Wolfram Doehner - Academia.edu (original) (raw)

Papers by Wolfram Doehner

Research paper thumbnail of Präoperative Evaluierung vor nicht-kardiochirurgischen Eingriffen

DMW - Deutsche Medizinische Wochenschrift, 2015

An update of the ESC/ESA Guidelines on cardiovascular assessment and management in patients with ... more An update of the ESC/ESA Guidelines on cardiovascular assessment and management in patients with on-cardiac surgery was published in 2014.In general the role of thorough clinical evaluation has been strengthened and the routing use of additional technical and invasive diagnostics has been restricted. Medical management has largely been downgraded to class II recommendations and the use of beta blockers has been strongly restricted. New recommendations on dual anti-platelet therapy and NOAC's have been included.

Research paper thumbnail of Nutrition, metabolism, and the complex pathophysiology of cachexia in chronic heart failure

Chronicheartfailureisacomplexcatabolic statethatcarriesadevastatingprognosis.Thetransitionfromsta... more Chronicheartfailureisacomplexcatabolic statethatcarriesadevastatingprognosis.Thetransitionfromstablediseasetocardiaccachexiais not well understood. Mechanisms that maintain the wasting process involve neurohormones and pro-inflammatory cytokines, which contribute to an imbalance in anabolic and catabolic pathways. A decrease in food intake alone rarely triggers the development of a wasting process, but dietary deficiencies in micronutrients and macronutrients contribute to the progression of the disease. Malabsorption from the gut as a

Research paper thumbnail of 245 Prognostic utility of growth-differentiation factor-15 in patients with chronic heart failure

European Journal of Heart Failure Supplements, 2007

Introduction: Chronic heart failure (CHF) trials have frequently reported that 6-min walk test (6... more Introduction: Chronic heart failure (CHF) trials have frequently reported that 6-min walk test (6-MWT) distance and NT-proBNP status are important prognostic indicators. We wished to provide a risk profile, adjusted by sex and beta-blocker (BBL) usage, from two large cohorts of patients in Germany and the UK. Methods: We included 1100 patients with systolic CHF from the University Hospital Heidelberg, Germany in a derivation cohort and validated these against 676 patients with similar aetiology from the Department of Academic Cardiology, University of Hull, UK. Serial log-rank analysis identified and validated the individual cut-off for optimal risk stratification for all-cause mortality according to sex and BBL status. Patients at increased risk according to 6-MWT distance were also stratified by NT-proBNP status. Results: In both cohorts, 6-MWT was an independent predictor of mortality. Patients not prescribed BBL with a 6-MWT distance of ≤430m (males) and ≤360m (females) had a higher all-cause mortality risk. For patients prescribed BBL, risk cut-points were adjusted accordingly: ≤370m (males), and ≤330m (females). Patients with an adverse 6-MWT had a risk profile based on NT-proBNP status of ≤650ng/l (males) and ≤710ng/l (females). Three clinical risk groups were formed with a 1-year mortality of 3.6%, 9.6% and 24.4%, respectively (P<0.0001).

Research paper thumbnail of Inflammatory biomarkers in heart failure revisited: much more than innocent bystanders

Heart failure clinics, 2009

Chronic heart failure is viewed as a state of chronic inflammation. Many inflammatory markers hav... more Chronic heart failure is viewed as a state of chronic inflammation. Many inflammatory markers have been shown to be up-regulated in patients who have this condition, but the markers' roles in clinical decision making have not yet been fully elucidated. A panel of biomarkers is likely to have a strong impact on patient management. Inflammatory biomarkers are interesting candidates that could answer specific clinical questions on their own or complement a multi-marker approach. This article provides a broad overview of several inflammatory biomarkers, including the pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-6, IL-1, IL-18, and the soluble receptors TNFR-1, TNFR-2, IL-6R, and gp130. In addition to these acute phase reactants, several adhesion molecules, and lipopolysaccharide-signaling pathways are discussed.

Research paper thumbnail of Meeting report from the 74th annual scientific sessions of the American Heart Association (AHA). Anaheim, CA, USA, November 11-14, 2001

Heart failure monitor, 2002

Research paper thumbnail of Impaired Insulin Sensitivity as an Independent Risk Factor for Mortality in Patients With Stable Chronic Heart Failure

The aim of this study was to determine the significance of insulin resistance as an independent r... more The aim of this study was to determine the significance of insulin resistance as an independent risk factor for impaired prognosis in patients with chronic heart failure (CHF). BACKGROUND In CHF, impaired insulin sensitivity (S I ) indicates abnormal energy metabolism and is related to decreased exercise capacity and muscle fatigue. The relationship between insulin resistance (i.e., low S I ) and survival in patients with CHF has not been established.

Research paper thumbnail of Inverse relation of body weight and weight change with mortality and morbidity in patients with type 2 diabetes and cardiovascular co-morbidity: An analysis of the PROactive study population

Context: Although weight reduction is a recommended goal in type 2 diabetes mellitus (T2DM), weig... more Context: Although weight reduction is a recommended goal in type 2 diabetes mellitus (T2DM), weight loss is linked to impaired survival in patients with some chronic cardiovascular diseases. Objective: To assess the association of weight and weight change with mortality and non-fatal cardiovascular outcomes (hospitalisation, myocardial infarction and stroke) in T2DM patients with cardiovascular co-morbidity and the effect of pioglitazone-induced weight change on mortality. Setting and participants: We assessed in a post hoc analysis body weight and weight change in relation to outcome in 5202 patients from the PROactive trial population who had T2DM and evidence of pre-existing cardiovascular disease. Patients were randomized to treatment with pioglitazone or placebo in addition to their concomitant glucoselowering and cardiovascular medication. Mean follow up was 34.5 months. Main outcome measure: The impact of body weight and body weight change on all-cause mortality, cardiovascular mortality, on non-fatal cardiovascular events and on hospitalisation. Results: The lowest mortality was seen in patients with BMI 30-35 kg/m 2 at baseline. In comparison to this (reference group), patients in the placebo group with BMI b 22 kg/m 2 (Hazard Ratio (95% confidence intervals) 2.96 [1.27 to 6.86]; P = 0.012) and BMI 22 to 25 kg/m 2 (HR 1.88 [1.11 to 3.21]; P = 0.019) had a higher all-cause mortality. Weight loss was associated with increased total mortality (HR per 1% body weight: 1.13 [1.11 to 1.16]; P b 0.0001), with increased cardiovascular mortality, all-cause hospitalisation and the composite of death, myocardial infarction and stroke. Weight loss of ≥7.5% body weight (seen in 18.3% of patients) was the strongest cut-point to predict impaired survival (multivariable adjusted HR 4.42 [3.30 to 5.94]. Weight gain was not associated with increased mortality. Weight gain in patients treated with pioglitazone (mean+ 4.0± 6.1 kg) predicted a better prognosis (HR per 1% weight gain: 0.96 [0.92 to 1.00] P = 0.037) compared to patients without weight gain. Conclusion: Among patients with T2DM and cardiovascular co-morbidity, overweight and obese patients had a lower mortality compared to patients with normal weight. Weight loss but not weight gain was associated with increased mortality and morbidity. There may be an "obesity paradox" in patients with type 2 diabetes and cardiovascular risk. The original PROactive trial is registered as an International Standard Randomized Controlled Trial (Number ISRCTN NCT00174993).

Research paper thumbnail of Effect of exogenous intravenous administrations of GLP-1 and/or GIP on circulating pro-atrial natriuretic peptide in subjects with different stages of glucose tolerance

Research paper thumbnail of Cardiovascular function and predictors of exercise capacity in patients with colorectal cancer

Journal of the American College of Cardiology, Jan 30, 2014

Patients with colorectal cancer (CRC) often present with dyspnea and fatigue. These are also freq... more Patients with colorectal cancer (CRC) often present with dyspnea and fatigue. These are also frequent symptoms in patients with chronic heart failure (CHF). We hypothesized that similar patterns of cardiovascular perturbations are present in CRC and CHF. We prospectively studied 50 patients with CRC, 51 patients with CHF, and 51 control subjects. The CRC group was divided into 2 subgroups: patients who underwent chemotherapy (n = 26) and chemotherapy-naive patients (n = 24). We assessed exercise capacity (spiroergometry), cardiac function (echocardiography), heart rate variability (Holter electrocardiography), body composition (dual-energy x-ray absorptiometry), and blood parameters. Compared with the control arm, the left ventricular ejection fraction (CRC group 59.4%; control group 62.5%) and exercise performance as assessed by peak oxygen consumption (peak VO2) (CRC group 21.8 ml/kg/min; control group 28.0 ml/kg/min) were significantly reduced in CRC patients (both p < 0.02). ...

Research paper thumbnail of Wasting as an independent predictor of mortality in patients with cystic fibrosis

Thorax, 2001

BACKGROUNDCystic fibrosis (CF) is the most common life threatening autosomal recessive disorder i... more BACKGROUNDCystic fibrosis (CF) is the most common life threatening autosomal recessive disorder in the white population. Wasting has long been recognised as a poor prognostic marker in CF. Whether it predicts survival independently of lung function and arterial blood gas tensions has not previously been reported.METHODS584 patients with CF (261 women) of mean (SD) age 21 (7) years were studied

Research paper thumbnail of Intestinal Blood Flow in Patients With Chronic Heart Failure

Journal of the American College of Cardiology, 2014

BACKGROUND Blood flow in the intestinal arteries is reduced in patients with stable heart failure... more BACKGROUND Blood flow in the intestinal arteries is reduced in patients with stable heart failure (HF) and relates to gastrointestinal (GI) symptoms and cardiac cachexia.

Research paper thumbnail of Serum phosphorus level is related to degree of clinical response to up-titration of heart failure pharmacotherapy

International Journal of Cardiology, 2014

Serum phosphorus abnormalities may pose a risk on the cardiovascular system. In heart failure (HF... more Serum phosphorus abnormalities may pose a risk on the cardiovascular system. In heart failure (HF) phosphorus homeostatic mechanisms are altered and may be modified by modern HF therapy. The impact of therapy optimization on phosphorus abnormalities and related outcome remains unknown. In 722 patients with HF subjected to treatment up-titration we analyzed the prevalence of serum phosphorus abnormalities and their relation to HF severity on top of optimal treatment, and we assessed adjusted risk of phosphorus abnormalities at different stages of HF. We analyzed predictors of hypo-and hyperphosphatemia and relation to prognosis. Hypophosphatemia was associated with better response to therapy, was more prevalent in milder HF, and the association was independent of age, sex, BMI, etiology of HF, kidney function and the use of diuretics. Hypophosphatemic patients lost more phosphorus into urine. They had also less catabolic profile. Patients with hyperphosphatemia on top of optimal therapy responded worse to treatment. Hyperphosphatemia was more prevalent in advanced HF, but the effect was attenuated after adjustment for potential confounders. Clinical and biochemical profiles of hyperphosphatemics suggested domination of catabolism. Neither hypophosphatemia nor hyperphosphatemia modifies the outcome Serum phosphorus abnormalities are related to HF severity on top of optimal therapy. Hypophosphatemia occurring on HF up-titration therapy likely has a multifactorial pathophysiology comprising of urinary phosphorus wasting and refeeding effects. Hyperphosphatemia is linked to the catabolic profile but the effect of renal impairment can't be ruled out. The prognostic impact of serum phosphorus abnormalities remain to be established.

Research paper thumbnail of The impact of body weight on mortality after stroke: the controversy continues

Research paper thumbnail of Bone marrow iron depletion is common in patients with coronary artery disease

International Journal of Cardiology, 2014

Iron deficiency (ID) may be an important, treatable co-morbidity complicating cardiovascular dise... more Iron deficiency (ID) may be an important, treatable co-morbidity complicating cardiovascular diseases, but considerable uncertainty exists about the diagnostic accuracy of blood tests. Accordingly, we investigated the relationship between blood tests for ID and iron stores in bone marrow aspirates, the diagnostic gold-standard for ID, in patients with stable coronary artery disease (CAD). Bone marrow aspirates were obtained from 65 patients with stable CAD undergoing cardiac surgery and 10 healthy controls. ID was defined as depleted extracellular iron stores (0-1 grade according to Gale scale) accompanied by ≤10% of erythroblasts containing iron. Bone marrow ID was found in 31 (48%) patients with CAD but in none of the controls (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01). Amongst patients with CAD, ID was present in 10 of 16 (63%) with and 21 of 49 (43%) without anaemia (p=0.17). The clinical profiles of patients with and without ID were similar. Of circulating biomarkers of ID, serum soluble transferrin receptor had the strongest association with bone marrow ID (area under curve: 0.876±0.048, 95% confidence interval: 0.762-0.948, for cut-off of ≥1.32mg/L-sensitivity: 67%, specificity: 97%). Almost half of patients with stable CAD have profound bone marrow iron depletion that can be accurately assessed non-invasively using serum soluble transferrin receptor.

Research paper thumbnail of Neurohormonal activation and inflammation in chronic cardiopulmonary disease: a brief systematic review

Wiener klinische Wochenschrift, 2009

Chronic cardiopulmonary disease typically induces and maintains (over)activation of several phylo... more Chronic cardiopulmonary disease typically induces and maintains (over)activation of several phylogenetically old adaptational and defensive mechanisms. Activation was usually needed for a limited period during acute danger or injury. In chronic disease conditions, however, those mechanisms are kept activated for longer periods. Eventually, irreversible damage is done and this contributes to impaired function and worse prognosis in a variety of chronic disease. Landmark trials in chronic heart failure have provided robust evidence for prognostic benefit for neurohormonal antagonists. Retrospective and epidemiological data for their beneficial effect in chronic obstructive pulmonary disease begin to accumulate and new fields (e.g. cancer and stroke) could be pending in the future.

Research paper thumbnail of Neurological and endocrinological disorders: orphans in chronic obstructive pulmonary disease

Respiratory Medicine, 2011

Patients with chronic obstructive pulmonary disease (COPD) are often characterised by a range of ... more Patients with chronic obstructive pulmonary disease (COPD) are often characterised by a range of characteristic co-morbidities that interfere with their pulmonary disease. In addition to a mere association with co-morbidities, a complex pathophysiological interaction and mutual augmentation occurs between COPD and its co-morbidities that may result in disease progression and increased morbidity and mortality. An interdisciplinary approach is required both for diagnosis and treatment to target co-morbidities early in the course of the disease. This review summarizes the current knowledge of the interaction with cerebrovascular disease and endocrinological co-morbidities in COPD patients. There is growing evidence that COPD is an independent risk factor for ischemic stroke, increasing the risk about twofold. Stroke risk in COPD patients increases with the severity of the disease as measured by the degree of airflow limitation. The presence of cardiovascular risk factors is of particular importance for stroke prevention in COPD patients. Endocrinological co-morbidities are also important and many are associated with increased cardiovascular risk. Impaired glucose metabolism ranges from insulin resistance to overt diabetes mellitus, which is a frequent finding and is associated with worse outcome.

Research paper thumbnail of Identification of Chronic Heart Failure Patients with a High 12-Month Mortality Risk Using Biomarkers Including Plasma C-Terminal Pro-Endothelin-1

PLoS ONE, 2011

Objectives: We hypothesised that assessment of plasma C-terminal pro-endothelin-1 (CT-proET-1), a... more Objectives: We hypothesised that assessment of plasma C-terminal pro-endothelin-1 (CT-proET-1), a stable endothelin-1 precursor fragment, is of prognostic value in patients with chronic heart failure (CHF), beyond other prognosticators, including N-terminal pro-B-type natriuretic peptide (NT-proBNP).

Research paper thumbnail of Rosiglitazone reduces body wasting and improves survival in a rat model of cancer cachexia

Nutrition, 2013

1 2 Objective 3 Rosiglitazone improves insulin sensitivity and promotes weight gain in patients w... more 1 2 Objective 3 Rosiglitazone improves insulin sensitivity and promotes weight gain in patients with 4

Research paper thumbnail of Altered Intestinal Function in Patients With Chronic Heart Failure

Journal of the American College of Cardiology, 2007

We evaluated morphology and function of the gut in patients with chronic heart failure (CHF).

Research paper thumbnail of Impaired Insulin Sensitivity as an Independent Risk Factor for Mortality in Patients With Stable Chronic Heart Failure

Journal of the American College of Cardiology, 2005

The aim of this study was to determine the significance of insulin resistance as an independent r... more The aim of this study was to determine the significance of insulin resistance as an independent risk factor for impaired prognosis in patients with chronic heart failure (CHF). BACKGROUND In CHF, impaired insulin sensitivity (S I ) indicates abnormal energy metabolism and is related to decreased exercise capacity and muscle fatigue. The relationship between insulin resistance (i.e., low S I ) and survival in patients with CHF has not been established.

Research paper thumbnail of Präoperative Evaluierung vor nicht-kardiochirurgischen Eingriffen

DMW - Deutsche Medizinische Wochenschrift, 2015

An update of the ESC/ESA Guidelines on cardiovascular assessment and management in patients with ... more An update of the ESC/ESA Guidelines on cardiovascular assessment and management in patients with on-cardiac surgery was published in 2014.In general the role of thorough clinical evaluation has been strengthened and the routing use of additional technical and invasive diagnostics has been restricted. Medical management has largely been downgraded to class II recommendations and the use of beta blockers has been strongly restricted. New recommendations on dual anti-platelet therapy and NOAC&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s have been included.

Research paper thumbnail of Nutrition, metabolism, and the complex pathophysiology of cachexia in chronic heart failure

Chronicheartfailureisacomplexcatabolic statethatcarriesadevastatingprognosis.Thetransitionfromsta... more Chronicheartfailureisacomplexcatabolic statethatcarriesadevastatingprognosis.Thetransitionfromstablediseasetocardiaccachexiais not well understood. Mechanisms that maintain the wasting process involve neurohormones and pro-inflammatory cytokines, which contribute to an imbalance in anabolic and catabolic pathways. A decrease in food intake alone rarely triggers the development of a wasting process, but dietary deficiencies in micronutrients and macronutrients contribute to the progression of the disease. Malabsorption from the gut as a

Research paper thumbnail of 245 Prognostic utility of growth-differentiation factor-15 in patients with chronic heart failure

European Journal of Heart Failure Supplements, 2007

Introduction: Chronic heart failure (CHF) trials have frequently reported that 6-min walk test (6... more Introduction: Chronic heart failure (CHF) trials have frequently reported that 6-min walk test (6-MWT) distance and NT-proBNP status are important prognostic indicators. We wished to provide a risk profile, adjusted by sex and beta-blocker (BBL) usage, from two large cohorts of patients in Germany and the UK. Methods: We included 1100 patients with systolic CHF from the University Hospital Heidelberg, Germany in a derivation cohort and validated these against 676 patients with similar aetiology from the Department of Academic Cardiology, University of Hull, UK. Serial log-rank analysis identified and validated the individual cut-off for optimal risk stratification for all-cause mortality according to sex and BBL status. Patients at increased risk according to 6-MWT distance were also stratified by NT-proBNP status. Results: In both cohorts, 6-MWT was an independent predictor of mortality. Patients not prescribed BBL with a 6-MWT distance of ≤430m (males) and ≤360m (females) had a higher all-cause mortality risk. For patients prescribed BBL, risk cut-points were adjusted accordingly: ≤370m (males), and ≤330m (females). Patients with an adverse 6-MWT had a risk profile based on NT-proBNP status of ≤650ng/l (males) and ≤710ng/l (females). Three clinical risk groups were formed with a 1-year mortality of 3.6%, 9.6% and 24.4%, respectively (P<0.0001).

Research paper thumbnail of Inflammatory biomarkers in heart failure revisited: much more than innocent bystanders

Heart failure clinics, 2009

Chronic heart failure is viewed as a state of chronic inflammation. Many inflammatory markers hav... more Chronic heart failure is viewed as a state of chronic inflammation. Many inflammatory markers have been shown to be up-regulated in patients who have this condition, but the markers' roles in clinical decision making have not yet been fully elucidated. A panel of biomarkers is likely to have a strong impact on patient management. Inflammatory biomarkers are interesting candidates that could answer specific clinical questions on their own or complement a multi-marker approach. This article provides a broad overview of several inflammatory biomarkers, including the pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-6, IL-1, IL-18, and the soluble receptors TNFR-1, TNFR-2, IL-6R, and gp130. In addition to these acute phase reactants, several adhesion molecules, and lipopolysaccharide-signaling pathways are discussed.

Research paper thumbnail of Meeting report from the 74th annual scientific sessions of the American Heart Association (AHA). Anaheim, CA, USA, November 11-14, 2001

Heart failure monitor, 2002

Research paper thumbnail of Impaired Insulin Sensitivity as an Independent Risk Factor for Mortality in Patients With Stable Chronic Heart Failure

The aim of this study was to determine the significance of insulin resistance as an independent r... more The aim of this study was to determine the significance of insulin resistance as an independent risk factor for impaired prognosis in patients with chronic heart failure (CHF). BACKGROUND In CHF, impaired insulin sensitivity (S I ) indicates abnormal energy metabolism and is related to decreased exercise capacity and muscle fatigue. The relationship between insulin resistance (i.e., low S I ) and survival in patients with CHF has not been established.

Research paper thumbnail of Inverse relation of body weight and weight change with mortality and morbidity in patients with type 2 diabetes and cardiovascular co-morbidity: An analysis of the PROactive study population

Context: Although weight reduction is a recommended goal in type 2 diabetes mellitus (T2DM), weig... more Context: Although weight reduction is a recommended goal in type 2 diabetes mellitus (T2DM), weight loss is linked to impaired survival in patients with some chronic cardiovascular diseases. Objective: To assess the association of weight and weight change with mortality and non-fatal cardiovascular outcomes (hospitalisation, myocardial infarction and stroke) in T2DM patients with cardiovascular co-morbidity and the effect of pioglitazone-induced weight change on mortality. Setting and participants: We assessed in a post hoc analysis body weight and weight change in relation to outcome in 5202 patients from the PROactive trial population who had T2DM and evidence of pre-existing cardiovascular disease. Patients were randomized to treatment with pioglitazone or placebo in addition to their concomitant glucoselowering and cardiovascular medication. Mean follow up was 34.5 months. Main outcome measure: The impact of body weight and body weight change on all-cause mortality, cardiovascular mortality, on non-fatal cardiovascular events and on hospitalisation. Results: The lowest mortality was seen in patients with BMI 30-35 kg/m 2 at baseline. In comparison to this (reference group), patients in the placebo group with BMI b 22 kg/m 2 (Hazard Ratio (95% confidence intervals) 2.96 [1.27 to 6.86]; P = 0.012) and BMI 22 to 25 kg/m 2 (HR 1.88 [1.11 to 3.21]; P = 0.019) had a higher all-cause mortality. Weight loss was associated with increased total mortality (HR per 1% body weight: 1.13 [1.11 to 1.16]; P b 0.0001), with increased cardiovascular mortality, all-cause hospitalisation and the composite of death, myocardial infarction and stroke. Weight loss of ≥7.5% body weight (seen in 18.3% of patients) was the strongest cut-point to predict impaired survival (multivariable adjusted HR 4.42 [3.30 to 5.94]. Weight gain was not associated with increased mortality. Weight gain in patients treated with pioglitazone (mean+ 4.0± 6.1 kg) predicted a better prognosis (HR per 1% weight gain: 0.96 [0.92 to 1.00] P = 0.037) compared to patients without weight gain. Conclusion: Among patients with T2DM and cardiovascular co-morbidity, overweight and obese patients had a lower mortality compared to patients with normal weight. Weight loss but not weight gain was associated with increased mortality and morbidity. There may be an "obesity paradox" in patients with type 2 diabetes and cardiovascular risk. The original PROactive trial is registered as an International Standard Randomized Controlled Trial (Number ISRCTN NCT00174993).

Research paper thumbnail of Effect of exogenous intravenous administrations of GLP-1 and/or GIP on circulating pro-atrial natriuretic peptide in subjects with different stages of glucose tolerance

Research paper thumbnail of Cardiovascular function and predictors of exercise capacity in patients with colorectal cancer

Journal of the American College of Cardiology, Jan 30, 2014

Patients with colorectal cancer (CRC) often present with dyspnea and fatigue. These are also freq... more Patients with colorectal cancer (CRC) often present with dyspnea and fatigue. These are also frequent symptoms in patients with chronic heart failure (CHF). We hypothesized that similar patterns of cardiovascular perturbations are present in CRC and CHF. We prospectively studied 50 patients with CRC, 51 patients with CHF, and 51 control subjects. The CRC group was divided into 2 subgroups: patients who underwent chemotherapy (n = 26) and chemotherapy-naive patients (n = 24). We assessed exercise capacity (spiroergometry), cardiac function (echocardiography), heart rate variability (Holter electrocardiography), body composition (dual-energy x-ray absorptiometry), and blood parameters. Compared with the control arm, the left ventricular ejection fraction (CRC group 59.4%; control group 62.5%) and exercise performance as assessed by peak oxygen consumption (peak VO2) (CRC group 21.8 ml/kg/min; control group 28.0 ml/kg/min) were significantly reduced in CRC patients (both p < 0.02). ...

Research paper thumbnail of Wasting as an independent predictor of mortality in patients with cystic fibrosis

Thorax, 2001

BACKGROUNDCystic fibrosis (CF) is the most common life threatening autosomal recessive disorder i... more BACKGROUNDCystic fibrosis (CF) is the most common life threatening autosomal recessive disorder in the white population. Wasting has long been recognised as a poor prognostic marker in CF. Whether it predicts survival independently of lung function and arterial blood gas tensions has not previously been reported.METHODS584 patients with CF (261 women) of mean (SD) age 21 (7) years were studied

Research paper thumbnail of Intestinal Blood Flow in Patients With Chronic Heart Failure

Journal of the American College of Cardiology, 2014

BACKGROUND Blood flow in the intestinal arteries is reduced in patients with stable heart failure... more BACKGROUND Blood flow in the intestinal arteries is reduced in patients with stable heart failure (HF) and relates to gastrointestinal (GI) symptoms and cardiac cachexia.

Research paper thumbnail of Serum phosphorus level is related to degree of clinical response to up-titration of heart failure pharmacotherapy

International Journal of Cardiology, 2014

Serum phosphorus abnormalities may pose a risk on the cardiovascular system. In heart failure (HF... more Serum phosphorus abnormalities may pose a risk on the cardiovascular system. In heart failure (HF) phosphorus homeostatic mechanisms are altered and may be modified by modern HF therapy. The impact of therapy optimization on phosphorus abnormalities and related outcome remains unknown. In 722 patients with HF subjected to treatment up-titration we analyzed the prevalence of serum phosphorus abnormalities and their relation to HF severity on top of optimal treatment, and we assessed adjusted risk of phosphorus abnormalities at different stages of HF. We analyzed predictors of hypo-and hyperphosphatemia and relation to prognosis. Hypophosphatemia was associated with better response to therapy, was more prevalent in milder HF, and the association was independent of age, sex, BMI, etiology of HF, kidney function and the use of diuretics. Hypophosphatemic patients lost more phosphorus into urine. They had also less catabolic profile. Patients with hyperphosphatemia on top of optimal therapy responded worse to treatment. Hyperphosphatemia was more prevalent in advanced HF, but the effect was attenuated after adjustment for potential confounders. Clinical and biochemical profiles of hyperphosphatemics suggested domination of catabolism. Neither hypophosphatemia nor hyperphosphatemia modifies the outcome Serum phosphorus abnormalities are related to HF severity on top of optimal therapy. Hypophosphatemia occurring on HF up-titration therapy likely has a multifactorial pathophysiology comprising of urinary phosphorus wasting and refeeding effects. Hyperphosphatemia is linked to the catabolic profile but the effect of renal impairment can't be ruled out. The prognostic impact of serum phosphorus abnormalities remain to be established.

Research paper thumbnail of The impact of body weight on mortality after stroke: the controversy continues

Research paper thumbnail of Bone marrow iron depletion is common in patients with coronary artery disease

International Journal of Cardiology, 2014

Iron deficiency (ID) may be an important, treatable co-morbidity complicating cardiovascular dise... more Iron deficiency (ID) may be an important, treatable co-morbidity complicating cardiovascular diseases, but considerable uncertainty exists about the diagnostic accuracy of blood tests. Accordingly, we investigated the relationship between blood tests for ID and iron stores in bone marrow aspirates, the diagnostic gold-standard for ID, in patients with stable coronary artery disease (CAD). Bone marrow aspirates were obtained from 65 patients with stable CAD undergoing cardiac surgery and 10 healthy controls. ID was defined as depleted extracellular iron stores (0-1 grade according to Gale scale) accompanied by ≤10% of erythroblasts containing iron. Bone marrow ID was found in 31 (48%) patients with CAD but in none of the controls (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01). Amongst patients with CAD, ID was present in 10 of 16 (63%) with and 21 of 49 (43%) without anaemia (p=0.17). The clinical profiles of patients with and without ID were similar. Of circulating biomarkers of ID, serum soluble transferrin receptor had the strongest association with bone marrow ID (area under curve: 0.876±0.048, 95% confidence interval: 0.762-0.948, for cut-off of ≥1.32mg/L-sensitivity: 67%, specificity: 97%). Almost half of patients with stable CAD have profound bone marrow iron depletion that can be accurately assessed non-invasively using serum soluble transferrin receptor.

Research paper thumbnail of Neurohormonal activation and inflammation in chronic cardiopulmonary disease: a brief systematic review

Wiener klinische Wochenschrift, 2009

Chronic cardiopulmonary disease typically induces and maintains (over)activation of several phylo... more Chronic cardiopulmonary disease typically induces and maintains (over)activation of several phylogenetically old adaptational and defensive mechanisms. Activation was usually needed for a limited period during acute danger or injury. In chronic disease conditions, however, those mechanisms are kept activated for longer periods. Eventually, irreversible damage is done and this contributes to impaired function and worse prognosis in a variety of chronic disease. Landmark trials in chronic heart failure have provided robust evidence for prognostic benefit for neurohormonal antagonists. Retrospective and epidemiological data for their beneficial effect in chronic obstructive pulmonary disease begin to accumulate and new fields (e.g. cancer and stroke) could be pending in the future.

Research paper thumbnail of Neurological and endocrinological disorders: orphans in chronic obstructive pulmonary disease

Respiratory Medicine, 2011

Patients with chronic obstructive pulmonary disease (COPD) are often characterised by a range of ... more Patients with chronic obstructive pulmonary disease (COPD) are often characterised by a range of characteristic co-morbidities that interfere with their pulmonary disease. In addition to a mere association with co-morbidities, a complex pathophysiological interaction and mutual augmentation occurs between COPD and its co-morbidities that may result in disease progression and increased morbidity and mortality. An interdisciplinary approach is required both for diagnosis and treatment to target co-morbidities early in the course of the disease. This review summarizes the current knowledge of the interaction with cerebrovascular disease and endocrinological co-morbidities in COPD patients. There is growing evidence that COPD is an independent risk factor for ischemic stroke, increasing the risk about twofold. Stroke risk in COPD patients increases with the severity of the disease as measured by the degree of airflow limitation. The presence of cardiovascular risk factors is of particular importance for stroke prevention in COPD patients. Endocrinological co-morbidities are also important and many are associated with increased cardiovascular risk. Impaired glucose metabolism ranges from insulin resistance to overt diabetes mellitus, which is a frequent finding and is associated with worse outcome.

Research paper thumbnail of Identification of Chronic Heart Failure Patients with a High 12-Month Mortality Risk Using Biomarkers Including Plasma C-Terminal Pro-Endothelin-1

PLoS ONE, 2011

Objectives: We hypothesised that assessment of plasma C-terminal pro-endothelin-1 (CT-proET-1), a... more Objectives: We hypothesised that assessment of plasma C-terminal pro-endothelin-1 (CT-proET-1), a stable endothelin-1 precursor fragment, is of prognostic value in patients with chronic heart failure (CHF), beyond other prognosticators, including N-terminal pro-B-type natriuretic peptide (NT-proBNP).

Research paper thumbnail of Rosiglitazone reduces body wasting and improves survival in a rat model of cancer cachexia

Nutrition, 2013

1 2 Objective 3 Rosiglitazone improves insulin sensitivity and promotes weight gain in patients w... more 1 2 Objective 3 Rosiglitazone improves insulin sensitivity and promotes weight gain in patients with 4

Research paper thumbnail of Altered Intestinal Function in Patients With Chronic Heart Failure

Journal of the American College of Cardiology, 2007

We evaluated morphology and function of the gut in patients with chronic heart failure (CHF).

Research paper thumbnail of Impaired Insulin Sensitivity as an Independent Risk Factor for Mortality in Patients With Stable Chronic Heart Failure

Journal of the American College of Cardiology, 2005

The aim of this study was to determine the significance of insulin resistance as an independent r... more The aim of this study was to determine the significance of insulin resistance as an independent risk factor for impaired prognosis in patients with chronic heart failure (CHF). BACKGROUND In CHF, impaired insulin sensitivity (S I ) indicates abnormal energy metabolism and is related to decreased exercise capacity and muscle fatigue. The relationship between insulin resistance (i.e., low S I ) and survival in patients with CHF has not been established.