| 1. |
- Deedwania, P. C., et al.
(författare)
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Efficacy, safety and tolerability of beta-adrenergic blockade with metoprolol CR/XL in elderly patients with heart failure
- 2004
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Ingår i: Eur Heart J. - : Oxford University Press (OUP). - 0195-668X. ; 25:15, s. 1300-9
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To study the efficacy and tolerability of beta-blockade in elderly patients with heart failure in the MERIT-HF study. METHODS AND RESULTS: Cox proportional hazards model was used to calculate hazard ratios (HR) with 95% confidence intervals (CI). Risk reduction was defined as (1-HR). In patients > or = 65 years total mortality was reduced by 37% (95% CI 17% to 52%; p=0.0008), sudden death by 43% (95% CI 17% to 61%; p=0.0032), and death from worsening heart failure by 61% (95% CI 32% to 77%; p=0.0005). Hospitalisations for worsening heart failure was reduced by 36% (p=0.0006). Elderly patients with severe heart failure (NYHA class III/IV with ejection fraction < 0.25; n=425, and patients above 75 years (n=490) showed similar risk reductions. Metoprolol CR/XL was safe and well tolerated both during initiating therapy and during long-term follow-up. CONCLUSIONS: Metoprolol CR/XL was easily instituted, safe and well tolerated in elderly patients with systolic heart failure. The data suggest that these are the patients in whom treatment will have the greatest impact as shown by number of lives saved and number of hospitalisations avoided. The time has come to overcome the barriers that physicians perceive to beta-blocker treatment, and to provide it to the large number of elderly patients with heart failure in need of this therapy.
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| 2. |
- Ghali, J. K., et al.
(författare)
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Consistency of the beneficial effect of metoprolol succinate extended release across a wide range dose of angiotensin-converting enzyme inhibitors and digitalis
- 2004
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Ingår i: J Card Fail. - 1071-9164. ; 10:6, s. 452-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The effects of beta-blockade with different extent of angiotensin-converting enzyme inhibitors (ACEI) and digitalization are unknown. To assess the effect of metoprolol succinate controlled release/extended release (CR/XL) combined with high versus low doses of ACEI and digitalis, we analyzed data from The Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF) in which patients with heart failure and left ventricular ejection fraction < or =40% were randomized to metoprolol CR/XL versus placebo. METHODS AND RESULTS: Outcome was analyzed separately for those on a low dose (< or =median) of the ACEI or digitalis versus high dose (> median). The mean dose of ACEI in the high-dose group (n = 1457) was 3 times higher than that in the low-dose group (n = 2094). Mortality was reduced to a similar extent in the high- and low-dose ACEI subgroups (RR = .69 versus .64, respectively). Corresponding figures for combined mortality/all hospitalization and for mortality/hospitalization for heart failure were .85 versus .83, and .70 versus .68, respectively. Likewise, reduction in total mortality with metoprolol CR/XL was similar in patients receiving no digitalis (n = 1447; RR = .56), low dose (n = 1122; RR = .71), or high dose (n = 1421; RR = .71). CONCLUSION: This analysis of MERIT-HF demonstrates consistent and similar improvement in outcome of patients receiving metoprolol CR/XL when combined with either a high or low dose of an ACEI or digitalis, or no digitalis at all. Thus regardless of ACEI and digitalis dose and whether patients are treated with digitalis or not, it is very important to add a beta-blocker to the existing heart failure therapy. beta-blockers should not be withheld until target doses of ACEI have been achieved.
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| 3. |
- Agewall, S, et al.
(författare)
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Insulin sensitivity and hemostatic factors in clinically healthy 58-year-old men.
- 2000
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Ingår i: Thrombosis and haemostasis. - 0340-6245. ; 84:4, s. 571-5
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this cross-sectional study was to investigate the relationship between factors of the coagulation- and fibrinolysis systems and insulin sensitivity in 104 clinically healthy, 58-years-old men. Insulin sensitivity (hyperinsulinemic euglycemic clamp) adjusted for lean body mass, the metabolic syndrome according to a suggested definition, and different factors in the coagulation- and fibrinolysis system were determined. Subjects with the metabolic syndrome were characterised by increases in PAI-1 activity, tPA antigen, protein C and protein S and low concentrations of tPA activity. Insulin sensitivity was independently and reversibly associated with PAI-1 (p = 0.014) and directly with tPA activity (p = 0.001). Insulin sensitivity was also significantly negatively associated with protein S and protein C and several components in the metabolic syndrome, however not remaining significant in multivariate analyses. Protein C and protein S were significantly associated with PAI-1 activity, tPA activity (negatively), tPA antigen and antithrombin III. In conclusion, the data indicated that insulin resistance and several of the clustering components in the metabolic syndrome are accompanied by increased plasma concentrations of the anticoagulatory proteins C and S which may represent a mechanism which counteracts the concomitantly occurring hypofibrinolysis.
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| 4. |
- Agewall, S, et al.
(författare)
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Multiple risk intervention trial in high risk hypertensive men: comparison of ultrasound intima-media thickness and clinical outcome during 6 years of follow-up
- 2001
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 249:1, s. 305-314
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Andersson, Bert, 1952, et al.
(författare)
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Dose-related effects of metoprolol on heart rate and pharmacokinetics in heart failure.
- 2001
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Ingår i: Journal of cardiac failure. - 1071-9164. ; 7:4, s. 311-7
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Tidskriftsartikel (refereegranskat)abstract
- The pharmacokinetics and pharmacodynamics of immediate-release (IR) metoprolol, 50 mg 3 times daily, were compared with those of different doses of controlled-release/extended-release metoprolol (CR/XL) given once daily.Fifteen patients with chronic heart failure were randomized to a 3-way crossover study to receive metoprolol IR 50 mg 3 times daily, CR/XL 100 mg once daily, and CR/XL 200 mg once daily for 7 days. On the seventh day of each treatment, serial plasma samples were drawn and standardized exercise tests and a 24-hour Holter recording were performed. Metoprolol IR 50 mg produced peak plasma levels comparable to those observed for CR/XL 200 mg (285 v 263 nmol/L). The difference in mean 24-hour heart rate between CR/XL 100 mg and IR 50 mg was 1.0 bpm (95% confidence interval [CI]), -2.9 to 4.9; NS) compared with -3.8 bpm (95% CI, -7.6 to -0.04; P = .048) between CR/XL 200 mg and IR 50 mg. Submaximal exercise heart rate was lower for patients receiving CR/XL 200 mg than those receiving IR 50 mg. No difference in tolerance or exercise performance was observed between treatment regimens.Peak plasma levels produced by metoprolol 200 mg CR/XL were similar to those of 50 mg IR. Metoprolol CR/XL 200 mg was associated with a more pronounced suppression of heart rate than metoprolol IR 50 mg. It is suggested that patients can safely be switched from multiple dosing of metoprolol IR 50 mg to a once-daily dose of metoprolol CR/XL.
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| 6. |
- Schmidt, Caroline, 1966, et al.
(författare)
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Chlamydia pneumoniae seropositivity is associated with carotid artery intima-media thickness
- 2000
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Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 31:7, s. 1526-1531
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Infection may both augment the atherosclerotic process and contribute to later manifestations of overt clinical disease. Chlamydia pneumoniae elementary bodies have been detected in atherosclerotic lesions. The aim of the present study was to investigate whether elevated titers of antibodies and circulating immune complexes to C pneumoniae were associated with ultrasound findings indicating presence of atherosclerosis in the carotid artery. METHODS: Serum titers of antibodies to C pneumoniae (IgM, IgA, IgG, and circulating immune complex) were related to intima-media thickness (IMT) and plaque status measured by B-mode ultrasound in the carotid artery in 113 men with treated hypertension and at least 1 of the following risk factors: hypercholesterolemia, smoking, or diabetes. RESULTS: Any of the titers was elevated in 56 (50%) men, and common carotid artery IMT was thicker in this group compared with the 57 men without any elevated titers (1.00 versus 0.92 mm, P<0.05). There were no accompanying differences in blood pressure, lipid levels, blood glucose, or smoking. Elevation of separate antibody types and circulation immune complex were also associated with increased IMT. In the latter group, systolic blood pressure was higher among seropositive patients compared with those who had no circulating immune complex. Seropositivity was not related to plaque status. CONCLUSIONS: Seropositivity for C pneumoniae was associated with an increased intima-media thickness in the common carotid artery but not plaque status in hypertensive men at high risk for cardiovascular disease.
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| 7. |
- Schmidt, Caroline, 1966, et al.
(författare)
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Multiple risk factor intervention reduces cardiovascular risk in hypertensive patients with echolucent plaques in the carotid artery
- 2003
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Ingår i: Journal of internal medicine. ; 253:4, s. 430-438
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In a previously published randomized 6-year study we observed that multiple risk factor intervention reduced cardiovascular risk in high-risk hypertensive men, and that this effect was confined to patients with carotid artery plaques. Hypothetically, the underlying mechanism might have been a stabilization of echolucent, instable, rupture-prone plaques. The aim of the present study was to examine plaque characteristics by B-mode ultrasound in the previous intervention study, and also to investigate the relationship between plaque characteristics at baseline and cardiovascular events during the 6-year follow-up in the two randomization groups. METHODS: High resolution B-mode ultrasound was used to characterize plaque echogenicity in four subgroups - dominantly echolucent, substantially echolucent, dominantly echogenic, and uniformly echogenic. RESULTS: In the usual care group 17 of 32 (53%) patients with echolucent plaques at baseline suffered from a combined end-point (any death or nonfatal myocardial infarction or nonfatal stroke) during follow-up compared with seven of 28 (25%) patients in the intervention group (P = 0.036). The corresponding numbers in patients with echogenic plaques were n = 4/13 (31%) and n = 4/17 (24%), respectively (NS). In the usual care group 11 of 33 (33%) patients with no plaques suffered from a combined end-point during follow-up compared with 11 of 30 (37%) in the intervention group. CONCLUSION: Our data indicate that the beneficial effect of the multiple risk intervention programme was confined to those patients with echolucent plaques. The data have to be confirmed with a large-scale trial.
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| 8. |
- Wallenfeldt, Karin, 1960, et al.
(författare)
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Apolipoprotein B/apolipoprotein A-I in relation to the metabolic syndrome and change in carotid artery intima-media thickness during 3 years in middle-aged men
- 2004
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Ingår i: Stroke. - 1524-4628. ; 35:10, s. 2248-52
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: The apolipoprotein B (apoB)/apolipoprotein A-I (apoA-I) ratio is a measure of the relationship between different lipoprotein particles and a powerful predictor of coronary death. The aim was to examine whether apoB/apoA-I was associated with the metabolic syndrome (MetS) at baseline and also with the future change in carotid artery intima-media thickness (IMT). METHODS: In 313 58-year-old men, carotid artery IMT was measured bilaterally by high-resolution B-mode ultrasound at baseline and after 3 years of follow-up. Serum apolipoprotein concentrations and the components of MetS were measured at study entry. RESULTS: ApoB/apoA-I showed statistically significant associations with body mass index, waist-to-hip ratio, high-density lipoprotein (HDL) cholesterol, triglycerides, low-density lipoprotein (LDL) particle size, insulin, and diastolic blood pressure. Two thirds of the patients with MetS had high apoB/apoA-I ratios (>0.90) compared with one third of those without the syndrome (P<0.001). The IMT change was associated with apoB, total cholesterol, LDL cholesterol, triglycerides, and inversely with HDL cholesterol and LDL particle size at entry, and there was a strong colinearity between these variables. The subjects with apoB/apoA-I above the first tertile (0.74) had a 20-microm-higher (95% CI, 7 to 33) annual increase in IMT compared with those below this level after adjustment for blood pressure and smoking. CONCLUSIONS: The apoB/apoA-I ratio was strongly associated with MetS and its components at baseline. ApoB/apoA-I at baseline was related to the change in carotid artery IMT during 3 years of follow-up. There was a strong colinearity between apoB/apoA and the atherogenic lipids.
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| 9. |
- Wallenfeldt, Karin, 1960, et al.
(författare)
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Oxidized low-density lipoprotein in plasma is a prognostic marker of subclinical atherosclerosis development in clinically healthy men
- 2004
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Ingår i: Journal of Internal Medicine. - 0954-6820. ; 256:5, s. 413-20
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the association between plasma oxidized low-density lipoprotein (OxLDL) and the progress of clinically silent atherosclerosis, as measured by ultrasound in the carotid arteries. DESIGN: Prospective, observational study with more than 3 years of follow-up. SETTING: One-centre study at university hospital. MATERIAL AND METHODS: The subjects (n = 326) were obtained by stratified sampling from a population sample of men who were 58 years old at baseline. Carotid artery intima-media thickness (IMT) was measured bilaterally by high-resolution B-mode ultrasound at baseline and after follow-up. Plasma OxLDL cholesterol concentrations and conventional cardiovascular risk factors were measured at study entry. Automated measurements of IMT were performed. Plaque occurrence and size were assessed (plaque status). Plasma OxLDL at entry was measured by a specific monoclonal antibody, mAb-4E6. RESULTS: OxLDL at entry, but not LDL cholesterol, was associated with the number and size of plaques at follow-up (P = 0.008), also after adjustment for plaque status at entry (P = 0.033). The plasma OxLDL concentration at entry was associated with change in carotid artery IMT (r = 0.17; P = 0.002) and in a stepwise multiple regression analysis this association remained after adjustment for other cardiovascular risk factors (P = 0.005). CONCLUSIONS: These results provide new information, supporting the concept that circulating OxLDL was associated with the silent phase of atherosclerosis progression in clinically healthy men independently of conventional risk factors.
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| 10. |
- Wiklund, Olov, 1943, et al.
(författare)
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Effect of controlled release/extended release metoprolol on carotid intima-media thickness in patients with hypercholesterolemia. A 3-year randomized study
- 2002
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Ingår i: Stroke. ; 33:2, s. 572-577
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Beta-adrenergic blockade has in several studies been shown to improve survival after myocardial infarction. In animal experiments beta-blockers have also shown an antiatherosclerotic effect. The aim of this study was to test the hypothesis that the beta-blocker metoprolol succinate controlled release/extended release (CR/XL), when given to patients with hypercholesterolemia on concomitant lipid-lowering therapy, provides an additional antiatherosclerotic effect to that provided by the statins, measured as carotid intima-media thickness (IMT). METHODS: We conducted a randomized, double-blind, placebo-controlled, single center trial to compare the effect of metoprolol CR/XL (100 mg once daily) and placebo on the progression of carotid IMT during 36 months of treatment in patients with hypercholesterolemia and signs of early atherosclerosis in the carotid artery. Most patients were prescribed lipid-lowering treatment with statins. RESULTS: A highly significant difference in the progression rate of the composite variable of carotid bulb IMT+common carotid IMT was observed between the metoprolol CR/XL and placebo groups after 1 year of treatment (-0.08 versus -0.01 mm; P=0.004), an effect that was sustained after 3 years of follow-up (-0.06 versus +0.03 mm; P=0.011). The patients had high levels of total cholesterol at randomization: 9.4 mmol/L in the metoprolol CR/XL group and 8.6 mmol/L in the placebo group. During the study the 2 randomization groups were treated with lipid-lowering drugs, mainly statins, to a similar extent, and total cholesterol was reduced to 6.4 mmol/L at end of follow-up in both groups. CONCLUSIONS: The results from the present study in patients with hypercholesterolemia under concomitant lipid-lowering therapy are the first clinical data to show an antiatherosclerotic effect of beta-blockade as additional therapy to statins. The data indicate that statin treatment and treatment with beta-blockers affect different mechanisms in the atherosclerotic process and have additive beneficial effects.
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| 11. |
- Wikstrand, John, 1938, et al.
(författare)
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Pharmacokinetic considerations of formulation: extended-release metoprolol succinate in the treatment of heart failure.
- 2003
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Ingår i: Journal of cardiovascular pharmacology. - 0160-2446. ; 41:2, s. 151-7
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Tidskriftsartikel (refereegranskat)abstract
- Extended-release (ER) metoprolol succinate is a controlled-release formulation designed to deliver metoprolol succinate at a near constant rate for approximately 20 h, independent of food intake and gastrointestinal pH. Once-daily dosing of ER metoprolol succinate 12.5-200 mg produces even plasma concentrations over a 24-h period, without the marked peaks and troughs characteristically observed with the immediate-release (IR) formulation. This leads to consistent beta1-blockade over 24 h, while maintaining cardioselectivity at doses up to 200 mg daily. Pharmacokinetic studies have also been performed in heart failure patients and have demonstrated that ER metoprolol succinate is associated with a more pronounced and even beta1-blockade over a 24-h period than the IR formulation. The efficacy and good tolerability of ER metoprolol succinate in heart failure patients has now been demonstrated in a large-scale clinical trial.
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