Introduction

Multimorbidity, the presence of more than one chronic disease in a patient, affects more than half of
the elderly population and almost all hospitalized geriatric patients [1]. Health systems do not
specifically consider this population and their unique healthcare requirements [2].

The clinical care of older individuals can be complicated by a high frequency of concomitant geriatric
syndromes. These syndromes consist of several conditions that are multifactorial in nature, rarely
limited to a single organic system, and commonly associated with poor health outcomes [3]. The
combination of multimorbidity and geriatric syndromes increases disability, mortality, and
institutionalization rates [4].

Despite a growing emphasis on comprehensive care for chronic diseases, the organizational structure of
current healthcare services is fragmented, with a strong emphasis on medical specializations [2].
Moreover, recommended management approaches to multimorbidity are lacking in most practice
guidelines, which are the main scientific evidence-based tool available to clinicians [5]. Consequently,
healthcare systems fail to appropriately address the healthcare needs of geriatric patients with
multimorbidity. Inadequate clinical assessment of older patients leads to iatrogenesis, duplication of
diagnostic and therapeutic interventions, and deviation

from the aspects of healthcare that are most important to the patients themselves (e.g., pain
elimination, preservation of functional and cognitive capacity, optimization of drug therapy) [6].

Recent studies have sought to identify systematic associations among diseases (i.e., associative
multimorbidity), and have confirmed the existence of clinically plausible multimorbidity patterns that
evolve over time [7]. Such beyond-chance associations among diseases may occur when one disease is
directly responsible for others (i.e., complicating multimorbidity) or when several diseases share
common or correlated risk factors (i.e., causal multimorbidity), which may be biological, socio-economic,
cultural, environmental or behavioural in nature [8]. In both cases, the potential for secondary and
tertiary prevention is high, underscoring the importance of these types of studies.

To date, the majority of studies of multimorbidity patterns have been limited to chronic diseases, so as
to increase the likelihood of co-occurrence of conditions [9]. Despite their clinical relevance, very few
studies have included geriatric syndromes in their analyses, probably due to the limited availability of
relevant data in existing patient databases. In fact, the few studies that did study geriatric syndromes
collected data either by comprehensive geriatric assessment [10,11] or patient self-reporting [4,12].
The present study explored multimorbidity patterns in geriatric patients attending an acute hospital,
examining both chronic diseases and geriatric syndromes. Better knowledge of how these conditions
cluster in older individuals could help clinicians and researchers better understand poor health
outcomes in certain types of patients. Furthermore, our results may help guide the implementation of
prevention strategies and the design of clinical practice guidelines adapted to the specific healthcare
needs of this population group.

Methods

Study design, population and variables

This retrospective observational study included patients of 65 years or more who attended the Unit of
Social and Clinical Assessment (UVSS) of the Miguel Servet University Hospital (HUMS) in Zaragoza
(Spain) during 2011. This UVSS is located in a public tertiary hospital of the Aragon Health Service
(SALUD) that serves a population of approximately 400,000 inhabitants. It consists of an interdisciplinary
team (geriatrician, nurse, and social and administrative worker), one of whose main objective is to
detect and evaluate recently hospitalized geriatric patients at risk of disability and dependency, and to
minimize these risks.

The dataset included information on the clinical, functional, cognitive and social statuses of all attended
patients. Functional assessment was conducted using the Barthel Index [13], and pre- and post-
admission cognitive assessment was carried out using the nationally validated Red Cross Mental Scale
(RCMS) [14] and Pfeiffer’s test [15], respectively. The diagnoses of each patient before and during
hospitalization were grouped in Expanded Diagnosis Clusters (EDCs) using the ACG System. Only chronic
EDCs included on a validated list of 115 EDCs published by Salisbury et al. [16] were considered.
Information on the following geriatric syndromes was included in the database: immobility, urinary
incontinence, constipation, pressure ulcers, cognitive decline, dementia, delirium, depression, falls,
insomnia, visual impairment, hearing loss, malnutrition, dysphagia, and pain.

Immobility was defined as a decreased ability to perform activities of daily living due to impairment of
motor functions. Urinary incontinence was defined as an objectively demonstrable involuntary loss of
urine. Constipation was defined as less than two bowel movements per week. Pressure ulcers were
defined according to the four grades established by the European Pressure Ulcer Advisory Panel (EPUAP)
[17]. Cognitive impairment was assessed using Pfeiffer’s test, which was performed at the time of
hospitalization, once a previous diagnosis of dementia and/or delirium had been ruled out. A previous
diagnosis of dementia was based on the patient’s medical record data and was established using the
RCMS. The ACG System included dementia and delirium in a single EDC category (NUR 11 “Dementia and
delirium”). The criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) [18]
were used for the diagnosis of depression and insomnia. A fall was defined as the result of any event
that caused the patient to end up on the ground against their will, according to the WHO definition [19].
Visual impairment and hearing loss were defined as self-reported difficulty hearing or seeing the
interviewer without technical assistance. Malnutrition was defined as an intake that was less than 50%
of the required daily allowance, as reported by the patient or caregiver, together with hypoalbuminemia
and hypocholesterolemia.

Pain was defined as any subjective complaint of an unpleasant sensory or emotional experience
associated with actual or potential tissue damage, either acute or chronic. Dysphagia was defined as a
difficulty swallowing liquids and/or solids that affected one or more phases of swallowing. This study
was approved by the Clinical Research Ethics Committee of Aragon (CEICA for its initials in Spanish).
Patient written consent was not required as the study did not involve interventions on individuals, the
use of human biological samples, or the analysis of personally identifiable data. The study involved the
statistical analysis of anonymous data contained in previously existing databases and obtained with prior
permission from the corresponding entity.

Statistical analysis and clinical interpretation

A preliminary characterization of the population was performed by calculating the frequencies of

To analyse the clustering of diseases and/or geriatric syndromes into patterns, we employed an
exploratory factor analysis, stratified by sex. This method identifies the tendencies of diseases to co-
occur by selecting sets of variables with potentially common underlying causal factors. This approach
thus provides results of etiological interest. The factors identified by this analysis can be interpreted as
multimorbidity patterns, i.e., diseases that are non-randomly associated with one other within the study
population (associative multimorbidity).

Factor analysis was performed using a tetrachoric correlation matrix to account for the dichotomous
nature of the variables (i.e., presence/absence of a given condition) [20]. The use of the classical
Pearson’s correlation coefficients for dichotomous variables results in mathematical artefacts, given the
absence of a linear relationship among the variables and the restriction of the number of categories
within one variable, which shrinks the magnitude of the correlations [21]. Factor extraction was
performed using the principal factor method, and the number of factors extracted was determined
using sedimentation graphs in which the eigenvalues of the correlation matrix were represented in
descending order. The number of factors extracted corresponds to the sequence number of the
eigenvalue that produces the inflection point of the curve.

To increase the epidemiological interest of the study, only health problems with prevalence rates >5%
were included in each group of men and women. To identify the conditions that defined each
multimorbidity pattern, those with scores 0.25 for each factor were selected (the same empirical
threshold employed in previous studies [7,22,23]). Higher factor scores (i.e., closer to 1) indicate
stronger associations between the condition and a given pattern. Conversely, if a given disease is
relatively independent of a given factor, the resulting obtained score will be closer to 0.

The final phase of the analysis was intended to determine the clinical relevance of the patterns
identified, and was conducted by five medical doctors (two geriatricians [MCS, NMV], two general
practitioners [IVM, PAH], and one specialist in public health [APT]), first independently and then all
together.

Statistical analyses were performed using STATA 12.0 software.

Results

The total study population consisted of 924 patients, of whom 99.7% experienced multimorbidity and
more than half (56.8%) were women. The mean age of the study population was 82.1 years (SD 7.2);
almost 85% of the patients were over 74 years, and nearly 40% were at least 85 years old. The mean age
of women was significantly higher than that of men (83.5 vs. 80.2 years, p<0.001).

Multimorbidity was present in all age and sex groups (Fig 1). Compared with women of the
corresponding age group, the multimorbidity burden was lower in men under 80 years but higher in
those over 80 years. The level of multimorbidity in women between 65 and 69 years corresponded to
that of men 15 years older.

Significant differences in functional and cognitive status were observed by sex; women showed higher
rates of severe/total dependency both before and after hospitalization (Table 2). Men were more
frequently on polymedication and showed higher rates of intense hospital use (p<0.05). Functional and
cognitive status decreased after admission to hospital in both men and women.

Immobility, urinary incontinence, hypertension, falls, dementia, cognitive decline, diabetes and
arrhythmia were among the 10 most frequent health problems in both sexes, with prevalence rates
above 20%. The next most frequent conditions were respiratory problems and dysphagia in men, and
dyslipidaemia, constipation and vision impairment in women (Table 1).
Four different multimorbidity patterns were identified in the population, all of which were present in
women and men (Tables 3 and 4). Out of the 31 health conditions included in the pattern identification
process, 27 were common to men and women. Another two conditions were present exclusively in men
(prostate malignant neoplasm and chronic obstructive pulmonary disease [COPD]) and two in women
(osteoporosis and hip fracture). Only seven conditions (anaemia and hearing loss in men and
constipation, dysphagia, pain, chronic renal failure and pressure ulcers in women) were present in more
than one pattern.

The first pattern, i.e., Cardiovascular pattern, grouped risk factors, such as hypertension, dyslipidaemia
and type II diabetes (factor score close to the cut-off point in women: 0.21) together with other
cardiovascular conditions such as valve disorders, arrhythmia, anaemia (factor score close to the cut-off
point in women: 0.22), ischemic heart disease, congestive heart failure, cerebrovascular disease and
chronic renal failure. Other cardiovascular disorders and constipation were exclusively present among
women. In men, COPD and prostate cancer were also present in this pattern.

The second pattern, i.e., Induced Dependency pattern, consisted of a constellation of geriatric
syndromes, most of which were common to both sexes (immobility, urinary incontinence, dysphagia,
pressure ulcers, cognitive decline and dementia/delirium). Hearing loss was present in men only, and
cerebrovascular disease and renal failure in women only.

The third pattern, i.e., Falls pattern, consisted of sensory deficits (i.e., vision and hearing), anaemia and
falls in men, and sensory deficits, osteoporosis, hip fracture, depression, pain and constipation in
women. Falls in women were close to the cut-off point (factor score: 0.22).

The last pattern, i.e., Osteoarticular pattern, differed between sexes. Arthropathy, fractures (other than
hip fractures), and pain were common to both sexes, while depression and constipation were observed
exclusively in men and anaemia, dysphagia and pressure ulcers in women only.