Muscle wasting and iron deficiency, a strong relationship in patients with heart failure

Background: Iron deficiency (ID) is a common comorbidity among patients with heart failure (HF), being present in up to 50% of all ambulatory patients. Skeletal muscle wasting, on the other side, has been reported with a prevalence between 19 to 52% and is strongly associated with poor prognosis. Due to the impact of iron on the skeletal muscle mass and oxygen transport, we investigate the association of muscle wasting (MW) with ID, anaemia, muscle strength and known predictors of MW.
Methods: In a retrospective analysis, we included 208 male patients with HF. Muscle wasting (MW) was defined as decrease in muscle mass by 2SD below the mean of a healthy young reference group, i.e. appendicular skeletal muscle index <7.26kg/m² for male patients as assessed by dual X-ray absorptiometry (DEXA) scan. Iron deficiency (ID) was defined as ferritin <100µg/L or ferritin between 100 and 299µg/L with transferrin saturation (TSAT) <20%. Anaemia was defined as decreased haemoglobin (Hb) values <13g/dL. Loss of muscle strength was defined as handgrip strength (HGS) <27kg.
Results: Prevalence of patients with MW, ID and anaemia were 45 (21.6%), 99 (47.6%) and 64 (30.8%), even though only 17 patients (8.1%) presented with the three comorbidities simultaneously. Low HGS was found only in 19 patients (9.5%). The comparison of the cohort with respect to MW and ID showed some differences regarding baseline characteristics. Patients with MW were older (72±9 vs. 66±11 years, p=0.002), had lower BMI (25±4 vs. 30±5 kg/m², p<0.001) and higher NT-proBNP values (1108 (574-3263) vs. 555 (175-1378) pg/mL, p=0.002), but showed no significant difference in ID status (p=0.737, p=0.076 and p=0.728, respectively). Similarities were found in the distribution of NYHA class III or IV (55.6% in MW group, 48.5% in ID group, both p<0.01) and presence of anaemia (46.6% in MW group, 42.4% in ID group, both p<0.01). Using univariate logistic regression analysis, predictors of MW were ID, ferritin, anaemia, age, NT-proBNP, NYHA class and peak VO2 (all p<0.01). In contrast, TSAT (odds ratio (OR) (95% confidence intervale[CI]): 0.24(0.05-1.13), p=0.071), eGFR, hsCRP and creatinine (all p>0.8) showed no association with MW. ID remained a strong predictor of MW (OR (95%CI): 3.05(1.37-6.81), p=0.006), together with age (OR (95%CI): 1.06(1.02-1.11), p=0.008) and independently of NYHA class III or IV, presence of anaemia and low HGS. This tendency remained the same by introducing NT-proBNP in the later multivariate model, but without statistical significance (OR (95%CI): 2.30 (0.89-5.93), p=0.086), age remained as unique predictor. Univariate predictors of low HGS were anaemia, age, peak VO2, NT-proBNP as well as ID and ferritin (all p<0.03), but not NYHA class. In a multivariate analysis for low HGS, anaemia presented with a stronger tendency for prediction than ID, but both were not statistical significant.
Conclusion: In our cohort, ID predicted loss of muscle mass and strength irrespective of age, NYHA class and anaemia. The effect was diluted when NT-proBNP was also present in the multivariate analysis. This might be due to NT-proBNP being an indicator of HF severity, which results to be a strong predictor of MW but not of ID. It is possible that ID may play a role in the development of loss of muscle mass and strength, parallel to worsening HF.