A TSAT ≤19.8% or a serum iron ≤13 µmol/L shows the best performance in selecting patients with ID and identifies HF patients at the highest risk of death. Our findings validate the currently used TSAT cutoff of <20% for the identification of ID in HF patients, but question the diagnostic value of ferritin.

Higher potassium levels are an independent predictor of enduring lower dosages of ACEi/ARB. Higher potassium levels do not attenuate the beneficial effects of ACEi/ARB uptitration.

BackgroundAlthough erythropoietin has been used for decades in the treatment of anemia, data regarding endogenous levels in the general population are scarce. Therefore, we determined erythropoietin reference ranges and its clinical, biochemical and genetic associations in the general population.MethodsWe used data from 6,777 subjects enrolled in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study. Fasting venous blood samples were obtained in the morning from all participants from 2001–2003. Serum erythropoietin concentrations were measured using a fully automated chemiluminescent enzyme-labeled immunometric assay. A genome-wide association study was performed to identify genetic determinants.ResultsMean age (± SD) was 53 ± 12 years and 50% were female. Median (IQR) erythropoietin concentrations were 7.6 (5.8–9.9) IU/L in men and 7.9 (6.0–10.6) IU/L in women. A strong positive correlation was found between erythropoietin and waist circumference, glucose and systolic blood pressure (all P < 0.05). In subjects with normal renal function there was a strong exponential relation between hemoglobin and erythropoietin, whereas in renal impairment (eGFR < 60 mL/min/1.73m²) this relation was linear (men) or absent (women) (P < 0.001 for interaction). Single-nucleotide polymorphisms at the HBS1L-MYB locus were shown to be related to erythropoietin levels (P < 9x10-21), more significantly than other erythrocyte parameters.ConclusionWe provide age-specific reference ranges for endogenous serum erythropoietin. Erythropoietin levels are positively associated with the components of the metabolic syndrome, except cholesterol. We show that even mild renal failure blunts erythropoietin production and propose the HBS1L-MYB locus as a regulator of erythropoietin.

AimsIron 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 resultsWe 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).ConclusionOur 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).