Einleitung: In dieser Arbeit wurde die Auswirkung der Fettgewebesurrogate Halsumfang (HU), Taillenumfang (TU) und Body Mass Index (BMI) auf die Prognose bei Patienten mit chronischer Niereninsuffizienz untersucht. Methoden: Datengrundlage dieser Arbeit war die German Chronic Kidney Disease (GCKD) Beobachtungsstudie. Eingeschlossen wurden Erwachsene mit GFR 30-60 ml/min/1,73m² oder GFR > 60 ml/min/1,73m² mit offensichtlicher Proteinurie. Ausschlusskriterien waren: nicht-kaukasische Ethnie, Organtransplantation, Malignome und Herzinsuffizienz NYHA IV. Untersuchte kombinierte Endpunkte (EP) waren: 1) 4P-MACE (Herzinfarkt, Schlaganfall, kardiovaskulärer Tod, pAVK-Ereignis) 2) Tod jeglicher Ursache 3) Nierenversagen (Dialyse, Transplantation). Es wurden Cox-Regressionen mit HU, TU, und BMI für jeden EP, adjustiert für Alter, Geschlecht, Nikotinkonsum, Diabetes mellitus, arterielle Hypertonie, LDL-Cholesterin, GFR, Urin-Albumin/Kreatinin Ratio (UACR) und CRP berechnet. Interaktionsterme des jeweiligen Surrogats mit dem Geschlecht wurden eingeschlossen. Ergebnisse: Von den 4537 analysierten Studienteilnehmern, waren 59% Männer mit einem Durchschnittsalter von 60 (±12) Jahren, einer mittleren GFR von 50 (±18) ml/min/1,73m² und einem UACR-Median von 49 (10–374) mg/g. Der mittlere HU war 42,7 (±3,6) cm bei Männern und 37,2 (±3,7) cm bei Frauen, der mittlere TU 107,6 (±13,6) cm bei Männern und 97,0 (±16,3) cm bei Frauen und der mittlere BMI 29,7 (±5,9) kg/m². Die mittlere Beobachtungszeit betrug 6,5 Jahre. Der TU war signifikant mit Tod assoziiert, mit einer HR von 1,014 pro cm (95% KI 1,005–1,024). HU war signifikant mit Tod bei Frauen assoziiert, Interaktionsterm HR 1,080 pro cm (95% KI 1,009–1,155). Der BMI hatte keinen signifikanten Einfluss auf untersuchte EP. Schlussfolgerung: Bei Patienten mit mittel- bis schwergradig eingeschränkter Nierenfunktion steigern ein erhöhter TU (bei beiden Geschlechtern), sowie bei Frauen ein erhöhter HU das Risiko für Tod jeglicher Ursache. / Introduction: Adiposity alters the risk of adverse outcome in chronic kidney disease. This work investigates the prognostic impact of the adiposity measures neck circumference (NC), waist circumference (WC) and body mass index (BMI). Methods: This study is based on data from the prospective observational German Chronic Kidney study which included adults with chronic kidney disease, defined as estimated glomerular filtration rate (GFR) 30–60 ml/min/1.73 m² or GFR > 60 ml/min/1.73 m² with overt proteinuria. Exclusion criteria were non-Caucasian ethnicity, solid organ transplant, active malignancy and heart failure NYHA IV. Investigated composite outcomes were: 1) 4P-MACE (stroke, myocardial infarction, cardiovascular death, peripheral artery disease event) 2) all-cause death 3) kidney failure (dialysis, transplantation). Cox-models for each outcome and adiposity measure, adjusted for age, sex, smoking, diabetes, hypertension, LDL-cholesterol, GFR, urine-albumin-creatinine ratio (UACR) and CRP, were calculated. Interaction terms of adiposity measures with sex were included. Results: Of the 4537 analysed participants, 59% were men with a mean age of 60 (±12) years, a mean GFR of 50 (±18) ml/min/1.73m² and a median UACR of 49 (10–374) mg/g. Mean NC was 42.7 (±3.6) cm in men and 37.2 (±3.7) cm in women, mean WC was 107.6 (±13.6) cm in men and 97.0 ± 16.3 cm in women, mean BMI was 29.7 (±5.9) kg/m². The mean follow-up time was 6.5 years. WC was associated with death, HR 1.014 per cm (95%CI: 1.005–1.024). NC in women was associated with death, interaction HR 1.080 per cm (95%CI: 1.009–1.155). No significant association of the BMI with the analysed outcomes was observed. Conclusion: In patients with moderate to moderately severe chronic kidney disease, WC in both sexes and NC in women were independently associated with death. BMI was not a relevant prognostic factor in these patients.

Obesity, assessed by body mass index (BMI), is considered a major public health problem worldwide. Studies in people without CVD, have shown that BMI between 22.5 to 24.9 kg/m2 is associated with the lowest risk of death in healthy non-smoker populations. However, studies in patients with acute coronary syndrome (ACS) have shown that overweight and obese patients have better survival than those in the normal BMI range. This phenomenon has been called the “obesity paradox”. This thesis has two main components: a systematic review with meta-analysis of the current literature of BMI and ACS, and an individual patient data meta-analysis from 8 randomized trials whose data base was accessible at the PHRI involving ACS patients. The study-level systematic review (35 studies) and meta-analysis (19 studies) demonstrates that there is a statistically significant adjusted 20% risk lower mortality among overweight and obese participants considered normal weight. Nevertheless, there was moderate to high heterogeneity of pooled estimates that could not be explained in subgroup analyses. Also, the systematic review detected major limitations in the current literature, including missing BMI and covariates data, lost to follow-up, enough number of events in high BMI categories, warranting more research in the area. The second component, the individual patient data meta-analysis (n = 81,553), confirmed a 20% lower mortality risk in the overweight and type I obesity categories, compared to the normal the BMI range. This lower risk was robust and remained consistent within several sensitivity analyses. Analysis of secondary outcomes suggests that a reduced risk of bleeding, and probably a reduced risk of ischemia and heart failure related deaths, are the responsible mechanisms. Given the limitations of observational research, prospective randomized interventional trials are required to clarify the optimal range of BMI in those with ACS. / Thesis / Master of Health Sciences (MSc)

This thesis comprises three chapters involving the analysis of the body mass index (BMI) in health economics. The first chapter evaluates two correction models that aim to address measurement error in self-reported (SR) BMI in survey data. This chapter is an addition to the literature as it utilizes two separate Canadian datasets to evaluate the transportability of these correction equations both over time and across different datasets. Our results indicate that the older method remains competitive and that when BMI is used as an independent variable, correction may even be unnecessary. The second chapter measures the relationship between long-term physician costs and BMI. The results show that obesity is associated with higher longterm physician costs only at older ages for males, but at all ages for females. We find that accounting for existing health conditions that are often associated with obesity does not explain the increase in long-term physician costs as BMI increases. This indicates that there is an underlying relationship between the two that we could not account for in our econometric models. Finally, the third chapter decomposes the differences in BMI distributions of Canada and the US. The results show that the differences between BMI levels, both over time and across countries, are increasing with BMI; meaning the highest difference is observed at the right tail of the two distributions. In analysis comparing two points in time, these differences are solely due to differences in the returns from attributes and the omitted variables that we cannot account for in our models. In cross-country analysis, there is evidence that the differences observed below the mean can be explained by the differences in characteristics of the two populations. The differences observed above the mean are again due to those in returns and the omitted variables. / Dissertation / Doctor of Philosophy (PhD)

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