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Biomedical subjects

L Hansson

Publications and source records attributed to L Hansson.

At least 217 records · Page 12Linked to original sources
PubMed1995

Effects of angiotensin-converting enzyme inhibition versus conventional antihypertensive therapy on the glomerular filtration rate.

Antihypertensive treatment has been shown to slow down the decline in glomerular filtration rate (GFR) with time. This has been most extensively studied in patients with diabetic nephropathy and, to some extent, with other forms of renal disease. Angiotensin-converting enzyme (ACE) inhibition has been shown to be more effective in this regard than conventional antihypertensive therapy. This important aspect of antihypertensive treatment has not been studied previously in patients with essential hypertension. Preliminary results regarding the effects of two different antihypertensive therapies on the loss of GFR with time, determined with 51Cr-EDTA clearance after 6, 12, and 24 months of treatment, are presented here. The GFR was assessed in a prospective, randomized, double-blind trial in 257 patients with essential hypertension. All had a normal renal function, and none had diabetes mellitus or glucosuria. The two therapeutic modalities were the ACE inhibitor cilazapril and the beta-adrenoceptor blocking agent atenolol. Both therapies were equally effective in lowering the systolic blood pressure. However, atenolol was slightly but significantly more effective in lowering the diastolic blood pressure after 6, 12, and 24 months. The decline in GFR with time was significantly smaller with cilazapril than with atenolol. After 6 months, the reduction in GFR was 1.0 (cilazapril) vs. 4.0 (atenolol) ml/min x 1.73 m2 (p < 0.01). After 12 months the corresponding changes were 2.0 vs. 4.5 ml/min x 1.73 m2 (p < 0.05) and after 24 months 3.0 vs. 4.0 ml/min x 1.73 m2 (n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

ACE inhibition preserves renal function better than beta-blockade in the treatment of essential hypertension.

Antihypertensive treatment can slow down the decline in glomerular filtration rate (GFR) with time. In patients with diabetic nephropathy, angiotensin converting enzyme (ACE) inhibition has been shown to be more effective in this regard than conventional antihypertensive therapy. Whether this applies to the much larger population of patients with essential hypertension is not yet known. In the present study, the effects of two different antihypertensive therapies on the loss of GFR with time, determined with Cr51-EDTA clearance after 6, 12 and 24 months of treatment, were assessed in a prospective, randomised, double-blind trial in 257 patients with essential hypertension. All had normal renal function and none had diabetes mellitus or glucosuria. Proteinuria (dipstick positive or trace) was detected in 7 patients initially. The two therapeutic modalities were the ACE inhibitor cilazapril and the beta-adrenoceptor blocking agent atenolol. Both therapies were equally effective in lowering systolic blood pressure (e.g. from 168 mmHg to 152 mmHg with cilazapril and from 170 mmHg to 155 mmHg with atenolol after 6 months, p < 0.001 for both). However, atenolol was slightly but significantly more effective in lowering the diastolic blood pressure at 6, 12 and 24 months. The decline in GFR with time was significantly smaller with cilazapril than with atenolol. After 6 months the reduction in GFR was 1.0 vs. 4.0 ml/min x 1.73 m2, p = 0.008 (cilazapril vs. atenolol) and after 12 months the corresponding changes were 2.0 vs. 4.5 ml/min x 1.73 m2, p = 0.04 and after 24 months 3.0 vs. 4.0 ml/min x 1.73 m2, respectively (n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

The antiatherosclerotic effect of calcium antagonists in man--what did MIDAS actually show? Multicenter Isradipine Diuretic Atherosclerosis Study.

The Multicenter Isradipine Diuretic Atherosclerosis (MIDAS) Study was a comparison between the dihydropyridine-derived calcium antagonist isradipine and hydrochlorothiazide in 883 hypertensive patients. B-mode ultrasonography of the carotid artery was used in order to evaluate changes in wall thickness and the development of atherosclerotic plaques during a 3-year period. The final publication has yet to appear in a medical journal. However, the study and its main findings have been presented at several international scientific meetings. In brief, isradipine was significantly more effective than hydrochlorothiazide in preventing an increase in intima-media thickness at several points of measurement in the carotid artery in spite of the fact that systolic blood pressure was not as effectively lowered by isradipine as by the diuretic therapy. Since the results and their implications are of great scientific as well as clinical importance we wish to briefly comment on some of the key aspects of the MIDAS Study, as presented at some international meetings.

Arteriosclerosis↗
PubMed1995

The Hypertension Optimal Treatment (HOT) Study: 12-month data on blood pressure and tolerability. With special reference to age and gender.

The Hypertension Optimal Treatment (HOT) Study is an ongoing prospective, randomized, multicenter trial conducted in 26 countries. Its two main aims are to evaluate the relationship between three levels of target diastolic blood pressure (< or = 90, < or = 85 or < or = 80 mmHg) and the incidence of cardiovascular morbidity and mortality in hypertensive patients and the effects on morbidity and mortality of a low dose, 75 mg daily, of acetylsalicylic acid (ASA, aspirin) compared with placebo. Altogether 19,193 patients have been recruited and randomized and one-year data are now available for all patients. This is a report on the blood pressures achieved, the tolerability and other available data after 12 months of follow-up of all patients. Special reference will be given to the subgroup of elderly patients (> or = 65 years, n = 6,113) as compared to younger patients (< 65 years, n = 13,080). On average, the target group < or = 90 mmHg in diastolic blood pressure has reached 86 mmHg, the target group < or = 85 mmHg has reached 83 mmHg and the target group < or = 80 mmHg has reached 81 mmHg. The percentage of patients that has obtained their target blood pressures is 84% in the target group < or = 90 mmHg, 72% in the target group < or = 85 mmHg and 57% in the target group < or = 80 mmHg at 12 months of follow-up. In the elderly subgroup (> or = 65 years of age) the percentage of patients at target is higher for all target groups, being 86, 76 and 61%, respectively, at 12 months. Antihypertensive treatment is initiated with a calcium antagonist, felodipine, at a dose of 5 mg once daily. If target blood pressure is not reached, additional antihypertensive therapy, with either an angiotensin converting enzyme (ACE) inhibitor or a beta-adrenoceptor blocking agent, is given. Further dose adjustments are made in accordance with a set protocol. As a fifth and final step a diuretic may be added. Side effects have been relatively few in this large multinational series of intensively treated hypertensive patients. Only ankle edema, 2.6% and 3.0%, and coughing, 1.3% and 0.8%, in young and elderly patients, respectively, exceed a frequency of 1%, and 88% of all patients are still taking their baseline therapy felodipine after one year. The one-year data presented here indicate that it should be possible to fulfill the primary aims of the HOT Study.

Age Factors↗
PubMed1995

Status of current therapies for hypertension.

Specific antihypertensive therapy has been in common clinical use for about four decades. During this relatively short period of time remarkable progress has been made in many regards. The value of lowering elevated arterial pressure has been documented in a number of intervention trials. Initially, such studies comprised patients with malignant hypertension only, but later large-scale studies have comprised patients with non-malignant forms of hypertension. At the same time numerous new pharmacological principles have been taken into clinical use in the treatment of hypertension. It is the purpose of this brief review to sum up some of the important steps that have been taken in this area during previous decades and to try to evaluate the status of current therapies for hypertension. Special emphasis will be given to some of the remaining issues and questions that are currently under investigation, such as the place of novel therapies, e.g. calcium antagonists and ACE-inhibitors, and the issue of the level to which blood pressure should be lowered in order to extract the maximum benefit of antihypertensive treatment. Some of the ongoing large-scale intervention trials in hypertension, e.g. the CAPPP Study, the NORDIL Study, the HOT Study and the STOP Hypertension-2 study, will be reviewed.

Aged↗
PubMed1995

Enhanced pressor responses to experimental and daily-life stress in borderline hypertension.

OBJECTIVE: It has been suggested that the blood pressure elevation in borderline hypertension is caused by hyperreactivity to stress. We addressed the questions: are subjects with borderline hypertension hyperreactive to mental stress, and, if so, is this reflected in greater blood pressure responses during daily-life activities, and does non-specific pressor amplification by structural vascular changes contribute to reactivity changes? METHODS: Standardized mental stress was performed during invasive monitoring in 54 borderline hypertensive subjects [systolic blood pressure (SBP) 140-160 or diastolic blood pressure (DBP) 84-95 mmHg, or both] and 20 normotensive control subjects (110-130/60-80 mmHg). Sixteen borderline hypertensive subjects had a cardiac index greater than the mean + 1SD of the normotensive control group (hyperkinetic subgroup) and 38 borderline hypertensive subjects had a cardiac index below that level (normokinetic subgroup). Minimal vascular resistance in the forearm and calf was assessed by plethysmography. Ambulatory 24-h blood pressure was recorded. RESULTS: Subjects with hyperkinetic borderline hypertension had similar intra-arterial blood pressure levels to normokinetic borderline hypertensive subjects. Total peripheral resistance was lower in hyperkinetic borderline hypertensive than in normokinetic borderline hypertensive or normotensive control subjects. Hyperkinetic borderline hypertensive subjects had a significantly lower forearm minimal vascular resistance than normokinetic borderline hypertensive subjects. SBP and mean arterial blood pressure responses to stress were augmented in both borderline hypertensive subgroups. Hyperkinetic borderline hypertensive subjects also showed diastolic hyperreactivity in response to mental stress, in comparison both with normokinetic borderline hypertensive and with normotensive control subjects. During ambulatory blood pressure recording, hyperkinetic borderline hypertensive subjects had greater DBP and mean blood pressure increases from night to day than normotensive control and normokinetic borderline hypertensive subjects. CONCLUSION: Borderline hypertension is characterized by pressor hyperreactivity to mental stress. In hyperkinetic borderline hypertensive subjects, stress hyperresponsiveness is also reflected by greater night-to-day blood pressure gradients during 24-h monitoring. Pressor hyperreactivity in hyperkinetic borderline hypertension is not explained by structural changes in the calf or forearm vasculature.

Adolescent↗
PubMed1995

Review of studies with urapidil in elderly hypertensives.

Urapidil, an antihypertensive agent with dual action (alpha 1-adrenergic antagonist and 5HT1A agonist) is well established in the treatment of arterial hypertension. The present brief review deals specifically with data obtained with urapidil in the treatment of elderly hypertensive patients. Some of these data, dealing with 245 patients aged > or = 65 years, have previously been published, but additional data from more than 5000 hypertensive patients in this age group on file will be reviewed as well. This unique and large data base clearly indicates that urapidil is an effective antihypertensive agent also when used in the treatment of elderly patients. Moreover, urapidil is well tolerated in this age group and has, in addition, a potentially favourable lipid profile. It may therefore be concluded that urapidil is well suited for the treatment of hypertension in the elderly.

Aging↗
PubMed1995

Blood pressure and serum lipids in hypertensive men and women aged 60-97 years.

OBJECTIVE: To report a large set of observations on blood pressure and blood lipids including high-density lipoprotein cholesterol in male and female hypertensive subjects aged 60 years or above. METHODS: Data on blood pressure (BP), total cholesterol (C), and high-density lipoprotein cholesterol (HDL-C) were made available on 5310 hypertensive subjects aged 60-97 years, from a European study on the effects of urapidil, a multifactorial antihypertensive agent (alpha 1-adrenoceptor antagonist+control 5HT1A-receptor stimulant). Observations before treatment were analysed to assess the male-female difference and the changes with age of BP and serum lipids. The subjects were divided into 7 groups, aged 60-62, 63-65, 66-68, 69-71, 72-76, 77-79, and 80+, respectively, and a 2-factor ANOVA (sex and age groups) was used. RESULTS: Systolic BP increased with increasing age in both sexes (p < 0.0001). Over the whole age range, SBP was higher in women than in men (p < 0.0001). Diastolic BP remained unchanged in men and decreased with increasing age in women (p < 0.001). The C level was almost the same in men as in women, but tended to decrease with increasing age in women (p < 0.05). HDL-C was unchanged in men, but increased with increasing age in women (p < 0.006). In all age ranges, the HDL-C level was higher in women than in men (p < 0.0001). CONCLUSION: This study reports observations on BP and serum lipids in a large sample of hypertensives subjects aged 60-97 years. This type of data, especially on high-density lipoprotein cholesterol, is rare in the elderly.

Aged↗
PubMed1995

Characteristics of an ideal antihypertensive therapy for elderly hypertensives.

Treatment of hypertension in the elderly has become not only accepted but also a highly ethical, effective and compelling procedure following the many clearly positive reports on the benefits of lowering elevated arterial pressure in elderly patients. So far most intervention studies in elderly hypertensive patients have used diuretics or beta-blockers or the two in combination as the moiety by which blood pressure has been lowered. However, from a theoretical point of view, more novel therapies could offer advantages that would translate into an even better reduction of cardiovascular morbidity and mortality than has been obtained with the traditional antihypertensive therapies used so far. Some of the studies in elderly hypertensives that are in progress using angiotensin converting enzyme inhibitors or calcium antagonists as the main therapies, e.g. the STOP-Hypertension-2 Study and the Syst-Eur Study, will be briefly reviewed here as will the large data base on urapidil, a dual action antihypertensive drug used in the treatment of elderly hypertensives. By careful evaluation of the effects of novel antihypertensive drugs, and the already existing data base on urapidil in elderly hypertensive patients, it is likely that still better reduction of risk can be obtained in the elderly hypertensives by the use of more novel therapies than diuretics and beta-blockers.

Adult↗
PubMed1995

The future role of losartan.

The past few decades have seen a remarkable development in the field of pharmacological therapy, one of the most notable examples being the treatment of arterial hypertension. Some of the early anti-hypertensive agents were relatively crude by today's standards, but gradually efficacy, tolerability, or both, of blood pressure-lowering (BP) drugs have been improved. It is presently possible to choose from a number of effective and well-tolerated compounds for the treatment of hypertension. The latest additions to the anti-hypertensive armamentarium are the angiotensin II receptor antagonists, the most advanced of these being losartan. It is perhaps most relevant to compare losartan to the angiotensin converting enzyme (ACE) inhibitors, another class of anti-hypertensive agents which acts mainly by interfering with the renin-angiotensin-aldosterone system (RAAS). Studies have shown that losartan lowers BP at least as effectively as ACE inhibitors. However, the side-effect profile of losartan is more favourable. In particular cough, a relatively common side-effect of ACE inhibitors, has been shown to be significantly less common during losartan treatment. This is probably because losartan does not interfere with bradykinin metabolism, unlike the ACE inhibitors. Regarding the reversal of left ventricular hypertrophy (LVH), a powerful risk indicator for cardiovascular disease, we have shown that losartan is more effective in this regard than treatment with the beta-blocker atenolol. It appears, based on these and other findings, that interference with the RAAS is particularly useful in causing reversal of the cardiovascular hypertrophic changes. The prognostic implications remain to be demonstrated, but it would be logical to expect a benefit from this effect. It was recently shown that polymorphism of the ACE gene is associated with increased risk of coronary heart disease even in the absence of conventional risk factors. If these findings are confirmed the interest in interfering with the RAAS as a therapeutic modality in hypertension would obviously be strengthened. It is not easy to predict the future role of any new therapeutic modality. The positive relation between efficacy and tolerability of losartan, as well as the fact that several observations suggest that interference with the RAAS could be favourable from a prognostic point of view, suggest that losartan may come to play an important role in the future treatment of hypertension.

Angiotensin II↗
PubMed1994

Substituted (S)-phenylpiperidines and rigid congeners as preferential dopamine autoreceptor antagonists: synthesis and structure-activity relationships.

A series of (S)-phenylpiperidines in which the substituents on the aromatic ring and nitrogen have been varied has been prepared. They have been evaluated pharmacologically to explore the importance of these substituents for the interaction with central dopamine (DA) receptors. On the basis of biochemical and behavioral data in rats, several of these compounds are characterized as centrally acting DA autoreceptor antagonists. (S)-Phenylpiperidines having an aromatic substituent with a high group dipole moment in the 3-position, i.e., meta with respect to the piperidine ring, and being N-substituted with a propyl group were found to be highly active in vivo on the synthesis and turnover of dopamine. However, they do not induce strong hypoactivity or catalepsy. Interestingly, the most active compounds in vivo were found to display only low affinity for DA D2 and D3 receptors in vitro. In addition, 7-triflate-substituted octahydrobenzo[f]quinolines and 6-triflate-substituted hexahydro-1H-benz[e]indoles have been prepared and pharmacologically evaluated. The trans isomers of these rigid structures were found to display a pharmacological profile similar to that of the flexible phenylpiperidines. The corresponding cis isomers were found to be inactive in vivo.

Animals↗