Iron deficiency in worsening heart failure is associated with reduced estimated protein intake, fluid retention, inflammation, and antiplatelet use.
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).
['van der Wal|Haye H|HH|', 'Grote Beverborg|Niels|N|', 'Dickstein|Kenneth|K|', 'Anker|Stefan D|SD|', 'Lang|Chim C|CC|', 'Ng|Leong L|LL|', 'van Veldhuisen|Dirk J|DJ|', 'Voors|Adriaan A|AA|', 'van der Meer|Peter|P|']
D000368:Aged D018798:Anemia, Iron-Deficiency D043303:Aryldialkylphosphatase D015415:Biomarkers D001826:Body Fluids D004435:Eating D005260:Female D006333:Heart Failure D006801:Humans D007249:Inflammation D000090463:Iron Deficiencies D008297:Male D008875:Middle Aged D020097:Natriuretic Peptide, Brain D010359:Patient Readmission D010446:Peptide Fragments D010975:Platelet Aggregation Inhibitors D015995:Prevalence D011379:Prognosis D011506:Proteins D051436:Renal Insufficiency, Chronic D013318:Stroke Volume D000071681:Tartrate-Resistant Acid Phosphatase D014168:Transferrin
Iron deficiency Heart failure Protein intake Fluid retention Inflammation Antiplatelets