Iron deficiency in worsening heart failure was independently associated with an increased risk of the composite of all-cause mortality and first heart failure rehospitalization (HR 1.25).
Cohort (n=2,357)
Yes
Is iron deficiency associated with worse outcomes and specific clinical/biomarker profiles in patients with worsening heart failure?
Iron deficiency in worsening heart failure is highly prevalent (61.6%) and independently associated with worse clinical outcomes, driven by a complex etiology including malnutrition, fluid overload, inflammation, and antiplatelet use.
Effect estimate: HR 1.25 (95% CI 1.06-1.46)
p-value: p=0.007
AIMS: Iron deficiency (ID) is common in heart failure (HF) patients and negatively impacts symptoms and prognosis. The aetiology of ID in HF is largely unknown. We studied determinants and the biomarker profile of ID in a large international HF cohort. METHODS AND RESULTS: We studied 2357 worsening HF patients from the BIOSTAT-CHF cohort. ID was defined as transferrin saturation <20%. Univariable and multivariable logistic regression models were constructed to identify determinants for ID. We measured 92 cardiovascular markers (Olink Cardiovascular III) to establish a biomarker profile of ID. The primary endpoint was the composite of all-cause mortality and first HF rehospitalization. Mean age (±standard deviation) of all patients was 69 ± 12.0 years, 26.1% were female and median N-terminal pro B-type natriuretic peptide levels (+interquartile range) were 4305 (2360-8329) ng/L. Iron deficiency was present in 1453 patients (61.6%), with highest prevalence in females (71.1% vs. 58.3%; P < 0.001). Independent determinants of ID were female sex, lower estimated protein intake, higher heart rate, presence of peripheral oedema and orthopnoea, chronic kidney disease, lower haemoglobin, higher C-reactive protein levels, lower serum albumin levels, and P2Y12 inhibitor use (all P < 0.05). None of these determinants were sex-specific. The biomarker profile of ID largely consisted of pro-inflammatory markers, including paraoxonase 3 (PON3) and tartrate-resistant acid phosphatase type 5. In multivariable Cox proportional hazard regression analyses, ID was associated to worse outcome, independently of predictors of ID (hazard ratio 1.25, 95% confidence interval 1.06-1.46; P = 0.007). CONCLUSION: Our data suggest that the aetiology of ID in worsening HF is complex, multifactorial and seems to consist of a combination of reduced iron uptake (malnutrition, fluid overload), impaired iron storage (inflammation, chronic kidney disease), and iron loss (antiplatelets).
Wal et al. (Wed,) conducted a cohort in Worsening heart failure (n=2,357). Iron deficiency (transferrin saturation <20%) vs. No iron deficiency was evaluated on Composite of all-cause mortality and first HF rehospitalization (HR 1.25, 95% CI 1.06-1.46, p=0.007). Iron deficiency in worsening heart failure was independently associated with an increased risk of the composite of all-cause mortality and first heart failure rehospitalization (HR 1.25).