Effect of iron status and red cell indices on exercise capacity and response of exercise training 01/12/2017 - 31/12/2018

Abstract

Besides its role in erythropoiesis, iron is a key factor in oxygen utilization and energy production. Indeed, iron is an essential component of haemoglobin, myoglobin, oxidative enzymes, and respiratory chain proteins. In the FAIR-HF trial, i.v. correction of iron deficiency improved exercise performance (distance on the 6MWT) in patients with CHF, regardless of anaemia (Anker SD et al, NEJM 2009). In addition, two recent studies reported that iron-deficient CHF patients had lower peak oxygen uptake (peakVO2) and elevated slope of the minute ventilation to carbon dioxide production (VE/VCO2) compared with patients that were not iron deficient, independent of other parameters traditionally linked with exercise intolerance (Okonko JACC et al 2011) Similarly, we recently reported that high RDW (red cell distribution width) values were significantly linked to exercise intolerance in 118 non-anaemic, non-iron-deficient patients with CHF (Van Craenenbroeck EM et al, Eur J Heart Failure 2011). Higher RDW values were associated with lower peakVO2, independent of other widely accepted determinants such as age, haemoglobin, renal function, NYHA class, and NT-proBNP values. In fact, RDW was the second strongest determinant of peakVO2, after age. RDW is also closely associated with iron deficiency, as we showed in a subanalysis of FAIR-HF trial (Van Craenenbroeck EM et al, Eur J Heart Failure 2013). However, the mechanism underlying this association is unclear. When it comes to HFpEF, less is known on iron deficiency and RDW as markers for exercise capacity. Very recently, the relation between LVEDP and RDW was investigated in 1,084 consecutive stable patients undergoing invasive angiography. High RDW levels were observed in patients with or without HF and independently associated with high LVEDP and with mortality (Senthong V et al, Am J Cardiol 2017) Aerobic exercise training requires lots of energy (ATP) production in skeletal muscle mitochondria, which is an iron-dependent process. Due to these higher requirements for iron use and to increased iron loss (sweating), athletes are at a higher risk of experiencing iron deficiency compared to non-athletes. The effect of exercise volume on iron stores has never been studied in HF before.

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