Obesity, Physical Activity, and Cardio-metabolic Disorders in Older Adults Klodian Dhana Acknowledgments The work presented in this thesis was conducted at the department of Epidemiology in the Erasmus Medical Center, Rotterdam, the Netherlands. All studies described in this thesis were performed within the Rotterdam Study, which is supported by Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research (NWO), the Netherlands Organization for Health Research and Development (ZonMw), the Dutch Heart Foundation, the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry of Health, welfare and Sports, the European Commission (DG XII), and the municipality of Rotterdam. The research described in this thesis is supported by Erasmus Mundus Western Balkans (ERAWEB), a project funded by the European Commission. Publication of this thesis was kindly supported by the Department of Epidemiology of Erasmus Medical Center, Rotterdam, the Netherlands. Additional financial support by the Dutch Heart Foundation for the publication of this thesis is gratefully acknowledged. ISBN: 978-94-6182-696-1 Cover design: ShutterStock/roustignac Printed by: Off Page, Amsterdam © 2016 Klodian Dhana The copyright is transferred to the respective publisher upon publication of the manuscript. No part of this thesis may be reproduced, stored in a retrieval system, or transmitted in any form or by any means without prior permission of the author or the publisher of the manuscript. Obesity, Physical Activity, and Cardio-metabolic Disorders in Older Adults Obesitas, fysieke activiteit, en cardio-metabolica aandoeningen bij oudere volwassenen Proefschrift ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van de rector magnificus Prof.dr. H.A.P. Pols en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op dinsdag 5 juli 2016 om 11.30 uur door Klodian Dhana geboren te Kucove, Albania Promotiecommissie Promotoren: Prof.dr. O.H. Franco Overige leden: Prof.dr. J.W. Deckers Prof.dr. A.H.E.M. Maas Dr. E.F.C. van Rossum Copromotor: Dr. M. Kavousi Paranimfen: A. Brahimaj J. Nano to Anisa and Mikel Contents Chapter 1 General introduction 11 Chapter 2 Novel versus traditional anthropometric measures of general and central 19 obesity in the middle-age and elderly 2.1 Body shape index in comparison with other anthropometric measures in prediction 21 of total and cause-specific mortality 2.2 Anthropometric measures in cardiovascular disease prediction: comparison of 43 laboratory-based versus non-laboratory-based model 2.3 Association of anthropometric measures with fat and fat-free mass in the elderly 61 Chapter 3 Overweight, obesity and metabolic risk 75 3.1 Metabolically healthy obesity and the risk of cardiovascular disease in the elderly. 77 3.2 Timing and duration of overweight in association with metabolic syndrome and 95 diabetes among middle-age and elderly Chapter 4 Obesity, cardiovascular disease and mortality 113 4.1 Obesity in older adults and life expectancy with and without cardiovascular disease 115 4.2 Trajectories of body mass index before the diagnosis of cardiovascular disease: a 137 latent class trajectory analysis Chapter 5 Obesity, physical activity and cardiovascular disease 157 5.1 The impact of physical activity on the association between overweight, obesity and 159 cardiovascular disease 5.2 Physical activity types and coronary heart disease risk in middle-aged and elderly 173 persons 5.3 Physical activity types and life expectancy with and without cardiovascular disease 191 Chapter 6 General discussion 217 Appendices 233 Summary 235 About the author 239 Word of thanks 241 Publications and manuscripts 243 PhD Portfolio Summary 245 MANUSCRIPTS BASED ON THE STUDIES DESCRIBED IN THIS THESIS Chapter 2 Dhana K, Kavousi M, Ikram MA, Tiemeier HW, Hofman A, Franco OH. Body shape index in comparison with other anthropometric measures in prediction of total and cause-specific mortality. J Epidemiol Community Health 2016; 70(1): 90-6. Dhana K, Ikram MA, Hofman A, Franco OH, Kavousi M. Anthropometric measures in cardiovascular disease prediction: comparison of laboratory-based versus non-laboratory-based model. Heart 2015; 101(5): 377-83. Dhana K, Koolhaas CM, Schoufour J, Rivadeneira F, Hofman A, Kavousi M, Franco OH. Association of anthropometric measures with fat and fat-free mass in the elderly: The Rotterdam study. Maturitas 2016; 88: 96-100. Chapter 3 Dhana K, Koolhaas CM, van Rossum EF, Ikram MA, Hofman A, Kavousi M, Franco OH. Metabolically healthy obesity and the risk of cardiovascular disease in the rlderly population. PLoS One 2016; 11(4): e0154273. Dhana K, Ligthart S, Hofman A, Dehghan A, Franco OH, Kavousi M. Timing and duration of overweight in association with metabolic syndrome and diabetes among middle-aged and elderly. Submitted for publication. Chapter 4 Dhana K, Berghout MA, Peeters A, Ikram MA, Tiemeier H, Hofman A, Nusselder W, Kavousi M, Franco OH. Obesity in older adults and life expectancy with and without cardiovascular disease. Int J Obes (Lond) 2016. Dhana K, van Rosmalen J, Vistisen D, Ikram MA, Hofman A, Franco OH, Kavousi M. Trajectories of body mass index before the diagnosis of cardiovascular disease: a latent class trajectory analysis. Eur J Epidemiol 2016. Chapter 5 Dhana K, Koolhaas CM, Ikram MA, Hofman A, Franco OH, Kavousi M. The impact of physical activity on the association between overweight, obesity and cardiovascular disease. Submitted for publication. Koolhaas CM, Dhana K, Golubic R, Schoufour JD, Hofman A, van Rooij FJ, Franco OH. Physical activity types and coronary heart disease risk in middle-aged and elderly persons: The Rotterdam Study. Am J Epidemiol 2016. Dhana K*, Koolhaas CM*, Berghout MA, Peeters A, Ikram MA, Tiemeier H, Hofman A, Nusselder W, Franco OH. Physical activity types and life expectancy with and without cardiovascular disease. Submitted for publication * Denotes equal contribution within a manuscript Chapter 1 General Introduction 11 12 General Introduction The World Health Organization (WHO) defines overweight and obesity as abnormal or excessive fat accumulation that presents a risk to an individual’s health.1 Physical activity is defined by WHO as any bodily movement produced by skeletal muscles that requires energy expenditure.2 Both obesity and physical inactivity constitute important public health problems because of the association with increased risk of numerous chronic conditions including diabetes, cardiovascular disease, cancer, and disability at older age.3 The increase in life expectancy due to improvement in health care over the last century has been accompanied by an increase in the prevalence of obesity and disability among the elderly.4 Novel and traditional anthropometric measures Body mass index (BMI) is the most common method of measuring overweight and obesity. For calculation of BMI, a person’s body weight (kilograms) is divided by the height (meters) squared.3 According to the WHO, an individual with a BMI of 30 or more is considered obese, and having a BMI equal to or more than 25 is considered overweight.5 To assess general adiposity, BMI is a reasonably good measure and is used commonly in clinical practice. Increased BMI is an established risk factor for diabetes, cardiovascular disease (CVD) and some cancers and consequently for mortality.6,7 However, the association between BMI and mortality is not consistent among young, middle aged and elderly adults and is prone to contradictory conclusions.8 To overcome limitations of BMI, current national and international guidelines advocate for the routine measurement of waist circumference (WC) and waist to hip ratio (WHR) in the assessment of adiposity.9 WC and WHR are measures of waist and hip circumference and provide information about distribution of body fat. Recently, a new anthropometric measure, a body shape index (ABSI), has been developed.10 ABSI has been derived from WC and is independent of height and weight. The added value of ABSI, next to BMI, WC and WHR, has not been addressed in association with total, CVD and cancer mortality among an elderly population. Considering the value of anthropometric measures as a predictive marker for CVD and mortality, these measures can potentially be used in risk prediction models.11 To simplify the traditional cardiovascular risk prediction models, BMI has been proposed to substitute lipids in prediction of CVD risk.12 The simplified cardiovascular risk prediction model is called the non-laboratory based model. This model has similar risk factors (i.e. age, sex, hypertension, smoking status, diabetes mellitus) as the traditional cardiovascular risk prediction model, termed the laboratory- based model, but uses BMI instead of lipids.13 Evidence shows that BMI becomes a less accurate reflection of fat mass in middle-aged and elderly adults and its role in CVD risk prediction seems to diminish with advancing age.14,15 Compared to BMI, assessment of other anthropometric measures, such as WC, WHR and ABSI, could provide better information on CVD risk among the elderly population. Therefore, these measures might be better tools for CVD risk assessment to replace lipids in a non-laboratory based model. Anthropometric measures have also been suggested to assist in identifying individuals at high risk of sarcopenic obesity, a condition defined as a decrease in fat-free mass (FFM) associated with an increase in fat mass (FM).16,17 However, previous research has shown limited evidence for the value of traditional anthropometric measures, such as BMI, in highlighting individuals at high risk for sarcopenic obesity.18 Traditional anthropometric measures, such as BMI and WC, could be attributed to an increase in both FM and FFM.18 The newly developed anthropometric 13 Chapter 1 measure, ABSI, is correlated with WC but is independent of height and weight.10 Therefore, ABSI could have a differential association with FM and FFM that cannot be distinguished by BMI and WC alone. This might highlight ABSI as a good candidate in identifying individuals at high risk of sarcopenic obesity.