Markers of microbial translocation predict hypertension in HIV-infected individuals.

OBJECTIVES: The aim of the study was to test the hypothesis that microbial translocation, quantified by levels of lipopolysaccharide (LPS) and subsequent monocyte activation [soluble (sCD14)], is associated with hypertension in HIV-infected individuals. METHODS: In this exploratory substudy, 42 patients were recruited from a larger, longitudinal HIV-infected cohort study on blood pressure. LPS and sCD14 levels were measured retrospectively at the time of nadir CD4 cell count, selecting untreated HIV-infected patients with both advanced immunodeficiency and preserved immunocompetence at the time of nadir. Patients with later sustained hypertension (n = 16) or normotension (n = 26) throughout the study were identified. LPS was analysed using the Limulus Amebocyte Lysate colorimetric assay (Lonza, Walkersville, MD) and sCD14 using an enzyme-linked immunosorbent assay (ELISA). Nonparametric statistical tests were applied. RESULTS: In the HIV-infected patients [median (interquartile range) age 42 (32-46) years; 79% male and 81% Caucasian], LPS and sCD14 levels were both negatively correlated with nadir CD4 cell count. Plasma levels of LPS (P < 0.001) and sCD14 (P = 0.024) were elevated in patients with later hypertension compared with patients with normotension. There was a stepwise increase in the number of patients with hypertension across tertiles of LPS (P = 0.001) and sCD14 (P = 0.007). Both LPS and sCD14 were independent predictors of elevated blood pressure after adjustment for age and gender. For each 10-unit increase in LPS (range 66-272 pg/ml), the increment in mean blood pressure in the first period of blood pressure recording was 0.86 (95% confidence interval 0.31-1.41) mmHg (P = 0.003). CONCLUSIONS: As LPS and sCD14 were both independently associated with elevated blood pressure, microbial translocation may be linked to the development of hypertension.

The relationship between various measures of obesity and arterial stiffness in morbidly obese patients.

BACKGROUND: Obesity is associated with increased risk of cardiovascular disease. Arterial stiffness assessed by carotid femoral pulse wave velocity (PWV) is an independent predictor of cardiovascular morbidity and mortality. We aimed to investigate how various measures of body composition affect arterial stiffness. METHODS: This is an analysis of cross-sectional baseline data from a controlled clinical trial addressing changes in arterial stiffness after either surgery or lifestyle intervention in a population of morbidly obese patients. High-fidelity applanation tonometry (Millar, Sphygmocor) was used to measure pulse wave velocity (PWV). Carotid femoral PWV is a direct measure of arterial stiffness and is considered to be the gold standard method. The Inbody 720 Body Composition Analyzer was used for bioelectrical impedance analysis (BIA). Spearman's correlation, independent samples t-test, chi-square tests, Fisher's exact test and multiple linear regression analyses were used as statistical methods. RESULTS: A total of 133 patients (79 women), with a mean (SD) age of 43 (11) years were included in the study. Men had a significantly higher prevalence of obesity related comorbidities and significantly higher PWV, 9.1 (2.0) m/s vs. 8.1 (1.8) m/s, p = 0.003, than women. In the female group, PWV was positively correlated with WC, WHtR, BMI and visceral fat area. In the male group, PWV was negatively correlated with BMI. Multiple linear regression analysis showed that increasing BMI, WC, WHtR, visceral fat area and fat mass were independently associated with higher PWV in women, but not in men, after adjustment for age, hypertension and type 2 diabetes. CONCLUSION: Most measures of general and abdominal obesity were predictors of arterial stiffness in female morbidly obese patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00626964.

"Real-World" use of cinacalcet for managing SHPT in different European countries: analysis of data from the ECHO observational study.

AIMS: The pan-European ECHO observational study evaluated cinacalcet in adult dialysis patients with secondary hyperparathyroidism (SHPT) in "real-world" clinical practice. A sub-analysis compared data for 7 European countries/country clusters: Austria, CEE (Czech Republic and Slovakia), France, Italy, Netherlands, Nordics (Denmark, Finland, Norway, and Sweden), and the UK/Ireland. METHODS: Data on serum intact parathyroid hormone (iPTH), phosphorous, calcium, as well as the usage of cinacalcet, active vitamin D analogues and phosphate binders were compared. RESULTS: 1,865 patients (mean age 58 years) were enrolled: median baseline iPTH levels ranged from 605 pg/ml in Austria to 954 pg/ml in the UK/Ireland. After ~1 year of cinacalcet, median iPTH reductions from baseline ranged from 38% in the UK/Ireland to 58% in the Netherlands. The proportion of patients achieving NKF/K-DOQITM iPTH targets (150 - 300 pg/ml) at Month 12 ranged from 14% in the UK/Ireland to 40% in CEE. In general, use of sevelamer decreased, while use of calcium-based phosphate binders increased, during cinacalcet treatment. Vitamin D changes were more variable. CONCLUSION: The iPTH level at which cinacalcet is initiated in clinical practice differs considerably among different countries: where cinacalcet was started at a lower iPTH level this resulted in better achievement of serum iPTH targets.

Acute kidney injury with renal replacement therapy in trauma patients.

BACKGROUND: Acute kidney injury (AKI) with renal replacement therapy (RRT) is rare in trauma patients. The primary aim of the study was to assess incidence, mortality and chronic RRT dependency in this patient group. METHODS: Adult trauma patients with AKI receiving RRT at a regional trauma referral center over a 12-year period were retrospectively reviewed. RESULTS: Population-based incidence of post-traumatic AKI with RRT was 1.8 persons per million inhabitants per year (p.p.m./year) [95% confidence the interval (CI) 1.5-2.1 p.p.m./year]. In trauma patients admitted to hospital, incidence was 0.5 per thousand (95% CI 0.3-0.7 per thousand) of those treated in intensive care unit (ICU), it was 8.3% (95% CI 5.9-10.8%). The median age was 46 years. Odds ratio (OR) for post-traumatic AKI requiring RRT was higher in males than in females in general population (OR 5.6, 95% CI 2.2-14.0), and in trauma patients admitted to hospital (OR 4.4, 95% CI 1.9-10.3) and ICU (OR 4.5, 95% CI 1.9-10.7). The in-hospital mortality rate was 24% (95% CI 11-37%), 3-month mortality 36% (95% CI 21-51%) and 1-year mortality 40% (95% CI 25-55%). Age was a risk factor for death after 1 year, with 57% (95% CI 7-109%) increased risk for each 10 years added. None of the survivors was dialysis-dependent 3 months or 1 year after trauma. CONCLUSION: AKI in trauma patients requiring RRT was rare in this single-center study. More males than females were affected. Mortality was modest, and renal recovery was excellent as none of the survivors became dependent on chronic RRT.

Association between HIV infection and attenuated diurnal blood pressure rhythm in untreated hypertensive individuals.

OBJECTIVE: Hypertensive cardiovascular complications are more closely associated with ambulatory blood pressure (ABP), particularly the attenuated diurnal blood pressure (BP) rhythm (i.e. a fall in systolic blood pressure <10% during the night compared with the day), than with casual BP. The aim of the study was to assess the ABP pattern in an HIV-infected cohort in which hypertension was newly diagnosed. METHODS: ABP over 24 h was compared between 77 newly diagnosed, untreated hypertensive HIV-positive individuals and 76 HIV-uninfected untreated hypertensive controls. RESULTS: More HIV-infected subjects had an attenuated ABP rhythm with a reduced nocturnal fall than HIV-negative hypertensive control subjects (60 vs. 33%, respectively; P=0.001). The dipping pattern was observed despite newly diagnosed hypertension, a low prevalence of microalbuminuria, and the absence of signs of overt kidney disease. Furthermore, the prevalence of nondipping in the HIV-infected subjects was independent of combination antiretroviral treatment. Multiple logistic regression analysis with dipping pattern as the dependent variable showed that HIV status was an independent predictor of nondipping BP [P=0.002; odds ratio (OR) 0.33; 95% confidence interval (CI) 0.17-0.66]; casual SBP (P=0.37; OR 1.001; 95% CI 0.99-1.04) and microalbuminuria (P=0.39; OR 1.56; 95% CI 0.57-4.28) were not associated with dipping pattern. CONCLUSIONS: The prevalence of a nondipping BP pattern in HIV-infected subjects with newly diagnosed hypertension who had not received antihypertensive treatment was high and significantly greater than in hypertensive control subjects.

Renal amyloidosis in intravenous heroin addicts with nephrotic syndrome and renal failure.

BACKGROUND: Renal amyloidosis has emerged as an important differential diagnosis when heroin addicts are admitted to renal clinics with proteinuria and nephrotic syndrome. MATERIAL: We present nine heroin addicts with renal AA amyloidosis, a condition previously not encountered in Norway, who were admitted to our renal clinic during the last 3.5 years. In the same time period a total of 209 patients were biopsied from native kidneys. RESULTS: Heroin abuse was associated with 70% of all biopsy-verified renal AA amyloidosis during this time period. Renal amyloidosis was found in 9 of the 12 heroin addicts that were biopsied. 6 of the 9 heroin addicts with amyloidosis required dialysis within 13 months after admission. CONCLUSION: Renal AA amyloidosis among heroin addicts seems to be associated with chronic suppurative skin infections. AA amyloidosis should always be considered in chronic heroin addicts presenting with proteinuria and renal impairment.

Tissue Doppler imaging describes diastolic function in men prone to develop hypertension over twenty years.

AIMS: Hypertension is one of several risk factors of cardiovascular disease and is associated with left ventricular (LV) systolic and diastolic dysfunction. A method for reliably detecting the onset of LV dysfunction before transition to irreversible damage of the myocardium would be of crucial importance in subjects with essential hypertension. METHODS AND RESULTS: Subjects with clear differences in BP level, development and duration of the hypertensive disease were examined at the age of 60 yrs: normotensives (n = 17), new hypertensives who developed hypertension over a 20 year period (n = 15) and hypertensives (n = 19). Relationships between conventional echocardiographic and tissue velocities imaging (TVI) parameters compared to LV parameters, and TVI as an estimate of LV function were explored. E'(Lat) (TVI peak early diastolic velocity) (P = 0.006) and E/E'(Lat) (P = 0.002) demonstrated differences in diastolic function between the groups. There were no significant differences regarding systolic myocardial velocities. E'(Lat) correlated to S'(Lat) (TDI peak systolic velocity) (r = 0.32, P = 0.026) and was independently predicted by S'(Lat) (R(2) = 0.24, P = 0.025) in multivariate analysis. E'(Lat) correlated negatively to LV mass index (r = -0.34, P = 0.012), also in multivariate regression analysis (R(2) = 0.12, P = 0.032). CONCLUSIONS: Myocardial diastolic velocities and mitral flow to annulus velocity ratio differentiated LV function between the hypertensive and normotensive groups. The parameters probably reflect changes in relaxation, recoil and contraction and parallel changes in LV mass index.

Improved insulin sensitivity with the angiotensin II-receptor blocker losartan in patients with hypertension and other cardiovascular risk factors.

We aimed to compare the effects of two different vasodilating principles, angiotensin II-receptor blockade and calcium channel blockade, on peripheral insulin-mediated glucose uptake in patients with hypertension and other cardiovascular risk factors. Twenty-one hypertensive patients (11 women and 10 men) with mean age 58.6 years (range 46-75 years), body mass index 29.2 +/- 1.0 kg/m(2) and blood pressure 160 +/- 3/96 +/- 2 mm Hg entered a 4-week run-in period with open-label amlodipine 5 mg. Thereafter they were randomized double-blindly to additional treatment with amlodipine 5 mg or losartan 100 mg. After 8 weeks of treatment, all patients underwent clinical examination and laboratory testing, and 17 of them underwent a hyperinsulinaemic isoglycaemic glucose clamp. After a 4-week open-label wash-out phase, the participants crossed over to the opposite treatment regimen and final examinations with hyperinsulinaemic isoglycaemic glucose clamp after another 8 weeks. Blood pressure was lowered to the same level in both treatment periods. The glucose disposal rate was significantly higher after treatment with losartan 100 mg + amlodipine 5 mg compared to amlodipine 10 mg (4.9 +/- 0.4 vs 4.2 +/- 0.5 mg/kg/min, P = 0.039). Thus our data suggest that angiotensin II-receptor blockade with losartan improves glucose metabolism at the cellular level beyond what can be expected by the vasodilatation and blood pressure reduction alone.

Metformin and antihypertensive therapy with drugs blocking the renin angiotensin system, a cause of concern?

BACKGROUND: The burden of diabetes mellitus type 2 (DM2) is increasing worldwide. The combination of DM2 and hypertension (HT) is frequently encountered. Concurrent use of drugs blocking the renin angiotensin system (angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB)) and metformin have become frequent in this group of patients. That combination can become life-threatening under certain circumstances. METHOD: We present 5 patients with DM2 and HT who developed severe metformin-associated lactic acidosis in a setting with acute renal failure, precipitated by dehydration and aggravated by the use of ACEI or ARB. RESULTS: None of the patients had reduced renal function before the acute illness. They were admitted to the hospital in critical condition with severe metabolic acidosis (pH 6.60 6.94), high S-lactate (14 - 23 mmol/l) and S-creatinine 796 1,621 micromol/l. They were all hypothermic and 3 were hypoglycemic. All developed circulatory and respiratory collapse. They were treated with either intermittent bicarbonate hemodialysis (HD) or with continuous venovenous hemodiafiltration (CVVHDF) and bicarbonate buffering. All patients recovered without renal sequela. CONCLUSION: We believe that the incidence of metformin-associated lactic acidosis in Norway may become more frequent due to increased use of metformin and drugs blocking the renin angiotensin system. The awareness of lactic acidosis as a complication to the use ofmetformin in predisposed individuals is important. General advice should be given to patients regarding reduction of dosage or withdrawal of the drugs during acute intercurrent illness with dehydration. Early diagnosis and treatment of metformin-associated lactic acidosis are crucial for the patient outcome. Hemodialysis can be life-saving and should be started without delay.

Comparison of doxazosin GITS and standard doxazosin in the treatment of high blood pressure.

OBJECTIVE: To examine (1) the relative therapeutic equivalence of 4 mg doxazosin gastrointestinal therapeutic system (DOX GITS) and 4 mg doxazosin standard (DOX-S4) and (2) the efficacy and safety of 4 mg DOX GITS versus 2 mg doxazosin standard (DOX-S2). PATIENTS: Male or female patients aged 18-80 diagnosed with mild-to-moderate essential hypertension (sitting diastolic blood pressure (DBP) 95-110 mmHg and systolic blood pressure (SBP) < 180 mmHg) were randomized into the study. METHODS: This double-blind, parallel, 9-week trial compared DOX-GITS with doxazosin standard (DOX-S) in 310 hypertensive patients. Following a 2-week placebo run-in phase, patients were randomized to receive DOX-GITS at 4 mg/d or DOX-S at 2 or 4 mg/d. DOX GITS dosage remained unchanged at 4 mg throughout the study. Titration in the DOX-S groups was initiated at Week 0 with 1 mg DOX-S and increased to 2 mg DOX-S at Week 1. Dosage in the DOX-S4 group was increased to 4 mg DOX-S at Week 3. Therapeutic equivalence was measured by the change from baseline in sitting diastolic BP (DBP). Efficacy was assessed using the change from baseline for all blood pressure measures. Safety analysis included evaluation of laboratory tests at clinic visits and adverse events (AEs). RESULTS: Therapeutic equivalences between DOX GITS and DOX-S4 and DOX-S2 were established at all study visits except for a significant difference in favor of DOX GITS at Week 1 (p = 0.019) when the dose of DOX-S was 1 mg. All groups had a significant decrease in BP at all study visits compared with baseline. The proportion of patients who reached goal sitting DBP (< 90 mmHg) was similar among the three treatment groups, except at Week 1, when more patients in the DOX GITS group had obtained the goal compared with those in the DOX-S2 group (40.6% vs. 22.3%; p = 0.005). The proportion of patients who reached sitting SBP (< 140 mmHg) goal was similar among groups. AE profiles among the groups were similar. CONCLUSION: DOX GITS was as effective as DOX-S in patients with mild-to-moderate hypertension. The improved pharmacokinetic profile of the GITS formulation compared with the standard formulation allows a therapeutic dose to be delivered earlier and without dose titration. Both formulations of doxazosin were well tolerated.

Increased plasma vasopressin in low renin essential hypertension.

Baseline plasma vasopressin concentrations were measured in 48 men (all 50 years old) with decreased plasma renin concentration and untreated, sustained essential hypertension and in 29 healthy normotensive men. Mean hypertensive plasma vasopressin concentration was more than twice as high as the corresponding normotensive level (15.7 +/- 2.2 [SE] vs 7.5 +/- 1.0 pg/ml; p less than 0.001). Plasma renin concentration in the hypertensive group was reduced compared with that in the normotensive group (0.28 +/- 0.04 vs 0.46 +/- 0.06 Goldblatt units X 10(-4)/ml). These differences appeared despite virtually identical serum osmolality, creatinine clearance, and urinary sodium excretion in the two groups. In the first 38 hypertensive subjects, arterial plasma epinephrine concentrations were significantly increased over those of the first 28 control subjects (99 +/- 12 vs 68 +/- 6 pg/ml; p less than 0.025). In contrast to those with low renin essential hypertension, 35 men with normal renin essential hypertension (all 40 years old) had normal plasma vasopressin levels that were not significantly different from those in a comparable normotensive control group (3.7 +/- 0.8 vs 3.5 +/- 0.4 pg/ml). Arterial epinephrine concentrations were not significantly different between normal renin subjects and the control group. After 6 weeks of treatment with the nonselective beta-adrenergic receptor blocker oxprenolol in 11 subjects with low renin hypertension, blood pressure was reduced and the plasma vasopressin concentration fell from 27.6 +/- 6.4 to 13.5 +/- 4.2 pg/ml (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular mass assessed by electrocardiography and albumin excretion rate as a continuum in untreated essential hypertension.

OBJECTIVE: To study an association between albumin excretion rate and left ventricular mass (LVM) determined by electrocardiogram (ECG)-based criteria, and with respect to ambulatory blood pressure, in patients with newly diagnosed and never-treated essential hypertension. METHODS: We measured 24 h ambulatory blood pressure, albumin excretion rate and LVM in 74 patients with newly diagnosed (within the past year) and never-treated essential hypertension, who were admitted to the hypertension clinic (Ulleval University Hospital). Albumin excretion rate was evaluated by determination of the albumin:creatinine ratio in the first-voided morning urine sample. LVM was assessed by ECG using Cornell voltage-QRS duration product and Sokolow- Lyon criteria. RESULTS: Albumin excretion rate was significantly related to ambulatory blood pressure. There was a weak but significant negative correlation between the decrease in diastolic blood pressure during the night and the rate of excretion of albumin. The patients classified as dippers had a significantly lower albumin excretion rate compared with the non-dippers (1.36+/-0.83 compared with 1.68+/-0.87 mg/mmol; P = 0.03). LVM was found to be significantly related to ambulatory blood pressure. A weak relationship was observed between albumin excretion rate and LVM as evaluated by Cornell criterion (r = 0.23, P = 0.045). When only normoalbuminuric patients were included (i.e. four patients with microalbuminuria were excluded), the relationship was stronger (r = 0.36, P = 0.002). CONCLUSIONS: The present findings show a continuous relationship between albumin excretion rate, LVM and ambulatory blood pressure in newly diagnosed patients with essential hypertension, and suggest the occurrence of early effects on target organs (kidneys and heart). These associations were observed using easily applicable methods such as ECG monitoring and determination of the albumin:creatinine ratio in morning urine samples.

Increased platelet and vascular smooth muscle reactivity to low-dose adrenaline infusion in mild essential hypertension.

During low-dose adrenaline infusion, platelet count, platelet size, plasma beta-thromboglobulin (BTG) and forearm vascular resistance (FVR) were measured in twelve 40-year-old men with mild, untreated hypertension. The average platelet count increased from 195 to 226 X 10(9)/l (P less than 0.001), platelet size from 7.31 to 7.53 X 10(-15)/l (P less than 0.01), BTG from 0.61 to 1.08 nmol/l (P less than 0.02) and FVR decreased from 97 to 58 (arbitrary units; P less than 0.001) during the infusion. The change in platelet count reflects splenic release of platelets, the change in plasma BTG reflects platelet release reaction, while the reduced FVR reflects vascular smooth muscle cell relaxation. In 11 normotensive men aged 40 years, platelet count increased from 187 to 201 X 10 g/l (P less than 0.01) during an equal low-dose adrenaline infusion. This increase in platelet count is significantly less than in the hypertensive group (P less than 0.01). There was statistically no significant change in platelet size, BTG or FVR in the normotensive group. Arterial adrenaline rose from 0.5 to 2.5 nmol/l in the hypertensive and from 0.5 to 2.4 nmol/l in the normotensive group. A third group of 12 normotensive men received saline infusion: neither platelet parameters nor FVR changed in this group. Thus, a small and equal dose of adrenaline elicited a greater increase in platelet count, an enhanced platelet release reaction and a more pronounced forearm vasodilation in hypertensive than in normotensive subjects.

Increased platelet size and release reaction in essential hypertension.

Basal platelet function was measured in 35 40-year-old men with untreated mild essential hypertension and compared with 44 age-matched normotensive men. The groups differed significantly with respect to platelet size in venous blood (hypertensive, 7.46 +/- 0.10 X 10(-15) l versus normotensive, 7.11 +/- 0.09 X 10(-15) l; P = 0.01) and arterial concentration of the platelet-specific protein beta-thromboglobulin (hypertensive, 1.11 +/- 0.23 nmol/l versus normotensive, 0.59 +/- 0.04 nmol/l; P = 0.02). The normotensive subjects had significantly higher beta-thromboglobulin (BTG) in venous than in arterial blood (P less than 0.01). The hypertensive men showed no such difference. In contrast to the normotensive subjects, the hypertensive group had reduced arterial compared with venous platelet count (P less than 0.01). This may reflect an increased liability in the hypertensive subjects to lose platelets through adherence to the cannula during arterial blood sampling. The above findings point to increased platelet activity in essential hypertension, particularly in arterial blood.

Lisinopril or nifedipine in essential hypertension? A Norwegian multicenter study on efficacy, tolerability and quality of life in 828 patients.

In a randomized, parallel, double-blind study, lisinopril (n = 412; average dose 18.8 mg) reduced systolic and diastolic blood pressure (change = 20.2/13.8 mmHg; P less than 0.01/P less than 0.01) more than nifedipine (n = 416; average dose 37.4 mg; change = 13.3/11.2 mmHg) after 10-week treatment in patients, aged 40-70 years, with mild-to-moderate essential hypertension. Lisinopril was better tolerated than nifedipine. The withdrawals from treatment were fewer in the lisinopril-treated group (11 versus 46; P less than 0.01). The frequency of adverse experiences reported after a general question of discomfort was significantly lower for lisinopril than for nifedipine (P less than 0.01). When questioned on specific symptoms, frequency of coughing was higher with lisinopril (P less than 0.01), while flushing, edema, palpitations, dizziness, tiredness and rash were reported more frequently (P less than 0.01, for all) in the nifedipine-treated group. Quality of life was assessed by both patients and spouses. No significant changes in wellbeing were observed for either drug, except for the highest dose level of nifedipine which caused a deterioration.

Decreased central dopaminergic activity in essential hypertension.

Baseline serum prolactin (PRL) was found to be similar in 35 men with untreated essential hypertension (149 +/- 2/98 +/- 1 mmHg; means +/- s.e.) and 44 healthy normotensive men (126 +/- 1/80 +/- 1 mmHg), all 40 years old. A correlation between baseline PRL and aldosterone was found in the normotensive (r = 0.534, P less than 0.001), but not in the hypertensive group (r = -0.011, NS). Ten subjects from each group received intravenous metoclopramide, a competitive dopamine antagonist, while another 12 normotensive subjects were given saline only, and the effect on PRL, vasopressin (AVP) and catecholamines was followed. An exaggerated PRL response to metoclopramide was observed in the hypertensive group compared with the normotensive (P less than 0.05), and the mean normotensive peak value never exceeded the hypertensive. Plasma noradrenaline increased significantly compared with baseline (P less than 0.05) and the control group (P less than 0.001), concomitant with increased heart rate (P less than 0.05), after the administration of metoclopramide both in the hypertensive and normotensive group. After intravenous injection of metoclopramide, forearm blood flow increased significantly by 50% in the hypertensive (P less than 0.001), and 80% in the normotensive group (P less than 0.001) compared with the control group. Mean blood pressure remained unchanged as did plasma AVP, dopamine and adrenaline. The present study indicates an altered central dopaminergic activity in essential hypertension. Even at rest, endogenous dopamine exerts a modulating effect on noradrenaline release in both hypertensive and normotensive men.

Reduced expression of endothelial cell markers after long-term transdermal hormone replacement therapy in women with coronary artery disease.

The effects of 12 months hormone replacement therapy (HRT) on biochemical markers associated with endothelial function were studied in 98 postmenopausal women with CAD, who were randomized to transdermal HRT or a control group. A significant reduction in the levels of von Willebrand factor in the HRT-group compared to controls was seen after 3 months, maintained after 12 months (p <0.001). Significant reduction in the HRT-group compared to controls was also seen in VCAM-1 after 3 months, sustained after 12 months (p = 0.013 and p = 0.045, respectively), and E-selectin was reduced by about 20% after 3 months on HRT, the reduction being statistically significant after 12 months (p <0.001). Significantly reduced levels of ICAM-1 were also seen after 12 months (p = 0.048). No effects could be observed on tPA-antigen or thrombomodulin. The reduction in procoagulant and proinflammatory markers of endothelial function after long-term transdermal HRT could indicate a beneficial effect on the endothelium and thus a potentially modulating effect on the progression of atherosclerosis in women with CAD.

The efficacy and tolerability of enalapril in a formulation with a very low dose of hydrochlorothiazide in hypertensive patients resistent to enalapril monotherapy.

The antihypertensive efficacy and tolerability of formulations of enalapril and low (12.5 mg) and very low (6 mg) doses of hydrochlorothiazide (HCTZ) were compared with enalapril and placebo. Four hundred and two patients with mild to moderate essential hypertension were treated with 20 mg enalapril for 8 weeks. Patients (n = 296) with persistent supine diastolic blood pressure > 95 mm Hg after enalapril monotherapy were randomized to receive enalapril/placebo (group I), 6 mg enalapril/HCTZ (group II), or 12.5 mg enalapril/HCTZ (group III) for another 8 weeks in a double-blind design. The mean reductions in blood pressure were significantly larger in groups II and III compared to group I, 7.3 (95% CI, -9.0; -6.2), 7.7 (-9.2;-6.3), and 4.1 (-5.9;-2.9) mm Hg, respectively P < .01 for groups II and III compared to group I). No difference in side effects was observed between the three groups. A very low dose of 6 mg HCTZ acts synergistically when given together with enalapril, but is devoid of adverse metabolic effects.

Association between albumin:creatinine ratio and 24-hour ambulatory blood pressure in essential hypertension.

Microalbuminuria (MAU) is often found in essential hypertension (EH) and represents a sign of renal and cardiovascular damage. In the present study, we aimed to look at the association between ambulatory blood pressure (BP) and urinary albumin excretion (UAE). We studied 140 patients aged 50.1 +/- 11.6 years referred for 24-h ambulatory blood pressure monitoring (ABPM) and, separately, 46 untreated subjects with newly diagnosed EH. Urinary albumin excretion was evaluated by determination of the albumin-to-creatinine ratio (ACR) in the first voided morning urine sample taken the same day as the ABPM was started. According to the ACR, patients were categorized as having normoalbuminuria (ACR < 1.5 mg/mmol), borderline MAU (1.5 < or = ACR < 3.0 mg/mmol), and overt MAU (ACR > or = 3.0 mg/mmol). Mean ACR was significantly higher in hypertensive than normotensive individuals (2.17 +/- 2.67 mg/mmol and 1.72 +/- 2.97 mg/mmol, respectively, P = .012). Average 24-h, daytime and nighttime systolic BP and diastolic BP were lower in patients with normoalbuminuria than in the other two groups and did not differ among the two microalbuminuric groups. Univariate regression analysis showed a close relationship between ACR and ambulatory BP. Strong correlation between BP and ACR in the normoalbuminuric and borderline microalbuminuric range was also obtained in the group of 46 newly diagnosed hypertensive patients. In conclusion, the threshold level of ACR > or = 3.0 mg/mmol currently used to define microalbuminuria may be not applicable to EH. Instead, a threshold level of ACR > or = 1. 5 mg/mmol may be more appropriate.

Mild essential hypertension in nonobese premenopausal women is characterized by low renin.

The pathophysiological mechanisms in hypertension may differ in men and women. Plasma renin activity was measured in 27 premenopausal, never-treated hypertensive women (blood pressure 141 +/- 2/93 +/- 1 mm Hg) and in 18 age-matched normotensive women (blood pressure 113 +/- 2/71 +/- 2 mm Hg). All subjects were unaware of their blood pressure status. The hypertensive women had on average lower plasma renin activity (0.21 +/- 0.03 nmol/L/h) than their normotensive controls (0.42 +/- 0.07 nmol/L/h, P less than .01). Serum estradiol was also lower in the hypertensive women (0.57 +/- 0.06 v 0.81 +/- 0.09 nmol/L, P less than .05). No difference in epinephrine, norepinephrine, atrial natriuretic peptide, or vasopressin was found between the groups. Plasma renin activity was positively correlated to plasma norepinephrine in the hypertensive women only (r = 0.41, P less than .05). Since low renin hypertension is associated with less cardiovascular complications, this may offer an explanation for the better prognosis of hypertension in women.