ORIGINAL ARTICLE

Age- and gender-specific differences in the prognosticvalue of CT coronary angiography

Kai Hang Yiu,1,2 Fleur R de Graaf,1 Joanne D Schuijf,1 Jacob M van Werkhoven,1,2

Nina Ajmone Marsan,1 Caroline E Veltman,1 Albert de Roos,3 Aju Pazhenkottil,4

Lucia J Kroft,3 Eric Boersma,5 Bernhard Herzog,4 Melissa Leung,6 Erica Maffei,7

Dominic Y Leung,6 Philipp A Kaufmann,4,8 Filippo Cademartiri,7 Jeroen J Bax,1

J Wouter Jukema1,2

ABSTRACTObjective To evaluate the potential age- and gender-specific differences in the incidence and prognostic valueof coronary artery disease (CAD) in patients undergoingCT coronary angiography (CTA).Design and patients In this multicentre prospectiveregistry study, 2432 patients (mean age 57612, 56%male) underwent CTA for suspected CAD. Patients werestratified into four groups according to age <60 or$60 years and, male or female gender.Main outcome measures A composite end point ofcardiac death and non-fatal myocardial infarction.Results CTA results were normal in 991 (41%) patients,showed non-significant CAD in 761 (31%) patients andsignificant CAD in the remaining 680 (28%) patients.During follow-up (median 819 days, 25e75th centile482e1142) a cardiovascular event occurred in 59 (2.4%)patients. The annualised event rate was 1.1% in the totalpopulation (men¼1.3% and women¼0.9%). In patientsaged <60 years, the annualised event rate of male andfemale patients was 0.6% and 0.5%, respectively. Amongpatients aged $60 years the annualised event rate was1.9% in male and 1.1% in female patients. Observations onCTA predicted events in male patients, both age <60 and$60 years and in female patients age $60 years (log-rank test in all groups, p<0.01). However, CTA providedlimited prognostic value in female patients aged<60 years(log-rank test, p¼0.45).Conclusions After age and gender stratification,CTA findings were shown to be of limited predictive valuein female patients aged<60 years as compared with malepatients at any age and female patients aged $60 years.

INTRODUCTIONCoronary artery disease (CAD) is the leading causeof mortality both in men and women. However, theincidence of obstructive CAD differs betweengenders; in premenopausal women, the incidence ofobstructive CAD appears to be approximately one-third that of age-matched men.1 With increasing agethis difference tends to diminish with similar inci-dences of obstructive CAD in men and women aged$75 years.1 Similar findings have been reported forthe extent of coronary plaque burden using bothinvasive and non-invasive imaging modalities.2 3

CT coronary angiography (CTA) is an emergingnon-invasive tool for detecting obstructive CAD

with high diagnostic accuracy.4 In addition to thedetection of obstructive coronary artery stenosis,however, the techniques allows non-invasive visu-alisation of non-obstructive CAD and plaquecomposition and significant coronary arterystenosis.5 6 Moreover, studies have shown thatCTA can provide important prognostic informationand risk stratification in patients with suspectedCAD.7e9 However, these studies have mainlyfocused on the general population and limited dataare available for gender-specific differences.Recently, Shaw et al showed, using 16-slice CTA,

that evaluation of CAD on CTA added incrementalvalue to clinical assessment for risk stratificationboth in men and women.3 Interestingly, the extentof non-obstructive CAD detected by CTA predictedmortality in women but not in men. However, theeffect of age was not taken into account in thisparticular study. Given the fact that differences incoronary atherosclerosis between genders are highlyage-dependent, it is conceivable that age maysubstantially influence the predictive value of CTAin women as compared with men. Therefore theaim of this study was to evaluate the potential age-and gender-specific differences of CAD incidenceand the prognostic value in patients undergoingCTA. Accordingly, the frequency of CAD and thepredictive value for cardiovascular (CVS) events byCTA was investigated in four subpopulationsstratified according to gender (male or female) andage (aged <60 or $60 years).

METHODSStudy populationThe study population consisted of 2474 patientswho underwent CTA for suspected CAD. Patientswere consecutively enrolled as part of an ongoingregistry assessing the predictive value of CTA forCVS events retrospectively at (1) the University ofZurich, Switzerland; (2) the Leiden UniversityMedical Center, The Netherlands; (3) AziendaOspedaliero-Universitaria, Parma, Italy and (4)Liverpool Hospital, University of New South Wales,Liverpool, New South Wales, Australia. Exclusioncriteria included cardiac arrhythmias, renal insuffi-ciency (defined as a glomerular filtration rate<30 ml/min/1.73 m2), known hypersensitivity toiodine contrast media, pregnancy, previous percu-taneous coronary intervention and myocardial

1Department of Cardiology,Leiden University MedicalCenter, Leiden, The Netherlands2The Interuniversity CardiologyInstitute of the Netherlands,Utrecht, The Netherlands3Department of Radiology,Leiden University MedicalCenter, Leiden, The Netherlands4Department of Cardiology,University Hospital Zurich,Zurich, Switzerland5Department of Cardiology,Erasmus Medical Center,Rotterdam, The Netherlands6Department of Cardiology,Liverpool Hospital, University ofNew South Wales, Sydney,Australia7Department of Radiology andCardiology, AziendaOspedaliero-Universitaria,Parma, Italy8Zurich Integrative HumanPhysiology, University of Zurich,Zurich, Switzerland

Correspondence toDr J Wouter Jukema,Department of Cardiology,Leiden University MedicalCenter, Albinusdreef 2, 2333 ZALeiden, The Netherlands;j.w.jukema@lumc.nl

Accepted 9 August 2011Published Online First13 September 2011

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infarction. Moreover, a total of 42 uninterpretable scans wereexcluded from the analysis (33 owing to motion artefact/poorscan quality, eight owing to high coronary calcification leadingto blooming artefact and one owing to non-diagnostic CTAstent image quality). Accordingly, 2432 patients were includedin the final analysis. The pre-test likelihood of obstructive CADwas evaluated using Diamond and Forrester ’s criteria.10 Patientswere entered prospectively into the departmental patientinformation system and retrospectively analysed. This studywas approved by the local ethics committees in all participatingcentres and all patients provided informed consent.

CT coronary angiography protocolExaminations were performed using one of the following scanners:(1) 320-row CTA scanner (Aquilion ONE, Toshiba MedicalSystems, Otawara, Japan) in 97 (4%) patients; (2) 64-row CTAscanner (Lightspeed VR 64, General Electrics (GE), Milwaukee,Michigan, USA or Aquillion64, Toshiba Medical Systems, TokyoJapan or Sensation64, Siemens, Forchheim, Germany) in 2335(96%) patients. Patients’ heart rate and blood pressure weremonitored before each CTA scan. In the absence of contraindica-tions, 44% patients with a heart rate >65 beats/min were givenb-blocking drugs (50e100 mg metoprolol, orally or 5e10 mgmetoprolol, intravenously) for heart rate optimisation. A descrip-tion of all scan parameters has been published previously.6 11e13

In brief, all images were acquired during a single inspiratory breath-hold of maximally 12 s. For 320-row CTA, the ECG was registeredsimultaneously for prospective triggering of the data.6 The entireheart was imaged in a single heart beat and maximal tube currentwas attained during 75% of the R-R interval in patients with stableheart rate <60 beats per minute (bpm), during 65e85% of the R-Rinterval in patients with a heart rate 60e65 bpm or during30e80% of the R-R interval in patients with a heart rate>65 bpm.In addition, a collimation of 32030.5 mm was used. Additionalscan parameters were as follows: 350 ms gantry rotation time,120e135 kV tube voltage and 400e580 mA (depending on bodymass index and thoracic geometry). For 64-row CTA, a helical-scanning technique was used as previously described, usinga collimation of 6430.5 mm.11e14 Specifically, retrospective gatingof the data was registered by simultaneous ECGmonitoring. Whenprospective triggering was performed, a small acquisition windowduring mid-diastolic phase of the R-R cycle was used (ie, 70e80%in the case of low heart rate).14 Retrospective gating of the datawas registered by the simultaneous ECG monitoring, and a colli-mation of 6430.5 mm was used. Additional scan parameters were400 ms or 500 ms gantry rotation time depending on the cardiacfrequency, 120 kV tube voltage and 300e350 mA (depending onbody mass index and thoracic geometry).

The estimated mean radiation dose for retrospective gatingwith 64-slice CT is 18.0 mSv (range 6.8e45.5 mSv).15 Forprospective triggering with 64-slice CTA the estimated meanradiation dose is 2.1 mSv (range 1.1e3.0 mSv).14 For prospectivetriggering using 320-row CTA, the estimated mean radiationdose is 3.9 mSv (range 2.7e26.2 mSv).6

Data analysisPost-processing of the CTA was performed on dedicated work-stations (Vitrea2, Vital Images, Minneapolis, Minnesota, USA orAdvantage, GE Healthcare, Waukesha, Wisconsin, USA or SyngoInSpace4D Application, Siemens, Munich, Germany orAquarius, TeraRecon, San Mateo, California, USA). Coronaryanatomy was assessed using a standardised method by dividingthe coronary arteries into 17 segments according to the modifiedAmerican Heart Association classification.16 CTA results were

defined as normal CTA (no identifiable plaque or minimal wallirregularities), non-obstructive CAD (<50% luminal narrowing),or obstructive CAD ($50% luminal narrowing).

Follow-up of patientsFollow-up data were collected by clinical visits or standardisedtelephone interviews with each patient or his or her directrelative, or with the referring doctor to discuss symptoms, theoccurrence of new events or change in clinical status, and anyhospital admission. A composite of CVS end point was definedas non-fatal myocardial infarction, and cardiac death (congestiveheart failure, fatal myocardial infarction or sudden cardiacdeath). Non-fatal myocardial infarction was defined based oncriteria of typical angina, elevated cardiac enzyme levels andtypical changes on the ECG.17

Statistical analysisContinuous variables are presented as mean6SD and comparedusing either the Student t test or Wilcoxon’s rank-sum test, asappropriate. Categorical data are presented as frequencies andpercentages and compared using the c2 or the Fisher exact test ifat least one cell had an expected cell count <5. KaplaneMeiercurves were constructed and the outcomes of CTA results indifferent patient subgroups were compared using the log-ranktest. All statistical analyses were performed using the statisticalpackage SPSS for windows (V.15.0, SPSS). A p value <0.05 wasconsidered to be statistically significant.

RESULTSBaseline clinical characteristicsThe study population consisted of 2432 patients presentingwith suspected CAD at the University of Zurich (n¼391),Leiden University Medical Center (n¼758), Azienda Ospeda-liero-Universitaria di Parma (n¼1169) and Liverpool Hospital(n¼114). The baseline characteristics of the patient populationare shown in table 1. The average age of all patients was56.5612.4 years and 56% of them were male. Comparingbetween genders, male patients were more likely to havea higher incidence of diabetes and smoking history while femalepatients were likely to be older, have a higher incidence ofhypertension and family history of CAD. A total of 2097 (86%)were referred for CTA owing to the presence of symptoms whilethe remaining 335 (14%) patients were asymptomatic. For bothmale and female patients, the majority presented with anintermediate pre-test likelihood while female patients hada slightly higher frequency of low pre-test likelihood.

CT coronary angiography resultsFor the whole study population, 991 (41%) patients hada normal CTA, 761 (31%) had non-obstructive CAD and 680(28%) had obstructive CAD. Male patients had a higher inci-dence of obstructive CAD (34% vs 21%, p<0.01) and femalepatients had a higher incidence of normal CTA results (49% vs34%, p<0.01) as shown in figure 1. The CTA results of the foursubgroups stratified according to age and gender are shown infigure 2. Male patients aged $60 years had more extensive CADwith nearly half of patients having obstructive CAD and lessthan 20% of patients having a normal CTA. On the other hand,two-thirds of female patients aged <60 years had a normal CTAresult while only 11% had obstructive CAD.

Follow-up resultsThe median follow-up was 8196335 (25the75th centile482e1142) days. A CVS event occurred in 59 patients (2.4%)

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including non-fatal myocardial infarction in 34 cases and CVSmortality in 25 cases. No difference in the occurrence of thecomposite end point was noted between male (aged <60¼10events, aged $60¼28 events) and female (aged <60¼5 events,aged $60¼16 events) patients (38 events (2.8%) vs 21 events(2.0%), p¼0.23).

Event ratesThe annualised event rate was 1.1% in the total population(men¼1.3% and women¼0.9%). In patients aged <60 years, theannualised event rate of male and female patients was 0.6% and0.5%, respectively. Among patients aged $60 years an annual-ised event rate of 1.9% was observed in male and 1.1% in femalepatients.

Predictive value of CT coronary angiography resultsin different age and gender subgroupsThe KaplaneMeier survival curves comparing CTA results inmen and women are shown in figure 3. In male patients,annualised event rates were 0.07%, 0.8% and 2.9% in the pres-ence of a normal CTA, non-obstructive CAD and obstructiveCAD, respectively. For women, these values were 0.2%, 1.2%and 2.1%, respectively. CTA findings were predictive of thecomposite end point for both male and female patients (log-ranktest p<0.01 for both analyses). In addition, the presence of non-obstructive or obstructive CAD was predictive of the compositeend point in both male (log-rank test p¼0.03 and p<0.01,respectively) and female (log-rank test p<0.01 for both analyses)patients compared with normal CTA. Both male and femalepatients were further divided into two age groups (aged<60 years or $60 years) and the corresponding KaplaneMeiersurvival curves are shown in figure 4.

In male patients aged <60 years, the annualised event rates inthe presence of normal CTA, non-obstructive CAD andobstructive CAD were 0.1%, 0.4% and 6.3%, respectively.Among male patients aged $60 years, annualised event rates

increased from 0% for normal coronary arteries to 1.1% inthe presence of non-obstructive CAD to 3.2% in the presenceof obstructive CAD. In male patients aged <60 years or$60 years, the predictive role of CTA was significant (log-ranktest p<0.01, p<0.01 for both groups). When compared withnormal CTA, the presence of obstructive CAD was significantlypredictive of the composite end point at both age groups(aged <60 years or $60 years) (log-rank test p<0.01, p<0.01respectively). In contrast, non-obstructive CAD was notpredictive of CVS events (log-rank test p¼0.35 and p¼0.11,respectively).In female patients aged <60 years, the annualised event rates

in the presence of normal CTA, non-obstructive CAD andobstructive CAD were 0.3%, 0.9% and 0.7%, respectively.Among female patients aged $60 years, annualised event ratesincreased from 0% for normal coronary arteries to 1.4% in thepresence of non-obstructive CAD to 2.4% in the presence ofobstructive CAD. In female patients aged $60 years, CTAresults were predictive of CVS events (log-rank test p<0.01).Moreover, both non-obstructive and obstructive CAD werepredictive of the composite end point when compared withnormal CTA (log-rank test p<0.01 and p<0.01, respectively).Interestingly, in female patients aged <60 years, the role of CTAin predicting CVS events was not significant (log-rank testp¼0.45). Further analysis showed that neither the presence ofnon-obstructive nor obstructive CAD was predictive of CVSevents in comparison with normal CTA (log-rank test p¼0.25and p¼0.35, respectively).

DISCUSSIONThis study is one of the first to evaluate gender-specific differ-ences in the incidence of CAD on CTA as well as in thepredictive role of CTA for CVS events with respect to age. Afterage stratification (<60 years or $60 years), observations on CTAremained predictive for CVS events in male patients regardless

Table 1 Clinical characteristics of study population

Characteristics All (n[2432) Male (n[1139) Female (n[958) p Value

Age (years) 56.5612.4 58.5612.4 61.0612.3 <0.01

Risk factors

Diabetes (%) 466 (19.2) 292 (21.4) 174 (16.3) <0.01

Hypertension (%) 1091 (44.9) 724 (53.1) 617 (57.8) 0.02

Hypercholesterolaemia (%) 1009 (41.5) 542 (39.7) 467 (43.7) 0.05

Family history of CAD (%) 1060 (43.6) 537 (39.4) 523 (49.0) <0.01

Current smoking (%) 637 (26.2) 439 (32.2) 198 (18.5) <0.01

Obesity BMI >30 kg/m2 (%) 473 (19.4) 256 (19.4) 217 (20.3) 0.35

Pre-test likelihood (n¼2097)

Low (%) 323 (15.4) 84 (7.4) 239 (24.9) <0.01

Intermediate (%) 1412 (67.3) 853 (74.9) 559 (58.4) <0.01

High (%) 362 (17.3) 202 (17.7) 160 (16.7) 0.29

BMI, body mass index; CAD, coronary artery disease.

Figure 1 Results of CT coronaryangiography (CTA) in (A) male and (B)female patients. CAD, coronary arterydisease.

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of age. Similarly, CTA was a strong predictor of CVS events infemale patients aged $60 years. In contrast, however, CTAprovided limited prognostic value in female patients aged<60 years.

Prevalence of CAD between genders in relation to ageIn concordance with previous studies, this investigation showedthat in patients referred for CTA, male patients had a substan-tially higher prevalence of obstructive CAD than femalepatients.3 18 19 Interestingly, male patients in our cohort werelikely to have a higher prevalence of diabetes mellitus andsmoking history, but were younger and with a lower prevalenceof hypertension as compared to female patients. Indeed, a recentstudy by Faletra and colleagues showed that male gender, olderage, diabetes and hypercholesterolaemia independently predictedthe presence of coronary artery plaque in 920 patients withouta previous history of CAD.20 Therefore, the clustering of severalCVS risk factors in male patients may further contribute toa higher prevalence of obstructive CAD as observed in ourcohort. Female patients aged <60 years had a lower overallprevalence of both non-obstructive and obstructive CAD thanmale patients. In elderly patients (aged $60 years), however, therate of non-obstructive CAD became similar between genders,although the rate of obstructive CAD remained higher in malepatients as compared with female patients. These observationsare in line with previous literature examining age and genderdifferences in CAD.21e24 Indeed, several pathological and imagingstudies have confirmed that in women an initial lag of approxi-mately 10 years in the development of CAD is present.2 21

Potentially, this delay in CAD development might be attributedto the protective effect of premenopausal female hormone as thedifference in CAD prevalence between genders tends to disappearat the start of the sixth decade.25

Prognostic value of CTA between gendersIn addition to providing an accurate diagnosis for CAD, recentstudies have demonstrated that CTA has independent prog-nostic value for CVS events in patients with suspected CAD.7e9

A recent meta-analysis with 9592 patients who underwent CTAdemonstrated that future CVS events increase with increasingseverity of CAD. In accordance with this, our study alsodemonstrated the prognostic value of CTA in male and femalepatients.26

Shaw et al demonstrated that the presence of obstructiveCAD had significant predictive value for future CVS events inboth genders.3 In addition, the presence of non-obstructive CADwas only predictive for future CVS events in female patients butnot in male patients. In concordance with their findings, this

Figure 2 Results of CT coronaryangiography (CTA) for the detection ofnon-obstructive and obstructivecoronary artery disease (CAD) in foursubgroups of patients: (A) man aged<60 years; (B) man aged $60 years;(C) woman aged <60 years; (D)woman aged $60 years.

Figure 3 Composite endpoint-free survival in patients with differentgender according to CT coronary angiography (CTA) results. (A)KaplaneMeier curves for composite end point in male patients with normalCTA, non-obstructive coronary artery disease (CAD) and obstructive CAD.(B) KaplaneMeier curves for composite end point in female patients withnormal CTA, non-obstructive CAD and obstructive CAD.

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investigation demonstrated that the presence of obstructiveCAD had significant prognostic value for both genders. Incontrast to their study, our study showed that non-obstructiveCAD was predictive for future CVS events in female patientsand also in male patients. Conceivably, non-obstructive plaquemay play a more important role in female patients, whereas itspredictive value may be less in male patients. Accordingly, thediscrepancy between the study by Shaw et al and ours may beexplained by the larger number of patients enrolled in our study.As compared with female patients, male patients had a largerseparation of survival curves between non-obstructive andobstructive CAD in comparison with normal CTA. This obser-vation could be partially explained by the altered coronaryreactivity that frequently occurred in women.27 In addition,a recent study by Pepine et al showed that coronary microvas-cular reactivity to adenosine provided prognostic value overangiographic CAD severity in female patients.28 Nevertheless,the underlying mechanism of non-obstructive CAD leading tomore adverse outcome in female patients than in male patientswith non-obstructive CAD will require further study.

In concordance with data from the National Institutes ofHealth, National Heart, Lung and Blood Institute, a lowannualised CVS event rate was seen in female patients aged<60 years in comparison with male patients with similar age.29

The low incidence of CVS events seen in young female patientsaged <60 years may partly be attributed by the protectivefemale sex hormone profile in the premenopausal state.30 31

Indeed, there is a paucity of data evaluating the age-specificprognostic role of CTA in male and female patients. Accordingly,patients in this cohort were stratified according to age(<60 years or $60 years old) to evaluate the impact of age onthe prognostic role of CTA between genders. For male patientsaged <60 years or $60 years, the presence of obstructive CAD

was significantly predictive for future CVS events. In femalepatients aged $60 years, the presence of non-obstructive CADwas shown to have a significant prognostic role in addition toobstructive CAD. Conversely, the prognostic value for CVSevents by CTA was limited in female patients aged <60 years.Possibly, other CVS factors, such as diabetes may have greaterprognostic impact in female patients than the presence of CADalone.32 Accordingly, while CTA may be a valuable technique torule out CAD and avoid unnecessary invasive coronary angiog-raphy, its prognostic value appears to be limited in womenaged <60 years.

LimitationsThe results of CTA were only evaluated visually, although thereis a lack of accurate and consensual quantitative algorithms.Patients with established CAD including previous myocardialinfarction or percutaneous coronary intervention were excluded.Moreover, only patient-basis data was recorded and thereforeanalysis of individual segments and location of disease was notavailable in this study. The overall events rate was low in thisstudy, which may be related to the use of only hard clinical endpoints (non-fatal myocardial infarction and CVS deaths) anda significant number of patients with low pre-test likelihood.Despite the incremental prognostic value of CTA, in particularthe high negative predictive value of normal CTA, a recent studyhas shown that the CVS events rate remains low even inpatients with positive CTA results.26 Nevertheless, the use ofCTA may identify those with negative CTA results who requireno further testing and those with extensive disease who requireimmediate referral and treatment. The ongoing SPARC trial,a prospective, multicentre, observational registry, aims to eval-uate the prognostic value and post-test resource use of multipleimaging modalities, including CTA.33 On the other hand, the

Figure 4 Composite endpoint-freesurvival in patients with different ageand gender subgroups according to CTcoronary angiography (CTA) results. (A)KaplaneMeier curves for compositeend point in male patients aged<60 years with normal CTA, non-obstructive coronary artery disease(CAD) and obstructive CAD. (B)KaplaneMeier curves for compositeend point in male patients aged$60 years with normal CTA, non-obstructive CAD and obstructive CAD.(C) KaplaneMeier curves for compositeend point in female patients aged<60 years with normal CTA, non-obstructive CAD and obstructive CAD.(D) KaplaneMeier curves for compositeend point in female patients aged$60 years with normal CTA, non-obstructive CAD and obstructive CAD.

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current guideline for the use of CTA is based on expertconsensus, and thus large-scale randomised studies are needed toevaluate the clinical effectiveness guided by the test results.34

Multivariate adjustment for the independent prognostic role ofCTA results was not performed owing to a lack of statisticalpower as a result of the limited cardiovascular events in eachsubgroup after age and gender stratification. Finally, it isimportant to realise that despite the reduced radiation burdendue to prospective ECG triggering, the risk of radiation exposureassociated with CTA should not be disregarded, particularly inyounger women.

CONCLUSIONThis study confirmed that male patients had a significantlyhigher frequency of obstructive CAD on CTA than femalepatients. Moreover, the presence of both non-obstructive CADand obstructive CAD on CTA was significantly predictive ofCVS events in both genders. Importantly, after age stratification,CTA findings were shown to be of limited predictive value infemale patients aged <60 years as compared with male patientsat any age and female patients aged $60 years.

Funding KHY receives reseach grants from the Hong Kong Heart Foundation. JWJreceives research grants from and was a speaker at meetings sponsored by Astellas,AstraZeneca, Biotronic, Boston Scientific, Bristol-Myers Squibb, Cordis, DaiichiSankyo, Eli Lilly and Company, Medtronic, Merck-Schering Plough, Pfizer, Orbus Neich,Novartis, Roche, Servier, the Netherlands Heart Foundation, the InteruniversityCardiology Institute of the Netherlands and the European Community framework KP7program. JJB receives grants from Biotronik, BMS medical imaging, Boston Scientific,Edwards Lifesciences, GE Healthcare, Medtronic and St Jude Medical. JvW isfinancially supported by a research grant from the Netherlands Society of Cardiology(Utrecht, The Netherlands). PAK is supported by a grant from the Swiss NationalScience Foundation (Berne, Switzerland) (SNSF-professorship grant nr.PPOOA-114706), The remaining authors: None.

Competing interests None.

Ethics approval This study was approved by the local ethics committees in allparticipating centres and all patients provided informed consent.

Contributors All authors contributed to the planning, collection and analysis of data,or finalising the manuscript.

Provenance and peer review Not commissioned; externally peer reviewed.

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Heart 2012;98:232e237. doi:10.1136/heartjnl-2011-300038 237

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doi: 10.1136/heartjnl-2011-300038 2012 98: 232-237 originally published online September 13, 2011Heart

 Kai Hang Yiu, Fleur R de Graaf, Joanne D Schuijf, et al. angiographyprognostic value of CT coronary Age- and gender-specific differences in the

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