Cardiovascular Journal of Africa: Vol 28 No 5 (September/October 2017)

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 28, No 5, September/October 2017 AFRICA 333
diagnose ID in HF in high-income countries. The unavailability
of biochemical iron markers in many SSA countries may limit
the use of these diagnostic criteria as applied in high-income
countries and this may underestimate the magnitude of iron
deficiency in this population.
Red cell indices such as mean corpuscular volume and the
degree of hypochromia, which are used in many SSA countries,
cannot distinguish between the presence or absence of sufficient
bone marrow iron in patients with chronic disease, thereby
offering a relatively low sensitivity (Table 3).35 This information
gap warrants serious attention if ID is to be intervened in by
the provision of diagnostic resources, allowing the use of serum
ferritin, which provides a considerably higher specificity and
sensitivity compared to haematological indices (Table 3).
Absolute ID and serum ferritin < 60–100 µg/l in HF
It has been suggested that cut-off levels of the order of
60–100 µg/l of ferritin rather than the normal < 30 µg/l, or indeed
previously reported 12–15 µg/l, should be used when screening for
absolute ID in people with co-existing inflammation, infection
and malignant conditions.29,30,41 This recommendation is based
on the fact that patients with acute or chronic disease usually
have elevated ferritin levels as a result of intracellular iron
accumulation and the inflammatory response. The explanation is
that serum ferritin is an acute-phase reactant. Even these higher
levels only slightly improve the sensitivity (Table 3).
The combined use of serum ferritin with inflammatorymarkers
such as erythrocyte sedimentation rate (ESR) or C-reactive
protein (CRP) in a discriminant analysis provide only marginal
improvement in sensitivity/specificity.42 Serum ferritin < 100 µg/l
has been widely used as a cut-off in high-income countries when
looking for absolute ID in patients with HF in most clinical trials.
Studies supporting its use in SSA are limited.34,43,44
Serum ferritin levels such as < 150 µg/l offer a better balance
between sensitivity and specificity than < 100 µ g/l (Table 4).29,39
Afro-Americans and black Africans tend to have a high level of
serum ferritin. 45,46 It is not clear whether this is genetic or due to
environmental changes as a result of common chronic infection.
In view of this, high cut-off values such as < 150 µg/l (rather than
< 100 µg/l) may be more appropriate but this requires further
study and validation. Such studies will pave the way to clinical
trials of relevance to SSA.
Treatment approaches with regard to iron
therapy in HF
Utility and beneficial effect of iron therapy in HF
In a series of controlled and uncontrolled clinical trials of
HF and ID (Table 5), all conducted in high-income countries, Table 3. Sensitivity and specificity of iron measures in chronic diseases
Study, year Iron marker
Sensitivity
(%)
Specificity
(%)
Punnonen et al .36 1996 % hypochromia 77 90
Punnonen et al .36 1996 Mean corpuscular volume 86
Means et al.37 1999 42 83
Punnonen et al .36 1996 % transferrin saturation 79
Means et al.37 1999 38 89
Van Tellingen et al.38 2001 Serum ferritin 79 97
Lee et al. 39 2001 87
Punnonen et al .36 1996 89
Joosten et al.40 2001 94 95
Table 4. Sensitivity and specificity of serum ferritin
Author, year
Ferritin cut-off
value (ng/ml)
Sensitivity
(%)
Specificity
(%)
Lockhat et al.47 2004 < 50 37 75
< 100 48 75
< 150 71 69
< 200 77 37
Tessitoreet al.48 2001 < 100 35 78
Kalantar-Zadeh et al.49 2004 < 200 41 100
Table 5. Studies on parental iron therapy in HF
Author, year Study design
Sample
size Type of parental iron Dose/duration Benefits
Ben-Assa et al. 54 2015 Uncontrolled 34 Ferric sucrose 200 mg, 6 weeks ↑Hb
Reed et al.53 2015 Uncontrolled 13 Ferric gluconate 250 mg bd/day, 3 days ↑Hb, ↑SF, ↑TSAT
Gaber et al.55 2011 Uncontrolled 40 Ferric dextran 200 mg/week, 4–8 weeks ↑NYHA, ↑6MWD, ↑SF, ↑TSAT, ↑exercise
capacity, ↑renal function, ↑QoL
Usmanov et al.52 2008 Uncontrolled 32 Ferric sucrose 100 mg 3×/week, then once/week, 26 weeks ↑Hb, ↑NYHA, ↑LV diameters
Bolger et al.56 2006 Uncontrolled 16 Ferric sucrose 1 g daily, 12 days Hb 12.55, ↑TSAT, ↑ 6MWD ↑NYHA
Toblliet al.57 2015 Controlled 60 Ferric sucrose 200 mg/week, 5 weeks ↑Hb, ↑ SF, ↑TSAT, ↑LV diameters, ↑LVEF,
↑ CrCl, ↑NT-proBNP
Ponikowski et al.33 2014 Controlled 304 Ferric carboxymaltose Total dose 500–2000 mg, in correction phase
500 mg, in maintenance 52 weeks
↑6MWD, ↑NYHA, ↑exercise capacity, ↑PGA,
↑QoL, ↑ hospitalisation, ↑fatigue score
Terrovitiset al. 58 2012 Controlled 40 Ferric sucrose 300 mg weekly, 6 weeks ↑Hb
Anker et al.32 2009 Controlled 459 Ferric carboxymaltose 200 mg, 24 weeks ↑Hb, ↑SF, ↑TSAT, ↑PGA, ↑ NYHA,
↑6MWD, trend ↓hospitalisation
Drakos et al.59 2009 Controlled 16 Ferric sucrose 300 mg/week, 6 weeks ↑Hb
Arutyunov et al.60 2009 Controlled 30
27
Ferric carboxymaltose
Ferric sucrose
200 mg weekly to calculated dose, then 200
mg every 4 weeks, 12 weeks
Not applicable
Okonko et al.50 2008 Controlled 35 Ferric sucrose 200 mg weekly, 16 weeks ↑Hb, ↑SF, ↑VO2, ↑exercise capacity,
↑ NYHA,↑PGA
Toblliet al.61 2007 Controlled 40 Ferric sucrose 200 mg/week, 5 weeks ↑Hb, ↑NT-proBNP, ↑LVEF, ↑NYHA,
↑exercise capacity, ↑renal function: ↑QoL
Hb: haemoglobin, SF: serum ferritin, TSAT: transferrin saturation, NYHA: New York Heart Association, 6MWD: six-minute walking distance, QoL: quality of life,
LV: left ventricular, LVEF: left ventricular ejection fraction, NT-proBNP: N-terminal pro B-type natriuretic peptide, CrCl: creatine clearance rate, PGA: patient’s global
assessment, pVO2: peak oxygen consumption, ↑: improved.