Heart failure inflammation might actually be an underrecognized therapeutic target, after analysis of the POSEIDON registry found that systemic inflammation is present in nearly half of heart failure patients, regardless of ejection fraction.
- High inflammatory risk is defined as hsCRP levels ≥2 mg/L.
- Researchers already knew that inflammation contributes to heart failure pathophysiology, but its prevalence and relevance were unknown until now.
To explore inflammation prevalence, the POSEIDON registry analyzed 11.8k heart failure patients with available hsCRP readings and found that their inflammatory burden proved remarkably uniform.
- Elevated hsCRP levels were consistent across HF sub-types, coming in at: 38.8% in HFpEF, 38.1% in HFmrEF, and 38.2% in HFrEF
- Within each HF subtype, patients who showed high hsCRP were more likely to be females and have CKD, obesity, worse NYHA class, and higher NT-proBNP levels.
- However, body mass index proved to be the exception, showing stronger association with hsCRP in HFpEF versus other subtypes.
These results parallel the adipokine-adiposity framework that was proposed last October in JACC, which hypothesizes that visceral fat increases cause secretion of an altered adipokine profile that leads to systemic inflammation alongside cardiac hypertrophy and fibrosis.
- That hypothesis consisted of three “domains” of adipokines (I,II,III) and more specifically, it suggested that Domain III played a major role in HFpEF development.
- Domain III adipokines are heightened by high body fat and drive the inflammation, hypertrophy, and fibrosis effects directly causing HFpEF.
So what does this mean for POSEIDON’s results? The key distinction here is the consistent high inflammation phenotype that 4 out of 10 HF patients exhibit (regardless of HF subtype).
- When taken in the context of the adipokine hypothesis, it means that there could be distinct pathophysiologies across and within each HF subtype.
That’s significant because it suggests the potential for inflammation specific therapeutic targets that are unique to about 40% of the HF patient spectrum.
The Takeaway
There’s a growing macro-trend within cardiology that is raising understanding and awareness of inflammation’s role as a CV risk factor. These results fit into that trend and are especially important to our understanding of inflammation’s impact on heart failure’s varying pathophysiologies.
