XXL – Gibt es ein Adipositas Paradox? Therapeutische Bedeutung ?

Präsentation zum Thema: "XXL – Gibt es ein Adipositas Paradox? Therapeutische Bedeutung ?"—  Präsentation transkript:

1 XXL – Gibt es ein Adipositas Paradox? Therapeutische Bedeutung ?
C. A. Schneider Klinik III für Innere Medizin Universität zu Köln

2 Was lehrt Bacchus uns? Bacchus Gott des Weins
(150 Kb); Oil on canvas, transferred from panel, 191 x cm (75 x 63 1/2 in); Hermitage, St. Petersburg Rubens, Peter Paul The Flemish baroque painter Peter Paul Rubens, b. June 28, 1577, d. May 30, 1640 was the most renowned northern European artist of his day, and is now widely recognized as one of the foremost painters in Western art history. Created in the last years of Rubens' life, this painting amazes the viewer with its virtuosity of style and unusual interpretation of the image of the god of wine and merriment. Bacchus is depicted as a grossly obese man, surrounded by a satyr, a maenad and putti. The rich palette, in which all the colours blend into one golden stream, and the natural, sketchy technique, enabled the artist to create a genuine sense of debauchery, or bacchanalia. This is a paean to human flesh. According to Rubens' nephew, Philip, this was not a commissioned work, and the artist kept it in his studio till the end of his life p

3 Leitlinie der Deutschen Adipositas-Gesellschaft aktuelle Version 2007

4 Overweight, Obesity, and Mortality in a Large Prospective Cohort of Persons 50 to 71 Years Old
Gesamtsterblichkeit 89 kg /1,60 m 51 kg/1,60 m Background Obesity, defined by a body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters) of 30.0 or more, is associated with an increased risk of death, but the relation between overweight (a BMI of 25.0 to 29.9) and the risk of death has been questioned. Methods We prospectively examined BMI in relation to the risk of death from any cause in 527,265 U.S. men and women in the National Institutes of Health–AARP cohort who were 50 to 71 years old at enrollment in 1995–1996. BMI was calculated from selfreported weight and height. Relative risks and 95 percent confidence intervals were adjusted for age, race or ethnic group, level of education, smoking status, physical activity, and alcohol intake. We also conducted alternative analyses to address potential biases related to preexisting chronic disease and smoking status. Results During a maximum follow-up of 10 years through 2005, 61,317 participants (42,173 men and 19,144 women) died. Initial analyses showed an increased risk of death for the highest and lowest categories of BMI among both men and women, in all racial or ethnic groups, and at all ages. When the analysis was restricted to healthy people who had never smoked, the risk of death was associated with both overweight and obesity among men and women. In analyses of BMI during midlife (age of 50 years) among those who had never smoked, the associations became stronger, with the risk of death increasing by 20 to 40 percent among overweight persons and by two to at least three times among obese persons; the risk of death among underweight persons was attenuated. Conclusions Excess body weight during midlife, including overweight, is associated with an increased risk of death. Normalgewicht Normalgewicht Follow up 10 Jahre NIH-AARP Kohorte Kenneth F. Adams et al. N Engl J Med 2006;355:

5 Body-mass index and cause-specific mortality in adults: collaborative analyses of 57 prospective studies Summary Background The main associations of body-mass index (BMI) with overall and cause-specifi c mortality can best be assessed by long-term prospective follow-up of large numbers of people. The Prospective Studies Collaboration aimed to investigate these associations by sharing data from many studies. Methods Collaborative analyses were undertaken of baseline BMI versus mortality in 57 prospective studies with participants, mostly in western Europe and North America (61% [n= ] male, mean recruitment age 46 [SD 11] years, median recruitment year 1979 [IQR 1975–85], mean BMI 25 [SD 4] kg/m²). The analyses were adjusted for age, sex, smoking status, and study. To limit reverse causality, the fi rst 5 years of follow-up were excluded, leaving deaths of known cause during a mean of 8 (SD 6) further years of follow-up (mean age at death 67 [SD 10] years): vascular; 2070 diabetic, renal or hepatic; neoplastic; 3770 respiratory; 7704 other. Findings In both sexes, mortality was lowest at about 22·5–25 kg/m². Above this range, positive associations were recorded for several specifi c causes and inverse associations for none, the absolute excess risks for higher BMI and smoking were roughly additive, and each 5 kg/m² higher BMI was on average associated with about 30% higher overall mortality (hazard ratio per 5 kg/m² [HR] 1·29 [95% CI 1·27–1·32]): 40% for vascular mortality (HR 1·41 [1·37–1·45]); 60–120% for diabetic, renal, and hepatic mortality (HRs 2·16 [1·89–2·46], 1·59 [1·27–1·99], and 1·82 [1·59–2·09], respectively); 10% for neoplastic mortality (HR 1·10 [1·06–1·15]); and 20% for respiratory and for all other mortality (HRs 1·20 [1·07–1·34] and 1·20 [1·16–1·25], respectively). Below the range 22·5–25 kg/m², BMI was associated inversely with overall mortality, mainly because of strong inverse associations with respiratory disease and lung cancer. These inverse associations were much stronger for smokers than for non-smokers, despite cigarette consumption per smoker varying little with BMI. Interpretation Although other anthropometric measures (eg, waist circumference, waist-to-hip ratio) could well add extra information to BMI, and BMI to them, BMI is in itself a strong predictor of overall mortality both above and below the apparent optimum of about 22·5–25 kg/m². The progressive excess mortality above this range is due mainly to vascular disease and is probably largely causal. At 30–35 kg/m², median survival is reduced by 2–4 years; at 40–45 kg/m², it is reduced by 8–10 years (which is comparable with the eff ects of smoking). The defi nite excess mortality below 22·5 kg/m² is due mainly to smoking-related diseases, and is not fully explained. -0,5 Jahre -3 Jahre -9 Jahre Lebenserwartung FU 8 Jahre Prospective Studies Collaboration 2009; Lancet 2009; 373: 1083–96

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7 Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies Summary Background Studies of the association between obesity, and total mortality and cardiovascular events in patients with coronary artery disease (CAD) have shown contradictory results. We undertook a systematic review to determine the extent and nature of this association. Methods We selected cohort studies that provided risk estimates for total mortality, with or without cardiovascular events, on the basis of bodyweight or obesity measures in patients with CAD, and with at least 6 months’ follow-up. CAD was defi ned as history of percutaneous coronary intervention, coronary artery bypass graft, or myocardial infarction. We obtained risk estimates for fi ve predetermined bodyweight groups: low, normal weight (reference), overweight, obese, and severely obese. Findings We found 40 studies with 250,152 patients that had a mean follow-up of 3·8 years. Patients with a low bodymass index (BMI) (ie, <20) had an increased relative risk (RR) for total mortality (RR=1·37 [95% CI 1·32–1·43), and cardiovascular mortality (1·45 [1·16–1·81]), overweight (BMI 25–29.9) had the lowest risk for total mortality (0·87 [0·81–0·94]) and cardiovascular mortality (0·88 [0·75–1·02]) compared with those for people with a normal BMI. Obese patients (BMI 30–35) had no increased risk for total mortality (0·93 [0·85–1·03]) or cardiovascular mortality (0·97 [0·82–1·15]). Patients with severe obesity (≥35) did not have increased total mortality (1·10 [0·87–1·41]) but they had the highest risk for cardiovascular mortality (1·88 [1·05–3·34]). Interpretation The better outcomes for cardiovascular and total mortality seen in the overweight and mildly obese groups could not be explained by adjustment for confounding factors. These fi ndings could be explained by the lack of discriminatory power of BMI to diff erentiate between body fat and lean mass. 40 Studien N= FU = 3,8 Jahre Bek. KHK Gomero-Corall A. et al. Lancet 2006; 368: 666–78

8 The relationship between body mass index, treatment, and mortality in patients with established coronary artery disease: a report from APPROACH Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease Aims Our objective was to examine the association between body mass index (BMI) and survival according to the type of treatment in individuals with established coronary artery disease (CAD). Methods and results Patients with CADwere identified in the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) registry between January 2001 and March Analyses were conducted separately by treatment strategy [medical management only, percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG)]. Patients were grouped according to six BMI categories. Multivariable-adjusted hazard ratios (HRs) for mortality were calculated using the Cox regression with the referent group for all analyses being normal BMI (18.5–24.9 kg/m2). The cohort included patients with a median follow-up time of 46 months. In the medically managed only group, BMIs of 25.0–29.9 and 30.0–34.9 kg/m2 were associated with significantly lower mortality compared with normal BMI patients (adjusted HR 0.72; 95% CI 0.63–0.83 and adjusted HR 0.82; 95% CI –0.98, respectively). In the CABG group, BMI of 30.0–34.9 kg/m2 had the lowest risk of mortality (adjusted HR 0.75; 95% CI 0.61–0.94), whereas in the PCI group, BMI of 35.0–39.9 kg/m2 had the lowest risk of mortality (adjusted HR 0.65; 95% CI 0.47–0.90). Patients who were overweight or have mild or moderate obesity were also more likely to undergo revascularization procedures compared with those with normal BMI, despite having lower risk coronary anatomy. Conclusion A paradoxical association between BMI and survival exists in patients with established CAD irrespective of treatment strategy. Patients with obesity may be presenting earlier and receiving more aggressive treatment compared with those with normal BMI. N= 31021 FU 84 Monate Oreopoulos A et al. European Heart Journal (2009) 30, 2584–2592

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10 OBESITY AND THE RISK OF HEART FAILURE
BSTRACT Background Extreme obesity is recognized to be a risk factor for heart failure. It is unclear whether overweight and lesser degrees of obesity also pose a risk. Methods We investigated the relation between the body-mass index (the weight in kilograms divided by the square of the height in meters) and the incidence of heart failure among 5881 participants in the Framingham Heart Study (mean age, 55 years; 54 percent women). With the use of Cox proportional-hazards models, the body-mass index was evaluated both as a continuous variable and as a categorical variable (normal, 18.5 to 24.9; overweight, 25.0 to 29.9; and obese, 30.0 or more). Results During follow-up (mean, 14 years), heart failure developed in 496 subjects (258 women and 238 men). After adjustment for established risk factors, there was an increase in the risk of heart failure of 5 percent for men and 7 percent for women for each increment of 1 in body-mass index. As compared with subjects with a normal body-mass index, obese subjects had a doubling of the risk of heart failure. For women, the hazard ratio was 2.12 (95 percent confidence interval, 1.51 to 2.97); for men, the hazard ratio was 1.90 (95 percent confidence interval, 1.30 to 2.79). A graded increase in the risk of heart failure was observed across categories of body-mass index. The hazard ratios per increase in category were 1.46 in women (95 percent confidence interval, 1.23 to 1.72) and 1.37 in men (95 percent confidence interval, 1.13 to 1.67). Conclusions In our large, community-based sample, increased body-mass index was associated with an increased risk of heart failure. Given the high prevalence of obesity in the United States, strategies to promote optimal body weight may reduce the population burden of heart failure. (N Engl J Med 2002; 347: ) Framingham Heart Study SATISH KENCHAIAHN et al. Engl J Med 2002; 347:305-13

11 Body Mass Index and Prognosis in Patients With Chronic Heart Failure Insights From the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) Program Background—In individuals without known cardiovascular disease, elevated body mass index (BMI) (weight/height2) is associated with an increased risk of death. However, in patients with certain specific chronic diseases, including heart failure, low BMI has been associated with increased mortality. Methods and Results—We examined the influence of BMI on prognosis using Cox proportional hazards models in 7599 patients (mean age, 65 years; 35% women) with symptomatic heart failure (New York Heart Association class II to IV) and a broad spectrum of left ventricular ejection fractions (mean, 39%) in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program. During a median follow-up of 37.7 months, 1831 patients died. After adjustment for potential confounders, compared with patients with BMI between 30 and 34.9, patients in lower BMI categories had a graded increase in the risk of death. The hazard ratios (95% confidence intervals) were 1.22 (1.06 to 1.41), 1.46 (1.24 to 1.71), and 1.69 (1.43 to 2.01) among those with BMI of 25 to 29.9, 22.5 to 24.9, and 22.5, respectively. The increase in risk of death among patients with BMI 35 was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.95 to 1.43). The association between BMI and mortality was not altered by age, smoking status, or left ventricular ejection fraction (P for interaction 0.20). However, lower BMI was associated with a greater risk of all-cause death in patients without edema but not in patients with edema (P for interaction 0.001). Lower BMI was associated with a greater risk of cardiovascular death and noncardiovascular death. Baseline BMI did not influence the risk of hospitalization for worsening heart failure or due to all causes. Conclusions—In patients with symptomatic heart failure and either reduced or preserved left ventricular systolic function, underweight or low BMI was associated with increased mortality, primarily in patients without evidence of fluid overload (edema). (Circulation. 2007;116:&NA;-. Satish Kenchaiah et al. Circulation. 2007;116:

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13 Weight-change as a prognostic marker in patients following acute myocardial infarction or with stable coronary artery disease Gesamt-Sterblichkeit >3% 3% Aims To examine the prognostic importance of weight-change in patients with coronary artery disease (CAD), especially following acute myocardial infarction (AMI). Methods and results In 4360 AMI patients (OPTIMAAL trial) without baseline oedema, we assessed 3-month weight-change, baseline body mass index (BMI), demographics, patient history, medication, physical examination, and biochemical analyses. Weight-change was defined as change kg/baseline BMI-unit. Patients were accordingly categorized into three groups; weight-loss, weight-stability, and weight-gain. Our findings were validated in 4012 AMI patients (CONSENSUS II trial) and 4178 stable CAD patients (79% with prior AMI, 4S trial). Median follow-up was 2.7 years, 3 months, and 4.4 years, respectively. In OPTIMAAL, 3-month weight-loss (vs. weight-stability) independently predicted increased all-cause death [n ¼ 471; hazard ratio (HR) 1.26; 95% CI 1.01–1.56; P ¼ 0.039] and cardiac death (n ¼ 299, HR 1.33, 95% CI 1.02–1.73, P ¼ 0.034). Weight-gain yielded risk similar to weight-stability (HR 1.07, P ¼ and 0.97, P ¼ 0.866, respectively). In CONSENSUS II, 3-month weight-loss independently predicted increased mortality (HR 3.87, P ¼ 0.008). Weight-gain yielded risk similar to weight-stability (HR 1.11, P ¼ 0.860). In 4S, 1-year weight-loss independently predicted increased mortality (HR 1.44, P ¼ 0.004). Weight-gain conferred risk similar to weight-stability (HR 1.05, P ¼ 0.735). Conclusion In patients following AMI or with stable CAD, weight-loss but not weight-gain was independently associated with increased mortality risk. N= 4360 OPTIMAAL trial Kennedey L et al. Eur Heart J 2006; 27:

14 Weight-change as a prognostic marker in patients following acute myocardial infarction or with stable coronary artery disease Aims To examine the prognostic importance of weight-change in patients with coronary artery disease (CAD), especially following acute myocardial infarction (AMI). Methods and results In 4360 AMI patients (OPTIMAAL trial) without baseline oedema, we assessed 3-month weight-change, baseline body mass index (BMI), demographics, patient history, medication, physical examination, and biochemical analyses. Weight-change was defined as change kg/baseline BMI-unit. Patients were accordingly categorized into three groups; weight-loss, weight-stability, and weight-gain. Our findings were validated in 4012 AMI patients (CONSENSUS II trial) and 4178 stable CAD patients (79% with prior AMI, 4S trial). Median follow-up was 2.7 years, 3 months, and 4.4 years, respectively. In OPTIMAAL, 3-month weight-loss (vs. weight-stability) independently predicted increased all-cause death [n ¼ 471; hazard ratio (HR) 1.26; 95% CI 1.01–1.56; P ¼ 0.039] and cardiac death (n ¼ 299, HR 1.33, 95% CI 1.02–1.73, P ¼ 0.034). Weight-gain yielded risk similar to weight-stability (HR 1.07, P ¼ and 0.97, P ¼ 0.866, respectively). In CONSENSUS II, 3-month weight-loss independently predicted increased mortality (HR 3.87, P ¼ 0.008). Weight-gain yielded risk similar to weight-stability (HR 1.11, P ¼ 0.860). In 4S, 1-year weight-loss independently predicted increased mortality (HR 1.44, P ¼ 0.004). Weight-gain conferred risk similar to weight-stability (HR 1.05, P ¼ 0.735). Conclusion In patients following AMI or with stable CAD, weight-loss but not weight-gain was independently associated with increased mortality risk. Kennedey L et al. Eur Heart J 2006; 27:

15 Weight loss and mortality risk in patients with chronic heart failure in the candesartan in heart failure: assessment of reduction in mortality and morbidity (CHARM) programme S. Pocock et al. European Heart Journal (2008) 29, 2641–2650

16 SCOUT Study Reductil

17 Diabetes

18 Effect of Weight Reduction on Outcome in Diabetic Patients
TI - Intentional weight loss and mortality among overweight individuals with diabetes [In Process Citation] AU - Williamson DF; Thompson TJ; Thun M; Flanders D; Pamuk E; Byers T SO - Diabetes Care 2000 Oct;23(10): OBJECTIVE: To estimate the effect of intentional weight loss on mortality in overweight individuals with diabetes. RESEARCH DESIGN AND METHODS: We performed a prospective analysis with a 12-year mortality follow-up ( ) of 4,970 overweight individuals with diabetes, years of age, who were enrolled in the American Cancer Society's Cancer Prevention Study I. Rate ratios (RRs) were calculated, comparing overall death rates, and death from cardiovascular disease (CVD) or diabetes in individuals with and without reported intentional weight loss. RESULTS: Intentional weight loss was reported by 34% of the cohort. After adjustment for initial BMI, sociodemographic factors, health status, and physical activity, intentional weight loss was associated with a 25% reduction in total mortality (RR = 0.75; 95% CI ), and a 28% reduction in CVD and diabetes mortality (RR = 0.72; ). Intentional weight loss of lb was associated with the largest reductions in mortality (approximately 33%). Weight loss >70 lb was associated with small increases in mortality CONCLUSIONS: Intentional weight loss was associated with substantial reductions in mortality in this observational study of overweight individuals with diabetes. 12 Jahre N= 4970 40-64 Jahre Williamson DF et al. Intentional weight loss and mortality among overweight individuals with diabetes Diabetes Care 2000 Oct;23(10):

19 Adipositas Paradox – epidemiologisches Artefakt ?
Analyse des Bauchumfangs besser?

20 Präford Studie – Korrelation BMI Bauchumfang Männer
kg/m² r=0.87 N=3867 Mittleres Alter 45

21 Obesity and the risk of myocardial infarction in participants from 52 countries: a case-control study Veränderung der Odds ratio für Herzinfarkt pro Zunahme des Parameters um 1 SD Waist = Bauchumfang Hip = Hüftumfang W-H Ratio:= Verhältnis Bauch Hüfte Yusuf S et al. The Lancet 2005; 366:

22 Measures of Obesity and Cardiovascular Risk Among Men and Women
Tödliche und nicht-tödliche kardiovaskuläre Ereignisse Männer (body mass index) (waist to height ratio) (waist circumference) (waist to hip ratio) Objectives This study examined associations between anthropometric measures (body mass index, waist circumference, waist-to-hip ratio, waist-to-height ratio [WHtR]) and risk of incident cardiovascular disease (CVD) (including nonfatal myocardial infarction, nonfatal ischemic stroke, and cardiovascular death). Background Controversy exists regarding the optimal approach to measure adiposity, and the utility of body mass index has been questioned. Methods Participants included 16,332 men in the Physicians’ Health Study (mean age 61 years in 1991) and 32,700 women in the Women’s Health Study (mean age 61 years in 1999). We used Cox proportional hazards models to determine relative risks and 95% confidence intervals (CIs) for developing CVD according to self-reported anthropometric indexes. Results A total of 1,505 CVD cases occurred in men and 414 occurred in women (median follow-up 14.2 and 5.5 years, respectively). Although WHtR demonstrated statistically the strongest associations with CVD and best model fit, CVD risk increased linearly and significantly with higher levels of all indexes. Adjusting for confounders, the relative risk for CVD was 0.58 (95% CI: 0.32 to 1.05) for men with the lowest WHtR (0.45) and 2.36 (95% CI: 1.61 to 3.47) for the highest WHtR (0.69; vs. WHtR 0.49 to 0.53). Among women, the relative risk was 0.65 (95% CI: 0.33 to 1.31) for those with the lowest WHtR (0.42) and 2.33 (95% CI: 1.66 to 3.28) for the highest WHtR (0.68; vs. WHtR 0.47 to 0.52). Conclusions The WHtR demonstrated statistically the best model fit and strongest associations with CVD. However, compared with body mass index, differences in cardiovascular risk assessment using other indexes were small and likely not clinically consequential. Our findings emphasize that higher levels of adiposity, however measured, confer increased risk of CVD. (J Am Coll Cardiol 2008;52:605–15) Physiscians‘ Health Study Womens Health Study N= 16332, N=32700 Mittleres Alter Jahre FU 14, 2 Jahre kg/m² < 20 22.5 to 24.9 > 35 Gelber R et al J Am Coll Cardiol 2008;52:605–15

23 Adipositas Paradox – epidemiologisches Artefakt ?
Bauchumfang besser als BMI? Dicke früher diagnostiziert? BNP niedrig –Luftnot? Dicke besser therapiert? Dicke besser gegen Nebenwirkungen von Medikamenten geschützt? Niedrigeres Blutungsrisiko bei Herzkathetern Dicke mehr Muskelmasse? TNFalpha -Schutz durch Fettgewebe (Rezeptoren)? Veränderte Zytokine-Balance Leptin, Adiponektin, Anti-Inflammation?

24 Adipositas Paradox – Zusammenfassung
Es spricht mehr dafür als dagegen! Kein Anhalt für Gewichtsreduktions-Empfehlung bei Dicken mit KHK und Herzinsuffizienz Diabetiker? Was empfehlen wir den Normal-gewichtigen/Untergewichtigen mit KHK oder Herzinsuffizienz? Katabolismus Bremse? Ernährungs-Empfehlungen?