International Journal of Cardiology 240 (2017) 25–29

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International Journal of Cardiology

journal homepage: www.elsevier.com/locate/ijcard

Serum uric acid on admission predicts in-hospital mortality in patients

with acute coronary syndrome
Marco Magnoni a, Martina Berteotti a, Ferruccio Ceriotti a, Vincenzo Mallia a, Vittoria Vergani a,
Giovanni Peretto a, Giulia Angeloni b, Nicole Cristell a, Attilio Maseri c, Domenico Cianflone a,⁎,1
a
IRCCS Ospedale San Raffaele and Università Vita-Salute San Raffaele, Milan, Italy
b
Department of Heart and Vessels, Careggi Hospital, University of Florence, Florence, Italy
c
Heart Care Foundation Onlus, Florence, Italy

a r t i c l e i n f o a b s t r a c t

Article history: Background: Despite the association between uric acid and cardiovascular disease has been known for decades,
Received 9 February 2017 the prognostic value of serum uric acid (UA) in all clinical manifestations of acute coronary syndrome (ACS),
Received in revised form 30 March 2017 namely ST-elevation myocardial infarction (STEMI), NSTEMI and unstable angina, has not been definitively
Accepted 10 April 2017 assessed.
Available online 11 April 2017
Methods: This retrospective analysis included patients from previous SPAI and FAMI studies with the aim to in-
vestigate the association between serum uric acid and major adverse cardiovascular events at 180 days from hos-
Keywords:
Acute coronary syndrome
pital admission.
Uric acid Results: 1548 patients were considered and divided in four groups, according UA concentration. Uricemia was
Biomarkers significantly associated with gender, BMI, arterial hypertension, HDL-cholesterol, triglycerides, metabolic
Prognosis syndrome and glomerular filtration rate in univariate analysis. Multivariate logistic regression indicated that
UA N 6.0 mg/dL on admission increased the risk of in-hospital mortality in overall population (OR 2.9, 95%CI
1.4–6.1; p = 0.0057) and in patients with de novo ACS (OR 3.2, 95%CI 1.5–6.8; p = 0.0033). Comparable results
were also obtained after adjusting the model for age, gender, body mass index, glomerular filtration rate,
metabolic syndrome, acute revascularization and ethnicity. A positive correlation was observed between UA
and C reactive protein concentrations in in-hospital deaths only (rho 0.41, p = 0.027).
Conclusion: In patients with acute coronary syndrome, uricemia levels above the current international reference
limit (6.0 mg/dl) were associated with in-hospital mortality, independently from ethnicity and renal function.
© 2017 Published by Elsevier Ireland Ltd.

1. Introduction
Acute coronary syndrome (ACS), a major clinical manifestation of
atherothrombosis, refers to a wide spectrum of clinical presentations in-
cluding ST-segment elevation myocardial infarction (STEMI), non-ST-
segment elevation myocardial infarction (NSTEMI) and unstable angina
[1]. Emerging evidence indicates that plaque phenotype, coronary blood
flow, endothelial dysfunction, microvascular dysfunction and inflam-
mation are pivotal mechanisms contributing to the onset of ACS [2].
Uric acid seems to be involved in many of these processes, thus contrib-
uting to atherosclerosis, plaque composition and vascular instability [3–
6]. Furthermore, uric acid may be an independent risk factor for both
cardiovascular disease [7–10] and kidney disease [10–11] and elevated
levels of uric acid predict the development of arterial hypertension [10,
12], obesity [13] and diabetes [14]. However, it is still controversial
whether uric acid is an independent predictor of cardiovascular disease
[15]. A recent retrospective study has demonstrated that elevated levels
of uric acid are an independent predictor of 1-year mortality in patients
with ACS treated with percutaneous coronary intervention in a single
site [16].
The aim of this study was to investigate the prognostic role of serum
uric acid (UA) on admission during a middle term follow up of 180 days
after hospital admission in a multi-ethnic international cohort of pa-
tients with the entire spectrum of ACS.
2. Material and methods

2.1. Study design

⁎ Corresponding author at: IRCCS Ospedale San Raffaele and Università Vita-Salute San
Raffaele, Via Olgettina 58, 20132 Milan, Italy.
E-mail address: cianflone.domenico@hsr.it (D. Cianflone).
1
This author takes responsibility for all aspects of the reliability and freedom from bias
of the data presented and their discussed interpretation.
This retrospective analysis included patients with ACS who participated at the
Stratificazione Prognostica Angina Instabile (SPAI) [17] and First Acute Myocardial Infarc-
tion (FAMI) [18] studies with available blood samples collected on admission, and appro-
priately stored for the measurement of UA concentration. The SPAI study was conducted

http://dx.doi.org/10.1016/j.ijcard.2017.04.027
0167-5273/© 2017 Published by Elsevier Ireland Ltd.
26 M. Magnoni et al. / International Journal of Cardiology 240 (2017) 25–29
from December 1997 to December 2001 and included patients with Braunwald class IIIB
unstable angina diagnosed in presence of: (1) ischaemic ECG changes during recurrent
chest pain; (2) evidence of myocardial ischaemia during exercise ECG stress test or during
exercise radionuclide studies or pharmacological echocardiographic stress tests (with ei-
ther dipyridamole or dobutamine); and (3) documentation of obstructive (N 50%) stenosis
in at least one major epicardial artery during coronary angiography [17]. Patients were
subsequently defined as NSTEMI and unstable angina according to high-sensitivity tropo-
nin levels. The FAMI study was conducted from October 2002 to April 2007 and involved
patients who had electrocardiographic evidence of STEMI, no previous history of coronary
artery disease and reported symptom onset of b6 h [18].
Patients who received allopurinol therapy, those with LVEF b 30% (STEMI) and LVEF
b 40% (NSTEMI) and undergoing urgent CABG were excluded from the current analysis.
Patients were followed by phone interview or clinical examination after 3 and 6 months
from discharge to evaluate clinical outcomes and therapies. Information about death
was obtained from hospital records, death certificates, or phone contact with relatives of
the patient or the referring physician. Written informed consent was obtained from all pa-
tients. The studies were carried out in accordance with the Declaration of Helsinki and was
approved by the institutional ethics committee (SPAI Study was approved by Ethics Com-
mittee of Università Cattolica del Sacro Cuore, Rome; approval date 22/09/1997; FAMI
Study was approved by Ethics Committee of Ospedale San Raffaele, Milan; approval date
8/11/2001).
2.2. Clinical evaluation
Each patient enrolled in the SPAI and FAMI studies underwent a physical examina-
tions and standard ECG. Reference blood pressure was measured during the stable
phase, after recovery from the acute phase or immediately before discharge. Information
about demographic factors, socioeconomic factors (income, employment, level of educa-
tion), lifestyle (physical activity during leisure and work time, dietary habits), psychoso-
cial factors, and personal and family history of cardiovascular disease and traditional risk
factors (smoking, diabetes, dyslipidaemia, hypertension) was collected in a structured
standardized questionnaire [17,18]. Height, weight, and abdominal circumference were
determined. Previous history of CHD, peripheral vascular disease and chronic renal disease
were also recorded.
Non-fasting blood samples were obtained immediately upon admission. Blood was
centrifuged, and serum and plasma samples were bar-coded and frozen at −80 °C until
assayed at a core laboratory. Lipids were measured with standard, automated laboratory
methods and serum C reactive protein was assayed by a high-sensitivity nephelometric
method (Nephelometric 100 Analyzer; Behring, Scoppito, Italy).
In the present study, for each patient with available blood samples stored in a dedicat-
ed biological bank, serum creatinine and serum uric (UA) acid were measured in a central
laboratory (Clinical Laboratory Service, IRCCS Ospedale San Raffaele, Milano), in a single
batch, by personnel unaware of patients' characteristics. UA concentrations were deter-
mined with standard, automated laboratory methods with an enzymatic colorimetric
test on a Cobas C 6000 (Roche Diagnostics, Monza Italy); the coefficient of variation was
2%, measured. Renal function was assessed through serum creatinine determination and
estimated glomerular filtration rate (eGFR) was obtained using the four-component Mod-
ified Diet Renal Disease (MDRD) formula.
3. Statistical analysis
Continuous variables were reported as mean and standard deviation
or median and interquartile range according to their distribution; com-
parison between groups were performed with ANOVA test and 2-sided
Student's t-test or Wilcoxon test and Kruskal-Wallis test, as appropriate.
Categorical variables were reported as percentage and compared with
chi-square test. A p value b 0.05 was considered statistically significant.
Univariate correlation was obtained with a Spearman Rank-Order
Correlation: Multivariate logistic regression models were used to assess
the relationship between UA and outcomes. Estimates of odds ratios
with their 95% confidence intervals were reported.
The study population was divided in four groups, per UA concentra-
tion. UA quartiles were: quartile 1 ≤ 4.2 mg/dl; quartile 2: 4.3 to
5.1 mg/dl; quartile 3: 5.2 to 6.0 and quartile 4 N 6.0 mg/dl. The primary
endpoint was mortality at 180 days from hospital admission; the num-
ber of major adverse cardiac events (MACEs) occurring within 180 days
was assessed; MACEs included death, heart failure, non-fatal stroke,
non-fatal STEMI. Recurrence of acute coronary syndrome (both STEMI
and NSTEMI) was also evaluated.
Premature ACS was defined as ACS in men aged ≤ 55 years and
women aged ≤ 65 years, following the criteria of premature ischemic
heart disease as applied to the definition of the family history for ische-
mic heart disease.
All statistical analysis and graphics were produced with JMP soft-
ware (version 11.0.0, SAS Institute Inc., Cary, North Carolina, USA).
4. Results
A total of 1548 patients with ACS from SPAI and FAMI studies were
included in the analysis. The UA concentrations ranged from 1.4 to
11.9 mg/dl and the population was divided in 4 quartiles according to
the 25th percentile (4.2 mg/dl), median (5.1 mg/dl), and 75th percentile
(6.0 mg/dl).
Baseline characteristics of each quartile group are listed in Table 1.
Supplementary Table 1 reports also pharmacological treatment at
discharged. The proportion of patients with NSTEMI/UA and STEMI
was similar among groups; de novo ACS and premature ACS also oc-
curred with similar frequency. No statistically significant differences
were observed in UA distribution between European and Chinese pa-
tients (Table 1).
The prevalence of men, patients with arterial hypertension and met-
abolic syndrome tended to be significantly higher with the increasing
quartiles of UA. BMI, Framingham Risk Score, triglycerides and serum
creatinine showed a graded increase, whereas HDL-cholesterol and
eGFR decreased according to the UA quartile.
In-hospital deaths and MACEs were assessed in the overall popula-
tion and patients suffering from de novo ACS. In both settings, a higher
proportion of in-hospital deaths was observed in quartile 4 while
MACEs frequencies were similar across groups (Table 2).
Considering UA as a categorical variable (cut off: 6.0 mg/dl, quartile
4), UA N6.0 mg/dL increased the risk of in-hospital mortality in both
overall population (OR 2.9, 95% CI 1.4–6.1, p = 0.0057) and de novo
ACS (OR 3.2, 95%CI 1.5–6.8, p = 0.0033). Multivariate logistic regression
analysis showed that the adjusted model for age, gender, eGFR classes,
and metabolic syndrome (Model 1), obtained similar results (Overall
population: OR 2.8, 95% CI 1.2–6.5, p = 0.0143; de novo ACS: OR 3.1,
95% CI 1.3–7.4, p = 0.0095). In addition to the variables considered in
the Model 1, two further variables were evaluated: revascularization
(Model 2) and revascularization and ethnicity (Model 3). In Model 2, in
the overall population OR was 2.8 (95% CI 1.2–6.4, p = 0.0187), while in
patients with de novo ACS OR was 3.0 (95% CI 1.3–7.4, p = 0.016); in
Model 3, in overall population OR was 2.7 (95%CI 1.2–6.3, p = 0.0226)
and in patients with de novo ACS OR was 3.0 (95%CI 1.3–7.3, p =
0.0127) (Table 3).
Furthermore, the correlation between UA and C-reactive protein
(CRP) levels was assessed in patients who survived at the follow up, in
patients who died during hospitalization and after hospital discharge.
UA and CRP concentrations positively correlated in in-hospital dead pa-
tients (rho 0.42, p = 0.038) only, whilst the correlation between UA and
CRP concentration was not observed in both survived patients and in
patients who died after discharge (Fig. 1).
5. Discussion
The present study describes the relationship among UA, cardiovas-
cular risk factors and outcome in a wide cohort of patients with ACS.
First, UA was significantly associated with other well-established risk
factors for cardiovascular disease, namely arterial hypertension, BMI,
HDL-cholesterol, triglycerides, the main component metabolic syn-
drome and renal function. The role of UA as independent cardiovascular
risk factor is still controversial. For decades, it has been described that
uric acid was implicated in cardiovascular disease [7–10,15,19,20].
However, even if UA per se might not represent a modifiable direct
risk factor for cardiovascular disease, it may be considered a predictive
marker for cardiovascular risk that can worsen other established risk
factors. In fact, evidence indicates that uric acid plays a role in hyperten-
sion, obesity, and diabetes [10–14].
Second, our study showed that elevated UA concentrations
(N6.0 mg/dl) on admission were associated with an increased risk of
 M. Magnoni et al. / International Journal of Cardiology 240 (2017) 25–29 27

Table 1
Baseline characteristics by quartiles of Serum Uric Acid (UA).

UA quartile (mg/dl)

1 2 3 4 p value

n = 386 n = 420 n = 359 n = 383

Demographic
Age, mean (SD), yrs 63.0 ± 11.2 63.4 ± 11.2 63.0 ± 11.4 61.4 ± 12.5 0.085
Males, no. (%) 231 (59.8) 294 (70.0) 281 (78.3) 315 (82.3) b0.0001
Ethnicity 0.52
Caucasian, no. (%) 288 (74.6) 313 (74.5) 258 (72.0) 271 (70.8)
Chinese, no. (%) 98 (25.4) 107 (25.5) 101 (28.0) 112 (29.2)
Clinical presentation 0.62
STEMI, no. (%) 231 (59.8) 263 (62.6) 219 (61.0) 246 (64.2)
NSTEMI/UA, no. (%) 155 (40.2) 157 (37.4) 140 (39.0) 137 (35.8)
De novo ACS, no. (%) 300 (77.7) 328 (78.1) 275 (76.6) 294 (76.8) 0.95
Premature ACS, no. (%) 145 (37.6) 139 (33.1) 116 (32.3) 140 (36.6) 0.34
CV risk factors
Family history of IHD, no. (%) 98 (25.4) 112 (26.7) 91 (25.4) 89 (23.2) 0.73
Arterial hypertension, no. (%) 164 (42.5) 212 (50.5) 167 (46.5) 216 (56.4) 0.001
Diabetes mellitus, no. (%) 74 (19.2) 84 (20.0) 50 (13.9) 67 (17.5) 0.13
Current smoking, no. (%) 83 (21.5) 105 (25.0) 69 (19.2) 78 (20.4) 0.57
BMI, mean (SD), kg/m2 25.7 ± 3.9 26.0 ± 3.7 26.5 ± 3.6 27.0 ± 3.9 b0.0001
Framingham risk score, mean (SD), % 13.6 ± 7.9 15.9 ± 7.9 16.2 ± 7.9 17.4 ± 7.7 b0.0001
Metabolic syndrome, no. (%) 108 (28) 150 (35.7) 136 (37.9) 172 (44.9) b0.0001
Laboratory data
Total cholesterol, mean (SD), mg/dl 212.6 ± 44.5 216.9 ± 48.3 214.8 ± 53.5 220.6 ± 49.4 0.15
LDL-Cholesterol, mean (SD), mg/dl 143.9 ± 45.2 150.0 ± 47.6 147.6 ± 55.8 150.7 ± 49.6 0.30
HDL-Cholesterol, mean (SD), mg/dl 44.2 ± 12.8 42.4 ± 11.7 41.1 ± 10.1 40.2 ± 10.5 b0.0001
Triglycerides, median (IQR), mg/dl 114.7 129.5 131.8 150.8 b0.0001
(78.8–158.4) (92.1–175.1) (95.0–183.3) (110.3–209.0)
C-Reactive protein, median (IQR), mg/l 2.7 2.8 3.4 3.3 0.20
(1.4–6.8) (1.3–6.3) (1.4–7.2) (1.6–7.5)
Serum creatinine, mean (SD), mg/dl 0.85 ± 0.22 0.97 ± 0.44 1.05 ± 0.53 1.23 ± 1.09 b0.0001
eGFR median (IQR), ml/min/173m2 96.6 85.3 78.4 70.0 b0.0001
(74.9–120.7) (66.2–108.9) (61.1–99.6) (51.3–90.5)

STEMI, ST-segment elevation myocardial infarction; NSTEMI, non-ST segment elevation myocardial infarction; UA, unstable angina; ACS, acute coronary syndrome; CV, cardiovascular;
IHD, ischemic heart disease; BMI, body mass index; SD, standard deviation; LDL, Low density lipoprotein; HDL, high density lipoprotein; IQR, interquartile range; eGFR, enhanced glomer-
ular filtration rate.

in-hospital mortality independently from age, gender, renal function,
metabolic syndrome, revascularization procedure and ethnicity. Con-
versely, no association was observed with MACEs, 180 days-mortality,
mortality and non-fatal myocardial infarction and recurrence of ACS.
It has been previously reported that in STEMI patients, who
underwent percutaneous coronary intervention, higher UA levels
(N6.5 mg/dl) were detectable in the 21.5% and were independently as-
sociated with in-hospital mortality [21]. The same group observed, in a
larger STEMI population, the association between higher UA level and
in-hospital complication but the association with mortality was lost
after adjustment for renal function and myocardial damage [22]. In an-
other single-site retrospective analysis including a large population
with STEMI, NSTEMI and unstable angina, Ndrepepa et al. showed that
every 1 mg/dl increase in UA corresponded to the adjusted risk for 1-
year mortality increase by 12% [16]. Subgroup analysis in accordance
with different clinical presentations of the entire spectrum of ACS
showed that in presence of a concentration of UA N 7.5 mg/dl the risk
for 1-year mortality was significantly increased in all types of ACS.
In a Japanese cohort of 1124 patients with acute myocardial infarc-
tion (MI), similar levels of UA (N7.5 mg/dl) resulted the best cut-off to
predict 30 days and long-term mortality, independently of Killip class
[23].
Our findings demonstrated the prognostic value of UA on mortality
in patients with ACS, but it was limited to short-term outcome only.

Table 2
Outcome distribution by quartiles of Serum Uric Acid (UA) in overall population and in patients with de novo ACS.

UA quartile (mg/dl)

Overall 1 2 3 4 p value

Overall
In-hospital death. no. (%) 29 (1.9) 5 (1.3) 6 (1.4) 4 (1.1) 14 (3.7) 0.017
180 days outcome (n 1431)
MACE no. (%) 199 (13.9) 43 (12.0) 57 (14.6) 45 (13.8) 54 (15.2) 0.62
Death no. (%) 69 (4.8) 16 (4.5) 19 (4.9) 12 (3.7) 22 (6.2) 0.47
Death/MI no. (%) 94 (6.6) 18 (5.0) 27 (6.9) 22 (6.7) 27 (7.6) 0.55
Recurrent ACS no. (%) 125 (8.7) 27 (7.5) 38 (9.7) 32 (9.8) 28 (7.9) 0.88
De novo ACS
In-hospital death no. (%) 28 (2.3) 5 (1.7) 6 (1.8) 3 (1.1) 14 (4.8) 0.015
180 days outcome (n 1088)
MACE no. (%) 119 (10.9) 29 (10.6) 33 (11.1) 21 (8.6) 36 (13.3) 0.38
Death no. (%) 47 (4.3) 11 (4.0) 11 (3.7) 7 (2.9) 18 (6.7) 0.16
Death/MI no. (%) 61 (5.6) 11 (4.0) 17 (5.7) 12 (4.9) 21 (7.8) 0.26
Recurrent ACS no. (%) 61 (5.6) 16 (5.8) 18 (6.0) 13 (5.3) 14 (5.2) 0.67

UA, serum uric acid; MACE, major adverse cardiovascular event; ACS, acute coronary syndrome; MI, myocardial infarction.
28 M. Magnoni et al. / International Journal of Cardiology 240 (2017) 25–29
Table 3
Logistic regression models for the association between UA and in-hospital mortality in overall population and in patients with de novo ACS.
Unadjusted Model 1
Overall OR (95%CI) p value OR (95%CI)
UA N 6.0 vs ≤6.0 mg/dl 2.9 (1.4–6.1) 0.0057 2.8 (1.2–6.5)
De novo ACS OR (95%CI) p value OR (95%CI)
UA N 6.0 vs ≤6.0 mg/dl 3.2 (1.5–6.8) 0.0033 3.1 (1.3–7.4)
Model 1: adjusted for age, gender, eGFR (categorical classes ≥90, 89–60 and b60 ml/min/173 m2), metabolic syndrome.
Model 2: adjusted for age, gender, eGFR, metabolic syndrome, revascularization.
Model 3: adjusted for age, gender, eGFR, metabolic syndrome, revascularization, ethnicity.
As compared to the results of previous studies, a younger age, lower UA
threshold for the upper quartile (6.0 mg/dl) and a lower incidence of
short- and mid-term mortality rates probably limited the ability of UA
to predict the long-term mortality in our study. However, for the same
reasons, the predictive value as well as the pathophysiological role of
UA in the setting of ACS is strengthened. Furthermore, unlike previous
studies, elevated UA levels and in-hospital mortality risk were signifi-
cantly associated in patients with ACS as the first clinical manifestation
of ischemic heart disease (de novo ACS), thus supporting the need to in-
clude UA in primary preventive strategies.
On the other hand, as recently demonstrated by the GISSI-
Prevenzione Trial, higher UA levels measured within 3 months of MI in
survived patients predicted long-term mortality, thus highlighting the
importance of considering UA as biomarker also for secondary prevention
[24].
Pathophysiological mechanisms involved in the increased in-
hospital mortality in patients with elevated UA levels on admission
are not completely understood. Increased UA levels enable to identify
a subgroup more prone to in-hospital adverse outcome, probably be-
cause UA reflects several complex adverse mechanisms ranging from
pre-existing relationship with other risk factors to the degree of myo-
cardial ischemia and the relative acute metabolic and inflammatory re-
sponse. Among cardiovascular risk factors, renal dysfunction is strictly
related to cardiovascular mortality and coronary disease. Kowalczyk
et al. reported that UA concentration predicted short- and long-term
mortality in patients with renal dysfunction who experienced MI and
were treated with PCI [25]. In our study, the predictive value of UA of
in-hospital mortality resulted independent from renal function classes.
Reflecting xanthine oxidase activity, UA is considered a marker of in-
creased oxidative stress and, thus, linked with several pathological pro-
cesses that may promote the worsening of adverse conditions during
myocardial ischemia, such as LDL-cholesterol oxidation and lipid perox-
idation processes [26–27], renin–angiotensin system [28], platelet [29]
and inflammatory activation [5]. Moreover, elevated UA levels contrib-
ute to impaired myocardial blood flow through more severe coronary
microvascular dysfunction [30,31].
Fig. 1. Correlation between UA and CRP concentration.
Model 2 Model 3
p value OR (95%CI) p value OR (95%CI) p value
0.0143 2.8 (1.2–6.4) 0.0187 2.7 (1.2–6.3) 0.0226
p value OR (95%CI) p value OR (95%CI) p value
0.0095 3.0 (1.3–7.4) 0.0106 3.0 (1.3–7.3) 0.0127
Previous studies reported that UA and inflammation markers were
positively correlated in apparently healthy individuals [5,32,33], in pa-
tients with ACS [16] and in patients with chronic heart failure [34].
Mechanisms underlying the role of uric acid in inflammation remain
to be clarified. However, it has been observed that uric acid induced
the release of MCP-1, IL-1β, IL-6, and TNFα [35,36]; in vitro, it promoted
vascular smooth muscle cells, favoured pro-inflammatory response, and
induced Cox-2 up-regulation and endothelial CRP production [36]. Pro-
inflammatory cytokines (TNFα, IL-1, INFγ), ROS-induced cell damages
and apoptosis activated xanthine oxidase to synthesize uric acid,
which may promote pro-inflammatory responses, independently from
its plasmatic concentration [37].
In this context, we found a positive relationship between UA and C-
reactive protein concentrations only in patients who died during the
hospitalization, whereas in the whole study population and in patients
who survived or died after the discharge a significant correlation was
not observed, likely due to the widespread and multifactorial inflamma-
tion during ACS. These findings support the hypothesis that a strictly re-
lationship between oxidative stress and inflammation during ACS may
promote enhanced pathological disorders, leading to adverse outcomes.
The study had some limitations. The follow-up duration did not
allow to assess a long-term association between UA levels and mortali-
ty. Long-term studies on ACS patients are advisable to better define a
prognostic value of UA, also within subclinical values, in patients with
ACS and concomitant cardiovascular risk factors and further clarify the
potential role of uric acid as cardiovascular risk factor. Although patients
were prospectively recruited in the original studies [17,18], the analysis
was retrospective.
More than a quarter of patients included in the analysis were Chi-
nese; therefore, our results may be independent from genetic co-
founders which may be present in more restricted or national trials
[16,23]. In addition, to obtain a more representative picture of the
real-world practice, we did not restrict the selection of patients who
only underwent PCI, as previously done [16,22], and included the entire
spectrum of ACS ranging from myocardial infarction to unstable angina.
 M. Magnoni et al. / International Journal of Cardiology 240 (2017) 25–29
Supplementary data to this article can be found online at http://dx.
doi.org/10.1016/j.ijcard.2017.04.027.
Disclosure
The authors report no relationships that could be construed as a con-
flict of interest.
Acknowledgement
We thank Elisa Sala, PhD, Independent Medical Writer, for her med-
ical editorial assistance with our report. We thank Mosè Barbaro and
Michele Raso for the technical assistance in uric acid measurement.
We thank Menarini International Operations Luxembourg S.A. for their
partial financial support by an unrestricted grant.
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