Iron deficiency in worsening heart failure is associated with reduced estimated protein intake, fluid retention, inflammation, and antiplatelet use.

Abstract

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).

• Authors: Haye H van der Wal, Niels Grote Beverborg, Kenneth Dickstein, Stefan D Anker, Chim C Lang, Leong L Ng, Dirk J van Veldhuisen, Adriaan A Voors, Peter van der Meer
• Journal: European heart journal (Eur Heart J) Vol. 40 Issue 44 Pg. 3616-3625 (11 21 2019) ISSN: 1522-9645 [Electronic] England
• PMID: 31556953 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.

Chemical References

• Biomarkers
• Peptide Fragments
• Platelet Aggregation Inhibitors
• Proteins
• Transferrin
• pro-brain natriuretic peptide (1-76)
• Natriuretic Peptide, Brain
• Tartrate-Resistant Acid Phosphatase
• Aryldialkylphosphatase
• PON3 protein, human

Topics

• Aged
• Anemia, Iron-Deficiency (chemically induced, complications, metabolism)
• Aryldialkylphosphatase (metabolism)
• Biomarkers (blood)
• Body Fluids (metabolism, physiology)
• Eating (physiology)
• Female
• Heart Failure (etiology, metabolism, mortality, physiopathology)
• Humans
• Inflammation (metabolism)
• Iron Deficiencies
• Male
• Middle Aged
• Natriuretic Peptide, Brain (metabolism)
• Patient Readmission (statistics & numerical data)
• Peptide Fragments (metabolism)
• Platelet Aggregation Inhibitors (adverse effects)
• Prevalence
• Prognosis
• Proteins (supply & distribution)
• Renal Insufficiency, Chronic (complications, metabolism)
• Stroke Volume (physiology)
• Tartrate-Resistant Acid Phosphatase (metabolism)
• Transferrin (metabolism)