Abstract
Introduction: Heart failure (HF) is a major global health concern with complex pathophysiological mechanisms. Iron, a crucial micronutrient for cardiac function, has been increasingly researched for its potential link with HF. This study aimed to investigate the association between serum iron levels and congestive heart failure (CHF) using cross-sectional data from the NHANES database (2017–2020), thereby contributing to the understanding and management of HF. Methods: This cross-sectional analysis utilized data from the National Health and Nutrition Examination Survey (NHANES), focusing on American adults. CHF status was identified through self-reported medical history. Serum iron levels were measured using the Roche Cobas 6000 analyzer. Covariates included demographics, lifestyle factors, and comorbidities. Statistical analyses involved logistic regression models, adjusting for potential confounders to evaluate the association between serum iron and CHF. Results: Among 7,298 participants (240 with CHF and 7,058 without CHF), those with CHF had significantly lower serum iron levels. Higher serum iron levels were associated with a reduced incidence of CHF, even after adjusting for covariates. Subgroup analyses revealed this association to be particularly significant in older adults, hypertensive, diabetic, smokers, obese, and those with renal impairment. The optimal serum iron cutoff value for CHF risk was identified as 15.1 μmol/L. Conclusion: This study demonstrates a negative association between serum iron levels and CHF occurrence, suggesting serum iron as a potential marker for CHF diagnosis and management.
Journal Section:
Congenital Heart Disease
References
1.
Bozkurt
B
, Coats
AJS
, Tsutsui
H
, Abdelhamid
CM
, Adamopoulos
S
, Albert
N
, et al. Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure – endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, and Chinese Heart Failure Association
. Eur J Heart Fail
. 2021
;23
(3
):352
–80
. 2.
Ziaeian
B
, Fonarow
GC
. Epidemiology and aetiology of heart failure
. Nat Rev Cardiol
. 2016
;13
(6
):368
–78
. 3.
Bertero
E
, Maack
C
. Metabolic remodelling in heart failure
. Nat Rev Cardiol
. 2018
;15
(8
):457
–70
. 4.
Tsutsui
H
, Kinugawa
S
, Matsushima
S
. Oxidative stress and heart failure
. Am J Physiol Heart Circ Physiol
. 2011
;301
(6
):H2181
–90
. 5.
Ouwerkerk
W
, Belo Pereira
JP
, Maasland
T
, Emmens
JE
, Figarska
SM
, Tromp
J
, et al. Multiomics analysis provides novel pathways related to progression of heart failure
. J Am Coll Cardiol
. 2023
;82
(20
):1921
–31
. 6.
Khan
MS
, Khan
F
, Fonarow
GC
, Sreenivasan
J
, Greene
SJ
, Khan
SU
, et al. Dietary interventions and nutritional supplements for heart failure: a systematic appraisal and evidence map
. Eur J Heart Fail
. 2021
;23
(9
):1468
–76
. 7.
Silvestre
OM
, Gonçalves
A
, Nadruz
W
Jr, Claggett
B
, Couper
D
, Eckfeldt
JH
, et al. Ferritin levels and risk of heart failure-the Atherosclerosis Risk in Communities Study
. Eur J Heart Fail
. 2017
;19
(3
):340
–7
. 8.
Palau
P
, Llàcer
P
, Domínguez
E
, Tormo
JP
, Zakarne
R
, Mollar
A
, et al. Iron deficiency and short-term adverse events in patients with decompensated heart failure
. Clin Res Cardiol
. 2021
;110
(8
):1292
–8
. 9.
Levey
AS
, Stevens
LA
, Schmid
CH
, Zhang
YL
, Castro
AF
3rd, Feldman
HI
, et al. A new equation to estimate glomerular filtration rate
. Ann Intern Med
. 2009
;150
(9
):604
–12
. 10.
Guyon
I
, Weston
J
, Barnhill
S
, Vapnik
V
. Gene selection for cancer classification using support vector machines
. Mach Learn
. 2002
;46
(1/3
):389
–422
. 11.
Tibshirani
R
. Regression shrinkage and selection via the lasso
. J Roy Stat Soc B
. 2018
;58
(1
):267
–88
. 12.
van Buuren
S
, Boshuizen
HC
, Knook
DL
. Multiple imputation of missing blood pressure covariates in survival analysis
. Stat Med
. 1999
;18
(6
):681
–94
. 13.
Xu
W
, Barrientos
T
, Mao
L
, Rockman
HA
, Sauve
AA
, Andrews
NC
. Lethal cardiomyopathy in mice lacking transferrin receptor in the heart
. Cell Rep
. 2015
;13
(3
):533
–45
. 14.
Oudit
GY
, Sun
H
, Trivieri
MG
, Koch
SE
, Dawood
F
, Ackerley
C
, et al. L-type Ca2+ channels provide a major pathway for iron entry into cardiomyocytes in iron-overload cardiomyopathy
. Nat Med
. 2003
;9
(9
):1187
–94
. 15.
Zhang
H
, Zhabyeyev
P
, Wang
S
, Oudit
GY
. Role of iron metabolism in heart failure: from iron deficiency to iron overload
. Biochim Biophys Acta Mol Basis Dis
. 2019
;1865
(7
):1925
–37
. 16.
Ghafourian
K
, Shapiro
JS
, Goodman
L
, Ardehali
H
. Iron and heart failure: diagnosis, therapies, and future directions
. JACC Basic Transl Sci
. 2020
;5
(3
):300
–13
. 17.
Paterek
A
, Mackiewicz
U
, Mączewski
M
. Iron and the heart: a paradigm shift from systemic to cardiomyocyte abnormalities
. J Cell Physiol
. 2019
;234
(12
):21613
–29
. 18.
Bayeva
M
, Gheorghiade
M
, Ardehali
H
. Mitochondria as a therapeutic target in heart failure
. J Am Coll Cardiol
. 2013
;61
(6
):599
–610
. 19.
Galy
B
, Ferring-Appel
D
, Sauer
SW
, Kaden
S
, Lyoumi
S
, Puy
H
, et al. Iron regulatory proteins secure mitochondrial iron sufficiency and function
. Cell Metab
. 2010
;12
(2
):194
–201
. 20.
Leszek
P
, Sochanowicz
B
, Szperl
M
, Kolsut
P
, Brzóska
K
, Piotrowski
W
, et al. Myocardial iron homeostasis in advanced chronic heart failure patients
. Int J Cardiol
. 2012
;159
(1
):47
–52
. 21.
Rineau
E
, Gaillard
T
, Gueguen
N
, Procaccio
V
, Henrion
D
, Prunier
F
, et al. Iron deficiency without anemia is responsible for decreased left ventricular function and reduced mitochondrial complex I activity in a mouse model
. Int J Cardiol
. 2018
;266
:206
–12
. 22.
Kalra
PR
, Cleland
JGF
, Petrie
MC
, Thomson
EA
, Kalra
PA
, Squire
IB
, et al. Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): an investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial
. Lancet
. 2022
;400
(10369
):2199
–209
. 23.
Lewis
GD
, Malhotra
R
, Hernandez
AF
, McNulty
SE
, Smith
A
, Felker
GM
, et al. Effect of oral iron repletion on exercise capacity in patients with heart failure with reduced ejection fraction and iron deficiency: the IRONOUT HF randomized clinical trial
. JAMA
. 2017
;317
(19
):1958
–66
. 24.
Dignass
A
, Farrag
K
, Stein
J
. Limitations of serum ferritin in diagnosing iron deficiency in inflammatory conditions
. Int J Chronic Dis
. 2018
;2018
:9394060
. 25.
Elsayed
ME
, Sharif
MU
, Stack
AG
. Transferrin saturation: a body iron biomarker
. Adv Clin Chem
. 2016
;75
:71
–97
. 26.
Drozd
M
, Tkaczyszyn
M
, Wegrzynowska-Teodorczyk
K
, Kasztura
M
, Dziegala
M
, Kobak
K
, et al. Intravenous iron therapy and circulating biomarkers of inflammation in men with heart failure with reduced ejection fraction
. Eur Heart J
. 2020
;41
(Suppl_2
). 27.
Maeder
MT
, Khammy
O
, dos Remedios
C
, Kaye
DM
. Myocardial and systemic iron depletion in heart failure implications for anemia accompanying heart failure
. J Am Coll Cardiol
. 2011
;58
(5
):474
–80
. 28.
Chen
W
, Lin
G
, Dai
C
, Xu
K
. Predictive value of serum iron on heart failure in patients with acute ST-segment elevation myocardial infarction
. Clin Cardiol
. 2023
;46
(4
):449
–53
. 29.
Karakas
Z
, Yilmaz
Y
, Bayramoglu
Z
, Karaman
S
, Aydogdu
S
, Karagenc
AO
, et al. Magnetic resonance imaging during management of patients with transfusion-dependent thalassemia: a single-center experience
. Radiol Med
. 2018
;123
(8
):572
–6
. 30.
Karadag
SIK
, Karakas
Z
, Yilmaz
Y
, Gul
N
, Demir
AA
, Bayramoglu
Z
, et al. Pituitary iron deposition and endocrine complications in patients with β-thalassemia: from childhood to adulthood
. Hemoglobin
. 2020
;44
(5
):344
–8
. 31.
Sevimli
C
, Yilmaz
Y
, Bayramoglu
Z
, Comert
RG
, Gul
N
, Dursun
M
, et al. Pancreatic MR imaging and endocrine complications in patients with beta-thalassemia: a single-center experience
. Clin Exp Med
. 2022
;22
(1
):95
–101
. 32.
Chawla
NV
, Bowyer
KW
, Hall
LO
, Kegelmeyer
WP
. SMOTE: synthetic minority over-sampling technique
. J Artif Intell Res
. 2002
;16
:321
–57
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