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1.  Hormone Replacement Therapy and Risk of New-Onset Atrial Fibrillation after Myocardial Infarction - A Nationwide Cohort Study 
PLoS ONE  2012;7(12):e51580.
Objectives
Our aim was to assess the association between use of hormone replacement therapy (HRT) and risk of new-onset atrial fibrillation (AF) after myocardial infarction.
Design, Setting and Participants
We used Danish nationwide registers of hospitalizations and prescriptions to identify all women admitted with myocardial infarction in the period 1997 to 2009 and with no known diagnosis of AF. Their use of overall HRT and HRT categories was assessed. Multivariable Cox proportional hazards analysis was used to calculate the risk of new-onset AF first year after discharge, comparing use of HRT to no use.
Main Outcome Measures
New-onset atrial fibrillation.
Results
In the period 1997 to 2009, 32 925 women were discharged alive after MI. In the first year after MI, new-onset AF was diagnosed in 1381 women (4.2%). Unadjusted incidence rates of AF decreased with use of HRT (incidence rate 37.4 for use of overall HRT and 53.7 for no use). Overall HRT was associated with a decreased risk of AF (HR 0.82, 95% confidence interval [CI] 0.68–1.00). The lowest risk of AF was found in women ≥80 years old for use of overall HRT and vaginal estrogen (HR 0.63, CI 0.42–0.94, and HR 0.58, CI 0.34–0.99, respectively). Decreased risk of AF with use of overall HRT and HRT categories was also found in other age groups.
Conclusions
Use of HRT is associated with a decreased risk of new-onset AF in women with myocardial infarction first year after discharge. The underlying mechanisms remain to be determined. Unmeasured confounding might be one of them.
doi:10.1371/journal.pone.0051580
PMCID: PMC3524193  PMID: 23284717
2.  The effect of chronic heart failure and type 2 diabetes on insulin-stimulated endothelial function is similar and additive 
Aim
Chronic heart failure is associated with endothelial dysfunction and insulin resistance. The aim of this investigation was to study insulin-stimulated endothelial function and glucose uptake in skeletal muscles in patients with heart failure in comparison to patients with type 2 diabetes.
Methods
Twenty-three patients with systolic heart failure and no history of diabetes, seven patients with both systolic heart failure and type 2 diabetes, 19 patients with type 2 diabetes, and ten healthy controls were included in the study. Endothelial function was studied by venous occlusion plethysmography. Insulin-stimulated endothelial function was assessed after intra-arterial infusion of insulin followed by co-infusion with serotonin in three different dosages. Forearm glucose uptake was measured during the insulin infusion.
Results
Patients with systolic heart failure had impaired insulin-stimulated endothelial function. The percentage increase in blood flow during co-infusion with insulin and serotonin dose response study was 24.74% ± 6.16%, 23.50% ± 8.32%, and 22.29% ± 10.77% at the three doses respectively, compared to the healthy control group 45.96% ± 11.56%, 67.40% ± 18.11% and 84.57% ± 25.73% (P = 0.01). Insulin-stimulated endothelial function was similar in heart failure patients and patients with type 2 diabetes, while it was further deteriorated in patients suffering from both heart failure and diabetes with a percentage increase in blood flow of 19.15% ± 7.81%, −2.35% ± 11.76%, and 5.82% ± 17.70% at the three doses of serotonin, respectively. Forearm glucose uptake was impaired in patients with heart failure compared to healthy controls (P = 0.03) and tended to be further impaired by co-existence of diabetes (P = 0.08).
Conclusion
Systolic heart failure and type 2 diabetes result in similar vascular insulin resistance and reduced muscular insulin-stimulated glucose uptake. The effects of systolic heart failure and type 2 diabetes appear to be additive.
doi:10.2147/VHRM.S25724
PMCID: PMC3253770  PMID: 22241951
insulin resistance; diabetes; heart failure; endothelial function
3.  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
4.  National Background is Associated with Disparities in Initiation and Persistence to Statin Treatment in Subjects with Diabetes in Denmark 
Background: To investigate the effects of statin use over the last 10 years among diabetic patients who initiated glucose-lowering medications (GLMs) in Denmark. Methods: we identified all Danish citizens 30 years and older who claimed their first GLM between 1997 and 2006, with follow-up until 2007. Use of medications, national background, income, and hospitalizations were obtained by cross-linkage of national registries in Denmark. We analyzed factors related to initiation and interruption of statin treatment. The analyses included country of birth, citizenship and, as proxy for ethnic origin, we constructed variables based on both the subjects and on their parent's country of birth. Countries were grouped as Denmark, Western countries, Eastern countries, and Africa. Results: the cohort included 143,625 subjects. Compared with persons of Danish origin, the initiation of a statin medication during follow-up was significantly lower among patients of non-Danish origin: Odds ratio for subjects of Eastern origin 0.61 [CI 0.49–0.76] and 0.37 for subjects of African origin, [CI 0.24–0.59], both p < 0.001. The risk of interrupting statin treatment once it had been initiated was also higher in these groups (hazard ratio 2.03, [CI 1.91–2.17] for Eastern subjects and 1.94, [CI 1.63–2.32] for African subjects, both p < 0.0001). Combination of ethnic parameters to refine identification of the cohort led to the same conclusions as the analysis based only on country of birth or citizenship respectively. Conclusion: diabetes patients of African and Eastern origin in Denmark have less chance of being treated with a statin than those of western and Danish origin despite similar access to the Danish health care system.
doi:10.3389/fphar.2010.00142
PMCID: PMC3153016  PMID: 21833181
statins; diabetes; epidemiology; registries
5.  Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist 
Background
The use of mechanical/physical devices for applying mild therapeutic hypothermia is the only proven neuroprotective treatment for survivors of out of hospital cardiac arrest. However, this type of therapy is cumbersome and associated with several side-effects. We investigated the feasibility of using a transient receptor potential vanilloid type 1 (TRPV1) agonist for obtaining drug-induced sustainable mild hypothermia.
Methods
First, we screened a heterogeneous group of TRPV1 agonists and secondly we tested the hypothermic properties of a selected candidate by dose-response studies. Finally we tested the hypothermic properties in a large animal. The screening was in conscious rats, the dose-response experiments in conscious rats and in cynomologus monkeys, and the finally we tested the hypothermic properties in conscious young cattle (calves with a body weight as an adult human). The investigated TRPV1 agonists were administered by continuous intravenous infusion.
Results
Screening: Dihydrocapsaicin (DHC), a component of chili pepper, displayed a desirable hypothermic profile with regards to the duration, depth and control in conscious rats. Dose-response experiments: In both rats and cynomologus monkeys DHC caused a dose-dependent and immediate decrease in body temperature. Thus in rats, infusion of DHC at doses of 0.125, 0.25, 0.50, and 0.75 mg/kg/h caused a maximal ΔT (°C) as compared to vehicle control of -0.9, -1.5, -2.0, and -4.2 within approximately 1 hour until the 6 hour infusion was stopped. Finally, in calves the intravenous infusion of DHC was able to maintain mild hypothermia with ΔT > -3°C for more than 12 hours.
Conclusions
Our data support the hypothesis that infusion of dihydrocapsaicin is a candidate for testing as a primary or adjunct method of inducing and maintaining therapeutic hypothermia.
doi:10.1186/1471-2261-10-51
PMCID: PMC2966451  PMID: 20932337
6.  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

Results 1-6 (6)