The Impact of the Renin-Angiotensin-Aldosterone System on Inflammation, Coagulation, and Atherothrombotic Complications, and to Aggravated COVID-19.

Atherosclerosis is considered a disease caused by a chronic inflammation, associated with endothelial dysfunction, and several mediators of inflammation are up-regulated in subjects with atherosclerotic disease. Healthy, intact endothelium exhibits an antithrombotic, protective surface between the vascular lumen and vascular smooth muscle cells in the vessel wall. Oxidative stress is an imbalance between anti- and prooxidants, with a subsequent increase of reactive oxygen species, leading to tissue damage. The renin-angiotensin-aldosterone system is of vital importance in the pathobiology of vascular disease. Convincing data indicate that angiotensin II accelerates hypertension and augments the production of reactive oxygen species. This leads to the generation of a proinflammatory phenotype in human endothelial and vascular smooth muscle cells by the up-regulation of adhesion molecules, chemokines and cytokines. In addition, angiotensin II also seems to increase thrombin generation, possibly via a direct impact on tissue factor. However, the mechanism of cross-talk between inflammation and haemostasis can also contribute to prothrombotic states in inflammatory environments. Thus, blocking of the renin-angiotensin-aldosterone system might be an approach to reduce both inflammatory and thrombotic complications in high-risk patients. During COVID-19, the renin-angiotensin-aldosterone system may be activated. The levels of angiotensin II could contribute to the ongoing inflammation, which might result in a cytokine storm, a complication that significantly impairs prognosis. At the outbreak of COVID-19 concerns were raised about the use of angiotensin converting enzyme inhibitors and angiotensin receptor blocker drugs in patients with COVID-19 and hypertension or other cardiovascular comorbidities. However, the present evidence is in favor of continuing to use of these drugs. Based on experimental evidence, blocking the renin-angiotensin-aldosterone system might even exert a potentially protective influence in the setting of COVID-19.

Use of proteomics to identify biomarkers associated with chronic kidney disease and long-term outcomes in patients with myocardial infarction.

BACKGROUND: Patients with chronic kidney disease (CKD) have poor outcomes following myocardial infarction (MI). We performed an untargeted examination of 175 biomarkers to identify those with the strongest association with CKD and to examine the association of those biomarkers with long-term outcomes. METHODS: A total of 175 different biomarkers from MI patients enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry were analysed either by a multiple reaction monitoring mass spectrometry assay or by a multiplex assay (proximity extension assay). Random forests statistical models were used to assess the predictor importance of biomarkers, CKD and outcomes. RESULTS: A total of 1098 MI patients with a median estimated glomerular filtration rate of 85 mL min-1 /1.73 m2 were followed for a median of 3.2 years. The random forests analyses, without and with adjustment for differences in demography, comorbidities and severity of disease, identified six biomarkers (adrenomedullin, TNF receptor-1, adipocyte fatty acid-binding protein-4, TNF-related apoptosis-inducing ligand receptor 2, growth differentiation factor-15 and TNF receptor-2) to be strongly associated with CKD. All six biomarkers were also amongst the 15 strongest predictors for death, and four of them were amongst the strongest predictors of subsequent MI and heart failure hospitalization. CONCLUSION: In patients with MI, a proteomic approach could identify six biomarkers that best predicted CKD. These biomarkers were also amongst the most important predictors of long-term outcomes. Thus, these biomarkers indicate underlying mechanisms that may contribute to the poor prognosis seen in patients with MI and CKD.

Overview of HOMEChem: House Observations of Microbial and Environmental Chemistry.

The House Observations of Microbial and Environmental Chemistry (HOMEChem) study is a collaborative field investigation designed to probe how everyday activities influence the emissions, chemical transformations and removal of trace gases and particles in indoor air. Sequential and layered experiments in a research house included cooking, cleaning, variable occupancy, and window-opening. This paper describes the overall design of HOMEChem and presents preliminary case studies investigating the concentrations of reactive trace gases, aerosol particles, and surface films. Cooking was a large source of VOCs, CO2, NOx, and particles. By number, cooking particles were predominantly in the ultrafine mode. Organic aerosol dominated the submicron mass, and, while variable between meals and throughout the cooking process, was dominated by components of hydrocarbon character and low oxygen content, similar to cooking oil. Air exchange in the house ensured that cooking particles were present for only short periods. During unoccupied background intervals, particle concentrations were lower indoors than outdoors. The cooling coils of the house ventilation system induced cyclic changes in water soluble gases. Even during unoccupied periods, concentrations of many organic trace gases were higher indoors than outdoors, consistent with housing materials being potential sources of these compounds to the outdoor environment. Organic material accumulated on indoor surfaces, and exhibited chemical signatures similar to indoor organic aerosol.

Pregnancy-associated plasma protein-A is positively correlated with first-trimester skin microvascular reactivity.

OBJECTIVE: To investigate the relationship between levels of circulating maternal pregnancy-associated plasma protein-A (PAPP-A) and first-trimester maternal vascular function. METHODS: This was a cross-sectional study of 53 healthy, non-smoking, nulliparous pregnant women in Stockholm, Sweden. PAPP-A levels and vascular function were assessed during gestational weeks 11-14. Forearm skin microcirculation was investigated by laser Doppler perfusion imaging during iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to assess endothelium-dependent and -independent microvascular vasodilatation, respectively. Microvascular endothelial function index was calculated as peak ACh/peak SNP. Endothelium-dependent and -independent vasodilatation in the brachial artery was evaluated, respectively, by postischemic hyperemia-induced flow-mediated vasodilatation (FMD) and by response to sublingual intake of glyceryl trinitrate (GTN). RESULTS: PAPP-A was correlated with skin microvascular endothelial function index (ß = 1.008 (95% CI, 0.34-1.68), r2  = 0.17, P = 0.004). PAPP-A also correlated inversely with FMD (ß = -0.052 (95% CI, -0.094 to -0.011), r2  = 0.13, P = 0.014) but did not relate to forearm endothelial function index (i.e. FMD/GTN). The results were retained in multivariate analyses including known confounding factors. CONCLUSIONS: First-trimester endothelium-dependent skin microvascular reactivity was positively related to PAPP-A levels. If confirmed, these novel findings suggest that first-trimester skin microvascular reactivity could be a useful early pregnancy marker of placental function. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Longitudinal study of vascular structure and function during normal pregnancy.

OBJECTIVE: To examine alterations in maternal vascular structure and function during normal pregnancy. METHODS: We assessed brachial and central blood pressure, pulse-wave velocity and augmentation index (by pulse-wave analysis and applanation tonometry), common carotid artery structure (by ultrasonography) and endothelial function in the brachial artery (by postischemic hyperemia-induced flow-mediated vasodilatation by glyceryl trinitrate) and in the forearm skin microcirculation (by laser Doppler perfusion imaging during iontophoretic administration of acetylcholine and sodium nitroprusside) in 52 healthy nulliparous women at 14, 24 and 34 weeks' gestation, and at 9 months postpartum. RESULTS: During pregnancy, brachial and central systolic and diastolic blood pressures initially decreased but subsequently increased (all P < 0.05). Flow-mediated vasodilatation in the brachial artery increased during early pregnancy (P < 0.05), whereas non-specific vasodilatation by glyceryl trinitrate decreased (P < 0.01), indicating improved endothelial function. Thus, endothelial function index (forearm blood flow/glyceryl trinitrate) increased during pregnancy (0.30 ± 0.18 in the non-pregnant state at 9 months postpartum and 0.51 ± 0.19, 0.61 ± 0.39 and 0.49 ± 0.30 in the first, second and third trimesters, respectively) (P < 0.001). Endothelium-dependent skin microvascular reactivity to acetylcholine also increased (P < 0.01). Carotid-femoral pulse-wave velocity decreased during pregnancy (5.88 ± 0.91 m/s in the non-pregnant state and 5.55 ± 0.67, 5.12 ± 0.66 and 5.62 ± 0.74 m/s in the first, second and third trimesters, respectively) (P < 0.001). CONCLUSION: During normal pregnancy, the blood volume expansion necessary for sufficient fetal growth is accommodated by early and marked changes in the matvascular system. This seems to be dependent on normal adaptive endothelial and vascular function. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Fetal growth is associated with first-trimester maternal vascular function.

OBJECTIVE: To investigate the relationship between maternal endothelial function in the first trimester, assessed in both the brachial artery and the forearm skin microcirculation, and fetal growth. METHODS: Vascular function was assessed in 56 pregnant women during gestational weeks 11-14. Vascular reactivity in the brachial artery was evaluated by postischemic hyperemia-induced flow-mediated vasodilatation (FMD) and by vasodilatation following administration of sublingual glyceryl trinitrate (GTN). Forearm skin microcirculation was investigated by laser Doppler perfusion imaging during iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to assess endothelium-dependent and -independent microvascular vasodilatation, respectively. Fetal growth was measured at study inclusion and birth-weight centile was calculated after delivery. RESULTS: FMD and GTN-induced vasodilatation were both associated with birth-weight centile. On multivariate analysis (adjusted for brachial artery diameter at rest, blood pressure, maternal age and heart rate), for FMD ß = 1.7 (95% CI, 0.06-3.34), r2 = 0.26 and P = 0.042, and for GTN-induced vasodilatation ß = 2.6 (95% CI, 0.44-4.68), r2 = 0.15 and P = 0.02. Endothelium-dependent and -independent microvascular reactivity were also associated with birth-weight centile: for ACh ß = 7.82 (95% CI, 1.81-13.83), r2 = 0.12 and P = 0.029, and for SNP ß = 6.27 (95% CI, 1.20-11.34), r2 = 0.11 and P = 0.016. CONCLUSION: First-trimester maternal vascular dilatation capacity (rather than endothelial function alone) is associated with fetal growth. These findings were consistent in both the brachial artery and the forearm skin microcirculation. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Antihypertensive treatment and control according to gender, education, country of birth and psychiatric disorder: the Swedish Primary Care Cardiovascular Database (SPCCD).

The reasons why women and men are treated with different antihypertensive drugs are not clear. Whether socioeconomic factors influence prescription patterns and blood pressure control differently in women and men has not been investigated. This cross-sectional study performed in a cohort of hypertensive patients from the Swedish Primary Care Cardiovascular Database (SPCCD) examined the influence of educational level, country of birth, gender and concomitant psychiatric disorder on prescription pattern and blood pressure control in 40,825 hypertensive patients. Men were more often than women treated with calcium channel blocker and angiotensin-converting enzyme inhibitor (ACEI), irrespective of education, country of birth and psychiatric disorder. Educational level influenced the prescription pattern to some extent, where the gender differences were reduced in patients with a higher educational level. In women, but not in men, high educational level and concomitant psychiatric disorder were associated with a higher proportion reaching target blood pressure. The predominant use of ACEI and calcium channel blockers in men is not influenced by educational level, country of birth or psychiatric disorder. Thus other explanations must be considered such as gender differences in side effects. Educational level seems to have a greater impact on reaching target blood pressure in women compared with men.

Blood pressure changes after renal denervation at 10 European expert centers.

We did a subject-level meta-analysis of the changes (Δ) in blood pressure (BP) observed 3 and 6 months after renal denervation (RDN) at 10 European centers. Recruited patients (n=109; 46.8% women; mean age 58.2 years) had essential hypertension confirmed by ambulatory BP. From baseline to 6 months, treatment score declined slightly from 4.7 to 4.4 drugs per day. Systolic/diastolic BP fell by 17.6/7.1 mm Hg for office BP, and by 5.9/3.5, 6.2/3.4, and 4.4/2.5 mm Hg for 24-h, daytime and nighttime BP (P0.03 for all). In 47 patients with 3- and 6-month ambulatory measurements, systolic BP did not change between these two time points (P0.08). Normalization was a systolic BP of <140 mm Hg on office measurement or <130 mm Hg on 24-h monitoring and improvement was a fall of 10 mm Hg, irrespective of measurement technique. For office BP, at 6 months, normalization, improvement or no decrease occurred in 22.9, 59.6 and 22.9% of patients, respectively; for 24-h BP, these proportions were 14.7, 31.2 and 34.9%, respectively. Higher baseline BP predicted greater BP fall at follow-up; higher baseline serum creatinine was associated with lower probability of improvement of 24-h BP (odds ratio for 20-µmol l(-1) increase, 0.60; P=0.05) and higher probability of experiencing no BP decrease (OR, 1.66; P=0.01). In conclusion, BP responses to RDN include regression-to-the-mean and remain to be consolidated in randomized trials based on ambulatory BP monitoring. For now, RDN should remain the last resort in patients in whom all other ways to control BP failed, and it must be cautiously used in patients with renal impairment.

OS083. Fetal growth and maternal vascular function in early pregnancy.

INTRODUCTION: Increasing evidence indicates that the rate of fetal growth is partly determined already in the first half of pregnancy. A number of authors have reported that if the fetus is smaller than expected at dating, the risk for a small for gestational age fetus increases. OBJECTIVES: To investigate if maternal vascular function in early pregnancy reflects fetal growth in the first trimester. METHODS: Fifty healthy women with singleton viable pregnancies were included in the study that were recorded the ultrasound department of UltraGyn Stockholm, Sweden for ultrasound dating in gestational week 11-14 . Of these, 25 women had their estimated date of delivery postponed ⩾ 7 days at ultrasound dating compared to last menstrual period in gestational week 11-14. As controls 25 women were fetal size were in accordance with the last menstrual period (defined as expected date of delivery moved less than six days) were recruited. The dating examinations were performed by specially trained midwives. To assess gestational age, biparietal diameter was used. Exclusion criteria were the use of oral contraceptives within three months before conception, uncertain date of the last menstrual period, irregular menstrual periods, fetuses that were ⩾ 21 days larger or smaller than expected, and fetal anomalies. Women that smoked were also excluded. Blood pressure was measured in the upper arm in a conventional way. The central blood pressure was calculated with a validated algorithm. Changes in skin microcirculation were measured using laser Doppler fluxmetri (LDF). Both endothelial dependent dilatation using assessment of acetylcholine (Ach) and local warming of skin to 44C for maximum micro vascular hyperaemia (MMH) and non endothelial dilatation using assessment of sodium nitroprusside (SNP) was examined. RESULTS: Fetuses that were smaller than expected at ultrasound dating compared to last menstrual period at gestational week 11-14, had an increased change in maximum micro vascular hyperaemia (p=0.034). There was no significant correlation between ACh-response (p=0.59) and SNP-response (p=0.23). No differences were seen in blood pressure. CONCLUSION: In the first trimester, changes in vascular function might reflect important adaptations that are required to facilitate normal fetal growth. This was highlighted by the findings of a positive correlation between fetal growth at 11-14 weeks gestation and changes in endothelial dependent microcirculation. Vascular function of these women will be followed longitudinally during pregnancy and related to obstetric outcome. If changes in microcirculation in the first trimester correlates to an increased risk for complications such as hypertensive disorders during pregnancy or intrauterine growth restriction this gives new insights into the early phase of these complications.

PP037. Family history of cardiovascular disease and maternal vascular function during early pregnancy.

INTRODUCTION: Women with a family history of cardiovascular disease (CVD) have an increased risk of hypertensive disorders during pregnancy. Pregnancy is associated with increased physical demands on the cardiovascular system and hemodynamic changes. Cardiac output increases by about 40-50%, blood volume by 10-20% and vascular resistance decreases. OBJECTIVES: Our hypotheses was that women with a family history of CVD fail to have an adequate cardiovascular adaptation during pregnancy. METHODS: Fifty healthy women with singleton viable pregnancies were included in the study who were recorded in the Ultrasound Department of UltraGyn Stockholm, Sweden for ultrasound dating in gestational week of 11-14. Of these, 25 women had a family history of CVD which was defined as having at least one first degree relative with the diagnosis of premature hypertension, myocardial infarct or stroke before the age of 55 (men) or 65 (women). Twenty five healthy women without a family history were included as controls. Smokers were excluded. Blood pressure was measured in the upper left arm in a conventional way. The pulse wave was registered in the radial artery (SphygmoCor Px and Vx, PWV Medical). The central blood pressure was calculated with a validated algorithm. The pulse wave was then registered in the femoral artery, the velocity was calculated and the arterial stiffness estimated. Flow mediated vasodilation was studied in the radial artery through measurement with ultrasound of diameter changes and blood flow before and after ischemia (Vivid 7, GE, 10MHz transducer). RESULTS: Systolic blood pressure in the upper left arm was significantly higher in women with a family history of CVD (median 109.5mmHg versus 105mmHg, p=0.04). Diastolic blood pressure did not differ. Aortic blood pressure also differed significantly in women with a family history of CVD, both systolic (median 95mmHg versus 86.3mmHg, p=0.0005) and diastolic (median 66mmHg versus 59.3mmHg, p=0.0024). No other results were significantly different. All values refer to examinations at gestational weeks 11-14. CONCLUSION: Changes in vascular function during the first trimester reflect important adaptations that are necessary for a normal pregnancy. Women with a family history of CVD had a significantly higher blood pressure at 11-14weeks of gestation although the values were within normal range. The pregnancy related decrease of vascular resistance may be less pronounced in women with a family history of CVD. Vascular function will be followed longitudinally during pregnancy and related to obstetric outcome in this group.

Antihypertensive treatment and control in a large primary care population of 21 167 patients.

The efficacy of antihypertensive drug therapy is undisputed, but observational studies show that few patients reach a target blood pressure <140/90 mm Hg. However, there is limited data on the drug prescribing patterns and their effectiveness in real practice. This retrospective observational survey of electronic patient records extracted data from 24 Swedish primary health-care centres, with a combined registered population of 330 000 subjects. We included all patients > 30 years with a recorded diagnosis of hypertension who consulted the centres in 2005 or 2006 (n=21 167). Main outcome measures were systolic and diastolic blood pressures, and prescribed antihypertensive drug classes. Only 27% had a blood pressure <140/90 mm Hg. The number of prescribed drugs increased with age, except among the oldest (> 90 years). Only 29% of patients given monotherapy had a blood pressure <140/90 mm Hg. Women more often received diuretics (52 vs 42%), and less often angiotensin-converting enzyme inhibitors (22 vs 33%) and calcium channel blockers (26 vs 31%) than men. ß-Blockers and diuretics were the most common drug classes prescribed, independent of comorbidity. In conclusion, one out of four primary care patients with hypertension reach target blood pressure. More frequent use of drug combinations may improve blood pressure control.

A randomized controlled trial on very early speech and language therapy in acute stroke patients with aphasia.

BACKGROUND: Aphasia affects one third of acute stroke patients. There is a considerable spontaneous recovery in aphasia, but impaired communication ability remains a great problem. Communication difficulties are an impediment to rehabilitation. Early treatment of the language deficits leading to increased communication ability would improve rehabilitation. The aim of this study is to elucidate the efficacy of very early speech and language therapy (SLT) in acute stroke patients with aphasia. METHODS: A prospective, open, randomized, controlled trial was carried out with blinded endpoint evaluation of SLT, starting within 2 days of stroke onset and lasting for 21 days. 123 consecutive patients with acute, first-ever ischemic stroke and aphasia were randomized. The SLT treatment was Language Enrichment Therapy, and the aphasia tests used were the Norsk grunntest for afasi (NGA) and the Amsterdam-Nijmegen everyday language test (ANELT), both performed by speech pathologists, blinded for randomization. RESULTS: The primary outcome, as measured by ANELT at day 21, was 1.3 in the actively treated patient group and 1.2 among controls. NGA led to similar results in both groups. Patients with a higher level of education (>12 years) improved more on ANELT by day 21 than those with <12 years of education (3.4 vs. 1.0, respectively). In 34 patients in the treatment group and 19 in the control group improvement was ≥1 on ANELT (p < 0.05). There was no difference in the degree of aphasia at baseline except for fluency, which was higher in the group responding to treatment. CONCLUSIONS: Very early intensive SLT with the Language Enrichment Therapy program over 21 days had no effect on the degree of aphasia in unselected acute aphasic stroke patients. In aphasic patients with more fluency, SLT resulted in a significant improvement as compared to controls. A higher educational level of >12 years was beneficial.

The economic consequences of non-adherence to lipid-lowering therapy: results from the Anglo-Scandinavian-Cardiac Outcomes Trial.

BACKGROUND: Adherence to lipid-lowering therapy in clinical practice is less than ideal. Analysis of registry data has indicated that this is associated with poor outcomes. The objective of the present analysis was to assess the impact of high adherence to drug (defined as > 80% of days covered), compared with low adherence to drug (< 50% of days covered) in terms of risk of events and long-term economic consequences. DESIGN: Open-label follow up of a randomised placebo-controlled trial in hypertensive patients. METHODS: Cox proportional hazards and Poisson regression models were used to assess the hazard ratio of patients with high adherence compared with low adherence while controlling for cardiovascular risk. A Markov model was used to predict the long-term costs and health outcomes associated with poor adherence during the follow-up period. RESULTS: Both statistical models indicated that high adherence is associated with improved prognosis [Cox model: 0.75; 95% confidence interval (CI): 0.56-0.98, Poisson model hazard ratio: 0.73; 95% CI: 0.58-0.98]. Discounted at 3.5% per year, the Markov model predicts that as a consequence of higher adherence during the follow-up period, costs would be higher (1689 pounds per patient compared with 1323 pounds per patient) because of higher drug costs, but the projected survival and quality-adjusted survival (QALY) would also be longer (10.83 compared with 10.81 life years and 8.13 compared with 8.11 QALYs). CONCLUSION: Given the higher risk of cardiovascular events associated with low adherence shown here, measures to improve adherence are an important part of the prevention of cardiovascular disease.

Self-association of naphthalene at the air-ice interface.

We present a molecular dynamics study of the interactions between two molecules of naphthalene present at air-water versus air-ice interfaces. In agreement with the inference from our previous experimental work [Kahan, T. F.; Donaldson, D. J. J. Phys. Chem. A 2007, 111, 1277], the results suggest that self-association of the molecules is more likely to take place on the ice surface than on the water surface. A shorter average distance between the two naphthalene molecules, in conjunction with a stronger interaction energy and free energy of association, point to a stronger tendency to self-associate on ice than on water. The distinct behavior at the two interfaces appears be due to more favorable interactions between naphthalene molecules on liquid water surfaces than on ice surfaces.

Angiotensin II infusion in man is proinflammatory but has no short-term effects on thrombin generation in vivo.

BACKGROUND: Angiotensin (Ang) II may be involved in the development of cardiovascular disease. We examined the potential proinflammatory and prothrombotic effects of Ang II in 16 healthy subjects and in 16 subjects with familial combined hyperlipidemia (FCHL), a condition associated with an increased risk of cardiovascular complications. METHODS: We studied the effects of a three hour intravenous infusion of Ang II (10 ng/kg/min) on plasma concentrations of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), circulating leukocyte count, tissue plasminogen activator/plasminogen activator inhibitor-1 (t-PA/PAI-1) complexes, prothrombin fragment 1+2 (F1+2), and thrombin-antithrombin (TAT) complexes. Blood was collected before, during and 1 h after Ang II infusion. RESULTS: IL-6 was higher in subjects with FCHL at rest (P < 0.05) and increased (P < 0.001) similarly in both groups by Ang II infusion. Also leukocyte count was higher in subjects with FCHL at rest (P < 0.001) and increased (P < 0.001) similarly in both groups by Ang II infusion. T-PA/PAI-1 complexes were higher in subjects with FCHL at rest (P < 0.001) and decreased (P < 0.001) similarly in both groups during Ang II infusion. TNF-alpha, F1+2 and TAT complexes were similar in the two groups at rest and did not change during or after the Ang II infusion. CONCLUSIONS: A three hour Ang II infusion increases inflammation and may enhance fibrinolysis but does not affect short term thrombin generation. Subjects with FCHL have signs of increased inflammation and impaired fibrinolysis.

Design and methods of a randomized controlled trial on early speech and language therapy in patients with acute stroke and aphasia.

PURPOSE: Most clinicians would recommend speech and language therapy (SLT) for aphasic patients. The question of when and for how long SLT should be administered still remains controversial. The aim of this trial is to evaluate the efficacy of early SLT in patients with acute stroke and aphasia in a randomized controlled trial. This report will present design and methods and discuss feasibility. METHOD: Consecutive patients with first ever ischemic stroke and aphasia are assessed by the Amsterdam-Nijmegen Everyday Language Test (ANELT) and a short version of the Norsk Grunntest for Afasi. The treatment is language enrichment therapy, and the therapy is given 45 min/day for 15 weekdays. The primary outcome is the difference in the degree of aphasia between the SLT treated group and the control group measured by ANELT at 3 weeks. RESULTS: Around 10% of acute consecutive patients with aphasia are included. Of the first 79 included patients, 86% have completed the study according to protocol. We intend to include 125 patients, which provide sufficient statistical power to detect a clinically significant difference in the degree of aphasia. CONCLUSION: It is feasible to conduct a randomized controlled study on very early SLT for acute aphasic patients.

Economic evaluation of ASCOT-BPLA: antihypertensive treatment with an amlodipine-based regimen is cost effective compared with an atenolol-based regimen.

OBJECTIVE: To compare the cost effectiveness of an amlodipine-based strategy and an atenolol-based strategy in the treatment of hypertension in the UK and Sweden. DESIGN: A prospective, randomised trial complemented with a Markov model to assess long-term costs and health effects. SETTING: Primary care. PATIENTS: Patients with moderate hypertension and three or more additional risk factors. INTERVENTIONS: Amlodipine 5-10 mg with perindopril 4-8 mg added as needed or atenolol 50-100 mg with bendroflumethiazide 1.25-2.5 mg and potassium added as needed MAIN OUTCOME MEASURES: Cost per cardiovascular event and procedure avoided, and cost per quality-adjusted life-year gained. RESULTS: In the UK, the cost to avoid one cardiovascular event or procedure would be euro18 965, and the cost to gain one quality-adjusted life-year would be euro21 875. The corresponding figures for Sweden were euro13 210 and euro16 856. CONCLUSIONS: Compared with the thresholds applied by NICE and in the Swedish National Board of Health and Welfare's Guidelines for Cardiac Care, an amlodipine-based regimen is cost effective for the treatment of hypertension compared with an atenolol-based regimen in the population studied.

Spectroscopic probes of the quasi-liquid layer on ice.

Raman spectra of the water OH-stretch region were acquired at air-ice and air-water interfaces at a glancing angle, which allowed observation of surface characteristics. The shapes of the OH-stretch bands indicate that the environment at the air-ice interface is different from that at the air-water interface and from that seen in bulk water. Water spectra measured at the surface of dodecane under low relative humidity indicate that this method is sensitive to fewer than 50 monolayers of water. Changes in the local environment of the surfacial water molecules may be induced by the presence of different solute species, giving rise to changes in the shape of the band. Dissolved sodium chloride disrupts hydrogen bonding in liquid water and has the same effect at the air-ice interface. However, when either HCl or HNO(3) is adsorbed from the gas phase onto an ice surface, the opposite effect is seen: Their presence appears to increase the extent of hydrogen bonding at the ice surface. At the same time, shifts in the laser-induced fluorescence spectra of acridine, a fluorescent pH-probe present at the air-ice interface, indicate that dissociation of acids occurs there. These observations suggest that the formation of hydronium ions at the air-ice interface enhances the hydrogen bonding of surfacial water molecules.

Cardiac repolarization and its relation to ventricular geometry and rate in reverse remodelling during antihypertensive therapy with irbesartan or atenolol: results from the SILVHIA study.

Hypertensive left ventricular (LV) hypertrophy is associated with a substantial risk for malignant arrhythmias and sudden death. According to recent results, antihypertensive therapy with the angiotensin II type 1 receptor blocker irbesartan reverses both structural and electrical remodelling. However, the relation between the LV geometric pattern (concentric vs eccentric) and electrical reverse remodelling has not been characterized, neither has the relation between repolarization and rate (QT/RR and JT/RR relation), which presumably reflects the propensity for bradycardia-dependent ventricular arrhythmia. In this study, repeat echocardiographic and electrocardiographic measurements were performed in hypertensive patients with LV hypertrophy, randomized to double-blind therapy with irbesartan (n = 44) or the beta(1)-adrenoceptor blocker atenolol (n = 48) for 48 weeks; 53 patients had concentric and 39 eccentric LV hypertrophy. In addition, 37 matched hypertensive subjects without LV hypertrophy and no current therapy served as controls. Irbesartan induced structural and electrophysiological reverse remodelling, independent of LV geometry. In contrast, atenolol had similar beneficial effect only in patients with concentric LV hypertrophy, while the response in those with eccentric hypertrophy was unfavourable with both prolonged repolarization time and an increased QT/RR slope (suggesting reverse-use dependence). In conclusion, there is a significant geometry-related difference in the reverse remodelling processes induced by irbesartan and atenolol. Echocardiographic characterization of the geometry in hypertension-induced LV hypertrophy might become an important step in the selection of optimal antihypertensive therapy.