The morning blood pressure surge is related to serum cholesterol.

A morning blood pressure surge (MBPS) may be either a mechanism for, or a marker of, increased cardiovascular events. This study has examined factors which may influence the morning surge: age, gender, metabolic factors, sympathetic function, blood pressure and arterial stiffness. Four measures of the MBPS were examined--sleep-trough surge, pre-awake surge, rate of blood pressure rise and a Power function. Subjects underwent ambulatory blood pressure monitoring, glucose tolerance test, central pulse wave velocity, sympathetic autonomic function tests (mental stress and sustained handgrip). MBPS was associated with age, hypertension, blood pressure variability and serum lipids. After adjustment for age and waist circumference, all four measures of MBPS remained positively associated with low-density lipoprotein (LDL) cholesterol. The novel finding of a significant relationship between measures of MBPS and LDL-cholesterol is an intriguing link between two major cardiovascular risk factors.

Advanced chronic kidney disease, cardiovascular events and the effect of diabetes: data from the Atherosclerosis and Folic Acid Supplementation Trial.

BACKGROUND: End-stage kidney disease registry data have reported increased mortality in patients with diabetes as compared with those without. Here we examine whether diabetes is independently associated with an increased risk of major cardiovascular events and death in patients with advanced chronic kidney disease (CKD). METHODS: Data from 315 participants with CKD in the Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) were assessed. Primary end-points were fatal or non-fatal cardiovascular events, including myocardial infarction, stroke, unstable angina, coronary revascularisation and peripheral vascular events assessed both jointly and separately using Cox-proportional hazard models. RESULTS: Twenty-three per cent reported diabetes. Median follow up was 3.6 years. In those with diabetes, an increased risk for major cardiovascular events was observed, crude hazard ratio (HR) 2.87 (95% confidence interval (CI) 2.11-3.90). After adjustment for age, gender, smoking, systolic blood pressure, body mass index, past ischaemic heart disease and use of preventive therapies, diabetes was associated with an HR of 1.83 (1.28-2.61) for major cardiovascular events. The risk for peripheral vascular events was also increased, adjusted HR 6.31 (2.61-15.25). For all-cause death, major coronary and stroke events, the risk in those with diabetes was not significantly increased (all-cause death, adjusted HR 1.31 (95% CI 0.80-2.14); major coronary events, adjusted HR 1.26 (95% CI 0.64-2.49); and major stroke events, adjusted HR 1.28 (95% CI 0.55-2.99)). CONCLUSIONS: Diabetes significantly increases the risk of major cardiovascular events, especially peripheral vascular events in patients with advanced CKD. Trials of multifactorial management of cardiovascular risk factors are required to determine if outcomes for this population may be improved.

Exchanges across land-water-scape boundaries in urban systems: strategies for reducing nitrate pollution.

Conservation in urban areas typically focuses on biodiversity and large green spaces. However, opportunities exist throughout urban areas to enhance ecological functions. An important function of urban landscapes is retaining nitrogen thereby reducing nitrate pollution to streams and coastal waters. Control of nonpoint nitrate pollution in urban areas was originally based on the documented importance of riparian zones in agricultural and forested ecosystems. The watershed and boundary frameworks have been used to guide stream research and a riparian conservation strategy to reduce nitrate pollution in urban streams. But is stream restoration and riparian-zone conservation enough? Data from the Baltimore Ecosystem Study and other urban stream research indicate that urban riparian zones do not necessarily prevent nitrate from entering, nor remove nitrate from, streams. Based on this insight, policy makers in Baltimore extended the conservation strategy throughout larger watersheds, attempting to restore functions that no longer took place in riparian boundaries. Two urban revitalization projects are presented as examples aimed at reducing nitrate pollution to stormwater, streams, and the Chesapeake Bay. An adaptive cycle of ecological urban design synthesizes the insights from the watershed and boundary frameworks, from new data, and from the conservation concerns of agencies and local communities. This urban example of conservation based on ameliorating nitrate water pollution extends the initial watershed-boundary approach along three dimensions: 1) from riparian to urban land-water-scapes; 2) from discrete engineering solutions to ecological design approaches; and 3) from structural solutions to inclusion of individual, household, and institutional behavior.

Is venous reflux a common disease in post-thrombotic patients with unilateral deep vein thrombosis episode?

OBJECTIVES: To investigate reflux development and changes in resting venous diameters in the DVT and the non-DVT lower limbs. METHODS: Twenty subjects (40 limbs) with acute unilateral proximal DVT diagnosed by ultrasound, who were treated with low-molecular-weight-heparin (LMWH), followed by at least three months of oral warfarin therapy, were enrolled in the study. The limbs were classified according to CEAP (clinical, aetiologic, anatomic, pathophysiology) clinical classification on a scale of 0-6. Duplex ultrasound (DUS) was employed to assess DVT resolution, vein diameter and venous reflux in both limbs at intervals of zero, three, six and 12 months. Venous reflux was defined as a valve closure time more than 1 s. RESULTS: There were 13 men and seven women, average age was 40.8 years and average body mass index 27.7 kg/m2. In the DVT limbs at three, six and 12 months, deep veins were non-occluded in 40%, 60% and 85%, respectively. By 12 months, 16 (80%) had developed venous reflux, mostly in the femoral (FV) and popliteal veins (PV); eight limbs (40%) were in clinical classes 4-6. In the contralateral 20 non-DVT limbs, four limbs developed borderline reflux at the sapheno-femoral junction (SFJ) after six months and mean diameters of SFJ, FV and PV increased significantly. CONCLUSIONS: Venous reflux is highly likely to occur in DVT limbs within a year follow-up period. Venous dilatation can occur in the contralateral unaffected lower limb, consistent with a systemic effect. Our results are suggestive and further studies are needed.

Overweight women with polycystic ovary syndrome have evidence of subclinical cardiovascular disease.

CONTEXT: Polycystic ovary syndrome (PCOS) is associated with insulin resistance (IR) and the metabolic syndrome. There are no adequate data demonstrating significantly increased cardiovascular disease (CVD) mortality. In the absence of clinical outcome studies, surrogate markers of early CVD can provide insight into early CVD. OBJECTIVE: The aim of this study was to clarify whether overweight women with PCOS have an increased prevalence of cardiovascular risk factors and early CVD, compared with age- and body mass index-matched controls, to determine the contribution of PCOS per se to CVD status. DESIGN AND PATIENTS: This was a case control study of 100 overweight women with PCOS and 20 subjects of similar body mass index and age. MAIN OUTCOME MEASURES: Noninvasive markers of early CVD [carotid intimal media thickness, pulse wave velocity (PWV), and brachial arterial flow-mediated vasodilation] were measured. Metabolic parameters studied included insulin, glucose, C-reactive protein, lipids, and androgens. RESULTS: Subjects with PCOS had elevated testosterone (2.5 +/- 0.2 vs. 1.3 +/- 0.1 nmol/liter), dehydroepiandrosterone sulfate (4.9 +/- 0.3 vs. 3.6 +/- 0.4 mmol/liter), fasting insulin (19.6 +/- 1.4 vs. 6.8 +/- 0.8 microU/ml), and homeostasis model assessment of IR (4.1 +/- 0.3 vs. 1.3 +/- 0.2), compared with controls. In addition, those with PCOS had elevated cholesterol (5.1 +/- 0.1 vs. 4.6 +/- 0.2 mmol/liter) and triglycerides (1.4 +/- 0.1 vs. 0.9 +/- 0.1 mmol/liter), whereas there were no differences in either C-reactive protein or 24-h ambulatory blood pressure parameters. Subjects with PCOS also had increased arterial stiffness (PWV, 7.4 +/- 0.1 vs. 6.6 +/- 0.2 m/sec) and endothelial dysfunction (flow-mediated vasodilation, 9.8 +/- 0.4 vs. 13.3 +/- 0.9), compared with controls. There was no difference in mean intimal media thickness between the groups. Stepwise regression in PCOS subjects showed that IR and lipids were independent predictors of PWV. CONCLUSION: Overweight women with PCOS have increased cardiovascular risk factors and evidence of early CVD, compared with weight-matched controls, potentially related to IR.

Vascular dysfunction and metabolic parameters in polycystic ovary syndrome.

CONTEXT: Polycystic ovary syndrome (PCOS) is associated with insulin resistance (IR) and the metabolic syndrome; however, the cardiovascular (CV) manifestations of PCOS remain unclear. OBJECTIVE: The objective of this study was to examine the relationships between IR, metabolic parameters, androgens, and markers of early CV disease in PCOS. DESIGN: We conducted an observational study examining noninvasive markers of early CV disease in women with PCOS including structural [carotid intimal media thickness (IMT)] and functional measures (arterial function with pulse wave velocity and endothelial function with brachial arterial flow-mediated vasodilation). Metabolic parameters included insulin and glucose during an oral glucose tolerance test and lipid and androgen levels. SETTING: Participants were recruited from the general community. PATIENTS: Eighty overweight women with PCOS who were nonsmokers and not on oral contraceptives or other medications known to affect IR participated in the study. RESULTS: Stepwise regression analysis showed that after adjustment for age and body mass index, IMT was significantly correlated with blood pressure (BP) load (P = 0.03) and inversely with dehydroepiandrosterone sulfate (DHEAS) (P = 0.01). After correction for androgen status, IMT was correlated with fasting glucose and area under curve (AUC) insulin. Flow-mediated vasodilation was inversely related to lipids (P = 0.02), whereas pulse wave velocity was related to BP (P < 0.001), AUC insulin (P = 0.04), and AUC glucose (P = 0.035). CONCLUSION: In overweight women with PCOS, insulin resistance and BP interacted negatively with arterial structural and functional measures. DHEAS correlated inversely with arterial structure, suggesting possible cardioprotective effects of endogenous DHEAS in women with PCOS. Additional research is needed to clarify these findings.

Vascular dysfunction and autonomic neuropathy in Type 2 diabetes.

AIMS: To test the hypothesis that arterial dysfunction in Type 2 diabetes is related to autonomic neuropathy. METHODS: Arterial function and autonomic neuropathy were assessed over two consecutive days in 45 Type 2 diabetic and control subjects. Systemic arterial compliance (SAC), arterial stiffness (pulse-wave velocity, PWV) and carotid intima thickness (IMT) were assessed; these markers reflect early vascular disease and predict clinical vascular events. Autonomic neuropathy was assessed using heart rate variability with continuous ECG recording during various breathing and postural manoeuvres and an overall autonomic score was generated. Fasting metabolic parameters including glucose, insulin, HbA(1c) and lipid profile were measured. RESULTS: Autonomic neuropathy tests were all repeatable in diabetic subjects. Compared with controls, diabetic subjects had arterial dysfunction with increased PWV (P = 0.009), IMT (P < 0.001) and reduced SAC (P = 0.053). After adjustment for age, central PWV correlated with fasting insulin (r(2) = 0.45, P < 0.05) and autonomic score (r(2) = 0.44, P < 0.05), peripheral PWV correlated with autonomic score (r(2) = 0.51, P < 0.005) and IMT correlated with fasting insulin (r(2) = 0.5, P < 0.005). The presence of autonomic neuropathy correlated with fasting insulin (P = 0.015), but not age, duration diabetes, lipids or blood pressure. CONCLUSION: Using repeatable measures of autonomic neuropathy and vascular function in Type 2 diabetic subjects, we have demonstrated associations between autonomic neuropathy, vascular dysfunction and hyperinsulinaemia. This may help to explain the excess cardiovascular mortality seen in diabetic subjects with autonomic neuropathy.

Randomized, placebo-controlled trial of intramuscular vitamin B12 for the treatment of hyperhomocysteinaemia in dialysis patients.

BACKGROUND: Plasma homocysteine is elevated in patients with end-stage renal disease (ESRD) and is a risk factor for cardiovascular disease. Folic acid has been shown to partially reduce homocysteine levels in dialysis patients. It is not known whether vitamin B12 reduces homocysteine independent of folic acid in patients who are not vitamin B12 deficient. AIM: To determine whether 1 mg vitamin B12 lowers homocysteine in stable, chronic, haemodialysis patients independent of folic acid. METHODS: Twenty-eight haemodialysis patients were randomized to receive three doses of 1 mg vitamin B12 or 1 mL saline placebo in a double-blind fashion at 1-month intervals. Fasting plasma total homocysteine, folic acid, red-cell folate, vitamin B12 and haemoglobin levels were determined prior to each dose and 4 weeks after the final injection. The study was powered to detect a 30% reduction in homocysteine over the 3 months. RESULTS: Both the two groups were well matched with respect to total homocysteine levels, folic acid, red-cell folate and vitamin B12 levels. Serum vitamin B12 levels were significantly higher in the treatment group compared to placebo (217.7 pmol/L; 95% confidence interval (CI) 103.0-332.5; P < 0.001) at the end of the trial but homocysteine levels were not significantly different (3.08 micromol/L; 95% CI -4.44-10.61; P= 0.406). CONCLUSIONS: The administration of intramuscular vitamin B12 over a 3-month period does not result in any reduction of plasma homocysteine levels in haemo-dialysis patients independent of folate status, however reductions of <30% cannot be excluded by the present study. High-dose folic acid remains the treatment of choice in reducing homocysteine, but whether this results in a reduction in cardiovascular events remains to be determined.

Placebo-controlled trial of transdermal estrogen therapy alone in postmenopausal women: effects on arterial compliance and endothelial function.

BACKGROUND: The cardiovascular effects of hormone replacement therapy (HRT) are controversial. Improvement in vascular function, potentially mediated, at least in part, via improvements in lipid profiles, is a proposed mechanism of estrogen action; however, there are few controlled human trials. We have studied the effects of HRT, independent of changes in lipid profile, with transdermal estrogen therapy, focusing on blood pressure, lipid profiles and vascular function, encompassing both biomechanical arterial properties (systemic arterial compliance and pulse wave velocity) and endothelial function (flow-mediated vasodilatation). METHODS: In this 2-year, double-blind, placebo-controlled, cross-over study, 34 healthy postmenopausal women were randomized to transdermal estrogen alone (Menorest, 50 micrograms) or placebo. After withdrawals, 25 women completed measurements at baseline, 6 weeks, 6 months and 12 months during both treatment phases. RESULTS: Transdermal estrogen did not improve blood pressure, lipid profiles or arterial function, compared with placebo. CONCLUSION: From this randomized, controlled trial, it appears that transdermal estrogen alone, in healthy postmenopausal women, does not improve lipid profiles or a spectrum of indices of arterial function, compared with placebo. These results would suggest that there might not be a beneficial effect of transdermal HRT on the vasculature in postmenopausal women.

Dietary soy has both beneficial and potentially adverse cardiovascular effects: a placebo-controlled study in men and postmenopausal women.

To address the cardiovascular effects of dietary soy containing phytoestrogens, we measured blood pressure (BP), lipids, vascular function (systemic arterial compliance and pulse wave velocity), and endothelial function (flow-mediated vasodilation) in a randomized, double-blind trial. Two hundred thirteen healthy subjects (108 men and 105 postmenopausal women), 50-75 yr old, received either soy protein isolate (40 g soy protein, 118 mg isoflavones) or casein placebo for 3 months. There were 34 withdrawals (16%), with 179 subjects (96 men and 83 women) completing the protocol. After intervention in the soy group, compared with casein placebo, urinary phytoestrogens increased, accompanied by a significant fall in BP reflected by the BP model (P < 0.01) encompassing mean change (+/-SEM) in systolic (-7.5 +/- 1.2 vs. -3.6 +/- 1.1 mm Hg, P < 0.05), diastolic (-4.3 +/- 0.8 vs. -1.9 +/- 0.7 mm Hg, P < 0.05), and mean BP (-5.5 +/- 1 vs. -0.9 +/- 1 mm Hg, P < 0.008). In the lipid model, soy induced greater changes, compared with placebo (P < 0.001). On individual analysis, significant contributors included a reduction in the low- to high-density lipoprotein ratio (-0.33 +/- 0.1 vs. 0.04 +/- 0.1 mmol/L, P < 0.05) and triglycerides (-0.2 +/- 0.05 vs. -0.01 +/- 0.05 mol/L, P < 0.05) and an increase in Lp(a) lipoprotein (+/- 95% confidence interval) [42 (range, 17-67) vs. 4 (range, -22-31) mg/L, P < 0.05], whereas total, low-density lipoprotein, and high-density lipoprotein cholesterol improved in both groups; but no treatment effect was demonstrated. The arterial functional model demonstrated no difference between groups; although again, overall function improved in both groups. On individual analysis, peripheral PWV (reflecting peripheral vascular resistance) improved with soy (P < 0.01), whereas flow-mediated vasodilation (reflecting endothelial function) declined (in males only), compared with casein placebo (P < 0.02). No effect of treatment on the hypothalamic-pituitary-gonadal axis was noted in males or females. In normotensive men and postmenopausal women, soy improved BP and lipids but, overall, did not improve vascular function. Potential adverse effects were noted, with a decline in endothelial function (in males only) and an increase in Lp(a). Further research in hypertensive and hyperlipidemic populations is needed.

Effects of combined oral hormone replacement therapy on tissue factor pathway inhibitor and factor VII.

Oral combined hormone replacement therapy (HRT) with oestradiol and norethisterone increases plasma levels of prothrombin fragment 1+2 (F1+2), indicating an increase in thrombin generation, but the mechanisms underlying this increase are uncertain. The aim of this randomized, placebo-controlled study was to determine whether an increase in factor VII, a factor that combines with tissue factor to activate the extrinsic pathway, or a decrease in tissue factor pathway inhibitor (TFPI), an inhibitor of extrinsic pathway activation, may contribute to increases in thrombin generation occurring with HRT. Healthy postmenopausal women aged 50-75 years received placebo (n=19) or oral combined HRT (n=18) and had blood collected for measurement of factor VII coagulation activity (VIIc), activated factor VII (VIIa) and TFPI at baseline and at 6 weeks. Baseline characteristics were similar in the two groups, including age, body mass index and cholesterol levels. As reported previously, HRT increased the F1+2 concentration by 20%. Placebo had no effect on VIIc, VIIa or TFPI, but 6 weeks of combined HRT decreased VIIc [from 1.11+/-0.06 (mean+/-S.E.M.) to 1.03+/-0.06 i.u./ml; P<0.03], VIIa [from 43.9; 10.8-198.3 (median; range) to 35.0; 6.3-66.8 m-units/ml; P<0.03] and TFPI [from 81.3+/-6.5 to 60.4+/-5.5 ng/ml; P<0.0001]. The decrease in TPFI with HRT was not correlated with the elevation in F1+2 levels. In conclusion, the increase in thrombin generation seen with HRT is not due to an effect on factor VII; in addition, while a contribution from the decrease in TFPI is possible, increased thrombin generation is not directly related to the decrease in TFPI.

Effects of oral combined hormone replacement therapy on platelet aggregation in postmenopausal women.

The effects of combined oestrogen/progestin hormone replacement therapy (HRT) on platelet aggregation were studied using women on HRT or placebo. The study involved 32 postmenopausal women (aged 50-75 years) who were enrolled in a double-blind randomized controlled trial, and who received either oral continuous combined HRT (Kliogest(R); 2 mg of oestradiol+1 mg of norethisterone) or placebo for a minimum of 6 months. Platelet aggregation was measured by whole-blood impedance aggregometry in response to the agonists collagen, arachidonic acid and ADP. To determine whether the effects of oestrogen on platelets were influenced by platelet-derived nitric oxide, exposure to collagen was repeated in the presence of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). Mean platelet volume was similar in the two groups. Compared with the placebo group, the women on HRT had similar rates and maximum values of platelet aggregation in response to collagen, arachidonic acid and ADP. Addition of L-NMMA did not alter the aggregation response to collagen in either the HRT or the placebo group. In conclusion, postmenopausal women on oral combined continuous HRT comprising oestradiol and norethisterone had similar whole-blood platelet aggregation rates and maximum platelet aggregation responses to higher doses of platelet agonists when compared with those on placebo. The endogenous platelet nitric oxide system did not appear to affect aggregation in either group.

A placebo-controlled trial of long-term oral combined continuous hormone replacement therapy in postmenopausal women: effects on arterial compliance and endothelial function.

OBJECTIVE: To study the effects of long-term combined continuous oral hormone replacement therapy (HRT) on vascular function in healthy postmenopausal women. BACKGROUND: The cardiovascular effects of HRT are controversial. Improvement in vascular function is a proposed mechanism of oestrogen action but there are no long-term controlled human trials in this area. In this study, we examined the effects of HRT on lipid profiles and vascular function, encompassing both biomechanical arterial properties [systemic arterial compliance (SAC) and pulse wave velocity (PWV)] and endothelial function [flow-mediated vasodilation (FMD)]. METHODS: In this 2-year, double-blind, placebo-controlled study, 59 healthy postmenopausal women were randomized to oral combined continuous oestrogen and progesterone [Kliogest, oestradiol (2 mg), norethisterone (1 mg)] or placebo, with end-points measured at baseline, 6 weeks and after 6,12 and 24 months of treatment. RESULTS: Oral combined HRT reduced lipoprotein a [Lp(a)], although other lipid benefits were not observed. There were no significant changes in SAC, PWV or FMD with oral combined HRT, compared to placebo. CONCLUSION: In this long-term, randomized placebo-controlled trial, oral continuous HRT with combined oestradiol and norethisterone in healthy postmenopausal women did not improve a spectrum of indices of arterial function compared to placebo. These results suggest that HRT might not be of cardiovascular benefit in postmenopausal women.

Impact of physical and physiological factors on arterial function.

1. Arterial function measurements are increasingly used as surrogate markers of cardiovascular disease and it is important to define which non-pathological factors may influence these measurements. 2. The present study examined the influence of gender, height, body mass index (BMI), waist : hip ratio, heart rate and arterial pressure on pulse wave velocity (PWV), systemic arterial compliance (SAC) and central pressure augmentation index (AI) in 285 normal subjects, 98 males and 187 females, aged 50-82 years. 3. There were significant gender differences in PWV (higher in men), SAC (higher in men) and central pressure AI (lower in men). 4. Both SAC and AI were correlated with height in men and women and height largely accounted for gender differences. 5. Systemic arterial compliance was positively, whereas AI was negatively, correlated with BMI. 6. Both PWV and AI were significantly correlated with heart rate and central pulse pressure. 7. These findings may have implications for cardiovascular disorders. Reduced central arterial compliance and increased central pressure augmentation are potential mediators for the increased cardiovascular risk of short stature. A slow heart rate may contribute to increased central arterial pressure with potentially adverse consequences in older subjects.

Carotid artery intima-medial thickness is increased in chronic renal failure.

1. Chronic renal failure (CRF) is associated with rapidly progressive atherosclerotic vascular disease. In the present study, carotid arterial intima-medial thickness (IMT) was assessed in a large cohort of patients with CRF and matched controls and related to risk factors. 2. A total of 159 subjects with CRF (serum creatinine > or =0.40 mmol/L) aged > 50 years (mean (+/-SD) 63.8+/-7.7 years) and 159 healthy controls matched for age, sex and smoking status were studied. 3. The IMT was determined using B-mode ultrasound measurements of the far wall of both common carotid arteries and presented as the mean IMT. Fasting plasma homocysteine (tHcy) was measured in the CRF group. 4. Intima-medial thickness was significantly greater in CRF patients than controls (0.89+/-0.17 vs 0.73+/-0.13 mm, respectively) after matching for age, sex and smoking status. Heart rate and pulse pressure were also significantly increased. The tHcy was increased two-fold in the CRF group (27.7+/-11.3 micromol/L; normal < 13.0 micromol/L) and did not correlate with carotid IMT. 5. Compared with controls after adjusting for traditional risk factors, patients with CRF exhibit significantly increased IMT.

Blockade of central angiotensin II does not affect the reduction in renal sympathetic nerve activity following a volume load in heart failure rabbits.

1. We investigated the role in sympathetic nerve regulation of endogenous angiotensin (Ang)II in the brain in heart failure by examining the effect of losartan on the resting mean arterial blood pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) and the reflex reduction in RSNA elicited by acute volume expansion in conscious rabbits. 2. Heart failure was induced with doxorubicin (1 mg/kg, i.v., twice weekly for 6 weeks). On the experimental day, MAP, HR and RSNA were recorded in conscious rabbits before and after losartan (10 microg; n = 6) or Ringer's (control; n = 5) injected in the fourth brain ventricle. Animals were then administered an acute volume load with the plasma expander Haemaccel (Hoechst Marion Roussel, Lane Cove, NSW, Australia; 2 mL/min, i.v., for 30 min). 3. Losartan did not significantly affect the resting basal levels of MAP, HR and RSNA. There was no significant difference between losartan- and Ringer's-treated animals. 4. Volume expansion in the control group elicited a significant reduction of 40% in RSNA. In the losartan-treated group, a similar reduction (42%) was observed. There was no significant difference between the treatments. The administration of losartan did not significantly affect MAP and HR during volume expansion compared with the control group. 5. We conclude that AngII in the brainstem does not play a major role in the maintenance of resting MAP, HR and RSNA or in the reflex reduction in RSNA elicited by volume expansion in the conscious rabbit with doxorubicin-induced heart failure.

Postmenopausal hormone replacement therapy increases coagulation activity and fibrinolysis.

Hormone replacement therapy (HRT) appears to be cardioprotective in postmenopausal women; however, concerns exist over its thrombogenic effects. To address the effects of combined HRT on coagulation and fibrinolysis, we have measured circulating markers of these processes in a double-blind placebo-controlled trial. Forty-two healthy postmenopausal women aged 50 to 75 years received continuous combined HRT with 2 mg estradiol+1 mg norethisterone or placebo for 6 weeks. Hormone profiles were measured at baseline, and lipid and hemostatic parameters were measured at baseline and after 6 weeks of therapy. Baseline characteristics were similar in the 2 groups. With change from baseline the main outcome measure, HRT increased the markers of coagulation (prothrombin fragments 1+2, 0.20+/-0.06 versus 0.06+/-0.04 nmol/L, P=0.0005; soluble fibrin, 2.3+/-0.4 versus 0.25+/-0.3 microgram/mL, P=0.0004), reduced plasma fibrinolytic inhibitory activity (plasminogen activator inhibitor-1, -0.67+/-0.16 versus 0.24+/-0.21 U/mL, P=0.002), and increased fibrinolysis (D-dimer, 24+/-12 versus -6+/-8 ng/mL, P=0.04) compared with placebo. Increases in soluble fibrin and D-dimer were positively correlated (r=0.59, P=0.02), but changes in plasminogen activator inhibitor-1 and D-dimer were unrelated. Although baseline hemostatic and lipid parameters were correlated, there were no associations between changes in hemostatic markers and lipids after treatment. Short-term oral combined continuous HRT (estradiol and norethisterone) increased thrombin and fibrin generation, reduced plasma fibrinolytic inhibitory activity, and increased fibrinolysis. Enhanced fibrinolysis was related to increased fibrin generation but not reduced plasma fibrinolytic inhibitory activity. Coagulation activation may partly explain the increases in venous thrombosis and cardiovascular events reported with the use of combined HRT.

The effects of soy protein containing phytoestrogens on menopausal symptoms in postmenopausal women.

OBJECTIVE: To analyze the impact of soy protein dietary supplements containing phytoestrogens on menopausal symptoms in healthy postmenopausal women. METHODS: A double-blind, placebo-controlled trial was conducted in 94 healthy postmenopausal women aged 50-75 years, with 44 randomized to soy supplements containing 118 mg of isoflavones (daidzein, genistein, glycitein and their respective glycosides), and 50 to an identically presented casein placebo. A validated questionnaire on menopausal symptoms was administered at baseline and at 3 months of treatment. Compliance was assessed by high-performance liquid chromatography assay of urinary phytoestrogens. Statistical analysis was completed using non-parametric statistical methods and multivariate analysis. RESULTS: At baseline 80% of women recruited were experiencing menopausal symptoms, although symptom severity was mild. Those consuming phytoestrogen supplements had 13- and 17-fold increases in urinary excretion of genistein and daidzein, respectively, with no change in the placebo group. Active soy supplements did not significantly alter either individual symptoms or specific symptom category scores when compared to placebo. Within-group comparisons revealed that the active group reported a significant improvement in vaginal dryness (p = 0.01), libido (p = 0.009), facial hair (p = 0.04) and dry skin (p = 0.027). However, similarly, those on placebo reported an improvement in libido (p = 0.015), facial hair (p = 0.014) and dry skin (p = 0.011) but not vaginal dryness. CONCLUSIONS: In this group of 94 older postmenopausal women with a high frequency of mild menopausal symptoms, 3 months of soy supplements containing phytoestrogens did not provide symptomatic relief compared with placebo.

Hormone replacement therapy in postmenopausal women protects against smoking-induced changes in vascular structure and function.

OBJECTIVES: The purpose of this study was to investigate the role of hormone replacement therapy (HRT) in postmenopausal women who smoke. BACKGROUND: Hormone replacement therapy appears to afford cardiovascular protection in postmenopausal women; however, in high risk individuals, specifically smokers, this has not been adequately studied. This question was addressed in a cross-sectional study of arterial structure, function and plasma lipids in postmenopausal smokers and nonsmokers. METHODS: Vascular ultrasound was performed in two age-matched groups of postmenopausal women, 70 on HRT (35 smokers) and 70 control subjects not on HRT (35 smokers). Indexes of arterial structure (carotid intima-media thickness [IMT]) and vascular function (systemic arterial compliance [SAC]) and lipid profiles were measured. RESULTS: Participant characteristics were similar in the two groups. Smokers on HRT, compared with smoking control subjects, had lower cholesterol (6.0+/-0.2 vs. 6.8+/-0.3 mmol/liter, p = 0.03) and more favorable mean values for IMT (0.64+/-0.02 vs. 0.74+/-0.03 mm, p = 0.007) and SAC (0.41+/-0.03 vs. 0.32+/-0.03 U/mm Hg, p = 0.03). Nonsmokers on HRT compared with nonsmoking control subjects had lower total cholesterol (5.7+/-0.2 vs. 6.5+/-0.2 mmol/liter, p = 0.02) and low density lipoprotein cholesterol (3.4+/-0.2 vs. 4.4+/-0.3 mmol/liter, p = 0.01). Mean IMT and SAC values in nonsmokers on HRT and control subjects were not significantly different. Multiple regression demonstrated significant correlation between HRT status and both IMT and SAC, in smokers and in those with increased cholesterol. In nonsmokers and those with lower cholesterol, HRT status was not significantly correlated with vascular parameters. CONCLUSIONS: In postmenopausal women who smoke there may be a beneficial effect of long-term estrogen therapy on indexes of arterial structure and function as surrogate markers of cardiovascular disease. Long-term controlled studies are needed to confirm these findings.