), and the total number of adverse events was significantly higher in this group (p0.001). There was no statistically significant difference in the incidence of flushes between the groups. There was no difference between the groups in Greene Menopause Symptom Scores, vaginal maturation value, levels of follicle stimulating hormone (FSH) or sex hormone-binding globulin (SHBG), or bone turnover markers.Powdered energy drinks are not commonly consumed in Australia and were poorly tolerated in this study. The high withdrawal rate and reporting of side-effects suggests that other methods of isoflavone delivery may be more appropriate in this culture, in future trials. At the dose used no benefit was seen in relief from menopausal symptoms, although for the sample size, the study could only have been expected to detect major differences between the groups.

Ten normal volunteers consumed 80 g of ethanol per day or abstained from ethanol for 4 consecutive days prior to measurements of blood pressure, heart rate, vascular responsiveness to noradrenaline (NA) and angiotensin II (AII) infusions and sympathetic responsiveness to isometric handgrip exercise in an open, random order, crossed study. Supine systolic and diastolic pressures and heart rates, and erect systolic pressures rose significantly following ethanol. Vascular responsiveness to NA infusions was reduced in all subjects following ethanol, while responses to AII infusions did not show a consistent pattern of change. Plasma renin activity, plasma NA and adrenaline concentrations, and concentrations of the NA metabolite 3,4 dihydroxyphenylethylene glycol (DHPG) did not significantly differ following ethanol and control treatments. The rise in plasma NA following 2 min isometric handgrip at 50% of maximal effort was greater following ethanol (0.24 +/- 0.21 nM) than control (0.12 +/- 0.10 nM) but the difference did not reach statistical significance. The pressor effect of regular ethanol consumption and the reduced vascular reactivity to NA may both be the result of an increase in sympathetic activity that was not large enough to measurably alter resting plasma NA concentrations.

In chronic cardiac failure, various neurohumoral mechanisms are activated to sustain blood volume, blood pressure, and organ perfusion. Using the coronary artery ligation model of heart failure in the rat, we have measured changes in vasoactive hormone secretion and related these changes to salt and water status during a 1-month period. When compared with controls, rats with infarction had a marked rise in plasma atrial natriuretic peptide (294 +/- 59 vs. 79 +/- 10 pg/ml, p less than 0.001) although there was no increase in total exchangeable body sodium. Plasma renin activity and plasma aldosterone concentrations were the same for both rats with infarction and controls. Similarly, there were no significant differences in plasma arginine vasopressin, plasma osmolality, or plasma sodium concentration in rats with infarction. Ventricular norepinephrine levels were reduced in animals with infarction (p less than 0.01). Plasma atrial natriuretic peptide levels were raised in this model of chronic left ventricular failure. However, there was no salt retention and little stimulation of the renin-angiotensin-aldosterone system or vasopressin. The results suggest that high circulating atrial natriuretic peptide levels may prevent or limit salt and water retention, either directly or indirectly, by inhibiting the renin-angiotensin-aldosterone system.

Plasma levels of norepinephrine (NE) and the NE metabolite 3,4-dihydroxyphenylethylene glycol (DHPG) were measured simultaneously following sympathetic activation induced by standing, cold pressor testing and bicycle exercise at progressively increasing workloads in normal volunteers. Free DHPG and NE levels both increased with sympathetic activation, but free NE levels were a more sensitive index of change. In addition, plasma free NE levels more closely reflected the fall in heart rate following exercise than free DHPG. In contrast to free levels, conjugated DHPG and NE levels did not change significantly after exercise. Supine resting free DHPG/ NE ratios were always greater than 2·0, but fell progressively with increasing sympathetic activation because of a proportionately greater rise in NE than DHPG. The simultaneous measurement of plasma free DHPG and NE does not offer advantages over free NE levels as an index of sympathetic activity in man, but may be of use in the diagnosis of pheochromocytoma and in studies of NE metabolism.

Blood pressure and vascular reactivity to infusions of noradrenaline and angiotensin II (ANG II) were measured in 10 normotensive volunteers who had consumed 80 g alcohol per day for 4 days after a similar period of abstaining from alcohol. Supine systolic and diastolic blood pressure and heart rate, and erect systolic blood pressures rose significantly following alcohol. Vascular reactivity to noradrenaline decreased following alcohol, while reactivity to ANG II did not change in a consistent manner. Although plasma noradrenaline levels did not alter following alcohol, the decrease in vascular reactivity to noradrenaline may indicate down-regulation of alpha-receptors and provide indirect evidence that increased sympathetic activity contributes to the rise in blood pressure that follows regular, moderate alcohol consumption.

Neuropeptide (NPY) and norepinephrine (NE) concentrations were measured in the right ventricle (RV) of rats with cardiac failure resulting from coronary artery ligation. RV NE concentrations fell significantly in rats with infarcts while RV NPY concentrations were unaltered.