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B Fagerberg

Publications and source records attributed to B Fagerberg.

At least 37 records · Page 2Linked to original sources
PubMed2001

Sodium/lithium countertransport, insulin resistance, insulin peptides and microalbuminuria in clinically healthy 58-year-old men.

The activity of the erythrocyte transport system, sodium/lithium countertransport (SLC), has been linked to the metabolic syndrome characterized by insulin resistance and compensatory hyperinsulinaemia. We measured SLC and insulin sensitivity with the euglycaemic hyperinsulinaemic clamp method in a patient sample (n = 93) randomly selected from a large clinically healthy group of 58-year-old men (n = 818). The lipid profile, blood pressure, body mass index (BMI) and insulin were also analysed. There was a significant difference (P < 0.001) in SLC between subjects with the metabolic syndrome (n = 19) and subjects without any components of this syndrome (n = 20). There was a highly significant correlation between SLC and BMI, waist/hip ratio, total body fat mass, serum triglycerides, plasma insulin, proinsulin split products and C-peptide in a univariate analysis. There was also a significant correlation between SLC and insulin sensitivity measured as insulin-mediated glucose uptake (P < 0.01). In multiple regression analysis, only two of the variables showing univariate significance were independently correlated to SLC, i.e. serum triglycerides (P < 0.001) and BMI (P < 0.01). The subjects with a SLC value in the highest tertile had a 6-fold higher prevalence of insulin resistance (low-insulin-mediated glucose uptake) as compared with those with a SLC value in the lowest tertile. We conclude that, in clinically healthy 58-year-old men from the general population, erythrocyte SLC is closely linked to metabolic syndrome, in particular to obesity, triglycerides and insulin resistance.

Albuminuria↗
PubMed2001

A new method to quantify postexercise ST-deviation--the ST-deficit. A study in men at high and low-risk for coronary heart disease.

BACKGROUND: Quantitative heart rate adjusted exercise ST criteria like microV/beats per minute (bpm) improve the diagnostic accuracy of the exercise ECG. However, there are few quantitative HR adjusted postexercise variables available. The aim of the present exercise study was to evaluate a new such variable from computerized averaging of the postexercise ECG. METHODS: The presence of possible myocardial ischaemia in a population based sample of 74 elderly male hypertensives at high-risk of coronary heart disease, and in 42 age-matched clinically healthy males (reference group) at low-risk was assessed by exercise ECG. All men had a normal resting ECG without signs of ischaemia. VARIABLES STUDIED: standard ST-criteria, ST/HR slope < or =-2.4 microV. bpm-1, shape of the rate-recovery loop, the latter also with a new quantitative variable, the ST-deficit. RESULTS: In spite of a normal resting ECG many subjects showed an abnormal ST/HR slope during exercise, 43% in the hypertension group and 26% in the reference group. An abnormal rate-recovery loop (ST-deficit) also contributed substantially to identify patients with possible myocardial ischaemia, 30 vs. 10%, respectively (P<0.02); cumulatively for the two HR adjusted criteria 53% vs. 29%, respectively (P<0.02). Mean ST-deficit was significantly lower in the high-risk group. CONCLUSIONS: Effort-related myocardial ischaemia is frequently silent in elderly high-risk hypertensives and necessitates testing, preferably with computerized exercise ECG and heart rate adjusted ST criteria. A new quantitative variable to assess the postexercise rate-recovery loop in the time domain, the ST-deficit is described. This variable seems to effectively discriminate between subjects with low and high-risk for coronary heart disease and thus provides new information. Further studies are warranted to validate this variable against myocardial perfusion scintigraphy and coronary angiography.

Aged↗
PubMed2001

Insulin resistance and intima-media thickness in the carotid and femoral arteries of clinically healthy 58-year-old men. The Atherosclerosis and Insulin Resistance Study (AIR).

OBJECTIVE: To examine whether insulin resistance was associated with ultrasound-assessed measures of atherosclerosis in men with varying degrees of obesity. DESIGN: A random selection of subjects from the general population were divided into quintiles of a body mass index/blood glucose score that was shown to be a valid and reproducible index of the degree of insulin sensitivity as assessed by the clamp technique. Every fourth man in quintiles 1 and 5 and every 20th man in quintiles 2-4 (in total, 104 men) were selected for an ultrasound examination of the carotid and femoral arteries and a euglycaemic hyperinsulinaemic clamp examination, adjusted for fat-free mass. SETTING: A university hospital. SUBJECTS: A total of 104 clinically healthy 58-year-old men of Swedish ancestry. RESULTS: The mean common carotid artery intima-media thickness (IMT), but not the common femoral IMT, correlated significantly with glucose infusion rate (GIR) (r = - 0.20, P < 0.05), systolic blood pressure (r = 0.20, P < 0.05), pulse pressure (r = 0.23 P < 0.01), heart rate (r = 0.20, P < 0.05), HDL cholesterol (r = - 0.18, P < 0.05), log triglycerides (r = 0.28, P < 0.01), apoA1 (r = - 0.20, P < 0.05), apoB (r = 0.21, P < 0.05), LDL particle size (r = - 0.22, P < 0.05) and plasma insulin (r = 0.20, P < 0.05). In a multiple regression, common carotid IMT was independently associated with log triglycerides (beta = 0.25, P = 0.012) and pulse pressure (beta = 0.21, P = 0.031) (R2 = 8.7%, P = 0.005) CONCLUSIONS: Insulin sensitivity, measured with the gold standard euglycaemic hyperinsulinaemic clamp method, showed similar associations with ultrasound-assessed measures of atherosclerosis in the carotid arteries as established cardiovascular risk factors, but only triglycerides and pulse pressure contributed independently to the variability in the common carotid intima-media thickness.

Arteriosclerosis↗
PubMed2001

Multiple risk intervention trial in high risk hypertensive men: comparison of ultrasound intima-media thickness and clinical outcome during 6 years of follow-up.

OBJECTIVES: The objective was to analyse whether a favourable change in risk factors, caused by a comprehensive risk factor modification programme, affected intima-media thickness (IMT) in the common carotid artery, and whether any such change was associated with a change in cardiovascular events during a 6-year follow-up. DESIGN: Patients were randomized 1 : 1 to special intervention or usual care. SETTING: Hypertension Unit at university hospital. SUBJECTS: A total of 164 patients were randomized. Inclusion criteria were male, aged 50-72 years (at randomization) and one or more of the following: Serum cholesterol level > 6.5 mmol L(-1), smoking or diabetes mellitus. All patients were prescribed antihypertensive treatment since many years. In 142 men good quality ultrasound recording of the common carotid IMT were achieved at baseline, 119 were re-examined after 3.3 years, and 97 patients were available for examination after mean follow-up time of 6.2 years. Cardiovascular events were available for all randomized patients. INTERVENTIONS: The nonpharmacological special intervention programme was based on one information meeting followed by five weekly 2-h sessions with participation of patients and spouses. The diet recommendations were similar to established guidelines. Overweight patients were instructed to lose weight, and diabetic patients were systematically taught self-monitoring of blood glucose. Smokers were invited to a smoking cessation programme with five weekly meetings. Follow-up visits were thereafter scheduled every 6 months. Lipid lowering drugs were recommended in the intervention group if the treatment goals using nonpharmacological measures were not achieved. Patients in the usual care group were told to quit smoking and to lower their consumption of fat and glucose. Antihypertensive treatment (i.e., selection of drugs) was on purpose kept similar in the two groups. MAIN OUTCOME MEASURES: The IMT of the common carotid artery as measured by ultrasound. Cardiovascular events during follow-up. RESULTS: Significant net reductions were seen for serum cholesterol, triglycerides, fasting glucose and smoking. No difference in change in IMT was observed during follow-up between the two randomization groups. The explanation was that patients with positive plaque status at baseline had a much larger increase in IMT over time than patients with negative plaque status, and that patients with positive plaque status more often survived and were available for re-examination after 6 years in the intervention group than in the usual care group. Total mortality was lower in the intervention group, compared with the usual care group, 13 and 29%, respectively (P=0.028). CONCLUSIONS: In high risk populations, long-term studies with surrogate endpoints may be misleading because of missing data in patients where a large increase in IMT would have been observed, had they been re-examined. Another important conclusion from our study was that the gloomy prognosis for this patient category may be improved by a dedicated risk factor intervention programme. The improved prognosis was observed mainly in those patients at highest risk judged from history of cardiovascular disease or positive ultrasound plaque status at baseline.

Aged↗
PubMed2001

Carotid and femoral atherosclerosis, cardiovascular risk factors and C-reactive protein in relation to smokeless tobacco use or smoking in 58-year-old men.

Objectives. To examine the associations between smokeless tobacco use, smoking, cardiovascular risk factors, inflammation and ultrasound-assessed measures of atherosclerosis in the carotid and femoral arteries. Subjects. The study was performed in a population-based sample of clinically healthy men (n = 391) all 58 years old. Exclusion criteria were cardiovascular or other clinically overt diseases or continuous medication with cardiovascular drugs. Methods. The habits of smoking and oral moist snuff use were assessed by questionnaires. C-reactive protein (CRP) was assessed by high sensitive enzyme-linked immunosorbent assay (ELISA). Intima-media thickness (IMT) in the carotid bulb, the common carotid artery and the common femoral artery and plaque occurrence were measured by ultrasound. Results. The use of oral moist snuff was associated with serum triglycerides and waist-hip ratio (WHR), but not with CRP or ultrasound-assessed measures of subclinical atherosclerosis. Smoking, on the other hand, was associated with CRP, the components in the metabolic syndrome and IMT as well as plaques in the carotid and femoral arteries. In comparison to never-smokers the current smokers had higher values of WHR, triglycerides, C-reactive protein and IMT in carotid bulb and femoral artery. Ex-smokers were in general more obese and had a femoral IMT that was in-between that of never-smokers and current smokers. Conclusions. Tobacco smoking, but not oral moist snuff use, was associated with carotid and femoral artery IMT, and increased levels of CRP. Current smoking was also associated with abdominal obesity. Ex-smokers though, are generally more obese. Smoking was also associated with hyperinsulinaemia, dyslipidaemia and high blood pressure, i.e. the metabolic syndrome. The inhaled smoke from the combustion of tobacco seems to be an important aetiological factor in the atherosclerotic process.

Analysis of Variance↗
PubMed2001

Low-density lipoprotein particle size, insulin resistance, and proinsulin in a population sample of 58-year-old men.

The relationship between insulin sensitivity and low-density lipoprotein (LDL) peak particle size was examined in 104 clinically healthy 58-year-old men recruited from the general population. Insulin sensitivity was measured by the euglycemic hyperinsulinemic clamp method with adjustment for lean body mass. LDL peak particle size was determined by gradient gel electrophoresis, and insulin, proinsulin, and 32,33 split proinsulin were determined by 2-site immunoradiometric assays. The results showed that 16 subjects (15%) had pattern B, with a predominance of small LDL particles. These cases and a small LDL peak particle size were characterized by the features of the insulin resistance syndrome, ie, general and central obesity, elevated diastolic blood pressure, low serum concentrations of high-density lipoprotein (HDL) and apolipoprotein A1 (apoA1), increases in serum triglycerides and circulating insulin peptides, and low insulin-mediated glucose uptake. The correlation between insulin sensitivity and LDL peak particle size was significant (r = .33, P = .001) and independent of obesity. In a traditional multiple regression analysis, LDL peak particle size was independently associated not with insulin-mediated glucose uptake but with circulating triglycerides and HDL cholesterol, which together explained 67% of the variability in LDL particle size (P = .000). Of all insulin peptides, only proinsulin showed an independent relation to LDL peak particle size, but it disappeared after adjustment for other variables. We conclude that a small LDL particle size was associated with insulin resistance among these clinically healthy men, but this was not independent of serum triglycerides and HDL cholesterol. Serum proinsulin was more directly related to LDL particle size than insulin.

Glucose↗
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

The clinical implications of cognitive impairment in elderly patients with chronic heart failure.

The purpose of this study was to examine whether cognitive dysfunction was associated with poor participation in an outpatient treatment program for patients with chronic heart failure and if it was related to specific patient characteristics. Cognitive function was measured with the Mini Mental State Examination (MMSE). Twenty-three of 78 (29%) patients randomized to structured care did not participate in this program and nonparticipation during 6-month follow-up was associated with an MMSE score below the median and a low calculated creatinine clearance (CrCl) (R2=0.15, p=0.0025) at entry. In the entire group long duration of heart failure and low blood hemoglobin concentration were independently associated with an MMSE score below the median at entry (R2=0.14, p < 0.0001). Among elderly patients hospitalized with moderate-severe chronic heart failure, judged to be eligible for a nurse-directed outpatient program after discharge, a low MMSE score predicted nonparticipation in such a program. Cognitive dysfunction, which was related to the duration of heart failure, should be evaluated in the treatment of patients with chronic heart failure.

Aged↗
PubMed2001

Antibodies to oxidized LDL in relation to intima-media thickness in carotid and femoral arteries in 58-year-old subjectively clinically healthy men.

Antibody (Ab) titers to oxidized low density lipoprotein (OxLDL) have been found to be independent predictors of the progression of carotid atherosclerosis. Ab titers against OxLDL may be related to the entire burden of atherosclerosis in the vascular tree or, more specifically, to the disease process in different arterial regions. Therefore, the aim of the present study was to investigate the relationship between IgG and IgM titers to modified LDL and intima-media thickness (IMT) in the carotid and femoral arteries in subjectively clinically healthy 58-year-old men. IMT was measured by ultrasound, and Ab titers to modified LDL were measured by ELISA. The results showed that the common carotid artery IMT was associated with elevated titers of IgG-OxLDL Ab and independently with systolic blood pressure, smoking, and body mass index. The femoral artery IMT showed a negative correlation to IgM-OxLDL Ab and independent associations with smoking, systolic blood pressure, and total cholesterol. To summarize, in 58-year-old subjectively clinically healthy men recruited from the general population, there was a positive association between IgG-OxLDL Ab and IMT in the common carotid artery and a negative association between IgM-OxLDL Ab and IMT in the common femoral artery. However, these associations were not independent of other risk factors.

Carotid Arteries↗
PubMed2001

Intact insulin, insulin propeptides, and intima-media thickness in the femoral artery in 58-year-old clinical healthy men--the Atherosclerosis and Insulin Resistance Study.

The aim of this study was to examine the association between intact insulin, insulin propeptides, and femoral artery intima-media thickness. The design was a cross-sectional study and the study group (n = 391) consisted of randomly recruited clinically healthy 58-year-old Swedish men. The intima-media thickness of the common femoral artery was measured with ultrasound. Fasting plasma insulin; intact insulin; proinsulin; 32,33 split-proinsulin; and C-peptide concentrations were assessed. The results showed that the common femoral artery intima-media thickness correlated significantly and univariately with waist-hip ratio, systolic blood pressure, serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, ApoB, low-density lipoprotein peak particle size, and cigarette years. Furthermore, of intact insulin and insulin propeptides, only intact insulin and C-peptide were univariately associated with common femoral artery intima-media thickness (r= 0.14, p < 0.01; r= 0.18, p < 0.01; respectively). In a multiple regression analysis, common femoral artery intima-media thickness was independently associated with systolic blood pressure (beta-coefficient = 0.004, p = 0.002), ApoB (beta-coefficient = 0.338, p < 0.001 ) and cigarette years (beta-coefficient = 0.0004, p < 0.001), (R2= 25%, p<O0.00). In conclusion, smoking, systolic blood pressure, and ApoB but not insulin or insulin propeptides were independently associated with femoral atherosclerosis.

Apolipoproteins B↗
PubMed2001

The metabolic syndrome, smoking, and antibodies to oxidized LDL in 58-year-old clinically healthy men.

BACKGROUND AND AIM: The aim was to examine whether the metabolic syndrome (as recently defined), its various components, and smoking were associated with circulating antibodies to oxidized low-density lipoproteins (IgG- and IgM-Ox-LDLAb) and malondialdehyde-treated LDL (IgG- and IgM-MDA-LDLAb) (ELISA) in a population sample of clinically healthy 58-year-old men (n = 391). METHODS AND RESULTS: LDL peak particle size (gradient gel electrophoresis) and antibody titers were measured in all patients. Trend analysis showed significantly higher IgG-Ox-LDLAb and IgG-MDA-LDLAb titers across the range of men with none of the criteria defining metabolic syndrome (n = 77), those with > or = 1 criterion (n = 252) and those fulfilling the criteria (n = 62), which remained after adjustment for smoking. IgG-Ox-LDLAb was associated with plasma insulin, body mass index (BMI), the waist/hip ratio (WHR) and smoking. IgG-MDA-LDLAb was, in addition, related to diastolic blood pressure, serum triglycerides and a small LDL peak particle size. The IgM antibody titers only inversely correlated with smoking. CONCLUSIONS: High serum titers of IgG antibodies to oxidized LDL and MDA-treated LDL were associated with the metabolic syndrome and smoking. Several of the factors in the metabolic syndrome were related to the IgG antibody titers to modified LDL. The high degree of intercorrelation among these factors makes it difficult to clarify the independent role of any specific factor.

Antibodies↗
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

MERIT-HF mortality and morbidity data.

This survival study was designed to address whether beta-1-blockade utilizing metoprolol CR/XL (controlled release/extended release) once daily added to standard therapy reduces mortality and morbidity in patients with decreased ejection fraction and symptoms of heart failure. Enrolled in a double-blind randomized study were 3991 patients with chronic heart failure in NYHA functional class II-IV and ejection fraction < or = 0.40 stabilized on optimal standard therapy. Randomization was preceded by a 2-week single blind placebo run-in period. The study medication was uptitrated during 8 weeks starting with 12.5 mg (NYHA functional class III-IV) or 25 mg once daily (NYHA functional class II). The target dose was 200 mg once daily. The primary endpoints were all-cause mortality and combined all-cause mortality and hospitalization (time to first event) and other objectives were cause-specific data on hospitalization, NYHA functional class and quality of life. Mean follow-up time was 1 year. All-cause mortality was reduced in the metoprolol CR/XL group compared with the placebo group, 145 versus 217 deaths, 7.2% per patient year of follow-up versus 11.0% with a relative risk of 0.66 (95% CI 0.53-0.81, nominal p = 0.00009, p adjusted for interim analysis = 0.0062). This effect was consistent across all predefined subgroups. Sudden deaths were fewer in the metoprolol group (79 versus 132 deaths), RR 0.59 (p = 0.0002). Also deaths from worsening heart failure were fewer in the metoprolol group (30 versus 58 deaths), RR 0.51 (p = 0.0023). The combined endpoint total mortality or all-cause hospitalizations was also reduced by metoprolol (641 versus 767 events), RR 0.81 (p = 0.00012). Total mortality or hospitalizations due to worsening heart failure was also reduced (311 versus 439 events), RR 0.69 (p < 0.00001). The number of hospitalizations due to worsening heart failure (317 versus 451, p < 0.00001) and days in hospital due to worsening heart failure (3401 versus 5303 days, p < 0.00001) were also reduced by metoprolol. There was also an improvement in NYHA functional class, assessed by the physicians as well as the McMaster Overall Treatment Evaluation questionnaire (OTE), assessed by the patients (p = 0.028 and p = 0.089, respectively). Permanent early discontinuation was 13.9% in the metoprolol group and 15.3% in the placebo group (RR = 0.90). In conclusion, in patients with symptomatic heart failure metoprolol CR/XL once daily improved survival by 34%, sudden death by 41%, and deaths from worsening of heart failure by 49%. In addition to improvement of survival there was also a reduced need of hospitalizations for worsening heart failure and an improved NYHA functional class and of quality of life assessed in a substudy. Metoprolol was well tolerated with no difference in early discontinuation rate from placebo treatment.

Adrenergic beta-Antagonists↗
PubMed2000

Screening, endpoint classification, and safety monitoring in the Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF).

The MERIT-HF study was designed to investigate the effect of once-daily dosing of metoprolol succinate CR/XL added to standard therapy in patients with chronic heart failure. A screening programme, aiming at identifying eligible patients for the study was used by 231 out of 313 sites, resulting in 8912 screened patients. These patients were older, more often women, had marginally higher ejection fraction and were more often in NYHA class IV compared to the finally randomised patients. There was a positive correlation between the number of screened and randomised patients and due to the high inclusion rate the number of randomised patients was increased from 3200 to 3991 patients. The clinical events were defined by a manual and were based on identical classifications made independently by two members of an Independent Endpoint Committee. Data from the case report form and the classifications made by the Endpoint Committee were in accordance for hospitalisation due to worsening heart failure on 722 occasions. On 207 occasions the data from the case report forms and the classification made by the committee differed regarding this clinical event. The Independent Safety Committee monitored safety aspects of the study by using asymmetric group sequential procedures. The study was stopped early on recommendation from the Independent Safety Committee, when the second pre-specified interim analysis (50% of total number of expected deaths) showed that the criterion for stopping due to benefit had been met and exceeded. In conclusion, a screening programme facilitated patient recruitment and showed the characteristics of the background population, the event classification was improved by using an independent endpoint committee, and the safety monitoring allowed an early closure of the study due to mortality benefit, without jeopardising the final analyses of the results.

Adrenergic beta-Antagonists↗
PubMed2000

The euglycemic hyperinsulinemic clamp examination: variability and reproducibility.

The aim was to examine the reproducibility of the euglycemic hyperinsulinemic clamp method. From a random population sample of 60-year-old clinically healthy men, 32 subjects with varying degrees of insulin sensitivity were recruited. Conventional 2-h clamp examinations were carried out at an interval of 2 weeks. Insulin was infused intravenously (priming for 10 min and thereafter 1.0 mU/kg body wt/min). Glucose was infused concomitantly aiming at a whole blood glucose of 5 mmol/L. The glucose infusion rate (GIR) was adjusted for body weight or fat free mass (FFM), the latter measured with dual-energy X-ray absorptiometry. During the final hour of each examination (60-120 min) the mean whole blood glucose concentrations were 5.06+/-0.15 and 5.09+/-0.17 mmol/L, respectively. Of the different time intervals studied, the glucose infusion rate during the final hour (GIR60-120) showed the highest correlation and lowest coefficient of variation (GIR60-120 adjusted by FFM: r=0.70, coefficient of variation=14.7%). Adjustment of GIR for weight instead of FFM underestimated insulin sensitivity in obese men. GIR60-120 adjusted for FFM tended to increase during the second examination. The measurement error was constant across all GIR. In summary, the euglycemic hyperinsulinemic clamp method has a coefficient of variation around 15%. The glucose infusion rate should be adjusted for fat free mass.

Body Mass Index↗
PubMed2000

The metabolic syndrome, LDL particle size, and atherosclerosis: the Atherosclerosis and Insulin Resistance (AIR) study.

An operative definition of the metabolic syndrome has been suggested by a working group associated with the World Health Organization in 1998. The aim of this study was to examine whether small, low density lipoprotein (LDL) particle size was associated with the metabolic syndrome and with subclinical atherosclerosis as measured by ultrasound in the carotid and femoral arteries. The study was performed in a population-based sample of clinically healthy men (N=391), all 58 years old and not undergoing any treatment with cardiovascular drugs. Exclusion criteria were cardiovascular or other clinically overt diseases or continuous medication with cardiovascular drugs. The results showed that subjects characterized by the metabolic syndrome (n=62) had a thicker mean intima-media complex (IMT) in both the carotid and femoral arteries (0.86 versus 0.77 mm, P:<0.001, and 1.03 versus 1. 00 mm, P:=0.022, respectively) and also lower mean values for LDL particle size (25.78 versus 26.80 nm, respectively, P:<0.001) compared with subjects with no risk factors (n=77). The group with the metabolic syndrome (n=62) also had higher mean values for serum cholesterol and heart rate. In the whole study group (N=391), there were significant but weak negative relationships between small LDL particle size, increasing IMT, and increasing cross-sectional intima-media area of the carotid and femoral arteries and also negative relationships between LDL particle size and plaque occurrence and size in the carotid and femoral arteries. In summary, this is the first large-scale study to demonstrate a relationship between the clustering of risk factors that constitute the metabolic syndrome and a small LDL particle size pattern and the occurrence of preclinical atherosclerosis in the carotid and femoral arteries, as assessed by the ultrasound technique, in healthy 58-year-old men recruited from the general population.

Arteriosclerosis↗