Beruflich Dokumente
Kultur Dokumente
12637
ORIGINAL ARTICLE
ABSTRACT
Background Malnutrition in elderly inpatients hospitalized on medical wards is a significant public health con-
cern. The aim of this study was to investigate nutritional markers as mortality predictors following discharge in
hospitalized medical elderly patients.
Materials and methods This is a prospective observational cohort study with follow-up of 48 months. Two
hundred and twenty-five individuals aged 60 and older admitted from the hospital emergency room in the past
48 h were investigated at the medical ward in the University hospital in Palermo (Italy). Anthropometric and
clinical measurements, Mini-nutritional Assessment (MNA) questionnaire, bioelectrical (BIA) phase angle (PA),
grip strength were obtained all within 48 h of admission. Mortality data were verified by means of mortality
registry and analysed using Cox-proportional hazard models.
Results Ninety (40%) participants died at the end of follow-up. There were significant relationships between
PA, MNA score, age and gender on mortality. Patients in the lowest tertile of PA (< 46°) had higher mortality
estimates [I vs II tertile: hazard ratio (HR) = 340; 95% confidence interval (CI): 201–577; II vs III tertile:
HR = 383; 95% CI: 221–664; log-rank test: v2 = 436; P < 0001]. Similarly, the survival curves demonstrated
low MNA scores (< 22) were associated with higher mortality estimates (HR = 185; 95% CI: 122–281
v2 = 82; P = 0004).
Conclusions The MNA and BIA-derived phase angle are reasonable tools to identify malnourished patients at
high mortality risk and may represent useful markers in intervention trials in this high-risk subgroup.
Keywords Bioimpedance, hospitalization, malnutrition, mini-nutritional assessment, mortality, phase angle.
Eur J Clin Invest 2016; 46 (7): 609–618
often is questioned in multimorbid patients, [15,17] particularly performed twice using standardized procedures (Omron M6;
in those with disturbed hydration due to medical illness. Omron Healthcare Co., Matsusaka, Mie, Japan). Height, body
Recently, the use of crude BIA measures such as phase angle weight (SECA; Hamburg, Germany) and body circumferences
(PA) or the vectorial representation of resistance and reactance (nondominant arm and calf circumference) were measured
has received increasing attention as a plausible indicator of with participants lightly dressed and without shoes. Body mass
intra/extracellular hydration and nutritional status [15]. index (BMI) was calculated as body weight (kg)/height2 (m2).
Despite the MNA and PA being possible screening tools for In the case of patients unable to maintain the upright position,
malnutrition, to our knowledge, there are no data available height was obtained using a predictive equation [19] based on
about whether they predict postdischarge mortality in hospi- the leg length measured using a calliper as the distance
talized older adults. We investigated whether these emerging between the heel and the kneecap. Grip strength was measured
nutritional markers predict mortality following discharge in a using a hydraulic hand dynamometer (JAMAR SH5001, Sae-
cohort of hospitalized medical elderly patients. han, Republic of Korea). Patients performed the test while sit-
ting with their shoulder adducted and forearm neutrally
Materials and methods rotated, elbow flexed to 90°, and forearm and wrist in a neutral
position. Patients were instructed to perform a maximal iso-
Participants of this prospective observational cohort study were
metric contraction. The test was repeated within 15–20 s, with
recruited each Monday and Wednesday from June 2010 to May
each hand and the average value (kg) of the three tests was
2011, among patients admitted to the Department of Internal
used for the analysis [20].
Medicine, Cardiovascular and Kidney Diseases of the University
of Palermo, in Italy. Inclusion criteria consisted of subjects aged
Bioimpedance analysis
≥ 60 years and admitted to the hospital from the hospital emer-
Bioelectrical impedance analysis was performed (GR, SM, VM,
gency room in the past 48 h. Exclusion criteria consisted of sub-
AB, NR) as previously described [21,22] using an 800 mA,
jects hospitalized within preceding 30 days; resident of a nursing
50 kHz, tetrapolar impedance plethysmograph (BIA; BIA-103,
home facility; the lack of a unique contact person to allow for
RJL, Detroit, USA/Akern Florence, Italy) to obtain body resis-
future telephone follow-up requests in case a participant expired
tance (R, Ohm), reactance (Xc, Ohm) and PA (PA
or was unable to provide data; lack of a telephone number; low
degrees = arctan (Xc/R)∙(180/p).). Patients were assessed in
levels of patient or caregiver education (illiterate or below pri-
the morning after an overnight fast, in the supine position with
mary school level); or the inability to perform BIA due to con-
arms and legs abducted from the body. Source and sensor
traindications such as pacemaker, metal implants, or amputation
electrodes were placed on the dorsum of both the hand and foot
of limbs. The study was conducted according to the guidelines
of the dominant side of the body.
laid down in the Declaration of Helsinki, and the protocol was
approved by the Institutional Review Boards at the Biomedical
Laboratory analysis
Department of Internal and Specialist Medicine (DIBIMIS) of the
Blood test results were abstracted from the medical record at
University of Palermo and at Dartmouth College. Each partici-
the time of admission. We recorded the following tests: fasting
pant approved and signed an informed consent form.
plasma glucose, cholesterol, triglycerides, high-density
A physician not involved in patient care (GP) abstracted the
lipoprotein (HDL) cholesterol, white blood cells (WBC), hae-
medical record of all participants. All information was obtained
moglobin, albumin. Low-density lipoprotein (LDL) cholesterol
through patient interview directly or, in the event they were
concentration was calculated using the Friedewald’s formula.
unable due to a health condition, a collateral history from a
family member or caregiver was obtained. The MNA was
Follow-up information
administered by GR, SM, VM, AB, NR as described elsewhere
Patients were contacted by telephone at 4-month intervals
[9,18]. A MNA total score of < 17 was indicative of malnutrition
( 1 month) following discharge. A 10- to 15-min telephone
and a score of 17–235 indicative of risk of malnutrition [18].
interview was conducted using a standardized template of
Discharge diagnoses were classified using International Clas-
questions by SM and VM. The interview determined changes in
sification of Diseases-9 codes and classified by the discharging
health status, new episodes of hospitalization, changes in
physician [http://www.who.int/classifications/icd/en
medications, socio-environmental and nutritional conditions.
accessed on 12 October 2013].
Patients or their caregivers were interviewed face to face in the
clinic or assessments performed by telephone. Mortality was
Clinical measurements ascertained by telephone interview by the study assistant who
Systolic blood pressure and diastolic arterial blood pressure obtained information from the family. Mortality data were
were assessed at 5-min intervals in the seated position and additionally verified by linking participants to the Sicilian
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MORTALITY AND NUTRITIONAL PREDICTORS
regional mortality registry at the Epidemiologic Observatory of Table 1 International Classification of Diseases-9 discharge
the Regional Department of Health (Palermo, Italy); this pro- diagnoses
cedure allowed also to obtain mortality data of participants that ICD-9 codes n %
were lost at telephone contact.
1–139 Infectious and parasitic diseases 2 09
60
Discussion
50 Our data are the first to identify the importance of considering
PA as a mortality predictor following discharge in elderly
40
inpatients. This important finding in a population at risk of
0 10 20 30 40 50 malnutrition provides additional evidence that tools other than
Time (months)
MNA should be considered to identify patients at risk of death
Time (months) 4 12 24 36 48 posthospitalization.
Our data are consistent with other studies demonstrating that
Deaths (n) 18 35 63 74 90 PA is predictive of in-hospital mortality in geriatric patients
[23] or in conditions with persons with multimorbidity,
MNA total score (< median value = blue; ≥ median value = green; median value = 22) including cancer [24–26], haemodialysis [27], human immun-
Log-rank test: χ2 = 8·2; P = 0·004 odeficiency virus infection [28], and amyotrophic lateral scle-
rosis [29]. Our study suggests that PA independently is
Figure 2 Kaplan–Maier survival probability curves according
to the median value of Mini-nutritional Assessment score in associated with mortality after discharge from hospital in
225 patients aged ≥ 65 years after discharge from Internal patients with different clinical conditions suggesting that even
Medicine hospital wards. in complex patients, there may be utility in using this measure
for predictive modelling.
Considering the three groups based on the tertiles of PA
(n = 127) of participants were at risk of malnutrition. Partici- groups (Appendix 1), we did not observe any significant dif-
pants who died were older, had a higher number of offspring, a ference in terms of age, gender and associated comorbidities;
lower hypertension rates and similar rates of coronary heart however, the low PA group exhibited characteristics suggestive
disease, type 2 diabetes and chronic renal failure. Patients who of malnutrition and frailty. In this group, we demonstrated
died had no different discharge diagnoses as compared to those lower body weight, muscle strength and MNA score, lower
alive at follow-up (data not shown). The clinical characteristics blood concentrations of albumin and haemoglobin and higher
of the participants classified according to the tertile of bioelec- WBC concentrations than higher PA groups. Notably, we did
tric phase angle are presented in Appendix 1. The MNA score not measure specific parameters of inflammation (i.e. hs-C-
was significantly correlated with BMI (r = 026; P < 0001). reactive protein, interleukin-6, tumour necrosis factor-a). The
Cox-proportional hazard model demonstrated significant finding of higher WBC concentrations in patients with poorer
relationships for PA, MNA score, age and gender on mortality, PA value may likely reflect a general tendency towards
while BMI, number of comorbidities, muscle strength, serum inflammation that has been associated with both increased risk
concentrations of haemoglobin and albumin had no significant of mortality [30,31] and malnutrition/frailty condition in the
effect (Table 3). Censoring participants at each time of follow- elderly hospitalized patient [32,33]. The value of using PA in
up resulted in different time models for death (Table 4). Age highlighting both individual clinical and nutritional conditions
and sex-specific interactions were tested in each model and may be explained using the BIA theory [34]. PA is inversely
were not significant (data not shown). In particular, only PA related with the extracellular/intracellular water ratio (ECW/
resulted significantly in associations with death at each study ICW); therefore, a low PA value is in consequence of high
time point. Figure 1 demonstrates Kaplan–Meier survival ECW/ICW value, a condition that occurs when the absolute or
curves suggesting that patients with the lowest tertile of PA relative amount of ECW is increased [15,35]. An increased
had higher adjusted mortality estimates. Similarly, the survival ECW/ICW value may result from compromised general clini-
curves demonstrated that the median MNA score discrimi- cal conditions due to altered cellular (i.e. membrane sodium/
nated survival probability (Fig. 2). potassium pumps) functioning as well as from altered nutri-
Of participants with both PA and MNA scores available tional states characterized by loss of body cell mass and the
(n = 192), 25 (13%) had a readmission within 4 months after consequent loss of ICW. Impaired clinical or nutritional
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MORTALITY AND NUTRITIONAL PREDICTORS
Table 2 Baseline characteristics of patients aged ≥ 65 years after discharge from hospital
Participants
All (N = 225) Alive (N = 135) Dead (N = 90) P*
Table 3 General-modelled Cox-proportional hazard for likely is a nonspecific measure suggestive of impaired home-
mortality in 192 patients aged ≥ 65 years after discharge from ostasis, a characteristic observed in frailty. Future study
Internal Medicine hospital wards should determine whether PA impacts shorter-term function
HR 95% CI and recovery from the negative effects of hospitalizations, but
also investigate the impact on serological inflammatory
Phase angle 078 064–095
biomarkers such as C-reactive protein, interleukin-6 and
MNA 095 090–099 tumour necrosis factor-a.
Age 104 101–107 Our results also paralleled those observed by others noting
that low MNA scores predict poor outcomes in geriatric hos-
Gender* 042 024–074
pitalized patients [37]. While this was not surprising, the fact
BMI 098 094–103 that the relationship was not modified by PA at 48 months
Muscle strength †
098 094–102 suggests that both could potentially be biomarkers for death in
‡ this at-risk population, at least in the long run. Surprisingly, we
Comorbidities 099 083–117
did not observe any impact of grip strength on mortality. One
Serum concentrations of possible explanation is there may be an interplay between
Haemoglobin 090 082–103 nutritional status and grip strength and that MNA score or PA
led to its nonsignificance. This is purely hypothetical, and we
Albumin 082 058–115
suggest further studies to reproduce these results.
HR, hazard ratio; CI, confidence interval; BMI, body mass index; MNA, Adequate data concerning the general prevalence of hospital
Mini-nutritional Assessment. malnutrition in Italy are lacking. As in other reports [38,39],
*Male = 1, female = 2.
†
Handgrip test.
we found a high prevalence of malnutrition and risk of mal-
‡
Total number of comorbidities: type 2 diabetes, hypertension, coronary nutrition among the nonsurgical elderly patients included in
heart disease, congestive heart failure, chronic obstructive pulmonary dis- this study. Our results are in agreement with a study
ease, chronic renal failure, liver cirrhosis, malignant cancer, dementia.
demonstrating poor outcomes in terms of in-hospital and long-
term mortality in geriatric hospitalized patients with low
conditions may be associated with low PA values and can MNA score [37]. The group of patients who died during fol-
possibly explain our findings that PA may predict mortality low-up exhibited poorer clinical and nutritional characteristics
and that PA is a measure of cell mass, nutritional risk and (Table 2). However, PA was uniquely associated with survival
general health [34]. In fact, BIA is not a direct method for the length probability. In fact, individuals with a PA < 46° at
assessment of body composition and its accuracy as an indi- admission had less chance of survival following discharge.
cator of body composition relies largely on the use of appro- These values closely approximate PA values that other studies
priate regression equations that may not be applicable in [16,23] demonstrated to be critical for survival in similar group
patients with disturbed hydration or altered distribution of of patients.
ECW/ICW. Our results suggest that we can bypass standard Our study also demonstrates that rate of rehospitalization
mathematical equations and use raw parameters to elicit 4 months after discharge was predicted by a low PA. This
hydration and body cell status [15]. Our study is based upon result may be analysed in view of the recently described
posthospitalization mortality that differs from those previously ‘posthospital syndrome’ a condition concerning patients dis-
published that describe in-hospital mortality [6, 7]. Future charged from hospital that have an acute medical problem
studies measuring the PA likely could permit to identify the within the subsequent 30 days necessitating another hospital-
subgroup of malnourished patients with high mortality risk to ization often for conditions different from the initial diagnosis
be included in nutritional intervention trials in order to [8,40–42]. The sample size of the cohort considered in this study
demonstrate the efficacy of treatment of illness-related malnu- was too small to analyse data relative to 30-day rehospitaliza-
trition, a field that is still lacking of adequate evidence [36]. tion rate; however, the results concerning 4-month rehospital-
Our mortality estimates are not trivial and potentially may ization are in agreement with the possibility that PA may also
provide a new line of research. Clinicians currently have be a good candidate to predict 30-day posthospital syndrome.
limited modalities in assessing malnutrition in hospitalized This is a hypothesis that remains to be investigated by specifi-
adults. These results suggest that BIA has improved predictive cally designed trials.
validity over MNA. This is important clinically in that BIA Our analysis has some important limitations that should be
can easily be performed in hospitalized patients, and is less acknowledged. First, BIA was not performed at discharge and
labour-intensive than the MNA. MNA requires trained staff this information would have greatly increased the quality of
spending at least 15 min with patients or caregivers. Low PA information. We relied on BIA measurement during the
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MORTALITY AND NUTRITIONAL PREDICTORS
109 (079–150) hospital stay and hence factors that could impact body com-
123 (093–161)
116 (091–146)
096 (079–116)
096 (079–116)
096 (081–114)
Comorbidities‡
Table 4 Time-modelled Cox-proportional hazard for mortality in 192 patients aged ≥ 65 years after discharge from Internal Medicine hospital wards
Total number of comorbidities: type 2 diabetes, hypertension, coronary heart disease, congestive heart failure, chronic obstructive pulmonary disease, chronic renal failure, liver
position and fluid shifts could conceivably impact our results. It
remains unclear whether mortality rate was lower in those
patients whose PA improved at discharge. A limitation is the
heterogeneity of the patient population; however, this may be a
result of our real-life study design and likely reflects reliability.
Another limitation of the present study is that the role of
Muscle strength†
101 (093–111)
099 (092–107)
099 (092–107)
097 (093–101)
097 (093–101)
096 (092–100)
comorbidities could not be investigated as the number of cases
included was rather limited to allow an adequate analysis of
the effect of comorbidity. We attempted to overcome this lim-
itation by including the number of comorbidities in the
regression analysis which was not significant. While we had
complete mortality ascertainment, future study with adequate
099 (088–112)
101 (093–112)
099 (092–107)
098 (093–103)
098 (093–103)
099 (095–104)
Acknowledgments
Gender*
Funding sources
This research was supported in part by the no profit Associ-
azione Onlus Nutrizione e Salute, Palermo, Italy.
Age
Address
Dipartimento Biomedico di Medicina Interna e Specialistica
MNA
*Male = 1, female = 2.
Correspondence to: Silvio Buscemi, Dipartimento Biomedico di 17 Montagnani M, Montomoli M, Mulinari M, Guzzo G, Scopetani N,
Medicina Interna e Specialistica (DIBIMIS), Laboratorio di Gennari C. Relevance of hydration state of the fat free mass in
estimating fat mass by body impedance analysis. Appl Radiat Isot
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Appendix 1 Anthropometric, demographic and clinical characteristics of the participants classified according to the tertile of bioelectric phase angle
Appendix 1 Continued
Phase angle tertile
I (N = 61) II (N = 68) III (N = 63) P†
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