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Background Controversy exists as to whether the threshold for blood pressure-lowering treatment should differ between people with and without type 2 diabetes. We aimed to investigate the effects of blood pressure-lowering treatment on the risk of major cardiovascular events by type 2 diabetes status, as well as by baseline levels of systolic blood pressure. Methods We conducted a one-stage individual participant-level data meta-analysis of major randomised controlled trials using the Blood Pressure Lowering Treatment Trialists' Collaboration dataset. Trials with information on type 2 diabetes status at baseline were eligible if they compared blood pressure-lowering medications versus placebo or other classes of blood pressure-lowering medications, or an intensive versus a standard blood pressure-lowering strategy, and reported at least 1000 persons-years of follow-up in each group. Trials exclusively on participants with heart failure or with short-term therapies and acute myocardial infarction or other acute settings were excluded. We expressed treatment effect per 5 mm Hg reduction in systolic blood pressure on the risk of developing a major cardiovascular event as the primary outcome, defined as the first occurrence of fatal or non-fatal stroke or cerebrovascular disease, fatal or non-fatal ischaemic heart disease, or heart failure causing death or requiring hospitalisation. Cox proportional hazard models, stratified by trial, were used to estimate hazard ratios (HRs) separately by type 2 diabetes status at baseline, with further stratification by baseline categories of systolic blood pressure (in 10 mm Hg increments from Findings We included data from 51 randomised clinical trials published between 1981 and 2014 involving 358 533 participants (58% men), among whom 103 325 (29%) had known type 2 diabetes at baseline. The baseline mean systolic/diastolic blood pressure of those with and without type 2 diabetes was 149/84 mm Hg (SD 19/11) and 153/88 mm Hg (SD 21/12), respectively. Over 4·2 years median follow-up (IQR 3·0–5·0), a 5 mm Hg reduction in systolic blood pressure decreased the risk of major cardiovascular events in both groups, but with a weaker relative treatment effect in participants with type 2 diabetes (HR 0·94 [95% CI 0·91–0·98]) compared with those without type 2 diabetes (0·89 [0·87–0·92]; pinteraction=0·0013). However, absolute risk reductions did not differ substantially between people with and without type 2 diabetes because of the higher absolute cardiovascular risk among participants with type 2 diabetes. We found no reliable evidence for heterogeneity of treatment effects by baseline systolic blood pressure in either group. In keeping with the primary findings, analysis using stratified network meta-analysis showed no evidence that relative treatment effects differed substantially between participants with type 2 diabetes and those without for any of the drug classes investigated. Interpretation Although the relative beneficial effects of blood pressure reduction on major cardiovascular events were weaker in participants with type 2 diabetes than in those without, absolute effects were similar. The difference in relative risk reduction was not related to the baseline blood pressure or allocation to different drug classes. Therefore, the adoption of differential blood pressure thresholds, intensities of blood pressure lowering, or drug classes used in people with and without type 2 diabetes is not warranted. Funding British Heart Foundation, UK National Institute for Health Research, and Oxford Martin School.

Findings 33 trials met the inclusion criteria, and included 260 447 participants with 15 012 cancer events. Median follow-up of included participants was 4?2 years (IQR 3?0?5?0). In the individual participant data meta-analysis comparing each drug class with all other comparators, no associations were identified between any antihypertensive drug class and risk of any cancer (HR 0?99 [95% CI 0?95?1?04] for ACEIs; 0?96 [0?92?1?01] for ARBs; 0?98 [0?89?1?07] for 13 blockers; 1?01 [0?95?1?07] for thiazides), with the exception of calcium channel blockers (1?06 [1?01?1?11]). In the network meta-analysis comparing drug classes against placebo, we found no excess cancer risk with any drug class (HR 1?00 [95% CI 0?93?1?09] for ACEIs; 0?99 [0?92?1?06] for ARBs; 0?99 [0?89?1?11] for 13 blockers; 1?04 [0?96?1?13] for calcium channel blockers; 1?00 [0?90?1?10] for thiazides). Summary Background Some studies have suggested a link between antihypertensive medication and cancer, but the evidence is so far inconclusive. Thus, we aimed to investigate this association in a large individual patient data meta-analysis of randomised clinical trials. Methods We searched PubMed, MEDLINE, The Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from Jan 1, 1966, to Sept 1, 2019, to identify potentially eligible randomised controlled trials. Eligible studies were randomised controlled trials comparing one blood pressure lowering drug class with a placebo, inactive control, or other blood pressure lowering drug. We also required that trials had at least 1000 participant years of follow-up in each treatment group. Trials without cancer event information were excluded. We requested individual participant data from the authors of eligible trials. We pooled individual participant-level data from eligible trials and assessed the effects of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), 13 blockers, calcium channel blockers, and thiazide diuretics on cancer risk in one-stage individual participant data and network meta-analyses. Cause-specific fixed-effects Cox regression models, stratified by trial, were used to calculate hazard ratios (HRs). The primary outcome was any cancer event, defined as the first occurrence of any cancer diagnosed after randomisation. This study is registered with PROSPERO (CRD42018099283). Findings 33 trials met the inclusion criteria, and included 260 447 participants with 15 012 cancer events. Median follow-up of included participants was 4 & middot;2 years (IQR 3 & middot;0 & ndash;5 & middot;0). In the individual participant data meta-analysis comparing each drug class with all other comparators, no associations were identified between any antihypertensive drug class and risk of any cancer (HR 0 & middot;99 [95% CI 0 & middot;95 & ndash;1 & middot;04] for ACEIs; 0 & middot;96 [0 & middot;92 & ndash;1 & middot;01] for ARBs; 0 & middot;98 [0 & middot;89 & ndash;1 & middot;07] for 13 blockers; 1 & middot;01 [0 & middot;95 & ndash;1 & middot;07] for thiazides), with the exception of calcium channel blockers (1 & middot;06 [1 & middot;01 & ndash;1 & middot;11]). In the network meta-analysis comparing drug classes against placebo, we found no excess cancer risk with any drug class (HR 1 & middot;00 [95% CI 0 & middot;93 & ndash;1 & middot;09] for ACEIs; 0 & middot;99 [0 & middot;92 & ndash;1 & middot;06] for ARBs; 0 & middot;99 [0 & middot;89 & ndash;1 & middot;11] for 13 blockers; 1 & middot;04 [0 & middot;96 & ndash;1 & middot;13] for calcium channel blockers; 1 & middot;00 [0 & middot;90 & ndash;1 & middot;10] for thiazides). Interpretation We found no consistent evidence that antihypertensive medication use had any effect on cancer risk. Although such findings are reassuring, evidence for some comparisons was insufficient to entirely rule out excess risk, in particular for calcium channel blockers.

It is well established that there is a continuous relationship between raised blood pressure and the risk of cardiovascular or cerebrovascular disease. Both systolic and diastolic hypertension are associated with increased risk, but systolic blood pressure appears to be a more important determinant of risk than diastolic blood pressure. Randomised controlled trials have clearly shown that lowering blood pressure results in significant reductions in cardiovascular mortality and morbidity, and hence current hypertension management guidelines recommend target blood pressures of below 140/90 mm Hg (135/85 mm Hg in the case of the WHO/ISH guidelines). Despite the clear evidence for the benefits of antihypertensive therapy, however, blood pressure is often not adequately controlled in clinical practice. Population surveys indicate that the proportion of patients achieving even conservative blood pressure targets may be only 20% or lower. A number of factors contribute to poor control of hypertension, including a focus by the physician on diastolic blood pressure, rather than the prognostically more important systolic pressure, and poor adherence to therapy by patients. Poor adherence may be largely attributable to adverse events, and there is evidence that the excellent tolerability profile of angiotensin II type 1 (AT(1))-receptor blockers may help to increase the proportion of patients remaining on therapy. AT(1)-receptor blockers could thus make a potentially important contribution to solving the problem of uncontrolled hypertension.

We wanted to test whether living environment, occupation and social position are risk factors for asthma and chronic bronchitis/emphysema (CBE). The prevalence of bronchial asthma, CBE, respiratory symptoms and smoking habits in a random sample of 12071 adults aged 20–59 years was assessed in a postal survey with a slightly modified questionnaire previously used in central and northern Sweden (The OLIN studies). Occupation was coded according to a socio-economic classification system. Six different living environment areas were defined; city–countryside, seaside–not seaside and living close to heavy traffic-not living close to heavy traffic. Multiple logistic regression analysis (forward conditional) was applied to estimate the association between the proposed set of risk factors and self-reported obstructive lung diseases and lower respiratory symptoms controlling for age, gender and smoking. After two reminders, the response rate was 70·1% (n=8469); 33·8% of the responders were smokers. In all, 469 subjects (5·5%) stated that they had asthma and 4·6% reported CBE. Besides smoking, which was a risk for both asthma and CBE, there were different risk patterns for self-reported asthma and CBE. In the economically active population there was a tendency that CBE was more common among ‘unskilled and semi-skilled workers’. This fact was further emphasized when the population was merged into the two groups ‘low social position’ and ‘middle/high social position’, with ‘low social position’ as a risk for CBE (OR=1·35, 95% CI=1·06–1·72). No social risk factors were identified for asthma. Living close to heavy traffic was a risk factor for asthma (OR=1·29, 95% CI=1·02–1·62) but not for CBE. Apart from this no living environmental risk factors for obstructive pulmonary diseases were identified. Asthma symptoms and long-standing cough were more common among those subjects living close to heavy traffic compared to those not living close to heavy traffic. To conclude, low social position was a risk factor for CBE and living close to heavy traffic was a risk factor for asthma.

There is a lack of knowledge to which extent heredity or familial risk factors are involved in the development of chronic bronchitis/emphysema (CBE). Smoking is regarded as the most important risk factor, but only about 15% of smokers develop airway obstruction. We evaluated the importance of familial risk factors compared to smoking and ex-smoking using an epidemiological approach. In 1992, a postal questionnaire was distributed to a study sample. In all, 43 questions were asked, in a previously evaluated questionnaire, regarding respiratory symptoms, self-reported lung diseases, smoking habits and familial occurrence of chronic bronchitis and asthma. The questionnaire was sent to 12,073 adults living in the southernmost part of Sweden. The age range was 20-59 years with an equal gender distribution. The study sample was drawn from the population records. The questionnaire was answered by 8469 subjects (70.1%), of whom 392 subjects (4.6%) stated that they had or had had CBE and 469 subjects (5.5%) stated that they had or had had asthma. In a model with logistic regression using the five explanatory variables gender, age, familial occurrence for asthma, familial occurrence for CBE and current or ex-smoking the most important risk factors for CBE were familial occurrence for chronic bronchitis [Odds ratios (OR): 5.19, 95% confidence interval (CI): 4.09-6.60, p = 0.000] and current or ex-smoking (OR: 1.74, 95% CI: 1.41-2.14, p = 0.000). The most important risk factors for asthma were familial occurrence for asthma (OR: 3.71, 95% CI: 3.06-4.51, p = 0.000) and current or ex-smoking (OR: 1.33, 95% CI: 1.09-1.61, p = 0.004). We have found that familial occurrence for CBE in first degree relatives together with smoking is a stronger risk factor for the development of CBE than is smoking.

Lidfeldt J, Lanke J, Sundquist J, Lindholm LH (Lund University, Lund, Sweden). Old patients with hypertension – a 25-year observational study of a geographically defined population (Dalby), aged 67 years at entry. J Intern Med 1998; 244: 469–78. Objectives. To evaluate the impact of hypertension and other risk factors on mortality, in particular cardiovascular mortality, in a geographically defined population of elderly subjects. Design. An observational 25-year study of a total population. Setting. The local health centre in the village of Dalby in southern Sweden. Subjects. All men and women born in 1902 or 1903, living in Dalby, were, at the age of 67, invited for medical and psychological examinations. The population comprised 188 subjects (109 men and 79 women); 156 (83%) of them took part in the first medical examination. Blood pressure, heart rate, weight and height were measured and laboratory tests performed at entry. Blood pressures were thereafter recorded six times, and this report is based on a 25-year follow-up period ending in October 1994. Main outcome measures. Survival analyses were performed, based on definition of underlying causes of death, divided into all-cause and cardiovascular. Results. At entry, females had higher blood pressure than males, both at baseline and during the first 16 years of the study, regardless of whether they were hypertensives or not. Most men smoked but only a few women. At the end of the follow-up of the present study in 1994, 138 out of 156 (88%) subjects had died and only 18 (12%) remained alive; 78 (57%) had died of a cardiovascular disease. In men, a diagnosis of hypertension as well as increased blood pressure at entry was associated with increased mortality. In women this was the case for blood pressure and risk of cardiovascular mortality. In men, both systolic and diastolic blood pressures during the study were significant risk factors for death, whereas in women this was not the case. Conclusions. Elderly male hypertensives ran an increased mortality risk even though they were treated according to the then current guidelines; female hypertensives seemed to run the same risk of dying as normotensive females.

Abstract —Losartan was the first available orally administered selective antagonist of the angiotensin II type 1 receptor developed for the treatment of hypertension. The Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of the β-blocker atenolol on the reduction of cardiovascular morbidity and mortality. Patients with essential hypertension, aged between 55 and 80 years, and ECG-documented left ventricular hypertrophy (LVH) were included. Altogether, 9223 patients in Scandinavia, the United Kingdom, and the United States were randomized from June 1995 through April 1997, and 9194 remain after exclusion of a study center at which irregularities were discovered. This population of hypertensives (mean systolic/diastolic blood pressure, 174.4/97.8 mm Hg) with LVH comprises women (54.1%) and men, mostly retired from active work (mean age, 66.9 years), with a high prevalence of overweight (mean body mass index, 28.0 kg/m 2 ), diabetes mellitus (12.3%), lipid disorders (18.0%), and symptoms or signs of coronary heart disease (15.1%). There were fewer current smokers (

The prevalence of obstructive lung diseases is increasing in Scandinavia and worldwide. The reasons for this are not known. The prevalence varies between countries but also between different areas within the same country. In northern Europe a north-south gradient and also an east-west gradient have been proposed. To our knowledge this is the first comprehensive epidemiological study concerning obstructive lung diseases and respiratory symptoms in the southern part of Sweden. The prevalence of bronchial asthma, chronic bronchitis/emphysema, respiratory symptoms, smoking habits and medication in a random sample of 12 071 adults aged 20–59 years was assessed in a postal survey with a slightly modified questionnaire previously used in central and northern Sweden (the OLIN Studies). The questionnaire was based on the British Medical Research Council (BMRC) questionnaire. We also compared the prevalence figures of asthma found in the postal survey with those reported in the medical records in a part of the study area. After two reminders, the response rate was 70·1% (n=8469); 33·8% of the responders were smokers. Among younger (20–39 year age group) individuals, smoking was most common in women, whereas in those aged 40–59 years, smoking was more common in men. In all, 469 subjects (5·5%) stated that they had asthma, 41·6% of whom reported a family history of asthma compared to 15·9% of the study sample not reporting asthma. Of all subjects reporting asthma, 60·1% (n=282) answered that they used asthma drugs. Inhaled steroids were used by 20·7%. Chronic bronchitis and/or emphysema was reported by 4·6% (n=392), 28·6% of whom reported a family history of chronic bronchitis or emphysema compared to 6·8% of the study sample not reporting chronic bronchitis. The most common respiratory symptom in the study population was ‘phlegm when coughing’ reported by 15·1% (n=1279). Our data show a prevalence of self-reported asthma of 5·5% compared with 7% reported by Lunbäck et al. in northern Sweden, which indicates a north-south gradient.

The treatment of hypertension mainly with diuretics and beta blockers reduces cardiovascular mortality and morbidity, largely due to a decreased incidence of stroke, whereas the beneficial effects of antihypertensive therapy on the occurrence of coronary events have been less than expected from epidemiological studies. Furthermore, treated hypertensive patients still have a higher cardiovascular complication rate, compared with matched normotensives. This is particularly evident in patients with left ventricular hypertrophy (LVH), a major independent risk indicator for cardiovascular disease. In addition to elevating blood pressure, angiotensin II (A-II) exerts an important influence on cardiac structure and function, stimulating cell proliferation and growth. Thus, to further reduce morbidity and mortality when treating hypertensive patients, it may be important to effectively block the effects of A-II. This can be achieved directly at the A-II receptor level by losartan, the first of a new class of antihypertensive agents. It therefore seems pertinent to investigate whether selective A-II receptor blockade with losartan not only lowers blood pressure but also reduces LVH more effectively than current therapy, and thus improves prognosis. The Losartan Intervention For Endpoint reduction (LIFE) in Hypertension study is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality in approximately 8,300 hypertensive patients (initial sitting diastolic blood pressure 95 to 115 mm Hg or systolic blood pressure 160 to 200 mm Hg) with electrocardiographically documented LVH. The study, which will continue for at least 4 years and until 1,040 patients experience one primary endpoint, has been designed with a statistical power that will detect a difference of at least 15% between groups in the incidence of combined cardiovascular morbidity and mortality. It is also the first prospective study with adequate power to link reversal of LVH to reduction in major cardiovascular events. The rationale of the study, which will involve more than 800 clinical centers in Scandinavia, the United Kingdom, and the United States, is discussed, and the major features of its design and general organization are described. On April 30, 1997, when inclusion was stopped, 9,218 patients had been randomized.

Physical exercise causes transient albuminuria. The mechanisms of postexercise albuminuria are not fully clarified but stimulation of the reninangiotensin system (RAS) probably plays a major role through intrarenal haemodynamic changes causing an elevated filtration pressure. In a randomised, double-blind, crossover study we compared the effects on urinary albumin excretion (UAE) of lisinopril (L) and atenolol (A) therapy, i.e. we aimed to investigate whether inhibition of the RAS or inhibition of beta1-adrenoceptor-mediated effects of the sympathetic nervous system differed with regard to changes in UAE. Sixteen patients with uncomplicated primary hypertension were studied. Four standardised bicycle ergometer exercise tests were performed, before and after each active treatment period. UAE 30 min postexercise, determined by radioimmunoassay, was significantly lowered by both treatments: -278 mu g center dot min-1 (L) and -199 mu g center dot min-1 (A). The reduction of postexercise UAE achieved by treatment with the angiotensin-converting enzyme (ACE) inhibitor (L) was significantly greater than that achieved by the beta1-selective adrenoceptor blocker treatment. Blood pressure (BP) at rest and during exercise were equally reduced by both drugs. In conclusion, this study showed that antihypertensive treatment with an ACE inhibitor was more effective in reducing exercise-induced albuminuria than a beta1-selective adrenoceptor-blocking agent with a similar degree of BP reduction in patients with uncomplicated primary hypertension. This suggests that the RAS plays a major role in postexercise albuminuria in hypertensive subjects. The clinical significance of this finding, however, remains to be clarified.

Different studies on the stability of high density lipoprotein cholesterol (HDL) in frozen serum or plasma have yielded conflicting results, namely increase, decrease, or no change at all during prolonged storage under freezing conditions. As part of a major trial on lipid-lowering strategies we statistically demonstrated a time-related decrease in HDL cholesterol during storage up to 46 months at -20 degrees C. We therefore re-analysed 85 frozen samples that had been analysed fresh and then stored from 26 to 46 months, using the dextran sulphate 500/Mg2+ method. A linear regression analysis of change in HDL cholesterol on time was performed. The slope was significantly negative (p < 0.0005). The regression equation was (decrease in HDL) = 0.05 - 0.008 x (time in months), i.e. after 6 months' storage at -20 degrees C there was almost a 1% decrease in the HDL cholesterol concentration per month of storage.

The Swedish Trial in Old Patients with Hypertension-2 (STOP-Hypertension-2) was designed by a project group of the Swedish Hypertension Society to test whether the "newer" treatment alternatives (ACE inhibitors and calcium antagonists) are as good as, better or less good than, the "older" ones (beta-blockers and diuretics) in terms of preventing cardiovascular morbidity and mortality in elderly hypertensives. The aim of the present paper is to report on the progress of the study.Prospective, open trial with blinded end-point committee and centralized randomization (PROBE design). STOP-Hypertension-2 may be regarded as a scientific follow-up of the previously published Swedish Trial in Old Patients with Hypertension (STOP-Hypertensioon-1) (6) using the same study organization.By the end of 1994 when recruitment was stopped, 6628 hypertensive men (34%) and women (66%) aged 70-84 (mean age 76) had been included at 312 Swedish health centres (out of approximately 850). In the whole cohort 11% are diabetics and 9% smokers. The mean total cholesterol value is 6.5 mmol/L.In the whole study cohort, blood pressure was lowered from 194/98 mmHg to 167/85 mmHg after one year. At the end of 1995, 319 fatal events (all-cause mortality) had been reported, corresponding to a mortality rate of 21.3 per 1000 person-years.In STOP-Hypertension-2, 6628 elderly hypertensive have been randomized to three different treatment regimes: beta-blocker+diuretics (the active treatment arm in STOP-Hypertension-1), ACE inhibitors, or calcium antagonists. Their average lowering of blood pressure was 27/13 mmHg and end-points have occurred at the expected rate. Thus, it should be possible to terminate STOP-Hypertension-2 within two to three years.

The cost of screening for hypercholesterolaemia in a clinical trial was investigated at a primary health care centre. A convenience sample of the population was screened for inclusion in a study of the effectiveness of a lipid lowering programme. Included in the study were adults 30-59 years of age with a S-Cholesterol of 6.50-7.79 mmol l-1 at randomization, plus two previous values > or = 6.50 mmol l-1 at screening and selection, with at least two other cardiovascular risk factors. In total 447 persons were screened and 37 were randomized into the lipid lowering programme. The mean cost per randomized person was estimated at about SEK 7500 (Swedish Crowns). An analysis of different inclusion criteria for treatment was also carried out. The cost of finding a patient to treat in the clinical trial was estimated to be more than three times as high with a total cholesterol cut-off point of 7.80 mmol l-1 compared with a cut-off point of 5.20 mmol l-1.

It is well established that hypertensive patients benefit from drug treatment of their disorder. In recent years three major out-come studies of antihypertensive treatment in elderly hypertensives have shown substantial benefits, i.e. a reduction in the risk of stroke and other cardiovascular mortality and morbidity. In all these studies beta-blockers and/or diuretics were used in comparison with placebo. Newer therapeutic alternatives have, however, at least theoretically, many advantages which could result in further improvements in prognosis. The initial Swedish Trial in Old Patients with Hypertension (STOP-Hypertension 1) was conducted in men and women aged 70-84 years. STOP-Hypertension 2 will evaluate the therapy used in STOP-Hypertension 1 against therapy based on either ACE-inhibitors (enalapril and lisinopril) or on calcium antagonists (isradipine and felodipine), using the PROBE design (Prospective, Randomised, Open, Blinded Endpoint evaluation). The primary aim will be to assess the effect on cardiovascular mortality. Statistical calculations indicate that 6,600 patients, followed for four years will be needed (2p or = 180/105 mmHg (and/or). Recruitment of patients started in September 1992 and so far more than 100 patients/week have been included.

In type 2 diabetes the degree of albuminuria is strongly related to progression of diabetic renal disease, as well as to the risk for cardiovascular complications. If normoalbuminuria is maintained, the risk of diabetic nephropathy is very low. In individuals with microalbuminuria, the rate of decline in glomerular filtration rate is closely related to the degree of albuminuria, and regression to normoalbuminuria slows down the rate of decline in renal function. Data from the LIFE-diabetes subgroup showed that levels of albuminuria well below what is usually defined as microalbuminuria, strongly predicted risk for cardiovascular complications. This indicates that when albuminuria is used as a risk predictor for cardiovascular events, so called normal values should be redefined. Traditional values for normo-micro-macroalbuminuria are primarily defined as predictors for the risk of development of diabetic nephropathy. In the LIFE-diabetes subgroup we found that reduction in albuminuria was more pronounced in losartan-based as compared with atenolol-based treatment. The benefit in favor of losartan was partly related to its major influence on albuminuria. Individuals with the highest baseline values of albuminuria had the greatest benefit in terms of reduction in cardiovascular morbidity and mortality on losartan as compared with atenolol. The level of albuminuria during treatment was closely related to the risk for cardiovascular events. We conclude that tiny amounts of albuminuria, well below traditional levels for microalbuminuria, predict cardiovascular morbidity and mortality. Reduction in albuminuria during treatment translates to reduction in cardiovascular events. Monitoring of albuminuria should be an integrated part of management of hypertension in diabetic as well as nondiabetic patients.

Hypertensive subjects who have received no treatment have been found to be hyperinsulinaemic in previous studies using different populations. The present study was carried out to further examine the metabolic disturbances in carefully treated hypertensive subjects [diastolic blood pressure (DBP) less than 90 mmHg] of both sexes from the Dalby population. Three hundred and ten subjects who had been hypertensive for more than 5 years [DBP 88.1 +/- 0.5 (mean +/- s.e.m.)] were compared with 288 normotensive controls, matched for sex and age and chosen from the same population. After an overnight fast and with no medication for 24 h, an oral glucose tolerance test was carried out. P-insulin and P-C-peptide were analysed and insulin sum (P-insulin at start + after 2 h of oral glucose tolerance test) and C-peptide sum were calculated. Insulin and C-peptide sums were higher (P less than 0.001) in the hypertensive than in the normotensive subjects; 0.69 +/- 0.03, 3.36 +/- 0.08 and 0.41 +/- 0.02, 2.74 +/- 0.06, respectively. The diagnosis of hypertension, not the attained blood pressure level, correlated with insulin and C-peptide sums in multivariate analyses; F-values 20.96 (n = 598; P less than 0.001) and 6.68 (P less than 0.01), respectively. Hypertensive subjects under treatment, using calcium antagonists as monotherapy (n = 21), did not differ in age or body mass index from other hypertensives, but they had lower values for insulin and C-peptide sums; 0.45 +/- 0.05 and 2.63 +/- 0.18. Angiotensin converting enzyme inhibitors were not frequently used for monotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND: In a postal questionnaire study, the prevalence of asthma in southern Sweden has been found to be 5.5%. However, the register prevalence of asthma obtained from the medical records in the same municipality and age groups was found to be only 2.1%. OBJECTIVES: The aims of the study were to investigate whether the low register prevalence of asthma was caused by an underdiagnosis of asthma in primary health care and to validate a first diagnosis of asthma set by GPs in primary health care. METHODS: During a period of 3 months in 1997, all patients seeking care in the primary health care units of the municipality of Lund (population 171 877) with upper or lower airway infections, prolonged cough, allergic rhinitis, fatigue or a first positive diagnosis of asthma were recorded ( n = 3025). RESULTS: In the whole group of 3025 patients, 99 patients were found to have received a diagnosis of asthma for the first time during the study period. The diagnosis was verified in 52 of those 68 patients who attended a follow-up and examination by a respiratory physician. Among the remaining 2926 patients, 221 patients were selected randomly to constitute a control group. In this group, three patients were found to have asthma. Thus, the specificity of an asthma diagnosis set in primary health care was 0.99 [95% confidence interval (CI) 0.99-1.00] and the sensitivity was 0.59 (95% CI 0.31-0.81). CONCLUSIONS: The GPs in this study were good at excluding those who did not have asthma (specificity 99%) but less good in correctly diagnosing those who actually had current asthma (sensitivity 59%), which suggests an underdiagnosis of asthma. (Less)

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.To assess the influence of age, sex, severity of hypertension and heart rate on treatment effects, in a sub-analysis.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 (P0.001).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 SBP170 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.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.

OBJECTIVE: The reason that only a minority of smokers develop chronic obstructive pulmonary disease (COPD) is still largely unknown. Glycosylation defects are involved in the pathological mechanisms in cystic fibrosis (CF), where chronic progressive obstructive lung disease dominates the clinical picture. Whether defects of protein glycosylation occur in COPD has not previously been examined. Increase in carbohydrate-deficient transferrin (CDT) in serum seems to function as an indicator of general defects of N-glycosylation. Recently, one study observed high serum CDT concentrations in CF patients. We examined whether subjects with COPD also have increased serum CDT levels. METHOD AND RESULTS: A total of 131 randomly selected individuals, 45-64 years of age, underwent a medical examination, spirometry and blood tests. Serum CDT was determined using high performance liquid chromatography. In subjects diagnosed as having COPD (n = 15), multiple logistic regression analyses demonstrated a significant relationship between the diagnosis of COPD and CDT, even after all efforts were made to take the influence of age and smoking into account (odds ratio 3.16, 95% CI 1.11-8.95). Also, in subjects with COPD there was an inverse partial correlation between forced expiratory volume in 1 s (FEV1) and serum CDT (r = -0.81, p = 0.001). CONCLUSION: These results suggest that protein glycosylation defects occur in COPD and, in addition, might be involved in the pathogenetic mechanisms of the disease. It seems that further investigation of the protein glycosylation in COPD is warranted. (Less)

There is a lack of knowledge to which extent heredity or familial risk factors are involved in the development of chronic bronchitis/emphysema (CBE). Smoking is regarded as the most important risk factor, but only about 15% of smokers develop airway obstruction. We evaluated the importance of familial risk factors compared to smoking and ex-smoking using an epidemiological approach. In 1992, a postal questionnaire was distributed to a study sample. In all, 43 questions were asked, in a previously evaluated questionnaire, regarding respiratory symptoms, self-reported lung diseases, smoking habits and familial occurrence of chronic bronchitis and asthma. The questionnaire was sent to 12,073 adults living in the southernmost part of Sweden. The age range was 20-59 years with an equal gender distribution. The study sample was drawn from the population records. The questionnaire was answered by 8469 subjects (70.1%), of whom 392 subjects (4.6%) stated that they had or had had CBE and 469 subjects (5.5%) stated that they had or had had asthma. In a model with logistic regression using the five explanatory variables gender, age, familial occurrence for asthma, familial occurrence for CBE and current or ex-smoking the most important risk factors for CBE were familial occurrence for chronic bronchitis [Odds ratios (OR): 5.19, 95% confidence interval (CI): 4.09-6.60, p = 0.000] and current or ex-smoking (OR: 1.74, 95% CI: 1.41-2.14, p = 0.000). The most important risk factors for asthma were familial occurrence for asthma (OR: 3.71, 95% CI: 3.06-4.51, p = 0.000) and current or ex-smoking (OR: 1.33, 95% CI: 1.09-1.61, p = 0.004). We have found that familial occurrence for CBE in first degree relatives together with smoking is a stronger risk factor for the development of CBE than is smoking.

The objective was to determine the impact of a multimedia device offering information about malignant melanoma on public knowledge, attitudes, and behaviors.Two municipalities in Sweden, Dalby and S Sandby, were chosen. The population of Dalby was exposed to the multimedia program during 1994-97, whereas the S Sandby population was not. A questionnaire was sent to random samples of the populations (10% of those aged 20-59 years) before (1994, n = 373 and n = 409, respectively) and after the intervention (1996, n = 375 and n = 418, respectively). Response rates were 74-89%.The groups were well balanced at baseline. In both areas women scored higher both at baseline and in 1996. Dalby women showed less fear of skin cancer in 1996 than in 1994 (2.13 vs 2.27, p0.01). This was not so in the controls. There was no major change in "sun behavior" in Dalby, whereas there was a negative change in S Sandby. After the intervention Dalby men had more "knowledge" (from 2.64 to 2.70, p0.05) and a tendency to better "sun behavior" (from 1.77 to 1.85, p = 0.076). There was no significant change over time in the S Sandby men.The multimedia program had a modest effect. The population in Dalby had more knowledge and changed its attitudes in a sun-protective direction. In the control area, the two-year follow-up sun behavior score was lower than at baseline. There was also significantly less fear of skin cancer after the intervention.

The benefits of treating hypertension in elderly diabetic patients, in terms of achieving reductions in cardiovascular morbidity and mortality, have been documented in several recent prospective trials. There has, however, been some controversy regarding the effect of different antihypertensive drugs on the frequency of myocardial infarction in this group of patients.STOP Hypertension-2 was a prospective, randomized, open trial with blinded endpoint evaluation.We studied 6614 elderly patients aged 70-84 years; 719 of them had diabetes mellitus at the start of the study (mean age 75.8 years). Patients were randomly assigned to one of three treatment strategies: conventional antihypertensive drugs (diuretics or beta-blockers), calcium antagonists, or angiotensin converting enzyme (ACE) inhibitors.Reduction in blood pressure was similar in the three treatment groups of diabetics. The prevention of cardiovascular mortality was also similar; the frequency of this primary endpoint did not differ significantly between the three groups. There were, however, significantly fewer (P = 0.025) myocardial infarctions during ACE inhibitor treatment (n = 17) than during calcium antagonist treatment (n = 32; relative risk 0.51, 95% confidence interval 0.28-0.92); but a (non-significant) tendency to more strokes during ACE inhibitor treatment (n = 34 compared with n = 29; relative risk 1.16, 95% confidence interval 0.71-1.91).Treatment of hypertensive diabetic patients with conventional antihypertensive drugs (diuretics, beta-blockers, or both) seemed to be as effective as treatment with newer drugs such as calcium antagonists or ACE inhibitors.

The 1999 hypertension management guidelines issued by the World Health Organization and the International Society of Hypertension emphasize the importance of blood pressure reduction in the prevention of cardiovascular events. Furthermore, they conclude that the benefits of treatment are due to blood pressure lowering per se, rather than to any specific antihypertensive therapy. The results of the second Swedish Trial in Old Patients with Hypertension (STOP-Hypertension-2) are consistent with these recommendations, since in this trial angiotensin converting enzyme (ACE) inhibitors and calcium antagonists reduced blood pressure to the same extent as conventional therapy with beta-blockers and diuretics in elderly hypertensive patients, and the three treatments produced similar reductions in the risk of cardiovascular events. Furthermore, a first subgroup analysis of cardiovascular mortality showed that the three treatments seemed equally effective in diabetic patients. The STOP-Hypertension-2 data, therefore, are fully consistent with the 1999 hypertension management guidelines, and underline the advantages offered by both older and newer antihypertensive therapies.

The Losartan Intervention For Endpoint (LIFE) reduction in hypertension study is a double-blind, prospective, parallel-group study comparing the effects of losartan with those of atenolol on the reduction of cardiovascular complications in patients (n = 9,194) with essential hypertension and with electrocardiographically (ECG) documented left ventricular hypertrophy (LVH). Baseline blood pressure was 174.4/97.8 mm Hg (mean), age 66.9 years, body mass index 28.0 kg/m2; 54.1% were women and 12.5% had diabetes mellitus. This population will be treated until at least 1,040 have a primary endpoint. After five scheduled visits and 12 months of follow-up, blood pressure decreased by 23.9/12.8 mm Hg to 150.5/85.1 mm Hg (target140/90 mm Hg). The mandatory titration level ofor = 160/95 mm Hg was reached by 72.1% of the patients. At the 12-month visit, 22.7% of all patients were taking blinded study drug alone, 44.3% were taking blinded drug plus hydrochlorothiazide (HCTZ), and 17.7% were taking blinded drugs plus HCTZ and additional drugs. Controlling for all other variables, patients in the US received more medication and had 2.4 times the odds of achieving blood pressure control than patients in the rest of the study (P.001). Previously untreated patients (n = 2,530) had a larger initial decrease in blood pressure compared with those previously treated. Diabetics (n = 1,148) needed more medication than nondiabetics to gain blood pressure control. Only 13.9% of the patients had discontinued blinded study drug and 1.4% missed the revisit at 12 months. These data demonstrate both the successful lowering of blood pressure during 12 months of follow-up in a large cohort of patients with hypertension and LVH on ECG, but also emphasize the need for two or more drugs to control high blood pressure in most of these patients. Being previously treated and having diabetes were associated with less blood pressure response, whereas living in the US indicated better blood pressure control. It has been possible to keep most of these patients with complicated hypertension taking blinded study drug for 12 months.

The effects seen in clinical trials may not translate to actual practice situations. We examined the persistence of blood pressure effects 31 months after a clinical trial of treatment with hypotensive agents.Nineteen previously untreated middle-aged men with hypertension had their office and ambulatory blood pressure recorded after 4 weeks of placebo treatment, 4 weeks of active treatment in a clinical trial, and 31 months of treatment in clinical practice. All recording was done by the same physician (IE).Mean 24-hour blood pressure was 138/92 mm Hg after 4 weeks of placebo treatment, 128/85 mm Hg after 4 weeks of active treatment in the clinical trial, and 136/87 mm Hg after a mean of 31 months of treatment in clinical practice. The corresponding blood pressure valuesor =140/90 mm Hg during the daytime were 47%, 24%, and 39%, and office blood pressures were 155/101, 145/93, and 150/91 mm Hg. Individual comparison revealed that 6 of the 19 patients had higher mean 24-hour blood pressure after several months of treatment in clinical practice than after 4 weeks of active treatment in the clinical trial.In our study, the significantly reduced blood pressure in the clinical trial did not persist when followed up in clinical practice. At follow-up, one third of the patients had blood pressure values similar to those before active treatment. The reason for this is unclear, but inconsistent compliance may play a part in the lack of durability of the improvements. Our results indicate that effects seen in short-term clinical trials may not translate to long-term benefits in clinical practice.

To evaluate the impact of hypertension and other risk factors on mortality, in particular cardiovascular mortality, in a geographically defined population of elderly subjects.An observational 25-year study of a total population.The local health centre in the village of Dalby in southern Sweden.All men and women born in 1902 or 1903, living in Dalby, were, at the age of 67, invited for medical and psychological examinations. The population comprised 188 subjects (109 men and 79 women); 156 (83%) of them took part in the first medical examination. Blood pressure, heart rate, weight and height were measured and laboratory tests performed at entry. Blood pressures were thereafter recorded six times, and this report is based on a 25-year follow-up period ending in October 1994.Survival analyses were performed, based on definition of underlying causes of death, divided into all-cause and cardiovascular.At entry, females had higher blood pressure than males, both at baseline and during the first 16 years of the study, regardless of whether they were hypertensives or not. Most men smoked but only a few women. At the end of the follow-up of the present study in 1994, 138 out of 156 (88%) subjects had died and only 18 (12%) remained alive; 78 (57%) had died of a cardiovascular disease. In men, a diagnosis of hypertension as well as increased blood pressure at entry was associated with increased mortality. In women this was the case for blood pressure and risk of cardiovascular mortality. In men, both systolic and diastolic blood pressures during the study were significant risk factors for death, whereas in women this was not the case.Elderly male hypertensives ran an increased mortality risk even though they were treated according to the then current guidelines; female hypertensives seemed to run the same risk of dying as normotensive females.

Losartan was the first available orally administered selective antagonist of the angiotensin II type 1 receptor developed for the treatment of hypertension. The Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality. Patients with essential hypertension, aged between 55 and 80 years, and ECG-documented left ventricular hypertrophy (LVH) were included. Altogether, 9223 patients in Scandinavia, the United Kingdom, and the United States were randomized from June 1995 through April 1997, and 9194 remain after exclusion of a study center at which irregularities were discovered. This population of hypertensives (mean systolic/diastolic blood pressure, 174.4/97.8 mm Hg) with LVH comprises women (54.1%) and men, mostly retired from active work (mean age, 66.9 years), with a high prevalence of overweight (mean body mass index, 28.0 kg/m2), diabetes mellitus (12.3%), lipid disorders (18.0%), and symptoms or signs of coronary heart disease (15.1%). There were fewer current smokers (17%) than in the general population, and approximately 7% were nonwhite. Almost 30% of participants had been untreated for at least 6 months when screened for the study. Only 1557 persons who entered the placebo run-in period of 14 days were excluded, predominantly because of sitting blood pressures above or below the predetermined range of 160-200/95-115 mm Hg and ECG-LVH criteria not met. By application of simple 12-lead ECG criteria for LVH (Cornell voltage QRS duration product formula plus Sokolow-Lyon voltage read by a core laboratory), hypertensive patients with LVH with an average 5-year coronary heart disease risk of 22.3% according to the Framingham score were identified. This population is now being treated (goal,140/90 mm Hg) in adherence with the protocol for at least 4 years after final enrollment (ie, through April 2001) and until at least 1040 patients suffer myocardial infarction, stroke, or cardiovascular death.

To improve general practice (GP) trainees' knowledge of and attitudes towards oncology and their management of cancer patients.A prospective study of 33 GP trainees who, after a first assessment, were randomized either to attend a two-year cancer course (n = 17) or to a control group (n = 16). Both groups were tested at the beginning (pretest) and end (post-test) of the two years. The maximum possible score was 76. All tests were corrected blindly by an oncologist and a general practitioner.The intervention group showed significant post-test-pretest improvements in the domains "knowledge" (mean difference 2.6, 95% CI 1.3-3.8) and "attitudes" (mean difference 2.9, 95% CI 0.8-5.0), but not in "patient management" (mean difference 0.3, 95% CI -0.6-1.2). There was no significant change in the test scores of the controls. The total mean (post-test-pretest) differences were 8.3 (95% CI 4.9-11.6 for the intervention group and -1.4 (95% CI -4.1-1.3) for the controls.A low-intensity two-year cancer course improved the knowledge and attitudes of GP trainees. Patient management, however, was not improved and may be more suited for hospital training. The current five-year specific training in general practice in Sweden seemed to be of limited value in the field of oncology. Thus, there is a need for further development of educational tools for cancer training of GP trainees, at least in Sweden.

To compare two losartan regimens (with and without hydrochlorothiazide) and amlodipine in treating mild-to-moderate hypertension regarding their blood-pressure-lowering effect, drug tolerability and quality of life.A 12-week, randomized, double-blind, parallel-group, multi-centre study. After 4 weeks of placebo, patients with a diastolic blood pressure (DBP) in the range 95-115 mmHg were allocated randomly to be administered 50 mg losartan (increased to 100 mg if the DBP was 90 mmHg or more after 6 weeks), 50 mg losartan (plus 12.5 mg hydrochlorothiazide under the above conditions), or 5 mg amlodipine (increased to 10 mg under the above condition). The tolerability of the treatment and the quality of life were evaluated by spontaneous reporting, active questioning and the Psychological General Well-Being (PGWB) index.In total 898 hypertensives, mainly referred from primary health care (mean age 57.8 years) of whom 52% were men.Administration of 50 mg losartan (plus 12.5 hydrochlorothiazide if necessary) and of 5 mg amlodipine (or 10 mg if necessary) lowered the blood pressure as well as or better than did 50 mg losartan (or 100 mg if necessary). The incidence of 'any discomfort' and 'swollen ankles' increased with amlodipine but not with losartan treatment. The opposite was found for 'dizziness upon standing'. The incidence of drug-related adverse events and the number of patients withdrawn from therapy were higher with amlodipine than they were with losartan treatment. The PGWB index at week 12 indicated that improvements from baseline had occurred in some domains for the losartan groups whereas it remained unchanged for the amlodipine group.Both losartan and amlodipine were effective in lowering the blood pressure and were tolerated well. Administration of 50 mg losartan (plus 12.5 mg hydrochlorothiazide if necessary) and of 5 mg amlodipine (or 10 mg if necessary) lowered the blood pressure equally well or better than did 50 mg losartan (or 100 mg if necessary). Drug-related adverse effects and withdrawal from the study were more common for the amlodipine group. The clinical significance of the improvements in the PGWB index with losartan needs to be studied further.

The treatment of hypertension mainly with diuretics and beta blockers reduces cardiovascular mortality and morbidity, largely due to a decreased incidence of stroke, whereas the beneficial effects of antihypertensive therapy on the occurrence of coronary events have been less than expected from epidemiological studies. Furthermore, treated hypertensive patients still have a higher cardiovascular complication rate, compared with matched normotensives. This is particularly evident in patients with left ventricular hypertrophy (LVH), a major independent risk indicator for cardiovascular disease. In addition to elevating blood pressure, angiotensin II (A-II) exerts an important influence on cardiac structure and function, stimulating cell proliferation and growth. Thus, to further reduce morbidity and mortality when treating hypertensive patients, it may be important to effectively block the effects of A-II. This can be achieved directly at the A-II receptor level by losartan, the first of a new class of antihypertensive agents. It therefore seems pertinent to investigate whether selective A-II receptor blockade with losartan not only lowers blood pressure but also reduces LVH more effectively than current therapy, and thus improves prognosis. The Losartan Intervention For Endpoint reduction (LIFE) in Hypertension study is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality in approximately 8,300 hypertensive patients (initial sitting diastolic blood pressure 95 to 115 mm Hg or systolic blood pressure 160 to 200 mm Hg) with electrocardiographically documented LVH. The study, which will continue for at least 4 years and until 1,040 patients experience one primary endpoint, has been designed with a statistical power that will detect a difference of at least 15% between groups in the incidence of combined cardiovascular morbidity and mortality. It is also the first prospective study with adequate power to link reversal of LVH to reduction in major cardiovascular events. The rationale of the study, which will involve more than 800 clinical centers in Scandinavia, the United Kingdom, and the United States, is discussed, and the major features of its design and general organization are described. On April 30, 1997, when inclusion was stopped, 9,218 patients had been randomized.

In Sweden, as in most Western countries, the incidence of malignant melanoma of the skin is rapidly increasing, and the disease is now one of the ten most common tumour types. It is at present increasing at an annual rate of more than 4% for both sexes, which is the highest rate for any malignancy[1].

To evaluate the cost-effectiveness of two types of advice (usual and intensive) to lower cardiovascular risk, with or without pharmacological medication aimed at lowering cholesterol levels.Prospective, randomized, controlled clinical study of 18 months' duration.Thirty-two primary health care centres in Sweden.A total of 384 males, aged 30-59 years, with at least one cardiovascular risk factor in addition to moderate primary hyperlipidaemia; of these, 355 completed the 18-month follow-up.Intensive advice consisted of group sessions led by a health care professional; the usual level of advice was given at follow-up visits. The pharmacological intervention consisted of pravastatin. The goal was to achieve a 15% reduction in cholesterol.Cost per life-year gained based on the change in serum cholesterol and the net intervention cost of the four treatment options.The usual level of advice and intensive advice in combination with pharmacological treatment achieved no incremental effects and were not considered in the cost-effectiveness analysis. The cost per life-year gained of pharmacological treatment compared with intensive advice decreased. The cost per life-year gained of pharmacological treatment compared with no treatment was about $61,000, if no adverse consequences on noncardiovascular mortality were assumed.According to the results of the CELL trial, intensive advice is not a cost-effective strategy compared with lipid-lowering drug treatment. However, it is also doubtful whether drug treatment as primary prevention is cost-effective compared with no treatment in the studied patient population.

Different studies on the stability of high density lipoprotein cholesterol (HDL) in frozen serum or plasma have yielded conflicting results, namely increase, decrease, or no change at all during prolonged storage under freezing conditions. As part of a major trial on lipid-lowering strategies we statistically demonstrated a time-related decrease in HDL cholesterol during storage up to 46 months at -20 degrees C. We therefore re-analysed 85 frozen samples that had been analysed fresh and then stored from 26 to 46 months, using the dextran sulphate 500/Mg2+ method. A linear regression analysis of change in HDL cholesterol on time was performed. The slope was significantly negative (p0.0005). The regression equation was (decrease in HDL) = 0.05 - 0.008 x (time in months), i.e. after 6 months' storage at -20 degrees C there was almost a 1% decrease in the HDL cholesterol concentration per month of storage.

Treatment of elderly hypertensives with beta-receptor blockers and/or diuretics is cost-effective according to the analyses of the results of the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). The cost-effectiveness ratios are low and of the same magnitude for both men and women. The results with respect to reduced risk of cardiovascular disease in STOP Hypertension are also supported by several other studies using the same groups of drugs. The more modern drugs (calcium antagonists, alpha 1 blockers, and ACE inhibitors) have not proven their efficacy in the reduction of cardiovascular events in prospective studies of primary hypertension. It has, however, been shown that they lower blood pressure well also in the elderly and that they are cost-effective among the elderly if treatment with beta-receptor blockers and/or diuretics is contraindicated, provided that they lower the incidence of cardiovascular disease to the same extent as do beta-receptor blockers and diuretics. Studies tackling this latter question are under way, also in the elderly.

Objectives. To observe blood pressure, cardiovascular events, and total mortality after withdrawing antihypertensive treatment for elderly patients. Design. Multicentre observational study. Setting. Sweden. A 5-year follow-up of 333 elderly hypertensive patients, aged 70–84 years (mean age 75.2 ± sd 3.8 years, 68% females). In all, 74 out of the 333 patients (22%) died during the study period. Method. After withdrawal of the antihypertensive therapy, all patients started in the untreated state and during the 5-year follow-up they could then either remain in the untreated state, or be reverted to blood-pressure-lowering drug treatment because of hypertension or other diseases, e.g. angina pectoris, oedema, congestive heart failure, etc. Results. The probability of remaining without treatment for 5 years was estimated to be 20%. During the state of no treatment the patients had a lower total mortality risk than that of the general Swedish population, matched for age and sex. They also had a lower risk of cardiovascular events than those in the treated states. Markers indicating a successful withdrawal were monotherapy in low doses and relatively low blood pressure before withdrawal. Conclusion. These results suggest that with frequent check-ups, withdrawal of antihypertensive therapy in the elderly can be tried without increased risk of cardiovascular events.

Objective: To evaluate the occurrence of asthma and dyspnoea precipitated or worsened byangiotensin converting enzyme inhibitors. Design: Summary of reports of adverse respiratory reaction in relation to treatment with angiotensin converting enzyme inhibitors that were submitted to Swedish Adverse Drug Reactions Advisory Committee and to World Health Organisation9s international drug information system until 1992. Sales of angiotensin converting enzyme inhibitors in Sweden were also summarised. Subjects: Patients receiving angiotensin converting enzyme inhibitors who reported adverse respiratory reactions. Main outcome measures: Clinical characteristics of adverse reactions of asthma, bronchospasm, and dyspnoea. Results: In Sweden 424 adverse respiratory reactions were reported, of which most (374) were coughing. However, 36 patients had averse drug reactions diagnosed as asthma, bronchospasm, or dyspnoea. In 33 of these cases the indication for treatment with angiotensin converting enzyme inhibitors was hypertension, in only three heart failure. The respiratory symptoms occurred in about half of the patients within the first two weeks of treatment, and about one third needed hospitalisation or drug treatment. Dyspnoea symptoms occurred in conjunction with other symptoms from the airways or skin in 23 out of the 36 cases. In the WHO database there were 318 reports of asthma or bronchospasm, 516 reports of dysponea, and 7260 reports of cough in relation to 11 different angiotensin converting enzyme inhibitors. Conclusion: Symptoms of airway obstruction in relation to treatment with angiotensin converting enzyme inhibitors seem to be a rare but potentially serious reaction generally occurring within the first few weeks of treatment.

We have investigated 1,051 treated hypertensives of both sexes in the Dalby primary health care (PHC) district, Sweden, to evaluate the organisation and the total cost of treatment. Male hypertensives (n = 486) made 1.78 physician visits annually and had a mean on-treatment BP of 160/91 mmHg. Correspondingly, female hypertensives (n = 565) made 1.67 visits and had a mean attained BP of 164/91 mmHg. The drug profile was dominated by the use of beta-receptor-blockers in 38% of all patients but the newer antihypertensive drugs (calcium antagonists, ACE inhibitors) were also commonly used. The total cost of treatment (drugs, consultations, time and travel expenses) was calculated to 2,680 SEK/patient/year, which is similar to that found in a previous study from another PHC district in Sweden, 2,660 SEK/drug-treated patient/year (after adjustment for increasing consumer price index, +29%, between the years of the studies, 1988-91). In conclusion, the hypertensives in Dalby were fairly well controlled according to BP levels. The treatment cost was higher than that of other PHC areas, which should be the focus of further analyses of cost-effectiveness.

It is well established that hypertensive patients benefit from drug treatment of their disorder. In recent years three major out-come studies of antihypertensive treatment in elderly hypertensives have shown substantial benefits, i.e. a reduction in the risk of stroke and other cardiovascular mortality and morbidity. In all these studies beta-blockers and/or diuretics were used in comparison with placebo. Newer therapeutic alternatives have, however, at least theoretically, many advantages which could result in further improvements in prognosis. The initial Swedish Trial in Old Patients with Hypertension (STOP-Hypertension 1) was conducted in men and women aged 70-84 years. STOP-Hypertension 2 will evaluate the therapy used in STOP-Hypertension 1 against therapy based on either ACE-inhibitors (enalapril and lisinopril) or on calcium antagonists (isradipine and felodipine), using the PROBE design (Prospective, Randomised, Open, Blinded Endpoint evaluation). The primary aim will be to assess the effect on cardiovascular mortality. Statistical calculations indicate that 6,600 patients, followed for four years will be needed (2p0.05, power 90%) to obtain significance if there is a 25% difference between the new and the established therapy. Patients in primary health care (300 centres) will be included if their supine blood pressure isor = 180/105 mmHg (and/or). Recruitment of patients started in September 1992 and so far more than 100 patients/week have been included.

Blood pressure (BP) measured by the patients themselves at home and at their workplaces (self BP) and office blood pressure (office BP) were compared with ambulatory BP (amb BP) in 41 middle-aged borderline hypertensive men when diagnosing hypertension. Ambulatory BP was used as the 'gold standard'. The mean (standard deviation) value for office BP was 142/89 (14/7), self BP 143/92 (14/8), and amb BP 134/88 (12/6) mmHg. There was no difference between diastolic office BP and self BP as instruments for diagnosing hypertension. Furthermore, combining the two added little to the diagnostic value obtained from only one of them.

Insulin resistance and hyperinsulinaemia are, in some prospective studies, linked to an increased cardiovascular risk, at least in men. We tested the hypothesis that hyperinsulinaemia may be reduced by non-pharmacological methods independently of other cardiovascular risk factors.In a non-pharmacological intervention study for 1 year three groups of subjects (hypertensives as well as normotensives) were selected after stratification for insulin level at baseline. Half of the hyperinsulinaemic subjects were randomly assigned to active intervention with physical exercise and dietary regulation (HI-A group), the other half were followed passively during the study period (HI-P group). Normo-insulinaemics and hypo(low)-insulinaemics also underwent active intervention (NI-A and LI-A groups, respectively).Primary health care in Sweden.During the 1-year follow-up subjects in the HI-A group reduced their weight, waist:hip ratio and systolic and diastolic blood pressure, as well as their low:high-density lipoprotein (LDL:HDL)-cholesterol ratio. Glucose levels before and during an oral glucose tolerance test did not change. However, plasma insulin and plasma-C-peptide decreased both in the fasting state and after 1 and 2 h of oral glucose tolerance testing. This decrease was independent of the previously mentioned reduction in weight, waist:hip ratio, blood pressure and LDL:HDL-cholesterol ratio. No reduction in insulin levels was seen in the HI-P, NI-A or LI-A groups, but in the HI-P group there was a slight decrease in fasting plasma-C-peptide levels. In the HI-A group dietary improvements were observed during the study period, with a reduction in energy intake, fat consumption and cholesterol intake. Fibre intake was increased. No major changes were seen in the HI-P group.We conclude that in hypertensive and normotensive subjects with hyperinsulinaemia insulin levels can be reduced by active non-pharmacological treatment for 1 year without altering glucose tolerance. This shows that insulin resistance may be lowered by non-pharmacological treatment, which may be of considerable importance, and not only for hypertensives.

OBJECTIVE--To evaluate and describe the clinical course of angio-oedema reactions induced by angiotensin converting enzyme inhibitors. DESIGN AND METHODS--All reports of angio-oedema reactions associated with angiotensin converting enzyme inhibitors submitted to Swedish Adverse Reactions Advisory Committee were reviewed and the clinical courses summarised. Numbers of cases judged to be induced by angiotensin converting enzyme inhibitors were related to their annual usage, estimated from total sales of defined daily doses, as well as to the estimated number of new patients. All cases of angio-oedema associated with angiotensin converting enzyme inhibitors reported to the World Health Organisation9s international drug information system were also summarised. RESULTS--36 of the 38 reported cases in Sweden between 1981 and 1990 were judged to be related to angiotensin converting enzyme inhibitors. During 1981 through 1990, altogether 1309 cases of angio-oedema associated with angiotensin converting enzyme inhibitors were registered with the international drug information system. The incidence of reported cases of angio-oedema increased largely in parallel with the increased sales (usage) of angiotensin converting enzyme inhibitors. Of the 36 Swedish patients, 77% experienced the reaction within the first three weeks after starting treatment. 10 patients needed hospitalisation, two of whom had life threatening laryngeal obstruction. With one exception all 36 patients were free of symptoms within one week after discontinuing the drug. CONCLUSIONS--Angio-oedema induced by angiotensin converting enzyme inhibitors is a rare but potentially life threatening reaction, which in most instances occurs shortly after the start of treatment. Any patient in whom the reaction is suspected should have the treatment interrupted and, if necessary, be admitted for observation.

We have established a research project in primary health care in Crete with the aim of surveying the cardiovascular risk profile of a defined 'low-risk' population. The study population comprised all men and women aged 15-79 years in the village of Spili (n = 445); the overall attendance rate was 77% (greater than or equal to 82% in those aged 45 years and above). In this cross-sectional study we found a high (44%) prevalence of smoking in men aged 45-64 years as well as a high alcohol intake (48% drank greater than or equal to 210 g of pure alcohol every week). Furthermore, there was a high cholesterol level (6.2 mmol.l-1), and a high prevalence of hypertension and diabetes. Against this background it is somewhat surprising that we did not find any signs of post-myocardial infarction in Spili men aged 63 and under. It is possible that positive factors, i.e. the closely knit social networks, the low unemployment rate, the hard water, and some of the dietary habits, e.g. the high consumption of olive oil, may counter-balance the negative factors mentioned above. It is also possible that the low risk factors in the past explain the low incidence of myocardial infarction today, and that this will change in the years to come.

Numerous intervention trials have demonstrated clear benefits when patients with hypertension have been treated with antihypertensive drugs. During the last five years, however, community-based studies from Dalby, Gothenburg and Glasgow have reported a high remaining risk of cardiovascular (especially cardiac) disease, even though the hypertensive patients have been well cared for and their blood pressure controlled. There may be several possible explanations for the high remaining risk. First, long-standing hypertension may have caused irreversible cardiovascular change and atherosclerosis, which contribute to the increased risk even when the elevated arterial blood pressure has been reduced to normotensive levels. Another possible explanation is that the antihypertensive drugs themselves, in addition to their desired and beneficial antihypertensive effect, have some adverse effects. Thus, by elevating serum lipoproteins or by lowering serum potassium, some agents could increase the risk of cardiovascular complications and, to a certain extent, offset the beneficial effects of lowering blood pressure. Different drugs may, of course, also differ in their ability to prevent cardiovascular disease. In the studies mentioned above, blood pressure had not been reduced to strictly normotensive levels. This may be a third reason for the high remaining risks. A fourth possibility is that other metabolic factors may be implicated, and it may be necessary to tackle other, non-biological factors, such as smoking, stress and unemployment, in order to reduce the excess risk in hypertensive patients. It is clearly necessary to focus on the overall risk profile of the patient, including smoking and alcohol habits, cholesterol level, diet, weight, etc., rather than the blood pressure level alone.(ABSTRACT TRUNCATED AT 250 WORDS)