Cohort Profile: Hong Kong Department of Health Elderly Health Service Cohort

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1 International Journal of Epidemiology, 2016, doi: /ije/dyu227 Advance Access Publication Date: 5 December 2014 Cohort Profile Cohort Profile Cohort Profile: Hong Kong Department of Health Elderly Health Service Cohort CM Schooling, 1 WM Chan, 2 SL Leung, 2 TH Lam, 1 * SY Lee, 2 C Shen, 1 JY Leung 1 and GM Leung 1 1 School of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China and 2 Department of Health, Government of Hong Kong SAR, China *Corresponding author. School of Public Health, Li Ka Shing Faculty of Medicine, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China. hrmrlth@hkucc.hku.hk This author has now retired. Accepted 10 November 2014 Abstract The Department of Health Elderly Health Service Cohort in Hong Kong was set up to promote understanding of ageing in a global context, to exploit the role of Hong Kong as a sentinel for populations currently experiencing very rapid economic development, to provide a developed non-western social laboratory where empirically derived hypotheses can be tested and to leverage the different patterns of common chronic diseases between East and West to generate novel hypotheses about their determinants. The initial cohort enrolled from July 1998 to the end of December 2001 includes people aged 65 years or older, forming about 9% of the population of this age. A comprehensive health assessment was made at enrolment and then repeated regularly on an ongoing basis. The health assessment included a comprehensive assessment of lifestyle, social circumstances, physical health and mental health, including an assessment of cognition and depressive symptoms. Health services use and deaths have been obtained by record linkage and confirmed, where necessary, by telephone interview. Currently, the data are not publicly available; we would welcome collaborations and research proposals. Key Messages In a developed non-western setting, smoking was positively associated with mortality into very old age; benefits of quitting at old age were also evident. In a developed non-western setting, where occasional alcohol use is typical, we found little evidence of moderate alcohol use being consistently associated with lower mortality, suggesting that observed benefits may be contextually specific rather than biologically based. VC The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association 64

2 International Journal of Epidemiology, 2016, Vol. 45, No Among older people, body mass index (BMI) was positively associated with mortality among people in good health and negatively associated with BMI among people in poor health, suggesting BMI may be acting as a marker of health status as well as of adiposity. Why was the cohort set up? Population ageing is a common concern, whose ramifications are not fully understood because the current older generation has had different lifetime experiences from previous generations. Longitudinal studies of older people have been set up to track health, functional status and health services utilization as people age, 1 11 mainly in Western Europe and North America. The lifetime experience of cohorts from these settings with a history of economic development since the Industrial Revolution is not representative of the vast majority of the global population, who have often experienced much more rapid economic development from pre-industrial living conditions over one lifetime. 12 Similar longitudinal studies are now being established in low- and middle-income countries, but represent cohorts ageing in a developing country setting. The Hong Kong population provides a unique bridge between experiences in developing and developed populations. Hong Kong has had a standard of living and social infrastructure similar to Western Europe or North America for some years, 16 but a population who in one lifetime have experienced economic transition from pre- to post-industrial living conditions, 17 as most of the current generation of older people in Hong Kong were born in pre-industrial China. 18,19 Hong Kong is also a very densely populated large city with, similar to many other metropolitan centres in Asia, high levels of air pollution 20 and potential stresses from extremes of temperature. As a setting for investigating some key public health questions, Hong Kong has some unique attributes. First, patterns of confounding in Hong Kong sometimes differ from Western populations, providing an opportunity to test empirically derived hypotheses from Western settings. For example, the typical alcohol drinker in Southern China tends to drink occasionally and to have healthier attributes than neverdrinkers, whereas moderate alcohol drinkers are more similar to never-drinkers. 21 In contrast, moderate alcohol users in Western settings tend to have healthier attributes than neverdrinkers. 22 Second, Hong Kong has different patterns of chronic diseases compared with Western populations, with, as is common in East Asia, high rates of diabetes in a relatively non-obese population, 23 alongside low rates, and possibly falling rates, of ischaemic heart disease, 24,25 for reasons which have not been clearly elucidated. 26,27 Thus research in Hong Kong generates novel questions, which may result in generalized insights. For example, the question of what makes thin people vulnerable to diabetes has focused attention on theroleofmusclemassanditsdriversindiabetes, 28,29 with potential global relevance. In view of the need to understand ageing in a global context, the role of Hong Kong as a sentinel and social laboratory, the different pattern of diseases and the relative dearth of non-western studies, Professor Tai Hing Lam of the School of Public Health at the University of Hong Kong and Drs Wai Man Chan and Kin Sang Ho of the Department of Health, the Government of Hong Kong Special Administrative Region far-sightedly took advantage of a service initiative to establish a cohort of older Chinese in Hong Kong. In July 1998 the Department of Health established 18 Elderly Health Centres in Hong Kong (Figure 1), one in each district (Figure 1), to offer older people screening services and medical examinations, aiming to enhance primary health care by improving self-care ability, encouraging healthy living and strengthening social integration. All residents of Hong Kong aged 65 years or older were eligible to enrol, with a low yearly membership fee (110 Hong Kong dollars, 14.1 US dollars), which is waived for those with financial hardship. These enrollees were then tracked prospectively, thus forming a large cohort in a unique setting. Who is in the cohort? The sampling frame of this study consists of all older people (65þ years) in Hong Kong. From July 1998 to the end of 2001, people, i.e., about 9% of older people in Hong Kong, enrolled at the Elderly Health Centres. The cohort is now being extended to include enrollees in subsequent years. Including the who enrolled from 1998 to 2001, there are now potentially some elders who have enrolled since How often have they been followed up and what is the attrition like? Older people enrolled at the Elderly Health Centres have a baseline examination and then may attend for repeat examinations on a regular basis. Given the close relations established over many years between the School of Public Health at the University of Hong Kong and the public healthcare service providers in Hong Kong, i.e. the Hospital Authority and the Department of Health, this cohort has been assembled via record linkage using a

3 66 International Journal of Epidemiology, 2016, Vol. 45, No. 1 common unique identifier (Hong Kong identity card number) to several sources of routinely collected data, to create a de-identified cohort. Deaths are obtained by the Department of Health from the very comprehensive death registration in Hong Kong, coded using International Classifications of Disease (ICD) 9th revision up to and including 2000, and ICD10 thereafter. Most deaths in Hong Kong occur in hospital, 30 facilitating accurate ascertainment of death, although as elsewhere autopsy rates are falling and inevitable misclassifications may occur. 31 Record linkage to use of public healthcare services is used to confirm that participants are alive and living in Hong Kong. For participants whose vital status cannot be ascertained, telephone interviews have been conducted to obtain vital status and cause of death (Figure 2). Hospitalizations, outpatient visits and prescriptions in the public sector have been similarly obtained by record linkage. In addition, surveys have been implemented for defined subsets to provide additional information on specific topics (Figure 2), such as health-related quality of life. 32 What has been measured? Physical examination Each enrollee had clinical and physical examinations at baseline, including recording of body mass index, blood pressure and spot cholesterol. Fresh serum samples or serum samples stored at 4 C for no more than 2 days were used to measure total cholesterol with an Abbot Aeroset analyser (Abbott Diagnostics, North Chicago, IL, USA). For those who reported having diabetes, but not others, glycated haemoglobin was measured using high-performance liquid chromatography (Variant II analyser with the Variant II HbA1c NU Kit; Bio-Rad Laboratories, Hercules, CA, USA). Face-to face interview Information on demographic characteristics, socioeconomic position, lifestyle (smoking, passive smoking, alcohol use and physical activity), social functioning, health status (medical history, current diseases and health service use), self-rated health, functional status and mental health is collected by nurses and doctors using a standardized structured questionnaire at each examination (Table 1). Cognitive status is assessed from the mini-mental test, 33,34 physical functioning from the Instrumental Activities of Daily Living scale 35,36 and depressive symptoms from the Geriatric Depression Scale. 37 What has it found? Key findings and publications Mean age is 72.4 years, ranging from 65 to 105 years, with 66% women. Many of the women had no formal Figure 1. Location of the Hong Kong Department of Health Elderly Health Service Cohort and the 18 Elderly Health Centres (inset).

4 International Journal of Epidemiology, 2016, Vol. 45, No education, which enables a different perspective on the role of education to be investigated in this cohort. As is typical in Southern China few women smoke or drink, with a high proportion of never drinkers among the men. although moderate alcohol use was associated with a higher risk of specifically oesophageal cancer, 53 as would be expected. Moderate alcohol use had similar associations with mortality from respiratory diseases as occasional Smoking Table 1. Summary of data collected at baseline in the Hong Kong Department of Health Elderly Health Service Cohort Smoking is known to kill; however, this is not always obvious at the start of the smoking epidemic nor among older people. In this cohort, the harmful effects of smoking are evident close to the end of life (Figure 3a) 38 with a higher risk of death from all-causes, respiratory diseases including tuberculosis, 39 cancer, cardiovascular disease including haemorrhagic stroke, 40 and influenza-related diseases, 41 whereas the benefits of quitting are evident even in old age. 42 Alcohol use The effects of alcohol on health are controversial, because the long-term health benefits observed for light to moderate drinkers 43,44 could be the result of attributes of people who choose and are able to drink in moderation, rather than of alcohol Evidence from long-term experimental studies is unlikely to become available for logistic and ethical reasons. Hong Kong provides a setting to test whether the benefits of moderate alcohol use observed in the West are due to biological pathways or contextual biases, because of the different types of alcohol used (mainly beer, spirits and rice wine with little grape wine) 49 and the different social patterning of moderate alcohol use. 50 In our setting, moderate alcohol use was not associated with a lower risk of death from ischaemic heart disease, 51 cardiovascular disease 52 or cancer (Figure 3b), 53 Exposure category Demographics and socioeconomic position Lifestyle Social functioning Health status Functional status Mental health Variable Age Sex Education Housing type Financial status Marital status Smoking history Passive smoking Alcohol use Physical activity Social contact Medical history Current diseases Family history of diseases Use of medication Hospitalizations in the past year Self-rated health Recent falls Body mass index Blood pressure Cholesterol Activities of daily living Instrumental activities of daily living Abbreviated mental test Mini mental state examination Geriatric Depression Scale Figure 2. Timeline for the Hong Kong Department of Health Elderly Health Services Cohort.

5 68 International Journal of Epidemiology, 2016, Vol. 45, No. 1 alcohol use, suggesting the association is not due to the biological properties of alcohol (Figure 3b). 50 A genetic variant, (inactive ALDH2 alleles) common in East Asia, affects alcohol use 54 by slowing metabolism of acetaldehyde, which is a common environmental exposure that causes bronchoconstriction; 55 so the observed associations may be a reflection of genetic confounding by ALDH2 alleles. 56 Moreover, associations of moderate alcohol use with overall mortality varied across strata of health status, 52 suggesting some of the associations might reflect alcohol use as a marker of health. Although these findings are somewhat different from observations in Western settings, 43,44 they are more consistent with a more nuanced interpretation of these studies, 57 as being a reflection of residual confounding, selection bias and changes in alcohol use with ill-health rather than an indicator of the biological effects of alcohol. 58 In addition, the body mass index at which mortality is lowest has increased over the past century. 59,60 Adiposity may have different physiological effects at different ages and at different times, or even have some benefits. However, it is unusual for the effects of a causal factor to have different effects on the same outcomes, 61 although for physiological reasons the same factor may have different effects on different outcomes. In this cohort, obesity was associated with a lower risk of lung cancer, 62 a lower risk of active tuberculosis 63 and a higher risk of influenza-associated mortality. 64 We took advantage of the large size of the cohort to show that the association of body mass index (BMI) with mortality varied with health status, and was not evident among those in good health (Figure 3c), 65 because in older people BMI may be a marker rather than a cause of health status. These findings are consistent with the concept of no healthy obesity. Obesity The association of adiposity with mortality also remains controversial because associations are not consistent, but instead vary with age and historic time, such that associations are stronger in younger people and in earlier periods. 59 Contextually specific patterns of disease Reasons for the variation in the pattern of and risk factors for common chronic diseases by setting are not clearly understood Given the Hong Kong population s lifetime experience, many older people experienced very Figure 3. Selected findings from the Hong Kong Department of Health Elderly Health Services Cohort. a) Ever-smoking and all-cause mortality by age. b) Alcohol use and mortality by cause. c) BMI and all-cause mortality by number of comorbidities. d)depression and mortality by cause.

6 International Journal of Epidemiology, 2016, Vol. 45, No limited early living conditions and tuberculosis is relatively common. Passive smoking and diabetes were associated with tuberculosis, 69,70 which in turn is associated with death from lung cancer. 71 Conversely, obstructive lung disease was not associated with lung cancer. 72 Depression was, as expected, strongly associated with suicide for both men and women, 73 but was not clearly associated with a higher risk of death from all-causes, 73 cardiovascular diseases, respiratory diseases or cancer, although both depression and depressive symptoms were associated with cardiovascular diseases among men only (Figure 3d). 73,74 Such inconsistent associations by sex for depression and cardiovascular disease suggest unmeasured confounding, and give impetus to obtaining a better understanding of the role of depression using suitable designs such as Mendelian randomization. Finally, self-reported diabetes in the cohort was associated with death from cardiovascular disease, as would be expected, but not with the cancers associated with obesity, but rather with the cancers associated with early-life infections. 75 The contextually specific effects of diabetes suggest contextually specific causes less related to obesity but perhaps more related to the poor early-life living conditions that might drive exposure to infections and preclude the development of substantial muscle mass. Next steps We are now planning on characterizing trajectories of key attributes with ageing, such as alcohol use, BMI and selfrated health or health status, to elucidate how these change with approaching death, and how these changes might inform interpretation of observed associations. Building on our previous work we also intend to characterize service use in the years before death and assess its determinants, 76 for service planning purposes. Given concerns about air pollution, a high priority is to assess the effects of air pollution on morbidity and mortality in this cohort. Finally, we plan to explore the role of environment by comparing the Elderly Health Service Cohort in Hong Kong with the Guangzhou Biobank Cohort Study 77 in the neighbouring province of Guangdong, because the participants share a common Cantonese heritage, may have been born into similar circumstances in similar places, but spent most of their lives in very different political and economic systems, i.e. under British colonial rule in Hong Kong until 1997 whereas Guangzhou was part of the People s Republic of China from its establishment in What are the main strengths and weakness? The Elderly Health Services Cohort provides a study of older people from an under-studied developed non-western population. The strengths of our cohort are the large sample size and long duration of follow-up (from 1998 till now). However, several limitations deserve attention. Our participants are volunteers, who might be healthier and more health-conscious than the general older population of Hong Kong. More women were enrolled than men; otherwise, age, socioeconomic position, current smoking status and hospital use were similar to the general older population in Hong Kong. 65 The volunteer nature of the cohort will only create a biased association if the association for the people enrolled in our cohort is different from the association for those not enrolled, which has to be assessed research question by research question. As with all cohorts of older people, survivor bias may occur if those particularly vulnerable to a particular exposure died before the age of 65 years. Again, this possibility has to be assessed exposure by exposure. Given the difficulty of collecting reliable dietary information, we do not have extensive information about diet in this cohort. We also do not have stored bio-materials, so we cannot use Mendelian randomization to substantiate causality of any observed associations. We are planning to collect bio-materials in the future. Can I get hold of the data? Where can I find out more? We have no immediate plans to make the data freely available in the public domain. Further details may be obtained from [hkusph@hku.hk]. We are keen to obtain full value from our cohorts and would welcome proposals to exploit this cohort from potential collaborators or from researchers interested in investigating specific questions independently. Funding Funding to build, expand and exploit this cohort includes grants from the Health Services Research Fund (S111016), Health and Health Services Research Fund ( , and ), Research Fund for the Control of Infectious Diseases ( and ), Research Grants Council (7448/05H and M), Government of Hong Kong SAR and the Wellcome Trust (WT094330MA). Acknowledgements We wish to thank the staff of the Elderly Health Service, Department of Health, particularly Shelley Chan, and the Hospital Authority, the Government of Hong Kong Special Administrative Region for their assistance in data collection and entry. We would also like to acknowledge the contribution of Dr PY Leung, when at the Department of Health, in facilitating the creation of the cohort. We also thank Dr Cindy Lin for generating Figure 1.

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9 72 International Journal of Epidemiology, 2016, Vol. 45, No Sun WJ, Xu L, Chan WM, Lam TH, Schooling CM. Are depressive symptoms associated with cardiovascular mortality among older Chinese: a cohort study of 64,000 people in Hong Kong?. Am J Geriatr Psychiatry 2013;21: Shen C, Schooling CM, Chan WM, Lee SY, Leung GM, Lam TH. Self-reported diabetes and mortality in a prospective Chinese elderly cohort study in Hong Kong. Prev Med 2014;64: McGhee SM, Schooling CM, Wong LC et al. Does smoking affect hospital use before death? A comparison of ever- and never-smokers in the last years of life. Med Care 2008;46: Jiang C, Thomas GN, Lam TH et al. Cohort Profile: The Guangzhou Biobank Cohort Study, a Guangzhou-Hong Kong-Birmingham collaboration. Int J Epidemiol 2006; 35: