parison of a treatment to a non-randomized control group. Statistics Med 1998;17:2265–2281.8. Dangas G, Mintz GS, Mehran R, Lansky AJ, Kornowski R, Pichard AD, SatlerLF, Kent KM, Stone GS, Leon MB. Preintervention arterial remodeling as anindependent predictor of target-lesion revascularization after nonstent coronaryintervention: an analysis of 777 lesions with intravascular ultrasound imaging.Circulation 1999;99:3149–3154.9. Mehran R, Dangas G, Mintz GS, Lansky AJ, Pichard AD, Satler LF, Kent KM,Stone GW, Leon MB. Atherosclerotic plaque burden and CK-MB enzymeelevation after coronary interventions: intravascular ultrasound study of 2256patients. Circulation 2000;10:604–610.10. Rao AK, Pratt C, Berke A, Jaffe A, Ockene I, Schreiber TL, Bell WR,Knatterud G, Robertson TL, Terrin ML. Thrombolysis in Myocardial Infarction(TIMI) Trial—phase I. Hemorrhagic manifestations and changes in plasma fi-brinogen and the fibrinolytic system in patients treated with recombinant tissueplasminogen activator and streptokinase. J Am Coll Cardiol 1988;11:1–11.11. Chew DP, Bhatt DL, Lincoff AM, Moliterno DJ, Brener SJ, Wolski KE,Topol EJ. Defining the optimal activated clotting time during percutaneous

coronary intervention: aggregate results from 6 randomized, controlled trials.Circulation 2001;103:961–966.12. Xiao Z, Theroux P. Platelet activation with unfractionated heparin at thera-peutic concentrations and comparisons with a low-molecular-weight heparin andwith a direct thrombin inhibitor. Circulation 1998;97:251–256.13. Knight CJ, Panesar M, Wilson DJ, Patrineli A, Chronos N, Wright C, ClarkeD, Patel D, Fox K, Goodall AH. Increased platelet responsiveness followingcoronary stenting. Heparin as a possible etiological factor in stent thrombosis.Eur Heart J 1998;19:1239–1248.14. Mascelli MA, Kleiman NS, Marciniak SJ Jr, Damaraju L, Weisman HF,Jordan RE. Therapeutic heparin concentrations augment platelet reactivity: im-plications for the pharmacologic assessment of the glycoprotein IIb/IIIa antago-nist abciximab. Am Heart J 2000;139:696–703.15. The EPILOG Investigators. Platelet glycoprotein IIb/IIIa receptor blockadeand low-dose heparin during percutaneous coronary revascularization. N EnglJ Med 1997;336:1689–1696.16. The ESPRIT Investigators. Novel dosing regimen of eptifibatide in plannedcoronary stent implantation (ESPRIT): a randomised, placebo-controlled trial.Lancet 2000;356:2037–2044.

Relation of Ischemia-Modified Albumin (IMA) LevelsFollowing Elective Angioplasty for Stable Angina

Pectoris to Duration of Balloon-InducedMyocardial Ischemia

Juan Quiles, MD, Debashis Roy, MD, David Gaze, BSc, Iris Paula Garrido, MD,Pablo Avanzas, MD, Manas Sinha, MD, and Juan Carlos Kaski, MD, DSc

The results in this study confirm and expand previousreports that ischemia-modified albumin (IMA) is anearly marker of ischemia in the setting of percutane-ous coronary intervention (PCI). We observed thatIMA levels are related to the number of inflations,inflation pressure, and duration of inflations. It istherefore likely that IMA reflects the magnitude andduration of ischemia induced during PCI. �2003 byExcerpta Medica, Inc.

(Am J Cardiol 2003;92:322–324)

Ischemia-modified albumin (IMA), as measured bythe Albumin Cobalt Binding (ACB) test (Ischemia

Technologies, Denver, Colorado), is a new marker oftransient myocardial ischemia. The ACB test mea-sures the binding capacity of exogenous cobalt to theN-terminus of human albumin. In the presence ofmyocardial ischemia, structural changes take place inthe N-terminus of albumin that rapidly reduce itsbinding capacity for transition metal ions.1,2 IMA hasbeen shown to be elevated in patients after percutane-ous coronary intervention (PCI) as a result of ischemiareperfusion injury.1,3 It is not known whether IMAlevels are correlated with the severity of myocardialischemia induced by balloon inflation during PCI. We

investigated the association between IMA levels andthe number of balloon inflations, inflation pressure,and duration of inflations in patients with coronaryartery disease who underwent elective PCI.

• • •We studied 34 patients (mean age 61 years; 25 men)

who underwent elective single-vessel PCI for the man-agement of stable angina pectoris. None of the patientshad a recent myocardial infarction, abnormal renal func-tion, stroke, transient ischemic attack, or peripheral vas-cular disease. Serum albumin measurements were withinthe normal range in all patients. The study was approvedby the local research ethics committee and all patientsgave written informed consent.

All patients received standard routine medical carebefore and after PCI and decisions regarding the num-ber of balloon inflations and the use of stents were atthe discretion of the interventional cardiologist. Bloodsamples were drawn from a femoral artery sheath 10minutes before PCI and within 5 minutes after the lastballoon inflation. Samples were frozen at �70°Cwithin 2 hours and stored until measurement. IMAwas measured by the ACB test on a Roche CobasMIRA PLUS instrument (ABX Ltd, London, UnitedKingdom). The ACB test method has been validated,as described in previous studies.1,4,5

Statistical analysis was performed with the SPSS11.0 statistical software package (SPSS Inc., Chicago,Illinois). Descriptive statistics are reported as meanand SD or percentage and interquartile range. Thevariables assessed were normally distributed. The me-dian value for the number of balloon inflations was 5,and this value was used as a cut-off point to recode thenumber of balloon inflations into a binary variable

From the Departments of Cardiological Sciences and Chemical Pa-thology, St. George’s Hospital Medical School, London, United King-dom. Drs. Quiles, Garrido, and Avanzas were supported by grantsfrom the Spanish Society of Cardiology, Madrid, Spain. Dr. Kaski’saddress is: Cardiological Sciences, St. George’s Hospital MedicalSchool, Cranmer Terrace, London SW17 0RE, United Kingdom. E-mail: jkaski@sghms.ac.uk. Manuscript received February 6, 2003;revised manuscript received and accepted April 28, 2003.

322 ©2003 by Excerpta Medica, Inc. All rights reserved. 0002-9149/03/$–see front matterThe American Journal of Cardiology Vol. 92 August 1, 2003 doi:10.1016/S0002-9149(03)00638-6

comparing 1 to 4 versus �5 inflations. The unpairedStudent’s t test was used to analyze the differencebetween means in groups; the paired t test was used toanalyze the evolving change in IMA levels (bothglobal change and changes in each group). Pearson’s2-way test was used to assess the relation between 2quantitative variables showing normal distributions inunivariate analysis.

We assessed independent predictors of post-PCIIMA levels with multiple regression analysis using thebackward method. Differences were considered to bestatistically significant if the null hypothesis could berejected with �95% confidence intervals. Intra-assayvariability for the ACB assay was calculated andreported as a percent coefficient of variation.

The study group clinical characteristics, IMA lev-els, and PCI variables are listed in Table 1. The vesseltreated was the left anterior descending coronary ar-tery in 12 patients (35%); the left circumflex in 10

patients (29%); and the right coronary artery in 12patients (35%). One or more stents were placed in 33patients (97%). PCI involved 1 to 4 balloon inflationsin 15 patients (44%) and �5 balloon inflations in 19patients (56%). Median number of balloon inflationswas 5, mean duration of inflations was 152 seconds,and mean pressure provided for inflations was 33 atm.IMA levels in all patients increased significantly afterPCI from baseline to post-PCI (59.9 to 80. 9 U/ml, p�0.0001). IMA levels were higher in patients withmore balloon inflations, higher pressure inflations, andlonger inflation duration. These 3 variables were cor-related with each other, and all 3 were correlated withincreased levels of IMA. Postprocedure IMA levelswere independent of patient age and gender, the vesseltreated, and the presence of coronary risk factors (e.g.,smoking, diabetes mellitus, hypertension, and hyper-cholesterolemia [total cholesterol �5 mmol/L]). Post-PCI IMA levels were significantly higher in patientswith �5 balloon inflations (88.8 U/ml) compared withpatients with �4 balloon inflations (70.9 U/ml) (p �0.016); no differences between IMA baseline levels

TABLE 1 Clinical Characteristics

Age (yrs) 61 � 10Men 25 (74%)Systemic hypertension 16 (47%)Smoker 13 (38%)Hypercholesterolemia (�5 mmol/L) 27 (79%)Diabetes mellitus 7 (21%)Family history of ischemic heart disease 18 (53%)Previous myocardial infarction 18 (58%)Previous angioplasty 8 (26%)Vessel treated

Left descending artery 12 (35%)Left circumflex 10 (29%)Right coronary artery 12 (35%)

Angioplasty variablesUse of stent 33 (97%)No. of inflations

�4 15 (44%)�5 19 (56%)

Duration of inflations (s) 151.6 � 101Mean pressure of inflations (atm) 32.6 � 15

IMA levels (U/ml)Before angioplasty 59.9 � 19After angioplasty 80.9 � 22

Data are expressed as mean � SD or number (percentage).

FIGURE 1. IMA values before and after PCI according to thenumber of balloon inflations.

FIGURE 2. The relation between IMA values and the duration ofthe inflations. CI � confidence interval.

FIGURE 3. The relation between IMA values and balloon inflationpressure. Abbreviation as in Figure 2.

BRIEF REPORTS 323

were found between these groups (Figure 1). We alsofound a significant correlation between IMA levelsand both inflation pressure (r � 0.4; p � 0.02) andduration of the inflations (r � 0.3; p � 0.04) (Figures2 and 3). After multivariate analysis, an increase be-tween 0.1 and 1.2 U/ml of IMA was observed for eachatmosphere of pressure used (p � 0.02); similarly,IMA increased between 0.002 and 0.15 U/ml for eachsecond of balloon inflation time (p � 0.04). The totalinterassay coefficient of variation was 4.9% to 7.5% at72.5 to 140.2 U/ml for quality control material and5.3% to 8.8% for human serum pools at 95.1 to 97.4U/ml, respectively.

• • •Previous studies have shown that IMA is an early

marker of myocardial ischemia,1,3–5 but that is doesnot increase acutely after skeletal muscle ischemia ortrauma.6 Increased levels of IMA have previouslybeen found in patients with acute chest pain andevidence of myocardial ischemia,1 and IMA was alsofound to be an early and sensitive predictor of cardiactroponin elevations in these patients.4,5 Studies byother investigators that used PCI as a model of tran-sient myocardial ischemia have also shown that IMAlevels increased very early after balloon inflation.3

This is the first study to evaluate whether IMAlevels correlate with severity of myocardial ischemia,as assessed by relation to PCI variables. We found thatthe only variables independently related to post-PCIIMA levels were balloon inflation pressure, inflationduration, and number of inflations. There is some

scatter in the correlations reported in this study, prob-ably a reflection that the duration and number ofinflations are some of the variables that may be in-volved in IMA production during PCI. Factors such asthe severity and extent of the lesion and the presenceor absence of collateral blood supply may also play arole in IMA levels. Our results suggest that IMA is notonly a marker of the occurrence of an ischemic eventbut also an indicator of the severity of ischemia.Further studies in a larger number of patients areneeded to confirm our findings and to define the roleof IMA in the clinical setting.

1. Bar-Or D, Lau E, Winkler JV. A novel assay for cobalt-albumin binding andits potential as a marker for myocardial ischemia—a preliminary report. J EmergMed 2000;19:311–315.2. Bar-Or D, Curtis G, Rao N, Bampos N, Lau E. Characterization of the Co(2�)and Ni(2�) binding amino-acid residues of the N-terminus of human albumin.An insight into the mechanism of a new assay for myocardial ischemia. EurJ Biochem 2001;268:42–47.3. Bar-Or D, Winkler JV, Vanbenthuysen K, Harris L, Lau E, Hetzel FW.Reduced albumin-cobalt binding with transient myocardial ischemia after elec-tive percutaneous transluminal coronary angioplasty: a preliminary comparison tocreatine kinase-MB, myoglobin, and troponin I. Am Heart J 2001;141:985–991.4. Wu AH, Morris DL, Fletcher DR, Apple FS, Christenson RH, Painter PC.Analysis of the Albumin Cobalt Binding (ACB) test as an adjunct to cardiactroponin I for the early detection of acute myocardial infarction. CardiovascToxicol 2001;1:147–151.5. Christenson RH, Duh SH, Sanhai WR, Wu AH, Holtman V, Painter P,Branham E, Apple FS, Murakami M, Morris DL. Characteristics of an AlbuminCobalt Binding Test for assessment of acute coronary syndrome patients: amulticenter study. Clin Chem 2001;47:464–470.6. Apple FS, Quist HE, Otto AP, Mathews WE, Murakami MM. Releasecharacteristics of cardiac biomarkers and ischemia-modified albumin as measuredby the albumin cobalt-binding test after a marathon race. Clin Chem 2002;48:1097–1100.

Comparison of Effects of a Thrombin-Based FemoralArtery Closure Device With Those of a Mechanical

Compression Device on Serum C-Reactive Protein andAmyloid A After Percutaneous Coronary Intervention

Nawsad Saleh, MD, Ann Olausson, RN, Tage Nilsson, MD, PhD,Lars-Olof Hansson, MD, PhD, and Per Tornvall, MD, PhD

The present study evaluates whether the closing pro-cedure of the femoral artery after percutaneous cor-onary intervention influences the degree of inflamma-tion related to the procedure as measured byC-reactive protein (CRP) and serum amyloid A (SAA).A thrombin-based device (Duett sealing device) wascompared with a mechanical compression device(FemoStop). �2003 by Excerpta Medica, Inc.

(Am J Cardiol 2003;92:324–327)

There has been considerable interest in the devel-opment of femoral artery closure devices, which

allow for removal of sheaths directly after catheter-ization and early ambulation compared with conven-tional closure, including manual or mechanical com-pression. Several devices deposit bovine microfibrillarcollagen together with a high-dose of bovine thrombindirectly above the femoral artery puncture site, result-ing in hemostasis.1–3 Thrombin does not only promotehemostasis but has proinflammatory activity throughstimulation of release of proinflammatory cytokines.4As a consequence, the liver synthesis of the acute-phase reactants C-reactive protein (CRP) and serumamyloid A (SAA) is increased and are released intoplasma.5

• • •We prospectively measured pre- and postproce-

From the Departments of Cardiology, Physiology and Thoracic Radi-ology, and Clinical Chemistry, Karolinska Hospital, Karolinska Insti-tute, Stockholm, Sweden. Dr. Saleh’s address is: Department of Car-diology, Karolinska Hospital, SE-171 76, Stockholm, Sweden. E-mail:nawsad.saleh@ks.se. Manuscript received January 16, 2003; re-vised manuscript received and accepted April 21, 2003.

324 ©2003 by Excerpta Medica, Inc. All rights reserved. 0002-9149/03/$–see front matterThe American Journal of Cardiology Vol. 92 August 1, 2003 doi:10.1016/S0002-9149(03)00639-8