Prevalence and Associations of Systemic Inflammation in Heart Failure Across the Spectrum of Ejection Fraction.

BACKGROUND: Systemic inflammation contributes to the pathophysiology of heart failure (HF). Inflammation in heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) has been linked to cardiovascular-kidney-metabolic conditions, whereas inflammation in heart failure and reduced ejection fraction (HFrEF) is thought to develop secondary to cardiac stress and circulatory derangements. OBJECTIVES: This study aims to characterize the prevalence and correlates of systemic inflammation across the spectrum of HF. METHODS: Patients with HF participating in 3 large outcome trials (SELECT, SOUL, and FLOW) were examined to identify the prevalence of systemic inflammation, defined as elevated high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L. Clinical characteristics associated with elevated hsCRP were examined by HF subtype and across the HF spectrum. RESULTS: Across the 3 trials, 3,204 patients had HFpEF, 1,246 had HFmrEF, and 1,018 had HFrEF. Elevated hsCRP was observed in 2,335 patients (52.5%) with HFpEF/HFmrEF and 503 patients (49.4%) with HFrEF. Compared with patients with lower hsCRP levels, those with higher hsCRP levels were more likely to be female and have obesity, diabetes, lower estimated glomerular filtration rate, higher albuminuria, and chronic obstructive pulmonary disease, without meaningful differences by HF subtype. hsCRP level was unrelated to ejection fraction (R2 < 0.001; P = 0.73) but increased linearly with the number of comorbidities for all HF subtypes (R2 = 0.94; P < 0.001). CONCLUSIONS: Systemic inflammation is present in one-half of patients with HF, and is associated with excess body fat, chronic kidney disease, albuminuria, and diabetes, and increases with comorbidity burden. These relationships are not specific to HFpEF/HFmrEF but are also common to HFrEF (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity [SELECT]; NCT03574597; A Research Study to See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease [FLOW]; NCT03819153; A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes [SOUL]; NCT03914326).