The clinical characteristics and investigations planned in patients

Clinical research

The clinical characteristics and investigationsplanned in patients with stable angina presentingto cardiologists in Europe: from the Euro HeartSurvey of Stable Angina

Caroline A. Daly1*, Felicity Clemens2, Jose L. Lopez Sendon3, Luigi Tavazzi4,Eric Boersma5, Nicholas Danchin6, Francois Delahaye7, Anselm Gitt8,Desmond Julian9, David Mulcahy10, Witold Ruzyllo11, Kristian Thygesen12,FreekVerheugt13, and KimM. Fox1 on behalf of the EuroHeart Survey Investigators

1Royal Brompton and Harefield NHS Trust, Sydney Street, London SW3 6NP, UK2London School of Hygiene and Tropical Medicine, London, UK3Hospital Universitario Gregorio Maranon, Madrid, Spain4Policlinico S Matteo, Pavia, Italy5Department of Cardiology, Erasmus Medical Centre, Rotterdam, The Netherlands6Hopital Europeen Georges Pompidou, Paris, France7Hopital Cardiovasculaire et Pneumologique Louis Pradel, Lyons, France8Herzzentrum Luwigshafen, Ludwigshafen, Germany9University of Newcastle upon Tyne, Newcastle upon Tyne, UK10Adelaide and Meath incorporating National Children’s Hospital, Dublin, Ireland11 Institute of Cardiology, Warsaw, Poland12Aarhus University Hospital, Aarhus, Denmark13University Medical Centre St Radboud, Nijmegen, The Netherlands

Received 15 September 2004; revised 7 January 2005; accepted 13 January 2005; online publish-ahead-of-print 18 March 2005

See page 949 for the editorial comment on this article (doi:10.1093/eurheartj/ehi294)

Aims The Euro Heart Survey of Stable Angina set out to prospectively study thepresentation and management of patients with stable angina as first seen by a cardio-logist in Europe, with particular reference to adherence to existing guidelines andregional variability in patient presentation and initial assessment.Methods and results Consecutive outpatients with a clinical diagnosis by a cardiolo-gist of stable angina were enrolled in the study and 3779 patients were included inthe analysis. The average age was 61 years and 58% were male. The majority ofpatients (88%) had mild to moderate angina, CCS class I or II. Despite a high prevalenceof recognized risk factors, 27% did not have cholesterol and 33% did not have glucosemeasured within 4 weeks of assessment. The resting ECG was abnormal in 41% ofpatients. An exercise ECG was performed or planned as part of initial investigationin 76% of patients and 18% had a stress imaging test such as perfusion scanning orstress echo. A coronary angiogram was performed or planned in 41%, and 64% hadan echo. The time from assessment to investigation varied widely, particularly forangiography. One in 10 patients had neither any form of stress test nor angiography,

& The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: [email protected]

KEYWORDSStable angina;

Presentation;

Cardiovascular risk factors;

Non-invasive investigation;

Stress testing;

Coronary angiography

* Corresponding author. Tel: þ44 207 3518289; fax: þ44 207 3518643.E-mail address: [email protected] or [email protected]

European Heart Journal (2005) 26, 996–1010doi:10.1093/eurheartj/ehi171

Dow

nloaded from https://academ

ic.oup.com/eurheartj/article/26/10/996/515006 by guest on 30 N

ovember 2021

withmarked regional variation. Availability of invasive facilities increased the likelihoodof both non-invasive and invasive investigations. Those with more severe symptoms orlonger duration of symptoms or a positive non-invasive test were more likely to haveangiography. In multivariable analysis, a positive stress test was the strongest predictorof the use of angiography, associatedwith a six-fold increase in the likelihood of invasiveinvestigation. However, gender and availability of facilities were also predictive.Conclusion Considerable variation in features at presentation and use of investigationshas been identified in the stable angina population in Europe. The evaluation ofbiochemical cardiovascular risk factors was suboptimal. Overall rates of non-invasiveinvestigation for angina and the clinical appropriateness of factors predictive of theuse of invasive investigationwere broadly in linewith guidelines. However, the influenceof access to facilities, and marked international variation in rates and timing ofinvestigation suggest that factors unrelated to clinical need are also influential in themanagement of patients with stable angina.

Introduction

Stable angina is the most prevalent manifestation ofcoronary artery disease, occurring as an initial presen-tation in almost half of patients with coronary disease.1

Despite its prevalence,2–6 data regarding the manage-ment of angina are sparse, in contrast to the abundanceof national and international surveys of the managementof acute coronary syndromes.7–11 Registries exist ofpatients who undergo coronary angiography,12–14 or whohave coronary disease detected at angiography,15 andthere are numerous studies using either administrativeor clinical data regarding the use of invasive investigationpost-MI or acute coronary syndrome,16 but few studiesdocument the complete sequence of investigation ofstable angina. Those that have been published areeither small, retrospective,17–19 and limited in scope,or restricted to a specific region.20–23 To obtainaccurate and up-to-date information concerning thepresentation and clinical course of stable angina, andto evaluate how the condition is managed with particularreference to the implementation of guidelines24–26 andregional or international variations in practice, the EuroHeart Survey (EHS) Programme has conducted aEuropean Survey of Stable Angina.Patients presenting ‘de novo’ to a cardiologistwith stable

angina were selected for study rather than a chronic reviewpopulation, to facilitate tracing the pattern of investi-gations implemented, including the temporal relationshipsbetween assessment and investigation in a prospectivemanner. This paper reports the clinical presentation ofstable angina, explores the use of investigations andfactors predictive of the use of stress testing and coronaryangiography in this condition, and evaluates how actualuse compares to guideline recommendations.

Methods

Patient population

To ensure that the population studied was representative of thestable angina population, and not just pre-selected patients

admitted to hospital for catheterization or revascularization,the survey was performed on community based, ambulatorypatients on a new presentation to a cardiologist as an out-patient. Investigators were asked to enrol consecutive newlypresenting patients over a 4–6 week time period or until aminimum target was enrolled. A new presentation was definedas a first ever presentation, or new referral or re-referral,after a period of at least 1 year of not attending or consultinga cardiologist. Patients were suitable for inclusion if the cardiol-ogist made a diagnosis, on the basis of clinical assessment, ofstable angina, caused by myocardial ischaemia due to coronarydisease. Patients were not obliged to have documented evidenceof ischaemia to be included, but they did have to have stableanginal symptoms that were due to coronary disease in theopinion of the physician investigator. Exclusion criteria includedunstable symptoms such as rapidly progressive symptoms, restpain, or Canadian Cardiovascular Society (CCS) class IV symptoms.Further exclusion criteria included hospitalization within 24 hof the initial consultation (as these patients were consideredpotentially likely to have unstable angina in a proportion ofcases); a prior history of revascularization, either percutaneousor surgical; or aetiology other than coronary disease, forexample significant aortic stenosis or hypertrophic cardiomyopa-thy. The survey originally included only patients without anyprior history of myocardial infarction, but from July 2002 toDecember 2002, patients with remote (.1 year) prior myocardialinfarction were also included, to increase enrolment. Selection ofpatients with a new presentation of stable angina without priorrevascularization was to facilitate the evaluation of patterns ofinitial assessment of stable angina, including the diagnosticapproach, risk stratification procedures, the temporal relation-ships between assessment and investigations, and comparisonsbetween variable patterns of investigation. Eligible patientswere enrolled in the study after consent had been obtainedin the manner deemed appropriate by the local regulatoryauthorities.

Angina severity was assessed using the CCS classification, andbreathlessness classified according to the New York HeartAssociation (NYHA) classification. Definitions for risk factors,comorbid conditions, and ECG abnormalities are reported inAppendix B.

Participating centres

As part of the EHS Programme, the Stable Angina Survey sharesmany organizational and logistic features with other EHSs.7,27

National coordinators were encouraged to recruit investigators

Patients with stable angina: Euro Heart Survey 997

Dow



ovember 2021

from a variety of clinical centres ranging from tertiary referral oruniversity teaching hospitals to regional or district centres in amanner which reflected facilities and practice on a nationallevel. Local investigators, who participated on a voluntarybasis, then collected data. Patients were enrolled from 197centres in 36 countries in Europe and the Mediterranean basin.The results are described from four pre-defined areas withinEurope, northern Mediterranean, central and western, in linewith the previous Euro Heart Surveys (EHSs) (Figure 1 ).7,27

Data collection

Data collection commenced in March 2002 and continued untilDecember 2002. Participating centres completed a questionnaireregarding centre-specific information including the availabilityof cardiac surgery, catheterization facilities, and non-invasivediagnostic facilities. The attending physician, or a data collectionofficer in consultation with the attending physician, completedthe case record forms (CRF), which contained information regard-ing demographic and clinical details of the patients, referralpathway, planned investigations, treatment recommended, andfollow-up procedure observed. Attending clinicians recorded inthe CRF whether a series of investigations were performed inadvance of or in preparation for the initial assessment (within4 weeks) or whether the test was planned by the cardiologist.If a test had been performed recently by the primary care

physician, this could be recorded as ‘performed or planned’by the investigator. Similarly, if the test was planned by the car-diologist but not yet performed within 4 weeks, it would still berecorded as performed or planned. For each test, the investi-gator recorded the timing of the test prior to assessment, ,4weeks after assessment, .4 weeks after assessment, or sched-uled on a waiting list. If the result was available at assessment,or within the 4 week period afterwards, that result wasrecorded.

Data management

The data were collected and stored centrally at the EuropeanSociety of Cardiology base in Nice. The data collection softwareran initial consistency checks at data entry level, with furtherchecking performed by submitting the database to consistencychecks as per a pre-written validation plan using SAS software.Missing or inconsistent values were thus highlighted auto-matically and queried by the data management team usingphone or e-mail contact with the investigators.

Statistical analysis

Statistical analysis was performed in collaboration with theLondon School of Hygiene and Tropical Medicine. Descriptive

Figure 1 Countries participating in the EHS of stable angina.

998 C.A. Daly et al.

Dow



ovember 2021

statistics were used to estimate the prevalence of risk factors,baseline clinical characteristics, and treatment at presentation.The Student’s t-test or ANOVA technique were used as appropri-ate to test differences in quantitative measures and the x2 testwas used to test differences in proportions. Two-sided P-valuesare reported with 0.05 used as critical value to define statisticalsignificance. To explore the variations in their use, logisticregression was employed to determine determinants of the useof exercise testing, stress imaging, or coronary angiography.Univariate analysis of predictors of the use of exercise testingincluded nine variables, age (.70 years vs. ,70 years), sex,employment, education, type of centre, comorbidity, symptomseverity (CCS class), duration of symptoms (�6 months vs. ,6months), and anti-anginal drug therapy prior to assessment(one or more anti-anginal drugs vs. one anti-anginal drug).Further variables added for analysis of stress echo and myocar-dial perfusion scanning as an outcome included the performanceof exercise testing (yes/no) and the result of exercise testing(positive vs. negative or inconclusive). For coronary angiography,to these variables were also added the result of stress echo-cardiography or myocardial perfusion imaging and non-invasiveestimation of LV function by echocardiography. Univariate analy-sis to identify the factors predictive of the use of non-invasivetesting and coronary angiography was performed separately foreach of the named regions. Multiple logistic regression using astepwise procedure was used to ascertain the demographic,clinical, and investigative factors that determined the use ofexercise testing, stress echo and perfusion imaging, and coro-nary angiography. Because of the substantial variation in therates of referral for coronary angiography, separate analysiswas also carried out for the countries which had a high rate ofreferral for coronary angiography (above median) and thosewhich had a low rate of referral (below median). In order tocheck the robustness of the models, a uniformly distributedrandom variable was generated. A cutoff was imposed at avalue of 0.5 for this variable, and the chosen models werere-run using the observations holding a value of �0.5 for thisrandom variable. Analysis was undertaken using STATATM

version 8 statistical software.

Results

A total of 3923 patients with stable angina were enrolledin the survey. In all, 144 were excluded because the CRFhad not been registered as completed, or there weremultiple missing values and the results presented arefor the remaining 3779 patients.

Participating centres and referral sources

Patients were enrolled in 197 centres. Of the participa-ting centres, 35% had non-invasive diagnostic facilitiesonly, 20% had non-invasive and invasive facilities, and34% had, in addition to a catheterization laboratory,cardiac surgery facilities on-site. Facilities were uncate-gorized in 11% of centres. The majority of patientsincluded (71%), had been referred by a primary carephysician, and only 5% were referred from an emergencydepartment for follow-up. Self referrals accounted for10% of the population, although this figure was appre-ciably higher in central and Mediterranean Europecompared with northern and western Europe (15 and17% vs. 0.2 and 2%, respectively, Figure 2 ). Patientswere assessed in specialist chest pain clinics, non-emergency clinics specifically for the purpose of assessingpatients with chest pain in 40% of cases. However, therewere marked international differences in the proportionsof patients assessed in such clinics, ranging from 0% incountries such as Denmark and Portugal to 93% ofpatients in Sweden.

Patients enrolled

Details of the numbers and basic demographics ofpatients enrolled from individual countries are presented

Figure 2 Distribution of referral sources for patients presenting to a cardiologist with stable angina in northern, western, central, and MediterraneanEurope.


Dow



ovember 2021

(see Supplementary material online, Table SI ). The mean(SD) age of patients included in the survey was 61 (11)years, ,5% were .80 years of age. Males represented58% of the population overall (Table 1 ). Females includedin the study were only marginally older than the males.Cardiovascular risk factors and other relevant medicalhistory are shown in Table 1. The prevalence of diabetesand hypertension increased with increasing age with theprevalence of diabetes in .70 year age group (22%)double that in the ,50 year age group (11%), and theprevalence of hypertension rising from 45% in those,50 years of age to 71% in those .70 years of age.Overall, the prevalence of comorbidity was low.Employment status was ascertained in 3511 patients, ofwhom 7.7% were unemployed and 48% retired.

On the whole, patients with stable angina from centralEurope were slightly younger (mean age 59.5 years),more likely to be hypertensive, and to have hyperlipi-daemia (P, 0.001 for differences in these parameterscompared with other regions), whereas patients fromMediterranean Europe were slightly older (mean age63.8 years), more often male, and more likely to havediabetes (P , 0.001 for differences in all of theseparameters).

Clinical details

All patients with a clinical history of myocardial infarc-tion within 1 year of assessment were excluded and2398 (63%) patients were enrolled while any prior myo-cardial infarction was an exclusion criterion for thestudy. Only 4% of patients had a history of remote (.1year) myocardial infarction. Angina class was assignedfor 3472 patients, 39% had CCS class I, 49% class II, and12% class III symptoms. The majority, 75% of patients,had symptoms for 1 year before assessment by a cardiol-ogist, but just 52 patients, ,2% of patients, had symp-toms for ,1 month. The median duration of symptomsprior to presentation to a cardiologist was 5 months anddid not vary according to symptom severity. Regional

variation was apparent, with symptom duration beforecardiology assessment ranging from a median of3 months in western Europe to 5 or 6 months in otherregions (P, 0.0001). This difference was most pro-nounced for patients with more severe (class III)symptoms.Severe heart failure symptoms, NYHA class III or IV,

were rare, occurring in 5 and 0.6% of patients, respecti-vely. Physical signs of heart failure, defined as a raisedjugular venous pressure, crepitations in the lung fields,a third heart sound, peripheral oedema, or hepatome-galy, were reported in only 8% of cases. The populationwas overweight, three-quarters had a body mass index(BMI) of 25ormore,meanBMI 28+ 5.Mean systolic anddias-tolic blood pressures were 144+ 21 and 85+ 11 mmHg,respectively.

Medical therapy prior to cardiology assessment

Almost half (49%) of patients were taking aspirin beforeassessment by a cardiologist. Only 22% of patients wereon a statin prior to assessment by the cardiologist, andeven of patients with recognized hyperlipidaemia only41% were on a statin, and 5% on an alternative lipid low-ering agent. Patients were taking at least one anti-anginal drug at presentation to the cardiologist in 62%of cases and two or more in 28%.

Investigations performed

Figure 3 is a flow diagram which depicts the overallpattern of the use of investigations.

Biochemical tests at presentationTable 2 shows the numbers of patients who had lipid andglucose analyses, either performed or planned. Only 72%of patients actually had a cholesterol measurement per-formed within 4 weeks of assessment (Table 3 ). Overallmean cholesterol levels were 5.8 mmol/L. Even in thosepatients who were taking a statin, mean cholesterol

Table 1 Cardiovascular risk factors and other clinical details of patients presenting with stable angina, overall and by Europeanregion

Overall(n ¼ 3779)

% North(n ¼ 521)

% West(n ¼ 951)

% Central(n ¼ 1341)

% Med(n ¼ 966)

%

% Male 2197/3779 58 315/521 60 489/951 51 784/1341 58 609/966 63Mean age (SD) 61 (11) 62 (10) 61 (10) 60 (13) 64 (11)Diabetic 652/3666 18 74/511 14 142/910 16 209/1309 16 227/936 24Hypertensive 2267/3676 62 245/512 48 485/901 54 921/1321 70 616/942 65Hyperlipidaemia 1843/3174 58 247/473 52 334/710 47 728/1125 65 534/866 62Current smoker 819/3553 23 100/500 25 222/762 29 277/1326 21 220/965 23Family history 1347/3161 43 223/453 49 361/745 48 474/1119 42 289/844 34Peripheral vascular disease 267/3779 7 13/521 3 67/951 7 114/1341 9 73/966 8CVA or TIA 197/3779 5 22/521 4 52/951 5 69/1341 5 54/966 6Chronic respiratory disease 313/3779 8 47/521 9 90/951 9 98/1341 7 78/966 8Chronic hepatic disease 72/3779 2 1/521 0.2 6/951 0.6 42/1341 3 23/966 3Chronic renal failure 54/3779 1 1/521 0.2 10/951 1 17/1341 1 26/966 3Malignancy 61/3779 2 9/521 2 21/951 2 13/1341 1 18/966 2

CVA, cerebrovascular accident; TIA, transient ischaemic attack; Med, Mediterranean.


Dow



ovember 2021

Figure 3 Flow diagram illustrating the referral sources and use of non-invasive and invasive investigations in patients from the EHS of stable angina.Asterisk indicates investigations performed prior to assessment are included in the overall number of tests performed or planned. Non-Card.Specialist, non-cardiological specialist; FU, follow-up; CXR, chest X-ray; Ex ECG, exercise ECG; SE, stress echo; MPS, myocardial perfusion scan;Angio., angiogram.


Dow



ovember 2021

levels were 5.7 mmol/L and just one-third of patients hadachieved target (,5.0 mmol/L) cholesterol. Glucoseanalysis, although planned in 77% of patients, was onlyperformed within 4 weeks in two-thirds of the populationoverall. Of the population without previously diagnoseddiabetes, 4% were found to have a fasting glucose in thediabetic range (WHO criteria for the diagnosis of diabetes,i.e. fasting glucose of .7.0 mmol/L).

Resting ECGA resting ECG was performed in the vast majority (99%)of patients and results recorded for 98% of patients inthe study. At least one pre-defined abnormality, atrialfibrillation or other rhythm disturbance, ST depression,T-wave inversion, pathological Q-wave, or left or rightbundle branch block, was recorded in 41% of ECGs.

ST depression and T-wave inversion were the most fre-quently observed abnormalities, occurring in 18 and19% of patients, respectively, overall.

Chest X-rayAlthough performed or planned in 51% of patients overall,performance of chest X-rays showed wide regional andinternational variability, ranging from 19 to 100% in indi-vidual countries. One-fifth of chest X-rays showed at leastone abnormality, most commonly cardiomegaly, whichwas reported in 13% of all X-rays performed. Pulmonarycongestion was reported in 5% of chest X-rays.

EchocardiographyEchocardiography was planned or performed in 2430patients, 64% of the population overall, but only in 24%of patients in northern Europe. Of patients fromwestern, central and Mediterranean Europe, 60, 84,and 63%, respectively, had a resting echo. At 4 weekfollow-up, an echo had been carried out and resultswere available for 80% of patients in whom the testwas planned. Left ventricular hypertrophy (LVH) wasdetected in 32% of echos, and regional wall motionabnormality (RWMA) in 21% overall. Moderately impairedand poor ventricular function was reported in 17 and 3%,respectively.

Exercise ECGExercise testing was planned or performed in 76% ofpatients (Figure 3 ), with less regional variation than forother investigations (Figure 4 ). In northern Europe com-pared with other parts of Europe, a greater proportion ofpatients, 65% of all patients in whom an exercise test wasplanned, had their exercise test performed prior to beingseen by a cardiologist. Results of 2328 exercise tests wereavailable within 4 weeks of assessment. A positive resultwas recorded in 57%, negative in 29%, and inconclusive in13%. Of patients with a positive test, 68% went on to havea coronary angiogram (Figure 3 ) compared with only 14%

Table 2 Number and proportion of patients who had lipid orglucose analysis performed or planned as part of cardiologyassessment of stable angina

Total numberplanned/performed(% of populationoverall)

Number with result availableto cardiologist within 4 weeks(% of population overall)

Fasting Fasting/non-fasting/unknown

Lipids 3125 (83%) TC 1924 (51%) 2720 (72%)LDL 1584 (42%) 2094 (55%)HDL 1360 (36%) 1891 (50%)TG 1786 (47%) 2377 (63%)

Glucose 2912 (77%) 1825 (48%) 2528 (66%)

TC, total cholesterol; TG, triglyceride.

Table 3 Cholesterol, lipid subfraction, and glucose levelsrecorded in patients with stable angina before or within 4weeks of presentation to a cardiologist, according to fastingor statin therapy status

Risk factor Timing ofspecimen

Therapy Mean (SD)(mmol/L)

Total cholesterol Fasting 5.8 (1.2)Non-fasting 5.8 (1.2)

Taking statin 5.7 (1.4)LDL-C Fasting 3.8 (1.1)

Non-fasting 3.6 (1.0)Taking statin 3.6 (1.2)

HDL-C Fasting 1.3 (0.4)Non-fasting 1.3 (0.5)

Triglycerides Fasting 1.8 (1.0)Non-fasting 2.2 (1.3)

Glucose Fasting 6.0 (1.9)Non-fasting 6.1 (2.0)

LDL-C, low density lipoprotein cholesterol; HDL-C, high densitylipoprotein cholesterol.

Figure 4 Regional distribution of the use, and timing relative to cardio-logy assessment, of exercise ECG in patients presenting with stableangina. .4 weeks, more than 4 weeks after cardiology assessment;,4 weeks, within 4 weeks or less of cardiology assessment; Prior, sameday or before cardiology assessment; Med, Mediterranean.


Dow



ovember 2021

of patients with a negative test (P, 0.001). Stress echoor perfusion scanning was performed in 8% of patientswith negative result, 29% of patients with an inconclusiveresult, and 11% of patients with a positive exercise ECGresult.

Patients who did not have an exercise test performedor plannedAn exercise test was neither performed nor planned in24% of the overall population. Among these patients,there were specific patient contra-indications to exerciseECG in 25%. Only 23 patients were reported not to havehad the exercise test because it was not available. Ofthe patients who had no exercise test, 26% had analternative form of non-invasive stress testing, eitherperformed or planned, and 39% had an angiogram per-formed or planned. Of the patients who had no exercisetest, 408 (45%) had neither another form of non-invasivestress testing nor coronary angiography (Figure 3 ). Thisgroup was composed of a higher proportion of elderlypatients than the overall population, 45% were .70years, and females were over-represented. Patientswho had neither any form of stress testing nor angio-graphy accounted for 11% of the overall population.Regionally, this corresponded to 18% (n ¼ 244) of allpatients in central Europe, 4% (n ¼ 19) in northernEurope, 7% (n ¼ 68) in western Europe, and 8% (n ¼ 77)in Mediterranean Europe.

Stress imaging testsThe use of stress echocardiography and myocardial per-fusion scanning was not widespread in this population,with one or other of these tests performed in only 18%of the population overall (Figure 5 ), although this roseto 34% among patients with a specific patient contra-indication to exercise ECG. Stress imaging techniqueswere not exclusively employed in patients who did notor could not have an exercise ECG as two-thirds ofpatients who were scheduled to have stress imagingalso had an exercise ECG.Exercise was the most common stressor in the case of

perfusion imaging and inotropes in the case of stressecho. Myocardial perfusion scanning was more frequently

used than stress echocardiography, but was less likely tobe completed within 4 weeks of assessment. Results wereavailable at 4 weeks for 71% of planned stress echos and60% of planned perfusion scans. Inconclusive or uninter-pretable stress imaging results were rare, reported inonly 1–2% of tests performed. A negative result wasreported in 17% of stress echos and 28% of perfusionscans, with evidence of fixed or reversible ischaemia in81 and 71%, respectively.

Coronary angiographyCoronary angiography was either planned or performed in1564 patients (41%) overall, with considerable regionalvariation as seen in Figure 6. The rate of coronary angio-graphy was low overall in western Europe, but this maskshigh performance rates in certain countries with rela-tively smaller numbers of patients such as in Germany(n ¼ 144), where 75% of patients had an angiogram per-formed or planned. Although coronary angiography wasplanned in 57% of patients with stable angina in northernEurope, there was frequently considerable delay beforeperformance of the test. Almost 9 out of 10 patients(88%) referred for angiography in northern Europe hadtheir angiogram scheduled .4 weeks after the time ofassessment. In central Europe, 62% of patients had towait for .4 weeks, 40% in Mediterranean, and only 18%in western Europe.At 4 week follow-up, the results of coronary angiogra-

phy were available for 799 patients. Of these patients,72% of patients had significant coronary disease,defined as at least 50% stenosis of an epicardial vesselor branch thereof.

Factors influencing the use of non-invasive tests

In univariate analysis, females and those .70 years ofage were significantly less likely to have an exercisetest, as were patients with one or more comorbid con-dition (see Supplementary material online, Table SII ).Patients with symptoms for .6 months, more severe

Figure 5 Regional distribution of the use of stress perfusion scanningand stress echocardiography in patients presenting with stable angina.Med, Mediterranean.

Figure 6 Regional distribution of the use, and timing relative to initialcardiology assessment, of coronary angiography in patients presentingwith stable angina. .4 weeks, more than 4 weeks after cardiology assess-ment; ,4 weeks, within 4 weeks or less of cardiology assessment; Prior,same day or before cardiology assessment; Med, Mediterranean.


Dow



ovember 2021

angina or those taking more than one anti-anginal drugwere also less likely to have an exercise test. Overall,patients enrolled in a centre with invasive facilitieswere �50% more likely to have an exercise test thanpatients enrolled in a centre with non-invasive facilitiesonly. A notable exception when regions were analysedseparately was the case of northern Europe, wherepatients from invasive centres were not more likely tohave an exercise test.

Stress echo or myocardial perfusion scanning weremore likely to be performed in centres with invasivefacilities, with the exception of central Europe, wherethese tests were significantly less likely to be performedin patients from invasive centres (see Supplementarymaterial online, Table SIII ).

Factors influencing the use of coronaryangiography

Women and (except in northern and western Europe)those .70 years were significantly less likely to havecoronary angiography performed or planned. More severesymptoms, symptoms of longer duration, or greater useof anti-anginal drug therapy were significant predictorsof the use of coronary angiography (see Supplementarymaterial online, Table SIV ) and remained consistently soacross all regions. Overall, patients in hospitals with inva-sive facilities were 26% more likely to have an angiogramperformed or planned than patients in a centre withnon-invasive facilities only.

Multivariable analysis

For exercise testing, age .70 years, comorbidity, andlonger symptom duration were independently associatedwith decreased likelihood of referral for exercise testing(Table 4 ). In countries with low rates of referral for

angiography, gender was an independent predictor ofthe use of exercise testing, but not in countries withhigh rates of angiography. For stress imaging techniques,not having an exercise ECG performed or planned was anindependent predictor of the use of either stress echo orperfusion imaging in all regions.Independent predictors of the use of coronary angio-

graphy included a positive exercise test, symptom seve-rity, and gender (Table 5 ). A positive exercise test wasassociated with an approximately six-fold increase inthe likelihood of angiography irrespective of the overallrate of angiography within a country. Age and type ofcentre were independent predictors of the use of angio-graphy only in countries with low rates of angiography.The validity of the multivariable models used wasassessed using a random subset of the data as outlinedpreviously. The models were found to be robust in theselection of which variables were predictive, and themagnitude of the effects observed were comparable tothe results obtained in the analysis of the full population.

Discussion

There is an abundance of national and internationalsurveys of acute coronary syndromes,7–11 and indeed ofheart failure27–30 in the recent literature, but remarkablyfew of stable angina. This survey represents the first reg-istry of patients with stable angina in a large cohort ofEuropean countries and is unique as a prospective studywith complete data on non-invasive and invasive investi-gations on a relatively unselected population of patientswith stable angina presenting for the first time to cardi-ologists. It is the only report regarding investigation ofangina to span multiple geographical areas and health

Table 4 Multivariable determinants of the use of exerciseECG in patients with stable angina from the EHS of newly pre-senting angina in countries with high and low national rates ofcoronary angiography

Variable OR 95% CI P-value z

Countries with less than median angiography rateAge .70 0.35 0.26–0.48 ,0.0001 26.73Centres with invasivefacilities

2.58 1.93–3.43 ,0.0001 6.48

Symptom duration(.6 months)

0.65 0.49–0.86 0.003 22.98

Comorbidity 0.66 0.47–0.92 0.014 22.46Female gender 0.73 0.55–0.96 0.027 22.21

Countries with greater than median angiography rateAge .70 0.55 0.42–0.75 ,0.0001 23.89Symptom duration(.6 months)

0.57 0.44–0.74 ,0.0001 24.22

CCS class II 0.55 0.41–0.76 ,0.0001 24.19Comorbidity 0.67 0.47–0.92 0.018 22.37CCS class III 0.66 0.48–0.93 0.056 21.91

Table 5 Multivariable determinants of the use of coronaryangiography in patients with stable angina from the EHS ofstable angina in countries with high and low national ratesof coronary angiography

Variable OR 95% CI P-value z

Countries with less than median angiography ratePositive Ex ECG 6.0 4.16–8.63 ,0.0001 9.65�2 Anti-anginal drug 2.10 1.46–3.03 ,0.0001 4.01CCS III 2.44 1.35–4.39 0.003 2.98Female gender 0.56 0.40–0.80 0.001 23.22Age .70 0.50 0.30–0.76 0.002 23.16Centres with invasivefacilities

1.70 1.16–2.49 0.007 2.72

Countries with greater than median angiography ratePositive Ex ECG 6.30 4.69–8.45 ,0.0001 12.27CCS class III 6.37 3.4–11.87 ,0.0001 5.83CCS class II 2.0 1.49–2.70 ,0.0001 4.57Female gender 0.63 0.47–0.84 0.002 23.10�2 Anti-anginal drug 1.45 1.05–2.01 0.025 2.25

Ex ECG, exercise ECG; anti-anginal drugs: nitrates, beta-blockers,calcium antagonists, nicorandil, or metabolic agents.


Dow



ovember 2021

care systems and is substantially larger than previousstudies in this field.

Patient profile

On the whole, the patient profile was similar in thedifferent European regions. Exceptions include agreater prevalence of diabetes in this population inMediterranean region and a higher proportion of hyper-tension and hyperlipidaemia in central Europe. There isa higher proportion of women then included in mosttrials of secondary prevention in coronary disease, butthis is not surprising if one considers that angina is themost frequent manifestation of coronary disease inwomen.31,32

Risk factor assessment

The 1997 European Society Guidelines on the manage-ment of stable angina advocate, as a minimum, an assess-ment of risk factors and resting electrocardiogram inaddition to clinical assessment for all patients, and aninitial strategy of non-invasive testing for most patients,which will assist in determining the need for coronaryangiography.24

Despite the relative ease and lesser expense of lipidand glucose measurements compared with other formsof investigation, lipid analysis was not performed within1 month in more than a quarter of patients and glucosemeasurement not performed in one-third of patients.Fewer than half of the 58% of patients with known hyper-lipidaemia were on lipid lowering drugs, and of evenamong those on statin therapy only one-third hadachieved target cholesterol levels, reflecting subthera-peutic dosing, and emphasizing the need for cholesterolmonitoring even among those on cholesterol loweringtherapy from their primary care physician. The low rateof lipid measurement is not dissimilar to that observedin the EUROASPIRE II study33 or studies of the penetrationof guidelines regarding the investigation and manage-ment of hypertension.34 It is higher than reported ratesof measurement during cardiac hospitalizations in theearly 1990s, which report as few as 14% of patienthaving cholesterol measurement.35,36 However, the rateof measurement of cholesterol can be increased con-siderably with strategic programmes at institutionallevel to raise awareness of the benefits of measuringand treating cholesterol, and standardize the approachto risk factor assessment in the ischaemic heart diseasepopulation. Such targeted programmes can also increasethe appropriate use of lipid lowering therapy.35

Although glucose measurement resulted in the disco-very of only an additional 4% of the population withpreviously unknown diabetes, a lower proportion ofnewly discovered diabetics than in studies of myocardialinfarction37 or the EHS of Diabetes and the Heart,38 this isnonetheless an important finding with consequences bothfor the prognosis of the individual, and for treatment.Clearly successful and effective secondary prevention

cannot be achieved if lipid and glucose status are notactively investigated, and routine measurement ofthese biochemical parameters should be an unquestionedpreliminary step in patient assessment.

Resting echocardiography

With the exception of northern Europe, a large pro-portion of patients surveyed underwent resting echo-cardiography as part of the work up for stable angina.It is well recognized that left ventricular function is acrucial factor in influencing prognosis in coronarydisease,39–41 and it is possible to use simple reproducibleechocardiographic measurements of ventricular dimen-sions to assign risk and to combine this information effec-tively with information obtained from stress testing todiscriminate between high and low risk groups.42 Therelatively high pick up rate of LVH (32%) and RWMAs(21%) in a population for the most part without clinicalheart failure or prior history of MI, are further vindicationof this course of action.

Non-invasive stress tests

The sequence of non-invasive investigation of anginaobserved in the study seems at first to be in line withexisting guidelines with regard to the use of functionalassessment in almost all patients. Between 70 and 80%of patients had an exercise test performed or planned,and stress imaging techniques were used in 26% of thepopulation who did not have an exercise ECG. However,imaging techniques were used more frequently as anadditional test rather than an alternative to exerciseECG in the majority of patients, with the highest rateof stress imaging among patients with inconclusiveexercise ECG results.Importantly, failure to perform some form of functional

assessment as a minimum was an issue for a considerableproportion of patients. This was particularly the case incentral Europe where neither functional assessment norangiography was planned in 18% of the populationreferred to cardiologists. These findings are reconcilablewith suggestions that, although modest, the contributionof differences in medical care to the east–west healthgap is not inconsequential.43,44

Nevertheless, the overall rate of non-invasive investi-gation stress testing compared favourably with thatreported from a US study of the use of diagnostictesting within 4 weeks in a population with new onsetchest pain, in which only 60% received a specificcardiac investigation, and 22% of patients who metnecessity criteria for testing were not tested.45

In this survey, patients with longer symptom duration,more severe symptoms, or those already on more thanone anti-anginal medication were less likely to have anexercise ECG or other stress test. This may indicateeither that these patients are thought to have moresevere disease and more likely to require revasculariza-tion and therefore go on to have coronary angiography


Dow



ovember 2021

directly or that in suchpatients, the diagnosis is consideredestablished and confirmatory testing not required. Thislatter approach does not take account of the importantrole exercise testing may have in risk stratifyingpatients.46–48 The use of the Duke treadmill score48

or other prognostic scores was not evaluated by thissurvey. As only 39% of patients who did not have anexercise test went on to have an angiogram, direct angio-graphy does not fully account for the observed referralpatterns and suggests under use of stress testing as aprognostic tool.

Invasive investigation: coronary angiography

The rate of coronary angiography recommended bycardiologists, 41%, is comparable to North Americanfigures from 1990, which estimated that 40% of incidentcases of angina undergo elective cardiac catheteriza-tion49 over a 5-year-period. Although there has been aprogressive increase in cardiac catheterization rates inthe USA,50 some reports suggest that referral of incidentcoronary disease for catheterization after stress testinghas not increased dramatically after the late 1980s.19

The variability in length of time between assessmentand angiography is a striking feature of the survey, withan almost five-fold difference in the proportion ofpatients having to wait more than a month for scheduledangiography between regions. This is also a cause forconcern given reported rates of adverse cardiac events(including death, MI, and hospitalization for unstableangina) of 9.4% over 8.4 months in previous studies,with increased probability of events as the waiting timefor angiography lengthened.51 Future guidelines mayneed to provide guidance on prioritization of patientsfor angiography to address this issue.

In line with previous findings,17–19 gender was a signifi-cant predictor of the use of coronary angiography in bothunivariate and multivariable analyses. Although less fre-quently documented in the literature, a bias againstthe use of angiography in older patients has beenreported22. However, in this survey, age was only inde-pendently associated with less angiography whereoverall rates of angiography are low, suggesting thatwhere services are constrained, or practice more con-servative, the elderly are less likely to be referredonwards for angiography or potential consideration forrevascularization, but where there is more liberal useof angiography age is not a deciding factor. The avail-ability of on-site cardiac catheterization facilities signifi-cantly increased the likelihood of referral for coronaryangiography in similar fashion to that shown in studiesof acute coronary syndrome.52 Again, however, centretype was only a predictive factor in multivariable analysisin countries where overall rates of angiography were low.

Important clinical factors related to appropriateness ofuse namely, a positive stress test or intensity of medicaltherapy (more than one anti-anginal at presentation)were universally independent predictors of the use ofcoronary angiography. But patient symptoms were moreinfluential, and availability of on-site facilities not an

influential factor in countries where angiography wasmore frequently undertaken.

Limitations

Although a survey of stable angina, this is not apopulation-based study and as such it is not possible tomake any inferences from the data about the incidenceof angina in any of the regions studied. Furthermore, asassessment by a cardiologist was chosen as the samplingpoint, the data regarding clinical characteristics maynot be generalizable to the overall population withstable angina in the community because of selectionbias, but the population is reflective of the patientprofile presenting to cardiologists and suitable for theinvestigation of their management practices. Inclusionin the study was based on the diagnosis of angina bythe attending physician and is thus also open to interpre-tation bias, but as patient management was based on theworking diagnosis of angina, the population is suitable forthe evaluation of patient management. Because of theexisting infrastructure in place at the time this surveywas initiated, the survey is somewhat biased towardslarger teaching or university affiliated centres, withmore centres with on-site catheterization facilities thanwould be the case in practice. The numbers of patientsfrom some of the 36 countries which contributed dataare too small to be representative of practice in thatindividual country, but where trends in prevalence orpractices emerge between countries in a region, thelarger regional sample size is likely to be representative.Finally, given the potential sources of bias in the analysis,the results must be considered as indicative rather thanfactual. In light of this, and as the nature of the studyis exploratory rather than definitive, caution is advisedin interpretation of the results, but the findings are none-theless worthy of consideration, and generate importantquestions as well as providing novel information in thisarea.

Conclusions

The survey documents a young population with a highprevalence of modifiable cardiovascular risk factors pre-senting for the most part with mild to moderate anginalsymptoms, uncomplicated by heart failure. This popu-lation, who have declared themselves at increased riskby virtue of their symptoms, but who for the most parthave not yet suffered major adverse cardiovascularevents, present a perfect opportunity to the cardiologistto improve prognosis while also reducing angina. Despitebeing comparable to the populations recruited in inter-national randomized controlled trials of secondary pre-vention to which the existing guidelines are mostapplicable, there is a clear gap between the guidelinesand practice with regard to the evaluation of the majorbiochemical measurements of cardiovascular risk, choles-terol and glucose.The widespread use of non-invasive investigations

appears broadly in line with existing guidelines, but


Dow



ovember 2021

improvements can certainly be made, particularly amongthe minority of patients who have no form of non-invasivestress test or angiogram, in standardizing the use of echo-cardiography, and in improving the temporal relation-ships between assessment and initial investigations insome regions.However, the influence of access to facilities, and

marked international variation in rates and timing ofangiography, suggest that factors unrelated to clinicalneed, including service capacity and patient preference,are also influential in the management of patients withstable angina. The challenge to the European cardiologycommunity is not only to ensure that clear guidelines onthe subject, backed by the available evidence, penetrateto all relevant professionals, but also to ascertain theoptimal strategies to ensure that the guidelines are putinto practice, through implementation of national orinstitutional programmes and to adapt such programmesto fit into highly variable existing services.

Supplementary material

Supplementary material is available at European HeartJournal online.

Appendix A

Organization of the survey

Angina Expert Committee: Kim Fox (Survey Chairman), UK;Caroline Daly (Research Fellow), UK; Nicolas Danchin, France;Francois Delahaye, France; Anselm Gitt, Germany; DesmondJulian, UK; Jose-Luis Lopez Sendon, Spain; David Mulcahy,Ireland; Witold Ruzyllo, Poland; Luigi Tavazzi, Italy; KristianThygesen, Denmark; Freek Verheugt, The Netherlands, EricBoersma, The Netherlands (Representative of the Committeefor Methodology and Data Management), David Wood, UK(Chair of Euro Heart Survey Programme).

Euro Heart Survey Team (European Heart House, France):Malika Manini, Operations Manager; Claire Bramley, DataMonitor; Valerie Laforest, Data Monitor; Charles Taylor,Database Administrator; Susan Del Gaiso, Administrator.

Main Investigator Centre (London, UK): Kim Fox (Chairman);Caroline Daly (Research Fellow).

Statistical Centre: London School of Hygiene and TropicalMedicine, Felicity Clemens, Bianca de Stavola.National Co-ordinators: Kurt Huber, Austria; Guy De Backer,Belgium; Vera Sirakova, Bulgaria; Roman Cerbak, CzechRepublic; Per Thayssen, Denmark; Seppo Lehto, Finland;Francois Delahaye, France; Bondo Kobulia, Georgia; UweZeymer, Germany; Dennis Cokkinos, Greece; Kristof Karlocai,Hungary; Emer Shelley, Ireland; Shlomo Behar, Israel; AldoMaggioni, Italy; Virginija Grabauskiene, Lithuania; Jaap Deckers,The Netherlands; Inger Asmussen, Norway; Janina Stepinska,Poland; Lino Goncalves, Portugal; Vyacheslav Mareev, Russia; IgorRiecansky, Slovakia; Miran F. Kenda, Slovenia; Jose Luis Lopez-Sendon, Spain; Annika Rosengren, Sweden; Peter Buser,Switzerland; Tugrul Okay, Turkey; Oleg Sychov, Ukraine; KevinFox, UK.

There was no national co-ordinator in the participatingcountries which are not mentioned in the previous list.

Euro Heart Survey Board Committee: Maarten Simoons(Chairman), The Netherlands; David Wood (Past Chairman), UK;Angeles Alonso, Spain; Shlomo Behar, Israel; Eric Boersma, TheNetherlands; Harry Crijns, The Netherlands; Kim Fox, UK;Anselm Gitt, Germany; Malika Manini, France; Keith McGregor,France; Barbara Mulder, The Netherlands; Markku Nieminen,Finland; Sylvia Priori, Italy; Lars Ryden, Sweden; Luigi Tavazzi,Italy; Alec Vahanian, France; Panos Vardas, Greece; WilliamWijns, Belgium; Uwe Zeymer, Germany.

List of Industry Sponsors: Servier Laboratories Ltd.

Participating Centres, Investigators, and Data Collection Offi-cers: Albania: Ahmet Kamberi, Tirana. Austria: DagmarBurkart-Kuttner, Georg Gaul, Katharina Hohenecker, Vienna.Bosnia Herzegovina: Vulic Dusko, Banjaluka, Republika Sprska.Belgium: Isabelle Liebens, Bruxelles. Bulgaria: Vera Sirakova,Varna; Valentin Asenov Petrov, Shoumen; Dimitar Raev, Sofia.Belarus: Igor Polonetsky, Nikolay Manak, Minsk. Cyprus: CostasZambartas, Helen Kleanthous, Loizos Antoniades, Nicosia;Joseph A. Moutiris, Marios Ioannides, Limassol. Czech Republic:Jiri Spac, J. Spinar, Brno; Ivana Pirochtova, Brno; RenataKolosova, Frydek-Mistek; Miroslav Rubacek, Ostrava; TomasBrabec, Brno. Germany: E. Blank, G. Sabin, L. Waldelich,Essen; H.M. Hoffmeister, Sollingen; C. Seibold, R. Morell,Furstenfeldbruck; Frank Rupprecht, Mainz; Norbert Schoen,Muhldorf; Ralf Hewing, Munster; Corinna Lenz, U. Zeymer,Kassel; B. Witzenbichler, Heinz Peter Schultheiss, Berlin; AchimGutersohn, R. Erbel, S. Churzidse, Essen; A. Gitt, KonstanzeGehrke, J. Senges, U. Zeymer, Ludwigshafen am Rhein.Denmark: Helle Cappelen, Lisette Okkels Jensen, P. Thayssen,Odense C; Jan Kyst Madsen, Marie Seibaek, Copenhagen.Spain: L. Lopez Bescos, Madrid; Luis Hilario Villanueva, RaulMoreno, Rosana Hernandez, Madrid; Fernando Olaz Preciado,M. Soledad Alcasena Juango, Pamplona; Josep M. Alegret,Tarragona; C. Permanyer Miralda, Barcelona; Luis Sosa Martin,San Lorenzo de El Escorial; Maria Irurita Latasa, Las Palmas deGran Canaria; Josep Sadurni i Serrasolsas, Vic; Juan RamonSiles Rubio, Norbero Herrera Guttierez, Cabra (Cordoba);Isabel Antorrena Miranda, Villajoyosa; Alicia Bautista Paves,Motril; Antonio Salvador Sanz, Valencia; A. Alonso Garcia,Almudena Castro Conde, Madrid; Francisco Marin Ortuno,Alicante; Maria Jesus Salvador Taboada, Barcelona; FransiscoEpelde Gonzalo, Terrassa; Ignacio Santos Rodriguez, PedroL. Sanchez Fernandez, Salamanca. Finland: Kirsti Savolainen,S. Lehto, Kuopio. France: Thierry Lefevre, Massy; Jean JacquesBlanc, Brest; Herve Le Breton, Jean Michel Clerc, Rennes. UK:Alistair Pell, Judith Anderson, Airdrie; Helen Gracey, JenniferAdgey, Belfast; Bev Durkin, Wakefield; Bronia Ward, IanRushmer, Robert Bain, Grimsby; M.A. Memon, Bridlington;R. Muthusamy, Rotherham; R.A. Perry, S. Aziz, Liverpool;Judith Beevers, Paul Brooksby, Pontefract; Christopher Travill,Susan Gent, Luton; J.M. Glancy, Hereford; Graham Ranson, PhilKeeling, Torquay; Steven Lindsay, Bradford; Ali Khaddam,Merseyside; Lesley Davies, William J. Penny, Cardiff; EmmaBirks, Sam Kaddura, London; D. Wood, Joanna Tenkorang,London; Fhiona Holland, Jonathan Pitts, St Leonards-on-Sea;Jane Burton, Moira Marriott, Robert Henderson, Nottingham.Georgia: Gulnara Tabidze, Tbilisi. Greece: Nastasia Tsiavou,Athanassios Dritsas, D. Cokkinos, Athens; Christina Chrysohoou,Athens; Ioannis Vogiatzis, Veria; Alexandros Gotsis, Komotini;Dimitrios Psirropoulos, Thelassoniki; Vasilios Kotsis, Athens;Mary Marketou, Heraklion, Crete; Ioannis Skoularigis, Larisa;Evdokia Adamopoulou, Pireus. Croatia: Vjeran Nikolic Heitzler,Zagreb; Ante Samodol, Sibenik; Josip Vincelj, Zagreb. Hungary:Bato Zoltan, Istvan Preda, Budapest. Israel: A. Battler,Alejandro Solodky, Petach Tikva; Aviva Grosbard, Gisella Kon,Beer Sheva; Mohammed Omari, N. Kogan, Nazareth. Italy:


Dow



ovember 2021

Alfredo Galassi, Giuseppe Giuffrida, Catania; F. Naccarella,Stefano Sdringola Maranga, Bologna; Colomba Falcone, Pavia;Giuseppe Sangiorgi, San Donato Milan; Salvatore Novo,Palermo; Giuseppe Ambrosio, Perugia; Carla Boschetti,Francesco Pelliccia, Roma; Francesco De Tommasi, SanGiovanni Valdamo; Paolo Testarmata, Ancona; EmanueleCarbonieri, San Bonifacio; Gaetano Nucifora, Paolo Fioretti,Udine; Antonella Muscella, Giacento Pettinati, Casarano;Massimo Villella, San Giovanni Rotondo; Alessandro Boccanelli,Giorgio Bottero, Roma; Dorita Chersevani, Monfalcone; AndreaAlbani, Bolzano; Bruno Casiraghi, Seriate; Gabriella Giuliano,Gorizia; Piera Costanzo, De Marie, Rita Trinchero, Torino;Alessandro Desideri, Castelfranco Veneto; Claudio Pandullo,Trieste. Lebanon: Elie Chammas, Beirut. Lithuania: RutaBabarskiene, Kaunas; Milda Kovaite, V. Grabauskiene, Vilnius;Vitas Vysniauskas, Marijampole; Eugenijus Kosinskas, Vilnius.Latvia: Gustavs Latkovskis, Uldis Kalnins, Riga. Macedonia:Biljana Filipovska Simic, Skopje. Moldova: Eleanora Vataman,Kishinau. The Netherlands: Chris Jansen, J. Deckers, GDRotterdam; Arno Breeman, E. de Swart, Metske van der Wal,AB Zwolle; Henriette Tebbe, R. Brons, KA Meppel; ChrisJansen, Jeroen Vos, EA Rotterdam; Chris Jansen, C.M.Leenders, TD Rotterdam; Chris Jansen, Rotterdam; E. deSwart, Metske van der Wal, Harderwijk; Adrie van den Dool,Heidi Fransen, Robby Nieuwlaat, Maastricht; Henriette Tebbe,M.J. De Boer, Zwolle; Herman Broers, Robby Nieuwlaat,Tilburg; Colinda Koppelaar, M. Bijl, Dordrecht. Poland: AlicjaKowalska, Krystyna Loboz-Grudzien, Wroclaw; BeataWozakowska-Kaplon, Kielce; Malgorzata Krzciuk, OstrowiecSwietokrzyski; M. Krzeminska-Pakula, Michal Plewka, Lodz; AnnaLewczuk, Teresa Stefankowska-Olenska, Bialystok; JoannaBakun, Suwalki; Antoni Torunski, Grazyna Swiatecka, Gdansk;Jaroslaw Krol, Miroslaw Dluzniewski, Warszawa; ElzbietaZinka, Marek Gksecki, Koszalin; Jerzy Jankowski, Poznan;Krystyna Jaworska, Malgorzata Wagrowska, UrszulaKazmierczak, Torun; Lidia Orzechowska-Slomska, Chelmza;Aleksander Kabara, Golub Dobrzyn; Michal Plewka,T. Waszyrowski, Lodz; Teresa Kawka-Urbanek, Michal Plewka,Pawel Wojewoda, Skierniewice; Piotr Kokowicz, Warszawa;Hanna Kalotka-Kreglewska, Warszawa; Joanna Biegajlo,Warszawa; Jerzy Sacha, Wladyslaw Pluta, Opole; Anna Madro,Teresa Widomska-Czekajska, Lublin; Arkadiusz Stasiewski,Krzysztof Sokolowski, Tadeusz Krzys, Poznan;B. Grzegorzewski, Malgorzata Dudek-Niechcial, M. Pruski,Katowice; Jolanta Surwillo, Przemyslaw Aponowicz,Koscierzyna; Wlodzimierz Krasowski, Gdansk; Michal Szpajer,Gdynia; Bozena Adamczyk, Dabrowa Gornicza; Anna Krol,Lipno; Janusz Kostrzewa, Rypin; Marek Bronisz, Inowroclaw;Wlodzimierz Rajewski, Bydgoszcz; Andrzej Stojek, Irena Kulon,Krakow; Andrzej Gebala, Krakow; P. Buszman, KazimierzRadwan, Iwona Szkrobka, Katowice. Portugal: H. Madeira, LuisSargento, Lisbon; Daniel Ferreira, Rafael Ferreira, Amadora;Joao Carlos Araujo Morais, Leira; Pedro Sarmento, Lisbon;Madalena Teixeira, Vasco Gama Ribeiro, Gaia. Romania:Mircea Ioachim Popescu, Oradea; Bostaca Ioan, Iasi; CodinT. Olariu, Arad; Istvan Albert, Sfantu Gheorge; Anca Dan,Khalid Tammam, Bucarest; A. Iancu, Camelia Stanescu, Cluj-Napoca; M. Dorobantu, Bucharest; D. L. Dumitrascu, Cluj.Georgia: Bondo Kobulia, Gulnara Tabidze, Irina Jashi, ZazaChapichadze, Tbilisi. Russia: D. Aronov, Elena Tikhomirova, OlgaGoudkova, Moscow; Mirolyubova Olga, Arkhangelsk. Sweden: JanErik Karlsson, Jokoping; Matthias Lidin, Pia Oblack, Stockholm;K. Astrom-Olsson, Lund; Cecilia Dahlen, Falun. Slovenia: IztokGradecki, Novo Mesto; I. Kranjec, Katja Prokselj, Ljubljana;Vojko Kanic, Maribor. Slovakia: Eva Hrbata, Kosice; DanielaOndusova, Martin Studencan, Kosice; Peter Kurray, BanskaBystrica; Juraj Cencarik, Presov; Jan Murin, Bratislava. Turkey:

Baris Ikitimur, Capa-Istanbul; Emrullah Basar, Kayseri; BahattinBalci, Osman Yesildag, Kuruelit/Samsun; Zerrin Yigit, HasekiIstanbul; Ayhan Olcay, Capa Istanbul; Jale Cordan, Gorukle/Bursa. Ukraine: Mariya Orynchak, Ivano-Frankivsk. Serbia &Montenegro: Masar Gashi, Prishtina.

Appendix B

Definitions provided automiatically by ‘help text’ on electronicCase Record Form.

For the purposes of recording ECGabnormalities

ST depression: defined as depression of the ST segment.0.5 mm or .0.05 mm below the isoelectric line.

T wave inversion: defined as inversion of the Twave of the QRScomplex except in leads AVR, V1, and lead III.

Pathological Q waves: defined as Q waves (except in AVR, V1,and III) which are .0.04 s wide and 0.2 mm deep or .20% ofthe accompanying R wave.

On examination, clinical signs of heart failurewere defined as the following

Elevated venous pressure, hepatomegaly, dependent oedema,crepitations, gallop rhythm, or evidence of cardiac enlargement.

Comorbid conditions and risk factors

Hepatic disease: chronic hepatitis or cirrhosis, or other hepaticdisease causing elevation of transaminases more than threetimes the upper limit of normal.

Peripheral vascular disease: claudication either at rest or exer-tion, amputation for arterial vascular insufficiency, vascularsurgery (reconstruction or bypass) or angioplasty to the extremi-ties, documented aortic aneurysm, or non-invasive evidence ofimpaired arterial flow.

Chronic renal failure: chronic dialysis or renal transplantationor serum creatinine .200 mmol/L.

Chronic respiratory disease: diagnosis previously made by phys-ician, or patient receiving bronchodilators, or values of FEV1,75%, arterial pO2 ,60%, or arterial pCO2 . 50% in priorstudies.

Chronic inflammatory conditions: diagnosis of rheumatoidarthritis, systemic lupus erythematosis or other connectivetissue diseases, polymyalgia rheumatica, etc.

Peptic ulcer disease: Active peptic ulcer disease or on treat-ment for peptic ulcer disease.

Malignancy: diagnosis within 1 year or active malignancy.

Hypertension: treated hypertension, on anti-hypertensivetherapy.

Hyperlipidaemia: treated hyperlipidaemia, on lipid loweringmedication, or specific dietary modification.

Diabetes: treated diabetes, on insulin or oral diabetic medi-cation, or specific dietary modification.

Family history of premature coronary artery disease (CAD): ahistory of angina pectoris, myocardial infarction or sudden deathamong first-degree relatives under the age of 55 years for malerelatives and 65 years for female relatives.


Dow



ovember 2021

References

1. Kannel WB, Feinleib M. Natural history of angina pectoris in theFramingham study. Prognosis and survival. Am J Cardiol 1972;29:154–163.

2. Phillips SJ, Whisnant JP, O Fallon WM et al. Prevalence of cardio-vascular disease and diabetes mellitus in residents of Rochester,Minnesota. Mayo Clin Proc 1990;65:344–359.

3. Mittlemark MB, Psaty BM, Rautaharju PM et al. for the CardiovascularHealth Study Collaborative Research Group. Prevalence of cardio-vascular diseases in older adults. Am J Epidemiol 1993;137:311–317.

4. Smith W, Kenicer M, Tunstall-Pedoe H et al. Prevalence of coronaryheart disease in Scotland: Scottish Heart Study. Br Heart J1990;65:344–359.

5. Shaper A, Cook D, Walker M et al. Prevalence of ischaemic heartdisease in middle aged British men. Br Heart J 1984;51:595–605.

6. Sigurdsson E, Thorgeirsson G, Sigvaldason H et al. Prevalence ofcoronary heart disease in Icelandic Men 1968-1986. The ReykjavikStudy. Eur Heart J 1993;14:584–591.

7. Hasdai D, Behar S, Wallentin L et al. A prospective survey of thecharacteristics, treatments and outcomes of patients with acutecoronary syndromes in Europe and the Mediterranean basin:the Euro Heart Survey of Acute Coronary Syndromes (Euro HeartSurvey ACS). Eur Heart J 2002;23:1190–1201.

8. Fox KA, Cokkinos DV, Deckers J et al. The ENACT study: a pan-European survey of acute coronary syndromes. European Networkfor Acute Coronary Treatment. Eur Heart J 2000;21:1440–1449.

9. Collinson J, Flather MD, Fox KA et al. Clinical outcomes, risk stratifi-cation and practice patterns of unstable angina and myocardialinfarction without ST elevation: Prospective Registry of AcuteIschaemic Syndromes in the UK (PRAIS-UK). Eur Heart J 2000;21:1450–1457.

10. Steg PG, Goldberg RJ, Gore JM et al. GRACE Investigators Baselinecharacteristics, management practices, and in-hospital outcomes ofpatients hospitalized with acute coronary syndromes in the GlobalRegistry of Acute Coronary Events (GRACE). Am J Cardiol 2002;90:358–363.

11. Hoekstra JW, Pollack CV Jr, Roe MT et al. Improving the care ofpatients with non-ST-elevation acute coronary syndromes in theemergency department: the CRUSADE initiative. Acad Emerg Med2002;9:1146–1155.

12. Sullivan A, Holdright D, Wright C et al. Chest pain in women: clinical,investigative and prognostic features. Br Med J 1994;308:883–886.

13. Mock M, Ringqvist I, Fisher L et al. Survival of medically treatedpatients in the Coronary Artery Surgery Study (CASS) Registry.Circinogenesis 1982;66:562–568.

14. Madsen JK, Bech J, Jorgensen E et al. Yield of 5,536 diagnosticcoronary arteriographies: results from a data registry. Cardiology2002;98:191–194.

15. Roeters van Lennep JE, Zwinderman AH, Roeters van Lennep HW.Gender differences in diagnosis and treatment of coronary arterydisease from 1981 to 1997. No evidence for the Yentl syndrome.Eur Heart J 2000;21:911–918.

16. Kressin N, Petersen L. Racial differences in the use of invasivecardiovascular procedures: review of the Literature and Prescriptionfor Future Research. Ann Intern Med 2001;135:352–366.

17. Tobin JN, Wassertheil-Smoller S, Wexler JP et al. Sex Bias in consider-ing coronary bypass surgery. Ann Intern Med 1987;107:19–25.

18. Shaw L, Miller D, Romeis J et al. Gender differences in the non inva-sive evaluation and management of patients with suspected coronaryartery disease. Ann Intern Med 1994;120:559–566.

19. Miller T, Roger V, Hodge D et al. Gender differences and temporaltrends in clinical characteristics, stress test results and use of inva-sive procedures in patients undergoing evaluation for coronaryartery disease. J Am Coll Cardiol 2001;38:690–697.

20. Lauer M, Pashkow F, Snader C et al. Age and referral to coronaryangiography after an abnormal treadmill thallium test. Am Heart J1997;133:139–146.

21. Wong Y, Rodwell A, Dawkins S et al. Sex differences in investigationresults and treatment in subjects refereed for investigation ofchest pain. Heart 2001;85:149–152.

22. Ghandi MM, Lampe F, Wood DA, Incidence of stable angina pectoris.Eur Heart J 1992;13:181–189.

23. Roger V, Jacobsen S, Pellika P et al. Gender differences in the use ofstress testing and coronary heart disease mortality: a populationbased study in Olmstead county, Minnesota. J Am Coll Cardiol 1998;32:345–352.

24. Management of Stable Angina Pectoris. Recommendations of the TaskForce of the European Society of Cardiology. Eur Heart J 1997;18:394–413.

25. Gibbons RJ, Chatterjee K, Daley J et al. ACC/AHA/ACP-ASIMGuidelines for the management of patients with chronic stableangina. J Am Coll Cardiol 1999; 33:2092–2197.

26. Gibbons RJ, Abrams J, Chatterjee K et al. American College ofCardiology; American Heart Association Task Force on PracticeGuidelines. Committee on the Management of Patients WithChronic Stable AnginaACC/AHA 2002 guideline update for the man-agement of patients with chronic stable angina—summary article: areport of the American College of Cardiology/American HeartAssociation Task Force on Practice Guidelines (Committee on theManagement of Patients With Chronic Stable Angina). Circulation2003;107:149–158.

27. Cleland J, Swedberg K, Follath F et al. The Euro Heart Failure SurveyProgramme—a survey on the quality of care among patients withHeart Failure in Europe. Part 1: patients characteristics and diagno-sis. Eur Heart J 2003;24:442–463.

28. Komajda M, Follath F, Swedberg K et al. The Euro Heart FailureSurvey Programme—a survey on the quality of care among patientswith Heart Failure in Europe. Part 2: treatment. Eur Heart J2003;24:464–475.

29. Cohen-Solal A, Desnos M, Delahaye F et al. A national survey of heartfailure in French hospitals. Eur Heart J 2000;3:503–507.

30. Cleland JGF, Cohen-Solal A, Cosin-Aguilar J et al. An InternationalSurvey of the Management of Heart Failure in Primary Care. TheIMPROVEMENT of Heart Failure Programme. Lancet 2002;360:1631–1639.

31. Lerner A, Kannel W. Patterns of Coronary Heart Disease morbidityand mortality in the sexes: a 26 year follow up of the Framinghampopulation. Am Heart J 1985;111:383–390.

32. Reunanen A, Suhonen O, Aromaa A et al. Incidence of differentmanifestations of coronary heart disease in middle-aged Finnishmen and women. Acta Med Scand 1985;218:19–26.

33. EUROASPIRE II study group. Lifestyle and risk factor managementand use of drug therapies in coronary patients from 15 countries;principal results from EUROASPIRE II Euro Heart Survey Programme.Eur Heart J 2001;22:554–572.

34. Cuspidi C, Michev I, Lonati L et al. Compliance to hypertensive guide-lines in clinical practice: a multicentre pilot study in Italy. J HumHypertens 2003;16:699–703.

35. Lacy CR, Suh DC, Barone JA et al. Impact of a targeted interventionon lipid lowering therapy in patients with coronary artery disease inthe hospital setting. Arch Intern Med 2002;162:468–473.

36. Malach M, Quinley J, Imperato PJ et al. Improving lipid evaluationand management in Medicare patients hospitalised for acute myocar-dial infarction. Arch Intern Med 2001;161:839–844.

37. Norhammer A, Tenerz A, Nilsson G et al. Glucose metabolism inpatients with acute myocardial infarction and no previous diagnosisof diabetes mellitus. Lancet 2002;359:2140–2144.

38. Bartnik M, Ryden L, Ferrari R et al. The prevalence of abnormalglucose regulation in patients with coronary artery disease acrossEurope. Eur Heart J 2004;25:1880–1890.

39. Hammermeister KE, De Rouen TA, Dodge HT. Variables predictive ofsurvival in patients with coronary disease. Selection by univariateand multivariable analysis from the clinical, exercise arteriographic,and quantitative angiographic evaluations. Circulation 1979;59:421–430.

40. Mock MB, Rinqvist I, Fisher L et al. and participants in the CoronaryArtery Surgery Study. Survival of medically treated patients in theCoronary Artery Surgery Study (CASS) Registry. Circulation 1982;66:562–568.

41. Marchioli R, Avansini F, Barzi F et al., on behalf of the GISSI-Prevenzione Investigators. Assessment of absolute risk of deathafter myocardial infarction by use of multiple-risk-factor assessmentequations. GISSI-Prevenzione mortality risk chart. Eur Heart J 2001;22:2085–2103.


Dow



ovember 2021

42. Daly C, Norrie J, Murdoch DL et al. for the TIBET group. The value ofroutine non-invasive tests to predict clinical outcome in stableangina. Eur Heart J 2003;24:532–540.

43. Boys RJ, Forster DP, Jozan P. Mortality from causes amenable andnon amenable to medical care: the experience of Central Europe.Br Med J 1991;303:879–883.

44. Velkova A, Wolleswinkel-van den Bosch JH, Mackenbach JP. TheEast-West life expectancy gap: differences in mortality from con-ditions amenable to medical intervention. Int J Epidemiol 1997;26:75–84.

45. Carlisle D, Leape L, Bickel S et al. Underuse and overuse of diagnostictesting for coronary artery disease in patients presenting with newonset chest pain. Am J Med 1999;106:391–398.

46. Weiner DA, Ryan TJ, Parsons L et al. Long term prognostic value ofexercise testing in men and women from the Coronary ArterySurgery Study (CASS) Registry. Am J Cardiol 1995;75:865–870.

47. Califf RM, Mark DB, Harrell FE et al. Importance of Clinical measuresof ischaemia in the prognosis of patients with documented coronarydisease. J Am Coll Cardiol 1988;11:20–26.

48. Mark D, Hlatky M, Harrell R et al. Exercise treadmill score for predict-ing prognosis in coronary artery disease. Ann Intern Med 1987;106:793–800.

49. Wittels E, Haty J, Gotto A. Medical costs of coronary artery disease inthe United States. Am J Cardiol 1990;65:432–440.

50. Verrilli D, Welch G. The impact of diagnostic testing on therapeuticinterventions. JAMA 1996;275:1189–1191.

51. Rosiano S, Tocchi M, Cutler D et al. Queuing for coronary angiographyduring severe supply-demand mismatch in a US public hospital.Analysis of a waiting list registry. JAMA 1999;282:145–152.

52. Steg G, Iung B, Feldman LJ et al. ENACT investigators determinants ofuse and outcomes of invasive coronary procedures in acute coronarysyndromes: results from ENACT. Eur Heart J 2003;24:613–622.


Dow



ovember 2021

Documents

The clinical characteristics and investigations planned in patients