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      Lifetime risk and multimorbidity of non-communicable diseases and disease-free life expectancy in the general population: A population-based cohort study

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Non-communicable diseases (NCDs) are leading causes of premature disability and death worldwide. However, the lifetime risk of developing any NCD is unknown, as are the effects of shared common risk factors on this risk.

          Methods and findings

          Between July 6, 1989, and January 1, 2012, we followed participants from the prospective Rotterdam Study aged 45 years and older who were free from NCDs at baseline for incident stroke, heart disease, diabetes, chronic respiratory disease, cancer, and neurodegenerative disease. We quantified occurrence/co-occurrence and remaining lifetime risk of any NCD in a competing risk framework. We additionally studied the lifetime risk of any NCD, age at onset, and overall life expectancy for strata of 3 shared risk factors at baseline: smoking, hypertension, and overweight. During 75,354 person-years of follow-up from a total of 9,061 participants (mean age 63.9 years, 60.1% women), 814 participants were diagnosed with stroke, 1,571 with heart disease, 625 with diabetes, 1,004 with chronic respiratory disease, 1,538 with cancer, and 1,065 with neurodegenerative disease. NCDs tended to co-occur substantially, with 1,563 participants (33.7% of those who developed any NCD) diagnosed with multiple diseases during follow-up. The lifetime risk of any NCD from the age of 45 years onwards was 94.0% (95% CI 92.9%–95.1%) for men and 92.8% (95% CI 91.8%–93.8%) for women. These risks remained high (>90.0%) even for those without the 3 risk factors of smoking, hypertension, and overweight. Absence of smoking, hypertension, and overweight was associated with a 9.0-year delay (95% CI 6.3–11.6) in the age at onset of any NCD. Furthermore, the overall life expectancy for participants without these risk factors was 6.0 years (95% CI 5.2–6.8) longer than for those with all 3 risk factors. Participants aged 45 years and older without the 3 risk factors of smoking, hypertension, and overweight at baseline spent 21.6% of their remaining lifetime with 1 or more NCDs, compared to 31.8% of their remaining life for participants with all of these risk factors at baseline. This difference corresponds to a 2-year compression of morbidity of NCDs. Limitations of this study include potential residual confounding, unmeasured changes in risk factor profiles during follow-up, and potentially limited generalisability to different healthcare settings and populations not of European descent.

          Conclusions

          Our study suggests that in this western European community, 9 out of 10 individuals aged 45 years and older develop an NCD during their remaining lifetime. Among those individuals who develop an NCD, at least a third are subsequently diagnosed with multiple NCDs. Absence of 3 common shared risk factors is associated with compression of morbidity of NCDs. These findings underscore the importance of avoidance of these common shared risk factors to reduce the premature morbidity and mortality attributable to NCDs.

          Abstract

          M. Arfan Ikram & colleagues assess the burden and preventability of co-occurring non-communicable diseases in the population-based Rotterdam Study.

          Author summary

          Why was this study done?
          • The burden and preventive potential of disease is typically estimated for each non-communicable disease (NCD) separately, yet NCDs often co-occur, which hampers reliable quantification of their overall burden as well as the potential to prevent NCDs jointly in the general population.

          • Smoking, hypertension, and overweight are 3 key risk factors that are shared by all NCDs, but their effects on the lifetime risk of developing any NCD, age at onset, and overall life expectancy with and without NCDs are uncertain.

          What did the researchers do and find?
          • Between 1989 and 2012, we continuously followed 9,061 community-dwelling individuals in the Dutch population-based Rotterdam Study for occurrence of NCDs (stroke, heart disease, diabetes, chronic respiratory disease, cancer, and neurodegenerative disease).

          • Nine out of 10 community-dwelling individuals aged 45 years and older will develop any NCD during their lifetime, with a third of them developing multiple NCDs during follow-up.

          • Individuals without the 3 risk factors of smoking, hypertension, and overweight develop their first NCD on average 9 years later than those with all 3 risk factors.

          • Absence of smoking, hypertension, and overweight is associated with a longer overall life expectancy of about 6 years, and a 2-year compression in lifetime spent with NCDs.

          What do these findings mean?
          • In this western European community, we showed that the burden of NCDs in the general population is extensive and their multimorbidity is common.

          • Absence of smoking, hypertension, and overweight is associated with a longer overall life expectancy, and most of this increase is due to an extension of disease-free life expectancy. This means that individuals without these risk factors not only live longer than individuals with these risk factors, but also spend less of their lifetime after the onset of symptomatic disease (which is referred to as compression of morbidity).

          • These findings underscore the potential to substantially reduce premature NCD morbidity and mortality in the general population through prevention of smoking, hypertension, and overweight.

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          Most cited references 22

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          A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010.

          Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2-7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5-7·0]), and alcohol use (5·5% [5·0-5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8-9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6-8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4-6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2-10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water and sanitation accounting for 0·9% (0·4-1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children. Bill & Melinda Gates Foundation. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            The Rotterdam Study: 2018 update on objectives, design and main results

            The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, otolaryngological, locomotor, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. Since 2016, the cohort is being expanded by persons aged 40 years and over. The findings of the Rotterdam Study have been presented in over 1500 research articles and reports (see www.erasmus-epidemiology.nl/rotterdamstudy). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods.
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              The potential for prevention of dementia across two decades: the prospective, population-based Rotterdam Study

              Background Cardiovascular factors and low education are important risk factors of dementia. We provide contemporary estimates of the proportion of dementia cases that could be prevented if modifiable risk factors were eliminated, i.e., population attributable risk (PAR). Furthermore, we studied whether the PAR has changed across the last two decades. Methods We included 7,003 participants of the original cohort (starting in 1990) and 2,953 participants of the extended cohort (starting in 2000) of the Rotterdam Study. Both cohorts were followed for dementia until ten years after baseline. We calculated the PAR of overweight, hypertension, diabetes mellitus, cholesterol, smoking, and education. Additionally, we assessed the PAR of stroke, coronary heart disease, heart failure, and atrial fibrillation. We calculated the PAR for each risk factor separately and the combined PAR taking into account the interaction of risk factors. Results During 57,996 person-years, 624 participants of the original cohort developed dementia, and during 26,177 person-years, 145 participants of the extended cohort developed dementia. The combined PAR in the original cohort was 0.23 (95 % CI, 0.05–0.62). The PAR in the extended cohort was slightly higher at 0.30 (95 % CI, 0.06–0.76). The combined PAR including cardiovascular diseases was 0.25 (95 % CI, 0.07–0.62) in the original cohort and 0.33 (95 % CI, 0.07–0.77) in the extended cohort. Conclusions A substantial part of dementia cases could be prevented if modifiable risk factors would be eliminated. Although prevention and treatment options of cardiovascular risk factors and diseases have improved, the preventive potential for dementia has not declined over the last two decades.
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: ResourcesRole: VisualizationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: MethodologyRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Academic Editor
                Journal
                PLoS Med
                PLoS Med
                plos
                plosmed
                PLoS Medicine
                Public Library of Science (San Francisco, CA USA )
                1549-1277
                1549-1676
                4 February 2019
                February 2019
                : 16
                : 2
                Affiliations
                [1 ] Department of Epidemiology, Erasmus MC–University Medical Center Rotterdam, Rotterdam, the Netherlands
                [2 ] Department of Neurology, Erasmus MC–University Medical Center Rotterdam, Rotterdam, the Netherlands
                [3 ] Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands
                [4 ] Department of Respiratory Medicine, Erasmus MC–University Medical Center Rotterdam, Rotterdam, the Netherlands
                [5 ] Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium
                [6 ] Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America
                [7 ] Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
                [8 ] Department of Radiology and Nuclear Medicine, Erasmus MC–University Medical Center Rotterdam, Rotterdam, the Netherlands
                [9 ] Department of Cardiology, Erasmus MC–University Medical Center Rotterdam, Rotterdam, the Netherlands
                Stanford University, UNITED STATES
                Author notes

                I have read the journal’s policy and the authors of this manuscript have the following competing interests: LL has received unrestricted research awards/grants from AstraZeneca and Chiesi, and provided expert consultation for Boehringer Ingelheim GmbH and Novartis, outside of the submitted work. MJGL reports grants from Prins Bernhard Cultuurfonds 2014; grants from De Drie Lichten Foundation 2014; grants from Erasmus University Trustfonds 2014; personal fees from American Heart Association (AHA) 2014; personal fees from Netherlands Epidemiology Society (VvE) 2014; personal fees from European Society of Cardiology (ESC) 2013; personal fees from Dutch Heart Foundation (DHF) 2016; personal fees from Capri Cardiac Rehabilitation Foundation Rotterdam 2016; grants from Albert Schweitzer Hospital Research Fund 2018; grants from Oncology Research Albert Schweitzer (ORAS) Foundation 2018; grants from Promoting Advanced Cardiology through Education (PACE) Foundation 2018; all outside of the submitted work.

                ‡ These authors are joint senior authors on this work.

                Article
                PMEDICINE-D-18-03486
                10.1371/journal.pmed.1002741
                6361416
                30716101
                © 2019 Licher et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Figures: 5, Tables: 2, Pages: 17
                Product
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100003061, Erasmus Medisch Centrum;
                Funded by: funder-id http://dx.doi.org/10.13039/501100001828, Erasmus Universiteit Rotterdam;
                Funded by: funder-id http://dx.doi.org/10.13039/501100001826, ZonMw;
                Funded by: Research Institute for Diseases in the Elderly (RIDE)
                Funded by: funder-id http://dx.doi.org/10.13039/501100003245, Ministerie van Onderwijs, Cultuur en Wetenschap;
                Funded by: funder-id http://dx.doi.org/10.13039/501100002999, Ministerie van Volksgezondheid, Welzijn en Sport;
                Funded by: European Commission (DG XII)
                Funded by: Municaplity of Rotterdam
                Funded by: funder-id http://dx.doi.org/10.13039/501100002996, Hartstichting;
                Award ID: 2012T008
                Funded by: funder-id http://dx.doi.org/10.13039/501100004622, KWF Kankerbestrijding;
                Award ID: 20157737
                The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. Further support was obtained from the Netherlands Consortium for Healthy Ageing and the Dutch Heart Foundation (2012T008) and the Dutch Cancer Society (NKI-20157737). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Epidemiology
                Medical Risk Factors
                Cancer Risk Factors
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                Oncology
                Cancer Risk Factors
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                Epidemiology
                Medical Risk Factors
                Biology and Life Sciences
                Population Biology
                Population Metrics
                Life Expectancy
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                Public and Occupational Health
                Life Expectancy
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                Cardiovascular Diseases
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                Vascular Medicine
                Blood Pressure
                Hypertension
                Medicine and Health Sciences
                Neurology
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                Neurology
                Cerebrovascular Diseases
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                Stroke
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Metabolic Disorders
                Diabetes Mellitus
                Custom metadata
                Rotterdam Study data can be made available to interested researchers upon request. Requests can be directed to data manager Frank J.A. van Rooij ( f.vanrooij@ 123456erasmusmc.nl ) or visit the following website for more information http://www.ergo-onderzoek.nl/wp/contact. We are unable to place data in a public repository due to legal and ethical restraints. Sharing of individual participant data was not included in the informed consent of the study, and there is potential risk of revealing participants’ identities as it is not possible to completely anonymize the data.

                Medicine

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