Biomedical subjects

H Wedel

Publications and source records attributed to H Wedel.

At least 37 records · Page 2Linked to original sources

PubMed2001

Challenges of subgroup analyses in multinational clinical trials: experiences from the MERIT-HF trial.

BACKGROUND: International placebo-controlled survival trials (Metoprolol Controlled-Release Randomised Intervention Trial in Heart Failure [MERIT-HF], Cardiac Insufficiency Bisoprolol Study [CIBIS-II], and Carvedilol Prospective Randomized Cumulative Survival trial [COPERNICUS]) evaluating the effects of b-blockade in patients with heart failure have all demonstrated highly significant positive effects on total mortality as well as total mortality plus all-cause hospitalization. Also, the analysis of the US Carvedilol Program indicated an effect on these end points. Although none of these trials are large enough to provide definitive results in any particular subgroup, it is natural for physicians to examine the consistency of results across various subgroups or risk groups. Our purpose was to examine both predefined and post hoc subgroups in the MERIT-HF trial to provide guidance as to whether any subgroup is at increased risk, despite an overall strongly positive effect, and to discuss the difficulties and limitations in conducting such subgroup analyses. METHODS: The study was conducted at 313 clinical sites in 16 randomization regions across 14 countries, with a total of 3991 patients. Total mortality (first primary end point) and total mortality plus all-cause hospitalization (second primary end point) were analyzed on a time to first event. The first secondary end point was total mortality plus hospitalization for heart failure. RESULTS: Overall, MERIT-HF demonstrated a hazard ratio of 0.66 for total mortality and 0.81 for mortality plus all-cause hospitalization. The hazard ratio of the first secondary end point of mortality plus hospitalization for heart failure was 0.69. The results were remarkably consistent for both primary outcomes and the first secondary outcome across all predefined subgroups as well as for nearly all post hoc subgroups. The results of the post hoc US subgroup showed a mortality hazard ratio of 1.05. However, the US results regarding both the second primary combined outcome of total mortality plus all-cause hospitalization and of the first secondary combined outcome of total mortality plus heart failure hospitalization were in concordance with the overall results of MERIT-HF. Tests of country by treatment interaction (14 countries) revealed a nonsignificant P value of.22 for total mortality. The mortality hazard ratio for US patients in New York Heart Association (NYHA) class III/IV was 0.80, and it was 2.24 for patients in NYHA class II, which is not consistent with causality by biologic gradient. We have not been able to identify any confounding factor in baseline characteristics, baseline treatment, or treatment during follow-up that could account for any treatment by country interaction. Thus we attribute the US subgroup mortality hazard ratio to be due to chance. CONCLUSIONS: Just as we must be extremely cautious in overinterpreting positive effects in subgroups, even those that are predefined, we must also be cautious in focusing on subgroups with an apparent neutral or negative trend. We should examine subgroups to obtain a general sense of consistency, which is clearly the case in MERIT-HF. We should expect some variation of the treatment effect around the overall estimate as we examine a large number of subgroups because of small sample size in subgroups and chance. Thus the best estimate of the treatment effect on total mortality for any subgroup is the estimate of the hazard ratio for the overall trial.

Adrenergic beta-Antagonists↗

PubMed2001

Age and angina as predictors of quality of life after myocardial infarction: a prospective comparative study.

OBJECTIVES: The objectives were to compare quality of life (QoL) after first myocardial infarction with an age- and sex-adjusted normative population and to test whether the 1-month QoL had predictive properties. DESIGN: QoL was assessed by self-administered questionnaires (SF-36 and Cardiac Health Profile) 1, 3 and 6 months after index-event. Participants were 60 consecutive patients (20% women) with a mean age of 58 +/- 7.4 years. RESULTS: Patients > or =59 years improved in Physical (PCS) and Mental Component Summary (MCS), scoring comparable to community norms at 6 months. However, patients <59 years improved in PCS but not in MCS. and scored significantly below community norms in both PCS (x = 44.7, CI 40.6-48.7 vs x = 50.3, CI 49.3-51.4) and MCS (x = 45.9, Cl 41.8-49.9 vs. x = 51.3, CI 50.3-52.4) at 6 months. Predictors for MCS were age (p = 0.025) and Vitality (p = 0.020) both positively related to QoL. Predictors for PCS were Physical Function (p = 0.003) and CCS score (p < 0.001) where angina grade was negatively related to QoL. CONCLUSION: Because of impaired mental recovery in younger post-infarction patients, their need of special attention in the rehabilitation process must not be overlooked.

Adult↗

PubMed2001

Socioeconomic status and mortality in Swedish women: opposing trends for cardiovascular disease and cancer.

We examined relations between socioeconomic status and cardiovascular disease, cancer, and diabetes mellitus in a 24-year prospective study of 1,462 Swedish women. Two socioeconomic indicators were used: the husband's occupational category for married women and a composite indicator combining women's educational level with household income for all women. The husband's occupational category was strongly associated with cardiovascular disease and cancer mortality in opposite directions, independent of age and other potential confounders. Women with husbands of lower occupational categories had an increased risk of cardiovascular disease mortality [relative risk (RR) = 1.60; 95% confidence interval (95% CI) = 1.09-2.33] while experiencing lower rates of all-site cancer mortality (RR = 0.69; 95% CI = 0.50-0.96). A similar relation was seen with the composite variable: women with low socioeconomic status had an increased risk of cardiovascular disease (RR = 1.37; 95% CI = 1.01-1.84) but a somewhat lower risk for cancer of all sites (RR = 0.86; 95% CI = 0.66-1.11). Finally, morbidity data (diabetes mellitus, stroke, and breast cancer) yielded results that were consistent with the mortality trends, and breast cancer appeared to account for a major part of the association between total cancer and high socioeconomic status. In summary, higher socioeconomic status was associated with decreased cardiovascular disease mortality and excess cancer mortality, in such a way that only a weak association was seen for all-cause mortality.

Adult↗

PubMed2001

Risk assessment and treatment benefit in intensively treated hypertensive patients of the hypertension Optimal Treatment (HOT) study.

BACKGROUND: The Hypertension Optimal Treatment (HOT) Study provided information about cardiovascular events in 18,790 hypertensives, subjected to pronounced blood pressure lowering for a mean of 3.8 years. METHODS AND RESULTS: The HOT Study data have been further analysed after risk stratification of the patients (1999 World Health Organization and International Society of Hypertension guidelines criteria): (i) no patients of the HOT Study were classified as low risk, 50% were classified as medium risk, 20.2% as high risk and 29.8% as very high risk; (ii) incidence of cardiovascular events in these patients with excellent blood pressure control [92% had diastolic blood pressure (DBP) < or = 90 mmHg] remained proportional to pretreatment risk. The relative risk of very high- versus medium-risk strata was between two and three both when HOT Study patients were considered independently of, or within the DBP target group they had been randomized to; and (iii) event rates in all risk strata were calculated to be much lower (possibly 60% lower) than rates expected from baseline risk calculated approximately by the Framingham equation. CONCLUSIONS: The low event rate in HOT Study patients is likely to result from pronounced blood pressure lowering, and is not explained by a lower risk profile than in previous controlled trials of antihypertensive treatment. The persistence of a risk gradient despite intensive blood pressure lowering suggests a combination of blood pressure control with other strategies of risk correction and the need to initiate antihypertensive therapy before complications develop.

Aged↗

PubMed2001

Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators.

OBJECTIVE: To test the primary hypothesis that a newer antihypertensive treatment regimen (calcium channel blocker +/- an angiotensin converting enzyme inhibitor) is more effective than an older regimen (beta-blocker +/- a diuretic) in the primary prevention of coronary heart disease (CHD). To test a second primary hypothesis that a statin compared with placebo will further protect against CHD endpoints in hypertensive subjects with a total cholesterol < or = 6.5 mmol/l. DESIGN: Prospective, randomized, open, blinded endpoint trial with a double-blinded 2 x 2 factorial component. SETTING: Patients were recruited mainly from general practices. PATIENTS: Men and women aged 40-79 were eligible if their blood pressure was > or = 160 mmHg systolic or > or = 100 mmHg diastolic (untreated) or > or = 140 mmHg systolic or > or = 90 mmHg diastolic (treated) at randomization. INTERVENTIONS: Patients received either amlodipine (5/ 10 mg) +/- perindopril (4/8 mg) or atenolol (50/ 100 mg) +/- bendroflumethiazide (1.25/2.5 mg) +K+ with further therapy as required to reach a blood pressure of < or = 140 mmHg systolic and 90 mmHg diastolic. Patients with a total cholesterol of < or = 6.5 mmol/l were further randomized to receive either atorvastatin 10 mg or placebo daily. MAIN OUTCOME MEASURE: Non-fatal myocardial infarction (MI) and fatal coronary heart disease (CHD). RESULTS: 19 342 men and women were initially randomized, of these 10297 were also randomized into the lipid-lowering limb. All patients had three or more additional cardiovascular risk factors. CONCLUSIONS: The study has 80% power (at the 5% level) to detect a relative difference of 20% in CHD endpoints between the calcium channel blocker-based regimen and the beta-blocker-based regimen. The lipid-lowering limb of the study has 90% power at the 1% level to detect a relative difference of 30% in CHD endpoints between groups.

Adrenergic beta-Antagonists↗

PubMed2001

Effects of individual risk factors on the incidence of cardiovascular events in the treated hypertensive patients of the Hypertension Optimal Treatment Study. HOT Study Group.

BACKGROUND: The Hypertension Optimal Treatment (HOT) Study has provided information about cardiovascular events in 18790 hypertensives, subjected to pronounced blood pressure (BP) lowering for a mean of 3.8 years. The HOT study data have subsequently been analysed after stratification of the patients according to global cardiovascular risk, and it has been found that, despite intensive blood pressure lowering in all risk strata, morbid event rates increased with increasing risk stratum. OBJECTIVES: Previously analysed global risk strata were based on combinations of risk factors. The analyses presented here were intended to provide information on the relative role that the presence of each individual factor may have in increasing cardiovascular risk, despite good BP control. METHODS: Risk ratios (RR) for patients with and those without a risk factor were calculated with 95% confidence intervals (CI) using a Cox proportional hazard model, and adjusted for all variables except the one under examination. RESULTS: For all risk factors considered and for all types of event, RR were always greater than 1, indicating a greater risk in the presence, compared with that in the absence of each factor. The male gender was a statistically significant risk for cardiovascular (CV) events, CV and total mortality and particularly for myocardial infarction (MI); age > or = 65 years for CV events, stroke, CV and particularly total mortality; smoking for all events analysed, but particularly for total mortality (twice higher in smokers than in non-smokers); high serum cholesterol (> 6.8 mmol/l) for CV events, MI and CV mortality; high serum creatinine (> 155 micromol/l) for CV events, stroke, CV and total mortality; diabetes for CV events, stroke, total mortality and particularly CV mortality; and ischaemic heart disease for all events analysed. Adjusted RR were often close to or greater than 2. CONCLUSIONS: Each of the risk factors considered was found to be an important cause of residual risk, despite good BP control. These findings emphasize the importance of addressing other correctable risk factors, e.g. smoking, hypercholesterolaemia and diabetes, as well as rigorous control of blood pressure, and of initiating antihypertensive therapy before cardiovascular and renal damage becomes manifest.

Aged↗

PubMed2001

Changes in the use of medications after acute myocardial infarction: possible impact on mortality after myocardial infarction and long-term outcome.

OBJECTIVE: To describe the change in the use of medication after acute myocardial infarction (AMI) and discuss its possible impact on risk and risk indicators for death. PATIENTS: All patients discharged alive after hospitalization for AMI at Sahlgrenska Hospital (covering half the community of Göteborg, i.e. 250,000 of 500,000 inhabitants) during 1986-1987 (period I) and at Sahlgrenska Hospital and Ostra Hospital (covering the whole community of Göteborg, 500,000 inhabitants) during 1990-1991 (period II). METHODS: Overall mortality was retrospectively evaluated during 5 years of follow-up. RESULTS: In all, 740 patients were included in the study during period I and 1448 during period II. The 5-year mortalities were 44.1% for period I patients and 39.3% for period II patients (P = 0.036). The relative risk of death for period II patients was 0.78 [95% confidence interval (CI) 0.67-0.89, P = 0.0005] after adjustment for differences at baseline. There was a significant interaction with a history of congestive heart failure; improvement in duration of survival was found only for patients without such a history. During period I, only 3% of patients were administered fibrinolytic agents, compared with 33% of patients during period II (P < 0.0001). During period I, aspirin was prescribed for 13% of patients discharged from hospital compared with 79% during period II. Other changes in treatment on going from period I to period II included increases in prescription of beta-blockers and angiotensin converting enzyme inhibitors. After adjustment for various risk indicators for death, relative risk of death for those administered fibrinolytic agents was 0.60 (95% CI 0.18-2.02) for patients in the period-I cohort and 0.68% (95% CI 0.51-0.91) for those in the period-II cohort. Adjusted relative risk of death for those prescribed aspirin upon discharge from hospital was 0.81 (95% CI 0.52-1.25) for period-I patients and 0.71 (95% CI 0.56-0.91) for period-II patients. The adjusted relative risk of death for those administered beta-blockers was 0.72 (95% CI 0.55-0.96) for period-I patients and 0.70 (95% CI 0.55-0.90) for period-II patients. CONCLUSION: Increased use of fibrinolytic agents and aspirin for AMI as well as a moderate increase in use of beta-blockers and angiotensin converting enzyme inhibitors was associated with a parallel reduction in age-adjusted mortality during the 5 years after discharge from hospital. However, this improvement was seen only for patients without histories of congestive heart failure.

Adult↗

PubMed2000

Follow-up study of patients randomized in the Scandinavian simvastatin survival study (4S) of cholesterol lowering.

The Scandinavian Simvastatin Survival Study (4S) and other randomized clinical trials have demonstrated that cholesterol-lowering treatment with statins improves prognosis in patients with coronary atherosclerosis compared with placebo. The effect of therapy with statins beyond the typical 5 to 6 years' duration of the trials, in particular regarding the risk of cancer, has not been investigated. This study examines the long-term effects of simvastatin for up to 8 years on cause-specific mortality in patients with coronary heart disease (CHD). We performed an observational, government registry-based study of mortality in the groups originally randomized to simvastatin or placebo in the 4S over an additional 2-year follow-up period, so that the median total follow-up period was 7.4 years (range 6.9 to 8.3 in surviving patients). Randomization took place at outpatient clinics at 94 clinical centers in Denmark, Finland, Iceland, Norway, and Sweden from 1988 to 1989. Of 4,444 patients with CHD, 2,223 and 2,221 were randomized to treatment with placebo or simvastatin therapy, respectively. Patients received treatment with simvastatin, starting at 20 mg/day, with titration to 40 mg/day at 12 or 24 weeks if total cholesterol was >5.2 mmol/L (200 mg/dl), or placebo. After the double-blind period, most patients in both treatment groups received simvastatin as open-label prescription. Of the 1,967 patients originally treated with placebo and surviving the double-blind period, 97 (4.9%) died during the following 2 years. In the group randomized to simvastatin the corresponding number was 74 of the 2, 039 survivors (3.6%). Adding these deaths to those occurring during the original trial, the total was 353 (15.9%) and 256 (11.5%) deaths in the groups originally randomized to placebo and simvastatin, respectively. The relative risk was 0.70 (95% confidence interval 0. 60 to 0.82, p = 0.00002). The total number of cancer deaths was 68 (3.1%) in the placebo group and 52 (2.3%) in the simvastatin group (relative risk 0.73, 95% confidence interval 0.51 to 0.05, p = 0. 087), and the numbers of noncardiovascular and other deaths were similar in both groups. We therefore conclude that treatment with simvastatin for up to 8 years in patients with CHD is safe and yields continued survival benefit.

Adult↗

PubMed2000

Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF). MERIT-HF Study Group.

CONTEXT: Results from recent studies on the effects of beta1-blockade in patients with heart failure demonstrated a 34% reduction in total mortality. However, the effect of beta1-blockade on the frequency of hospitalizations, symptoms, and quality of life in patients with heart failure has not been fully explored. OBJECTIVE: To examine the effects of the beta1-blocker controlled-release/extended-release metoprolol succinate (metoprolol CR/XL) on mortality, hospitalization, symptoms, and quality of life in patients with heart failure. DESIGN: Randomized, double-blind controlled trial, preceded by a 2-week single-blind placebo run-in period, conducted from February 14, 1997, to October 31, 1998, with a mean follow-up of 1 year. SETTING: Three hundred thirteen sites in 14 countries. PARTICIPANTS: Patients (n = 3991) with chronic heart failure, New York Heart Association (NYHA) functional class II to IV, and ejection fraction of 0.40 or less who were stabilized with optimum standard therapy. INTERVENTIONS: Patients were randomized to metoprolol CR/XL, 25 mg once per day (NYHA class II), or 12.5 mg once per day (NYHA class III or IV), titrated for 6 to 8 weeks up to a target dosage of 200 mg once per day (n = 1990); or matching placebo (n = 2001). MAIN OUTCOME MEASURES: Total mortality or any hospitalization (time to first event), number of hospitalizations for worsening heart failure, and change in NYHA class, by intervention group; quality of life was assessed in a substudy of 741 patients. RESULTS: The incidence of all predefined end points was lower in the metoprolol CR/XL group than in the placebo group, including total mortality or all-cause hospitalizations (the prespecified second primary end point; 641 vs 767 events; risk reduction, 19%; 95% confidence interval [CI], 10%-27%; P<.001); total mortality or hospitalizations due to worsening heart failure (311 vs 439 events; risk reduction, 31%; 95% CI, 20%-40%; P<.001), number of hospitalizations due to worsening heart failure (317 vs 451; P<.001); and number of days in hospital due to worsening heart failure (3401 vs 5303 days; P<.001). NYHA functional class, assessed by physicians, and McMaster Overall Treatment Evaluation score, assessed by patients, both improved in the metoprolol CR/XL group compared with the placebo group (P = .003 and P = .009, respectively). CONCLUSIONS: In this study of patients with symptomatic heartfailure, metoprolol CR/XL improved survival, reduced the need for hospitalizations due to worsening heart failure, improved NYHA functional class, and had beneficial effects on patient well-being.

Adrenergic beta-Antagonists↗

PubMed2000

Lowering of blood pressure and predictors of response in patients with left ventricular hypertrophy: the LIFE study. Losartan Intervention For Endpoint.

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 (target < 140/90 mm Hg). The mandatory titration level of < or = 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.

Aged↗

PubMed2000

Long-term mortality after acute myocardial infarction in relation to prescribed dosages of a beta-blocker at hospital discharge.

This study was designed to describe the 5-year mortality rate in relation to the dose of metoprolol prescribed at hospital discharge after hospitalisation for acute myocardial infarction (AMI). All patients discharged alive after being hospitalized for AMI at Sahlgrenska Hospital (covering half of the community of Göteborg, with 500,000 inhabitants) during 1986-1987 (period I) and all patients discharged alive after hospitalization for AMI at Sahlgrenska Hospital and Ostra Hospital (covering the whole area of the community of Göteborg) in 1990-1991 (period II) were included. Overall mortality was retrospectively evaluated over 5 years of follow-up. In all there were 2161 patients who were discharged after AMI. Seventy-three percent of these patients were prescribed a beta-blocker and 59% were prescribed metoprolol. Of the patients prescribed metoprolol, 34% were on 200 mg, 46% on 100 mg, and 20% on 50 mg or less. Information on 5-year mortality was available for 2142 of the 2161 patients (99.1%). The 5-year mortality was 24% among patients prescribed 200 mg, 33% among patients prescribed 100 mg, and 43% among patients prescribed 50 mg (P < 0.0001). Patients prescribed another beta-blocker had a 5-year mortality of 39%, and patients prescribed no beta-blocker at all had a 5-year mortality of 61%. When correcting for dissimilarities at baseline, patients who were prescribed < or =100 mg had an adjusted risk ratio for death of 0.79 (95% confidence limit 0.64-0.96; P = 0.021) as compared with patients not prescribed a beta blocker. The corresponding figure for patients prescribed >100 mg was 0.63 (95% confidence limit 0.48-0.84; P = 0.001). Both patients prescribed high and low doses of metoprolol after AMI appeared to benefit from treatment. There was a trend indicating more benefit when larger doses were prescribed.

Acute Disease↗

PubMed2000

Incidence of chronic myeloproliferative disorders in the city of Göteborg, Sweden 1983-1992.

An estimation of the incidence of polycythaemia vera (PV), essential thrombocythaemia (ET) and chronic idiopathic myelofibrosis (CIM) in the city of Göteborg, Sweden during the period 1983-1992 was made from a retrospective case analysis of patients registered as chronic myeloproliferative disorders (CMPD) at the Departments of Medicine and the Department of Pathology of the two major hospitals in the city. A total of 125 cases of PV, 56 males and 69 females were identified. The number of cases as well as the age-specific incidence increased with age. The over all annual gender-specific incidence was 2.69 cases per 10(5) male inhabitants and 3.12 cases per 10(5) female inhabitants. The incidence of PV in relation to the European Standard Population was 2.02 cases per 10(5) inhabitants and year. There were 72 cases, 20 males and 52 females, with ET. The age-specific incidence was in all ages higher for females than for males and increased with age. The annual gender-specific incidence was 0.96 per 10(5) male inhabitants and 2.35 per 10(5) female inhabitants. The incidence of ET in relation to the European Standard Population was 1.28 per 10(5) persons and year. There were 20 cases of CIM, 11 males and 9 females. The annual gender-specific incidence of CIM was 0.53/10(5) male inhabitants and 0.41/10(5) female inhabitants. The incidence of CIM in relation to the European Standard Population was 0.31 per 10(5) persons and year. Seven persons, 2 males and 5 females, had a CMPD that could not be included in any of the above-mentioned groups, but were registered as CMPD, unclassified.

Adolescent↗

PubMed2000

Differentiated long-term effects of intentional weight loss on diabetes and hypertension.

The beneficial effects of weight loss in the obese have been widely accepted. Still, there is a lack of controlled studies displaying large maintained weight losses over long periods (>4 years). We wanted to examine the results of long-standing intentional weight loss on the development of diabetes and hypertension in severely obese individuals over an 8-year period. In the ongoing prospective Swedish Obese Subjects (SOS) study, 346 patients awaiting gastric surgery were matched with 346 obese control subjects on 18 variables by a computerized matching program. The controls were drawn from a registry consisting of 1508 obese potential controls examined at primary health care centers in Sweden. Of the 692 selected patients (body mass index 41.2+/-4.7 kg/m(2) [mean+/-SD]), 483 (70%) were followed for 8 years. No significant weight changes occurred in the obese control group over 8 years. Gastric surgery resulted in a maximum weight loss of -31.1+/-13.6 kg after 1 year. After 8 years, the maintained weight loss was still 20.1+/-15.7 kg (16.3+/-12.3%). Whereas this weight reduction had a dramatic effect on the 8-year incidence of diabetes (odds ratio 0.16, 95% CI 0.07 to 0.36), it had no effect on the 8-year incidence of hypertension (odds ratio 1.01, 95% CI 0.61 to 1.67). A differentiated risk factor response was identified: a maintained weight reduction of 16% strongly counteracted the development of diabetes over 8 years but showed no long-term effect on the incidence of hypertension.

Adult↗

PubMed1999

Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long-term results from the Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study.

BACKGROUND: The Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study addressed prognostic factors and the effects of concomitant treatment and glycometabolic control in diabetic patients with myocardial infarction (AMI). METHODS AND RESULTS: Of 620 diabetic patients with AMI, 306 were randomly assigned to a >/=24-hour insulin-glucose infusion followed by multidose subcutaneous insulin. Three hundred fourteen patients were randomized as controls, receiving routine antidiabetic therapy. Thrombolysis and beta-blockers were administered when possible. Univariate and multivariate statistical analyses were applied to study predictors of long-term mortality. During an average follow-up of 3.4 years (range, 1.6 to 5.6 years), 102 patients (33%) in the intensive insulin group and 138 (44%) in the control group died (P=0. 011). Old age, previous heart failure, diabetes duration, admission blood glucose, and admission Hb AIc were independent predictors of mortality in the total cohort, whereas previous AMI, hypertension, smoking, or female sex did not add independent predictive value. Metabolic control, mirrored by blood glucose and Hb AIc, improved significantly more in patients on intensive insulin treatment than in the control group. beta-Blockers improved survival in control subjects, whereas thrombolysis was most efficient in the intensive insulin group. CONCLUSIONS: Mortality in diabetic patients with AMI is predicted by age, previous heart failure, and severity of the glycometabolic state at admission but not by conventional risk factors or sex. Intensive insulin treatment reduced long-term mortality despite high admission blood glucose and Hb AIc.

Aged↗

PubMed1999

Reduction in incidence of diabetes, hypertension and lipid disturbances after intentional weight loss induced by bariatric surgery: the SOS Intervention Study.

OBJECTIVE: To examine the effect of a large, long standing and intentional weight reduction on the incidence of diabetes, hypertension and lipid disturbances in severely obese individuals as compared to weight-stable obese controls. RESEARCH METHODS AND PROCEDURES: The ongoing prospective SOS (Swedish Obese Subjects) intervention consists of a surgically treated group and a matched control group obtaining conventional obesity treatment. This report is based on 845 surgically treated patients and 845 controls (BMI 41.0+/-4.6 kg/m2 (mean+/-standard deviation [S])) followed for 2 years. RESULTS: Surgically treated patients lost 28+/-15 kg and controls 0.5+/-8.9 kg (p<0.0001). Two-year incidence of hypertension, diabetes, hyperinsulinemia, and lipid disturbances was compared in the two treatment groups. Adjusted odds ratios (95% CI) for the surgically treated group versus controls were 0.38 (0.22, 0.65) for hypertension, 0.02 (0.00, 0.16) for diabetes, 0.10 (0.03, 0.28) for hyperinsulinemia, 0. 10 (0.04, 0.25) for hypertriglyceridemia, 0.28 (0.16, 0.49) for low HDL-cholesterol and 1.24 (0.84, 1.8) for hypercholesterolemia. Compared to controls, the 2-year recovery rates from hypertension, diabetes, hypo-HDL, and hypertriglyceridemia were significantly higher in the surgically treated group. DISCUSSION: Intentional weight loss in the obese causes a marked reduction in the 2-year incidence of hypertension, diabetes and some lipid disturbances. The results suggest that severe obesity can and should be treated.

Adult↗

PubMed1999

Similar risk reduction of death of extended-release metoprolol once daily and immediate-release metoprolol twice daily during 5 years after myocardial infarction.

The pooled results from five placebo-controlled postinfarction studies with metoprolol have shown a significant reduction in total mortality. All five studies used immediate-release metoprolol twice daily. An extended-release formulation of metoprolol for once-daily use has since been developed. The aim of the present study was to compare the two different forms of metoprolol with regard to the risk reduction of death for 5 years postinfarction and to analyze whether treatment with the beta-blocker metoprolol is associated with a reduced mortality after the introduction of modern therapies such as thrombolysis, aspirin, and ACE inhibitors. All patients discharged after an acute myocardial infarction (AMI) from Sahlgrenska University Hospital (SU) during 1986-1987 (n = 740, Period I) and during 1990-1991 (n = 1446, Period II) from both SU and Ostra Hospital, Göteborg, Sweden, were included in the study. During Period I, 56% were prescribed immediate-release metoprolol compared with 61% prescribed extended-release metoprolol during Period II. Immediate-release metoprolol was not available for outpatient use during Period II. In a multivariate analysis, all variables significantly associated with either increased or decreased postinfarction mortality during Periods I and II (univariate analysis of patient characteristics, medical history, complications during the AMI medication at discharge) studied were with Cox's proportional hazards model. Treatment with immediate-release metoprolol was significantly associated with reduced mortality over 5 years during Period I (relative risk reduction for total mortality, -34%, P = 0.003; 95% CI for RR, 0.51-0.87), and treatment with extended-release metoprolol was significantly associated with reduced mortality during Period II (-34%, P < 0.0001; 95% CI for RR, 0.53-0.82). Thrombolysis and the use of aspirin and ACE inhibitors were more frequently used during Period II. The results showed that postinfarction treatment with extended-release metoprolol given once daily was associated with a similar risk reduction of death over 5 years as immediate-release metoprolol given twice daily. The data, furthermore, indicate that the beta-blocker metoprolol is associated with a reduced risk of death after the introduction of modern therapy such as thrombolysis, aspirin, and ACE inhibitors.

Adrenergic beta-Antagonists↗

PubMed1999

Sick leave and disability pension before and after treatment for obesity: a report from the Swedish Obese Subjects (SOS) study.

OBJECTIVES: To analyse sick leave and disability pension among surgically and conventionally treated obese patients. DESIGN: A prospective study over five years. Differences in sick leave and disability pension were analysed using multiple and logistic regressions. Possible confounding factors were analysed and controlled for. SETTING: Nine counties in Sweden. SUBJECTS: 369 surgically treated patients and 371 matched obese controls, included in the Swedish Obese Subjects (SOS) study. At baseline, mean body mass index (BMI) was 42 kg/m2 in surgical patients and 41 kg/m2 in controls. After four years of treatment, weight reduction was 20% among surgical patients while the control patients kept their initial weight. INTERVENTION: Gastric bariatric surgery. MEASUREMENTS: Days of sick leave plus disability pension, and days of disability pension. RESULTS: In the year prior to treatment, adjusted average number of days of sickness due to sick leave plus disability pension was similar in surgical patients and controls. Compared with controls, the surgical group had 35% more days of sickness during the first year after initiation of treatment, but 10-14% fewer days during years 2-3. During year four, days of sickness tended to be lower in the surgical group (P = 0.07). In the sub-group, aged above the median, surgical patients had 14-18% fewer days of sickness than controls, during years 2-3 after initiation of treatment This difference did not occur in the group below median age. CONCLUSION: Surgical treatment of obesity results in a reduction of sick leave and disability pension, compared to controls, particularly in subjects aged 47-60 y.

Adult↗

PubMed1999

Standard serum concentrations and normal fluctuations of CEA, CA 50 and CA 242 during twelve months in men and women aged 60-64 years without malignant disease.

OBJECTIVE: To establish standard serum concentrations of carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 50 and CA 242 in cancer-free subjects in the age group during which cancers are likely to develop. DESIGN: Prospective study. SETTING: University hospital, Sweden. INTERVENTIONS: Blood samples obtained by venepuncture on four occasions during one year. MAIN OUTCOME MEASURES: Consultation with the Regional Cancer Registry to exclude those who had previously had malignant disease diagnosed or developed cancer during and up to two years after the end of the clinical part of the study. Serum concentrations of CEA, CA 50, and CA 242. RESULTS: The 90th centile was 5.6 ng/ml for CEA, 30.1 U/ml for CA 50, and 24.5 U/ml for CA 242. The mean (SD) serum concentrations were 2.6 ng/ml (2.2) for CEA, 13.2 U/ml (11.4) for CA 50, and 10.6 U/ml (9.6) for CA 242. Serum concentrations of CEA were significantly higher (p < 0.001) among smokers. The intraindividual fluctuations were 16%, 16%, and 14%, respectively. CONCLUSIONS: Serum concentrations of CEA, CA 50, and CA 242 were higher in this study than previously reported, probably because the subjects were older than in other reports. The fluctuations were small. Serum concentrations of CEA were higher in smokers than in non-smokers.

Antigens, Tumor-Associated, Carbohydrate↗