Elsevier

Archives of Gerontology and Geriatrics

Volume 67, November–December 2016, Pages 130-138
Archives of Gerontology and Geriatrics

Review
Multimorbidity and mortality in older adults: A systematic review and meta-analysis

https://doi.org/10.1016/j.archger.2016.07.008Get rights and content

Highlights

  • Multimorbidity increase the risk of death regardless its operationalization form.

  • The high heterogeneity on multimorbidity measurement continues to be a challenge.

  • Few studies included all possible confundiment variables.

  • Future studies should include more robust analytical models.

Abstract

Objective

To review literature and provide a pooled effect for the association between multimorbidity and mortality in older adults.

Methods

A systematic review was performed of articles held on the PUBMED database published up until January 2015. Studies which used different diseases and other conditions to define frailty, evaluated multimorbidity related only to mental health or which presented disease homogeneity were not included. A meta-analysis using random effect to obtain a pooled effect of multimorbidity on mortality in older adults was conducted only with studies which reported hazard ratio (HR). Stratified analysis and univariate meta-regression were performed to evaluate sources of heterogeneity.

Results

Out of 5806 identified articles, 26 were included in meta-analysis. Overall, positive association between multimorbidity and mortality [HR: 1.44 (95%CI: 1.34; 1.55)] was detected. The number of morbidities was positively related to risk of death [HR: 1.20 (95%CI: 1.10; 1.30)]. Compared to individuals without multimorbidity, the risk of death was 1.73 (95%CI: 1.41; 2.13) and 2.72 (95%CI: 1.81; 4.08) for people with 2 or more and 3 or more morbidities, respectively. Heterogeneity between studies was high (96.5%). The sample, adjustment and follow-up modified the associations. Only nine estimates performed adjustment which included demographic, socioeconomic and behaviour variables. Disabilities appear to mediate the effect of multimorbidity on mortality.

Conclusions

Multimorbidity was associated with an increase in risk of death. Multimorbidity measurement standardization is needed to produce more comparable estimates. Adjusted analysis which includes potential confounders might contribute to better understanding of causal relationships between multimorbidity and mortality.

Introduction

Multimorbidity is a frequent problem, mainly in the elderly population, among whom prevalence was found to be greater than 60% (Fortin, Stewart, Poitras, Almirall, & Maddocks, 2012). Although studies of this problem are recent, available data have shown negative consequences related to multimorbidity including an increased risk of disability, frailty and decrease in quality of life, as well as associations with mortality (Fortin et al., 2004, Gijsen et al., 2001, Marengoni et al., 2011; Mello, Engstrom, & Alves, 2014).

The biological plausibility of association between multimorbidity and mortality is analogous to physiologic mechanisms which increase the risk of death in individuals with a specific disease. Moreover, multimorbidity increases the risk of complications and consequences on the physiological system due to interactions between morbidities and disease treatment (American Geriatrics Society Expert Panel on the Care of Older Adults with Multimorbidity, 2012; Guthrie, Payne, Alderson, McMurdo, & Mercer, 2012; Mallet, Spinewine, & Huang, 2007; Marengoni et al., 2011, Salisbury, 2012, van Weel and Schellevis, 2006). Some studies have found higher risk of death among elderly people with multimorbidity compared to those without diseases (Landi et al., 2010; Marengoni, von Strauss, Rizzuto, Winblad, & Fratiglioni, 2009; Menotti et al., 2001, Wang et al., 2009), while other studies did not find differences (St. John, Tyas, Menec, & Tate, 2014; Woo & Leung, 2014). Furthermore, mortality in the elderly is multifactorial and includes environmental (Beelen et al., 2014; Meijer, Rohl, Bloomfield, & Grittner, 2012; Silva, Cesse, & Albuquerque, 2014), demographic (Luy & Gast, 2014) and socioeconomic characteristics (Silva et al., 2014), as well as being influenced by social relationships (Holt-Lunstad, Smith, & Layton, 2010), geriatric conditions (Landi et al., 2010, Landi et al., 2012; Shamliyan, Talley, Ramakrishnan, & Kane, 2013; Theou et al., 2012, Woo and Leung, 2014) and healthcare actions (Veras et al., 2014).

Despite this context, to the best of our knowledge, a pooled effect on the association between multimorbidity and mortality does not exist. The description of characteristics which modify association might be useful to inform future interventions to measure actions and programs related to elderly (Moraes, 2012, Salisbury, 2012, Salive, 2013). Thus, the objective of this study was, by means of a systematic review and meta-analysis, to evaluate and quantify the association between multimorbidity and mortality in older adults.

Section snippets

Search strategy and selection criteria

A systematic review of literature held on the PUBMED database published up until January 22nd 2015 was conducted. Manuscripts in English, Portuguese and Spanish were searched. The following terms were used: (“comorbidity” OR “co-morbidity” OR “multimorbidity” OR “multi-morbidity” OR “multiple diseases” OR “multiple morbidities” OR “multimorbid” OR “multiple pathology” OR “disease clustering” OR “Risk Adjustment” OR “Severity of Illness Index”) AND (“Mortality” OR “survival rate” OR “cause of

Results

The search identified 5806 studies. After title and abstract reading, 200 manuscripts were selected for full-text reading. The majority of these were excluded because they did not have effect measurement for association between multimorbidity and mortality or included comorbidity evaluation (disease index) (Fig. 1). Eight additional records were identified through references list of selected papers, reaching 32 papers in qualitative synthesis. Then, 26 articles were included in the

Discussion

Multimorbidity increases the risk of death regardless of its operationalization. High heterogeneity between studies was observed. A positive gradient between number of diseases and mortality was found, and ≥3 diseases as the cut-off point showed the strongest association with risk of death. Small samples, population-based studies, more comprehensive adjustment, multimorbidity without disease severity measurement and multimorbidity comparison groups were characteristics that appear to reduce the

Conflict of interest statement

The authors declare that they have no competing interests.

Funding

BPN, TRF and GIM are supported by Coordination for the Improvement of Higher Level- or Education- Personnel (CAPES). LAF is supported by Brazilian National Research Council (CNPq). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

References (70)

  • F. Landi et al.

    Disability, more than multimorbidity, was predictive of mortality among older persons aged 80 years and older

    Journal of Clinical Epidemiology

    (2010)
  • F. Landi et al.

    Sarcopenia and mortality among older nursing home residents

    Journal of the American Medical Directors Association

    (2012)
  • L. Mallet et al.

    The challenge of managing drug interactions in elderly people

    The Lancet

    (2007)
  • A. Marengoni et al.

    Aging with multimorbidity: A systematic review of the literature

    Ageing Research Reviews

    (2011)
  • F. Mazzella et al.

    Social support and long-term mortality in the elderly: Role of comorbidity

    Archives of Gerontology and Geriatrics

    (2010)
  • M. Meijer et al.

    Do neighborhoods affect individual mortality? A systematic review and meta-analysis of multilevel studies

    Social Science & Medicine (1982)

    (2012)
  • A. Menotti et al.

    Prevalence of morbidity and multimorbidity in elderly male populations and their impact on 10-year all-cause mortality: The FINE study (Finland, Italy, Netherlands, Elderly)

    Journal of Clinical Epidemiology

    (2001)
  • C. Salisbury

    Multimorbidity: Redesigning health care for people who use it

    The Lancet

    (2012)
  • T. Shamliyan et al.

    Association of frailty with survival: A systematic literature review

    Ageing Research Reviews

    (2013)
  • L. Tooth et al.

    Weighted multimorbidity indexes predicted mortality, health service use, and health-related quality of life in older women

    Journal of Clinical Epidemiology

    (2008)
  • C. van Doorn et al.

    Risk adjustment for older hospitalized persons: A comparison of two methods of data collection for the Charlson index

    Journal of Clinical Epidemiology

    (2001)
  • C. van Weel et al.

    Comorbidity and guidelines: Conflicting interests

    The Lancet

    (2006)
  • American Geriatrics Society Expert Panel on the Care of Older Adults with Multimorbidity

    Guiding principles for the care of older adults with multimorbidity: An approach for clinicians

    Journal of the American Geriatrics Society

    (2012)
  • A. Calderon-Larranaga et al.

    Multimorbidity, polypharmacy, referrals, and adverse drug events: Are we doing things well?

    The British Journal of General Practice: The Journal of the Royal College of General Practitioners

    (2012)
  • T.C. Chan et al.

    Development and validation of a prognostic index for 2-year mortality in Chinese older residents living in nursing homes

    Geriatrics & Gerontology International

    (2012)
  • T.C. Chan et al.

    Validation study of Charlson Comorbidity Index in predicting mortality in Chinese older adults

    Geriatrics & Gerontology International

    (2014)
  • L.A. Chwastiak et al.

    Association of psychiatric illness and all-cause mortality in the National Department of Veterans Affairs Health Care System

    Psychosomatic Medicine

    (2010)
  • A.K. Dahl et al.

    Body mass index, change in body mass index, and survival in old and very old persons

    Journal of the American Geriatrics Society

    (2013)
  • K.B. DeSalvo et al.

    Mortality prediction with a single general self-rated health question. A meta-analysis

    Journal of General Internal Medicine

    (2006)
  • C.P. Diederichs et al.

    How to weight chronic diseases in multimorbidity indices? Development of a new method on the basis of individual data from five population-based studies

    Journal of Clinical Epidemiology

    (2011)
  • M. Drame et al.

    Derivation and validation of a mortality-risk index from a cohort of frail elderly patients hospitalised in medical wards via emergencies: The SAFES study

    European Journal of Epidemiology

    (2008)
  • G.G. Fillenbaum et al.

    Comorbidity of five chronic health conditions in elderly community residents: Determinants and impact on mortality

    The Journals of Gerontology Series A: Biological Sciences and Medical Sciences

    (2000)
  • F. Formiga et al.

    Utility of geriatric assessment to predict mortality in the oldest old: The Octabaix study 3-year follow-up

    Rejuvenation Research

    (2013)
  • M. Fortin et al.

    Multimorbidity and quality of life in primary care: A systematic review

    Health and Quality of Life Outcomes

    (2004)
  • M. Fortin et al.

    A systematic review of prevalence studies on multimorbidity: Toward a more uniform methodology

    Annals of Family Medicine

    (2012)
  • Cited by (411)

    View all citing articles on Scopus
    View full text