Association of Cardiometabolic Multimorbidity With Mortality

Emerging Risk Factors Collaboration, Emanuele Di Angelantonio, Stephen Kaptoge, David Wormser, Peter Willeit, Adam S Butterworth, Narinder Bansal, Linda M O'Keeffe, Pei Gao, Angela M Wood, Stephen Burgess, Daniel F Freitag, Lisa Pennells, Sanne A Peters, Carole L Hart, Lise Lund Håheim, Richard F Gillum, Børge G Nordestgaard, Bruce M Psaty, Bu B Yeap, Matthew W Knuiman, Paul J Nietert, Jussi Kauhanen, Jukka T Salonen, Lewis H Kuller, Leon A Simons, Yvonne T van der Schouw, Elizabeth Barrett-Connor, Randi Selmer, Carlos J Crespo, Beatriz Rodriguez, W M Monique Verschuren, Veikko Salomaa, Kurt Svärdsudd, Pim van der Harst, Cecilia Björkelund, Lars Wilhelmsen, Robert B Wallace, Hermann Brenner, Philippe Amouyel, Elizabeth L M Barr, Hiroyasu Iso, Altan Onat, Maurizio Trevisan, Ralph B D'Agostino Sr, Cyrus Cooper, Maryam Kavousi, Lennart Welin, Ronan Roussel, Frank B Hu, Shinichi Sato, Karina W Davidson, Barbara V Howard, Maarten J G Leening, Maarten Leening, Annika Rosengren, Marcus Dörr, Dorly J H Deeg, Stefan Kiechl, Coen D A Stehouwer, Aulikki Nissinen, Simona Giampaoli, Chiara Donfrancesco, Daan Kromhout, Jackie F Price, Annette Peters, Tom W Meade, Edoardo Casiglia, Debbie A Lawlor, John Gallacher, Dorothea Nagel, Oscar H Franco, Gerd Assmann, Gilles R Dagenais, J Wouter Jukema, Johan Sundström, Mark Woodward, Eric J Brunner, Kay-Tee Khaw, Nicholas J Wareham, Eric A Whitsel, Inger Njølstad, Bo Hedblad, Sylvia Wassertheil-Smoller, Gunnar Engström, Wayne D Rosamond, Elizabeth Selvin, Naveed Sattar, Simon G Thompson, John Danesh, Eric A Whitsel, Lisa Miller Wruck, Elizabeth Selvin, Wayne D Rosamond, Jonathan E Shaw, Paul Z Zimmet, Elizabeth LM Barr, Matthew W Knuiman, Mark Divitini, Peter H Whincup, S Goya Wannamethee, Richard W Morris, Stefan Kiechl, Johann Willeit, Siegfried Weger, Arno Gasperi, Debbie A Lawlor, Shah Ebrahim, John Gallacher, Yoav Ben-Shlomo, John WG Yarnell, Edoardo Casiglia, Paul J Nietert, Susan E Sutherland, David L Bachman, Mary Cushman, Bruce M Psaty, Richard A Kronmal, Randi Selmer, Anne J Søgaard, Lise L Håheim, Børge G Nordestgaard, Anne Tybjærg-Hansen, Ruth Frikke-Schmidt, Gorm B Jensen, Simona Giampaoli, Salvatore Panico, Diego Vanuzzo, Luigi Palmieri, Ronan Roussel, Fabrice Bonnet, Stephane Cauchi, Frédéric Fumeron, Leon A Simons, Judith Simons, Jackie F Price, Stela McLachlan, Amanda Lee, Caroline L Phillips, Jack M Guralnik, James O Taylor, Robert B Wallace, Frank Kohout, Jack M Guralnik, Caroline L Phillips, Jack M Guralnik, Dan G Blazer, Caroline L Phillips, Jack M Guralnik, Joanne M McGloin, Kay-Tee Khaw, Nicholas J Wareham, Hermann Brenner, Ben Schöttker, Kai-Uwe Saum, Dietrich Rothenbacher, Aulikki Nissinen, Chiara Donfrancesco, Simona Giampaoli, Veikko Salomaa, Erkki Vartiainen, Pekka Jousilahti, Kennet Harald, Ralph B D'Agostino Sr, Joseph M Massaro, Vasan S Ramachandran, Kurt Svärdsudd, Henry Eriksson, Georgios Lappas, Catharina Welin, Annika Rosengren, Henry Eriksson, Georgios Lappas, Catharina Welin, Lennart Welin, Henry Eriksson, Georgios Lappas, Catharina Welin, Cecilia Björkelund, Dorothea Nagel, Cyrus Cooper, Elaine M Dennison, Leon Flicker, Graeme J Hankey, Paul E Norman, Osvaldo P Almeida, Jon Golledge, Beatriz Rodriguez, Coen DA Stehouwer, Jacqueline M Dekker, Giel Nijpels, Frank B Hu, Shinichi Sato, Jussi Kauhanen, Jukka T Salonen, Tomi-Pekka Tuomainen, Sudhir Kurl, Sari Voutilainen, Dorly JH Deeg, Jan L Poppelaars, Renate T de Jongh, Tom W Meade, WM Monique Verschuren, Bo Hedblad, Olle Melander, Carole L Hart, Naveed Sattar, Alex McConnachie, Graham Watt, Annette Peters, Christa Meisinger, Barbara Thorand, Wolfgang Koenig, WM Monique Verschuren, Lars Wilhelmsen, Henry Eriksson, Georgios Lappas, Catharina Welin, Gunnar Engström, Peter M Nilsson, Dorothea Nitsch, Chris Bulpitt, Lewis H Kuller, Greg Grandits, Randi Selmer, Sidsel Graff-Iversen, Richard F Gillum, Karina W Davidson, Jonathan A Shaffer, Hiroyasu Iso, Shinichi Sato, Randi Selmer, Sidsel Graff-Iversen, Lise L Håheim, Pim van der Harst, Stephan JL Bakker, Hans L Hillege, Ron T Gansevoort, Carlos J Crespo, Philippe Amouyel, Jean Dallongeville, Gerd Assmann, Helmut Schulte, Yvonne T van der Schouw, Joline WJ Beulens, J Wouter Jukema, Ian Ford, David J Stott, Gilles R Dagenais, Bernard Cantin, Jean-Pierre Després, Benoît Lamarche, Elizabeth Barrett-Connor, Alka M Kanaya, Kimbach T Carpiuc, Assiamira Ferrara, Trevisan Maurizio, Oscar H Franco, Albert Hofman, Frank JA van Rooij, M Arfan Ikram, Maryam Kavousi, Abbas Dehghan, Jan Heeringa, Jessica C Kiefte-de Jong, Maarten JG Leening, Symen Ligthart, Janine F Felix, Loes Jaspers, Hugh Tunstall-Pedoe, Mark Woodward, Marcus Dörr, Stephan B Felix, Roberto Lorbeer, Henry Völzke, Barbara V Howard, Lyle Best, Yoav Ben-Shlomo, Altan Onat, Inger Njølstad, Johan Sundström, Johan Ärnlöv, Lars Lind, Erik Ingelsson, Sylvia Wassertheil-Smoller, Michael Marmot, Astrid Fletcher, Eric J Brunner, Daan Kromhout, Emerging Risk Factors Collaboration, Emanuele Di Angelantonio, Stephen Kaptoge, David Wormser, Peter Willeit, Adam S Butterworth, Narinder Bansal, Linda M O'Keeffe, Pei Gao, Angela M Wood, Stephen Burgess, Daniel F Freitag, Lisa Pennells, Sanne A Peters, Carole L Hart, Lise Lund Håheim, Richard F Gillum, Børge G Nordestgaard, Bruce M Psaty, Bu B Yeap, Matthew W Knuiman, Paul J Nietert, Jussi Kauhanen, Jukka T Salonen, Lewis H Kuller, Leon A Simons, Yvonne T van der Schouw, Elizabeth Barrett-Connor, Randi Selmer, Carlos J Crespo, Beatriz Rodriguez, W M Monique Verschuren, Veikko Salomaa, Kurt Svärdsudd, Pim van der Harst, Cecilia Björkelund, Lars Wilhelmsen, Robert B Wallace, Hermann Brenner, Philippe Amouyel, Elizabeth L M Barr, Hiroyasu Iso, Altan Onat, Maurizio Trevisan, Ralph B D'Agostino Sr, Cyrus Cooper, Maryam Kavousi, Lennart Welin, Ronan Roussel, Frank B Hu, Shinichi Sato, Karina W Davidson, Barbara V Howard, Maarten J G Leening, Maarten Leening, Annika Rosengren, Marcus Dörr, Dorly J H Deeg, Stefan Kiechl, Coen D A Stehouwer, Aulikki Nissinen, Simona Giampaoli, Chiara Donfrancesco, Daan Kromhout, Jackie F Price, Annette Peters, Tom W Meade, Edoardo Casiglia, Debbie A Lawlor, John Gallacher, Dorothea Nagel, Oscar H Franco, Gerd Assmann, Gilles R Dagenais, J Wouter Jukema, Johan Sundström, Mark Woodward, Eric J Brunner, Kay-Tee Khaw, Nicholas J Wareham, Eric A Whitsel, Inger Njølstad, Bo Hedblad, Sylvia Wassertheil-Smoller, Gunnar Engström, Wayne D Rosamond, Elizabeth Selvin, Naveed Sattar, Simon G Thompson, John Danesh, Eric A Whitsel, Lisa Miller Wruck, Elizabeth Selvin, Wayne D Rosamond, Jonathan E Shaw, Paul Z Zimmet, Elizabeth LM Barr, Matthew W Knuiman, Mark Divitini, Peter H Whincup, S Goya Wannamethee, Richard W Morris, Stefan Kiechl, Johann Willeit, Siegfried Weger, Arno Gasperi, Debbie A Lawlor, Shah Ebrahim, John Gallacher, Yoav Ben-Shlomo, John WG Yarnell, Edoardo Casiglia, Paul J Nietert, Susan E Sutherland, David L Bachman, Mary Cushman, Bruce M Psaty, Richard A Kronmal, Randi Selmer, Anne J Søgaard, Lise L Håheim, Børge G Nordestgaard, Anne Tybjærg-Hansen, Ruth Frikke-Schmidt, Gorm B Jensen, Simona Giampaoli, Salvatore Panico, Diego Vanuzzo, Luigi Palmieri, Ronan Roussel, Fabrice Bonnet, Stephane Cauchi, Frédéric Fumeron, Leon A Simons, Judith Simons, Jackie F Price, Stela McLachlan, Amanda Lee, Caroline L Phillips, Jack M Guralnik, James O Taylor, Robert B Wallace, Frank Kohout, Jack M Guralnik, Caroline L Phillips, Jack M Guralnik, Dan G Blazer, Caroline L Phillips, Jack M Guralnik, Joanne M McGloin, Kay-Tee Khaw, Nicholas J Wareham, Hermann Brenner, Ben Schöttker, Kai-Uwe Saum, Dietrich Rothenbacher, Aulikki Nissinen, Chiara Donfrancesco, Simona Giampaoli, Veikko Salomaa, Erkki Vartiainen, Pekka Jousilahti, Kennet Harald, Ralph B D'Agostino Sr, Joseph M Massaro, Vasan S Ramachandran, Kurt Svärdsudd, Henry Eriksson, Georgios Lappas, Catharina Welin, Annika Rosengren, Henry Eriksson, Georgios Lappas, Catharina Welin, Lennart Welin, Henry Eriksson, Georgios Lappas, Catharina Welin, Cecilia Björkelund, Dorothea Nagel, Cyrus Cooper, Elaine M Dennison, Leon Flicker, Graeme J Hankey, Paul E Norman, Osvaldo P Almeida, Jon Golledge, Beatriz Rodriguez, Coen DA Stehouwer, Jacqueline M Dekker, Giel Nijpels, Frank B Hu, Shinichi Sato, Jussi Kauhanen, Jukka T Salonen, Tomi-Pekka Tuomainen, Sudhir Kurl, Sari Voutilainen, Dorly JH Deeg, Jan L Poppelaars, Renate T de Jongh, Tom W Meade, WM Monique Verschuren, Bo Hedblad, Olle Melander, Carole L Hart, Naveed Sattar, Alex McConnachie, Graham Watt, Annette Peters, Christa Meisinger, Barbara Thorand, Wolfgang Koenig, WM Monique Verschuren, Lars Wilhelmsen, Henry Eriksson, Georgios Lappas, Catharina Welin, Gunnar Engström, Peter M Nilsson, Dorothea Nitsch, Chris Bulpitt, Lewis H Kuller, Greg Grandits, Randi Selmer, Sidsel Graff-Iversen, Richard F Gillum, Karina W Davidson, Jonathan A Shaffer, Hiroyasu Iso, Shinichi Sato, Randi Selmer, Sidsel Graff-Iversen, Lise L Håheim, Pim van der Harst, Stephan JL Bakker, Hans L Hillege, Ron T Gansevoort, Carlos J Crespo, Philippe Amouyel, Jean Dallongeville, Gerd Assmann, Helmut Schulte, Yvonne T van der Schouw, Joline WJ Beulens, J Wouter Jukema, Ian Ford, David J Stott, Gilles R Dagenais, Bernard Cantin, Jean-Pierre Després, Benoît Lamarche, Elizabeth Barrett-Connor, Alka M Kanaya, Kimbach T Carpiuc, Assiamira Ferrara, Trevisan Maurizio, Oscar H Franco, Albert Hofman, Frank JA van Rooij, M Arfan Ikram, Maryam Kavousi, Abbas Dehghan, Jan Heeringa, Jessica C Kiefte-de Jong, Maarten JG Leening, Symen Ligthart, Janine F Felix, Loes Jaspers, Hugh Tunstall-Pedoe, Mark Woodward, Marcus Dörr, Stephan B Felix, Roberto Lorbeer, Henry Völzke, Barbara V Howard, Lyle Best, Yoav Ben-Shlomo, Altan Onat, Inger Njølstad, Johan Sundström, Johan Ärnlöv, Lars Lind, Erik Ingelsson, Sylvia Wassertheil-Smoller, Michael Marmot, Astrid Fletcher, Eric J Brunner, Daan Kromhout

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.

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.

Source: PubMed

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