Prognostic value of serum albumin and C-reactive protein levels in the elderly for assessing morbidity and mortality in a tertiary care center

Sanjo K John; N Padmaja; I V. Ramachandra Rao; Subalin Priya; Centina Rose John; Tittu Thomas James

doi:10.4103/jiag.jiag_60_22

ORIGINAL ARTICLE

Year : 2023 | Volume : 19 | Issue : 1 | Page : 24-28

Prognostic value of serum albumin and C-reactive protein levels in the elderly for assessing morbidity and mortality in a tertiary care center

Sanjo K John¹, N Padmaja¹, I V. Ramachandra Rao¹, Subalin Priya², Centina Rose John³, Tittu Thomas James⁴
¹ Department of General Medicine, S. V. Medical College, Tirupati, Andra Pradesh, India
² Department of Obstetrics and Gynaecology, Government Medical College, Cuddalore, Tamil Nadu, India
³ Department of Cleft and Craniofacial Surgery, Inga Health Foundation, Bengaluru, Karnataka, India
⁴ Physiotherapy Center, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka, India

Date of Submission	01-Nov-2022
Date of Decision	04-Jan-2023
Date of Acceptance	07-Jan-2023
Date of Web Publication	17-Mar-2023

Correspondence Address:
Tittu Thomas James
Physiotherapy Center, National Institute of Mental Health and Neuro Sciences, Bengaluru - 560029, Karnataka
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jiag.jiag_60_22

Abstract

Introduction: There is an increased population of elderly globally due to advancement of technology in health care. Elderly individuals are susceptible to various diseases, owing to deficits in nutrition or healthy lifestyle. Serum albumin and C-reactive protein (CRP) are found to be sensitive to nutritional status as well as inflammation. This study is an attempt to analyze the prognostic value of CRP and serum albumin and analyze its usefulness as a prognostic marker in assessing morbidity and mortality in elderly patients. Methodology: One hundred patients above the age of 65 years and were admitted to the emergency care facilities of our tertiary care center were recruited for the study. Serum albumin and CRP estimation was done on the day of admission along with Charlson Comorbidity Index (CCI), and was follow-up till discharge. Statistical analysis was performed to evaluate relationship between the serum values and CCI scores. Results: It was observed that 83.3% (10/12) of deaths occurred in those with low serum albumin levels, and 91.6% (11/12) with high CRP levels. The hazard ratio shows a 6% increased probability of death with one unit increase in CRP, whereas a one unit increase in serum albumin value decrease the probability of death. Conclusion: The present study concludes that low serum albumin and high CRP levels at the time of admission in the elderly population are associated with high CCI scores, longer hospital stay, and increased risk of mortality, demanding their estimation in the elderly in emergency and acute care facilities.

Keywords: C-reactive protein, elderly, morbidity, mortality, serum albumin

How to cite this article:
John SK, Padmaja N, Rao I V, Priya S, John CR, James TT. Prognostic value of serum albumin and C-reactive protein levels in the elderly for assessing morbidity and mortality in a tertiary care center. J Indian Acad Geriatr 2023;19:24-8

How to cite this URL:
John SK, Padmaja N, Rao I V, Priya S, John CR, James TT. Prognostic value of serum albumin and C-reactive protein levels in the elderly for assessing morbidity and mortality in a tertiary care center. J Indian Acad Geriatr [serial online] 2023 [cited 2023 Mar 22];19:24-8. Available from: http://www.jiag.com/text.asp?2023/19/1/24/371906

Introduction

In our society, due to advancements in health facilities, the proportion of older people is increasing. They are the fastest-growing segment of the population. The nutritional status of the elderly population has a crucial role in their health. Nutritional risk factors such as over-nutrition, undernutrition, vitamin deficiencies, and malabsorption also are the major cause of death. Nutritional risk factors can lead to diabetes, heart disease, stroke, and even cancers.^[1],[2] A detailed assessment of each of the physical and social impairments pertaining to the individual, the clinician can assess and ensure optimal nutrition in the elderly populations.^[3],[4]

Elderly individuals often fail to exercise enough to lead a healthy life. Regular physical activity can slow down the decline in the functional capacity associated with aging and can increase life span for up to 7 years.^[5] Some of the serious health issues faced by the elderly population who are aged >65 years are cardiovascular diseases such as myocardial infarction, cardiomyopathies, heart failure, hypertension, diabetes mellitus, thyroid disorders, osteoporosis, infections, neurodegenerative diseases, stroke, and cancers. Treating the elderly population is a huge challenge due to their multiple comorbidities, their lack of adherence to medications, and lack of social supports.^[6]

Frailty is an important geriatric syndrome. It is described by Van Abellan et al., (2008) as “a state of increased vulnerability, which results from the decreased physiological reserve, multisystem dysregulation, and limited capacity to maintain homeostasis.”^[7] The most widely accepted criteria for frailty is the Fried criteria.^[8] Old age is also associated with osteoporosis, frequent falls, psychiatric disorders, joint disorders, decreased vision, hearing loss, neurodegenerative disease, and cancer. Special care should be given regarding treatment strategy to have healthy and positive aging by decreasing the inflammatory process. As per Feinstein's definition, comorbidity is “any distinct additional entity that has existed or may occur during the clinical course of a patient who has the index disease under study.”^[9]

Serum albumin is a marker of the nutritional status of an individual as well as an acute-phase protein. Serum albumin levels decrease in inflammatory conditions, and thus it is a negative acute-phase protein. Serum albumin levels in elderly hospitalized patients have an inverse relation to morbidity and mortality in hospital admitted patients with acute medical conditions.^[10],[11] In hospitalized patients, higher albumin level correlated with improvement in the functional status of patients over a shorter period.^[12]

C-reactive protein (CRP) is an acute-phase protein. Plasma levels of CRP increase by at least 25% during an acute inflammatory condition.^[13] The majority of studies found out that CRP levels are elevated in cardiovascular diseases and stroke.^[14] During inflammation, interleukin (IL)-6 is secreted, and it induces the production of C-reactive protein. Studies have demonstrated that an increase in IL 6 correlates with an increase in CRP.^[15] Studies have also shown that variations in CRP and albumin levels independently affect the outcome of elderly hospitalized patients.^[16],[17] Thus levels of serum albumin and CRP can predict morbidity and mortality in elderly hospitalized patients.

In view of this, the pattern of change in acute-phase protein is of great clinical significance as it can assess the potential prognostic value of the medical condition. CRP is an acute-phase protein that has both pro-inflammatory and anti-inflammatory actions, and its levels are elevated in inflammatory processes. Albumin levels are decreased in both inflammation and malnutrition, whereas inflammation alone is associated with a greater decrease in albumin levels. This study is an attempt to analyze the prognostic value of CRP and serum albumin and analyze its usefulness as a prognostic marker in assessing morbidity and mortality in elderly patients.

Methodology

Subjects and methods

This study was a prospective analytical study, conducted during March 2019 to February 2020. The study was performed at the emergency department and acute medical care facilities of a tertiary care center. The study recruited 100 patients above the age of 65 years diagnosed with any medical illness and admitted to the emergency department of the institution. The inclusion and exclusion criteria of the study were as follows;

Inclusion criteria

Elderly individuals more than 65 years of age
Individuals diagnosed with any medical illness and admitted to the emergency department.

Exclusion criteria

Patients undergoing steroid treatment
Patients with tuberculosis
Patients left the hospital against medical advice
Patients with psychiatric illness
Patients administered with albumin infusion before getting admitted to the hospital.

Ethical clearance was obtained from the institution ethical board before initiation of the study. The caregiver/relative of all the recruited patients were briefed about the purpose of the study, and written informed consent was obtained from the caregiver/relative before any data collection process. All investigations were done free of cost, and no financial burden was imposed on the patients for the study.

Once the patient was recruited to the study, they were assessed with a detailed history and physical examination. The blood samples of the patients were taken on the day of admission for estimating the serum albumin and CRP levels. Charlson Comorbidity Index (CCI) was assessed in all patients on the day of admission, which predicts 1-year mortality for a patient who has multiple comorbidities.^[18] The patients were also follow-up till the date of discharge to record an event of death occurred or not. The patient recruitment and follow-up is depicted in the [Figure 1].

Figure 1: Flow chart depicting patient recruitment and study process

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Statistical analysis

Pearson correlation test is used to assess the correlation between serum albumin levels, CRP levels, and CCI score. The cross-tabulation analysis was performed between participants with normal serum albumin and abnormal levels against the event of death during the hospital stay to assess the odds ratio (OR) and relative risk (RR). Survival analysis was performed for serum albumin and CRP values against in hospital death in the population under study. The level of significance was set at P < 0.05. The analysis was done using SPSS (IBM SPSS Statistics for Windows, Version 22.0, Armonk, NY, USA: IBM Corp. Released 2013).

Results

A total of 100 patients were recruited for the study during 1 year, between the ages of 66–81 years. The mean age of the population was 70.09 ± 4.24 years. The majority of the patients were in the age group of 66–70 years (68%) and the least were in the group of more than 81 years (2%). The study population had 56 males and 44 females within the population. The majority of the participants presented with central nervous system diseases (35%), particularly cerebrovascular accident, followed by cardiovascular diseases (23%). Most of the participants had hypertension (47%) and diabetes (38%).

The mean serum albumin levels among males were 3.42 ± 0.71, whereas it was 3.32 ± 0.81 in females. Serum CRP levels of males were 31.11 ± 41.58, whereas in females it was 36.32 ± 45.56. The mean CCI values of the study population was 5.17 ± 2.06 (minimum = 2, maximum = 12). The CCI score among the various levels of serum albumin and CRP is depicted in [Table 1].

Table 1: Charlson Comorbidity Index scores in serum albumin and C-reactive protein levels

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The Pearson correlation analysis identified serum albumin levels found to have a negative correlation with CCI (r = −0.69, P < 0.001), whereas CRP had a positive correlation (r = 0.61, P < 0.001). This suggest an increased morbidity assessed using CCI in patients with low levels of serum albumin and high levels of CRP. Both correlation analysis was found to be statistically significant. The scatterplot illustrating the relationship between serum albumin and CRP values are given in [Figure 2] and [Figure 3], respectively.

Figure 2: Correlation between serum albumin and CCI values. CCI: Charlson Comorbidity Index

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Figure 3: Correlation between CRP levels and CCI values. CRP: C-reactive protein, CCI: Charlson Comorbidity Index

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Pearson analysis was also done to analyze the relationship between serum albumin and CRP values on hospital stay. Albumin values correlated negatively (r = −0.46, P = 0.64), whereas the CRP values correlated positively (r = 0.08, P = 0.41). Hospital stay was observed to be longer in individuals with low serum albumin and high CRP values. However, the relationship was not statistically significant.

A total of 12 participants died during the follow-up. The cross-tabulation analysis was performed between participants with normal serum albumin and abnormal levels against the event of death during the hospital stay in the study population. It was observed that 83.3% (10/12) of deaths occurred in those with low serum albumin levels and 16.6% (2/12) deaths in those with normal serum albumin. The risk analysis performed for serum albumin values according to the cross-tabulation identified an OR of 5.233, which shows that individuals with abnormal low albumin values are 5.233 times more likely to face the event (in-hospital death) than those with normal serum albumin levels. The RR was identified to be 4.434, which suggests the risk of 4.434 times to have an in-hospital death in individuals with low serum albumin levels than that of individuals with normal levels of serum albumin.

Cross-tabulation analysis was performed between participants with normal CRP levels and high levels against the event of death during the hospital stay in the study population. It was observed that 91.6% (11/12) deaths occurred in those with high CRP levels, and 8.3% (1/12) deaths in those with normal CRP levels. The risk analysis performed for CRP values according to the cross tabulation identified an OR of 1.737 which shows that individuals with high CRP values are 1.737 times more likely to face the event (in hospital death) than those with normal CRP levels. The RR was identified to be 1.644 which suggest the risk of 1.644 times to have an in hospital death in individuals with high CRP levels than that of individuals with normal levels of CRP.

Survival analysis was performed for serum albumin and CRP values against in-hospital death in the population under study [Figure 4]. The model was found to be significant with Chi-square (χ²) value of 11.192 (P = 0.004). The coefficient (B) of serum albumin and CRP was – 1.003 and 0.006, respectively. This is in accordance with the other analysis outcomes of the study. The hazard ratio (Exp[B]) of serum albumin and CRP was found to be 0.367 and 1.006, respectively. The hazard ratio shows a 6% increased probability of death with one unit increase in CRP, whereas a one unit increase in serum albumin value decrease the probability of death.

Figure 4: Cumulative survival plot of the participants

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Discussion

The present study identified the prognostic value of serum albumin and CRP in assessing the prognosis in the elderly patients with respect to the length of hospital stay, morbidity, and mortality.

In our study, we observed that there was no significant association with male-to-female ratio and hospital admission of the elderly population. The majority of admitted patients had neurological problems (35%) followed by cardiovascular diseases (23%) in the present study, constituting the major illness among the elderly seeking admissions at a tertiary care center. These findings were similar to a study conducted by Iwata et al.,^[19] in which central nervous system diseases constituted 26.9%, and cardiovascular diseases constituted 19.2%.

It was observed from the study that mean albumin level decreases when age increases. Literature suggest a reduction in serum albumin with aging, in the elderly of 72 years of age and above.^[20] Lower levels of albumin with increasing age can be attributed to poor nutritional status and acute or chronic inflammatory conditions that affect serum albumin levels by altering hepatic protein metabolism and inducing capillary leakage. Weaving et al.^[21] concluded that serum albumin value in females becomes close to male values around 60 years of age.

The study also identified a significantly higher CCI (6.36 ± 1.9) in those with serum albumin levels < 3.5 mg/dl in comparison to normal serum albumin levels. Literatures suggest a strong negative correlation between albumin levels and CCI scores in the elderly,^[22],[23] and reduced albumin levels to be associated with increased risk of mortality.^[24],[25] The study by Marinella and Markert,^[26] which recruited 5894 patients, the 30-day mortality in patients with hypoalbuminemia was 16.3% in comparison with 4.3% among patients with normal albumin levels. Studies have also reported a positive correlation of CRP with CCI as well as a significant increase in morbidity and mortality with an increase in CRP values.^[27],[28] This implicates that multiple comorbidities lead to increased inflammation in the body, and if it is not under control can subsequently result in increased mortality. We also found that lower serum albumin levels and high CRP values are associated with increased CCI scores, which in turn predicts increased mortality. This result may also probably because of the multiple comorbidities in the patients admitted to the institution. However, the serum values were not suggestive of predicting hospital stay in patients.

While analyzing albumin levels and hospital death, it was observed that patients with hypoalbuminemia (serum albumin <3.5 mg/dl) were 5.2 times likely to face in-hospital death compared to subjects with normal serum albumin levels. Evidence also report a higher mean length of hospitalization, with 7 ± 8 days and 9 ± 11 days in participants with mild and marked hypoalbuminemia, respectively.^[24] Higher CRP levels were also found to be associated with increased length of hospital stay (26 days) in critically ill patients in the intensive care unit, also 23% increased mortality.^[29],[30] Participants with elevated CRP and IL-6 were 2.6 times more likely to die compared to participants with normal CRP and IL-6.^[31]

Albumin indirectly determines the nutritional status and, in turn, the immunity of an individual. Low albumin levels in elderly individuals decrease immunity and prolong hospital stay and poor prognosis. Recent studies have shown that rather than a nutritional marker, albumin is a marker of inflammation. Thus, in the present study, low serum albumin may be due to inflammatory processes in elderly participants with multiple medical illnesses. In the present study, participants with CRP levels >5 mg/dl were 1.73 times likely to have in-hospital death compared to participants with normal CRP levels. However, the study by Iwata et al.^[19] reported that serum albumin was superior to CRP in predicting in-hospital death. The current study confirm that low serum albumin and high CRP may be associated with longer hospital stays, mortality, and poor outcome in elderly patients admitted to medical care facilities.

Limitations and suggestions

The study had a smaller sample size, with a heterogeneous group of population, could have influenced the results. The study also failed to correlate the nutritional status of the patients along with the serum values. Future studies must also focus on long-term follow-up after discharge from the medical care facility to identify a long-term prognosis of serum albumin and CRP values.

Conclusion

The present study concludes that low serum albumin and high CRP levels at the time of admission in the elderly population are associated with high CCI scores, longer hospital stay, and increased risk of mortality. Thus, CRP and serum albumin may be considered prognostic markers in assessing the morbidity and mortality in elderly hospitalized patients, which helps in screening those who require urgent and continuous medical care in an emergency or acute care setup.

Level of evidence – 2b.

Clinical relevance

CRP and serum albumin levels may be assessed at admission in an acute care setup for geriatric population as part of screening to assess their prognosis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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