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Am J Cardiol. 2011 August 1; 108(3): 385–390. doi:10.1016/j.amjcard.2011.03.056.

Usefulness of Plasma Galectin-3 Levels in Systolic Heart Failure

to Predict Renal Insufficiency and Survival
W. H. Wilson Tang, MDa, Kevin Shrestha, ABa, Zhili Shao, MD PhDa, Allen G. Borowski,
RDCSa, Richard W. Troughton, MBBSb, James D. Thomas, MDa, and Allan L. Klein, MDa

aDepartment of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic,

Cleveland, Ohio bChristchurch School of Medicine and Health Sciences, Christchurch, New
Zealand

Abstract
Galectin-3 plays an important role in fibroblast activation and fibrosis in animal models. Elevated
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galectin-3 levels are associated with poor long-term survival in heart failure (HF). We examined
the relation between plasma galectin-3 levels and myocardial indices of systolic HF. We measured
plasma galectin-3 in 133 chronic HF and 45 advanced decompensated HF subjects with
echocardiographic and hemodynamic evaluation. In our chronic HF cohort, median plasma
galectin-3 level was 13.9ng/mL [interquartile range: 12.1–16.9ng/mL]. Higher galectin-3 was
associated with more advanced age (r=0.22, p=0.010) and poor renal function (estimated
glomerular filtration rate [eGFR]: r= −0.24, p=0.007; cystatin C: r= 0.38, p<0.0001), and
predicted all-cause mortality (Hazard ratio [HR] 1.86 [95% confidence interval: 1.36–2.54],
p<0.001). In multivariate analysis, galectin-3 remained an independent predictor of all-cause
mortality after adjusting for age, eGFR, left ventricular (LV) ejection fraction (EF), and mitral E/
septal Ea (HR 1.94 [1.30–2.91], p=0.001). However, galectin-3 did not predict the combined
endpoint of all-cause mortality, cardiac transplantation, or HF hospitalization (p>0.05).
Furthermore, there were no relations between galectin-3 and LV end-diastolic volume index (r=
−0.05, p=0.61), LVEF (r= 0.10, p=0.25), or LV diastolic function (mitral E/septal Ea: r= 0.06,
p=0.52; left atrial volume index: r= 0.08, p=0.41). In our advanced decompensated HF cohort, we
did not observe any relation between galectin-3 and echocardiographic or hemodynamic indices.
In conclusion, high plasma galectin-3 levels were associated with renal insufficiency and poorer
survival in patients with chronic systolic HF. However, we did not observe a relation between
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galectin-3 and echocardiographic or hemodynamic indices.

Keywords
Heart failure; galectin-3; renal function; prognosis

© 2011 Excerpta Medica, Inc. All rights reserved

Corresponding author: W. H. Wilson Tang, MD Section of Heart Failure and Cardiac Transplantation Medicine Department of
Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic 9500 Euclid Avenue, Desk J3-4, Cleveland, OH 44195.
Phone: (216) 444-2121 / Fax: (216) 445-6165 [email protected].
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our
customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of
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discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Disclosures All other authors declared no relationships to disclose.
 Tang et al. Page 2

Introduction
Increasing evidence has implicated galectin-3 in the pathogenesis and progression of heart
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failure (HF). In animal models, galectin-3 has been demonstrated to be robustly expressed in
the failing heart and linked to myocardial fibrosis and remodeling1–4 in addition to renal
fibrosis5. Intra-pericardial infusion of recombinant galectin-3 in healthy rats triggers
inflammation involving macrophage and mast cell infiltration, cardiac interstitial and
perivascular fibrosis, hypertrophy, and left ventricular systolic and diastolic dysfunction1,4.
In chronic stable and acute decompensated HF patients, elevated plasma galectin-3 levels
have been linked to renal dysfunction and increased all-cause mortality risk6–8, and within
the chronic HF setting, serum galectin-3 levels have been demonstrated to correlate with
serum markers of cardiac extracellular matrix turnover9. Hence there is direct implication
that galectin-3 is a mediator in the development of cardiac hypertrophy and fibrosis, and a
potential biomarker for HF. Herein, we examine the relation between galectin-3 levels and
echocardiographic indices of cardiac structure and function in patients with chronic stable
HF, as well as echocardiographic and hemodynamic indices of cardiac structure and
function in patients with advanced decompensated systolic HF.

Methods
We investigated the role of galectin-3 in human systolic HF in two separate cohorts. This
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study was approved by the Cleveland Clinic Institutional Review Board, and all subjects
gave informed consent. In our chronic systolic HF cohort, we studied 133 patients enrolled
in the Assessment of Doppler Echocardiography Prognosis and Therapy study, a single-
center, prospective cohort study examining the natural history of stable but symptomatic
chronic systolic HF patients with careful echocardiographic and biochemical phenotyping.
Subjects enrolled were 18 to 75 years of age, had a diagnosis of HF for at least 3 months, a
left ventricular (LV) ejection fraction (EF) ≤35% at the time of enrollment, New York Heart
Association (NYHA) functional class I–IV symptoms, and were free of significant renal,
hepatic, and valvular diseases10. Estimated glomerular filtration rate (eGFR) was calculated
using the standard 4-variable Modification of Diet in Renal Disease equation11. Subjects
were followed prospectively by telephone follow-up and chart review for heart failure
hospitalizations and adverse events, with all-cause mortality data confirmed by Social
Security Death Index up to 5 years of follow-up. In our advanced decompensated HF cohort,
we measured plasma galectin-3 levels in 45 patients with advanced HF admitted to the HF
intensive care unit with hemodynamic assessment and monitoring at the Cleveland Clinic
for intensive medical therapy including vasoactive drugs. Subjects were 18 years of age or
older, had an LVEF ≤35% for at least 6 months, elevated filling pressures defined by a
pulmonary capillary wedge pressure >18 mmHg and/or a central venous pressure >8 mmHg.
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Exclusion criteria included mechanical ventilation, renal replacement therapy, post-cardiac

transplantation and post tricuspid valve surgery.

In both studies, patients underwent comprehensive echocardiographic evaluation of cardiac

structure as well as systolic and diastolic performance by an experienced research
sonographer at the time of blood sample collection. Comprehensive transthoracic
echocardiography was performed using commercially available HDI 5000 (Phillips Medical
Systems, N.A., Bothell, Washington) and Acuson Sequoia (Siemens Medical Solutions USA
Inc., Malvern, Pennsylvania) machines for our chronic systolic HF cohort and commercially
available Vingmed, System Seven (General Electric Healthcare, USA) machine for our
advanced decompensated systolic HF cohort. Two-dimensional and color Doppler imaging
was performed in standard parasternal and apical views. Diastolic indices (including pulse-
wave Doppler, color M-mode, and tissue Doppler imaging) were acquired over ten
consecutive beats using sweep speeds of 50 and 100 cm/s using previously described

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 Tang et al. Page 3

techniques and diastolic staging10,12. The LVEF and cardiac volumes were measured using
Simpson's biplane method. LV mass was calculated according to previously published
recommendations13. All ventricular volume and mass measurements were indexed to body
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surface area. Measurements were averaged over three cycles (five cycles for atrial
fibrillation).

All samples were collected into ethylenediaminetetraacetic acid plasma vacuum collecting
tubes on ice simultaneously at the time of echocardiography and hemodynamic evaluation
by delegated research personnel. Plasma was immediately separated, processed, and
preserved in aliquots at −80°C until analysis. Plasma galectin-3 levels were determined by a
commercially available sandwich enzyme-linked immunosorbent assay kit (Cat. No.
BMS279/2, Bender MedSystems GmbH, Vienna, Austria) according to the manufacturer's
protocol. A 2-fold dilution was utilized to bring concentrations within the measuring range
of the assay 0.39–25ng/mL. Intra-assay and inter-assay coefficients of variation were <5%.
Plasma cystatin C levels were determined by the N Latex cystatin C assay (Dade-Behring,
Deerfield IL), a latex-enhanced nephelmetric immunoassay using rabbit polyclonal
antibodies. The measuring range was 0.25–7.90 mg/L. Intra-assay and inter-assay
coefficients of variation were < 1.8%. Recovery was 92.4–101.3% and the values were
comparable between serum and plasma14. Plasma amino-terminal pro-B-type natriuretic
peptide (NT-proBNP) levels were assayed using a commercially available assay (Roche
Elecsys® proBNP assay, Roche Diagnostics, Indianapolis IN). All laboratory analyses were
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performed by investigators blinded to clinical outcomes.

Continuous variables were summarized as mean ± standard deviation if normally

distributed, and as median and interquartile range if non-normally distributed. Normality
was assessed by the Shapiro-Wilk W test. Spearman's rank correlation method was used as a
nonparametric measure of association between continuous plasma galectin-3 levels and
clinical and echocardiographic indices. The Wilcoxon rank-sum or Kruskal-Wallis test were
used to compare differences in continuous plasma galectin-3 levels across categorical
clinical or echocardiographic indices. The Cox proportional hazards model was used to
assess the clinical risk associated with increasing continuous standardized increments of
natural logarithm-transformed plasma galectin-3 levels. The optimal receiver operating
characteristic curve cut-off value for prediction of adverse clinical events was chosen as the
value maximizing sensitivity plus specificity. The proportional hazards assumption was
verified with log (time) vs. log[-log(survival)] plots. Kaplan-Meier survival plots were
calculated from baseline to time of all-cause mortality. All p-values reported are from two-
sided tests and a p-value <0.05 was considered statistically significant. Statistical analyses
were performed using JMP 8.0.2 and SAS 9.0 (SAS Institute, Cary, NC).
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Results
In our chronic HF cohort, the mean and median plasma galectin-3 levels were 14.8 ± 4.0ng/
mL and 13.9 [interquartile range (IQR) 12.1–16.9]ng/mL, respectively (Table 1). Higher
plasma galectin-3 levels were associated with advanced age (Spearman's r=0.22, p=0.010),
poor renal function (eGFR: r= −0.24, p=0.007; cystatin C: r=0.38, p<0.0001) (Table 2), and
higher NYHA functional class (rank sums p=0.026). Plasma galectin-3 levels were lower
with beta-blocker use (13.4 [IQR 11.9–16.3] versus 14.9 [IQR 12.6–17.6] ng/mL, p=0.024)
and spironolactone use (13.1 [IQR 11.0–15.3] versus 14.3 [IQR 12.3–17.2] ng/mL,
p=0.043), but did not differ according to gender (p=0.92), ethnicity (p=0.48), diabetic status
(p=0.58), or ischemic etiology (p=0.24). In our advanced decompensated HF cohort, the
mean and median plasma galectin-3 levels were 14.7 ± 4.0ng/mL and 14.7 [IQR 12.1–
17.0]ng/mL, respectively (Table 1). Again, higher plasma galectin-3 levels demonstrated
even stronger association with poor renal function (eGFR: r= −0.39, p=0.024; cystatin C: r=

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0.40, p=0.006) (Table 2) and with ischemic etiology (p=0.013), but were not associated with
age (p=0.65), NYHA functional class (p=0.54), gender (p=0.64), diabetic status (p=0.07), or
beta-blocker or spironolactone use (p>0.10 for both).
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In our chronic HF cohort, there was no correlation between plasma galectin-3 levels and
indices of LV structure, including indexed LV mass or LV end-systolic or end-diastolic
volume (p>0.48 for both), indices of left or right ventricular systolic function, including
LVEF or right ventricular systolic wave (p>0.25 for both), or indices of LV diastolic
function, including ratio of the mitral inflow early wave to the early diastolic myocardial
relaxation velocity at septal mitral annulus, pulmonary vein systolic/diastolic ratio, or left
atrial volume index (p>0.41 for all, Table 2). Furthermore, plasma galectin-3 levels did not
correlate indices of right ventricular function including semi-quantitative right ventricular
systolic function severity. There was weak correlation between galectin-3 and NT pro-BNP
that reached marginal significance (r=0.18, p=0.053) (Table 2). In our advanced
decompensated HF cohort, plasma galectin-3 levels were not associated with indices of LV
structure (p>0.46 for all), LVEF or indices of LV diastolic dysfunction or right ventricular
function (p>0.32 for all, Table 2). Also, plasma galectin-3 was not associated with any
hemodynamic measures measured by pulmonary artery catheter, including pulmonary
capillary wedge pressure (p=0.45) and cardiac index (p=0.70), as well as pulmonary artery
mean pressure (p=0.99) and central venous pressure (p=0.76).
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We have up to 5-year long-term follow-up of our chronic HF cohort, which demonstrated

that higher galectin-3 levels were associated with higher all-cause mortality, particularly in
those with elevated cystatin C levels (Table 3, Figure 1). In multivariate analysis, galectin-3
remained an independent predictor of mortality after adjusting for age, eGFR, LVEF, and
ratio of the mitral inflow early wave to the early diastolic myocardial relaxation velocity at
septal mitral annulus (Table 3). Galectin-3 also predicted mortality independent of age and
cardiac structure, or age and cystatin C levels in this cohort (Table 3). However, galectin-3
did not predict the composite endpoint of all-cause mortality, cardiac transplantation, or HF
hospitalization (p=0.34).

Discussion
The major findings of this study include: 1) the lack of a strong relation between galectin-3
and echocardiographic measurements of cardiac structure and function in chronic stable
systolic HF, and between galectin-3 and invasive hemodynamic measurements in advanced
decompensated HF; and 2) the relatively stronger relation between galectin-3 and indices of
renal dysfunction including cystatin C levels. Taken together, these data emphasize that
galectin-3 is a pleotropic molecule mediating immune response, inflammation, and
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fibrogenesis rather than specific to cardiac (or renal) performance alone.

Galectin-3 is a macrophage-derived mediator, which can activate fibroblasts and induce

their proliferation and collagen deposition1,5,15. In pre-clinical studies, increased expression
of galectin-3 is associated with subsequent development of cardiac dysfunction1. Several
human studies have indicated that elevated levels of galectin-3 provide independent
prognostic value in HF. In the ProBNP Investigation of Dyspnea in the Emergency
Department (PRIDE) study, higher galectin-3 levels measured by the same research assay
were associated with poorer survival at 1-year follow-up in 209 subjects with a diagnosis of
acute decompensated heart failure seen at the Emergency Department, as well as at 4-year
follow-up in a subset of patients6,16. In the Deventer-Alkmaar heart failure study (DEAL-
HF), 232 elderly subjects with advanced symptoms from chronic HF were followed for 6.5
years, and elevated galectin-3 was also found to be a significant predictor of mortality risk
even following adjustment for age, eGFR, and NT-proBNP (hazard ratio 1.24, 95%

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 Tang et al. Page 5

confidence interval 1.03–1.50, p=0.026)8. The results within our chronic systolic HF cohort
corroborate those from DEAL-HF, with higher plasma galectin-3 levels predicting increased
risk of all-cause mortality. In contrast, we found a lack of relation between plasma
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galectin-3 levels and some of the strongest cardiac-specific echocardiographic or

hemodynamic predictors of poor survival in systolic HF. The lack of any clear association
with cardiac-specific indices in our study is surprising considering the fact that cardiac
fibrosis is an important component of myocardial stiffness, and our findings are discrepant
with prior reports. In the echocardiographic subset of the PRIDE study, where 76 subjects
with acute decompensated HF and 39 non-HF patients underwent echocardiographic
evaluation between 23–73 hours after hospital contact, galectin-3 levels were modestly
associated with early diastolic myocardial relaxation velocity at mitral annulus (r=−0.246,
p=0.03) and ratio of the mitral inflow early wave to early diastolic myocardial relaxation
velocity at mitral annulus (r=0.345, p=0.01), as well as tricuspid and mitral regurgitation
that was not seen in our cohort. It is important to recognize that the patient population in the
PRIDE study was very different from our studies, with a mean LVEF 45.5±15%, a mean LV
end-diastolic volume of 109±44ml, and a mean ratio of the mitral inflow early wave to early
diastolic myocardial relaxation velocity at mitral annulus of 12.3±6 in the acute HF cohort
(n=76)16. Only 15% of subjects in PRIDE admitted for acute decompensated HF had history
of cardiomyopathy. In comparison, our study populations consisted of more advanced
systolic HF (mean LVEF 26 and 28%, mean LV end-diastolic volume of 218 and 231ml,
and mean ratio of the mitral inflow early wave to early diastolic myocardial relaxation
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velocity at mitral annulus of 15.5 and 20.3 in our chronic and acute systolic HF cohorts,
respectively for acute and chronic HF), with echocardiographic measurements performed at
the time of blood draw. Different assays used between different studies may also affect the
findings, even though all the studies to date showed consistency in demonstrating relations
between galectin-3 with renal function and all-cause mortality. Nevertheless, the mere
differences in baseline echocardiographic characteristics may potentially explain the marked
differences in the observations regarding the relationships between galectin-3 and cardiac
structure and function.

While this discrepancy requires confirmation in future human studies, we hypothesize a few
potential explanations. First, not all diastolic dysfunction in chronic systolic HF can be
explained by myocardial fibrosis. In fact, extensive remodeling with cardiac enlargement
inevitably causes myocyte stretch and altered relaxation as a result of myocardial
deformities. Other non-fibrotic contributors of diastolic dysfunction include ischemia,
altered energetics, and even disruption of normal calcium homeostasis. In addition, there
may be a disassociation between tissue and circulating galectin-3 levels such that systemic
levels of galectin-3 may not reflect the myocardial expression and consequences of
galectin-3. An alternative explanation for our observation of a discrepancy between the
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ability of galectin-3 to predict risk without clear association with cardiac structure and
function may lie in the relatively stronger relation between galectin-3 levels and renal
function. This relation observed in our study is consistent with prior reports. In both PRIDE
and DEAL-HF study, there was a strong inverse relation between galectin-3 levels and
eGFR8,16. Interestingly, a recent report from the same investigators of DEAL-HF identified
stronger prognostic value within subgroup of patients with HF and preserved ejection
fraction, who may be more dependent on renal insufficiency as contributor of congestive
symptoms17. Indeed, galectin-3 expression and secretion has been linked to the development
of renal fibrosis in animal models5. In an experimental glomerulonephritis model, galectin-3
has been shown to modulate renal mesangial cell proliferation and led to alterations in
extracellular matrix18. The availability of cystatin C measurements in our cohort, which
demonstrated a strong correlation with galectin-3, further illustrated the tight association
between circulating galectin-3 levels and renal insufficiency. It is interesting to note that
cystatin C itself is a cysteine protease inhibitor endogenously and ubiquitously produced in

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all nucleated cells, which has been associated with alterations in extracellular matrix
production9,19,20 and the presence of left ventricular hypertrophy in non-heart failure
subjects21,22. It is therefore conceivable that the pathophysiologic role of galectin-3 leading
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to progressive renal compromise may be more prominent than its impact on cardiac
pathology, and such an association with renal impairment may in part determine galectin-3's
prognostic role in heart failure. Further investigations regarding the clinical utility of
galectin-3 are warranted.

Acknowledgments
Dr. Tang has previously received research grant support from Abbott Laboratories, which has a licensing agreement
with BG Medicine in the development of galectin-3 assay.

Funding sources: This work was supported by the American Society of Echocardiography Sonographer's Grant, the
National Institutes of Health Clinical and Translational Science Award (CTSA UL1-RR024989), and the National
Space Biomedical Research Institute (NASA NCC 9-58).

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Figure 1.

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Kaplan-Meier analysis of 5-year all-cause mortality in chronic systolic HF patients (n=133)

with patients stratified according to optimal receiver operating characteristic curve
galectin-3 cut-off value for prediction of all-cause mortality (14.4ng/mL, Figure 1A), with
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median cystatin C levels (1.23ng/mL, Figure 1B) and amino-terminal pro-B-type natriuretic
peptide (1,240pg/mL, Figure 1C).
Abbreviations: +, above or equal to cut-off or median; −, below cut-off or median; Gal-3,
Galectin-3; CysC, Cystatin C; NT-proBNP, amino-terminal pro-B-type natriuretic peptide.
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Table 1
Baseline Subject Characteristics for Chronic Heart Failure (n=133) and Advanced Decompensated Heart
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Failure (n=45) Cohorts

Variable Chronic Heart Failure (n=133) Advanced Decompensated

Heart Failure (n=45)

Age (years) 57 ± 13 55 ± 14
Body mass index (kg/m2) 28 ± 5 28 ± 6
Men 99 (74%) 39 (87%)
Ischemic heart failure etiology 56 (42%) 21 (47%)
NYHA class III or IV 46 (35%) 35 (95%)
Hypertension 75 (58%) 15 (33%)
Diabetes mellitus 36 (27%) 12 (27%)
Echocardiographic indices:
Left ventricular mass index (g/m2) 156 ± 46 186 ± 64

Indexed left ventricular end-diastolic volume (mL/m2) 109 ± 34 111 ± 52

Left ventricular ejection fraction (%-unit) 26 ± 6 28 ± 8
Diastolic stage III 44 (37%) 41 (91%)
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Medications:
Angiotensin converting enzyme inhibitors and/or angiotensin 122 (94%) 12 (29%)
receptor blockers
Other vasodilators 15 (11%) 25 (56%)
Beta-blockers 84 (64%) 14 (33%)
Spironolactone 35 (28%) 13 (31%)
Digoxin 74 (60%) 15 (36%)
Laboratory Data:
Aminoterminal pro-B-type natriuretic peptide (pg/mL) 1,240 [529 – 3407] 4,582 [2286 – 7537]
Estimated glomerular filtration rate (mL/min/1.73m2) 70 ± 23 78 ± 47
Cystatin C (ng/mL) 1.23 [1.03 – 1.62] 1.63 [1.19 – 2.67]
Galectin-3 (ng/mL) 13.9 [12.1 – 16.9] 14.7 [12.1 – 17.0]
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Table 2
Univariate Correlations between Plasma Galectin-3 Levels and Clinical and Echocardiographic Characteristics
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for Chronic Heart Failure (n=133) and Advanced Decompensated Heart Failure (n=45) Cohorts

Variable Chronic Heart Failure Advanced

(n=133) Decompensated Heart
Failure (n=45)

r p r p
Age (years) 0.22 0.010 0.07 0.647
Body mass index (kg/m2) 0.01 0.913 0.00 0.974
Echocardiographic indices:
Left ventricular structure:
Left ventricular mass index (g/m2) 0.04 0.688 −0.12 0.460

Left ventricular end-systolic volume index (mL/m2) −0.07 0.482 −0.08 0.607

Left ventricular end-diastolic volume index (mL/m2) −0.05 0.608 −0.07 0.650
Left ventricular systolic function:
Left ventricular ejection fraction (%) 0.10 0.253 0.04 0.825
LV Diastolic Function:
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Mitral ratio of peak early to late diastolic filling velocity 0.05 0.596 0.18 0.357
Mitral deceleration time (ms) 0.02 0.867 0.07 0.631
Early diastolic myocardial relaxation velocity at septal mitral annulus (cm/s) 0.00 0.974 −0.01 0.945
Early diastolic myocardial relaxation velocity at lateral mitral annulus (cm/s) 0.07 0.426 0.04 0.822
Averaged early diastolic myocardial relaxation velocity at mitral annulus (cm/ 0.08 0.354 0.02 0.925
s)
Ratio of the mitral inflow early wave to the early diastolic myocardial 0.06 0.516 0.10 0.539
relaxation velocity at septal mitral annulus
Ratio of the mitral inflow early wave to the early diastolic myocardial 0.07 0.434 0.10 0.511
relaxation velocity at lateral mitral annulus
Ratio of the mitral inflow early wave to the averaged early diastolic 0.09 0.321 0.15 0.361
myocardial relaxation velocity at mitral annulus
Pulmonary vein systolic/diastolic ratio −0.05 0.599 −0.19 0.323
Left atrial volume index (mL/m2) 0.08 0.413 −0.08 0.596
Right ventricular systolic function:
Right ventricular systolic wave −0.10 0.273 0.10 0.529
Right ventricular diastolic function:
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Ratio of the tricuspid inflow early wave to the early diastolic myocardial 0.05 0.603 0.02 0.900
relaxation velocity at tricuspid annulus
Hepatic vein systolic/diastolic ratio 0.08 0.454 −0.13 0.668
Right atrial volume index (mL/m2) 0.02 0.842 −0.30 0.052
Estimated Right-sided Pressures:
Tricuspid regurgitation jet velocity (cm/s) 0.12 0.182 0.21 0.240
Right ventricular systolic pressure (mmHg) 0.13 0.209 0.14 0.384
Laboratory Data:
Estimated glomerular filtration rate (mL/min/1.73m2) −0.24 0.007 −0.39 0.024
Cystatin C (mg/L) 0.38 <0.0001 0.40 0.006
Aminoterminal-proB-type natriuretic peptide (pg/mL) 0.18 0.053 0.04 0.793

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Table 3
Univariate and Multivariate Cox Proportional Hazards Analyses of 5 Year All-Cause Mortality for Patients
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with Chronic Systolic Heart Failure (37 events; n=133)

Natural logarithm galectin-3 (pg/mL)* Hazard Ratio (95% Confidence p-value

interval)

Univariate Model 1.87 (1.36 – 2.55) <0.001

Multivariate Model 1: Adjusted for age, eGFR, and NT-proBNP. 1.75 (1.18 – 2.58) 0.005

Multivariate Model 2: Adjusted for age, eGFR, left ventricular ejection fraction, and ratio of 1.94 (1.30 – 2.91) 0.001
the mitral inflow E wave to the early diastolic myocardial relaxation velocity at septal mitral
annulus

Multivariate Model 3: Adjusted for age, left ventricular mass index, left ventricular end- 1.56 (1.09 – 2.23) 0.016
systolic volume index, and left ventricular end-diastolic volume index

Multivariate Model 4: Adjusted for age and cystatin C 1.60 (1.09 – 2.34) 0.015

*
Hazard ratios per 1 standard deviation increments (1 standard deviation for natural logarithm galectin-3 = 0.26 ng/mL; 1 standard deviation for
age = 13 years; 1 standard deviation for estimated glomerular filtration rate [eGFR] = 30 ml/min/1.73m2; 1 standard deviation for natural logarithm
aminoterminal pro-B-type natriuretic peptide [NT-proBNP] = 1.36 pg/mL; 1 standard deviation for left ventricular ejection fraction = 6.4%; 1
standard deviation for ratio of the mitral inflow E wave to the early diastolic myocardial relaxation velocity at septal mitral annulus = 12; 1
standard deviation for left ventricular end-systolic volume index = 30 mL/m2; 1 standard deviation for left ventricular end-diastolic volume index =
34 mL/m2; 1 standard deviation for cystatin C = 0.94 mg/L).
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