Systemic Inflammation and Adverse Heart Failure Outcomes
4 affiliations
- 1Division of Cardiology, Department of Medicine, University of California Los Angeles, Los Angeles, California, USA; Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, California, USA
- 2Palo Alto Veterans Affairs Healthcare System, Palo Alto, California, USA; Division of Cardiology, Stanford University School of Medicine, Stanford, California, USA
- 3Novo Nordisk Inc., Plainsboro, New Jersey, USA
- 4Palo Alto Veterans Affairs Healthcare System, Palo Alto, California, USA
Abstract
Background: The association between systemic inflammation (SI) and outcomes among patients with heart failure with preserved ejection fraction (HFpEF) or mildly reduced ejection fraction (HFmrEF) is uncertain. Objectives: This study aimed to evaluate the association between SI and clinical and economic outcomes among individuals with HFpEF/HFmrEF. Methods: We identified Veterans with HFpEF/HFmrEF with outpatient high-sensitivity C-reactive protein (hsCRP) testing from 2008 to 2022. We classified Veterans as with SI (hsCRP 2-10 mg/L) and without SI (hsCRP <2 mg/L). The primary outcome was the 3-component major adverse cardiovascular event (MACE) outcome of death, HF hospitalization, and HF-related emergency department encounters. Additional outcomes included acute care utilization and costs. We evaluated the adjusted associations between SI and clinical outcomes, acute care utilization, and costs via Cox regression, negative binomial regression, and gamma regression, respectively. Results: We identified 49,986 Veterans with HFpEF/HFmrEF with outpatient hsCRP levels. We compared 8,696 (17.4%) Veterans without SI (hsCRP <2 mg/L) and 25,352 (50.7%) Veterans with SI (hsCRP ≥2 mg/L and ≤10 mg/L Over a median follow-up of 3.4 years (IQR: 1.8-5.8), MACE incidence was 15.1/100 patient-years (95% CI: 14.9-15.4) among those with SI vs 11.8/100 patient-years (95% CI: 11.4-12.1) among those without SI ( P < 0.001). After adjustment, SI was associated with increased MACE (HR: 1.28; 95% CI: 1.24-1.33). SI was also associated with increased all-cause hospitalizations (incidence rate ratio: 1.19; 95% CI: 1.137-1.246) and $9,112 (95% CI: 6,135−12,089) in additional per-patient costs over 1 year. Conclusions: Among Veterans with HFmrEF/HFpEF, SI is associated with increased adverse clinical outcomes and higher costs.
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BibTeX
@article{alexandertsandhu2026systemic,
title = {{Systemic Inflammation and Adverse Heart Failure Outcomes}},
author = {Alexander T. Sandhu, MD, MS and Adam Furst, MS and Anubodh S. Varshney, MD and Karim Sallam, MD and Stephanie Hsiao, MD and Anthony Gromovsky, PhD and Kat Wolf Khachatourian, PharmD, MBA and Natasha Din, MBBS, MAS and Jeffrey R. Skaar, PhD and Ivy Tonnu-Mihara, PharmD, MS},
journal = {JACC: Advances},
year = {2026},
month = oct,
doi = {10.1016/j.jacadv.2026.103346},
url = {https://doi.org/10.1016/j.jacadv.2026.103346},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Systemic Inflammation and Adverse Heart Failure Outcomes
AU - Alexander T. Sandhu, MD, MS
AU - Adam Furst, MS
AU - Anubodh S. Varshney, MD
AU - Karim Sallam, MD
AU - Stephanie Hsiao, MD
AU - Anthony Gromovsky, PhD
AU - Kat Wolf Khachatourian, PharmD, MBA
AU - Natasha Din, MBBS, MAS
AU - Jeffrey R. Skaar, PhD
AU - Ivy Tonnu-Mihara, PharmD, MS
PY - 2026
DA - 2026/10/23
JO - JACC: Advances
DO - 10.1016/j.jacadv.2026.103346
UR - https://doi.org/10.1016/j.jacadv.2026.103346
AB - Background: The association between systemic inflammation (SI) and outcomes among patients with heart failure with preserved ejection fraction (HFpEF) or mildly reduced ejection fraction (HFmrEF) is uncertain. Objectives: This study aimed to evaluate the association between SI and clinical and economic outcomes among individuals with HFpEF/HFmrEF. Methods: We identified Veterans with HFpEF/HFmrEF with outpatient high-sensitivity C-reactive protein (hsCRP) testing from 2008 to 2022. We classified Veterans as with SI (hsCRP 2-10 mg/L) and without SI (hsCRP <2 mg/L). The primary outcome was the 3-component major adverse cardiovascular event (MACE) outcome of death, HF hospitalization, and HF-related emergency department encounters. Additional outcomes included acute care utilization and costs. We evaluated the adjusted associations between SI and clinical outcomes, acute care utilization, and costs via Cox regression, negative binomial regression, and gamma regression, respectively. Results: We identified 49,986 Veterans with HFpEF/HFmrEF with outpatient hsCRP levels. We compared 8,696 (17.4%) Veterans without SI (hsCRP <2 mg/L) and 25,352 (50.7%) Veterans with SI (hsCRP ≥2 mg/L and ≤10 mg/L Over a median follow-up of 3.4 years (IQR: 1.8-5.8), MACE incidence was 15.1/100 patient-years (95% CI: 14.9-15.4) among those with SI vs 11.8/100 patient-years (95% CI: 11.4-12.1) among those without SI ( P < 0.001). After adjustment, SI was associated with increased MACE (HR: 1.28; 95% CI: 1.24-1.33). SI was also associated with increased all-cause hospitalizations (incidence rate ratio: 1.19; 95% CI: 1.137-1.246) and $9,112 (95% CI: 6,135−12,089) in additional per-patient costs over 1 year. Conclusions: Among Veterans with HFmrEF/HFpEF, SI is associated with increased adverse clinical outcomes and higher costs.
SN - 2772-963X
ER -