European Journal of Cardiovascular Medicine

Timely identification of clinical deterioration due to underlying inflammation is a critical goal in the management of hospitalized patients. Progression of inflammation, whether driven by infectious, autoimmune, or other pathophysiological processes, is associated with a higher risk of morbidity, longer hospital stays, and increased resource utilization. Early detection of escalating inflammation allows clinicians to initiate targeted interventions, potentially preventing organ dysfunction and reducing mortality[1-2].

Inflammation represents the body’s complex biological response to harmful stimuli, such as pathogens, damaged cells, or irritants. Its clinical manifestations are often non-specific and may lag behind biochemical changes, making reliance solely on clinical assessment insufficient for early risk stratification. Laboratory biomarkers, therefore, are indispensable tools in monitoring disease severity and predicting patient outcomes[3-6].

Ferritin and C-reactive protein (CRP) have emerged as two of the most practical and informative biomarkers in this context. Ferritin, commonly recognized for its role in iron storage, is an acute-phase reactant whose levels are upregulated during systemic inflammation. Its elevation is mediated by pro-inflammatory cytokines, macrophage activation, and increased cellular turnover, and has been linked to heightened immune activation observed in severe infections, autoimmune flare-ups, and critical illness. Hyperferritinemia, even at moderate levels, can reflect an underlying cytokine storm or macrophage activation syndrome, which necessitates prompt therapeutic escalation[7-11].

CRP, synthesized by hepatocytes primarily under the influence of interleukin-6, rises rapidly within hours of an inflammatory insult and is one of the most sensitive markers for acute-phase reactants. As compared to many other inflammatory biomarkers, CRP possesses a relatively short half-life and displays a dynamic response to evolving pathological states, making it ideally suited to serial monitoring during hospitalization. Persistently or progressively elevated CRP levels have been associated with increased severity of infection, risk of complications, and poor prognosis in diverse medical and surgical settings[12,13].

While isolated “snapshot” measurements offer useful diagnostic clues, recent evidence supports the greater prognostic value of serial biomarker assessments. Serial tracking of ferritin and CRP provides insight into the trajectory of inflammation and can uncover early signals of deterioration well before overt clinical symptoms manifest. Furthermore, integrating serial trends into risk models enhances their predictive accuracy and complements clinical judgment[14].

In light of these considerations, we conducted this study to evaluate the utility of serial serum ferritin and CRP measurements in the early detection of inflammatory progression among hospitalized patients. By examining differences in both baseline values and temporal trends across patients with and without clinical worsening, we aimed to identify reliable biochemical predictors that could guide preemptive clinical intervention, optimize resource allocation, and ultimately improve patient outcomes. This approach reflects a shift from static to dynamic assessment in modern hospital medicine, with the goal of achieving precision and personalization in the care of patients at risk for rapid deterioration.

Study Setting and Design

This prospective observational study was conducted at a tertiary care hospital. A total of 73 adult inpatients, admitted with various inflammatory conditions, were consecutively recruited. The study was designed to assess the role of serial biomarker measurements in the early detection of inflammatory progression.

Study Groups

Upon enrollment, patients were stratified into two distinct groups based on their clinical course during hospitalization:

• Progression group: Patients who exhibited clinical deterioration, defined by the development of new or worsening symptoms or by the need for treatment escalation (such as critical care admission or organ support) during their hospital stay (n=25).
• No-progression group: Patients who remained clinically stable and did not require escalation of care (n=48).

Procedure and Data Collection

At admission, detailed demographic data (age, sex) and comorbidities (hypertension, diabetes mellitus, chronic kidney disease, chronic obstructive pulmonary disease, ischemic heart disease, malignancy) were recorded for each participant. Clinical status was closely monitored throughout hospitalization.

Venous blood samples were systematically collected from each patient at three time points:

• Day 1 (D1): upon admission,
• Day 3 (D3): third day after admission,
• Day 5 (D5): fifth day after admission.

Serum ferritin and C-reactive protein (CRP) concentrations were measured at each time point using standardized laboratory assays Figure 1. CONSORT flow diagram.

Outcome Measures

The primary outcome was the difference in serial ferritin and CRP trends between groups. Secondary outcomes included the association between baseline variables (demographics, comorbidities, baseline biomarker levels) and risk of progression, assessed by multivariable analysis.

Statistical Analysis

Continuous variables were summarized as mean ± standard deviation or as median (interquartile range), as appropriate. Intergroup differences were evaluated using Student’s t-test or Mann-Whitney U test for continuous data, and chi-square or Fisher’s exact test for categorical data. Serial biomarker trends were analyzed with repeated measures statistical approaches. Independent predictors of progression were identified using multivariable logistic regression (results as odds ratios [OR] with 95% confidence intervals). Analyses were conducted with significance set at a two-tailed p-value <0.05. All data were processed with standard statistical software.

Figure 1. CONSORT flow diagram illustrating patient enrollment, group allocation, serial biomarker measurement, and inclusion in analysis.

Baseline Demographic and Clinical Characteristics

At admission, patients in the progression group were significantly older than those without progression, whereas sex distribution and comorbidities showed no statistically significant differences. Details are shown in Table 1.

Table 1. Baseline characteristics of patients (n = 73)

*Values are presented as mean ± standard deviation (SD) or number (%). CKD – chronic kidney disease; COPD – chronic obstructive pulmonary disease; IHD – ischemic heart disease. p-values: Student’s t-test for continuous variables; †Chi-square or Fisher’s exact test for categorical variables.

Figure 2. Baseline Demographic and Clinical Characteristics

Older age was a significant predictor of progression at baseline, while other variables such as sex and comorbidities showed no statistical significance, though comorbidities were more frequent in progressors.

Baseline Biomarker Levels

Baseline median serum ferritin and CRP were significantly higher in the progression group, indicating a potential role as early predictors of deterioration (Table 2).

Table 2. Baseline ferritin and CRP levels

Values are median [interquartile range (IQR)]. CRP – C-reactive protein. p-values: ‡Mann–Whitney U test.

Both biomarkers were significantly elevated in patients who progressed, highlighting their importance as baseline indicators of higher inflammatory burden.

Serial Biomarker Trends

Serial measurements revealed substantial increases in ferritin and CRP over days 1, 3, and 5 among progressors, whereas non-progressors maintained stable or improving levels (Table 3).

Table 3. Serial ferritin and CRP values (mean ± SD)

Values are mean ± SD. CRP – C-reactive protein. Percent change (D5 vs D1) for both biomarkers was statistically significant (p < 0.001, repeated measures analysis).

Rising ferritin and CRP levels over time were strongly associated with clinical progression, supporting their use in continuous patient monitoring.

Multivariable Predictors of Progression

Multivariable logistic regression identified baseline CRP and ferritin as independent predictors after adjusting for age, sex, and comorbidity (Table 4).

Table 4. Multivariable logistic regression for inflammatory progression

OR – odds ratio; CI – confidence interval; CRP – C-reactive protein. Variables were entered into the model if p < 0.1 in univariate analysis.

CRP had the strongest independent association with progression, followed by ferritin, underscoring the prognostic relevance of these inflammatory markers.

ROC and Correlation Analyses

The ROC curve (Figure 3A) demonstrated excellent discrimination for CRP percent change (AUC 0.996, sensitivity 96%, specificity 100%, optimal cut-off +33.6%). Scatter plots (Figure 3B) revealed strong positive correlations between ferritin and CRP on days 1, 3, and 5, with the correlation coefficient increasing over time.

Figure 3. Biomarker performance and correlation over time

AUC – area under the ROC curve; ROC – receiver operating characteristic; CRP – C-reactive protein. Correlation assessed using Pearson’s r Panel A: ROC curve for CRP percent change from day 1 to day 5.Panel B: Scatter plots with regression lines for ferritin–CRP correlation at days 1, 3, and 5.

CRP percent change is a near-perfect discriminator of progression risk, and the strengthening correlation between ferritin and CRP over time suggests these biomarkers track parallel inflammatory pathways.

This study provides compelling evidence that both baseline and serial measurements of serum ferritin and C-reactive protein (CRP) are strong prognostic indicators of disease progression in hospitalized patients. We observed that individuals in the progression group presented with significantly higher levels of these biomarkers at admission and that these levels continued to rise over the first five days of hospitalization. Importantly, these associations remained significant even after adjusting for age, sex, and comorbidity, underscoring the independent predictive value of these inflammatory markers. Patients who progressed were notably older than those who remained stable, suggesting that age remains an important determinant of clinical outcomes. This is consistent with the established understanding that advancing age is associated with impaired immune regulation, heightened baseline inflammation, and diminished physiological reserve[15,16]. Although the prevalence of comorbidities such as hypertension, diabetes, and chronic kidney disease was higher in the progression group, these differences were not statistically significant. This pattern may reflect the dominant role of acute inflammatory responses—captured by ferritin and CRP—over static demographic or comorbidity profiles in driving short-term deterioration. The elevated baseline ferritin and CRP levels in progressors mirror findings from both critical care and infectious disease contexts. Recent ICU-based studies, such as Deepak et al. (2025), have demonstrated that incorporating CRP and ferritin into early diagnostic and prognostic workflows significantly improves the ability to identify high-risk sepsis patients. Our results are also consistent with observations in hyperinflammatory autoimmune conditions reported in our earlier work, including cases of adult-onset Still’s disease with ankylosing spondylitis (Hait, Sengupta, & Choudhary, 2024) and pyrexia of unknown origin in Sjögren’s syndrome (Hait, Baladaniya, & Choudhary, 2025), where elevated ferritin paralleled systemic inflammatory activity. These parallels across disease states highlight ferritin and CRP as broadly relevant markers of adverse inflammatory trajectories[17,18].

Serial biomarker trends in our study provided even greater prognostic insight than baseline measurements alone. Progressors showed consistent upward trajectories in both ferritin and CRP, whereas non-progressors demonstrated stable or declining levels. Such dynamic changes are increasingly recognized as superior to single time-point assessments in predicting outcomes. This is well supported by longitudinal pediatric sepsis studies, where concurrent elevations and persistent rises in ferritin and CRP have been associated with greater risk of shock and mortality[19]. The trajectory-based approach used by Deepak et al. (2025), combining biomarker patterns with rapid diagnostic tools, resonates with our findings and reinforces the importance of serial monitoring in hospitalized patients. In our multivariable logistic regression model, baseline CRP and ferritin were both independently associated with progression, with CRP showing a stronger statistical association. CRP’s relatively rapid turnover and sensitivity to acute changes likely account for this finding, whereas ferritin—being more reflective of sustained macrophage activation—may capture the persistence and intensity of inflammation rather than its immediate fluctuations. These complementary characteristics make the combined monitoring of CRP and ferritin a rational approach for risk stratification, as seen in both infectious disease (Hait & Choudhary, 2025) and ICU sepsis (Deepak et al., 2025) contexts. The diagnostic performance of CRP percent change in our study was particularly striking, with a +33.6% increase from day 1 to day 5 yielding an area under the ROC curve of 0.996, 96% sensitivity, and 100% specificity. This level of discrimination surpasses many previously reported cut-offs for inflammatory biomarkers in predicting adverse outcomes. While few studies have employed percent-change metrics, the concept aligns with trajectory-based risk models in critical care, where persistently high or rising CRP patterns are strongly predictive of mortality[20].

Pathophysiologically, the progressive strengthening of correlation between ferritin and CRP over the course of hospitalization in our progression group likely reflects the convergence of shared upstream inflammatory drivers, notably interleukin-6 and other pro-inflammatory cytokines. These mediators stimulate hepatic CRP synthesis and ferritin release from activated macrophages, amplifying the acute-phase response. This parallel biomarker elevation is a recognized hallmark of hyperinflammatory states, as documented in our prior case-based research in infectious and rheumatological conditions, and further substantiates their joint utility in monitoring disease trajectories[21].

Clinically, these findings advocate for integrating ferritin and CRP monitoring into both early triage and ongoing patient management strategies. Elevated baseline values, particularly in older patients, could inform early escalation of care, while dynamic thresholds—such as the +33.6% CRP rise identified here—could serve as actionable triggers for intervention before overt clinical deterioration. Such an approach is feasible and potentially impactful in diverse care settings, from tertiary hospitals to ICUs, and is supported by the practical outcomes observed in Deepak et al. (2025). Nevertheless, this study has limitations that warrant consideration. It was conducted at a single center with a modest sample size, which may limit the generalizability of the findings. Treatment variability was not controlled for and could have influenced biomarker kinetics[22,23]. Future research should validate these results in larger, multicenter cohorts, explore mechanistic links between ferritin–CRP co-elevation and inflammatory progression, and assess whether biomarker-driven algorithms improve patient outcomes when integrated into clinical decision-making pathways.

This study provides compelling evidence that both baseline and serial measurements of serum ferritin and C-reactive protein (CRP) are strong prognostic indicators of disease progression in hospitalized patients. We observed that individuals in the progression group presented with significantly higher levels of these biomarkers at admission and that these levels continued to rise over the first five days of hospitalization. Importantly, these associations remained significant even after adjusting for age, sex, and comorbidity, underscoring the independent predictive value of these inflammatory markers. Patients who progressed were notably older than those who remained stable, suggesting that age remains an important determinant of clinical outcomes. This is consistent with the established understanding that advancing age is associated with impaired immune regulation, heightened baseline inflammation, and diminished physiological reserve[15,16]. Although the prevalence of comorbidities such as hypertension, diabetes, and chronic kidney disease was higher in the progression group, these differences were not statistically significant. This pattern may reflect the dominant role of acute inflammatory responses—captured by ferritin and CRP—over static demographic or comorbidity profiles in driving short-term deterioration. The elevated baseline ferritin and CRP levels in progressors mirror findings from both critical care and infectious disease contexts. Recent ICU-based studies, such as Deepak et al. (2025), have demonstrated that incorporating CRP and ferritin into early diagnostic and prognostic workflows significantly improves the ability to identify high-risk sepsis patients. Our results are also consistent with observations in hyperinflammatory autoimmune conditions reported in our earlier work, including cases of adult-onset Still’s disease with ankylosing spondylitis (Hait, Sengupta, & Choudhary, 2024) and pyrexia of unknown origin in Sjögren’s syndrome (Hait, Baladaniya, & Choudhary, 2025), where elevated ferritin paralleled systemic inflammatory activity. These parallels across disease states highlight ferritin and CRP as broadly relevant markers of adverse inflammatory trajectories[17,18].

Serial biomarker trends in our study provided even greater prognostic insight than baseline measurements alone. Progressors showed consistent upward trajectories in both ferritin and CRP, whereas non-progressors demonstrated stable or declining levels. Such dynamic changes are increasingly recognized as superior to single time-point assessments in predicting outcomes. This is well supported by longitudinal pediatric sepsis studies, where concurrent elevations and persistent rises in ferritin and CRP have been associated with greater risk of shock and mortality[19]. The trajectory-based approach used by Deepak et al. (2025), combining biomarker patterns with rapid diagnostic tools, resonates with our findings and reinforces the importance of serial monitoring in hospitalized patients. In our multivariable logistic regression model, baseline CRP and ferritin were both independently associated with progression, with CRP showing a stronger statistical association. CRP’s relatively rapid turnover and sensitivity to acute changes likely account for this finding, whereas ferritin—being more reflective of sustained macrophage activation—may capture the persistence and intensity of inflammation rather than its immediate fluctuations. These complementary characteristics make the combined monitoring of CRP and ferritin a rational approach for risk stratification, as seen in both infectious disease (Hait & Choudhary, 2025) and ICU sepsis (Deepak et al., 2025) contexts. The diagnostic performance of CRP percent change in our study was particularly striking, with a +33.6% increase from day 1 to day 5 yielding an area under the ROC curve of 0.996, 96% sensitivity, and 100% specificity. This level of discrimination surpasses many previously reported cut-offs for inflammatory biomarkers in predicting adverse outcomes. While few studies have employed percent-change metrics, the concept aligns with trajectory-based risk models in critical care, where persistently high or rising CRP patterns are strongly predictive of mortality[20].

Pathophysiologically, the progressive strengthening of correlation between ferritin and CRP over the course of hospitalization in our progression group likely reflects the convergence of shared upstream inflammatory drivers, notably interleukin-6 and other pro-inflammatory cytokines. These mediators stimulate hepatic CRP synthesis and ferritin release from activated macrophages, amplifying the acute-phase response. This parallel biomarker elevation is a recognized hallmark of hyperinflammatory states, as documented in our prior case-based research in infectious and rheumatological conditions, and further substantiates their joint utility in monitoring disease trajectories[21].

Clinically, these findings advocate for integrating ferritin and CRP monitoring into both early triage and ongoing patient management strategies. Elevated baseline values, particularly in older patients, could inform early escalation of care, while dynamic thresholds—such as the +33.6% CRP rise identified here—could serve as actionable triggers for intervention before overt clinical deterioration. Such an approach is feasible and potentially impactful in diverse care settings, from tertiary hospitals to ICUs, and is supported by the practical outcomes observed in Deepak et al. (2025). Nevertheless, this study has limitations that warrant consideration. It was conducted at a single center with a modest sample size, which may limit the generalizability of the findings. Treatment variability was not controlled for and could have influenced biomarker kinetics[22,23]. Future research should validate these results in larger, multicenter cohorts, explore mechanistic links between ferritin–CRP co-elevation and inflammatory progression, and assess whether biomarker-driven algorithms improve patient outcomes when integrated into clinical decision-making pathways.

1. Kell DB, Pretorius E. Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells. Metallomics. 2014;6(4):748-773.
2. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999;340(6):448-454.
3. Tan L, Wang Q, Zhang D, et al. Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study. Signal Transduct Target Ther. 2020;5:33.
4. Lee YH, Song GG. Serum C-reactive protein levels in inflammatory and non-inflammatory diseases. Int J Rheum Dis. 2015;18(2):182-187.
5. Henry BM, Aggarwal G, Wong J, et al. Lactate dehydrogenase levels predict coronavirus disease 2019 (COVID-19) severity and mortality: a pooled analysis. Am J Emerg Med. 2020;38(9):1722-1726.
6. Deepak A, Gobind AP, Kumar SN, Periasamy P, Choudhary AK. Comparative evaluation of rapid diagnostic modalities and prognostic biomarkers in ICU sepsis patients. Asian J Pharm Clin Res. 2025;18(6):92-8.
7. Hait A, Choudhary AK. Hematological manifestations of undiagnosed tuberculosis. Ro J Infect Dis. 2025;28(1):64-71.
8. Hait A, Baladaniya M, Choudhary AK. Pyrexia of unknown origin and deep vein thrombosis in Sjögren’s syndrome. Fortune J Rheumatol. 2025;7:01-06.
9. Hait A, Sengupta S, Choudhary AK. Adult-onset Still’s disease in ankylosing spondylitis. Ro J Rheumatol. 2024;33(4):26-9.
10. He Q, Zhao W, Li X, Wang Z, Xu Y. Serum ferritin as an independent predictor of mortality in patients with sepsis: a retrospective cohort study using the MIMIC-IV database. BMC Infect Dis. 2023;23:412.
11. Carcillo JA, Sward KA, Bennett TD, et al. Longitudinal study of C-reactive protein and ferritin trajectories to identify high-risk pediatric sepsis phenotypes. Crit Care Med. 2022;50(3):e226-e239.
12. Horvat CM, Squire EN, MacDonald S, et al. Association of C-reactive protein and ferritin with pediatric sepsis mortality risk stratification. Pediatr Crit Care Med. 2017;18(8):752-60.
13. de Nooijer AH, Varkila MRJ, Kox M, Pickkers P. Clinical impact of C-reactive protein trajectory patterns in adult sepsis patients: a multicenter observational study. Sci Rep. 2023;13:13472.
14. Rosario C, Zandman-Goddard G, Meyron-Holtz EG, D’Cruz DP, Shoenfeld Y. The hyperferritinemic syndrome: macrophage activation syndrome, Still’s disease, septic shock and catastrophic antiphospholipid syndrome. BMC Med. 2013;11:185.
15. Mehta P, Cron RQ, Hartwell J, Manson JJ, Tattersall RS. Silencing the cytokine storm: the use of intravenous anakinra in hyperinflammatory COVID-19. Lancet Rheumatol. 2020;2(6):e358-e365.
16. Dinarello CA. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev. 2018;281(1):8-27.
17. Kanda N, Watanabe S. C-reactive protein in the pathogenesis of atherosclerosis. J Atheroscler Thromb. 2003;10(5):249-256.
18. Shoenfeld Y, Agmon-Levin N. ‘ASIA’ - Autoimmune/inflammatory Syndrome induced by Adjuvants. J Autoimmun. 2011;36(1):4-8.
19. Sorensen CJ, Pociot F, Binder CJ. C-reactive protein and risk of cardiovascular disease in patients with chronic inflammatory conditions: a review. Eur Heart J. 2021;42(8):748-758.
20. Vetter P, Vu DL, L’Huillier AG, et al. Clinical features of COVID-19. BMJ. 2020;369:m1470.
21. Clark R, Pitre T, Cowan J, et al. Biomarkers and clinical scoring systems in COVID-19: a review. Can J Infect Dis Med Microbiol. 2020;2020:8869453.
22. Shakoory B, Carcillo JA, Chatham WW, et al. Interleukin-1 receptor blockade is associated with reduced mortality in sepsis patients with features of macrophage activation syndrome: reanalysis of a prior phase III trial. Crit Care Med. 2016;44(2):275-281.
23. Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003;111(12):1805-1812.a