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Lennart Hansson

Publications and source records attributed to Lennart Hansson.

34 records · Page 2Linked to original sources
PubMed2002

Natural allergen exposure does not diminish the sensitivity of cytokine production to glucocorticosteroids in blood cells of seasonal allergic asthma and rhinitis patients.

Glucocorticosteroid (GCS) inhibition of cytokine production is a major anti-inflammatory mechanism. However, increased production of pro-inflammatory cytokines during allergic airway inflammation has been proposed to reduce GCS effects. This study aimed to investigate whether allergic airway inflammation due to natural allergen exposure might decrease the sensitivity of granulocyte-macrophage colony-stimulating factor (GM-CSF) production to GCS in blood cells. Blood samples were collected from patients with seasonal allergic asthma (n = 10) and rhinitis (n = 8) and healthy subjects (n = 9), before, during, and after the birch pollen season. Whole blood cultures were stimulated with LPS (10 ng/ml) and treated with budesonide (10(-11)-10(-7) M) for 20 h. GM-CSF levels were analysed using immunoassay. Birch pollen exposure did not alter LPS-stimulated GM-CSF production, although disease symptoms and blood eosinophils increased in the patients. There were no significant differences in budesonide inhibition of GM-CSF production by blood cells of asthma and rhinitis patients compared with cells of healthy subjects before, during or after the birch pollen season and no change in response to allergen exposure. A concentration of 1 nM budesonide inhibited GM-CSF production by more than 50% at all time points. In conclusion, natural allergen exposure did not reduce the sensitivity of GM-CSF production to GCS inhibition in blood cells of seasonal allergic asthma and rhinitis patients.

Adult↗
PubMed2002

Comparison of home and office blood pressure in treated hypertensives in the Nordic Diltiazem (NORDIL) Study.

The aim of the Nordic Diltiazem (NORDIL) Study was to compare cardiovascular morbidity and mortality in calcium-antagonist-based treatment with diltiazem and conventional diuretic/beta-blocker-based treatment in essential hypertension. The objective of the present sub-study was to compare self-measured home blood pressure with office blood pressure at a time-point in the study when the patients' blood pressures had been treated to the level that the investigators conceived to be the blood pressure target. The NORDIL study was prospective, randomized, open and endpoint-blinded. It enrolled 10881 patients aged 50-74 years at health centers in Norway and Sweden who had diastolic blood pressure (BP) of 100 mmHg or more. The present sub-study group (n = 87) was small but fairly representative for the entire study population regarding baseline characteristics. Both systolic (4.0 mmHg, p = 0.01) and diastolic blood pressures (3.1 mmHg, p < 0.001) were significantly lower at home than in the office. Pearson correlation coefficients between the respective office and home readings were statistically highly significant (p < 0.001), but of moderate strength ranging from r = 0.41 for heart rate to r = 0.46 and r = 0.58 for diastolic and systolic blood pressures, respectively. Altman plots also gave statistical support to some inconsistency between the two methods of measurements. Pearson correlation coefficients between afternoon and morning measurements showed strong relationships with r-values >0.9 for both blood pressures and heart rate. The Altman plots also suggested excellent consistency between afternoon and morning measurements. Thus, motivated and trained hypertensive patients can perform home recordings of blood pressure and heart rate with precision; however, there are differences between recordings at home and in the investigators' offices that suggest some degree of "white coat effect" in these treated hypertensives.

Aged↗
PubMed2002

Excess morbidity and cost of failure to achieve targets for blood pressure control in Europe.

AIM: To estimate the burden of failing to achieve targets for blood pressure (BP) control in France, Germany, Italy, Sweden and the UK. METHODS: A cost of illness model was constructed to estimate the impact of uncontrolled hypertension to each national healthcare system. Prevalence of uncontrolled hypertension was taken from published data. Relationships between achieved BP and the cardiovascular events of symptomatic acute myocardial infarction, congestive heart failure and stroke were estimated from the HOT study. Costs were taken from public sources. The acute medical costs of these events were estimated at current prevalence of uncontrolled hypertension and if BP were treated to target. RESULTS: The model estimated that 29 million adults in the five countries (13% population) have BP levels above 160/95 mmHg, and an additional 46 million (21% population) have BP in the range 140/90-160/95 mmHg. The model estimated that healthcare system costs of 1.26 billion euros could be avoided if hypertension management did achieve BP targets. This does not consider the cost of interventions required to reduce the risk of cardiovascular disease. CONCLUSIONS: Failing to achieve BP targets contributes substantially to healthcare system costs and preventable events in the countries studies.

Adolescent↗
PubMed2002

Cognitive function and health-related quality of life in elderly patients with hypertension--baseline data from the study on cognition and prognosis in the elderly (SCOPE).

The Study on COgnition and Prognosis in the Elderly (SCOPE) study is a multi-centre, prospective, randomized, double-blind, and parallel-group study aiming at comparing the effects of candesartan cilexetil and placebo on cardiovascular events and cognitive function in elderly patients with hypertension. The aim of this sub-analysis was to present data on cognitive function and health-related quality of life (HRQL) at baseline (randomization), and to investigate whether cognitive function was related to HRQL. More specifically, the main aim was to investigate the possible relationship between the Mini-Mental State Examination on one hand, and the Psychological General Well-Being (PGWB) index, the Subjective Symptom Assessment (SSA-P) Profile and the EuroQoL Health Utility Index (EQ-5D) on the other. All the instruments are extensively validated. A general finding was that cognitive function was positively associated with higher well-being (PGWB total score and self-control) and higher utility value (EQ-SD current health) but was unrelated to the occurrence of subjective adverse symptoms (SSA-P). Age and the use of psychotropic drugs, but not gender and education level, influenced this relationship significantly.

Aged↗
PubMed2002

Low-dose aspirin does not interfere with the blood pressure-lowering effects of antihypertensive therapy.

BACKGROUND: It has been reported that aspirin (ASA) may interfere with the blood pressure (BP)-lowering effect of various antihypertensive agents and attenuate the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in patients with congestive heart failure. METHODS AND RESULTS: Data from the Hypertension Optimal Treatment (HOT) Study, in which 18 790 intensively treated hypertensive patients were randomized to either ASA 75 mg daily or placebo for 3.8 years (with a 15% reduction in cardiovascular events and a 36% reduction in myocardial infarction in ASA-treated patients), were reanalysed for the whole group of patients and for various subgroups with particular attention to the possible effects of ASA on BP and renal function. In ASA-treated and placebo-treated patients: (1) systolic blood pressure (SBP) and diastolic blood pressure (DBP) values achieved with antihypertensive treatment were superimposable, with clinically irrelevant differences; (2) these superimposable SBP and DBP were achieved with antihypertensive therapies, that were quantitatively and qualitatively similar, and (3) changes in serum creatinine and in estimated creatinine clearance and the number of patients developing renal dysfunction were also similar. Furthermore, the cardiovascular benefits of ASA were of the same magnitude in hypertensive patients receiving or not receiving ACE-inhibitors. CONCLUSIONS: Even long-term, low-dose ASA does not interfere with the BP-lowering effect of antihypertensive agents, including combinations with ACE inhibitors, or with renal function. No negative interaction occurs between ACE inhibition and the cardiovascular benefits of small dose of ASA. Our conclusions cannot be extended to larger doses of ASA, or to patients with congestive heart failure.

Aged↗
PubMed2002

Influence of age, sex and blood pressure on the principal endpoints of the Nordic Diltiazem (NORDIL) Study.

BACKGROUND: The aim of the Nordic Diltiazem (NORDIL) Study was to compare patients with essential hypertension receiving calcium-antagonist-based treatment with diltiazem and similar patients receiving conventional diuretic/beta-blocker-based treatment, with respect to cardiovascular morbidity and mortality. OBJECTIVE: To assess the influence of age, sex, severity of hypertension and heart rate on treatment effects, in a sub-analysis. METHODS: The NORDIL study was prospective, randomized, open and endpoint-blinded. It enrolled, at health centres in Norway and Sweden, 10 881 patients aged 50-74 years who had diastolic blood pressure (DBP) of 100 mmHg or more. Systolic blood pressure (SBP) and DBP were decreased by 20.3/18.7 mmHg in the diltiazem group and by 23.3/18.7 mmHg in the diuretic/beta-blocker group - a significant difference in SBP (P < 0.001). RESULTS: The incidence of the primary endpoint - a composite of cardiovascular death, cerebral stroke and myocardial infarction - was similar for the two treatments. Fatal and non-fatal stroke occurred in 159 patients in the diltiazem group and in 196 patients in the conventional treatment group [relative risk (RR) 0.80, 95% confidence interval (CI) 0.65 to 0.99; P = 0.040], whereas there was a non-significant inverse tendency with respect to all myocardial infarction. There were significantly fewer cerebral strokes in patients receiving diltiazem in the subgroups with baseline SBP > 170 mmHg (n = 5420, RR 0.75, 95% CI 0.58 to 0.98; P = 0.032), DBP >/= 105 mmHg (n = 5881, RR 0.74, 95% CI 0.57 to 0.97; P = 0.030) and pulse pressure >/= 66 mmHg (n = 5461, RR 0.76, 95% CI 0.58 to 0.99, P = 0.041), and more myocardial infarctions in those with heart rate less than 74 beats/min (n = 5303, RR 1.13, 95% CI 1.01 to 1.87; P = 0.040). However, the tendencies for fewer strokes and greater incidence of myocardial infarction were present across subgroups when results were analysed for age, sex, severity of hypertension and heart rate, and treatment-subgroup interaction analyses were not statistically significant. CONCLUSIONS: Compared with a conventional diuretic/beta-blocker-based antihypertensive regimen, there were additional 25% reductions in stroke in the diltiazem-treated patients with blood pressure or pulse pressure greater than the medians, and an increase in myocardial infarction in those with heart rate less than the median. Such findings may be attributable to chance, but the consistency of, in particular, the stroke findings may also suggest an ability of diltiazem, beyond conventional treatment, to prevent cerebral stroke in hypertensive patients with the greatest cardiovascular risk.

Adrenergic beta-Antagonists↗
PubMed2002

Benefit and harm of low-dose aspirin in well-treated hypertensives at different baseline cardiovascular risk.

BACKGROUND: The effects of aspirin in subjects without cardiovascular disease are controversial. In the intensively treated patients of the Hypertension Optimal Treatment (HOT) Study, randomization to low-dose aspirin (75 mg daily) versus placebo significantly reduced cardiovascular events (-15%) and myocardial infarction (-36%), but increased major bleedings (+65%). The present analyses of HOT Study data aim at identifying subgroups of hypertensives with different benefit-to-harm ratios from aspirin, in order to provide recommendations about the use of aspirin in hypertension. METHODS: The 18 790 hypertensive patients (aspirin 9399, placebo 9391; average treatment duration 3.8 years) were stratified for global cardiovascular risk and for individual risk factors. Subgroup-treatment interaction analyses (end points: cardiovascular events, myocardial infarction, major bleedings) were performed by a Cox proportional hazard model. Relative and absolute benefits and harms were calculated. RESULTS: Interaction analyses indicated that of all subgroups, only patients with serum creatinine > 1.3 mg/dl had a significantly greater reduction of cardiovascular events and myocardial infarction (-13 and -7/1000 patient-years), while risk of bleeding was not significantly different between subgroups. In addition to patients with higher creatinine, a favourable balance between benefit and harm of aspirin was found in subgroups of patients at higher global baseline risk and baseline systolic pressure > or = 180 or diastolic pressure > or = 107 mmHg. CONCLUSIONS: Low-dose aspirin should be recommended to well-treated hypertensive patients with even moderate increase in serum creatinine. Aspirin may also be recommended in well-treated hypertensives at higher global cardiovascular risk or higher initial blood pressures.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Baseline Characteristics and Early Blood Pressure Control in the CONVINCE Trial.

-Blood pressure (BP) control rates around the world are suboptimal. Part 2 of the National Health and Nutrition Educational Survey (NHANES) III indicates that only 27.4% of hypertensive Americans aged 18 to 74 years have a BP of <140/90 mm Hg. We wanted to assess BP control during the first 2 years and to describe the baseline characteristics of patients enrolled in the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Study, an international clinical trial that compares outcomes in hypertensive patients randomized to initial treatment with either controlled-onset extended-release verapamil or the investigator's choice of atenolol or hydrochlorothiazide. At randomization, BP was <140/90 mm Hg in only 20.3% of the 16 602 subjects (average+/-SD age 65.6+/-7.4 years; 56% women, 84% white/7% black/7% Hispanic). The average BP at enrollment was 148/85 mm Hg for patients taking BP medications (n=13 879) and 161/94 mm Hg for previously untreated patients (n=2723). After medication titration, with a transtelephonic computer that recommended an increase in the dose or number of antihypertensive agents whenever the BP was 140/90 mm Hg, 84.8% of the subjects attained the goal BP. During 2 years of treatment, BP control was maintained in 67% to 69% of the subjects (69% to 71% for systolic BP of <140 mm Hg and 90% for diastolic BP of <90 mm Hg). These data suggest that the control of systolic BP is more difficult than the control of diastolic BP. The US national goal of having 50% of hypertensives with a BP of <140/90 mm Hg may be achievable if a forced titration strategy is used. Interested investigators, free care and medications, and well-educated subjects may make the attainment of such a goal easier in the CONVINCE study than in the general population.

Journal Article↗
PubMed2001

Renal function and intensive lowering of blood pressure in hypertensive participants of the hypertension optimal treatment (HOT) study.

This article reports further analyses of the Hypertension Optimal Treatment (HOT) Study data with the aim to describe (1) the value of baseline serum creatinine and its clearance (estimated by Cockroft and Gault formula) as predictors of cardiovascular events, (2) the effects of intensive lowering of BP on cardiovascular events and renal function in patients with reduced renal function, and (3) the effects on cardiovascular events of adding acetylsalicylic acid to antihypertensive therapy in patients with reduced renal function. The results show that (1) baseline elevation in serum creatinine and a reduction in estimated creatinine clearance are powerful predictors of cardiovascular events and death. (2) Reduced renal function at baseline did not preclude the desired control of BP. In contrast to patients with normal renal function, the incidence of major cardiovascular events did not differ in the three groups of patients with mild renal insufficiency randomized to different diastolic BP targets. No significant changes in serum creatinine were seen at the end of the 3.8-yr treatment period in the great majority of patients. However, there was a small group of patients (0.58% of the total study population) whose renal function deteriorated (increase > or =30% over baseline and final serum creatinine concentration > or =2 mg/dl) despite satisfactory reduction of diastolic BP. (3) The results of this reanalysis of the HOT Study suggest though do not prove that the association of acetylsalicylic acid with intensive antihypertensive therapy offers additional benefit in hypertensive patients with reduced renal function.

Aged↗
PubMed1999

Treatment of Hypertension and the J Curve.

The optimal reduction in blood pressure when treating hypertension is obviously the one which reduces hypertension related cardiovascular morbidity and mortality as much as possible. Today's approach to the treatment of high blood pressure usually does not achieve this goal. In other words, treated hypertensive patients are still at increased risk of cardiovascular complications, such as strokes and myocardial infarcts, in spite of being treated with antihypertensive drugs. One possible explanation for this could be that the treated blood pressure rarely is brought down to strictly normotensive levels, as shown in numerous studies. This would suggest that a more vigorous lowering of blood pressure would provide greater benefit when treating hypertensive patients. On the other hand, the fact that the relationship between the level of blood pressure and risk may be J shaped suggests that vigorous lowering of blood pressure may increase cardiovascular risks, if blood pressure is brought down too far. A few open, retrospective, nonrandomized studies and one randomized placebo controlled study in the elderly (SHEP) have analyzed this issue. The Hypertension Optimal Treatment (HOT) study,1,2 which was published in June 1998,3 has addressed this problem in a prospective randomized trial. The discussions around the J curve with some emphasis on the HOT study will be briefly reviewed. (c)1999 by Le Jacq Communications, Inc.

Journal Article↗
PubMedDate not supplied

Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial.

CONTEXT: Hypertensive patients are often given a calcium antagonist to reduce cardiovascular disease risk, but the benefit compared with other drug classes is controversial. OBJECTIVE: To determine whether initial therapy with controlled-onset extended-release (COER) verapamil is equivalent to a physician's choice of atenolol or hydrochlorothiazide in preventing cardiovascular disease. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized clinical trial conducted at 661 centers in 15 countries. A total of 16 602 participants diagnosed as having hypertension and who had 1 or more additional risk factors for cardiovascular disease were enrolled between September 1996 and December 1998 and followed up until December 31, 2000. After a mean of 3 years of follow-up, the sponsor closed the study before unblinding the results. INTERVENTION: Initially, 8241 participants received 180 mg of COER verapamil and 8361 received either 50 mg of atenolol or 12.5 mg of hydrochlorothiazide. Other drugs (eg, diuretic, beta-blocker, or an angiotensin-converting enzyme inhibitor) could be added in specified sequence if needed. MAIN OUTCOME MEASURES: First occurrence of stroke, myocardial infarction, or cardiovascular disease-related death. RESULTS: Systolic and diastolic blood pressure were reduced by 13.6 mm Hg and 7.8 mm Hg for participants assigned to the COER verapamil group and by 13.5 and 7.1 mm Hg for partcipants assigned to the atenolol or hydrochlorothiazide group. There were 364 primary cardiovascular disease-related events that occurred in the COER verapamil group vs 365 in atenolol or hydrochlorothiazide group (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.88-1.18; P =.77). For fatal or nonfatal stroke, the HR was 1.15 (95% CI, 0.90-1.48); for fatal or nonfatal myocardial infarction, 0.82 (95% CI, 0.65-1.03); and for cardiovascular disease-related death, 1.09 (95% CI, 0.87-1.37). The HR was 1.05 (95% CI, 0.95-1.16) for any prespecified cardiovascular disease-related event and 1.08 (95% CI, 0.93-1.26) for all-cause mortality. Nonstroke hemorrhage was more common with participants in the COER-verapamil group (n = 118) compared with the atenolol or hydrochlorothiazide group (n = 79) (HR, 1.54 [95% CI, 1.16-2.04]; P =.003). More cardiovascular disease-related events occurred between 6 AM and noon in both the COER verapamil (99/277) and atenolol or hydrochlorothiazide (88/274) groups; HR, 1.15 (95% CI, 0.86-1.53). CONCLUSIONS: The CONVINCE trial did not demonstrate equivalence of a COER verapamil-based antihypertensive regimen compared with a regimen beginning with a diuretic or beta-blocker. When considered in the context of other trials of calcium antagonists, these data indicate that the effectiveness of calcium-channel therapy in reducing cardiovascular disease is similar but not better than diuretic or beta-blocker treatment.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Discovery of biomarker candidates within disease by protein profiling: principles and concepts.

Proteins and peptides present within clinical samples represent a valuable library of information regarding the ongoing processes within cells and tissues in health and disease. We have developed and validated novel technology applications that can be used to characterize the patterns of global protein expression in tissue and biofluids in either gel-based systems or by automated multidimensional nanocapillary liquid chromatography. Mass spectrophotometry platforms using MALDI MS and MS/MS or LTQ ion trap MS were capable of delivering sensitive and accurate identifications of hundreds of proteins contained in individual samples including individual forms of processing intermediates such as phospho peptides. The Systems Biology approach of integrating protein expression data with clinical data such as histopathology, clinical functional measurements, medical imaging scores, patient demographics, and clinical outcome provides a powerful tool for linking biomarker expression with biological processes that can be segmented and linked to disease presentation.

Animals↗