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Clin Geriatr Med. Author manuscript; available in PMC 2017 May 1.
Published in final edited form as:
PMCID: PMC4848462

Magnitude and impact of multimorbidity on clinical outcomes in older adults with cardiovascular disease: A literature review

Mayra Tisminetzky, MD PhD,a,b,d Robert Goldberg, PhD,a,c,d and Jerry H. Gurwitz, MDa,b,d



To synthesize the current literature on the magnitude and impact of multiple chronic conditions on clinical outcomes, including total in-hospital and post discharge mortality and hospitalizations, in older adults with cardiovascular disease (CVD).


A comprehensive literature review was conducted. Four electronic databases including Medline, PubMed, Medline Plus, Embase, as well as article bibliographies were searched for publications from 2005 to 2015 addressing the impact of multimorbidity on clinical outcomes in older adults with CVD. Identified studies were screened using pre-defined criteria for eligibility.


Fifteen studies met our inclusion criteria. Most studies reported a significant association between number of chronic conditions or selected morbidities and the risk of dying. The most frequently examined conditions were diabetes, chronic kidney disease, anemia, chronic pulmonary disease, and dementia/cognitive impairment. Multimorbidity was assessed either by simply counting the numbers of conditions or by use of the Charlson and/or Elixhauser indices.


Multimorbidity is highly associated with the risk of dying in patients with CVD, but there are only very limited data on universal health outcomes (i.e., health related quality of life, symptom burden, and function) in this high risk population. There is also a lack of consistency in the manner in which the burden of multimorbidity has been assessed and characterized. Very few studies have addressed the true complexity of older patients with CVD. How best to characterize multimorbidity in these patients and to relate multimorbidity to clinical outcomes remains a substantial challenge.

Keywords: multimorbidity, elderly, clinical outcomes, cardiovascular disease


Approximately two thirds of American men and women 65 years of age and older have been diagnosed with cardiovascular disease (CVD).1 CVD in older men and women adversely impacts quality of life and it is the leading cause of death in older Americans. As the U.S. population has aged, the prevalence of CVD has increased dramatically, together with other chronic conditions. 24 There is increasing awareness that older individuals with CVD and multiple chronic conditions experience higher levels of healthcare use and poorer outcomes.410 Moreover, the clinical management of persons with CVD with multiple chronic conditions can be especially challenging due to complex therapeutic regimens, the involvement of multiple healthcare providers, and competing priorities impacting decision-making in the care of these patients.11

Despite the high prevalence of CVD and multimorbidity in the elderly, there remains a lack of consensus regarding how best to assess and measure multimorbidity and to determine how the presence of multiple chronic conditions impacts clinical outcomes.11 The aim of this paper is to review the current literature on the magnitude and impact of multimorbidity on clinical outcomes in older adults with CVD.


Search Strategy and Information Sources

The available published literature was reviewed by searching the electronic databases Medline, PubMed, Medline Plus, and Embase, for the time period January, 2005 through August, 2015. We used the following search terms: cardiovascular disease , myocardial infarction, heart failure,; comorbidities, multimorbidity, multiple chronic conditions; clinical outcomes, mortality, hospital readmission, rehospitalization. Search limits were used in each database to restrict our search to clinical studies, articles in the English language, and studies in the last 10 years (excluding animal studies). (See Appendix 1).

In addition to the electronic search of these databases, we hand searched the references of original articles. All references identified by the above searches were merged into a single bibliographic database.

After compiling the search results of the databases, the yield obtained by hand searching, and removing duplicate articles, the studies were reviewed by the coauthors. One of the reviewers independently examined the titles and abstracts to determine eligibility for inclusion. If the title and abstract appeared to be potentially relevant by one of the raters, the article was marked for a full text review. Any article that was marked as unsure by the rater was also marked for full text review.

The studies reviewed in our report included patients 18 years or older with confirmed CVD cared for in the hospital and clinic setting. We excluded case reports, letters to the editors, or situations where only an abstract was provided. (See PRISMA checklist for details.)


Search Results

A total of 261 articles was identified from our initial literature search; after 204 duplicates were removed, and 57 articles were excluded on the basis of title and abstract review, 36 articles were retrieved for more detailed assessment. Of these, 15 studies met our inclusion criteria (Figure 1). No additional articles were identified from the references of the included articles.

Figure 1
search strategy

Study characteristics

The characteristics of included articles are detailed in Table 1. Five studies included patients with acute myocardial infarction, and 10 included patients with heart failure as the cardiovascular condition of interest. Six of the included studies were retrospective cohort studies,3,9,10,12,14 four were cross-sectional,5,15,16,17 three were prospective cohort studies,18,19,20 and two were randomized controlled trials.21,22 Seven were US-based studies;3,5,9,10,14,16,20 non-US-based studies (n= 8) were performed in Canada 13,22 and several European countries , including Italy,17 Spain,15 Portugal,12 Denmark, 21 France,18 and the Netherlands. 19 Eleven studies utilized medical records for data collection, 3,5,9,10,12,13,15,18,19,20,21 three employed claims-based data,14,16,17 and one group of authors analyzed data on multimorbidity collected in the context enrolling subjects in a large randomized controlled trial (SOLVD).22

Table 1
Study Population Characteristics

Study sample sizes ranged from 9319 to more than 182,00016 participants; eight of the 15 studies 3,5,9,10,14,16,21,22 included <1,000 subjects. All 15 studies provided information about the average age of the study sample, which ranged from 5922 to 8312 years; the percentage of women ranged from 5%3 to 80%.18 Six of the seven US-based studies 3,5,9,10,16,20 provided data on race/ethnicity and the majority of subjects in those studies was Caucasian.

Assessment and magnitude of multimorbidity

The number of chronic conditions was assessed by simple counts of chronic conditions 3,5,9,10,12,14,16,18,20,21,22 (n=11), by combination of the Elixhauser and Charlson indices15 (n=1), and by the Charlson index alone 13, 17, 19 (n=3) (Table 2). The prevalence of chronic conditions ranged from at least one additional morbidity in 10%5 to 77%9 of persons; the frequency of four or more additional chronic conditions ranged from 5%9 to 60%.20 The most common morbidities considered were diabetes,3,18,20 chronic kidney disease,3,14,16,20,21 anemia,3,18, 21 chronic obstructive pulmonary disease, 3,20,21 and dementia/cognitive impairment. 3,16,20

Table 2
Assessment of Multimorbidity

Multimorbidity and clinical outcomes

All the studies reviewed found a positive association between the cumulative effect of multimorbidity and the risk of dying (Tables 36). Three studies reported a significant association between unspecified multimorbidity and long-term mortality.9,13,22 One study found a significant association between a score of four or more on the Charlson index and long-term mortality.19 Three studies found a significant association between number of morbidities and the hospital case fatality rate (CFR),5,10,12 and one study reported a significant association between a higher Charlson score and hospital CFR.15 As an example, of the positive association between number of morbidities and long term-mortality, one study found that in a cohort of 9,500 patients hospitalized due to an acute myocardial infarction, one-year mortality odds ratio (ORs) ranged from 1.16 (1.01; 1.34) to 2.31 (1.92; 2.78) for those presenting with one or four or more chronic conditions, respectively, as compared to those without any chronic conditions.9 Another study found that patients with heart failure and hypertension had a hazard ratio (HR) for death of 1.32 (1.12;1.54) and those presenting with heart failure and diabetes had a HR of 1.55 (1.28;1.88), as compared to those without these chronic conditions.22

Table 3
Assessment of Outcomes and Limitations.
Table 6
Hospitalization Rates and Adjusted Analysis Findings (detailed)

Another study demonstrated a positive association between the number of morbidities and hospital case fatality rates (CFRs); the ORs ranged from 2.00 (95% confidence interval: 1.05, 3.82) to 2.80 (1.43, 5.49) in those patients with acute myocardial infarction and presenting with two or four or more chronic conditions, respectively, as compared to those without any morbidities.10 As an example of studies that examined the impact of specific chronic conditions on mortality, in a cohort of 5,275 patients that had experienced a previous hospitalization for an acute myocardial infarction, researchers reported ORs of 2.97(2.47, 3.56) for those with heart failure and ORs of 1.61(1.36; 1.93) for those with arrhythmias as compared to patients without these conditions.15

Of note, we identified only one study that reported on outcomes falling in to the category of “universal outcomes.”17 In a cohort of 628 patients with heart failure, the investigators found a statistically significant association between the overall burden of comorbidity, as assessed by the Charlson comorbidity index, and worse physical and emotional quality of life (Pearson’s correlation coefficients were reported for this analysis; for example, for emotional quality of life, the coefficient decreased from 0.16 in those with one to 0.04 in those with four chronic conditions based on the Charlson index.)17


In this review, we found that there is a significant association between number and types of chronic conditions and the risk of dying; the most frequent morbidities examined were diabetes, chronic kidney disease, anemia, chronic pulmonary disease, and dementia/cognitive impairment. Whereas our findings highlight the very high prevalence of multimorbidity in patients with CVD, and the association of the cumulative effect of number of chronic conditions with outcomes such as mortality or the risk of rehospitalization, only very limited data are available on the magnitude and impact of multimorbidity on universal health outcomes such as symptom burden, functional capacity, and self-rated health among older adults with CVD.

Despite the high prevalence of CVD, and additional chronic conditions in these individuals, our findings suggest that there is a lack of consistency in the manner in which the burden of multimorbidity is assessed and characterized.3,5,10,12,13,14,15,16,17,18,19,20,21,22 Although a number of different approaches exist for measuring multimorbidity, none of these is considered to be a “gold standard.” Simply counting morbidities is seemingly straightforward; however, this approach does not take into account the clinical severity of a condition or the varying impact across conditions. Comorbidity indices are relatively easy to apply, but may also lack sufficient specificity to adequately characterize the complexity of patients presenting with multimorbidity and CVD. Summary scores derived from various indices of multimorbidity can also be challenging to apply and integrate into clinical decision-making relevant to the care of individual patients.

Although the use of claims data to characterize multimorbidity in large populations in a ‘real-world’ setting may be highly efficient, these data are often inadequate to fully and accurately characterize the severity of disease and time of initial diagnosis of chronic conditions, and pose substantial challenges in addressing outcomes such as health-related quality of life, symptom burden, and function.

A relatively recent systematic review aimed to compare multimorbidity measures employing administrative data.23 The most common instrument used was the Charlson index, followed by the Elixhauser index. The authors concluded that “the performance of a given comorbidity measure depends on the patient group and outcome” being assessed.23 Future studies, combining data from claims databases and supplemented by other sources of data, such as electronic health records, may serve to improve our current understanding of the impact of multimorbidity on clinical outcomes in older adults with CVD.

The overarching aim of our review was to summarize findings from studies examining the association between the presence of multiple chronic conditions and clinical outcomes in patients with CVD. All the studies included in this review found a positive significant association between the burden of multimorbidity and short and long-term mortality. Although prior literature has suggested that multimorbidity plays an important role in quality of life and other universal health outcomes, in our review, only one study examined quality of life associated with the presence of multimorbidity.17

In 2011, the National Institute on Aging, in collaboration with the Agency for Healthcare Research and Quality, convened an expert panel on health outcome measures for older persons with multimorbidity. The goal of this effort was to develop recommendations for the content of a core set of well-validated universal patient-centered outcome measures that could be routinely assessed in health care settings.24 Among the recommended health outcomes to be measured were: symptom burden, physical function and mobility, mental health outcomes, cognitive function, and social health outcomes. This expert panel concluded that universal outcome measures have emerged as a strong complement to disease-specific measures for comparative effectiveness research among older adults with multimorbidity.24 The panel also suggested that the routine assessment of these measures would facilitate meaningful and interpretable results that could be used by patients and providers to better communicate the balance between benefit versus risk of various interventions. Furthermore, another recent study evaluated function-related indicators in administrative claims data from the US Medicare beneficiaries with a hospitalization for acute myocardial infarction during 2007.25 The investigators suggested that an “expanded concept of general illness severity that incorporates indicators of potentially diminished functional status can better capture the heterogeneity of patients with multimorbidity.”25

A number of limitations of our review must be acknowledged. This review was limited to studies published in English. The extent to which our inability to review studies published in languages other than English affected our findings is unknown. Since our review included only peer-reviewed publications, there is a potential for introducing possible publication bias. Because we allowed for heterogeneity of the multimorbidity assessment measures included in this review, a quantitative meta-analysis was not feasible. Finally, since the majority of participants in the included studies were white, the generalizability of our findings to other race/ethnic groups may be limited. Future studies should examine potential racial and ethnic differences in the magnitude and impact of multimorbidity on clinical outcomes in patients presenting with CVD.


While multimorbidity is highly associated with the risk of dying in patients with CVD, there are only very limited data on the impact of multimorbidity on universal health outcomes (i.e., health related quality of life, symptom burden, and function). In addition, our review of the literature suggests a profound lack of consistency in the manner in which the burden of multimorbidity has been assessed and characterized across studies. Capturing the true complexity of older patients with CVD remains an ongoing challenge. Until that challenge is addressed, the value of available research on multimorbid patients with CVD for informing clinical decision-making is questionable.

Table 4
In-Hospital CFRs (detailed)
Table 5
Long-term CFRs (detailed)

Key points

  • Multimorbidity is highly prevalent in older adults with cardiovascular disease and is related to higher levels of healthcare use and mortality.
  • There are inconsistencies in the manner in which multimorbidity has been characterized in older adults presenting with cardiovascular disease.
  • Limited data exist on the impact of multimorbidity on universal health outcomes (e.g.; health related quality of life, symptom burden, and function) in older adults with cardiovascular disease.


Drs. Gurwitz and Tisminetzky are supported by award number: 1R24AG045050 from the National Institute of Aging, Advancing Geriatrics Infrastructure & Network Growth (AGING). Partial salary support was provided to Dr. Goldberg by National Institutes of Health Grant 1U01HL105268–01 and R01 HL35434.

Appendix 1

MEDLINE Search Strategy

#1Cardiovascular disease [title/abstract]
#2Myocardial infarction [title/abstract]
#3Heart failure [title/abstract]
#4# 1 OR #2 OR #3
#5Comorbidities [title/abstract]
#6Multimorbidity [title/abstract]
#7Multiple chronic conditions [title/abstract]
#8#5 OR #6 OR #7
#9Clinical outcomes [title/abstract]
#10Mortality [title/abstract]
#11Hospital readmission [title/abstract]
#12Rehospitalization [title/abstract]
#13#9 OR #10 OR #11 OR #12
#14# 4 AND # 8 AND #13
#15#14 AND full text[sb] AND "last 10
years"[PDat] AND Humans


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