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Biomedical subjects

Wolfram Doehner

Publications and source records attributed to Wolfram Doehner.

At least 19 recordsLinked to original sources
PubMed2006

Anorexia in chronic obstructive pulmonary disease--association to cachexia and hormonal derangement.

BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD) weight loss frequently occurs that may ultimately lead to cachexia as a serious co-morbidity, indicating severely impaired functional capacity, health status and increased mortality. Increased energy expenditure due to mechanic and metabolic inefficiency and systemic inflammation are determinants of a hypermetabolic state that is not balanced by dietary intake. Anorexia may importantly contribute to weight loss in COPD, however, the association between immune and hormonal derangement and altered appetite has not been studied in detail. AIM: The aim of the present study was to investigate whether anorexia in COPD is related to inflammation and hormonal derangement in association to weight loss. METHODS: We prospectively enrolled 103 consecutive patients with COPD (age 59.8+/-1.3 years, 35% female, mean FEV1 38.3+/-1.7%) in comparison to healthy controls of similar age (n=15). RESULTS: In 34 patients (33%) cachexia was diagnosed (weight loss >7.5%, BMI < or = 24 kg/m2). Cachectic COPD patients had lower BMI (19.0+/-0.5 vs 25.6+/-0.7 kg/m2) and impaired lung function (FEV1 31+/-2% vs 42+/-2%, FVC 51+/-3 vs 59+/-3%, both p<0.001). Inflammatory immune activation (IL-6 and IL-6/IL-10 ratio) was significantly higher in cachectic COPD patients. Analysis of the extent of anorexia (visual analogue scale) revealed that cachectic COPD patients had significantly decreased subjective desire to eat compared to non-cachectic patients (3.5+/-0.3 vs 6.3+/-0.2, p<0.001). Patients with COPD and cachexia showed evidence of acquired GH resistance (decreased IGF-1/GH ratio) and insulin resistance (HOMA). Anorexia showed a direct correlation with the IGF-1/GH ratio (r=0.34, p<0.05) and was further related to BMI and % weight loss (both p<0.001). CONCLUSION: In COPD anorexia relates to hormonal derangement and inflammatory immune activation. Anorexia contributes to development of cachexia. The concept of appetite stimulating therapy emerges as a novel therapeutic option in cachectic COPD patients.

Anorexia↗
PubMed2006

Metabolic disturbances in chronic heart failure: a case for the "macho" approach with testosterone?!

Chronic heart failure (CHF) primarily affects the cardiovascular system. In addition, there is strong evidence that CHF is a complex metabolic disorder. Metabolic abnormalities include insulin resistance and lack of anabolic hormone activity. To date there have been few interventional trials targeting insulin sensitivity. A recent study suggests a link between testosterone therapy and improvements in insulin sensitivity, measured using the homeostatic model assessment (HOMA-IR). We discuss this study in detail. Further studies are needed to substantiate this link and to generally explore the value of testosterone therapy in CHF patients.

Heart Failure↗
PubMed2006

Nutrition, metabolism, and the complex pathophysiology of cachexia in chronic heart failure.

Chronic heart failure is a complex catabolic state that carries a devastating prognosis. The transition from stable disease to cardiac cachexia is 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 result of bowel wall edema and decreased bowel perfusion also plays an important role. This article describes the complex interplay of hormonal systems in energy balance in patients with chronic heart failure as well as other factors such as malabsorption and dietary deficiencies that contribute to the wasting process. Finally, therapeutic approaches are discussed. These include dietary advice, ongoing studies, and future possibilities.

Adrenergic beta-Antagonists↗
PubMed2005

Impaired insulin sensitivity as an independent risk factor for mortality in patients with stable chronic heart failure.

OBJECTIVES: 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. METHODS: We prospectively studied 105 male patients with CHF due to ischemic (63%) or non-ischemic (37%) etiology. All patients were in clinically stable condition (age 62 +/- 1 year, New York Heart Association [NYHA] functional class 2.6 +/- 0.1, left ventricular ejection fraction [LVEF] 28 +/- 2%, peak oxygen uptake [Vo(2)] 18.2 +/- 0.7 ml/kg/min). Insulin sensitivity was assessed from glucose and insulin dynamic profiles during an intravenous glucose tolerance test using the minimal model technique. RESULTS: During a mean follow-up period of 44 +/- 4 months, 53 patients (50%) died. Patients with S(I) below the median value (median: 1.82 min(-1) x microU x ml(-1).10(4); n = 52) had worse survival (at two years 61% [range 47% to 74%]) than patients with S(I) above the median value (n = 53; at two years 83% [range 73% to 93%]; risk ratio [RR] 0.38, 95% confidence interval [CI] 0.21 to 0.67; p = 0.001). Both patient groups were similar in terms of age, NYHA functional class, and body composition parameters (dual-energy X-ray absorptiometric scan; p > 0.2), but patients with a lower S(I) had a lower LVEF (24 +/- 2% vs. 33 +/- 3%) and peak Vo(2) (16.8 +/- 1.0 ml/kg/min vs. 19.7 +/- 1.0 ml/kg/min; both p < 0.05). On univariate Cox analysis, higher S(I) predicted better survival (RR 0.56, 95% CI 0.35 to 0.89; p = 0.015). On stepwise multivariate analysis, S(I) predicted mortality independently of other variables. CONCLUSIONS: In patients with CHF, lower S(I) relates to higher mortality, independent of body composition and established prognosticators. Impaired S(I) may have implications in the pathophysiology of CHF disease progression. Therapeutically targeting impaired insulin sensitivity may potentially be beneficial in patients with CHF.

Chronic Disease↗
PubMed2005

Association of deranged adrenal steroid metabolism with anemia in chronic heart failure.

The relation between adrenal steroid hormone imbalance, as quantified by the cortisol/dehydroepiandrosterone (DHEA) ratio, and hemoglobin concentrations was appraised in 92 men with stable chronic heart failure (CHF). The cortisol/DHEA ratio was independently and inversely associated with hemoglobin concentrations, suggesting that alterations of the steroid milieu may play a role in the pathogenesis of anemia in CHF.

Adrenal Glands↗
PubMed2005

Whole blood endotoxin responsiveness in patients with chronic heart failure: the importance of serum lipoproteins.

BACKGROUND: Endotoxin [lipopolysaccharide (LPS)] may be an important stimulus for cytokine release in patients with chronic heart failure (CHF). We sought to investigate the relationship between whole blood endotoxin responsiveness and serum lipoprotein concentrations. It is not known if low-dose LPS is sufficient to stimulate immune activation. METHODS AND RESULTS: Whole blood from 32 CHF patients (mean age 66+/-2 years, NYHA class 2.7+/-0.2, five female) and 11 healthy control subjects (mean age 47+/-4 years, six female) was stimulated with LPS at nine different concentrations (0.001 to 10 ng/mL), and tumor necrosis factor (TNF-alpha) release was quantified. Reference standard endotoxin at concentrations of 0, 0.6, 1, and 3 EU/ml was added to whole blood from nine CHF patients (age 64+/-9.1 years, all NYHA class II, eight male) and incubated for 6 h, the TNF-alpha production being measured. Serum lipoproteins were quantified using standard techniques. In CHF patients, there was an inverse relationship between whole blood TNF-alpha release and serum cholesterol which was strongest at 0.6 ng/mL of LPS (r=-0.53, p=0.002). A similar although weaker relationship was found for serum HDL. No such correlation was found in healthy subjects or with serum LDL (all r(2)<0.1). Low concentrations of LPS induced a stepwise increase in TNF-alpha release from whole blood to concentrations well above those seen in CHF. CONCLUSIONS: Serum lipoproteins may play an important role in regulating LPS bioactivity in CHF. Very low LPS activity, at levels seen in vivo in CHF, can induce significant TNF-alpha production ex vivo.

Aged↗
PubMed2005

Cellular endotoxin desensitization in patients with severe chronic heart failure.

BACKGROUND: Increased levels of bacterial lipopolysaccharide (LPS) have been demonstrated in chronic heart failure (CHF). LPS can induce cellular desensitization, with specific down-regulation of LPS-mediated cellular tumor necrosis factor (TNF-alpha) production which does not affect other cytokine parameters. It is not known if LPS desensitization occurs in CHF. METHODS AND RESULTS: Mononuclear cells from 24 CHF patients (mean age 70+/-2 years, age range 58 to 78 years, NYHA class 3.0+/-0.2) and 11 healthy controls (mean age 53+/-3 years, age range 39 to 75 years) were separated from venous blood and cultured for 24 h with LPS (E. coli, 0-10 ng/mL). Culture supernatants were tested for TNF-alpha and interleukin-1 receptor antagonist (IL-1RA). Patients were subgrouped into mild (n=10), moderate (n=5), and severe (n=9) CHF. Independently of age, mononuclear cells from patients with severe heart failure produced less TNF-alpha than controls (p<0.05) and patients with mild (p<0.001) or moderate CHF (p<0.05). IL-1RA release was higher for CHF patients as a group, compared with controls (p<0.05). There was no significant difference in IL-1RA release between CHF patient subgroups. CONCLUSIONS: Mononuclear cells from patients with severe heart failure produce significantly less TNF-alpha than healthy controls or patients with mild to moderate disease. Production of IL-1RA is not affected. This resembles a picture indicative of LPS desensitization occurring in patients with severe CHF.

Aged↗
PubMed2005

Uric acid in chronic heart failure.

The pathophysiologic understanding of chronic heart failure (CHF) has shifted from a mere hemodynamic disorder to a much more complex approach including changes and imbalances in neurohormonal, immune, and metabolic functions. Among metabolic abnormalities, hyperuricemia is a constant finding in CHF. The xanthine oxidase metabolic pathway increasingly is appreciated as an important contributor to both symptoms of CHF as well as progression of the disease. Recent data suggest hyperuricemia to be an independent marker of impaired prognosis in CHF. In this article, the significance of the xanthine oxidase metabolic pathway in CHF is discussed. Data on xanthine oxidase inhibition are reviewed, which suggest a beneficial effect of therapeutically targeting this enzymatic pathway.

Allopurinol↗
PubMed2005

Anemia and inflammation in COPD.

BACKGROUND: Anemia in patients with COPD and its pathophysiology is an understudied issue. METHODS: In a group of 101 COPD patients (FEV(1) percentage of predicted, 37 +/- 2% [mean +/- SEM]; mean age, 61 +/- 1 years; 35% female gender), the prevalence of anemia and its relationship to body mass and weight loss, inflammatory parameters, and erythropoietin levels was determined. Data were compared to a control group (healthy persons with matched age) in order to identify potential factors that may influence the development of anemia in patients with COPD. RESULTS: Anemia was diagnosed in 13 patients (hemoglobin levels < 13.5 mg/dL in male patients and < 12.0 mg/dL in female patients), which represents a prevalence of 13%. Anemic COPD patients showed elevated erythropoietin levels (41.8 +/- 25.4 U/L vs 16.3 +/- 2.9 U/L) and an increased inflammatory response compared to nonanemic patients. A significant inverse correlation of hemoglobin vs erythropoietin (r = - 0.84, p < 0.01) was observed in anemic COPD patients, but not in the nonanemic group. CONCLUSION: Anemic COPD patients show high erythropoietin levels, which may indicate presence of erythropoietin resistance. The latter may be mediated through inflammatory mechanisms, which is typical for anemia of chronic illness.

Anemia↗
PubMed2004

Prediction of mortality in chronic heart failure from peak oxygen consumption adjusted for either body weight or lean tissue.

BACKGROUND: Peak oxygen consumption (pVO2) reflects oxygen extraction from the skeletal muscles, but is routinely corrected for body weight. We hypothesized that correcting pVO2 for lean tissue rather than total body weight would improve the prediction of prognosis in patients with chronic heart failure (CHF). METHODS AND RESULTS: A total of 272 CHF outpatients (mean age 61 +/- 12 years, New York Heart Association [NYHA] class 2.3 +/- 0.8) underwent a cardiopulmonary exercise testing and body composition assessment by dual-energy X-ray absorptiometry. During a median follow-up of 608 days (range 8-3656), 75 patients died. Univariate survival analysis showed strong survival prediction from pVO2 adjusted for total weight or lean tissue (chi2 17.7, P < .001; chi2 27.5, P < .0001, respectively). Both predicted survival significantly in bivariate analysis, (chi2 4.6, P = .032; chi2 16.6, P < .0001). The predictive effects were independent of exercise protocol (treadmill versus cycle ergometer) (both P < .001). Multivariate analysis showed that pVO2 adjusted for lean tissue had prognostic importance independently of NYHA class, ejection fraction, and ventilation and carbon dioxide production slope (P < .05 for each). In patients with NYHA class I and II (n = 160), pVO2 adjusted for lean tissue predicted outcome (P = .03). CONCLUSION: Adjustment for lean tissue instead for body weight increases the prognostic power of pVO2, particularly in patients with mild heart failure.

Absorptiometry, Photon↗
PubMed2004

Wasting of the left ventricle in patients with cardiac cachexia: a cardiovascular magnetic resonance study.

BACKGROUND: The "cachectic heart" has been described as a pathologic decrease in the size and mass of the heart, but no in vivo studies have shown changes in cardiac dimensions or left ventricular (LV) mass over time in chronic heart failure (CHF) associated with body wasting (cardiac cachexia). Cardiovascular magnetic resonance (CMR) has high reproducibility and is more sensitive than other techniques. METHODS: CMR studies of LV volumes and mass were performed at baseline and a mean of 15 months later in nine CHF patients with cardiac cachexia and 28 matched CHF controls without cachexia (mass index 23 +/- 1 vs. 29 +/- 5 kg/m2, P=0.0005). RESULTS: At baseline, LV end-diastolic volume (197 +/- 78 vs. 203 +/- 65 ml), end-systolic volume (131 +/- 75 vs. 126 +/- 63 ml), LV mass (213 +/- 44 vs. 222 +/- 62 g), and LV ejection fraction (38 +/- 19% vs. 40 +/- 16%) did not differ between cachectic patients and controls (all P>0.10). During follow-up, there was a significant decrease in LV mass in patients with cachexia (-16 g, P<0.05) and a trend to increase in LV mass in patients without cachexia (+7 g, P=0.12, comparison between groups: P=0.010). CONCLUSIONS: The direction of changes over time in LV mass differs in CHF patients with cachexia as compared with non-cachectic controls. A significant decrease in LV mass occurs in patients with cardiac cachexia. This study documents in vivo the occurrence of wasting of the left ventricle in patients with CHF who demonstrate general body wasting.

Aged↗
PubMed2004

Heat shock protein 70 in patients with chronic heart failure: relation to disease severity and survival.

BACKGROUND: Heat shock protein 70 (Hsp70) is essential for cellular recovery, survival and maintenance of cellular function. Research into the possible use of Hsp70 as a cytoprotective therapeutic agent is ongoing. Chronic heart failure (CHF) is a state associated with systemic inflammation, particularly in patients with cardiac cachexia. We hypothesised that circulating Hsp70 levels are elevated in patients with CHF, more so in cachechtic patients, and that Hsp70 levels would relate to mortality. METHODS AND RESULTS: We studied 107 patients (28 female, age 67+/-1 years, NYHA class 2.6+/-0.6 and LVEF 29+/-1%, mean+/-SEM) and 21 controls. Cardiac cachexia was present in 32 patients. Hsp70 was detectable in 41% of CHF patients and in only 10% of controls. Overall serum levels were significantly higher in CHF patients vs. controls (7.13+/-1.34 vs. 0.38+/-0.26 ng/ml, p=0.004). Hsp70 levels were also higher in patients with advanced CHF according to NYHA class or the presence of cachexia (all p<0.05). There was no relation between Hsp70 and left ventricular ejection fraction, maximal oxygen consumption and several inflammatory cytokines (all p>0.05). During a median follow-up of 208 days (range 4-2745 days) 38 patients died. Cox proportional hazards analysis showed that increased Hsp70 did not predict survival (p=0.17). CONCLUSION: Hsp70 levels are elevated in CHF patients, particularly in those with cardiac cachexia and Hsp70 relates to disease severity but not to survival. The significance of the relationship of Hsp70 expression and morbidity in CHF needs further evaluation.

Aged↗
PubMed2003

The relationship between cholesterol and survival in patients with chronic heart failure.

OBJECTIVES: We sought to describe the relationship between cholesterol and survival in patients with chronic heart failure (CHF). BACKGROUND: Increasing lipoprotein levels are a cardiovascular risk factor. In patients with CHF, the prognostic value of endogenous lipoproteins is not fully clarified. METHODS: A group of 114 patients with CHF recruited to a metabolic study was followed for a minimum of 12 months (derivation study). The results were applied to a second group of 303 unselected patients with CHF (validation study). The relationship between endogenous lipoproteins and survival was explored. RESULTS: In the derivation study, survival at 12 months was 78% (95% confidence interval [CI] 70% to 86%) and 56% (95% CI 51% to 62%) at 36 months. Increasing total serum cholesterol was a predictor of survival (hazard ratio 0.64, 95% CI 0.48 to 0.86), independent of the etiology of CHF, age, left ventricular ejection fraction, and exercise capacity. Receiver-operating characteristic curves demonstrated a best cut-off value of </=5.2 mmol/l (200.8 mg/dl) as being the best predictor of mortality at 12 months (sensitivity 80.0%, specificity 62.9%). In the validation population, one-year survival was 88% (95% CI 84 to 91%) and three-year survival was 68% (95% CI 63 to 73%). The chance of survival increased 25% for each mmol/l increment in total cholesterol. Survival rates above and below the cut-off value for cholesterol in patients with ischemic heart disease (n = 181) were 92% (95% CI 89 to 94) versus 75% (95% CI 64 to 85%) at one year and 72% (95% CI 67 to 76%) versus 50% (95% CI 43 to 56%) at three years. CONCLUSIONS: In patients with CHF, lower serum total cholesterol is independently associated with a worse prognosis.

Age Factors↗