578405

research-article2015
TAK0010.1177/1753944715578405Therapeutic Advances in Cardiovascular DiseaseM George, E Shanmugam

Therapeutic Advances in Cardiovascular Disease Original Research

Value of pentraxin-3 and galectin-3 in

Ther Adv Cardiovasc Dis

2015, Vol. 9(5) 275­–284

acute coronary syndrome: a short-term DOI: 10.1177/

1753944715578405

prospective cohort study

© The Author(s), 2015.
Reprints and permissions:
http://www.sagepub.co.uk/
journalsPermissions.nav

Melvin George, Elangovan Shanmugam, Varsha Srivatsan, Karunamoorthy Vasanth,

Balaji Ramraj, Muthukumar Rajaram, Amrita Jena, Aruna Sridhar, Minakshi Chaudhury
and Ilango Kaliappan

Abstract
Background: Acute coronary syndrome (ACS) continues to be a leading cause of morbidity and
mortality worldwide. Galectin-3 and pentraxin-3 are two prognostic biomarkers that have been
studied in heart failure (HF). However, there are limited data on these biomarkers in the ACS
population. The objective of the study was to determine the variables that are most affected by
high concentrations of pentraxin-3 and galectin-3, and the influence they have on outcomes of
all-cause mortality in patients with ACS.
Methods: We included a total of 160 patients [ST elevation myocardial infarction (STEMI),
n = 64; non STEMI/unstable angina (NSTEMI/UA), n = 38; and control subjects with chronic
stable angina (CSA)/microvascular angina (MVA) n = 58]. Plasma pentraxin-3 and galectin-3
levels were assessed from these patients at the time of hospital admission. Major adverse
cardiovascular events including all-cause mortality, rehospitalizations and coronary artery
bypass graft surgery (CABG) were assessed at 6 months.
Results: The median concentration of pentraxin-3 and galectin-3 were significantly higher
in STEMI than in NSTEMI patients (p < 0.005) or controls (p < 0.005). Greater numbers of
deaths (4 versus 0) were observed in STEMI patients with higher levels of these biomarkers. In
Correspondence to:
addition, ACS patients with high levels of pentraxin-3 and galectin-3 had lower left ventricular Melvin George, MD, DM
ejection fraction (LVEF) (p < 0.005), and a moderate correlation was observed between LVEF Department of Cardiology,
SRM Medical College
and pentraxin-3 levels (r = -0.45, p < 0.005). Patients with higher galectin-3 levels were Hospital & Research
also observed to have a lower estimated glomerular fraction rate (eGFR), and a moderate Centre, Kattankulathur,
Kancheepuram, Chennai,
correlation was observed between them (r = -0.34, p < 0.005). Tamil Nadu 603203, India
melvingeorge2003@
Conclusion: Pentraxin-3 and galectin-3 hold much promise in the ACS population as gmail.com
prognostic biomarkers. Elangovan Shanmugam,
MD, DM
Varsha Srivatsan, MSc
Keywords:  acute coronary syndrome, all-cause mortality, estimated glomerular filtration rate, Muthukumar Rajaram,
Mpharm
galectin-3, left ventricular ejection fraction, pentraxin-3 Amrita Jena, MSc
Aruna Sridhar, MSc
Department of Cardiology,
SRM Medical College
Introduction patients die within 24 hours of onset, and 15% of Hospital & Research
Acute coronary syndrome (ACS) remains a major the patients with UA/NSTEMI die or experience Centre, Chennai, India

public health problem causing significant mor- reinfarction 30 days post diagnosis. Once diag- Karunamoorthy Vasanth,
MSc
bidity and mortality. The spectrum of ACS nosed with ACS, approximately 30% of the Minakshi Chaudhury,
includes ST segment elevation myocardial infarc- patients are rehospitalized within 6 months [Go MTech
Ilango Kaliappan, PhD
tion (STEMI), non-ST segment elevation myo- et  al. 2014]. Forecasts covering 10 years in the ISISM, SRM University,
cardial infarction (NSTEMI) and unstable angina US, France, Germany, Italy, Spain, the UK and Chennai, India
Balaji Ramraj, MD
(UA). They share common pathophysiological Japan observe that the incidence of hospitalized Department of Community
origins related to plaque vulnerability with or cases of ACS will increase from 1.29 million cases Medicine, SRM Medical
College Hospital &
without luminal thrombosis and vasospasm. It in 2012 to 1.43 million cases in 2022 at the rate of Research Centre, Chennai,
has been estimated that about a third of STEMI 1.04% per year [Market Research Reports, 2014]. India

http://tac.sagepub.com 275
Therapeutic Advances in Cardiovascular Disease 9(5)
In India, the mortality attributed to cardiovascu-
lar diseases (CVD) alone is expected to rise by
104% in men and 90% in women between 1985
and 2015 [Bulatao and Stephens, 1992]. The data
from the CREATE (Treatment and outcomes of
acute coronary syndromes in India) registry
showed that the percentage of STEMI cases were
significantly higher in the Indian population
(61%) compared with the Western population
(30–40%) despite them being 5–10 years younger
[Xavier et al. 2008].
In 1998, the Biomarkers Definitions Working
Group at the US National Institutes of Health
defined a biomarker as ‘a characteristic that is
objectively measured and evaluated as an indica-
tor of normal biological processes, pathogenic
processes, or pharmacologic responses to a thera-
peutic intervention’ [Biomarkers Definitions
Working Group, 2001; Atkinson et al. 2001].
Cardiovascular biomarkers have been increas-
ingly used in the past few years to facilitate the
screening, diagnosis or prognosis of disease. For
instance, troponins and creatine phosphokinases
are indicative of the extent of myocardial damage.
B-type natriuretic peptide (BNP) and N-terminal
pro-brain natriuretic peptide (NT-pro BNP) have
been approved by the US Food and Drug
Administration (FDA) for the diagnosis and man-
agement of congestive heart failure (CHF). A
number of biomarkers such as myeloperoxidase,
metalloproteinase, soluble CD40 ligand, ischemia
modified albumin, pregnancy-associated plasma
protein-A, cystatin C, fatty acid binding protein,
and placental growth factor (PlGF) are under
investigation for diagnostic/prognostic use in dif-
ferent stages of ACS [Nagesh and Roy, 2010].
While a combination of biomarker results and
standard testing aids the diagnosis of ACS, pre-
dicting the prognosis of ACS patients remains a
challenge. Thus there is ample scope for develop-
ing biomarkers that can accurately predict cardio-
vascular outcomes.
Pentraxin-3 is an inflammatory biomarker from
the C-reactive protein (CRP) family which has
been shown to be expressed at the site of athero-
sclerotic plaques and cardiac myocytes [Kunes
et  al. 2012]. A significantly higher level of pen-
traxin-3 was found in ACS subjects than in
healthy controls [Ustündağ et  al. 2011].
Complementarily Matsui and colleagues found
that a higher level of pentraxin-3 in their cohort of
NSTEMI and UA patients efficiently predicted
6-month cardiac events of death or rehospitaliza-
tion [Matsui et al. 2010].
276 http://tac.sagepub.com
Galectin-3 has been approved by the FDA as a
prognostic biomarker in CHF to be used in con-
junction with clinical evaluation [Yin et al. 2014].
Galectin-3 is a soluble β-galactoside binding lec-
tin that mediates profibrotic pathways [Sharma
et al. 2004]. A number of studies have evaluated
the utility of galectin-3 in heart failure (HF) pop-
ulations, but only a handful of studies have been
conducted in ACS populations. Grandin and col-
leagues observed that, in patients with acute myo-
cardial infarction (AMI), those with galectin-3
greater than median had a higher risk of new or
recurrent HF [Grandin et al. 2012]. Tsai and col-
leagues found that patients with STEMI had
higher circulating levels of galectin-3 than healthy
controls, and STEMI patients with high galec-
tin-3 levels experienced a greater rate of 30-day
mortality [Tsai et al. 2012].
A number of studies have investigated the role of
pentraxin-3 and galectin-3 in HF. However, there
is a dearth of data in the ACS population, giving
us the impetus to perform this study. We thus
sought to determine the variables that are most
affected by high concentrations of pentraxin-3
and galectin-3, and the influence they have on
outcomes of all-cause mortality in ACS patients.
Methods
The study protocol was approved by the Institution
Ethics Committee, SRM Medical College
Hospital and Research Centre, Kancheepuram,
and was conducted between April 2013 and June
2014. Written informed consent was obtained
from all patients who participated in the study. We
included a total of 160 patients, of whom 64 were
diagnosed with STEMI, 38 with NSTEMI/UA,
and 58 were control subjects with chronic stable
angina (CSA)/microvascular angina (MVA).
Patients with prior HF, severe valvular heart dis-
ease, coexisting cancers, connective tissue diseases
and cirrhosis were excluded from the study.
Demographic characteristics, clinical variables
and patient history were obtained from patient
interviews and medical records.
A total of 5ml of peripheral blood was collected in
ethylenediamine tetraacetic acid (EDTA) coated
Vacutainer tubes from each patient within 48
hours of admission to the cardiac intensive care
unit (ICU). Plasma galectin-3 and pentraxin-3
levels were assessed using an enzyme linked
immunosorbent assay (ELISA) (R&D Systems,
USA). Patients were followed up at 6 months
 M George, E Shanmugam et al.

Table 1.  Baseline characteristics of study patients.

Variables STEMI (n = 64) NSTEMI and UA (n = 38) Controls (n = 58)

Age 51.48 ± 10.60 54.82 ± 10.03 53.22 ± 9.45
Gender (male, %) 84.4* 63.2 67.2
BMI, kg/m2 24.99 ± 2.85 25.84 ± 3.85 25.64±3.8
LVEF, % 44.18 ± 9.20 53.30±11.38 52.82 ±12.87**a
Killip class (I/II/III/IV) 89.06/6.25/3.12/1.56 NA NA
eGFR, ml/min 80.30 ± 27.24 80.88 ± 24.62 81.66 ± 28.84
Risk factors, %  
Diabetes mellitus 43.8 50 48.3
Hypertension 40.6 39.5 48.3
Dyslipidemia 46.9 39.5 39.6
Smoking 45.3** 18.4 12.5
Family history of CAD 28.1 34.2 20.7
Galectin-3, ng/ml 12.3 (9.63–14.65) 9.44 (7.8–11.09)**a 9.71 (7.78–12.15)**a
Pentraxin-3, ng/ml 6.77 (3.54–13.93) 2.46 (1.71–4.31)**a 3.99 (1.92–7.2)**a

Data expressed as mean ± standard deviation, percentage or median with interquartile range. *p<0.05;**p<0.005;
a compared to STEMI group;

ACS, acute coronary syndrome; BMI, body mass index, CAD, coronary artery disease, eGFR, estimated glomerular filtra-
tion rate, LVEF, left ventricular ejection fraction; NA, not applicable; NSTEMI, non-ST segment elevation myocardial
infarction; STEMI: ST segment elevation myocardial infarction; UA: unstable angina.

through telephonic interview by investigators
blinded to the biomarker levels to assess major
adverse cardiovascular events that include all-
cause mortality, rehospitalizations and coronary
artery bypass graft surgery (CABG).
Data were expressed as mean ± standard devia-
tion (SD) or median with interquartile range
(IQR). The differences in the patient characteris-
tics between the three study groups were com-
pared using one way analysis of variance (ANOVA)
for continuous variables or Pearson’s chi-squared
test for variables with frequency distribution.
Pearson correlation was used to measure correla-
tion between different variables. Data were log
transformed when they did not follow a Gaussian
distribution. A p value <0.05 was considered as
statistically significant. Statistical analysis was
performed using computer software programs
such as Statistical Package for Social Scientists,
SPSS version.16 (Chicago, IL, USA) and
GraphPad Prism version 5.01 for Windows (San
Diego, CA, USA).
Results
An ACS cohort consisting of patients with STEMI
(n = 64), NSTEMI (n = 38) and non-ACS popu-
lations consisting of a small cohort of patients
with CSA/MVA (n = 58) were compared for age,
sex, body mass index (BMI), left ventricular ejec-
tion fraction (LVEF), estimated glomerular filtra-
tion rate (eGFR) and risk factors such as diabetes,
hypertension and dyslipidemia. Family history of
coronary artery disease (CAD) and their smoking
status were also recorded and compared between
the groups. Between the three groups, LVEF and
smoking emerged as being significantly different
(Table 1).
Galectin-3, pentraxin-3 and LVEF
In the cohort of ACS patients, the cutoffs derived
from receiver operating characteristic (ROC)
curves for galectin-3 and pentraxin-3 were 11.02
ng/ml and 6.45 ng/ml, respectively. Patients were
divided into two groups based on galectin-3 and
pentraxin-3 levels greater and lesser than the cut-
off (Table 2).
In patients that had biomarker levels greater than
cutoff, LVEF was found to be significantly lower.
However, in those that had greater pentraxin-3
levels, a higher percentage of these patients were
found to be diabetic and hypertensive.
Consistent with the impact of galectin-3 and pen-
traxin-3 on LVEF, both the biomarkers were
found to be negatively correlated with LVEF in
ACS and myocardial infarction (MI) patients. In

http://tac.sagepub.com 277
Therapeutic Advances in Cardiovascular Disease 9(5)

Table 2.  Comparison of ACS patient characteristics based on the cutoff derived from ROC curve of the biomarkers.

Characteristics Galectin-3 ⩾ 11.02 Galectin-3 < 11.02 Pentraxin-3 ⩾ 6.45 Pentraxin-3 < 6.45
Age 54.19 ± 10.04 51.39 ± 10.84 54.24 ± 9.53 52.40 ± 10.46
Gender (male, %) 72.3 83.3 78.4 75.9
BMI, kg/m2 24.80 ± 3.0 25.70 ± 3.45 24.68 ± 3.00 25.67 ± 3.45
LVEF, % 43.14 ± 8.66 51.14 ± 11.45** 42.40 ± 8.43 51.04 ± 10.94**
eGFR, ml/min 73.69 ± 25.16 86.35 ± 26.11* 73.97 ± 26.39 82.37 ± 24.03
Risk factors (%)  
Diabetes mellitus 51.1 42.6 62.2 37.9*
Hypertension 46.8 35.2 56.8 32.8*
Dyslipidemia 42.6 46.3 45.9 44.8
Smoking 31.9 37 29.7 34.5
Family history of CAD 25.5 33.3 27.0 32.8
Data expressed as means ± standard deviation, percentage or median with interquartile range.
*p < 0.05;**p < 0.005.
ACS, acute coronary syndrome; BMI, body mass index, CAD, coronary artery disease, eGFR, estimated glomerular filtration rate, LVEF, left
ventricular ejection fraction; NSTEMI, non-ST segment elevation myocardial infarction; STEMI: ST segment elevation myocardial infarction; UA:
unstable angina.

MI patients, both the biomarkers observed a sig-

nificant association with ACS patients. In ACS
patients, there was a weak association between
galectin-3 and LVEF (r = -0.2392, p < 0.05),
while a relatively stronger association was detected
between pentraxin-3 and LVEF (r = -0.4539,
p < 0.005). In the MI subcohort, a weak associa-
tion between the biomarkers and LVEF was
observed (galectin-3: r = -0.3483, p < 0.05,
­pentraxin-3: r = -0.3232, p < 0.05) (Figure 1).
Galectin-3 and eGFR
When the ACS cohort was divided based on
galectin-3 levels, a significant difference was
observed between the two groups, with the group
with higher galectin-3 level having a significantly
lower eGFR. eGFR was negatively associated
with galectin-3, showing a moderate but signifi-
cant correlation when analysed in the cohort of
ACS patients (r = -0.2881. p < 0.005) (Figure 2).
Events
In our study, we defined higher levels of bio-
marker as concentrations greater than the optimal
cutoff value derived from the ROC curve (Figure
3a,b). A total of 24 events occurred during the
study, with 17 events occurring in ACS patients.
Among the patients that experienced ST-ACS,
four of them died, five underwent CABG surgery
and three were rehospitalized. Among the non
ST-ACS patients, five were rehospitalized for
CABG surgery. The four patients that died had
higher levels of both pentraxin-3 and galectin-3.
It was observed that LVEF was significantly lower
and that BMI was higher in those patients who
experienced events Table 3.
Discussion
To the best of our knowledge, this is the first pro-
spective study conducted in Indian populations
which evaluates the levels of pentraxin-3 and
galectin-3 in ACS. Our study demonstrated that
the median concentrations of the biomarkers pen-
traxin-3 and galectin-3 were significantly higher
in the MI population and that the cohort with
biomarker levels greater than the cutoff derived
from ROC had greater number of deaths, thus
indicating that their measurement may be suita-
ble indicators of poor prognosis.
Earlier studies in HF populations suggest that
higher levels of pentraxin-3 and galectin-3 are
indicative of advanced disease progression and
reduced response to therapy. In our study per-
formed in ACS populations we found that pen-
traxin-3 levels were significantly higher in the
STEMI population compared with NSTEMI/
controls. The median pentraxin-3 concentration
observed in our study was comparable with other
studies in the ACS population [Matsui et al.2010;
Lee et  al. 2010]. Galectin-3 was significantly
higher in the STEMI patients than in the control
population and these findings concurred with

278 http://tac.sagepub.com

Figure 1.  Galectin-3 and LVEF in (a) ACS patients and (b) MI patients. Pentraxin-3 and LVEF in (a) ACS patients
and (b) MI patients.
ACS, acute cardiac syndrome; LVEF, left ventricular ejection fraction; MI, mycardial infarction; Ln, Natural Logarithm.
Figure 2.  Galectin-3 and eGFR in ACS patients.
ACS, acute cardiac syndrome; eGFR: estimated glomerular
filtration rate; Ln, Natural Logarithm.
that of Tsai and colleagues [Tsai et  al. 2012].
Although most studies report levels greater than
those reported in our study, comparable concen-
trations have also been reported [Milting et  al.
2008; Van Kimmenade et al. 2008].
When patients in the ACS cohort were divided
based on their pentraxin levels, it was found that
a greater number of events occurred in the
cohort with pentraxin levels greater than cutoff
derived from ROC (6.45 ng/ml). The STEMI
http://tac.sagepub.com 279
M George, E Shanmugam et al.
patients that died had elevated levels of pen-
traxin-3 measured within 48 hours before acute
event. While the role of the inflammatory bio-
marker pentraxin-3 in atherosclerosis is still
unclear, studies do suggest that pentraxin levels
are higher in ACS populations. After an acute
event, a study reported that the expression of
pentraxin-3 increased over time in patients with
AMI, and peaked at 7.5 hours post AMI and
returns to normal levels after 3 days [Peri et al.
2000]. We collected samples from our patients
within 48 hours of the acute event, and the raised
concentration of pentraxin-3 may reflect the
triggered inflammatory process during myocar-
dial infarction. CRP and pentraxin-3 belong to
the same family of proteins. An earlier study
found that CRP was markedly elevated in
STEMI patients compared with NSTEMI
patients [Habib et al. 2011] and the level of CRP
was hypothesized to reflect the degree of intrac-
oronary thrombosis[Arroyo-Espliguero et  al.
2004; Zairis et al. 2005; Zouridakis et al. 2004].
It was also observed that LVEF, diabetic and
hypertension status significantly differed between
the two groups divided based on pentraxin-3 lev-
els. A greater percentage of patients with higher
levels of pentraxin were found to be hypertensive,
Therapeutic Advances in Cardiovascular Disease 9(5)

Figure 3.  Receiver operating characteristics (ROC) for baseline (a) pentraxin-3 and (b) galectin-3 in prediction
of adverse events at 6 months.
For (a): AUC = 0.62; 95% CI - 0.46 to 0.78; optimal cutoff 6.45 ng/mL; sensitivity 58.8%; specificity 65.4%.
For (b): AUC = 0.50; 95% CI - 0.37 to 0.64; optimal cutoff 11.02 ng/mL; sensitivity 56.3%; specificity 55.3%.
AUC, area under curve; CI, confidence interval.

Table 3.  Comparison of ACS patient characteristics based on event status.

Events (+) Events (-)

n 17 85
Age 54.06 ± 8.26 52.46 ± 10.88
Gender (% male) 78.40 78.80
BMI, kg/m2 26.73 ± 3.30* 25.03 ± 3.21
LVEF, % 38.80 ± 8.50** 49.013 ± 10. 56
eGFR, ml/min 74.22 ± 17.60 81.73 ± 27.46
Risk factors  
Diabetes mellitus (%) 58.80 43.50
Hypertension (%) 41.20 40.0
Dyslipidemia (%) 35.30 45.90
Smoking (%) 17.60 37.60
Family history CAD (%) 35.30 29.40
Galectin-3, ng/ml 11.31 (8.90–13.75) 10.64 (8.86–14.10)
Pentraxin-3, ng/ml 6.64 (2.81–26.55) 4.25 (2.15–8.41)

*p = 0.05; **p = 0.001

Data are expressed as mean ± standard deviation, median (interquartile range) or percentage;
ACS, acute coronary syndrome; BMI, body mass index; CAD, coronary artery disease; eGFR, estimated glomerular filtra-
tion rate; LVEF, left ventricular ejection fraction.

diabetic and having a lower LVEF. Another study
also found that a significantly large number of
hypertensive patients had high pentraxin levels
[Matsui et  al. 2010]. Hypertension and diabetes
are low-grade inflammatory processes and the
release of pentraxin suggests the occurrence of
vascular inflammatory processes. An observational
study found pentraxin-3 to be 15 times the normal
limit of the upper range in newly diagnosed
hypertensive patients. As suggested by Parlak and
colleagues, vascular inflammation could link
hypertension to atherosclerotic process driving
cardiovascular disorders [Parlak et  al. 2012]. A
direct association between insulin resistance and

280 http://tac.sagepub.com

pentraxin-3 has been found in other populations.
However, to the best of our knowledge, this has
not been documented in ACS populations.
Furthermore, when we explored the relationship
between LVEF and pentraxin-3, we found a sig-
nificant moderate correlation between the two in
ACS populations. However, we found a weak but
significant correlation between LVEF and pen-
traxin-3 in the MI subcohort. To the best of our
knowledge, the association between LVEF and
pentraxin-3 has not yet been studied in the ACS
populations. However, Matsubara and colleagues
observed that there is no association between
LVEF and pentraxin in HF population [Matsubara
et  al. 2011]. We found that the eGFR did not
emerge to be significantly different between the
groups with high and low pentraxin-3 levels.
Furthermore, no correlation was observed
between the two variables in ACS populations.
However, in a cohort of NSTEMI patients from
the GUSTO-IV study, multiple linear regression
analysis found a significant association between
eGFR and pentraxin-3 [Eggers et  al. 2013]. A
study by Kanbay and colleagues found that pen-
traxin-3 levels was associated with CAD risk in
stage II and III chronic kidney disease (CKD)
patients [Kanbay et al. 2011]
In our study, when ACS patients that experienced
events were divided based on galectin levels (cut-
off based on ROC: 11.02 ng/ml), a greater num-
ber of people died at 6 months in the group with
galectin levels greater than cutoff. In fact, all
patients who died had STEMI at the time of
admission, and elevated galectin-3 levels when
measured within 48 hours of the acute event. In
the PRIDE study, galectin-3 levels were higher in
HF than non-HF patients; 29% of the acute heart
failure (AHF) patients experienced recurrent HF,
while 8% of them died. Based on the sensitivity
and specificity of galectin-3, the authors defined a
cutoff of 9.58 (ng/ml) to predict 60-day mortality
[Van Kimmenade et al. 2006]. Galectin-3 has also
been implicated in inflammatory processes
[Sharma et al. 2004; De Boer et al. 2010] and it is
possible that the raised levels indicate the inflam-
mation that occurs during atherosclerosis.
However, it is also possible that its raised levels
may reflect the initiation of a cascade of events
resulting in fibrosis.
We further looked into other factors that may be
influenced by galectin-3 levels and we found that
LVEF was significantly lower in the cohort with
http://tac.sagepub.com 281
M George, E Shanmugam et al.
high galectin-3 levels. Also, in our study we found
that the cohort with higher galectin-3 levels had a
lower LVEF and observed a greater number of
events. Furthermore, galectin-3 and LVEF showed
a weak correlation in the ACS cohort and in the
MI subcohort. Similar findings were observed by
Weir and colleagues where baseline galectin-3 lev-
els negatively correlated with 24-week LVEF [Weir
et  al. 2013]. In a community study by Motiwala
and colleagues, higher baseline galectin-3 pre-
dicted a decrease in LVEF with an odds ratio (OR)
= 8.11 (p = 0.02) [Motiwala et al. 2013]. However,
studies such as the ones by Mayr and colleagues
and Szadkowska and colleagues found no correla-
tion between LVEF and galectin-3, although we
should note that both these studies were per-
formed in post percutaneous coronary interven-
tion (PCI0 patients. Therefore, there is a need to
perform more studies to assess this relationship,
and the role of galectin-3 as a fibrosis marker
[Mayr et al. 2013; Szadkowska et al. 2013].
We found a significant moderate correlation
between eGFR and galectin-3. The cohort of
patients with high galectin-3 levels had signifi-
cantly lower eGFR. Such an association has also
been found by Anand and colleagues in whose
study 20% variability in baseline galectin-3 levels
could be attributed to the strong association
between galectin-3 and eGFR [Anand et  al.
2013]. Gopal and colleagues found that plasma
galectin-3 levels were 2 fold higher in HF patients
with eGFR <30 ml/min than in normal controls
[Gopal et  al. 2012]. Meijers and colleagues
observed that, while plasma galectin-3 levels were
significantly higher, fractional galectin-3 excre-
tion was lower in HF patients compared with
healthy controls. The authors speculate that the
high plasma levels of galectin-3 could be due to
the impaired renal clearance of the biomarker in
HF patients. Mechanistic studies that may serve
to disentangle the seemingly complicated bio-
chemistry behind the role of galectin along the
cardio renal axis may serve as an important tool
to reduce disease burden [Meijers et al. 2014].
Pentraxin-3 is a biomarker of the CRP family,
sharing 98% identity with tumour necrosis factor
(TNF) stimulated gene 14 [Breviario et al. 1992;
Lee et  al. 1994]. Endothelial cells, macrophages,
myeloid cells and dendritic cells produce PTX3
upon stimulation by cytokines and endotoxins
such as interleukin 1 (IL-1) and TNF. Several
studies have examined the role of pentraxin-3 in
CVD, and studies conducted in mice suggest that
Therapeutic Advances in Cardiovascular Disease 9(5)
the plasma levels of the biomarker may increase as
a protective mechanism against cardiac tissue
damage. Exogenous pentraxin-3 has been shown
to reverse the phenotypes of increased inflamma-
tory response characterized by increased neutro-
phil infiltration and apoptotic cardiomyocytes in
pentraxin-3 knockout mice induced with AMI by
coronary artery litigation [Inoue et al. 2012; Salio
et al. 2008]. Maugeri and colleagues showed that
lowest PTX3 expression was found in early MI
(< 6 hours) and the released PTX3 was found to
aggregate with platelets thereby inhibiting their
prothombotic and proinflammatory activity,
and possibly illustrating its cardioprotective
activity[Maugeri et al. 2011]. Galectin-3, however,
belongs to the evolutionary conserved family of
the soluble β-galactoside binding lectin, which are
expressed in macrophages, neutrophils, mast cells,
fibroblasts and osteoclasts. The lectin is found in
the nucleus, cytosol and extracellular space, where
it plays numerous roles as a mediator of pre
mRNA splicing in the nucleus, as a factor inhibit-
ing apoptosis, controlling survival, regulating exo-
cytosis in the cytosol, and exhibiting numerous
autocrine and paracrine properties [Dagher et al.
1995; Hughes, 2001; Sato and Hughes, 1994]
While galectin-3 has not been found in cardiomy-
ocytes, it is found in high levels in cardiac fibro-
blasts. Animal model studies by Sharma and
colleagues showed that rat models that progressed
to HF expressed high levels of galectin-3, and the
infusion of galectin-3 in the pericardium of rats
induced myocardial collagen deposition and
remodeling. These effects were reversed by the
antifibrotic peptide, N-acetyl-seryl-aspartyl-lysyl-
proline [Sharma et al. 2004].
A number of studies have thus investigated the
role of galectin-3 as a diagnostic and prognostic
marker for cardiovascular diseases. Considering
that the disparate pathways through which pen-
traxin-3 and galectin-3 operate, we found a weak
correlation between the two biomarkers in our
study.
Limitations
While our study contributes to the growing wealth
of evidence on cardiovascular biomarkers in ACS,
it is not without limitations. Since the sample size
was small, the number of events observed in our
study was comparatively low. Logistical reasons
prevented us from performing a more intense fol-
low up of patients during the 6-month period.
While a control population of healthy adults
282 http://tac.sagepub.com
would have been ideal, we used patients with
MVA and CSA as controls. We have also not
accounted for the influence of drug therapies on
biomarker levels and other procedures such as
PCI on the event rate.
Conclusion
Pentraxin-3 and galectin-3 are novel circulatory
biomarkers found to be elevated in cardiovascular
diseases. In our study, we found that patients with
ACS had higher levels of these biomarkers.
Patients with elevated levels of these biomarkers
experienced higher number of deaths and had a
lower mean LVEF. Furthermore, there is a dearth
of studies investigating the role of pentraxin-3 in
ACS and this area calls for more research. Finally,
determining the role of pentraxin-3 and galec-
tin-3 in ACS patients is worth investigating using
larger populations.
Funding
We thank the Office of the Honorable Pro Vice
Chancellor of SRM Medical College Hospital,
Kattankulathur, Kancheepuram, for funding the
study.
Conflict of interest statement
The authors declare no conflicts of interest in
preparing this article.
References
Anand, I., Rector, T., Kuskowski, M., Adourian, A.,
Muntendam, P. and Cohn, J. (2013) Baseline and
serial measurements of galectin-3 in patients with
heart failure: relationship to prognosis and effect of
treatment with valsartan in the Val-HeFT. Eur J Heart
Fail 15: 511–518.
Arroyo-Espliguero, R., Avanzas, P., Cosín-Sales, J.,
Aldama, G., Pizzi, C. and Kaski, J. (2004) C-reactive
protein elevation and disease activity in patients with
coronary artery disease. Eur Heart J 25: 401–408.
Atkinson, A., Colburn, W., DeGruttola, V., DeMets,
D., Downing, G., Hoth, D. et al. (2001) Biomarkers
and surrogate endpoints: preferred definitions and
conceptual framework. Clin Pharmacol Ther 69: 89–95.
Biomarkers Definitions Working Group (2001)
Biomarkers and surrogate endpoints: preferred
definitions and conceptual framework. Clin Pharmacol
Ther 69: 89–95.
Breviario, F., d’Aniello, E., Golay, J., Peri, G.,
Bottazzi, B., Bairoch, A. et al. (1992) Interleukin-1-
inducible genes in endothelial cells. Cloning of a new

gene related to C-reactive protein and serum amyloid
P component. J Biol Chem 267: 22190–22197.
Bulatao, R. and Stephens, P. (1992) Global Estimates
and Projections of Mortality by Cause, 1970–2015.
Washington, DC: World Bank.
Dagher, S., Wang, J. and Patterson, R. (1995)
Identification of galectin-3 as a factor in pre-mRNA
splicing. Proc Natl Acad Sci U S A 92: 1213–1217.
De Boer, R., Yu, L. and van Veldhuisen, D. (2010)
Galectin-3 in cardiac remodeling and heart failure.
Curr Heart Fail Rep 7: 1–8.
Eggers, K., Armstrong, P., Califf, R., Johnston, N.,
Simoons, M., Venge, P. et al. (2013) Clinical and
prognostic implications of circulating pentraxin 3
levels in non ST-elevation acute coronary syndrome.
Clin Biochem 46: 1655–1659.
Go, A., Mozaffarian, D., Roger, V., Benjamin, E.,
Berry, J., Blaha, M. et al. (2014) Executive summary:
heart disease and stroke statistics – 2014 update:
a report from the American Heart Association.
Circulation 129: 399–410.
Gopal, D., Kommineni, M., Ayalon, N., Koelbl, C.,
Ayalon, R., Biolo, A. et al. (2012) Relationship of
plasma galectin-3 to renal function in patients with
heart failure: effects of clinical status, pathophysiology
of heart failure, and presence or absence of heart
failure. J Am Heart Assoc 1: e000760.
Grandin, E., Jarolim, P., Murphy, S., Ritterova, L.,
Cannon, C., Braunwald, E. et al. (2012) Galectin-3
and the development of heart failure after acute
coronary syndrome: pilot experience from PROVE
IT-TIMI 22. Clin Chem 58: 267–273.
Habib, S., Kurdi, M., Al Aseri, Z. and Suriya,
M.(2011) CRP levels are higher in patients with
ST elevation than non-ST elevation acute coronary
syndrome. Arq Bras Cardiol 96: 13–17.
Hughes, R. (2001) Galectins as modulators of cell
adhesion. Biochimie 83: 667–676.
Inoue, K., Kodama, T. and Daida, H. (2012)
Pentraxin 3: a novel biomarker for inflammatory
cardiovascular disease. Int J Vasc Med 2012:
e657025.
Kanbay, M., Ikizek, M., Solak, Y., Selcoki, Y.,
Uysal, S., Armutcu, F. et al. (2011) Uric acid and
pentraxin-3 levels are independently associated with
coronary artery disease risk in patients with stage 2
and 3 kidney disease. Am J Nephrol 33: 325–331.
Kunes, P., Holubcova, Z., Kolackova, M. and
Krejsek, J (2012) Pentraxin 3(PTX 3): an endogenous
modulator of the inflammatory response. Mediators
Inflamm 2012: e920517.
Lee, D., Jeon, H., You, J., Park, M., Lee, S., Kim, S.
et al. (2010) Pentraxin 3 as a novel marker predicting
http://tac.sagepub.com 283
M George, E Shanmugam et al.
congestive heart failure in subjects with acute coronary
syndrome. Korean Circ J 40: 370–376.
Lee, G., Goodman, A., Lee, T. and Vilcek, J. (1994)
Relationship of TSG-14 protein to the pentraxin
family of major acute phase proteins. J Immunol 153:
3700–3707.
Market Research Reports (2014) EpiCast Report:
Acute coronary syndrome (ACS) - epidemiology forecast to
2023. Lewes, DE, USA and Bangalore, India: Market
Research Reports Inc.
Matsubara, J., Sugiyama, S., Nozaki, T., Sugamura,
K., Konishi, M., Ohba, K. et al. (2011) Pentraxin
3 is a new inflammatory marker correlated with left
ventricular diastolic dysfunction and heart failure
with normal ejection fraction. J Am Coll Cardiol 57:
861–869.
Matsui, S., Ishii, J., Kitagawa, F., Kuno, A., Hattori,
K., Ishikawa, M. et al. (2010) Pentraxin 3 in unstable
angina and non-ST-segment elevation myocardial
infarction. Atherosclerosis 210: 220–225.
Maugeri, N., Rovere-Querini, P., Slavich, M., Coppi,
G., Doni, A., Bottazzi, B. et al. (2011) Early and
transient release of leukocyte pentraxin 3 during acute
myocardial infarction. J Immunol 187: 970–979.
Mayr, A., Klug, G., Mair, J., Streil, K., Harrasser,
B., Feistritzer, H. et al. (2013) Galectin-3: relation
to infarct scar and left ventricular function after
myocardial infarction. Int J Cardiol 163:
335–337.
Meijers, W., van der Velde, A., Ruifrok, W., Schroten,
N., Dokter, M., Damman, K. et al. (2014) Renal
handling of galectin-3 in the general population,
chronic heart failure, and hemodialysis. J Am Heart
Assoc 3: e000962.
Milting, H., Ellinghaus, P., Seewald, M., Cakar,
H., Bohms, B., Kassner, A. et al. (2008) Plasma
biomarkers of myocardial fibrosis and remodeling
in terminal heart failure patients supported by
mechanical circulatory support devices. J Heart Lung
Transplant 27: 589–596.
Motiwala, S., Szymonifka, J., Belcher, A., Weiner, R.,
Baggish, A., Sluss, P. et al. (2013) Serial measurement
of galectin-3 in patients with chronic heart failure:
results from the ProBNP Outpatient Tailored Chronic
Heart Failure Therapy (PROTECT) study. Eur J
Heart Fail 15: 1157–1163.
Nagesh, C. and Roy, A. (2010) Role of biomarkers in
risk stratification of acute coronary syndrome. Indian J
Med Res 132: 627–633.
Parlak, A., Aydoğan, U., Iyisoy, A., Dikililer, M., Kut,
A., Cakır, E. et al. (2012) Elevated pentraxin-3 levels
are related to blood pressure levels in hypertensive
patients: an observational study. Anadolu Kardiyol
Derg 12: 298–304.
Therapeutic Advances in Cardiovascular Disease 9(5)
Peri, G., Introna, M., Corradi, D., Iacuitti, G.,
Signorini, S., Avanzini, F. et al. (2000) PTX3, a
prototypical long pentraxin, is an early indicator of
acute myocardial infarction in humans. Circulation
102: 636–641.
Salio, M., Chimenti, S., De Angelis, N., Molla, F.,
Maina, V., Nebuloni, M. et al. (2008) Cardioprotective
function of the long pentraxin PTX3 in acute
myocardial infarction. Circulation 117: 1055–1064.
Sato, S. and Hughes, R. (1994) Regulation of
secretion and surface expression of Mac-2, a
galactoside-binding protein of macrophages. J Biol
Chem 269: 4424–4430.
Sharma, U., Pokharel, S., van Brakel, T., van Berlo,
J., Cleutjens, J., Schroen, B. et al. (2004) Galectin-3
marks activated macrophages in failure-prone
hypertrophied hearts and contributes to cardiac
dysfunction. Circulation 110: 3121–3128.
Szadkowska, I., Wlazel, R., Migala, M., Bajon-
Laskowska, K., Szadkowski, K., Zielińska, M. et al.
(2013) The association between galectin-3 and
occurrence of reinfarction early after first myocardial
infarction treated invasively. Biomarkers 18: 655–659.
Tsai, T., Sung, P., Chang, L., Sun, C., Yeh, K.,
Chung, S. et al. (2012) Value and level of galectin-3
in acute myocardial infarction patients undergoing
primary percutaneous coronary intervention.
J Atheroscler Thromb 19: 1073–1082.
Ustündağ, M., Orak, M., Güloğlu, C., Sayhan,
Visit SAGE journals online M., Alyan, O. and Kale, E. (2011) Comparative
http://tac.sagepub.com
diagnostic accuracy of serum levels of neutrophil
SAGE journals activating peptide-2 and pentraxin-3 versus troponin-I
284 http://tac.sagepub.com
in acute coronary syndrome. Anadolu Kardiyol Derg
11: 588–594.
Van Kimmenade, R., Januzzi, J., Ellinor, P., Sharma,
U., Bakker, J., Low, A. et al. (2006) Utility of amino-
terminal pro-brain natriuretic peptide, galectin-3, and
apelin for the evaluation of patients with acute heart
failure. J Am Coll Cardiol 48: 1217–1224.
Weir, R., Petrie, C., Murphy, C., Clements, S.,
Steedman, T., Miller, A. et al. (2013) Galectin-3
and cardiac function in survivors of acute myocardial
infarction. Circ Heart Fail 6: 492–498.
Yin, Q., Shi, B., Dong, L. and Bi, L. (2014)
Comparative study of galectin-3 and B-type
natriuretic peptide as biomarkers for the diagnosis of
heart failure. J Geriatr Cardiol 11: 79–82.
Xavier, D., Pais, P., Devereaux, P., Xie, C.,
Prabhakaran, D., Reddy, K. et al. (2008) Treatment
and outcomes of acute coronary syndromes in India
(CREATE): a prospective analysis of registry data.
Lancet 371: 1435–1442.
Zairis, M., Lyras, A., Bibis, G., Patsourakos, N.,
Makrygiannis, S., Kardoulas, A. et al. (2005)
Association of inflammatory biomarkers and cardiac
troponin I with multifocal activation of coronary
artery tree in the setting of non-ST-elevation acute
myocardial infarction. Atherosclerosis 182:
161–167.
Zouridakis, E., Avanzas, P., Arroyo-Espliguero,
R., Fredericks, S. and Kaski, J. (2004) Markers
of inflammation and rapid coronary artery disease
progression in patients with stable angina pectoris.
Circulation 110: 1747–1753.