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1.  Endothelial function is unaffected by changing between carvedilol and metoprolol in patients with heart failure-a randomized study 
Background
Carvedilol has been shown to be superior to metoprolol tartrate to improve clinical outcomes in patients with heart failure (HF), yet the mechanisms responsible for these differences remain unclear. We examined if there were differences in endothelial function, insulin stimulated endothelial function, 24 hour ambulatory blood pressure and heart rate during treatment with carvedilol, metoprolol tartrate and metoprolol succinate in patients with HF.
Methods
Twenty-seven patients with mild HF, all initially treated with carvedilol, were randomized to a two-month treatment with carvedilol, metoprolol tartrate or metoprolol succinate. Venous occlusion plethysmography, 24-hour blood pressure and heart rate measurements were done before and after a two-month treatment period.
Results
Endothelium-dependent vasodilatation was not affected by changing from carvedilol to either metoprolol tartrate or metoprolol succinate. The relative forearm blood flow at the highest dose of serotonin was 2.42 ± 0.33 in the carvedilol group at baseline and 2.14 ± 0.24 after two months continuation of carvedilol (P = 0.34); 2.57 ± 0.33 before metoprolol tartrate treatment and 2.42 ± 0.55 after treatment (p = 0.74) and in the metoprolol succinate group 1.82 ± 0.29 and 2.10 ± 0.37 before and after treatment, respectively (p = 0.27). Diurnal blood pressures as well as heart rate were also unchanged by changing from carvedilol to metoprolol tartrate or metoprolol succinate.
Conclusion
Endothelial function remained unchanged when switching the beta blocker treatment from carvedilol to either metoprolol tartrate or metoprolol succinate in this study, where blood pressure and heart rate also remained unchanged in patients with mild HF.
Trial registration
Current Controlled Trials NCT00497003
doi:10.1186/1475-2840-10-91
PMCID: PMC3212926  PMID: 21999413
Heart failure; Endothelial function; Beta blocker
2.  Temporal trends in the initiation of glucose-lowering medications after a first-time myocardial infarction - a nationwide study between 1997 and 2006 
Background
Type 2 diabetes is a well-established risk factor for cardiovascular disease and is common among patients with acute myocardial infarction (MI). The extent to which patients with first-time MI develop diabetes requiring glucose-lowering medications (GLM) is largely unknown. The aim of the study was to investigate temporal trends in the initiation of GLM among patients discharged after first-time MI.
Methods
All Danish residents aged ≥ 30 years without prior diabetes hospitalized with first-time MI between 1997 and 2006 were identified by individual-level-linkage of nationwide registers. Initiation of GLM during follow-up was assessed by claimed prescriptions from pharmacies. Temporal trends in initiation of GLM were assessed by incidence rate calculations in the MI population as in the general population. Multivariable Cox proportional-hazard models were used to investigate the likelihood of initiating GLM within a year post-MI.
Results
The population comprised 66,788 patients. Among these patients 3962 patients initiated GLM, of whom 1567 started within one year post-MI. An increase in incidence rates of GLM initiation in the MI population from 19.6 per 1000 person years in 1997 to approximately 27.6 in 2001 was demonstrated. After 2001 the incidence rates stabilized. A similar trend was observed in the general population where the incidence rates increased from 2.8 in 1997 to 4.0 in 2004 and then stabilized.
Conclusion
Our study demonstrated an increase in incidence rates of GLM initiation within the first year post- MI. A similar trend was observed in the general population suggesting that the increase in GLM among MI patients was primarily the effect of a general increased awareness of diabetes. From a public heath perspective, this study underscores a continuous need for diagnostic and therapeutic improvement in the care of MI patients that develop diabetes.
doi:10.1186/1475-2840-10-5
PMCID: PMC3031215  PMID: 21247456
3.  Effects of oral glucose-lowering drugs on long term outcomes in patients with diabetes mellitus following myocardial infarction not treated with emergent percutaneous coronary intervention - a retrospective nationwide cohort study 
Background
The optimum oral pharmacological treatment of diabetes mellitus to reduce cardiovascular disease and mortality following myocardial infarction has not been established. We therefore set out to investigate the association between individual oral glucose-lowering drugs and cardiovascular outcomes following myocardial infarction in patients with diabetes mellitus not treated with emergent percutaneous coronary intervention.
Materials and methods
All patients aged 30 years or older receiving glucose-lowering drugs (GLDs) and admitted with myocardial infarction (MI) not treated with emergent percutaneous coronary intervention in Denmark during 1997-2006 were identified by individual-level linkage of nationwide registries of hospitalizations and drug dispensing from pharmacies. Multivariable Cox regression models adjusted for age, sex, calendar year, comorbidity, and concomitant pharmacotherapy were used to assess differences in the composite endpoint of non-fatal MI and cardiovascular mortality between individual GLDs, using metformin monotherapy as reference.
Results
The study comprised 9876 users of GLDs admitted with MI. The mean age was 72.3 years and 56.5% of patients were men. A total of 3649 received sulfonylureas and 711 received metformin at admission. The average length of follow-up was 2.2 (SD 2.6) years. A total of 6,171 patients experienced the composite study endpoint. The sulfonylureas glibenclamide, glimepiride, glipizide, and tolbutamide were associated with increased risk of cardiovascular mortality and/or nonfatal MI with hazard ratios [HRs] of 1.31 (95% confidence interval [CI] 1.17-1.46), 1.19 (1.06-1.32), 1.25 (1.11-1.42), and 1.18 (1.03-1.34), respectively, compared with metformin. Gliclazide was the only sulfonylurea not associated with increased risk compared with metformin (HR 1.03 [0.88-1.22]).
Conclusions
In patients with diabetes mellitus admitted with MI not treated with emergent percutaneous coronary intervention, monotherapy treatment with the sulfonylureas glibenclamide, glimepiride, glipizide, and tolbutamide was associated with increased cardiovascular risk compared with metformin monotherapy.
doi:10.1186/1475-2840-9-54
PMCID: PMC2946277  PMID: 20843380
4.  Diabetes is an independent predictor of survival 17 years after myocardial infarction: follow-up of the TRACE registry 
Background
In patients hospitalized for myocardial infarction, there are limited data examining the long-term prognostic effect of diabetes.
The aim of this study was to systematically evaluate the development of diabetes as an independent long-term prognostic factor after myocardial infarction.
Methods
Prospective follow-up of 6676 consecutive MI patients screened for entry in the Trandolapril Cardiac Evaluation (TRACE) study. The patients were analysed by Kaplan-Meier survival analysis, landmark analysis and Cox proportional hazard models and outcome measure was all-cause mortality.
Results
The mortality in patients with diabetes was 82,7% at 10 years of follow-up and 91,1% at 15 years of follow-up, while patients without diabetes had a mortality of 60,2% at 10 years of follow-up and 72,9% at 15 years of follow-up (p < 0.0001). Landmark analysis continued to show prognostic significance of diabetes throughout the duration of follow-up. Multivariable Cox proportional-hazards model showed that the hazard ratio for death in patients with diabetes overall was 1.47 (95% confidence intervals (CI) 1.35-1.61) and varied between 1.19 (CI 1.04-1.37) and 2.13 (CI 1.33-3.42) in the 2-year periods of follow-up.
Conclusions
Diabetes is an important independent long-term prognostic factor after MI and continues to predict mortality even 17 years after index MI.
This underscores the importance of aggressive diagnostic and therapeutic approach in diabetes patients with MI.
doi:10.1186/1475-2840-9-22
PMCID: PMC2893120  PMID: 20525192
5.  Metoprolol compared to carvedilol deteriorates insulin-stimulated endothelial function in patients with type 2 diabetes - a randomized study 
Aim
Studies of beta blockade in patients with type 2 diabetes have shown inferiority of metoprolol treatment compared to carvedilol on indices of insulin resistance. The aim of this study was to examine the effect of metoprolol versus carvedilol on endothelial function and insulin-stimulated endothelial function in patients with type 2 diabetes.
Method
24 patients with type 2 diabetes were randomized to receive either 200 mg metoprolol succinate or 50 mg carvedilol daily. Endothelium-dependent vasodilation was assessed by using venous occlusion plethysmography with increasing doses of intra-arterial infusions of the agonist serotonin. Insulin-stimulated endothelial function was assessed after co-infusion of insulin for sixty minutes. Vaso-reactivity studies were done before and after the two-month treatment period.
Results
Insulin-stimulated endothelial function was deteriorated after treatment with metoprolol, the percentage change in forearm blood-flow was 60.19% ± 17.89 (at the highest serotonin dosages) before treatment and -33.80% ± 23.38 after treatment (p = 0.007). Treatment with carvedilol did not change insulin-stimulated endothelial function. Endothelium-dependent vasodilation without insulin was not changed in either of the two treatment groups.
Conclusion
This study shows that vascular insulin sensitivity was preserved during treatment with carvedilol while blunted during treatment with metoprolol in patients with type 2 diabetes.
Trial registration
Current Controlled Trials NCT00497003
doi:10.1186/1475-2840-9-21
PMCID: PMC2893119  PMID: 20500877
6.  Diabetes is associated with impaired myocardial performance in patients without significant coronary artery disease 
Background
Patients with diabetes mellitus (DM) have high risk of heart failure. Whether some of the risk is directly linked to metabolic derangements in the myocardium or whether the risk is primarily caused by coronary artery disease (CAD) and hypertension is incompletely understood. Echocardiographic tissue Doppler imaging was therefore performed in DM patients without significant CAD to examine whether DM per se influenced cardiac function.
Methods
Patients with a left ventricular (LV) ejection fraction (EF) > 35% and without significant CAD, prior myocardial infarction, cardiac pacemaker, atrial fibrillation, or significant valve disease were identified from a tertiary invasive center register. DM patients were matched with controls on age, gender and presence of hypertension.
Results
In total 31 patients with diabetes and 31 controls were included. Mean age was 58 ± 12 years, mean LVEF was 51 ± 7%, and 48% were women. No significant differences were found in LVEF, left atrial end systolic volume, or left ventricular dimensions. The global longitudinal strain was significantly reduced in patients with DM (15.9 ± 2.9 vs. 17.7 ± 2.9, p = 0.03), as were peak longitudinal systolic (S') and early diastolic (E') velocities (5.7 ± 1.1 vs. 6.4 ± 1.1 cm/s, p = 0.02 and 6.1 ± 1.7 vs. 7.7 ± 2.0 cm/s, p = 0.002). In multivariable regression analyses, DM remained significantly associated with impairments of S' and E', respectively.
Conclusion
In patients without significant CAD, DM is associated with an impaired systolic longitudinal LV function and global diastolic dysfunction. These abnormalities are likely to be markers of adverse prognosis.
doi:10.1186/1475-2840-9-3
PMCID: PMC2818623  PMID: 20082690

Results 1-6 (6)