Hormone replacement therapy and distensibility of carotid arteries in postmenopausal women: a randomized, controlled trial

OBJECTIVES: The study objective was to clarify in a randomized, controlled, observer-blind trial whether hormone replacement therapy (HRT) improves elastic properties of the common carotid artery in women with signs of subclinical atherosclerosis, especially in subgroups with increased risk, and whether less progestin enhances the effect. BACKGROUND: Previous observational studies have yielded conflicting results on the influence of HRT on central arteries. Some studies reported improvement of distensibility by estrogen alone or in the subgroup of smokers. METHODS: A total of 321 postmenopausal women were randomized to 1 mg 17beta-estradiol plus 0.025 mg gestodene for 12 days every month (HRT 1), or 1 mg 17beta-estradiol plus 0.025 mg gestodene for 12 days every third month (HRT 2), or no-HRT, during 48 weeks. In 173 women, distensibility of the common carotid artery was determined before and after therapy by M-mode ultrasound and brachial blood pressure measurement. RESULTS: Change of distensibility was small and similar in the three treatment groups. In the subgroup of current smokers, HRT 2 (low progestin) increased distensibility by 32% (HRT 2: 8.2+/-11.7; HRT 1:0.6+/-6.0; no HRT: -1.8+/-6.8 x 10(-3)/kPa, p = 0.025 for no-HRT vs. HRT 2). In the subgroups with elevated blood pressure, high low density lipoprotein (LDL) cholesterol, or high age, no effect of HRT was detected. CONCLUSIONS: This randomized intervention study demonstrates that long-term HRT with estrogen and progestin does not substantially influence distensibility of central arteries. Yet, in currently smoking postmenopausal women, HRT with low progestin seems to improve distensibility; this merits further study in a specifically designed trial.     

Effect of oral postmenopausal hormone replacement on progression of atherosclerosis : a randomized, controlled trial

-Postmenopausal hormone replacement therapy (HRT) is associated with low cardiovascular morbidity and mortality in epidemiological studies. Yet, no randomized trial has examined whether HRT is effective for prevention of coronary heart disease (CHD) in women with increased risk. The objective of this study was to determine whether HRT can slow progression of atherosclerosis, measured as intima-media thickness (IMT) in carotid arteries. Carotid IMT is an appropriate intermediate end point to investigate clinically relevant effects on atherogenesis. This randomized, controlled, observer-blind, clinical, single-center trial enrolled 321 healthy postmenopausal women with increased IMT in >/=1 segment of the carotid arteries. For a period of 48 weeks, subjects received either 1 mg/d 17ss-estradiol continuously plus 0.025 mg gestodene for 12 days every month (standard-progestin group), or 1 mg 17ss-estradiol plus 0.025 mg gestodene for 12 days every third month (low-progestin group), or no HRT. Maximum IMT in 6 carotid artery segments (common, bifurcation, and internal, both sides) was measured by B-mode ultrasound before and after intervention. HRT did not slow IMT progression in carotid arteries. Mean maximum IMT in the carotid arteries increased by 0.02+/-0.05 mm in the no HRT group and by 0.03+/-0.05 and 0.03+/-0.05 mm, respectively, in the HRT groups (P:>0.2). HRT significantly decreased LDL cholesterol, fibrinogen, and follicle-stimulating hormone. In conclusion, 1 year of HRT was not effective in slowing progression of subclinical atherosclerosis in postmenopausal women at increased risk.     

Temporal changes in clinic and ambulatory blood pressure during cyclic post-menopausal hormone replacement therapy

OBJECTIVE: Post-menopausal hormone replacement (HRT) might protect against cardiovascular disease, possibly by arterial vasodilation and reduced blood pressure. Progestogens are needed to avoid endometrial disease but vascular effects are controversial. The objective was to assess temporal changes in blood pressure (BP) by two measurement techniques during a cyclic hormone replacement regimen. DESIGN AND METHODS: Sixteen healthy and normotensive post-menopausal women (age 55 +/- 3 years) were studied in a placebo-controlled, randomized crossover study, and were randomized to 17beta-oestradiol plus cyclic norethisterone acetate (NETA) or placebo in two 12-week periods separated by a 3-month washout Clinic blood pressure was measured sitting by the same observer with a mercury manometer at four visits in each period. Twenty-four hour ambulatory blood pressure was measured at baseline and in the ninth weeks of treatment in both periods. RESULTS: Clinic systolic and diastolic BP were reduced after 10 days of oestradiol (-5.1 and -3.2 mmHg respectively, P < or = 0.05). After 9 weeks of cyclic HRT, prior to progestogen addition, clinic BP returned to baseline. During addition of NETA, diastolic blood pressure was again reduced (-3.6 mmHg, P= 0.037). Mean 24 h ambulatory systolic and diastolic blood pressures were significantly lower than clinic measurements (-15.7 and -5.9 mmHg, P < 0.001) but were unaffected by HRT. CONCLUSIONS: Clinic blood pressure is reduced during a cyclic HRT regimen but the reduction varies with the HRT regimen, which might explain the diversity in previous BP findings during HRT. Norethisterone acetate might possess additive blood pressure-lowering effects in postmenopausal women.     

The effect of 17beta-estradiol on endothelial and inflammatory markers in postmenopausal women: a randomized,controlled trial

BACKGROUND: Intervention trials in postmenopausal women with coronary artery disease have failed to demonstrate beneficial effects of hormone replacement therapy (HRT) on the course of disease, potentially due to pro-inflammatory effects of conjugated equine estrogens. We characterized the effects of 48 weeks treatment with two estradiol-based HRT regimens on nonspecific (high sensitivity C-reactive protein [hs-CRP], blood sedimentation rate [BSR], fibrinogen) and specific endothelial markers (cell adhesion molecules: ICAM-1, VCAM-1, E-selectin). METHOD AND RESULTS: Postmenopausal women randomly received either 1 mg 17beta-estradiol daily plus 25 microg gestodene for the last 12 days of each 28 day cycle (=standard dose progestin; n=65), or gestodene added each third cycle only (=low dose progestin; n=65), or no HRT (n=73). Both HRT regimens reduced levels of ICAM-1 (-9%), VCAM-1 (-9%), E-selectin (-11%), fibrinogen (-12%), BSR (-5%). No effect was observed on hs-CRP levels in any group. In smokers, E-selectin remained unchanged whereas ICAM-1 and VCAM-1 were lowered. Subjects on antihypertensive or lipid lowering medication showed effects comparable to the whole cohort. Effects of low and standard dose progestin were not different. CONCLUSION: We conclude that a combination therapy with 1 mg 17beta-estradiol favourably affects the vascular inflammation processes as indicated by a neutral effect on hs-CRP and reduction of cell adhesion molecules.     

Different circulatory response to melatonin in postmenopausal women without and with hormone replacement therapy

In young men and women, melatonin influences vascular reactivity and reduces blood pressure and norepinephrine levels. Herein, we investigated whether these effects are conserved in postmenopausal women without and with hormone replacement therapy (HRT). Oral melatonin (1 mg) or placebo was randomly and in double blind fashion administered to 18 untreated and 13 postmenopausal women who were treated continuously with transdermal estradiol (50 microg/day) plus cyclic medroxyprogesterone acetate (5 mg/day x 12 days every 28 days). Internal carotid artery pulsatility index (PI), an index of downstream resistance to blood flow, blood pressure and catecholamine levels were evaluated. In untreated postmenopausal women, melatonin was ineffective, while in HRT-treated women, studied during the only estrogenic phase, melatonin reduced, within 90 min, systolic (-8.1 +/- 9.9 mmHg; P = 0.054), diastolic (-5.0 +/- 7.0 mmHg; P = 0.049) and mean (- 6.0 +/- 6.6 mmHg; P = 0.037) blood pressure. Norepinephrine (-50.1 +/- 66.7 pg/mL; P = 0.019), but not epinephrine levels, were also significantly reduced. Similarly, resistance to blood flow in the internal carotid artery, as evaluated by the PI, decreased (-0.190 +/- 0.15; P = 0.0006) in a way that was linearly related to pre-existing PI values (r2 = 0.5; P = 0.0059). These data show that the circulatory response to melatonin is conserved in postmenopausal women on HRT but not in untreated postmenopausal women. Possible physiological and pharmacological implications of these data on the cardiovascular risk of postmenopausal women can be envisioned.     

Effects of hormone replacement therapy on ambulatory blood pressure and vascular responses in normotensive women

The effects of chronic oestrogen replacement therapy (ERT) (conjugated equine oestrogen 0.625 mg/day) and combined oestrogen and progestogen replacement therapy (HRT) (ERT plus continuous medroxyprogesterone acetate 5 mg/day) on 24-h ambulatory blood pressure recordings, forearm vascular resistance (FVR) and FVR responses to noradrenaline, angiotensin II, acetylcholine and nitroprusside were studied in 17 normotensive postmenopausal women in a 3-month randomized, double-blind, placebo-controlled crossover trial with 1 month of therapy in each treatment arm. During the last few days of each 1-month treatment period, the subjects underwent 24-h ambulatory blood pressure recordings and measurements of FVR responses. ERT and HRT reduced mean 24-h diastolic blood pressure by 4 and 5 mmHg, systolic blood pressure by 6 and 9 mmHg and mean 24-h heart rate by 5 and 3 beats/min, respectively for ERT and HRT (p < 0.05). Basal FVR was reduced by approximately 18% by ERT and HRT, but FVR responses to noradrenaline, angiotensin II, acetylcholine and nitroprusside were unaffected. ERT and HRT therapy for 1 month lowers blood pressure and basal FVR, but does not appear to influence FVR responses to acetylcholine, nitroprusside, noradrenaline and angiotensin II.     

Increased plasma concentrations of TGF-beta1 after hormone replacement therapy

OBJECTIVES AND DESIGN: Hormone replacement therapy (HRT) in postmenopausal women may reduce the cardiovascular risk. A dominant protective role of transforming growth factor beta (TGF-beta1) on coronary arteries has been proposed. Lp(a) lipoprotein may block the activation of latent TGF-beta1. Given this background, we examined the effects of HRT on TGF-beta1 and Lp(a) lipoprotein in 99 postmenopausal women. The women had angiographically documented coronary heart disease (CHD) and were randomized to either sequential transdermal 17beta-oestradiol for 14 weeks and then medroxyprogesterone (MPA) for 14 days (HRT) or to a control group (C). RESULTS: Serum levels of TGF-beta1 were increased in the HRT group compared with the C group after 3 months' treatment and this effect was sustained after 12 months. There was a significant reduction in Lp(a) lipoprotein serum levels after 3 months' treatment in the HRT group compared with the C group. However, after 12 months, no significant difference in changes in Lp(a) lipoprotein serum levels was detected between the two groups. CONCLUSION: The novel observation that transdermal 17beta-oestradiol in postmenopausal women increases levels of TGF-beta1 and lowers the concentration of Lp(a) lipoprotein suggests yet another possible mechanism for the cardioprotective effect of HRT. Whereas combination therapy of oestradiol and MPA preserves the beneficial effect on TGF-beta1, it reduces the unopposed oestradiol effects on Lp(a) lipoprotein.     

A dose-response study of hormone replacement in young hypogonadal women: effects on intima media thickness and metabolism

OBJECTIVE: Young hypogonadal women appear to have an increased risk of cardiovascular disease. We studied the influence of increasing doses of hormone replacement therapy (HRT) on markers of metabolism and vascular physiology. DESIGN: Nine-month sequential dose-ranging study. PATIENTS: A total of 25 young hypogonadal women (Turner Syndrome, n = 14; 46,XX gonadal dysgenesis, n = 9), hypogonadotrophic hypogonadism (n = 2), mean age 31.9 years (range 18.5-42.2). All subjects sequentially received oral 17beta-oestradiol 1,2 and 4 mg daily in a cyclical formulation for 12 weeks each. MEASUREMENTS: Metabolic markers and vascular physiology measurements to assess intima media thickness (IMT); arterial stiffness: pulse wave velocity (PWV) and augmentation index (AIx); endothelial function: flow-mediated dilatation (FMD). Results Increasing doses of oestrogen resulted in a reduction in IMT (0.63 +/- 0.06 vs. 0.58 +/- 0.06 vs. 0.56 +/- 0.06 mm at 1 mg, 2 mg and 4 mg 17beta-oestradiol, respectively, P = 0.001). RESULTS: were similar in women with Turner Syndrome and normal karyotype. High-density lipoprotein (HDL) cholesterol concentrations increased (1.9 +/- 0.4 vs. 2.0 +/- 0.5 vs. 2.2 +/- 0.4 mmol/l, P = 0.001) and plasma glucose (4.8 +/- 0.4 vs. 4.7 +/- 0.3 vs. 4.6 +/- 0.6 mmol/l, P = 0.038) decreased slightly with the increasing dose of HRT. There was no correlation between the changes in IMT and HDL. Increasing HRT dose had no significant impact on blood pressure, weight, other lipid parameters, insulin, C-reactive protein, interleukin-6 and fibrinogen concentrations or FMD, PWV and AIx. CONCLUSIONS: Increasing doses of HRT result in a reduction in carotid IMT in young hypogonadal women, along with increased serum HDL and decreased plasma glucose. This study raises the possibility that exogenous oestrogen may be cardioprotective in young women, but this observation needs to be balanced against a prothrombotic effect which is predominant in postmenopausal women.     

Starke Blutdrucksenkung durch hochdosierte Kombinationstherapie von 160 mg Valsartan und 25 mg HCT in der alltäglichen Behandlungspraxis bei Patienten mit erhöhtem kardiovaskulären Risiko

BACKGROUND AND PURPOSE: Hypertension is one of the most common cardiovascular risk factors. Thus, achievement and maintenance of a sufficient reduction of blood pressure markedly contribute to successful risk prevention. Therefore, the primary objective of this observational postmarketing study MACHT II was to examine the efficacy and the tolerability of the combined therapy with 160 mg valsartan plus 25 mg hydrochlorothiazide (HCT) in a large population of patients with a well-defined individual risk profile and treatment status at baseline. PATIENTS AND METHODS: This multicenter, open singlearm trial involved 17,591 patients, either without or with insufficient prior antihypertensive medication. RESULTS: The mean absolute blood pressure improvement obtained for the total population was -26.8 mmHg systolic and -13.5 mmHg diastolic. The maximum absolute improvement in blood pressure was observed in patients with severe hypertension: on average, the systolic blood pressure decreased by 41.7 mmHg and the diastolic blood pressure by 20.5 mmHg compared to baseline. The results demonstrated an effective blood pressure reduction in every subgroup analyzed: mean values of systolic and diastolic blood pressure decreased to high normal values. More than two thirds of the patients achieved normalization of the diastolic blood pressure. Normalization of diastolic blood pressure was observed in 65.2% of the patients with previous antihypertensive medication and in 74.3% of those without previous antihypertensive medication. The overall incidence of adverse drug reactions was 0.6%. CONCLUSION: The combined antihypertensive therapy with 160 mg valsartan plus 25 mg HCT shows a high degree of efficacy and a very favorable safety profile.     

Seasonal variations in office and home blood pressures in hypertensive patients treated with antihypertensive drugs

OBJECTIVE: To analyze various factors influencing season variations in blood pressure under ordinary circumstances. METHODS: We examined home and office blood pressures in 315 outpatients with essential hypertension. The majority (88%) were being administered antihypertensived drugs. Their office and home blood pressures were recorded in 1993. The patients were 156 men and 159 women, aged 60.8 +/- 0.6 years (mean +/- SEM). The office blood pressure was measured monthly by the same physicians. The home blood pressure was measured every day by the patients, in the morning and evening. RESULTS: The home blood pressures both in men and in women exhibited significant seasonal variations, to a similar extent. The winter-summer difference in home blood pressure was 3.9 +/- 0.5 mmHg systolic and 1.7 +/- 0.3 mmHg diastolic for the men and 4.6 +/-0.5 mmHg systolic and 2.4 +/- 0.3 mmHg diastolic for the women. The office blood pressure of the men also exhibited significant seasonal variation. There was no seasonal variation in office systolic blood pressure in the women. The levels of home blood pressure in the men and women were similar during each season, whereas the office systolic blood pressure of the women was significantly higher than that of men throughout the year. For the total group of patients, the winter-summer differences in home systolic blood pressure was positively correlated to age. The seasonal variations in blood pressure were not affected by body mass index, smoking status, and administration of antihypertensive medication.CONCLUSIONS: Seasonal variations in blood pressure existed both for male and for female hypertensive patients and occurred even for subjects being treated with antihypertensive drugs. However, there was no seasonal variation in the office systolic blood pressure of women, suggesting that the differences between the office and home blood pressures and between thermoregulatory mechanisms for the sexes may have obscured it.     

Spectral analysis of 24 h blood pressure monitoring in the assessment of trough: peak ratio. A randomized, placebo-controlled, cross-over comparison of ramipril and enalapril

BACKGROUND: The ratio between the magnitude of blood pressure reduction during the steady-state dosage interval (trough) and the maximum blood pressure reduction (peak) is an integrated in-vivo index both of the pharmacokinetic properties and of pharmacodynamic activity of an antihypertensive drug. Angiotensin converting enzyme inhibitors are often characterized by a low (often lower than 50%) trough: peak ratio but no direct drug comparisons are available. OBJECTIVE: To compare the absolute blood pressure reduction and the trough: peak ratio of daily doses of two angiotensin converting enzyme inhibitors, 5 mg ramipril and 10 mg enalapril. METHOD: After a 1-month wash-out and a 2-week placebo run-in, 25 mild hypertensives aged 47 +/- 4 years (17 men and eight women) were randomly assigned to treatments separated by a 2-week interval. Ambulatory blood pressure monitoring was performed and trough: peak ratio was calculated by the fast Fourier transform analysis of placebo-effect-subtracted data. RESULTS: After 1 month of ramipril treatment, 24 h blood pressure decreased from 139 +/- 10 to 129 +/- 11 mmHg for systolic (P < 0.05) and from 89 +/- 8 to 81 +/- 5 mmHg for diastolic blood pressure (P < 0.01). Also enalapril treatment caused a significant 24 h reduction in blood pressure both for systolic (to 132 +/- 7 mmHg, P < 0.05) and for diastolic blood pressure (to 84 +/- 5 mmHg, P < 0.05). Placebo caused a 24 h reduction in blood pressure (to 136 +/- 8 mmHg for systolic and 87 +/- 5 mmHg for diastolic blood pressure, NS, versus wash-out period). The two drugs were equally effective in reducing ambulatory blood pressure, but ramipril produced a trough: peak ratio significantly higher than that with enalapril both for systolic (48 +/- 11%, range 34-74%, versus 38 +/- 11%, range 21-67%, P < 0.005)and for diastolic blood pressure (47 +/- 11%, range 30-79 %, versus 37 +/- 12%, range 21-68%, P < 0.05). CONCLUSION: The low trough : peak ratios could have been due to the daily pattern of blood pressure of mild hypertensives, many of whom are normotensives at night-time, so that the main antihypertensive effect is exerted during daytime rather than during the night or early morning.     

Effects of oestrogen-only and oestrogen-progestogen replacement therapy upon circulating angiotensin I-converting enzyme activity in postmenopausal women

OBJECTIVE: Levels of angiotensin I-converting enzyme (ACE) in blood are associated with variation in cardiovascular disease risk. Serum ACE activity in women may be reduced by combined oestrogen-progestogen hormone replacement therapy (HRT). However, the relative contribution of each hormonal component to this observation is uncertain. We investigated ACE activity in two groups of healthy postmenopausal women receiving HRT regimens. DESIGN: The first group received placebo or oestrogen-only HRT randomly (oral conjugated equine oestrogens or transdermal 17 beta-oestradiol). The second group was treated with oestrogen-only HRT (oral 17 beta-oestradiol) followed by sequential oestrogen-progestogen HRT (17 beta-oestradiol and dydrogesterone). MEASUREMENTS: Assay of blood for soluble ACE activity before and whilst receiving HRT. RESULTS: In the first group, oral conjugated equine oestrogens significantly reduced (P < 0.01) ACE activity by 18% on average relative to pretreatment whereas non-significant changes of -9% and +7% were seen with transdermal 17 beta-oestradiol or placebo treatment, respectively. In the second group oestrogen-only HRT significantly reduced (P < 0.001) ACE activity by 15% on average. The reduction during both the oestrogen-only and combined phases of sequential treatment was 12% and 19%, respectively, compared with pretreatment values (P < 0.01 and P < 0.001). ACE activity also differed significantly (P < 0.05) between the two phases of sequential treatment. CONCLUSIONS: Both oestrogen-only and oestrogen-progestogen HRT may reduce ACE activity in blood. Oestrogen and progestogen may exhibit additive effects on blood ACE activity.     

Blood pressure in middle-aged women: are androgens involved? A population-based study of Swedish women: the Women's Health in the Lund Area study

OBJECTIVE: To assess the prevalence of hypertension and use of antihypertensive drug therapy in relation to menopausal status and to delineate perceived associations between androgens and blood pressure in perimenopausal women. METHODS: A population-based sample of women aged 50-59 (n = 6893). Women were divided into three groups according to their hormonal status: premenopausal, postmenopausal without hormone therapy, and postmenopausal with hormone therapy. RESULT: In the premenopausal, postmenopausal without hormone therapy, and postmenopausal with hormone therapy groups, the prevalence of high blood pressure (>/= 140 mmHg systolic or >/= 90 mmHg diastolic) was 43.9, 49.9 and 45.8%, respectively. In women with normal blood pressure, adjusting for age, body mass index and smoking, there were negative associations between serum testosterone and systolic blood pressure in the total sample (P < 0.01) and the postmenopausal without hormone therapy group (P < 0.05).In women using antihypertensive drug therapy with a blood pressure of at least 140/90 mmHg, positive associations were found between serum testosterone and systolic blood pressure in the total series (P < 0.05) and in the postmenopausal without hormone therapy group (P < 0.05). CONCLUSION: Abnormal blood pressure is common in middle-aged women regardless of hormonal status. Our findings suggest that testosterone could have a dual influence on blood pressure in perimenopausal women.     

Analysis of ambulatory blood pressure monitoring: the problem of 'white-coat' hypertension, responders and non-responders

OBJECTIVE: To analyse a randomized study undertaken to compare the antihypertensive efficacy of dihydropyridine calcium antagonists in patients with essential hypertension. METHOD: Blood pressure was measured both conventionally by a doctor and by non-invasive ambulatory monitoring. RESULTS: During amlodipine therapy (5 mg once a day for 4 weeks, n = 121), the mean daytime diastolic blood pressure was lowered by 8.2+/-7.1 and 0.9+/-7.4 mmHg (means +/- SD) in patients with a pretreatment daytime diastolic blood pressure >/= 90 (n = 89) and < 90 mmHg (n = 32), respectively. In 60 (67%) among the 89 patients who had an initial daytime diastolic blood pressure >/= 90 mmHg the daytime diastolic blood pressure was lowered by >/= 5 mmHg, with a mean fall of 12.0+/- 5.2 mmHg. The decrease in daytime diastolic blood pressure averaged 0.6+/- 3.5 mmHg in the remaining non-responder patients (n = 29). CONCLUSION:It seems important to evaluate the efficacy of a given antihypertensive drug by analysing patients with white-coat hypertension separately from responders to the medication. This allows one to gain maximum information concerning the effect of therapy in the individual hypertensive patients.     

Co-administration of an ACE-inhibitor (moexipril) and hormonal replacement therapy in postmenopausal women.

Co-administration of antihypertensive drug therapy and hormonal replacement therapy (HRT) is frequent in postmenopausal women but it is not known whether HRT interacts with concomitant antihypertensive therapy. The present study was designed to investigate efficacy and safety of the ACE inhibitor moexipril in comparison to placebo in hypertensive, postmenopausal women on HRT. After a 4-week placebo run-in phase, 95 postmenopausal women (35-74 years of age) who had a sitting diastolic blood pressure (BP) of 95-114 mm Hg and were treated with HRT were randomised to a 12-week treatment with moexipril 15 mg or placebo. Efficacy and safety were assessed by measuring changes in sitting BP and metabolic parameters associated with cardiovascular disease including triglycerides, total cholesterol, HDL, LDL, total cholesterol/HDL ratio and glucose. Adverse events were recorded continuously. After 12 weeks of treatment, moexipril 15 mg was significantly more effective in reducing sitting systolic and diastolic BP from baseline than placebo (-12.2/-9.9 mm Hg vs -1.6/-4.3 mm Hg, P < 0.001). Metabolic parameters were not affected by treatment with moexipril: mean levels of triglycerides, total cholesterol, HDL, LDL, total cholesterol/HDL ratio and glucose remained unchanged throughout the study. Fibrinogen, an independent cardiovascular risk factor, increased after placebo (+35.0 mg/dl) and decreased after treatment with moexipril (-33.6 mg/dl), the difference, however, was not statistically significant. Moexipril was well-tolerated by postmenopausal women using HRT. The most frequent adverse events included headache (21.3%), cough (12.8%) and rhinitis (10.6%) and there were no significant differences in the number and severity of adverse events between the moexipril and placebo groups. This study indicates that moexipril is effective and well tolerated in the treatment of hypertensive, postmenopausal women and can safely be co-administered to HRT.     

Effect of hormone replacement therapy on age-related increase in carotid artery intima-media thickness in postmenopausal women

The aim of this study was to determine the changes in carotid artery intima-media thickness as measured by B-mode ultrasound in postmenopausal women receiving hormone replacement therapy (HRT) or not. One hundred and fifty-nine healthy postmenopausal women aged 45-65 years were recruited from our menopause clinic. All the selected women were free of cardio-vascular diseases and had no cardio-vascular risk factors. None of the women were receiving lipid-lowering or antihypertensive drugs. Because carotid artery intima-media thickness was shown to be strongly and positively correlated with age in women aged 55 years and older but not before, women were divided into four groups according to age (<55 vs. > or =55 years) and use of HRT (current users vs. never users). All the treated women received non-oral 17beta-estradiol with a non-androgenic progestin and had started HRT within the first year after menopause. Scanning of the right common carotid artery was performed with a B-mode ultrasound imager and thickness of the intima-media complex as well as luminal diameter of the artery were determined using an automated computerized procedure. Within each age group (i.e. <55 or > or =55 years), women had comparable demographic characteristics and only differed by HRT use. Long-term treated women had significantly lower total cholesterol levels than untreated women (P=0.005). Triglycerides, low-density lipids (LDL)-cholesterol and high-density lipids (HDL)-cholesterol levels, systolic and diastolic blood pressure were not significantly different between users and non-users. In women <55 years, no significant difference in carotid intima-media thickness was found between current users (mean 2.5+/-1.4 years) and non users. In older women, the mean values of carotid intima-media thickness were significantly smaller in current users (mean 6.9+/-3.3 years) than in never treated women: 0.50+/-0.05 versus 0.56+/-0.07 mm, P<0.0001. Carotid artery intima-media thickness was significantly correlated to age in never users (r=0.5, P<0.0001) but not in women who were currently receiving HRT (r=0.2, ns). These findings suggest an apparent protective effect of long-term HRT on age-related thickening of the intima-media of the right common carotid artery. This may contribute to explain the apparent cardio-protective effect of HRT after the menopause.     

Association of arginine vasopressin and arterial blood pressure in a population-based sample

BACKGROUND: The role of arginine vasopressin (AVP) in the development and maintenance of arterial hypertension is controversial. Furthermore, it remains unclear whether chronic treatment with antihypertensive agents modulates levels of AVP, with potential secondary effects on vascular tone and fluid homeostasis. OBJECTIVE: To investigate the relation between plasma AVP and arterial blood pressure in a population-based sample of 534 middle-aged subjects. RESULTS: Overall, levels of AVP were higher in hypertensive subjects (2.15 +/- 0.26 pg/ml; n = 289) than in normotensive subjects (1.45 +/- 0.15 pg/ml; n = 245; P < 0.05). (Hypertension was defined as systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 95 mmHg, or receiving antihypertensive medication.) In untreated individuals, plasma levels of AVP were found to be correlated with both systolic (r = 0.15, P = 0.002) and diastolic (r = 0.14, P = 0.005) blood pressure. The differences between the lowest and highest quartile of AVP levels were 5.1 mmHg (P = 0.03) and 2.6 mmHg (NS) for systolic and diastolic blood pressure, respectively, after adjustment for age and sex. Moreover, it appeared that the relation between AVP and blood pressure was particularly strong in subjects with low levels of renin (< 10 mU/l; n = 118; systolic blood pressure r = 0.24, P = 0.007; diastolic blood pressure r = 0.19, P = 0.03). Specifically, patients receiving monotherapy with diuretics (n = 39) or beta-blockers (n = 54) displayed elevated plasma levels of AVP (2.93 +/- 0.98 pg/ml and 2.74 +/- 0.74 pg/ml respectively); however, only in patients taking diuretics was this finding apparently independent of confounding variables. Other monotherapies with angiotensin-converting enzyme inhibitors (n = 9) or Ca(2+)-antagonists (n = 19) were not associated with levels of AVP. CONCLUSION: The data suggest that plasma levels of AVP display a discernible relationship with arterial blood pressure and hypertension, particularly when renin levels are low. In addition, with the exception of diuretics, no modulation of AVP levels is attributable to the intake of antihypertensive agents as it occurs in a population-based sample.     

Effect of combination therapy of angiotensin-converting enzyme inhibitor plus calcium channel blocker on urinary albumin excretion in hypertensive microalbuminuric patients with type II diabetes.

It has been demonstrated that antihypertensive treatment of hypertensive diabetic patients is quite effective in preventing macrovascular and microvascular complications and improving prognosis. Nevertheless, the target blood pressure level of antihypertensive treatment in hypertensive diabetic patients with microalbuminuria (i.e., with early diabetic nephropathy) remains to be established. In this study, we evaluated the effect of intensive blood pressure control (diastolic blood pressure <80 mmHg) on urinary albumin excretion in hypertensive, type II diabetic patients with microalbuminuria. We examined the effects of a combination therapy using an angiotensin-converting enzyme (ACE) inhibitor plus a long-acting calcium channel blocker (amlodipine), and compared them with the effect of an ACE inhibitor alone. Thirty hypertensive, type II diabetic patients with microalbuminuria were treated with either an ACE inhibitor alone (group I, n=17) or an ACE inhibitor plus amlodipine (group II, n=13) for 32 weeks. With treatment, blood pressures in both groups were significantly reduced, and diastolic blood pressure was lowered to a much greater extent in group II (76 +/- 2 mmHg) than in group I (83 +/- 2 mmHg, p < 0.05). Although the urinary albumin excretion rate was decreased in both groups, the decrease attained statistical significance only in group II (from 141 +/- 25 mg/day to 69 +/- 18 mg/day, p < 0.05); the extent of reduction in microalbuminuria during antihypertensive treatment was significantly greater in group II (50 +/- 10%) than in group I (14 +/- 13%, p < 0.05). In conclusion, this study showed that in hypertensive microalbuminuric type II diabetic patients, the combination of an ACE inhibitor plus amlodipine resulted in a more pronounced decreased in blood pressure (diastolic blood pressure <80 mmHg) and a greater reduction in urinary albumin excretion than did use of an ACE inhibitor alone. This combination strategy should thus be a more effective tool for obtaining optimal blood pressure control in patients with diabetic nephropathy.     

Hormone replacement therapy and interrelation between serum interleukin-6 and body mass index in postmenopausal women: a population-based study

Postmenopausal women are at increased risk to develop osteoporosis, coronary artery disease, heart failure, and hypertension. Interleukin-6 (IL-6) may be a pathogenetic element in these disorders. Serum IL-6 levels increase during aging and seem to be related to increased body fat mass. In the present retrospective study we aimed to investigate the role of hormone replacement therapy (HRT) on serum IL-6 levels and the interrelation of IL-6 and body fat mass. Parameters were assessed in a population-based sample of postmenopausal women (n = 302) and, for comparison, 245 men of the same age. Women with HRT (n = 92) had significantly lower serum IL-6 levels compared to subjects without HRT, which was independent of age, antihypertensive therapy, smoking habits, and blood pressure (1.5 +/- 0.1 vs. 2.9 +/- 0.6 pg/mL; P = 0.017). In women without HRT, the body mass index (BMI) was correlated with serum IL-6 levels (P < 0.001). Multivariate analysis controlling simultaneously for the effects of blood pressure and heart rate confirmed the positive correlation (P = 0.001). However, in subjects with HRT no such correlation between IL-6 and BMI was demonstrated, which was confirmed after controlling covariates. In male subjects, BMI correlated with serum IL-6 (P = 0.009), which was, however, blunted after controlling for blood pressure and heart rate, probably indicating an influence of the sympathetic nervous system on this interrelation. In conclusion, women receiving HRT display lower serum IL-6 levels and a blunted interrelation of IL-6 and BMI. As IL-6 may be a pathogenetic factor in age-related diseases, HRT-related inhibition of IL-6 secretion could be an important element for the favorable effects of HRT in postmenopausal women.     

Non-pharmacological treatment of hypertension in primary health care: a 2-year open randomized controlled trial of lifestyle intervention against hypertension in eastern Finland

OBJECTIVE: To assess whether lifestyle counselling is effective in non-pharmacological treatment of hypertension in primary health care. DESIGN: Open randomized controlled trial. SETTING: Ten municipal primary health care centres in eastern Finland. PATIENTS: Seven hundred and fifteen subjects aged 25-74 years with systolic blood pressure 140-179 mmHg and/or diastolic blood pressure 90-109 mmHg or antihypertensive drug treatment. INTERVENTIONS: Systematic health counselling given by local public health nurses for 2 years. MAIN OUTCOME MEASURES: Blood pressure, lipids and lifestyle data were collected annually. RESULTS: Among participants with no antihypertensive drug treatment, the net reductions after 1 year both in systolic blood pressure [-2.6 mmHg; 95% confidence interval (CI), -4.7 to -0.5 mmHg] and in diastolic blood pressure (-2.7 mmHg; 95% CI, -4.0 to -1.4 mmHg) were significant in favour of the intervention group. This difference in blood pressure change was maintained during the second year. In participants with antihypertensive drug treatment, no significant difference in blood pressure reduction was seen between the groups during the study. CONCLUSIONS: A relatively modest, but systematic counselling in primary health care can, at least among untreated hypertensive subjects, produce reductions in blood pressure levels that are modest for the individual, but very important from the public health point of view.