Neoadjuvant carboplatin before radiotherapy in stage IIA and IIB seminoma.

BACKGROUND: Extended field radiotherapy is a standard of care for low volume stage II testicular seminoma. We hypothesized that neoadjuvant carboplatin might reduce the recurrence risk. PATIENTS AND METHODS: In a single-arm study, 51 patients were treated between May 1996 and November 2011 with a single cycle of carboplatin followed by radiotherapy. The radiation field was reduced from an extended abdomino-pelvic field to just the para-aortic region, and the radiation dose from 35 Gy to 30 Gy in 39 patients. RESULTS: After a median follow-up of 55 months (range 8-151 months) with 38 (74%) of the patients having been followed for >2 years, there have been no relapses (95% confidence limits of 5-year relapse-free survival of 93%-100%). Toxicity has been low with grade 3 toxicity limited to four patients with grade 3 haematological toxicity (with no clinical sequelae) and one patient with grade 3 nausea (during radiotherapy). No patients experienced grade 4 toxicity. CONCLUSIONS: The results of this pilot study suggest that a single cycle of neoadjuvant carboplatin before radiotherapy may reduce recurrence risk compared with radiotherapy alone and permit a smaller radiation field, and this approach is proposed for further investigation.

Achieving the relocation accuracy of stereotactic frame-based cranial radiotherapy in a three-point thermoplastic shell.

AIMS: To compare the accuracy of fractionated cranial radiotherapy in a standard three-point thermoplastic shell using daily online correction with accuracy in a Gill-Thomas-Cosman relocatable stereotactic frame. MATERIALS AND METHODS: All patients undergoing fractionated radiotherapy for benign intracranial tumours between March 2009 and August 2010 were included. Patients were immobilised in the frame with those unable to tolerate it immobilised in the shell. The ExacTrac imaging system was used for verification/correction. Daily online imaging before and after correction was carried out for shell patients and systematic and random population set-up errors calculated. These were compared with frame patients who underwent standard departmental imaging/correction with fractions 1-3 and weekly thereafter. Set-up margins were calculated from population errors. RESULTS: Systematic and random errors were 0.3-0.7 mm/° before correction and 0.1-0.2 mm/° after correction in all axes in the frame, and 0.6-1.5 mm/° before correction and 0.1-0.4 mm/° after correction in the shell. Isotropic margins required for patient set-up could be reduced from 2 mm to <1 mm in the frame and from 5 mm to <1 mm in the shell. CONCLUSION: Similar set-up accuracy can be achieved in the standard thermoplastic shell as in a relocatable frame despite less precise immobilisation. The use of daily online correction precludes the need for larger set-up margins.

Outcomes of surgical management of bowel obstruction in relapsed epithelial ovarian cancer (EOC).

OBJECTIVE: To describe the outcomes of surgical management of bowel obstruction in relapsed epithelial ovarian cancer (EOC) so as to define the criteria for patient selection for palliative surgery. METHODS: 90 women with relapsed EOC underwent palliative surgery for bowel obstruction between 1992 and 2008. RESULTS: Median age at time of surgery for bowel obstruction was 57 years (range, 26 to 85 years). All patients had received at least one line of platinum-based chemotherapy. Median time from diagnosis of primary disease to documented bowel obstruction requiring surgery was 19.5 months (range, 29 days-14 years). Median interval from date of completed course of chemotherapy preceding surgery for bowel obstruction was 3.8 months (range, 5 days-14 years). Ascites was present in 38/90(42%). 49/90(54%) underwent emergency surgery for bowel obstruction. The operative mortality and morbidity rates were 18% and 27%, respectively. Successful palliation, defined as adequate oral intake at least 60 days postoperative, was achieved in 59/90(66%). Only the absence of ascites was identified as a predictor for successful palliation (p=0.049). The median overall survival (OS) was 90.5 days (range, <1 day-6 years). Optimal debulking, treatment-free interval (TFI) and elective versus emergency surgery did not predict survival or successful palliation from surgery for bowel obstruction (p>0.05). CONCLUSION: Surgery for bowel obstruction in relapsed EOC is associated with a high morbidity and mortality rate especially in emergency cases when compared to other gynaecological oncological procedures. Palliation can be achieved in almost two thirds of cases, is equally likely in elective and emergency cases but is less likely in those with ascites.

24 h non-invasive ambulatory blood pressure monitoring: do the number of recordings per hour and/or ways of analyzing day and night matter?

OBJECTIVE: To analyze whether the number of blood pressure registrations per hour and/or different ways of defining day and night have any influence on the result of ambulatory blood pressure monitoring. DESIGN AND METHODS: The study used blood pressure data from 40 normotensive subjects (20 men) and 40 (20 men) treated hypertensive patients who had undergone 24 h non-invasive ambulatory blood pressure monitoring twice (on a work day and a non-work day), three recordings per hour being made. Calculations were made based on all recordings and with one and two recordings per hour randomly removed. The definition of night was the subject's own (from going to bed until getting up), and an arbitrary designation of 2200 h-0600 h. RESULTS: The mean blood pressure (systolic/diastolic and standard deviation) over 24 h showed no significant difference between calculations based on three, two or one blood pressure registrations per hour in either hypertensives or normotensives, nor was there any significant difference when the same kind of calculation for day and night was made based on the subject's own statement or on arbitrary dividing lines. The between-patient standard deviation increased, albeit marginally, with fewer registrations. Individual comparisons revealed a difference over 24 h of 8.4/6.7 mm Hg between three and one registrations per hour in one hypertensive patient during a non-work day. All the others had lesser and very small differences. CONCLUSION: An analysis of our data revealed no major differences in mean blood pressure if one, two or three recordings per hour were used. Arbitrary dividing lines for day and night or according to the individual's own statement did not have any major effect on the result. This must be considered to be an advantage when data from different studies are compared or pooled. It may, however, be wise to perform recordings no less than every 30 min when evaluating individual patients.

Durability of improvement achieved in a clinical trial. Is compliance an issue?

BACKGROUND: 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. METHODS: 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). RESULTS: 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 values > or =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. CONCLUSIONS: 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.

Difference in blood pressure, but not in heart rate, between measurements performed at a health centre and at a hospital by one and the same physician.

BACKGROUND: Blood pressure (BP) has been found to vary between examiners, for example it is often higher when measured by a physician than by a nurse. Whether the location for the physician-measured BP is also a source of variation has, however, not been studied. Hence, we found it of interest to find out if the location used for examination was of any significance. OBJECTIVE: To explore if BP and/or heart rate measured in the same subjects by the same general practitioner in the health centre and at the hospital, differed. METHOD: Twenty-five hypertensive and 25 age-matched normotensive middle-aged men had their office BP and heart rate recorded by one and the same female general practitioner (IE) who was well known to them, at both the health centre before ambulatory BP equipment was attached to the subject and at the clinical physiological department before an exercise test. The hypertensive patients performed an exercise test and ambulatory BP was measured before and after being treated. RESULTS: The hypertensive patients' office BP was lower at the health centre than at the hospital, both when they were untreated and after they were treated. The difference (systolic/diastolic (s.d.)) was 9.4/6.0 (7.4/2.7) mm Hg (P < 0.001 for systolic and diastolic BP), when they were untreated. Corresponding figures when they were treated were 5.4/4.0 (9.4/4.7) mm Hg, a significant difference in diastolic BP (P < 0.001). The normotensive subjects also had a lower office BP at the health centre than at the hospital. The difference (systolic/diastolic (s.d. ) was 1.8/5.3 (7.0/5.0) mm Hg (P < 0.001 for diastolic BP). Heart rate did not differ between recordings in the health centre and in the hospital, either in the hypertensives or in the normotensives. CONCLUSION: Office BP differed significantly between measurements performed in the health centre and at the hospital. Hence, being examined at a hospital seemed to be a stronger stimuli in most patients than to be examined in a health centre. When diagnosing or evaluating treatment in hypertension, this may have implications. Journal of Human Hypertension (2000) 14, 355-358

Organ damage in treated middle-aged hypertensives compared to normotensives: results from a cross-sectional study in general practice.

BACKGROUND: High blood pressure contributes to organ damage. However, during the past two decades there have been great advances in the medical treatment of hypertension. Technical progress has also made it easier to visualize organ damage. Hence we found it of interest to examine heart, brain and retina in a group of middle-aged treated hypertensives, comparing the results with those from a group of middle-aged normotensives. METHODS: The subjects were 40 (20 men) treated hypertensives and 40 (20 men) normotensives, who had previously taken part in a study in which ambulatory blood pressure monitoring had been performed. The heart was examined by echocardiography, the retina by photography and the brain by magnetic resonance imaging. RESULTS: Office blood pressure and 24-h systolic/diastolic blood pressure (S/D) were 141/86 (13/7) mmHg and 128/81 (11/6) mmHg in the hypertensives and 125/78 (10/8) mmHg and 118/74 (8/5) mmHg in the normotensives, respectively. Left ventricular mass was 101 (27) g/m2 in the hypertensives and 85 (18) g/m2 in the normotensives (p = 0.0025). The corresponding figures for the left atrium were 21.1 (3.1) mm/m2 in the hypertensives and 19.5 (2.2) mm/m2 in the normotensives (p < 0.001). E/A wave quotient was 1.09 (0.26) in the hypertensives and 1.26 (0.26) in the normotensives (p = 0.0045), while left ventricular systolic function did not differ between the groups. Ten hypertensives and one normotensive subject had left ventricular mass above normal range. Narrow retinal arteries were found in 22 hypertensives and 8 normotensives (p < 0.001). Brain magnetic resonance changes (deep white matter and/or periventricular) were found in 19 hypertensives and 9 normotensives (p = 0.0431). CONCLUSIONS: The hypertensives differed significantly from the normotensives concerning left ventricular mass, left atrium, left ventricular diastolic function and retinal vessel changes. Deep white matter and periventricular changes in the brain were also significantly different in the two groups. We can only speculate as to whether earlier antihypertensive treatment or further blood pressure reduction could have affected these differences.

[Is antihypertensive treatment a risk factor of coronary disease? Therapy-related triglyceride increase nor diabetes increase the risk]. / Behandling av hypertoni riskfaktor för koronarsjukdom? Terapirelaterad triglyceridökning och diabetes ökar inte risken.

In an observational study designed to determine whether metabolic changes during long-term antihypertensive drug treatment are associated with an increased risk of coronary heart disease (CHD), 686 middle-aged hypertensive men recruited from a random population screening sample were followed up for 15 years. Antihypertensive treatment predominantly consisted of beta-adrenoceptor blockers and/or thiazide diuretics. CHD and diabetes mellitus were checked for at annual examinations. Time-dependent Cox regression analysis was used to determine correlation between the incidence of CHD and entry characteristics, the monitored serum levels of cholesterol and triglyceride concentrations and the development of diabetes mellitus. Univariate analysis showed the presence of diabetes mellitus a entry to the study and increased baseline serum concentrations of cholesterol and of triglycerides each to be a significant predictor of CHD, the respective relative risks (RR) being 2.12, 1.21 and 1.21. However, analysis of monitored levels of metabolic variables during follow-up showed only an increased serum cholesterol concentration to be significantly and independently associated with CHD (RR 1.07). Although serum triglyceride concentrations increased slightly during follow-up, they were unrelated to the incidence of CHD; nor was onset of diabetes mellitus during follow-up significantly associated with an increased risk of CHD (RR 1.48. Thus, the study showed the presence of metabolic disturbances such as diabetes mellitus and hyperlipidaemia before the start of antihypertensive treatment to be of positive predictive value in middle-aged hypertensive men, and an increase in the monitored serum cholesterol level to be an independent predictor of CHD, whereas neither drug-related diabetes nor an increase in the monitored serum triglyceride concentration seemed to be associated with the occurrence of CHD.

Diabetes mellitus and raised serum triglyceride concentration in treated hypertension--are they of prognostic importance? Observational study.

OBJECTIVE: To analyse whether metabolic changes during long term treatment with antihypertensive drugs are associated with an increased risk of coronary heart disease. DESIGN: Observational study. SETTING: Gothenburg, Sweden. SUBJECTS: 686 middle aged hypertensive men, recruited after screening of a random population sample, and followed for 15 years during treatment with predominantly beta adrenoceptor blockers or thiazide diuretics, or both. Coronary heart disease and diabetes mellitus were registered at yearly patient examinations. Entry characteristics, as well as within study serum concentrations of cholesterol and triglycerides and the development of diabetes mellitus, were related to the incidence of coronary heart disease in a time dependent Cox's regression analysis. MAIN OUTCOME VARIABLE: Coronary heart disease morbidity. RESULTS: Diabetes mellitus, raised serum cholesterol and triglyceride concentrations present at the beginning of the study were all significantly predictive of coronary heart disease in univariate analysis. The relative risk of diabetes mellitus and of a 1 mmol/l increase in the cholesterol and triglyceride concentrations was 2.12 (95% confidence interval 1.11 to 4.07), 1.21 (1.05 to 1.39), and 1.21 (1.03 to 1.43) respectively. However, when the within study metabolic variables were analysed, only the serum cholesterol concentration was significantly and independently associated with coronary heart disease (relative risk 1.07 (1.02 to 1.13)). Although the triglyceride concentrations increased slightly during the follow up, the within study serum triglyceride concentrations were not associated with the incidence of coronary heart disease (1.04 (0.96 to 1.10)). New diabetes mellitus-that is, onset during follow up-was not significantly associated with an increased risk for coronary heart disease (1.48 (0.37 to 6.00)). CONCLUSIONS: Metabolic disturbances such as diabetes mellitus and hyperlipidaemia presenting before the start of antihypertensive treatment have a prognostic impact in middle aged, treated hypertensive men. Moreover, while within study cholesterol concentration was an independent predictor of coronary heart disease, drug related diabetes mellitus and raised serum triglyceride concentrations that are associated with treatment do not seem to have any major impact on the coronary heart disease prognosis in this category of patients.

Does it matter whether ambulatory blood pressure is recorded during a work day or a non-work day?

OBJECTIVE: To compare ambulatory blood pressure recorded during a work day with that recorded during a non-work day. DESIGN: A cross-over randomized study in middle-aged treated hypertensives and normotensives. SETTING: Primary health care. SUBJECTS: Forty treated hypertensives (20 men) and 40 normotensives (20 men). MAIN OUTCOME MEASURE: Individual difference between ambulatory blood pressures recorded during a work day and during a non-work day. RESULTS: The systolic/diastolic blood pressure of the hypertensives was 2/3 (7/5) [mean (SD)] mmHg higher and that of the normotensives 3/3 (5/4) mmHg higher during the work day 24 h monitoring. The blood pressure of the normotensives showed a statistically significant difference between the two monitoring periods both for systolic and for diastolic blood pressure during 24 h and daytime. The corresponding comparison in the hypertensives showed a significant difference only for diastolic blood pressure. During night-time there was no statistically significant difference between the two monitoring periods, neither in the hypertensives nor in the normotensives. Individual comparisons revealed large variations between the two monitoring periods in many subjects. Among the hypertensives the percentage of subjects with a systolic blood pressure difference > 10 mmHg (higher or lower during their work day monitoring period) was 20% during 24 h, 32.5% during daytime and 15% during night-time. The corresponding values for a diastolic blood pressure difference > 5 mmHg were 40% during 24 h, 32.5% during daytime and 40% during night-time. Among the normotensives the corresponding values for systolic/diastolic blood pressure differences between the two monitoring periods were 5/27.5% during 24 h, 5/27.5% during daytime and 2.5/27.5% during night-time. CONCLUSION: Ambulatory blood pressure recorded during a work day might differ from that recorded during a non-work day. It is important to be aware of this fact when evaluating individual blood pressure graphs, although the importance of this for the development of organ damage is not known. To perform more than a single 24 h blood pressure monitoring can be of value to obtain a better idea of the blood pressure variability of a patient.

Reversal of left ventricular hypertrophy in hypertensive patients. A metaanalysis of 109 treatment studies.

This is a metaanalysis of all available studies as of December 1990 that have evaluated the effect of antihypertensive pharmacologic therapy on left ventricular structure examined by echocardiography. We applied preset inclusion criteria to the analysis. A total of 109 studies comprising 2357 patients (28% previously untreated) with an average age of 49 years (range 30 to 71) were included. Overall left ventricular mass (LVM) was reduced by 11.9% [95% confidence interval (CI) 10.1 to 13.7] in parallel with a reduction of mean arterial pressure of 14.9% (CI 14 to 15.8). To differentiate between first-line therapies and to adjust for differences between studies, we performed ANCOVA. Angiotensin converting enzyme (ACE) inhibitors reduced LVM by 15% (CI 9.9 to 20.1), beta-blockers by 8% (CI 4.8 to 11.2), calcium antagonists by 8.5% (CI 5.1 to 11.8), and diuretics by 11.3% (CI 5.6 to 17). When we calculated LVM using the same formula for all studies the absolute reductions in grams were 44.7 g with ACE inhibitors, 22.8 g with beta-blockers, 26.9 g with calcium antagonists, and 21.4 g with diuretics. Except for diuretics, all therapies mainly affected wall thickness, while diuretics predominantly reduced ventricular diameter. In conclusion, this metaanalysis shows that ACE inhibitors, beta-blockers, and calcium antagonists all reduce LVM by reversing wall hypertrophy, and that the effect is most pronounced with ACE inhibitors. Conversely, diuretics reduce LVM mainly through a reduction of left ventricular volume. Based on these data, we hypothesize that ACE inhibitors are more effective than other first-line therapies in reducing LVM. However, this theory and its possible prognostic implications need to be evaluated in controlled prospective trials.

Effects of reperfusion and superoxide dismutase on myocardial infarct size in a closed chest pig model.

OBJECTIVE: The aim was to study the effects on myocardial infarct size of reperfusion alone or of CuZn superoxide dismutase (SOD) as an adjunct to reperfusion. METHODS: Occlusion was induced in closed chest, pentobarbitone anaesthetised, mechanically ventilated pigs by injection of a 2 mm ball into a preselected coronary artery. Reperfusion was achieved by retraction of the ball via an attached filament. Twenty nine placebo treated and 25 SOD treated animals were subjected to 30 (n = 21), 60 (n = 21), and 90 (n = 12) min of coronary occlusion followed by reperfusion to 24 h; a control group of 24 pigs was subjected to a sustained occlusion for 24 h. Infarct size was assessed by tetrazolium staining and plasma creatine kinase (CK), aspartate aminotransferase (ASAT), and lactate dehydrogenase (LD). In the CuZn SOD group, 200 mg bovine CuZn SOD was given as a bolus intravenously immediately before reperfusion followed by a continuous infusion (100 mg) for 60 min. The size of the ischaemic myocardium at risk was measured from post mortem autoradiograms. RESULTS: Infarct size as percent of myocardium at risk was 46.0(SD 15.5)%, 80.1(9.9)%, and 88.9(5.0)% respectively in placebo animals with 30, 60, and 90 min occlusion, and 94.2(5.1)% in pigs with 24 h sustained occlusion. Compared to 24 h sustained occlusion, limitation of infarct size by reperfusion was only demonstrated in the 30 (p less than 0.001) and 60 min groups (p less than 0.001). Plasma values of CK, ASAT, and LD at 90 min post-reperfusion correlated closely with infarct size as assessed by tetrazolium staining and were related to occlusion duration. No myocardial salvage, as assessed by plasma ASAT, CK, or LD, was shown in the SOD treated groups. CONCLUSIONS: Early reperfusion resulted in myocardial salvage as assessed by tetrazolium staining and peak ASAT, CK, and LD at 90 min after the reperfusion. No limitation of infarct size by SOD could be demonstrated from analyses of plasma CK, ASAT, or LD.

Regression of left ventricular hypertrophy--a meta-analysis.

Left ventricular hypertrophy (LVH) is an independent risk indicator of cardiovascular disease. Obtaining reversal of hypertension-induced cardiac hypertrophy seems to be a desirable objective of antihypertensive treatment. A total of 2,357 patients were included in a meta-analysis on the effect of antihypertensive pharmacological therapy on LVH. Overall left ventricular mass (LVM) was reduced by 11.9% (95% confidence interval (CI) 10.1-13.7) in parallel with a reduction of mean arterial pressure of 14.9% (CI 14.0 to 15.8). When evaluating the effect of first-line therapies on calculated LVM using the same formula for all studies, the absolute reductions in g were 44.7 (ACE-inhibitors), 22.8 (beta-blockers), 26.9 (calcium antagonists) and 21.4 (diuretics) when adjusted for differences between studies (ANCOVA). It can be concluded that effective antihypertensive therapy reduces LVM. ACE-inhibitors, beta-blockers and calcium antagonists reduce LVM by reducing wall hypertrophy, the effect of ACE-inhibitors being the most pronounced. Diuretics reduce LVM mainly through an effect on left ventricular inner diameter. How these effects affect prognosis is still an open question.

A comparative study of lisinopril and atenolol on low degree urinary albumin excretion, renal function and haemodynamics in uncomplicated, primary hypertension.

The presence of slightly increased urinary albumin excretion (UAE), even at levels well below levels detectable by an ordinary dipstick, has been suggested as a predictor of cardiovascular morbidity and as a reflection of the degree of overall vascular permeability. The aim of the present investigation was to study the effects of two different antihypertensive drug regimens, an ACE inhibitor and a beta-adrenoceptor antagonist, on the low UAE rate observed in subjects with uncomplicated, mild to moderate primary hypertension. After a 4-week placebo run-in period, 49 patients (mean age 54 y) were randomly assigned in a double blind manner either to further 4 weeks on placebo (P, n = 15), 8 weeks on lisinopril (L, n = 17; 20 mg/40 mg o.d.) or 8 weeks on atenolol (A, n = 17; 50 mg/100 mg o.d.). The 24-h UAE was measured every second week. At entry and after 4 weeks the glomerular filtration rate and the renal plasma flow were measured. Both drugs lowered blood pressure (BP) to a similar extent after 4 and 8 weeks of treatment; the blood pressures were 160/106 (P), 159/104 (L) and 154/103 (A) at entry, and 133/83 (L) and 134/87 (A) at the end of the study after 8 weeks. On entry the 24-h UAE in all patients ranged from 4 to 49 mg (mean 14.1 mg), and it did not differ significantly between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The J-shaped relationship between coronary heart disease and achieved blood pressure level in treated hypertension: further analyses of 12 years of follow-up of treated hypertensives in the Primary Prevention Trial in Gothenburg, Sweden.

The relationship between the blood pressure level achieved through antihypertensive treatment and the incidence of coronary heart disease (CHD) was studied in 686 middle-aged hypertensive men. The patients studied came from a random population sample and were followed-up for 12 years, yielding a total of 6563 patient-years for the study. Eighty-seven patients suffered a non-fatal myocardial infarction or died from CHD. The incidence of CHD showed a J-shaped distribution in relation to achieved treated systolic and diastolic blood pressure levels. The incidence of CHD, adjusted for entry characteristics, age, serum cholesterol, blood pressure and smoking habits, decreased with reductions in blood pressure achieved through treatment, to a level of about 150/85 mmHg, below which the incidence rate again increased. This J-shaped pattern was also observed when data from patients with pre-existing signs or symptoms of ischemic heart disease at entry were excluded. Using a quadratic term as the best fit to the observed relationship between achieved treated diastolic blood pressure level and the incidence of CHD, a Cox regression analysis showed that the nadir of the J-shaped incidence curve was at a diastolic blood pressure value of 81 mmHg. There did not seem to be any association between the absolute size of the blood pressure reduction during treatment and the incidence of CHD. Although we cannot exclude the possibility that the increased incidence of CHD in patients with a low treated blood pressure is due primarily to pre-existing but subclinical ischemic heart disease, our findings indicate that an excessive lowering of blood pressure in hypertensive patients may be harmful.(ABSTRACT TRUNCATED AT 250 WORDS)

Factors of importance for prognosis in men with angina pectoris derived from a random population sample. The Multifactor Primary Prevention Trial, Gothenburg, Sweden.

A random population sample of middle-aged men from the Primary Prevention Trial was followed for 11.3 years from a first screening when different factors known to be associated with coronary artery disease (CAD) were analyzed. Men with uncomplicated angina pectoris (AP) (n = 167) derived from this population had an incidence of fatal and nonfatal CAD events 3 times higher than that of men without AP or myocardial infarction (n = 5,774). Men with myocardial infarction with or without AP had an incidence of CAD events 7 to 8 times higher than that of men without AP or myocardial infarction. Similar differences were found for new cases of uncomplicated AP (n = 128) and myocardial infarction detected at a second screening after 4 years and followed for 7.3 years. Pooled data from this series of men with uncomplicated AP showed the following factors to be associated in multivariate analysis with nonfatal or fatal CAD endpoints during follow-up: elevated serum cholesterol, elevated blood pressure, smoking and attack score. The risk increase associated with the first 3 factors was similar to the general population. These findings indicate that the same factors affecting prognosis after a first appearance of AP affect similarly patients with myocardial infarction and clinically healthy subjects. Preventive measures against these risk factors seem to be of similar importance among patients with AP, post-infarct patients and healthy subjects.

Cardiovascular morbidity in relation to change in blood pressure and serum cholesterol levels in treated hypertension. Results from the primary prevention trial in Göteborg, Sweden.

The relationship of cardiovascular disease (CVD) to the control of blood pressure (BP) and serum cholesterol levels was studied in 686 treated, middle-aged hypertensive men whose condition was followed up for 12 years. Both mean in-study BP (P less than .001) and serum cholesterol levels (P less than .001) were better predictors for CVD than the respective entry levels (both not significant) in multivariate analysis. Surprisingly, for mean in-study systolic and diastolic BP there seemed to be a level (approximately 150 and 85 mm Hg, respectively) below which further reduction of BP had no additional benefit from treatment. Analyses of CVD morbidity in relationship to changes in BP and serum cholesterol levels clearly showed that a combined reduction of both risk factors was necessary to achieve a substantial reduction in morbidity. These study findings indicate that (1) it may be unfavorable to reduce BP below a certain level in middle-aged hypertensive men; and (2) other risk factor interventions must be improved to improve the patient's prognosis.

Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial.

Men aged 40-64 years with mild to moderate hypertension [diastolic blood pressure (DBP) 100-130 mmHg] were randomized to treatment with a diuretic (n = 3272) or a beta-blocker (n = 3297), with additional drugs if necessary, to determine whether a beta-blocker based treatment differs from thiazide diuretic based treatment with regard to the prevention of coronary heart disease (CHD) events and death. Patients with previous CHD, stroke or other serious diseases, or with contraindications to diuretics or beta-blockers were excluded. If normotension (DBP less than 95 mmHg) was not achieved by monotherapy, other antihypertensive drugs were added, but the two basic drugs were not crossed over. Patients were assessed at 6-monthly intervals. The mean follow-up for end-points was 45.1 months. Blood pressure (BP) side effects and end-points were recorded in a standardized manner. Entry characteristics and the BP reduction achieved were very similar in both treatment groups. All analyses were made on an intention-to-treat basis. The incidence of CHD did not differ between the two treatment groups. The incidence of fatal stroke tended to be lower in the beta-blocker treated group than in the diuretic treated group. Total mortality and the total number of end-points were similar in both groups. The percentage of patients withdrawn due to side effects was similar, whereas the number of reported symptoms, according to a questionnaire, was higher for patients on beta-blockers. The incidence of diabetes did not differ between the two groups. Subgroup analyses did not detect a difference in the effect of beta-blockers compared with diuretics in smokers as opposed to non-smokers, and beta-blockers also had the same effects as diuretics in the quartile with the highest predicted risk for CHD. Beta-blockers and thiazide diuretics were approximately equally well tolerated. The two drugs had a similar BP reducing effect although additional drugs had to be given more often in the diuretic group. Antihypertensive treatment based on a beta-blocker or on a thiazide diuretic could not be shown to affect the prevention of hypertensive complications, including CHD, to a different extent.

The efficacy and tolerability of antihypertensive treatment based on atenolol in the prevention of stroke and the regression of left ventricular hypertrophy.

Nine hundred and thirty nine moderate to severe hypertensive patients were treated with a combination of atenolol, a beta 1 selective receptor blocker, diuretics and where required, additional vasodilator therapy to achieve adequate blood pressure (BP) control. Patients were followed up for a period of 10.2 years (mean 6.1 years). Amassed clinical exposure amounted to 5465 patient years. Mean BP fell from 183.0 +/- 1.0/109.2 +/- 0.5 mmHg to 145.1 +/- 0.6/89.3 +/- 0.3 mmHg and treatment resulted in a significant regression of the electrocardiographic signs of left ventricular hypertrophy (LVH). Side effects of treatment were consistent with those expected from a regime comprising a combination of a beta 1 selective hydrophilic beta-blocker, diuretics and vasodilators. Reported side effects appeared to diminish with time; were more common in the elderly than in the young and increased in frequency as the dose of atenolol increased. Biochemical disturbance was minimal. Total mortality (n = 91) and mortality from myocardial infarction (n = 40) were positively related to treated systolic blood pressure (SBP). A J-shaped curvilinear relationship between treated diastolic blood pressure (DBP) and death rate from myocardial infarction has been shown. Although the number of deaths from stroke was small (n = 21), there appeared to be a positive relationship with treated DBP: by contrast the data suggest that in the elderly, lowering SBP to below about 140 mmHg might be associated with an increased incidence of death from stroke.

Low mortality from all causes, including myocardial infarction, in well-controlled hypertensives treated with a beta-blocker plus other antihypertensives.

The aim of the present study was to monitor the efficacy of treatment, morbidity and mortality over a 10-year period in 939 moderate to severe hypertensive patients. All patients were treated in the same hypertension clinic with the beta 1-selective agent atenolol, administered either alone or more usually with a diuretic with or without a vasodilator or other agents. Survival rates were compared with predicted survival rates, had the hypertension not been treated, and also with those of a local reference population matched for age and sex. After a mean follow-up time of 6.1 years, mean blood pressure (BP) was significantly lowered from 183/109 to 145/87 mmHg. Biochemical disturbance was minimal. There were 79 withdrawals from treatment, of whom 37 were lost to follow-up. There were 91 deaths on intention to treat. Systolic blood pressure (SBP) on treatment, and not initial BP, was a powerful predictor of mortality. Patients of all age groups with well-controlled SBP were less likely to die, particularly from myocardial infarction, than those with less well controlled SBP (P less than 0.001). However, due to possible J-curve relationships between treated BP and outcome, lowering SBP below 140-150 mmHg in the elderly, and the diastolic blood pressure (DBP) below about 85 mmHg, may not be beneficial. Total mortality and mortality due to myocardial infarction was about 60% [corrected], of predicted level, had a high BP not been treated, being similar to that in a local reference control population (age- and sex-matched). The death rate from stroke was reduced to about 50% of that predicted. Patients who died showed a mean fall in mean serum triglyceride concentration in contrast to the mean increase that occurred in survivors. It is concluded that patients with moderate to severe hypertension who obtain a high level of general health care and optimal control of BP for up to 10 years, experience a significant decrease in total mortality rate and death from myocardial infarction and stroke.