Effects of cerivastatin on forearm vascular responses, blood pressure responsiveness and ambulatory blood pressure in type 2 diabetic men.

OBJECTIVE: The objective of the study was to investigate the effects of cerivastatin therapy on forearm endothelial dependent acetylcholine (ACH) and independent (nitroprusside) vasodilator responses, blood pressure (BP) responses to intravenous infusions of angiotensin II (AII) and noradrenaline (NA) and on 24-h ambulatory BP recordings in type 2 diabetic men. DESIGN: Eleven type 2 diabetic men aged 59 +/- 9 years with total cholesterol levels of 5.0 +/- 1.26 mmol/l, triglycerides of 2.23 mmol/l and high-density lipoprotein cholesterol levels of 1.24 mmol/l completed a double-blind, randomized, crossover trial comparing 8 weeks of cerivastatin therapy (800 microg of nocte) with placebo. Forearm vascular resistance (FVR) responses to intrabrachial-arterial infusions of ACH (3-24 microg/min), nitroprusside (2-16 microg/min), the nitric oxide(NO) synthase inhibitor l-nitro-mono-methyl arginine (l-nmma) (8 micromol/min), ACH during l-NMMA infusion and BP responses to intravenous infusions of AII (12.5-50 ng/min) and NA (20-400 ng/min) were measured at the end of each treatment period. Twenty-four-hour ambulatory BP recordings were also performed. RESULTS: FVR responses to ACH during l-NMMA infusion were significantly (p = 0.026) greater during cerivastatin than during placebo therapy. In contrast, FVR responses to ACH in the absence of NO synthase inhibition did not differ significantly between cerivastatin and placebo therapies (p = 0.81). FVR increased by 31.4 +/- 57.3% in response to l-NMMA infusion during cerivastatin therapy compared with 6.1 +/- 41.2% during placebo therapy (p = 0.20). FVR responses to nitroprusside did not differ between cerivastatin and placebo therapies (p = 0.28), nor did BP responses to AII (systolic BP, p = 0.99; diastolic BP, p = 0.98) or NA (systolic BP, p = 0.21; diastolic BP, p = 0.48). Mean 24-h BP was similar during cerivastatin (123 +/- 10 or 70 +/- 7 mmHg) and placebo therapies (129 +/- 11 or 74 +/- 7 mmHg) (systolic BP, p = 0.26; diastolic BP, p = 0.41). CONCLUSION: Cerivastatin increases FVR responses to ACH in type 2 diabetic men with mild dyslipidaemia but only following NO synthase inhibition. This may indicate an improvement in endothelium-derived hyperpolarizing factor-mediated responses.

The effects of dietary supplementation with isoflavones from red clover on cognitive function in postmenopausal women.

OBJECTIVE: To examine the effects of dietary isoflavone supplementation with an extract from red clover on cognitive function in postmenopausal women. DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Effects of dietary supplementation with isoflavones from red clover on ambulatory blood pressure and endothelial function in postmenopausal type 2 diabetes.

OBJECTIVE: 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. DESIGN: 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. RESULTS: 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, p < 0.05). 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, p < 0.05), 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. CONCLUSION: Isoflavone supplementation from red clover may favourably influence blood pressure and endothelial function in postmenopausal type 2 diabetic women.

Effects on menopausal symptoms and acceptability of isoflavone-containing soy powder dietary supplementation.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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 (p < 0.001). 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. CONCLUSIONS: 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.

The effects of dietary supplementation with isoflavones from red clover on the lipoprotein profiles of post menopausal women with mild to moderate hypercholesterolaemia.

The effects of dietary isoflavone supplementation using a purified extract of red clover containing approximately biochanin A 26 mg, formononetin 16 mg, daidzein 0.5 mg and genistein 1 mg per tablet at doses of one or two tablets per day were compared to placebo in a three-period, randomised, double blind, ascending dose study in 66 post menopausal women with plasma cholesterol levels between 5.0 and 9.0 mmol/l. Each treatment period lasted 4 weeks and a further nine women received placebo for the full 12-week period. All women consumed a low isoflavone diet for 2 weeks preceding the commencement of the study and for the 12-week study period. Urinary isoflavone excretion was very low in subjects receiving placebo but increased in a dose-dependent manner during therapy with one and two of isoflavone tablets. Dietary supplementation with isoflavones did not significantly alter total plasma cholesterol, LDL cholesterol, HDL cholesterol or plasma triglyceride levels. However, inverse correlations were found between urinary genistein excretion and plasma triglyceride levels and between urinary O-DMA excretion (an isoflavone metabolite) and plasma triglyceride levels in subjects receiving one isoflavone tablet, suggesting a weak relationship between isoflavone intake and plasma triglycerides which may be influenced by individual differences in isoflavone absorption or metabolism. The results suggest that isoflavone phytoestrogens from red clover in the proportions and quantities studied do not significantly alter plasma lipids in post menopausal women with moderately elevated plasma cholesterol levels.

The effect of Promensil, an isoflavone extract, on menopausal symptoms.

OBJECTIVES: The primary aim was to assess whether the use of an isoflavone extract containing 40 mg or 160 mg of total isoflavones affects the frequency of menopausal flushes and other symptoms. The secondary aims were assessments of possible effects on menopause symptom scores and biological measures of estrogen activity. METHODS: A randomized, double-blind, placebo-controlled prospective trial of 37 postmenopausal women with symptoms of estrogen deficiency was performed over a 12-week period. The women were randomized to three treatment groups: placebo, 40 mg or 160 mg, delivered in tablet form. RESULTS: There was no significant difference in the incidence of flushes between the three groups at trial conclusion. There was no difference between the groups in Greene Menopause Symptom Scores, vaginal pH, levels of follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG) or total cholesterol, liver function or blood parameters. A statistically significant increase in high-density lipoprotein (HDL) cholesterol of 18.1% (p = 0.038) occurred in the 40-mg group. CONCLUSION: A large placebo response and inadvertent use of dietary isoflavones in the placebo group may have obscured a significant change in flushing frequency. Previous uncontrolled studies claiming a beneficial effect of foods with a high isoflavone content on menopausal symptoms may have been confounded by a large placebo response.

Alcohol consumption and blood pressure in recently hospitalised patients.

One-thousand-four-hundred-and-fifty-three patients admitted to a teaching hospital, haemodynamically stable and not severely ill nor in significant pain, were interviewed within 48 h of admission and demographic data and a detailed drinking history were obtained. Supine blood pressures (BP) were recorded on the day following admission. The mean age of the population was 60.5 +/- 19.9 years (range 16-99 years) and the mean reported alcohol consumption was 67.8 +/- 273 g/week (range 0-6125 g/ week). Thirty-six percent of patients were currently receiving antihypertensive drug therapy. On multivariant analysis, reported alcohol intake was not significantly related to systolic BP (beta = 0.000, p = 0.902) or diastolic BP (beta = 0.028, p = 0.281). Age (beta = 0.331, p = 0.0001) and body weight (beta = 0.121, p = 0.0002) were significant independent predictors of systolic BP, and body weight was a significant independent predictor of diastolic blood pressure (beta = 0.207, p < 0.0001). A relationship between alcohol consumption and blood pressure was not apparent in this population of patients following admission to hospital. A positive association between alcohol consumption and blood pressure may not be a universal finding and may be contributed to by a "white coat" effect.

Benzodiazepine prescribing in a Sydney teaching hospital.

OBJECTIVES: To determine the pattern of benzodiazepine prescribing in hospital and at discharge in relation to prior benzodiazepine therapy. DESIGN: Patient interview within 48 hours of admission to determine benzodiazepine, alcohol and other psychotropic drug use before admission and review of medical records after discharge to document drugs prescribed in hospital and at discharge. SETTING: Tertiary teaching hospital, January to August 1995. RESULTS: 1453 patients (mean age, 60 [SD, 19] years; 52.7% female) were interviewed; 277 patients (19.1%) were taking benzodiazepines regularly (one or more doses per week) before admission. Of these, 28.5% did not have benzodiazepine therapy continued while in hospital and 63.9% did not receive benzodiazepines at the time of discharge. Of the remaining 1176 patients (those not previously taking benzodiazepines), 277 (23.6%) were prescribed them for the first time in hospital and 5.3% received benzodiazepines at the time of discharge. Older age, female sex, marital status (single, divorced or widowed) and the use of antidepressants and Schedule 8 narcotic analgesics were all statistically significant predictors of benzodiazepine use before admission, but alcohol consumption was not. CONCLUSIONS: A substantial number of patients do not have their benzodiazepine therapy continued in hospital and at the time of discharge, and are thus at risk of developing benzodiazepine withdrawal syndromes, including delirium. A small but clinically significant number of patients who do not usually take benzodiazepines receive them at the time of discharge and may be at risk of becoming long term users.