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. 2015 Jul 7;314(1):52-60.
doi: 10.1001/jama.2015.7008.

Association of Cardiometabolic Multimorbidity With Mortality

Emerging Risk Factors CollaborationEmanuele Di Angelantonio  1 Stephen Kaptoge  1 David Wormser  1 Peter Willeit  1 Adam S Butterworth  1 Narinder Bansal  1 Linda M O'Keeffe  1 Pei Gao  1 Angela M Wood  1 Stephen Burgess  1 Daniel F Freitag  1 Lisa Pennells  1 Sanne A Peters  2 Carole L Hart  3 Lise Lund Håheim  4 Richard F Gillum  5 Børge G Nordestgaard  6 Bruce M Psaty  7 Bu B Yeap  8 Matthew W Knuiman  8 Paul J Nietert  9 Jussi Kauhanen  10 Jukka T Salonen  11 Lewis H Kuller  12 Leon A Simons  13 Yvonne T van der Schouw  2 Elizabeth Barrett-Connor  14 Randi Selmer  15 Carlos J Crespo  16 Beatriz Rodriguez  17 W M Monique Verschuren  18 Veikko Salomaa  19 Kurt Svärdsudd  20 Pim van der Harst  21 Cecilia Björkelund  22 Lars Wilhelmsen  22 Robert B Wallace  23 Hermann Brenner  24 Philippe Amouyel  25 Elizabeth L M Barr  26 Hiroyasu Iso  27 Altan Onat  28 Maurizio Trevisan  29 Ralph B D'Agostino Sr  30 Cyrus Cooper  31 Maryam Kavousi  32 Lennart Welin  33 Ronan Roussel  34 Frank B Hu  35 Shinichi Sato  36 Karina W Davidson  37 Barbara V Howard  38 Maarten J G Leening  32 Maarten Leening  32 Annika Rosengren  39 Marcus Dörr  40 Dorly J H Deeg  41 Stefan Kiechl  42 Coen D A Stehouwer  43 Aulikki Nissinen  19 Simona Giampaoli  44 Chiara Donfrancesco  44 Daan Kromhout  45 Jackie F Price  46 Annette Peters  47 Tom W Meade  48 Edoardo Casiglia  49 Debbie A Lawlor  50 John Gallacher  51 Dorothea Nagel  52 Oscar H Franco  32 Gerd Assmann  53 Gilles R Dagenais  54 J Wouter Jukema  55 Johan Sundström  20 Mark Woodward  56 Eric J Brunner  57 Kay-Tee Khaw  1 Nicholas J Wareham  58 Eric A Whitsel  59 Inger Njølstad  60 Bo Hedblad  61 Sylvia Wassertheil-Smoller  62 Gunnar Engström  61 Wayne D Rosamond  63 Elizabeth Selvin  64 Naveed Sattar  3 Simon G Thompson  1 John Danesh  1
Collaborators, Affiliations

Association of Cardiometabolic Multimorbidity With Mortality

Emerging Risk Factors Collaboration et al. JAMA. .

Erratum in

Abstract

Importance: The prevalence of cardiometabolic multimorbidity is increasing.

Objective: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity.

Design, setting, and participants: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates.

Exposures: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI).

Main outcomes and measures: All-cause mortality and estimated reductions in life expectancy.

Results: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy.

Conclusions and relevance: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

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Conflict of interest statement

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

Figures

Figure 1
Figure 1
All-Cause Mortality for the Emerging Risk Factors Collaboration by Disease Status of Participants at Baseline The mortality rates were calculated using a Poisson regression model and are sex-adjusted rates to the age of 60 years. The hazard ratios were calculated using a Cox proportional hazards regression model and are stratified by sex and adjusted by age at baseline. Analyses were based on participants from 91 studies. MI indicates myocardial infarction. a Mortality rate is per 1000 person-years.
Figure 2
Figure 2
All-Cause Mortality From the Emerging Risk Factors Collaboration Compared With the UK Biobank and Previous Reports The hazard ratios were adjusted for sex when appropriate and age, except those for the Hispanic Established Population for the Epidemiological Study of the Elderly, which were adjusted for additional variables. MI indicates myocardial infarction. The size of the data markers is proportional to the information content in each study. a For participant-level analyses in the Emerging Risk Factors Collaboration and the UK Biobank, participants with the disease status indicated at baseline have been compared with participants within the same cohorts without diabetes, stroke, or myocardial infarction at baseline. b For previously published studies, participants with cardiometabolic multimorbidity at baseline were compared with participants without any such conditions. c Used history of coronary heart disease instead of history of MI.
Figure 3
Figure 3
Modeling of Years of Life Lost by Disease Status of Participants at Baseline Compared With Those Free of Diabetes, Stroke, and Myocardial Infarction (MI) The estimates of cumulative survival from 40 years of age onward among the 8 baseline disease groups were calculated by applying hazard ratios (specific to age at risk and sex) for all-cause mortality associated with baseline disease status to US cause-specific death rates at the age of 40 years or older.

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