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Soluble CD14 and Risk of Heart Failure and Its Subtypes in Older Adults
Sadeer G Al-Kindi1, Petra Buzkova2, Sanyog G Shitole3
1Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center and Case Western Reserve University, Cleveland, Ohio.
Insights
Soluble CD14 (sCD14) is linked to new heart failure (HF) cases, particularly HF with preserved ejection fraction (HFpEF), independently of other inflammation markers. Higher sCD14 levels predict HF incidence in older adults.
Area of Science:
- Cardiovascular Medicine
- Immunology
- Gerontology
Background:
- CD14 is a key inflammatory marker expressed by myeloid cells.
- Elevated soluble CD14 (sCD14) indicates poor prognosis in chronic heart failure (HF).
- The predictive value of sCD14 for HF incidence remains unclear.
Purpose of the Study:
- To investigate the association between sCD14 and the incidence of HF and its subtypes.
- To determine if sCD14 predicts HF independently of other inflammatory biomarkers in older adults.
Main Methods:
- Analysis of data from the Cardiovascular Health Study including 5217 participants without prior HF.
- Cox regression models were used to assess the association of baseline sCD14, hsCRP, IL-6, and WBC with incident HF over 13.6 years.
- Adjustments were made for clinical and laboratory covariates, including other inflammatory markers.
Main Results:
- A total of 1878 participants developed incident HF.
- Increased sCD14 levels were significantly associated with a higher risk of incident HF (HR: 1.56 per doubling), an association stronger than hsCRP, IL-6, and WBC.
- The association between sCD14 and HF was primarily driven by HF with preserved ejection fraction (HFpEF) (HR: 1.50), with no significant association observed for HF with reduced ejection fraction (HFrEF).
Conclusions:
- Plasma sCD14 is an independent predictor of incident HF, showing a stronger association than other major inflammatory markers.
- The predictive association of sCD14 with HF appears specific to HFpEF.
- Further research is needed to confirm these findings and explore potential therapeutic implications.
Background:
CD14 is a membrane glycoprotein primarily expressed by myeloid cells that plays a key role in inflammation. Soluble CD14 (sCD14) levels carry a poor prognosis in chronic heart failure (HF), but whether elevations in sCD14 precede HF is unknown. We tested the hypothesis that sCD14 is associated with HF incidence and its subtypes independent of major inflammatory biomarkers among older adults.
Methods And Results:
We included participants in the Cardiovascular Health Study without preexisting HF and available baseline sCD14. We evaluated the associations of sCD14, high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, and white blood cell count (WBC) with incident HF and subtypes using Cox regression. Among 5217 participants, 1878 had incident HF over 13.6 years (609 classifiable as HF with preserved ejection fraction [HFpEF] and 419 as HF with reduced ejection fraction [HFrEF]). After adjusting for clinical and laboratory covariates, sCD14 was significantly associated with incident HF (hazard ratio [HR]: 1.56 per doubling, 95% confidence interval [CI]: 1.29-1.89), an association that was numerically stronger than for hsCRP (HR per doubling: 1.10, 95% CI: 1.06-1.15), IL-6 (HR: 1.18, 95% CI: 1.10-1.25), and WBC (HR: 1.24, 95% CI: 1.09-1.42), and that remained significant after adjustment for the other markers of inflammation. This association for sCD14 was observed with HFpEF (HR: 1.50, 95% CI: 1.07-2.10) but not HFrEF (HR: 0.99, 95% CI: 0.67-1.49).
Conclusions:
Plasma sCD14 was associated with incident HF independently and numerically more strongly than other major inflammatory markers. This association was only observed with HFpEF in the subset with classifiable HF subtypes. Pending replication, these findings have potentially important therapeutic implications.
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