The role of C-reactive protein-albumin and red blood cell distribution width to albumin level ratio change in patients with heart failure in the sodium-glucose cotransporter-2 era

    Authors

    Abstract

    **Introduction**: Chronic inflammation plays a role in heart failure (HF) progression across its subtypes (reduced, mildly reduced, and preserved ejection fraction (EF) (1). While C-reactive protein (CRP) and albumin are known prognostic markers (2), the potential of the CRP-to-albumin ratio (CAR) and red blood cell distribution width-to-albumin ratio (RAR) as prognostic indicators in HF remains underexplored. **Patients and Methods**: This prospective observational study was conducted at Dubrava University Hospital (CaRD registry, NCT06090591), enrolling HF patients between May 2021 and March 2024. Data on demographics, comorbidities, serum biomarkers, EF, and adverse events (death, HF-related emergencies, or hospitalizations) were collected. Patients with complete CRP and albumin measurements at baseline and 6-month follow-up were included. **Results**: Among 1170 hospitalized HF patients, 368 were included. The median age was 67 years (IQR 60-74), 30% females (**Table 1**). Over the 6-month follow-up, CAR significantly decreased from 0.12 (95% CI 0.106-0.147) to 0.063 (95% CI 0.056-0.071), p<0.0001, with no significant difference between empagliflozin and dapagliflozin groups (p=0.922). There were 40 HF composite events. CAR and RAR were both correlated with HF composite events (CAR: r= 0.163, p= 0.0017; RAR: r= 0.157, p= 0.0025), particularly in the HFpEF group (CAR: r= 0.32, p= 0.0032; RAR: r= 0.307, p= 0.0047). ### TABLE 1: Baseline characteristics of participants (n=386). | **Category** | **Number** | **%** | | --- | --- | --- | | *Sex* | | | | Male | 258 | 66.8 | | Female | 110 | 28.5 | | Dapagliflozin | 195 | 50.5 | | Empagliflozin | 173 | 49.5 | | *NYHA status* | | | | NYHA I | 15 | 3.9 | | NYHA II | 174 | 45.1 | | NYHA III | 156 | 40.4 | | NYHA IV | 23 | 5.9 | | BMI (C, IQR) | 28.5 (25.6-32.6) | | | Smoking | 128 | 33.1 | | *Comorbidities* | | | | Atrial fibrillation | 171 | 44.3 | | Hypertension | 302 | 78.2 | | Diabetes mellitus | 158 | 40.9 | | Coronary artery disease | 177 | 45.9 | | Peripheral artery disease | 62 | 16.1 | | Dyslipidemia | 256 | 66.3 | | Stroke / TIA | 32 | 8.3 | | COPD / asthma | 38 | 9.8 | | HFrEF | 240 | 62.1 | | HFmrEF | 45 | 11.7 | | HFpEF | 83 | 21.5 | | *Ejection fraction* | | | | EF in HFrEF (C, IQR) | 30 (25-35) | | | EF in HFmrEF (C, IQR) | 45 (43-46) | | | EF in HFpEF (C, IQR) | 55 (50-60) | | | *Serum values* | | | | Hemoglobin (C, IQR) | 138 (127-148.5) | | | eGFR (C, IQR) | 66.8 (49.9-84.6) | | | NT-proBNP C, IQR) | 2612 (1143-6806) | | | Albumin (C, IQR) | 41 (38-43) | | | CRP (C, IQR) | 5 (2.1-11.35) | | | RDW (C, IQR) | 14.1 (13.4-15.2) | | | CAR (C, IQR) | 0.12 (0.05-0.28) | | | RAR (C, IQR) | 0.35 (0.32-0.4) | | [†] NYHA = New York Heart Association functional classification, BMI = body mass index, C = median, IQR = interquartile range, TIA = transient ischemic attack, COPD = chronic obstructive pulmonary disease, EF = ejection fraction, HFrEF = heart failure with reduced ejection fraction, HFmrEF = heart failure with mildly reduced ejection fraction, HFpEF = heart failure with preserved ejection fraction, eGFR = estimated glomerular filtration rate, NT-proBNP = N-terminal prohormone of brain natriuretic peptide, CRP = C-reactive protein, RDW = red blood cell distribution width, CAR = C-reactive protein to albumin ratio, RAR = red blood cell distribution width to albumin ratio **Conclusion**: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) significantly reduced CAR over the 6-month follow-up period, irrespective of the specific SGLT2i agent. Both CAR and RAR were independently associated with adverse HF outcomes, particularly in the HFpEF cohort, highlighting the significance of inflammatory processes in HF and the potential role of SGLT2i in modulating these markers in clinical practice.

    Keywords

    heart failure, sodium-glucose cotransporter-2 inhibitors, inflammation

    DOI

    https://doi.org/10.15836/ccar2024.446

    Literature

    1. Danesh J, Whincup P, Walker M, Lennon L, Thomson A, Appleby P, et al. Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. BMJ. 2000 July 22;321(7255):199–204. https://doi.org/10.1136/bmj.321.7255.199
    2. Yamada T, Haruki S, Minami Y, Numata M, Hagiwara N. The C-reactive protein to prealbumin ratio on admission and its relationship with outcome in patients hospitalized for acute heart failure. J Cardiol. 2021 October;78(4):308–13. https://doi.org/10.1016/j.jjcc.2021.05.009
    Cardiologia Croatica
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    The role of C-reactive protein-albumin and red blood cell distribution width to albumin level ratio change in patients with heart failure in the sodium-glucose cotransporter-2 era

    Extended Abstract
    Issue11-12
    Published
    Pages446-447
    PDF via DOIhttps://doi.org/10.15836/ccar2024.446
    heart failure
    sodium-glucose cotransporter-2 inhibitors
    inflammation

    Authors

    Marin Viđak*ORCIDDubrava University Hospital, Zagreb, Croatia
    Fran ŠalerORCIDDubrava University Hospital, Zagreb, Croatia
    Jasmina ĆatićORCIDDubrava University Hospital, Zagreb, Croatia
    Jelena KursarORCIDDubrava University Hospital, Zagreb, Croatia
    Petra VitlovORCIDDubrava University Hospital, Zagreb, Croatia
    Ana ŠermanORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Miroslav RagužORCIDDubrava University Hospital, Zagreb, Croatia
    Diana RudanORCIDDubrava University Hospital, Zagreb, Croatia
    Andrej NovakORCIDUniversity of Zagreb, Faculty of Science, Zagreb, Croatia
    Ivan ZeljkovićORCIDDubrava University Hospital, Zagreb, Croatia
    Šime ManolaORCIDDubrava University Hospital, Zagreb, Croatia
    Ivana JurinORCIDDubrava University Hospital, Zagreb, Croatia

    *Correspondence email: marin.vidjak@gmail.com

    Abstract

    **Introduction**: Chronic inflammation plays a role in heart failure (HF) progression across its subtypes (reduced, mildly reduced, and preserved ejection fraction (EF) (1). While C-reactive protein (CRP) and albumin are known prognostic markers (2), the potential of the CRP-to-albumin ratio (CAR) and red blood cell distribution width-to-albumin ratio (RAR) as prognostic indicators in HF remains underexplored. **Patients and Methods**: This prospective observational study was conducted at Dubrava University Hospital (CaRD registry, NCT06090591), enrolling HF patients between May 2021 and March 2024. Data on demographics, comorbidities, serum biomarkers, EF, and adverse events (death, HF-related emergencies, or hospitalizations) were collected. Patients with complete CRP and albumin measurements at baseline and 6-month follow-up were included. **Results**: Among 1170 hospitalized HF patients, 368 were included. The median age was 67 years (IQR 60-74), 30% females (**Table 1**). Over the 6-month follow-up, CAR significantly decreased from 0.12 (95% CI 0.106-0.147) to 0.063 (95% CI 0.056-0.071), p<0.0001, with no significant difference between empagliflozin and dapagliflozin groups (p=0.922). There were 40 HF composite events. CAR and RAR were both correlated with HF composite events (CAR: r= 0.163, p= 0.0017; RAR: r= 0.157, p= 0.0025), particularly in the HFpEF group (CAR: r= 0.32, p= 0.0032; RAR: r= 0.307, p= 0.0047). ### TABLE 1: Baseline characteristics of participants (n=386). | **Category** | **Number** | **%** | | --- | --- | --- | | *Sex* | | | | Male | 258 | 66.8 | | Female | 110 | 28.5 | | Dapagliflozin | 195 | 50.5 | | Empagliflozin | 173 | 49.5 | | *NYHA status* | | | | NYHA I | 15 | 3.9 | | NYHA II | 174 | 45.1 | | NYHA III | 156 | 40.4 | | NYHA IV | 23 | 5.9 | | BMI (C, IQR) | 28.5 (25.6-32.6) | | | Smoking | 128 | 33.1 | | *Comorbidities* | | | | Atrial fibrillation | 171 | 44.3 | | Hypertension | 302 | 78.2 | | Diabetes mellitus | 158 | 40.9 | | Coronary artery disease | 177 | 45.9 | | Peripheral artery disease | 62 | 16.1 | | Dyslipidemia | 256 | 66.3 | | Stroke / TIA | 32 | 8.3 | | COPD / asthma | 38 | 9.8 | | HFrEF | 240 | 62.1 | | HFmrEF | 45 | 11.7 | | HFpEF | 83 | 21.5 | | *Ejection fraction* | | | | EF in HFrEF (C, IQR) | 30 (25-35) | | | EF in HFmrEF (C, IQR) | 45 (43-46) | | | EF in HFpEF (C, IQR) | 55 (50-60) | | | *Serum values* | | | | Hemoglobin (C, IQR) | 138 (127-148.5) | | | eGFR (C, IQR) | 66.8 (49.9-84.6) | | | NT-proBNP C, IQR) | 2612 (1143-6806) | | | Albumin (C, IQR) | 41 (38-43) | | | CRP (C, IQR) | 5 (2.1-11.35) | | | RDW (C, IQR) | 14.1 (13.4-15.2) | | | CAR (C, IQR) | 0.12 (0.05-0.28) | | | RAR (C, IQR) | 0.35 (0.32-0.4) | | [†] NYHA = New York Heart Association functional classification, BMI = body mass index, C = median, IQR = interquartile range, TIA = transient ischemic attack, COPD = chronic obstructive pulmonary disease, EF = ejection fraction, HFrEF = heart failure with reduced ejection fraction, HFmrEF = heart failure with mildly reduced ejection fraction, HFpEF = heart failure with preserved ejection fraction, eGFR = estimated glomerular filtration rate, NT-proBNP = N-terminal prohormone of brain natriuretic peptide, CRP = C-reactive protein, RDW = red blood cell distribution width, CAR = C-reactive protein to albumin ratio, RAR = red blood cell distribution width to albumin ratio **Conclusion**: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) significantly reduced CAR over the 6-month follow-up period, irrespective of the specific SGLT2i agent. Both CAR and RAR were independently associated with adverse HF outcomes, particularly in the HFpEF cohort, highlighting the significance of inflammatory processes in HF and the potential role of SGLT2i in modulating these markers in clinical practice.

    Literature

    1. 1.
      Danesh J, Whincup P, Walker M, Lennon L, Thomson A, Appleby P, et al. Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. BMJ. 2000 July 22;321(7255):199–204.DOI
    2. 2.
      Yamada T, Haruki S, Minami Y, Numata M, Hagiwara N. The C-reactive protein to prealbumin ratio on admission and its relationship with outcome in patients hospitalized for acute heart failure. J Cardiol. 2021 October;78(4):308–13.DOI