Summary
Objectives:
To evaluate the relationship between C-reactive protein (CRP)/prealbumin and CRP/albumin ratios, Clinical Frailty Scale (CFS) scores, and short-term (first 3 days) and long-term (28 days) mortality in geriatric patients hospitalized in the intensive care unit.
Methods:
After obtaining ethical approval and informed consent, 213 patients aged 65 years and older were included. Patients discharged within 24 hours, those discharged and readmitted during the study period, those receiving routine albumin replacement, and patients with cirrhosis or undergoing chronic dialysis were excluded. Demographic characteristics, admission diagnoses, chronic comorbidities, frailty scores at admission, and laboratory values, including albumin, prealbumin, and CRP levels measured within the first 24 hours were recorded.
Results:
The study population comprised 97 (45.5%) female and 116 (54.5%) male patients, with a mean age of 78.8 years. The most common diagnosis was septicemia (56.33%), and the most prevalent comorbidities were hypertension (65.25%), malignancy (35.6%) and diabetes (34.7%). Both CRP/prealbumin and CRP/albumin ratios were higher in patients who experienced early and late mortality. Frailty scores did not differ in cases of early mortality; however, patients with higher frailty scores were more likely to experience long-term mortality. Additionally, the length of intensive care unit stay was longer in patients with a frailty score ≥7 compared to those with a score ≤6.
Conclusion:
The CFS, CRP/prealbumin, and CRP/albumin ratios are valuable predictors of long-term mortality in older patients receiving intensive care.
Keywords: Critical care, C-reactive protein, Frailty, Mortality, Prealbumin, Serum albumin
Introduction
With increasing life expectancy, the evolving demographic structure necessitates ongoing modernization of healthcare practices. Recent studies have aimed to improve existing scoring systems by incorporating laboratory biomarkers, their dynamics, and interrelationships to enhance the early prediction of mortality and morbidity. Such advancements can enable timely and effective interventions while reducing unnecessary procedures and healthcare costs [1].
C-reactive protein is a well-established serum acute-phase reactant commonly used to monitor infections, tissue injury, and autoimmune diseases [2]. Albumin plays a critical role in maintaining osmotic pressure, regulating pH levels, and transporting drugs and hormones, making it a valuable indicator of liver and kidney function [3]. Prealbumin serves as an important biomarker for assessing liver function, inflammation, and thyroid function, while also providing timely and sensitive information on nutritional status [4].
Clinical Frailty Scale was initially developed in 2005 and has undergone periodic updates, with the latest revision in 2020 [5]. This scale is a practical tool for evaluating frailty in geriatric patients and can aid in guiding treatment decisions, predicting outcomes, and optimizing resource allocation.
The ratios of these routinely measured laboratory biomarkers, which are commonly used for assessing mortality, morbidity, and treatment response, can support more personalized and effective patient management. The CRP/albumin and CRP/prealbumin ratios have gained attention as potential prognostic indicators in recent studies [6,7].
We aimed to evaluate the relationship between CRP/prealbumin and CRP/albumin ratios, CFS scores at admission, and short-term (first 3 days) and long-term (28 days) mortality in geriatric intensive care unit (ICU) patients.
Method
This prospective observational study included patients aged 65 years and older who were admitted to ICUs between November 2022 and December 2023. The study was approved by the Ethical Committee of Clinical Research (decision number: 17/52) and informed consent was obtained from either the patients or their legal representatives.
Patients were included if they were 65 years or older, stayed in the ICU for more than 24 hours, voluntarily participated in the study (either personally or through legal representatives), and had complete medical records. Patients were excluded if they had incomplete medical records, declined participation (or their legal representatives refused consent), were admitted for surgical reasons, had ICU stays shorter than 24 hours, were discharged and readmitted during the study period, received routine albumin replacement, had a history of cirrhosis or liver failure, were hospitalized due to autoimmune disease exacerbations, were immunosuppressed, or were on routine dialysis.
After obtaining consent, demographic data such as age and sex, acute physiology and chronic health evaluation II (APACHE II) scores, reasons for ICU admission, comorbidities, and laboratory values (prealbumin, albumin, and CRP levels) measured within the first 24 hours were recorded. Additionally, CRP/prealbumin and CRP/albumin ratios, CFS scores, and 28-day mortality status were documented. Patients were monitored throughout their ICU stay, and those transferred to general wards were followed up in their respective departments. Information on discharged patients was obtained via telephone follow-ups. Subgroup analyses were performed to distinguish between early mortality (within the first 3 days) and long-term mortality (within 28 days).
Statistical analyses
A power analysis, based on the study by Doğu et al. [7] (Can C-reactive protein/prealbumin ratio predict 48-hour mortality in intensive care unit patients?), indicated that a minimum of 204 patients was required, assuming 90% sensitivity, a 95% confidence level, and a 15% data loss rate. Descriptive statistics were reported as mean ± standard deviation, median, minimum–maximum, frequency, and percentage values. The Kolmogorov–Smirnov test was used to assess the distribution of variables. Independent sample t-tests and Mann–Whitney U tests were used to analyze quantitative independent data, whereas the chi-square test was used to analyze qualitative independent data. Receiver operating characteristic (ROC) curve analysis was performed to determine predictive performance and optimal cut-off values. All statistical analyses were performed using SPSS version 27.0.
Results
A total of 458 patients were admitted to the ICU during the study period. After excluding patients admitted for surgical reasons, those who died within 24 hours, patients with a history of chronic dialysis, those diagnosed with cirrhosis, patients who declined participation, and those with incomplete medical records 213 patients met the inclusion criteria. The mean age of the study population was 78.8 years, with 45.5% females and 54.5% males. The distribution of patient data is presented in Table 1.
Table 1.
Demographic data of patients, laboratory findings at the time of admission, clinical frailty scale scores, indication for ICU admission, length of intensive care stay, mortality rates and mortality days.
| Variables | Min-Max | Median | Mean± standard deviation |
|---|---|---|---|
| Age | 65.0–100.0 | 78.0 | 78.8 ± 9.4 |
| Gender n (%) | |||
| Female | 97 (45.5%) | ||
| Male | 116 (54.5%) | ||
| Apache II score | 9.0–53.0 | 23.0 | 24.8 ± 9.1 |
| Prealbumin (mg/dl) | 0.0–0.3 | 0.1 | 0.1 ± 0.1 |
| Albumin (g/l) | 10.0–44.0 | 28.0 | 27.6 ± 6.3 |
| CRP (mg/l) | 0.4–337.0 | 97.2 | 109.0 ± 84.0 |
| CRP/Prealbumin ratio | 3.8–30408.0 | 1089.0 | 2458.7 ± 4412.7 |
| CRP/Albumin ratio | 0.0–18.6 | 3.4 | 4.5 ± 4.1 |
| CFS | 3.0–8.0 | 6.0 | 6.4 ± 1.0 |
| ICU Stay (days) | 2.0–70.0 | 9.0 | 13.4 ± 12.3 |
| In-hospital mortality n (%) | 121 | 56.8% | |
| Short-term mortality (3 days), n (%) | 15 | 7.0% | |
| Long-term mortality (28 days), n (%) | 97 | 45.5% | |
| Mortality day | 2.0–182.0 | 14.0 | 19.7 ± 21.7 |
Values are presented as mean±SD unless otherwise indicated. CFS: Clinical frailty score, ICU: Intensive care unit, CRP: C-reactive protein.
The indications for ICU admission are listed in Table 2. Analysis of comorbidities revealed the following prevalence: hypertension 65.2%, malignancy 35.6%, diabetes mellitus 34.7%, coronary artery disease 32.8%, congestive heart failure 25.8%, and chronic lung disease 24.8%.
Table 2.
Indications for intensive care unit admission of patients.
| Indication for admission | |
|---|---|
| Septicemia | 120 (56.3%) |
| Cardiovascular disease | 53 (24.8%) |
| Lung disease | 43 (20.1%) |
| Bleeding | 11 (0.05%) |
| Cerebrovascular disease | 9 (0.04%) |
No significant differences were observed in age or sex distribution between patients who experienced short-term mortality and survivors (within 3 days). However, the APACHE II scores were significantly higher in the early mortality group. While prealbumin and albumin levels were associated with mortality, CRP levels were not. Ratios of CRP/prealbumin and CRP/albumin were significantly higher in the mortality group, indicating an association with increased mortality risk Table 3.
Table 3.
Short-term mortality (first 3 days) analysis.
| No mortality within 3 days | Mortality within 3 days | ||||
|---|---|---|---|---|---|
|
|
|
||||
| Variables | Mean±sd | Median | Mean±sd | Median | P-value |
|
| |||||
| Age | 78.8 ± 9.4 | 78.5 | 78.3 ± 9.9 | 78.0 | 0.853m |
| Gender, n (%) | |||||
| Female | 89 | 44.9% | 8 | 53.3% | 0.530X2 |
| Male | 109 | 55.1% | 7 | 46.7% | |
|
| |||||
| APACHE-2 Score | 24.0 ± 8.7 | 22.0 | 34.5 ± 9.0 | 34.0 | 0.000 m |
| Prealbumin (mg/dl) | 0.10 ± 0.06 | 0.09 | 0.06 ± 0.05 | 0.05 | 0.003 m |
| Albumin (g/l) | 27.9 ± 6.2 | 28.0 | 24.5 ± 8.0 | 23.0 | 0.049 t |
|
| |||||
| CRP (mg/l) | 105.7 ± 81.4 | 93.0 | 153.1 ± 106.3 | 135.1 | 0.097m |
| CRP/Prealbumin ratio | 2127.3 ± 3718.9 | 1044.7 | 6833.5 ± 8843.0 | 2252.3 | 0.023 m |
| CRP/Albumin ratio | 4.3 ± 3.9 | 3.2 | 7.2 ± 4.9 | 9.6 | 0.041 m |
|
| |||||
| CFS | 6.4 ± 1.0 | 6.0 | 6.7 ± 1.1 | 7.0 | 0.321m |
: Independent Sample t test
: Mann-Whitney U test
: Chi-square test, Values are presented as mean±SD unless otherwise indicated.
In the long-term analysis, the sex and age distributions were similar between the mortality and survival groups. However, APACHE II scores, CRP/prealbumin ratios, CRP/albumin ratios, and CFS scores were higher in the long-term nonsurvivor group. In contrast, prealbumin and albumin levels were lower in these patients, and CRP levels were notably elevated in patients with long-term mortality Table 4.
Table 4.
Long-term mortality (28 days) analysis.
| No Mortality | Long-Term Mortality | ||||
|---|---|---|---|---|---|
|
|
|
||||
| Variables | Mean±SD | Median | Mean±SD | Median | P-value |
|
| |||||
| Age | 78.9 ± 8.8 | 79.0 | 78.7 ± 10.1 | 78.0 | 0.802m |
| Gender, n(%) | |||||
| Female | 55 | 47.4% | 42 | 43.3% | 0.548X2 |
| Male | 61 | 52.6% | 55 | 56.7% | |
|
| |||||
| APACHE-2 Score | 21.3 ± 8.0 | 19.5 | 28.9 ± 8.7 | 28.0 | 0.000 m |
| Prealbumin (mg/dl) | 0.12 ± 0.06 | 0.11 | 0.08 ± 0.06 | 0.07 | 0.000 m |
| Albumin (g/l) | 28.9 ± 5.7 | 29.5 | 26.1 ± 6.7 | 26.0 | 0.001 t |
| CRP (mg/l) | 90.9 ± 77.6 | 75.0 | 130.6 ± 86.6 | 119.2 | 0.000 m |
|
| |||||
| CRP/Prealbumin ratio | 1559.1 ± 3176.3 | 739.6 | 3534.6 ± 5363.6 | 2113.0 | 0.000 m |
| CRP/Albumin ratio | 3.6 ± 3.6 | 2.6 | 5.7 ± 4.2 | 4.5 | 0.000 m |
|
| |||||
| CFS | 6.3 ± 1.0 | 6.0 | 6.6 ± 1.0 | 7.0 | 0.006 m |
| Length of Stay | 14.8 ± 15.0 | 8.0 | 11.8 ± 7.5 | 11.0 | 0.787m |
: Independent Sample t test
: Mann-Whitney U test
: Chi-square test.
The ROC curve analysis was performed to determine the predictive performance and optimal cut-off values of CRP/prealbumin and CRP/albumin ratios, as well as CFS scores at admission, for 28-day mortality. The determined cut-off values were: CRP/prealbumin ratio = 2100, CRP/albumin ratio = 6.9, and CFS score = 7. Patients with a CFS score of ≥7 had significantly longer ICU stays and higher mortality rates Table 5.
Table 5.
Comparison of patients with Clinical Frailty Scale ≤6 and ≥7.
| CFS ≤6 | CFS ≥7 | ||||
|---|---|---|---|---|---|
|
|
|
||||
| Variables | Mean±SD/n-% | Median | Mean±SD/n-% | Median | P-value |
| Age | 77.8 ± 9.0 | 77.5 | 79.8 ± 9.8 | 80.0 | 0.131m |
| Gender | |||||
| Female | 46 | 42.6% | 51 | 48.6% | 0.381X2 |
| Male | 62 | 57.4% | 54 | 51.4% | |
|
| |||||
| APACHE-2 score | 22.5 ± 8.5 | 21.0 | 27.1 ± 9.3 | 26.0 | 0.000 m |
| Prealbumin (mg/dl) | 0.10 ± 0.06 | 0.09 | 0.10 ± 0.06 | 0.08 | 0.324m |
| Albumin (g/l) | 28.6 ± 5.8 | 29.0 | 26.7 ± 6.8 | 26.0 | 0.031 t |
| CRP (mg/l) | 108.5 ± 84.6 | 97.3 | 109.6 ± 83.8 | 95.9 | 0.857m |
|
| |||||
| CRP/Prealbumin ratio | 2279.4 ± 3943.2 | 1100.8 | 2643.2 ± 4860.9 | 1068.8 | 0.581m |
|
| |||||
| CRP/Prealbumin ratio | |||||
| < 2100 | 73 | 67.6% | 73 | 69.5% | 0.762X2 |
| ≥ 2100 | 35 | 32.4% | 32 | 30.5% | |
|
| |||||
| CRP/Albumin ratio | 4.2 ± 3.8 | 3.6 | 4.8 ± 4.3 | 3.1 | 0.476m |
|
| |||||
| CRP/Albumin ratio | |||||
| < 6.9 | 86 | 79.6% | 74 | 70.5% | 0.122X2 |
| ≥ 6.9 | 22 | 20.4% | 31 | 29.5% | |
|
| |||||
| Length of stay in intensive care | 10.5 ± 10.1 | 7.0 | 16.4 ± 13.6 | 12.0 | 0.000 m |
|
| |||||
| Mortality/Discharge | |||||
| Discharged | 62 | 57.4% | 30 | 28.6% | 0.000 X2 |
| Mortality | 46 | 42.6% | 75 | 71.4% | |
| Mortality Day | 18.7 ± 27.5 | 11.5 | 20.3 ± 17.4 | 16.0 | 0.163m |
: Independent Sample t test
: Mann-Whitney U test
: Chi-square test.
Discussion
We aimed to examine the role of biochemical and clinical markers in predicting mortality in geriatric intensive care patients and found that the CRP/prealbumin and CRP/albumin ratios, along with the CFS score, were effective in predicting 28-day mortality.
The mean age of the patients was 78.8 years, with 45.5% female and 54.5% male, and an overall mortality rate of 56.8%. Fowler et al. [8] demonstrated that 60.1% of patients admitted to the ICU were male, and no difference was observed between the sexes in terms of APACHE-2 and APACHE-3 scores upon ICU admission. Nielsson et al. [9] reported a mean age of 64 years at ICU admission and noted an increase in the geriatric patient population over time. In this study, the 30-day-mortality rate in the older patients was 43.7%. In a cohort of 7,265 geriatric patients, mortality was observed in 56% of those aged > 85 years and 36.2% of those aged 65–75 years, indicating that age is a significant factor influencing ICU mortality in patients older than 75 years [10]. The sex distribution and mortality rate of the ICU patients in our study were consistent with findings from other studies involving older patients. The high mortality rate observed in our cohort is likely due to the advanced age of the patients and exclusion of those admitted for surgical reasons.
A previous study involving 552 ICU patients reported a proportional increase in mortality with higher APACHE-2 scores [11]. Consistent with these findings, the APACHE-2 scores in our study were lower in survivors than in both the early and long-term mortality groups. Furthermore, the mean APACHE-2 score was higher in the early mortality group than in the long-term mortality group.
In a study involving 145 geriatric patients evaluating various nutritional indices, prealbumin was more effective than other nutritional markers in predicting in-hospital mortality [12]. Similarly, analysis in patients with anorexia nervosa reported that albumin, prealbumin, and transferrin levels remained within normal in non-terminal patients, despite being recognized nutritional indicators. These findings suggest that serum proteins such as prealbumin are influenced not only by nutritional status but also by inflammatory processes. In our cohort, prealbumin levels differed significantly between survivors and patients with early- or long-term mortality, indicating that prealbumin may serve as an independent predictor of mortality in ICU patients.
Albumin is a key determinant of oncotic pressure and buffering capacity and plays an essential role in drug transport and glycocalyx function. Hypoalbuminemia is common among ICU patients and is associated with poor outcomes. In a study involving 2,010 patients, including those with acute cranial hemorrhage, hypoalbuminemia upon admission was an independent predictor of pneumonia, sepsis, and mortality [13]. In another study involving 276 patients with infective endocarditis, preoperative hypoalbuminemia was found to be a significant predictor of early mortality. Moreover, this value can be added to the European Cardiac Operative Risk Evaluation System and Charlson score to improve the predictive value of these scoring systems [14]. In our study, albumin levels at admission were lower in both the early and long-term mortality groups than in survivors, supporting the existing literature.
A meta-analysis of intensive care patients who had been hospitalized for more than 24 hour following various surgeries showed that CRP levels > 62.8 mg/L correlated with mortality [15]. A study of 177 patients with cirrhosis demonstrated that adding CRP levels to the model for end-stage liver disease (MELD) score improved the 30-day mortality prediction [16]. In our study, although CRP levels were significantly different in the long-term mortality group, no significant relationship was found between CRP levels and early mortality.
In one study, the CRP/prealbumin ratio was identified as an independent predictor of mortality and associated with length of hospital stay [17]. It was concluded that this ratio, which reflects both inflammation and nutritional status, does not contribute to complications and is more effective in predicting prognosis. In our study, CRP/prealbumin ratios were significantly higher in patients who experienced early mortality compared to survivors. During the 28-day follow-up, both the cutoff value of 2100 for the CRP/prealbumin ratio and the differences between patient groups remained significant. These findings suggest that the CRP/prealbumin ratio can serve as an independent predictor of mortality in ICU patients, particularly those admitted for medical reasons, reliably forecasting 28-day mortality.
Yakışık et al. [18] reported that the CRP/albumin ratio could serve as an independent prognostic marker in patients with sepsis. Similarly, Park et al. [6] demonstrated that the CRP/albumin ratio independently predicted 28-day mortality in ICU patients. In our study, a cut-off value of 6.9 for the CRP/albumin ratio effectively predicted 28-day mortality.
It has been demonstrated that chronological age alone is insufficient to predict the prognosis of older ICU patients [19]. The concept of frailty, which assesses physiological responses to stressors rather than age, has become an important factor in clinical management. The CFS has been successfully used in numerous large-scale studies assessing frailty and predicting mortality in older patients [20,21]. Unlike other biomarkers, frailty does not reflect temporary or transient conditions. This phenomenon requires long-term follow-up and management. In their FACTS study, Rosenberg et al. [22] showed that frailty assessment predicted mortality more accurately than a chronic disease diagnosis. They reported that survival was approximately 13 months for patients with a CFS score of 7 or higher, comparable to the prognosis of stage 4 lung cancer. In a study of 433 patients aged > 75 years who were followed up for ischemic stroke, the CFS was found to be effective in predicting the 28-day mortality [23]. Furthermore, Semelka et al. [24] reported that frail patients were more likely to be discharged to nursing homes than their non-frail counterparts, highlighting the importance of early planning for post-ICU care in this population. In line with these findings, the CFS is increasingly recognized as an essential tool not only for predicting mortality but also for informing healthcare resource allocation, guiding patients and family decisions, and supporting ICU triage. Early identification of frail patients allows for prompt intervention when reversible causes are present. However, even with adequate medical support, frail patients with reduced resilience to acute stressors may still experience mortality over time due to insufficient internal reserves and the depletion of resources in the face of critical illness. In our study, no differences in CFS scores were observed between patients who died within the first 3 days and those who survived. However, during the 28-day follow-up, a statistically significant difference was observed between patients with CFS scores of 6 or lower and those with CFS scores of 7 or higher in terms of 28-day mortality. These results indicate that the CFS is a valuable tool for predicting 28-day mortality in ICU patients.
Study limitation
One limitation of our study is that it included only geriatric ICU patients admitted for nonsurgical reasons. Multicenter studies with larger patient populations are needed regardless of the reason for ICU admission. In this study, the mortality was assessed at 28 days. Extending the follow-up period beyond 28 days would provide more comprehensive information on long-term prognosis.
In conclusion, early mortality in geriatric ICU patients admitted for non-surgical reasons was associated with elevated CRP/prealbumin and CRP/albumin ratios measured within the first 24 hour of ICU admission. For long-term outcomes, a combined increase in the CFS score, along with cutoff values of 2100 for the CRP/prealbumin ratio, 6.9 for the CRP/albumin ratio, and 7 for the CFS, effectively predicted mortality.
Disclosure Statement
AI tool (Chat GPT) is utilized specifically only in Arabic Translation of the abstract. The manuscript or essence of its contents is not previously published in partial or full in the website or printed journal in other language than English.
Acknowledgement
We would like to thank Editage (https://www.editage.com/) for the English language editing.
Disclosure
Authors have no conflict of interests and the work was not supported or funded by any drug company.
Contributor Information
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