Relation Between Coronary Calcium and Major Bleeding After

Percutaneous Coronary Intervention in Acute Coronary Syndromes

(from the Acute Catheterization and Urgent Intervention Triage
Strategy and Harmonizing Outcomes With Revascularization
and Stents in Acute Myocardial Infarction Trials)
Philippe Généreux, MDa,b,c,*, Mahesh V. Madhavan, BAa, Gary S. Mintz, MDa,b, Akiko Maehara, MDa,b,
Ajay J. Kirtane, MD, SMa,b, Tullio Palmerini, MDd, Madhusudhan Tarigopula, MD, MPHb,
Tom McAndrew, MSb, Alexandra J. Lansky, MDe, Roxana Mehran, MDb,f, Sorin J. Brener, MDb,g,
and Gregg W. Stone, MDa,b

Percutaneous coronary intervention (PCI) of calcified coronary lesions has been associated
with increased rates of adverse ischemic events. However, the potential association between
the presence and severity of calcific deposits and bleeding complications has yet to be
investigated. Data from 6,855 patients with noneST-segment elevation acute coronary
syndrome (NSTEACS) or ST-segment elevation myocardial infarction (STEMI) treated
with PCI were pooled from 2 large-scale randomized controlled trials—Acute Catheteri-
zation and Urgent Intervention Triage Strategy and Harmonizing Outcomes with Revas-
cularization and Stents in Acute Myocardial Infarction. Patients were stratified into 3
groups according the grade of target PCI lesion calcium (none to mild, moderate, and
severe) as assessed by an independent angiographic core laboratory. Thirty-day bleeding
event rates were assessed and compared among groups. In the total cohort undergoing PCI,
none-to-mild target lesion calcium was found in 4,665 patients (68.1%), moderate target
lesion calcium in 1,788 patients (26.1%), and severe target lesion calcium in 402 patients
(5.9%). The 30-day rates of nonecoronary artery bypass graft surgery major bleeding
increased significantly with each degree of coronary calcium (none to mild [ 5.9%,
moderate [ 7.2%, and severe [ 11.2%, p [ 0.0003). By multivariable analysis, presence of
severe calcium was an independent predictor of nonecoronary artery bypass graft major
bleeding after PCI (hazard ratio 1.54, 95% confidence interval 1.09 to 2.17, p [ 0.01). In
conclusion, in patients undergoing PCI for noneST-segment elevation acute coronary
syndrome and ST-segment elevation myocardial infarction, target lesion coronary calcium
was an independent predictor of major bleeding events. Further studies are needed to
elucidate mechanisms underlying this finding and to optimize treatment of this high-risk
population. Ó 2014 Elsevier Inc. All rights reserved. (Am J Cardiol 2014;113:930e935)

Percutaneous coronary intervention (PCI) in heavily
calcified coronary lesions results in suboptimal acute results
with increased rates of recurrent ischemic events and mor-
tality.1e6 Coronary calcium is often associated with sys-
temic vascular calcific deposits.7 The presence of femoral
a pooled databases from the large-scale Acute Catheterization
New York-Presbyterian Hospital and Columbia University Medical
Center, New York, New York; bCardiovascular Research Foundation,
New York, New York; cHôpital du Sacré-Coeur de Montréal, Université
de Montréal, Montréal, Quebec, Canada; dIstituto di Cardiologia, University
of Bologna, Bologna, Italy; eYale School of Medicine, New Haven,
Connecticut; fMount Sinai Medical Center, New York, New York; and
g
New York Methodist Hospital, New York, New York. Manuscript received
October 9, 2013; revised manuscript received and accepted November 23,
2013.
Dr. Généreux and Mr. Madhavan contributed equally to this report.
See page 934 for disclosure information.
*Corresponding author: Tel: (646) 434-4383; fax: (646) 434-4464.
E-mail address: pg2295@columbia.edu (P. Généreux).
arterial calcium may predispose to bleeding by alteration of
mechanical properties and homeostatic capacity. Moreover,
patients with coronary calcium may have other co-morbid-
ities that increase the likelihood of bleeding. We therefore
hypothesized that the presence and severity of coronary
calcium may be associated with an increase in bleeding
events after PCI. To examine this issue, we analyzed the
and Urgent Intervention Triage Strategy (ACUITY)8 and the
Harmonizing Outcomes with Revascularization and Stents
in Acute Myocardial Infarction (HORIZONS-AMI) trials.9
Methods
The present study represents a patient-level pooled
analysis of 2 large-scale, prospective, randomized trials,
which evaluated bivalirudin as an anticoagulant in acute
coronary syndrome (ACS): the ACUITY trial in patients
with noneST-segment elevation acute coronary syndrome
(NSTEACS) and the HORIZONS-AMI trial in patients with

0002-9149/14/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. www.ajconline.org
http://dx.doi.org/10.1016/j.amjcard.2013.11.053
 Coronary Artery Disease/Coronary Artery Calcium and Bleeding 931

Table 1
Baseline characteristics stratified by the degree of target lesion calcium
Variable Quantity of Calcium Overall p Value

None/Mild (n ¼ 4,665) Moderate (n ¼ 1,788) Severe (n ¼ 402)

Age (yrs) 59.2 (51.7e69.0) 63.1 (55.0e72.0) 65.3 (55.8e74.0) <0.0001

Men 3,385/4,665 (72.6) 1,342/1,788 (75.1) 292/402 (72.6) 0.12
Diabetes mellitus 1,143/4,651 (24.6) 418/1,784 (23.4) 103/402 (25.6) 0.52
Insulin treated 324/4,651 (7.0) 114/1,784 (6.4) 35/402 (8.7) 0.25
Hypertension* 2,849/4,652 (61.2) 1,112/1,784 (62.3) 249/402 (61.9) 0.71
Hyperlipidemia† 2,452/4,630 (53.0) 934/1,780 (52.5) 201/399 (50.4) 0.60
Current smoker 1,842/4,658 (39.5) 667/1,779 (37.5) 141/401 (35.2) 0.10
Previous myocardial infarction 1,076/4,598 (23.4) 406/1,765 (23.0) 72/398 (18.1) 0.054
Previous PCI 1,440/4,652 (31.0) 493/1,782 (27.7) 93/401 (23.2) 0.0005
Previous coronary bypass 579/4,658 (12.4) 243/1,786 (13.6) 58/402 (14.4) 0.28
Previous stroke 165/2,609 (6.3) 54/804 (6.7) 11/144 (7.6) 0.78
Renal insufficiencyz 642/4,362 (14.7) 326/1,657 (19.7) 107/374 (28.6) <0.0001
Left ventricular ejection fraction (%) 62.6 (53.8e70.8) 61.3 (52.1e69.0) 59.6 (51.7e67.8) <0.0001
White blood cell count (103/L) 9.1 (7.1e11.6) 9.4 (7.4e11.8) 10.0 (7.8e12.2) <0.0001
Hemoglobin (g/dl) 14.3 (13.2e15.3) 14.2 (13.2e15.3) 14.1 (13.1e15.3) 0.33
Platelet count (103/mm3) 236 (197e282) 237 (199e279) 238 (195e286) 0.84
Biomarker positive 1,389/2,457 (56.5) 441/742 (59.4) 81/131 (61.8) 0.22
Unstable angina pectoris 1,233/4,665 (26.4) 368/1,788 (20.8) 60/402 (14.9) <0.0001
NoneST-segment elevation myocardial infarction 1,396/4,665 (29.9) 444/1,788 (24.8) 86/402 (21.4) <0.0001
STEMI 2,036/4,665 (43.6) 976/1,788 (54.6) 256/402 (63.7) <0.0001
Mehran bleeding score 11.86  7.19 13.24  7.26 14.69  7.65 <0.0001

Values are presented as mean  SD, median (interquartile range), or n/N (%).
* Hypertension is defined as taking antihypertensive medication on admission.
†
Hyperlipidemia is defined as taking lipid-lowering medication on admission.
z
Renal insufficiency is defined as creatinine clearance rate <60 ml/min by the Cockcroft-Gault equation.

ST-segment elevation myocardial infarction (STEMI). The
study designs and primary results have previously been
described in detail.8e11
In brief, ACUITY was a multicenter, prospective, ran-
domized trial of 13,819 patients with moderate- and high-
risk NSTEACS who were treated with an early invasive
strategy. Before coronary angiography, patients were
randomly assigned to heparin (unfractionated or low mo-
lecular weight) plus a glycoprotein IIb/IIIa inhibitor (GPI),
bivalirudin plus a GPI, or bivalirudin monotherapy. Angi-
ography was performed within 72 hours of randomization,
and depending on coronary anatomy, patients were triaged to
PCI, coronary artery bypass graft (CABG) surgery, or
medical therapy. In patients undergoing PCI, stent choice
(bare metal or drug eluting) was per operator discretion. Dual
antiplatelet therapy with aspirin and clopidogrel was rec-
ommended for at least 1 year. In HORIZONS-AMI, 3,602
patients with ST-segment elevation myocardial infarction
presenting within the first 12 hours of symptom onset, in
whom primary PCI was planned, were randomly assigned to
treatment with unfractionated heparin plus GPI or bivalir-
udin monotherapy. Patients were randomly assigned to either
TAXUS (Boston Scientific, Natick, Massachusetts) pacli-
taxel-eluting stents or bare-metal stents in a 3:1 ratio. Aspirin
and clopidogrel were administered before catheterization and
were continued for at least 1 year.9,11 An independent clin-
ical events committee, blinded to treatment assignment,
adjudicated all major adverse events in these 2 trials,
including major bleeding.10,11
Our primary objective was to assess the relation between
target lesion coronary calcium and the risk of major bleeding
after PCI for ACS at 30 days. The databases of the ACUITY
and HORIZONS-AMI trials were combined, and patients
were stratified in 3 groups based on the presence and severity
of target lesion coronary artery calcium (none to mild,
moderate, and severe). For the present study, we included
only patients from the PCI subgroup in whom quantitative
coronary angiography was performed by an independent core
laboratory, blinded to randomization and clinical outcomes
(Cardiovascular Research Foundation, New York, New
York).12 This comprised all patients from HORIZONS-AMI
and a prespecified subset of 6,921 patients enrolled in the formal
ACUITY angiographic substudy.13 Moderate lesion calcium
was defined in the core laboratory as radiopaque densities noted
during the cardiac cycle involving only 1 side of the vascular
wall, and severe lesion calcium was defined as radiopaque
densities noted without cardiac motion before contrast injection
generally involving both sides of the arterial wall.
As per the ACUITY and HORIZONS protocols,10,11 major
bleeding was defined as intracranial or intraocular bleeding,
access site hemorrhage requiring intervention, hematoma

5 cm in diameter, reduction in hemoglobin levels
4 g/dl
without or
3 g/dl with an overt source, reoperation for
bleeding, or any blood product transfusion. Bleeding according
to the Thrombolysis In Myocardial Infarction major and/or
minor scale was determined in both studies as well.14 We
classified major bleeding according to whether it arose from the
vascular access site.15,16 Major access site bleeding was defined
as bleeding from the access vessel that resulted in interven-
tional or surgical correction, hematoma
5 cm, retroperitoneal
bleeding, or hemoglobin drop
3 g/dl with prolonged access
site bleeding (>30 minutes), or ecchymosis or hematoma.
932 The American Journal of Cardiology (www.ajconline.org)

Table 2
Angiographic characteristics and procedural strategies stratified by the degree of target lesion coronary calcium
Variable Quantity of Calcium Overall p Value

None/Mild (n ¼ 4,665) Moderate (n ¼ 1,788) Severe (n ¼ 402)

Antithrombotic medication
Bivalirudin þ GPI 901/4,665 (19.3) 284/1,788 (15.9) 51/402 (12.7) <0.0001
Bivalirudin monotherapy 1,914/4,665 (41.0) 735/1,788 (41.1) 173/402 (43.0) 0.73
Heparin þ GPI 1,850/4,665 (39.7) 769/1,788 (43.0) 178/402 (44.3) 0.02
Intraprocedural GPI 2,751/4,665 (59.0) 1,053/1,788 (58.9) 229/402 (57.0) 0.73
Number of vessels treated 1.11  0.33 1.14  0.37 1.12  0.35 0.003
Number of lesions treated 1.31  0.67 1.40  0.75 1.38  0.86 <0.0001
Number of stents 1.31  0.74 1.50  0.89 1.53  0.96 <0.0001
Drug-eluting stent 3,660/4,609 (79.5) 1,376/1,764 (78.0) 303/380 (79.7) 0.44
Bare-metal stent 929/4,609 (20.2) 402/1,764 (22.8) 84/380 (22.1) 0.06
Baseline QCA
Lesion length (mm) 13.0 (10.0e19.0) 14.4 (10.1e21.0) 14.9 (10.0e20.0) <0.0001
RVD (mm) 2.79 (2.41e3.15) 2.80 (2.45e3.19) 2.84 (2.43e3.19) 0.08
Diameter stenosis (%) 80.2 (66.3e98.0) 81.0 (66.6e100.0) 84.3 (67.2e100.0) 0.0004
Total occlusion 1,444/5,824 (24.8) 720/2,428 (29.7) 211/550 (38.4) <0.0001
Thrombus 2,144/5,813 (36.9) 1,073/2,422 (44.3) 299/549 (54.5) <0.0001
Bifurcation present 2,218/5,829 (38.1) 1,121/2,430 (46.1) 264/550 (48.0) <0.0001
ACC/AHA classification
A/B1 2,155/5,818 (37.0) 308/2,424 (12.7) 57/549 (10.4) <0.0001
B2 985/5,818 (16.9) 459/2,424 (18.9) 89/549 (16.2) 0.07
C 2,678/5,818 (46.0) 1,657/2,424 (68.4) 403/549 (73.4) <0.0001
Discharge medications
Aspirin 4,287/4,605 (93.1) 1,635/1,742 (93.9) 370/391 (94.6) 0.33
Thienopyridine 4,211/4,607 (91.4) 1,604/1,742 (92.1) 363/391 (92.8) 0.47
Aspirin þ thienopyridine 4,074/4,605 (91.4) 1,555/1,742 (89.3) 354/391 (90.5) 0.36
30-Day medications
Aspirin 4,396/4,497 (97.8) 1,639/1,694 (96.8) 373/384 (97.1) 0.08
Thienopyridine 4,317/4,499 (96.0) 1,617/1,698 (95.2) 367/384 (95.6) 0.44
Aspirin þ thienopyridine 4,469/4,499 (99.3) 1,684/1,698 (99.2) 383/384 (99.7) 0.47

Values are presented as mean  SD, median (interquartile range), or n/N (%).
ACC/AHA ¼ American College of Cardiology/American Heart Association; QCA ¼ quantitative coronary angiography; RVD ¼ reference vessel diameter.

We also assessed for major bleeds not limited to the access
site only (i.e., noneaccess site only, both noneaccess site
and access site, and indeterminate source). Noneaccess site
was defined as intracranial, intraocular, or a reduction in
hemoglobin levels
3 g/dl with an overt noneaccess site
source (e.g., gastrointestinal or genitourinary).
The Mehran bleeding score17 was determined for each
patient using the following clinical variables and compared
among groups of calcium severity: gender, age, serum
creatinine (mg/dl), white blood cell count (109/L), anemia,
ACS clinical presentation, and antithrombotic regimen
(heparin vs bivalirudin).
All analyses were done by intention to treat. Continuous
data are presented as mean  SD and were compared using
analysis of variance. Thirty-day event rates were estimated
using Kaplan-Meier methodology and compared using the
log-rank test. Multivariable regression analysis using Cox
proportional hazard models for 30-day time points was per-
formed to assess the association between coronary calcium
and major bleeding with variable entry/stay criteria of 0.1/0.1.
Multivariable analysis included stepwise adjustment for the
following pool of variables based on clinical importance and
those that differed significantly between calcium severity
groups: severe target lesion calcium (vs none-to-mild cal-
cium), moderate target calcium (vs none-to-mild calcium),
male gender, age, randomization to heparin plus GPI versus
bivalirudin with or without GPI, diabetes, hypertension,
baseline creatinine clearance <60 ml/min, baseline hemo-
globin, and baseline platelet count. We also performed a
separate multivariable analysis with moderate and severe
target lesion calcium grouped together (vs none-to-mild cal-
cium) with the same covariates listed previously. p Values
<0.05 were considered to be statistically significant. Statis-
tical analyses were performed using SAS, version 9.2 (SAS
Institute, Cary, North Carolina).
Results
A total of 6,855 patients were treated by PCI and
analyzed by quantitative coronary angiography analysis
(3,587 with NSTEACS from ACUITY and 3,268 with
STEMI from HORIZONS-AMI), representing the study
population. In them, 4,665 patients (68.1%) had none-to-
mild target lesion calcium, 1,788 (26.1%) had moderate
target lesion calcium, and 402 (5.9%) had severe target
lesion calcium.
Baseline clinical, angiographic, and procedural charac-
teristics, stratified by the degree of target lesion calcium, are
presented in Tables 1 and 2. Patients with more severely
calcified lesions were older, more likely to have renal
 Coronary Artery Disease/Coronary Artery Calcium and Bleeding 933

Table 3
Thirty-day major bleeding event rates stratified by degree of coronary calcium
Variable (A) None/Mild (B) Moderate (C) Severe Overall (A vs B) (A vs C) (B vs C)
(n ¼ 4,665) (n ¼ 1,788) (n ¼ 402) p Value p Value p Value p Value

Major bleeding (non-CABG) 273 (5.9) 128 (7.2) 43 (11.2) 0.0003 0.05 0.0001 0.02
Retroperitoneal bleed 34 (0.7) 14 (0.8) 1 (0.7) 0.51 0.81 0.27 0.25
Access site hemorrhage 19 (0.4) 5 (0.3) 3 (0.8) 0.39 0.46 0.32 0.16
Puncture site hematoma
5 cm 86 (1.8) 37 (2.1) 7 (1.8) 0.80 0.54 0.88 0.67
Hemoglobin drop
4 g/dl without overt source 82 (1.8) 50 (2.8) 16 (4.0) 0.001 0.008 0.002 0.21
Hemoglobin drop
3 g/dl with overt source 88 (1.9) 41 (2.3) 16 (4.0) 0.02 0.28 0.004 0.06
Any blood product transfusion 136 (2.9) 62 (3.5) 24 (6.5) 0.003 0.23 0.0007 0.02
Major access site bleeding only 121 (2.6) 50 (2.8) 10 (2.9) 0.87 0.63 0.90 0.73
Major bleeding not limited to access site 194 (4.2) 96 (5.4) 35 (9.2) <0.0001 0.03 <0.001 0.01
Major noneaccess site bleeding only 11 (0.2) 5 (0.3) 4 (1.0) 0.03 0.75 0.007 0.04
TIMI major/minor bleeding 280 (6.0) 135 (7.6) 40 (10.0) 0.002 0.02 0.002 0.12
TIMI major bleeding 84 (1.8) 50 (2.8) 13 (3.3) 0.01 0.01 0.04 0.65
TIMI minor bleeding 233 (5.0) 101 (5.7) 34 (8.5) 0.01 0.27 0.003 0.04

Event rates shown are Kaplan-Meier estimates presented as n (%).

Table 4
Independent predictors of 30-day major bleeding
Variable Hazard Ratio (95% CI) p Value

Severe calcium (vs none/mild) 1.54 (1.09e2.17) 0.01

Moderate calcium (vs none/mild) 1.15 (0.92e1.44) 0.22
Renal insufficiency* 1.75 (1.35e2.27) <0.0001
Male sex 0.55 (0.44e0.68) <0.0001
Diabetes mellitus 1.39 (1.12e1.72) 0.003
Randomization to heparin þ GPI 1.30 (1.07e1.58) 0.01
Age 1.01 (1.00e1.02) 0.01

CI ¼ confidence interval.
* Renal insufficiency is defined as a calculated creatinine clearance rate
of <60 ml/min determined by the Cockcroft-Gault equation.

444 patients (6.5%), and was strongly associated with target

Figure 1. Kaplan-Meier curves showing non-CABG major bleeding event
rates through 30 days. Comparison of the non-CABG major bleeding events
at 30 days stratified by none-to-mildly, moderately, and severely calcified
target lesions.
insufficiency, lower left ventricular ejection fraction, and
higher baseline white blood cell counts compared with those
with none-to-mild calcium. They were also more likely to
have STEMI than non-STEMI or unstable angina at initial
clinical presentation. Not surprisingly, severe target lesion
calcium was also associated with more complex lesion
characteristics as summarized in Table 2. Patients with greater
degrees of coronary calcium were slightly less likely to have
received bivalirudin plus a GPI as procedural anticoagulation,
although rates of bivalirudin monotherapy and other antico-
agulants were similar among the groups, as was use of
discharge and 30-day antiplatelet agents. The calculated
Mehran bleeding score increased with the extent of calcium.
Rates of 30-day major bleeding end points stratified by
degree of coronary calcium are presented in Table 3 and
Figure 1. Major bleeding not related to CABG developed in
lesion calcium. Thrombolysis In Myocardial Infarction
major and minor bleeding were also associated with the
degree of target lesion calcium. Patients in the severely
calcified lesion group required transfusions more frequently
than those in the moderate and none-to-mild calcium groups
(6.5% vs 3.5% vs 2.9% respectively, p ¼ 0.003). Specif-
ically, however, the relation between major bleeding and
target lesion calcium was explained by an increase in bleeds
not limited to the access site and noneaccess site bleeding
but not access siteerelated bleeding with more severe cor-
onary calcium (Table 3).
By multivariable analysis, severe target lesion calcium
was an independent predictor of protocol-defined non-
CABG major bleeding (Table 4). When entered into the
multivariate model together as a single variable, moderate
and/or severe calcium remained a significant predictor of
non-CABG major bleeding (hazard ratio 1.24, 95% confi-
dence interval 1.02 to 1.52, p ¼ 0.03).
Discussion
The present study, drawn from a pooled cohort of 6,855
patients with ACS from the ACUITY and HORIZONS-AMI
clinical trials, is the first to demonstrate that target lesion
coronary calcium has a strong association with major bleeding
934 The American Journal of Cardiology (www.ajconline.org)
after PCI. The main findings of the present study are as fol-
lows: (1) the 30-day rates of non-CABG major bleeding after
PCI increased in a stepwise fashion with the degree of target
lesion coronary calcific deposits, (2) bleeds not limited to the
access site after PCI were significantly associated with the
extent and severity of calcium, whereas access site bleeding
was not, and (3) severe target lesion coronary calcium was a
significant independent predictor of major bleeding events
after PCI.
Several mechanisms may underlie the association between
more severe target lesion coronary calcium and greater major
bleeding events after PCI. First, calcific deposits within the
intima-media space may predispose to bleeding by weak-
ening the vessel wall, increasing vascular stiffness, and
decreasing vessel elasticity.18e21 Although the pathogenesis
of vessel calcium remains to be fully elucidated, systemic
inflammation leading to repetitive plaque rupture followed by
subsequent healing has been implicated.22,23 This hypothesis
is supported by the elevated white blood cell counts in the
more severely calcified groups, a factor that has previously
been demonstrated to be independently associated with the
occurrence of bleeding after PCI for ACS.24 Second, infil-
tration of calcium into the vessel wall may impair the biologic
and mechanical hemostatic capacity of the vessel, thus
limiting its ability to appropriately respond to trauma (e.g.,
sheath placement and removal).21 Third, the well-known
relationship between severe target lesion calcium and pro-
cedural complexity ischemic complications1,2,5,18,25 may
compel operators to adjust their procedural strategies,
including use of more potent antithrombotic regimens, which
may increase the risk for intra- or postprocedural bleeding.26
Similarly, by increasing the complexity and technical diffi-
culty of intervention, coronary calcium also may have
increased the likelihood for iatrogenic hemorrhagic events.
Finally, the presence of coronary calcium is associated with
shared risk factors that predispose to bleeding events. Indeed,
advanced age and renal insufficiency are associated with the
presence of medial artery calcium,18 and have been previ-
ously identified as independent predictors of major bleeding
in patients with ACS.17,27 This concept is further supported
by the observation from our study that the Mehran bleeding
score increased with the degree of coronary calcium.
In the present study, the severity of target lesion coronary
calcium was more strongly associated with major bleeding
not limited to the access site (including noneaccess site
bleeding) than with access siteerelated bleeding. Although
perhaps surprising, this finding emphasizes the common
etiologic pathways leading to more extensive and severe
atherosclerosis, adverse ischemic outcomes, and systemic
bleeding propensity. This is potentially important because
noneaccess site bleeding has been shown to have a more
profound effect on mortality than access site bleeds.16,28 As
it has been suggested that safer and more appropriate anti-
coagulation regimens may help to reduce rates of bleeding
complications,16,29 such measures may be particularly
important in patients with extensive coronary calcium. Our
study cannot distinguish, however, the extent to which
bleeding complications contribute to the poor prognosis of
patients with coronary calcific deposits.
This report has limitations, which should be mentioned.
As an observational post hoc analysis, the present analysis
can only identify correlations and not prove causality.
Despite adjustment for potential confounders, unmeasured
variables may not have been fully controlled. These find-
ings, therefore, should be considered hypothesis generating.
Although the pooled sample of 6,855 patients allows a well-
powered study across the spectrum of patients with
NSTEACS and STEMI, the results of this study do not
necessarily apply to patients with stable coronary disease
undergoing PCI. Finally, as target lesion coronary calcium
was assessed by a core laboratory, interobserver variability
may influence reproducibility of findings.30
Disclosures
Drs. Généreux and Palmerini have received speaker fees
from Abbott Vascular (Santa Clara, California). Mr. Madhavan
was supported by a grant from the Doris Duke Charitable
Foundation to Columbia University to fund a clinical research
fellowship. Dr. Mehran has received research grants from
Sanofi-Aventis (Bridgewater, New Jersey), The Medicines
Company (Parsipanny, New Jersey), Abbott Vascular, Boston
Scientific (Natick, Massachusetts), Bristol-Myers Squibb
(New York, New York), AstraZeneca (Wilmington, North
Carolina), and has served as consultant/advisory board for Eli
Lilly (Indianapolis, Indiana) and Daiichi Sankyo (Ch uo,
Tokyo). Dr. Stone has served as consultant for Boston Scien-
tific and Cardiovascular Systems, Inc (St. Paul, Minnesota).
The other authors report no disclosures.
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