Pernille Holmager

Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE)—a multicentre, double-blind, randomised, placebo-controlled trial

To determine the effect of the glucagon‐like peptide‐1 analogue liraglutide on left ventricular function in chronic heart failure patients with and without type 2 diabetes.

A protocol for a randomised, double-blind, placebo-controlled study of the effect of LIraglutide on left VEntricular function in chronic heart failure patients with and without type 2 diabetes (The LIVE Study)

Introduction Heart failure is one of the most common cardiovascular complications of diabetes and the most disabling and deadly complication too. Many antidiabetic agents have been associated with increased morbidity and mortality in a subset of patients with chronic heart failure (CHF); thus, new treatment modalities are warranted. Interestingly, a beneficial effect of the incretin hormone, GLP-1, on cardiac function has been suggested in patients with diabetes and patients without diabetes. Liraglutide (Victoza) is a GLP-1 analogue developed for the treatment of type 2 diabetes (T2D); however, its impact on cardiac function has not previously been investigated in patients with CHF. This prompted us to investigate whether liraglutide treatment for 24 weeks improves left ventricular ejection fraction (LVEF) in patients with CHF with and without T2D compared with placebo treatment. Methods and analysis An investigator-initiated, multicentre, randomised, double-blind, parallel, placebo-controlled intervention trial. In total, 240 patients with CHF (with and without T2D) with LVEF≤45% will be randomised to either subcutaneous injection of liraglutide 1.8 mg or matching placebo once daily for 24 weeks. The effect of liraglutide on left ventricular function will be evaluated by advanced echocardiography, including three-dimensional contrast echocardiography. Ethics and dissemination The study will be performed and monitored according to the Good Clinical Practice-International Conference on Harmonisation (GCP-ICH) regulations and conducted according to the principles of the Helsinki Declaration. The Danish Medicines Agency, the local Research Ethics Committee and the Danish Data Protection Agency have approved the study. Trial registration number ClinicalTrials.gov Identifier: NCT01472640.

Pressure pain sensitivity: a new method of stress measurement in patients with ischemic heart disease.

Abstract Background. Chronic stress is prevalent in patients with ischemic heart disease (IHD) and worsens the long-term prognosis. Chronic stress is vaguely defined, but is associated with depressive symptoms, reduced psychological wellbeing, and reduced quality of life (QOL). Stress seems to induce hyperalgesia.The aim of the present study was to evaluate hyperalgesia by pressure pain sensitivity (PPS) in patients with IHD, and compare PPS to questionnaires measuring depressive symptoms, reduced psychological wellbeing, and QOL as markers of stress. Design. A cross-sectional study of 361 subjects with IHD. Methods. PPS was measured on the sternum, and compared to the questionnaires: Clinical stress symptoms score (CSS), Major Depression Inventory (MDI), WHO-5 Wellbeing Index, and SF-36 QOL score. Results. PPS correlated to CSS (r = 0.20, p < 0.001), MDI (r = 0.14, p = 0.02), SF-36 mental component summary score (MCS) (r = − 0.10, p = 0.049), SF-36 physical component summary score (PCS) (r = − 0.17, p = 0.001), and self-perceived stress level (r = 0.15, p = 0.006). CSS correlated similarly (r = 0.5–0.7, all p < 0.001). Comparing subjects within the lowest vs. highest tertiles of PPS and CSS, the mean MDI score was 4 vs. 15, WHO-5 was 77 vs. 53, SF-36 PCS was 53 vs. 43, and SF-36 MCS was 58 vs. 46; all p < 0.001. Conclusions. PPS reflected to a modest degree markers of chronic stress in IHD. PPS and CSS together might be useful as easy-to use tools for evaluating these markers in IHD patients.

Long-term L-Triiodothyronine (T3) treatment in stable systolic heart failure patients: a randomised, double-blind, cross-over, placebo-controlled intervention study

Chronic heart failure (HF) is characterized by reduced serum T3 levels and increased activity of the T3 degrading enzyme deiodinase D3. This may result in an intracellular composition of the cardiomyocyte mimicking that of hypothyroidism. Short‐term T3‐administration to systolic HF patients might be beneficial.

Diabetes and ischemic heart disease: double jeopardy with regard to depressive mood and reduced quality of life

The aim of this study was to test i) whether patients having diabetes and ischemic heart disease (IHD), i.e., patients suffering from two chronic diseases, demonstrate a higher degree of chronic stress when compared with patients suffering from IHD alone, and ii) whether suffering from the two chronic diseases results in an elevation in specific elements of the chronic stress concept. A total of 361 participants with IHD were included, of whom 47 suffered from concomitant diabetes. Stress was measured by pressure pain sensitivity (PPS) and by the following questionnaires: the Major Depression Inventory (MDI), the SF-36 Quality of Life questionnaire (SF-36 QOL), the WHO-5 Well-being Index, and the clinical stress signs (CSSs) scale. Participants with diabetes and IHD had a higher MDI score, a lower SF-36 physical component summary score, and a lower score of several sub-measurements of the SF-36 mental component score when compared with patients with IHD without diabetes. No significant differences were observed regarding stress measured by the PPS measure, the WHO-5 Well-being Index, or the number of CSSs. In conclusion, the combination of diabetes and IHD seems to be associated with increased depressive symptoms, lower overall physical QOL, and reduced mental QOL on several sub-elements of the questionnaire. This should be recognized in the management of patients with double diagnoses.

Galectin-3 and fibulin-1 in systolic heart failure - relation to glucose metabolism and left ventricular contractile reserve

BackgroundHeart failure (HF) patients with diabetes (DM) have an adverse prognosis and reduced functional capacity, which could be associated with cardiac fibrosis, increased chamber stiffness and reduced left ventricular (LV) contractile reserve. Galectin-3 (Gal-3) and fibulin-1 are circulating biomarkers potentially reflecting cardiac fibrosis. We hypothesize that plasma levels of Gal-3 and fibulin-1 are elevated in HF patients with DM and are associated with reduced LV contractile reserve in these patients.MethodsA total of 155 patients with HF with reduced ejection fraction underwent a low-dose dobutamine echocardiography and blood sampling for biomarker measurements. Patients were classified according to history of DM and an oral glucose tolerance test (OGTT) as: normal glucose tolerance (NGT) (n = 70), impaired glucose tolerance (IGT) (n = 25) and DM (n = 60).ResultsGalectin-3 levels were elevated in DM patients as compared to non-diabetic patients (P = 0.02), while higher fibulin-1 levels were observed in HF patients with IGF and DM (P = 0.07). Reduced LV contractile reserve was associated with increasing Gal-3 levels (β = −0.19, P = 0.03) although, this association was attenuated after adjustment for estimated glomerular filtration rate (P = 0.66). Fibulin-1 was not associated with LV contractile reserve (P = 0.71).ConclusionsGalectin-3 and fibulin-1 levels were elevated in HF patients with impaired glucose metabolism. However, reduced LV contractile reserve among HF patients with DM does not to have an independent impact on plasma Gal-3 and fibulin-1 levels.

Pressure pain sensitivity

Introduction: the relationship between psychiatric symptoms and cancer has sparked a lot of interest in the scientific community. The available literature is mostly on the impact of cancer diagnosis. However, little is known about the patients psychological status before that. Studies in this area show that cancer patients often present depressive symptoms before the diagnosis of neoplastic disease, probably due to cytokine production by the tumors. Low concentrations of cytokines would be sufficient to change the patient’s emotional state. Case description: to alert clinicians to the possibility that psychiatric symptoms may be a signal of underlying cancer disease, especially in patients above 50 years without psychiatric history, we present the following case. A woman of 53 years, followed in the Portuguese Institute of Oncology of Coimbra since October 2009 for mixed adenocarcinoma of the lung (stage IB). Approximately 1 month later, in November 2009, she was referred to psychiatric consultation because of depressive symptoms and complains since 1 year before. She also reported history of thyroid goiter, emphysema, and depressive episode occurred 10 years begore. Since the cancer was diagnosed, depression has shown a fluctuating evolution. Various therapeutic settings were made, being currently medicated with venlafaxine 225 mg, trazodone 150 mg AC i.d., and lorazepam 2.5 mg i.d.. Comment: the emergence of psychiatric symptoms, especially in patients above 50 years, should alert the physician to the presence of a possible hidden cancer, especially in the case of patients without psychiatric history.Introduction: Stress has been hypothesized to be involved in obesity development. Apart from a direct pathway through cortisol, stress may indirectly facilitate obesity by influencing other lifestyle factors: stressed persons may consume more comfort foods, may have a more sedentary behaviour and may suffer from sleep problems. Methods: In 326 Belgian children (5-12y) of the ChiBS study, the longitudinal relation between stress and body composition was examined over two years. Stress was measured by salivary cortisol (4 samples/day, 2 days) and questionnaires concerning negative life events, problem behaviour and emotions. For body composition, BMI, waist-to-height and fat% estimation by air displacement were used. Furthermore, physical activity, screentime, food consumption, eating behaviour and sleep duration were measured as lifestyle factors. Cross-lagged analyses with Mplus and moderation by cortisol and lifestyle factors were tested. Results: Children with higher stress scores had a less healthy lifestyle. They had an unhealthier diet especially due to more sweet food consumption, performed more emotional eating, were less active and slept less. Two years later, these stressed children maintained the same unhealthy life style except that they were more physical active instead of less. Salivary cortisol and lifestyle were moderators in the stress-obesity relation: stressed children had also more overweight or a higher fat percentage, but only when they had an unhealthier lifestyle or higher cortisol. Discussion: These results confirm that stress can deteriorate lifestyle and cortisol homeostasis already in childhood and that these changes make them vulnerable to overweight. Consequently, obesity prevention should target both lifestyle and stress.

Pressure pain sensitivity: a new method of stress 2 measurement in patients with ischemic heart disease

Introduction: the relationship between psychiatric symptoms and cancer has sparked a lot of interest in the scientific community. The available literature is mostly on the impact of cancer diagnosis. However, little is known about the patients psychological status before that. Studies in this area show that cancer patients often present depressive symptoms before the diagnosis of neoplastic disease, probably due to cytokine production by the tumors. Low concentrations of cytokines would be sufficient to change the patient’s emotional state. Case description: to alert clinicians to the possibility that psychiatric symptoms may be a signal of underlying cancer disease, especially in patients above 50 years without psychiatric history, we present the following case. A woman of 53 years, followed in the Portuguese Institute of Oncology of Coimbra since October 2009 for mixed adenocarcinoma of the lung (stage IB). Approximately 1 month later, in November 2009, she was referred to psychiatric consultation because of depressive symptoms and complains since 1 year before. She also reported history of thyroid goiter, emphysema, and depressive episode occurred 10 years begore. Since the cancer was diagnosed, depression has shown a fluctuating evolution. Various therapeutic settings were made, being currently medicated with venlafaxine 225 mg, trazodone 150 mg AC i.d., and lorazepam 2.5 mg i.d.. Comment: the emergence of psychiatric symptoms, especially in patients above 50 years, should alert the physician to the presence of a possible hidden cancer, especially in the case of patients without psychiatric history.Introduction: Stress has been hypothesized to be involved in obesity development. Apart from a direct pathway through cortisol, stress may indirectly facilitate obesity by influencing other lifestyle factors: stressed persons may consume more comfort foods, may have a more sedentary behaviour and may suffer from sleep problems. Methods: In 326 Belgian children (5-12y) of the ChiBS study, the longitudinal relation between stress and body composition was examined over two years. Stress was measured by salivary cortisol (4 samples/day, 2 days) and questionnaires concerning negative life events, problem behaviour and emotions. For body composition, BMI, waist-to-height and fat% estimation by air displacement were used. Furthermore, physical activity, screentime, food consumption, eating behaviour and sleep duration were measured as lifestyle factors. Cross-lagged analyses with Mplus and moderation by cortisol and lifestyle factors were tested. Results: Children with higher stress scores had a less healthy lifestyle. They had an unhealthier diet especially due to more sweet food consumption, performed more emotional eating, were less active and slept less. Two years later, these stressed children maintained the same unhealthy life style except that they were more physical active instead of less. Salivary cortisol and lifestyle were moderators in the stress-obesity relation: stressed children had also more overweight or a higher fat percentage, but only when they had an unhealthier lifestyle or higher cortisol. Discussion: These results confirm that stress can deteriorate lifestyle and cortisol homeostasis already in childhood and that these changes make them vulnerable to overweight. Consequently, obesity prevention should target both lifestyle and stress.