Archives of Cardiovascular Disease (2015) 108, 675—682

Available online at

ScienceDirectwww.sciencedirect.com

REVIEW

Screening for coronary artery disease inasymptomatic individuals: Why and how?Pourquoi et comment dépister la maladie coronaire chez le sujetasymptomatique ?

Philippe Degrell a,b,c, Emmanuel Sorbetsa,b,c,Laurent J. Feldmana,b,c, Philippe Gabriel Stega,b,c,d,Gregory Ducrocqa,b,c,∗

a Département hospitalo-universitaire fibrose, inflammation, remodelage (FIRE), FrenchAlliance for Cardiovascular clinical Trials (FACT) and F-CRIN network, universitéParis-Diderot, Sorbonne Paris Cité, Paris, Franceb Hôpital Bichat and hôpital Avicenne, Assistance publique—Hôpitaux de Paris, hôpitauxuniversitaires Paris Nord Val-de-Seine, Paris, Francec Inserm U-1148, Paris, Franced National Heart and Lung Institute, Royal Brompton Hospital, London, United Kingdom

Received 26 August 2015; received in revised form 4 October 2015; accepted 5 October 2015Available online 16 November 2015

KEYWORDSCardiovascular risk;Coronary artery

Summary Cardiovascular disease is still the main cause of death in the world, and coronaryartery disease is the largest contributor. Screening asymptomatic individuals for coronary arterydisease in view of preventive treatment is therefore of crucial interest. Apart from established

disease;Coronary arterycalcium score;Screening;Prevention

risk scores based on traditional risk factors such as the Framingham or SCORE risk scores, newbiomarkers and imaging methods have emerged (high-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2 and secretory phospholipase A2, coronary artery calcium score,

Abbreviations: ABI, ankle-brachial index; ACC, American College of Cardiology; AHA, American Heart Association; BARI-2D, bypassangioplasty revascularization investigation 2 diabetes; CACS, coronary artery calcium score; CI, confidence interval; CIMT, carotid intima-media thickness; COURAGE, clinical outcomes utilizing revascularization and aggressive drug evaluation; ESC, European Society of Cardiology;FRS, Framingham risk score; hs-CRP, high-sensitivity C-reactive protein; Lp-PLA2, lipoprotein-associated phospholipase A2; MESA, Multi-Ethnic Study of Atherosclerosis.

∗ Corresponding author. Service de cardiologie, hôpital Bichat, 46, rue Henri-Huchard, 75877 Paris cedex 18, France.E-mail address: gregory.ducrocq@bch.aphp.fr (G. Ducrocq).

http://dx.doi.org/10.1016/j.acvd.2015.10.0011875-2136/© 2015 Elsevier Masson SAS. All rights reserved.

676 P. Degrell et al.

carotid intima-media thickness and ankle-brachial index). Their added value on top of theclassic risk scores varies considerably and the most convincing evidence exists for coronaryartery calcium score in intermediate-risk asymptomatic individuals.© 2015 Elsevier Masson SAS. All rights reserved.

MOTS CLÉSRisquecardiovasculaire ;Maladie coronaire ;Score calcique ;Dépistage ;Prévention

Résumé Les maladies cardiovasculaires représentent toujours la première cause de mortalitédans le monde, et la coronaropathie en constitue la majeure partie. Le dépistage de la maladiecoronaire chez les sujets asymptomatiques dans le but d’instaurer un traitement préventifprésente donc un intérêt majeur. À côté des scores de risque établis basés sur les facteursde risque traditionnels, comme le score de Framingham ou la méthode SCORE, de nouveauxbiomarqueurs ou méthodes d’imagerie ont fait leur apparition (la protéine C-réactive ultra-sensible, la phospholipase A2 associée aux lipoprotéines et la phospholipase A2 sécrétoire, lescore calcique, l’épaisseur intima-media carotidienne et l’index de pression systolique). Leurvaleur ajoutée aux scores de risque classiques varie fortement en fonction du marqueur utilisé.Les preuves les plus solides existent pour le score calcique chez les sujets asymptomatiques àrisque intermédiaire.© 2015 Elsevier Masson SAS. Tous droits réservés.

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oronary heart disease: the leading causef death worldwide

espite an important reduction in cardiovascular mortalityn western countries [1,2], cardiovascular diseases are stillhe main causes of mortality in the world. In 2010, one inour deaths was attributable to ischaemic heart disease ortroke, compared to one in five in 1990 [3]. Likewise, inurope, cardiovascular diseases were responsible for morehan half of deaths in women and 42% of deaths in men,ainly due to coronary heart disease [4]. Data are similar

n low-income countries, with more than 12 million deathselated to cardiovascular causes [5].

hy should we screen asymptomaticndividuals for cardiovascular disease?

therosclerosis is a slowly progressing disease, character-zed by a long asymptomatic period of several decades.ipid-rich plaques develop in the arterial vessel walls anday be revealed by typical symptoms, such as anginaectoris or intermittent claudication, in stable patients.owever, the disease can also be revealed by an acutevent, such as an acute coronary syndrome or stroke, with-ut any preceding symptoms and, in the worst case, byudden death. It is therefore crucial to develop a screeningtrategy in asymptomatic individuals before potentially fatalvents occur.

Cardiovascular screening in asymptomatic individualsims at the identification of intermediate- or high-riskndividuals. The objective is to initiate strategies that

ould reduce their incidence of ischaemic events (includingyocardial infarction) and ultimately cardiovascular death.ifferent preventive strategies have been proposed.

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First, cardiovascular risk can be reduced by optimal riskactor management and lifestyle changes. Smoking cessations a cornerstone of cardiovascular disease prevention andepresents a public health problem because of the effectf passive smoking [6]. All smokers should be encouragedo quit smoking by various smoking-cessation therapies [7].urthermore, a healthy diet and regular exercise are partf the general cardiovascular prevention measures appli-able to the entire population [8,9]. Thus, around halff the reduction in deaths from coronary heart disease isttributable to better management of cardiovascular riskactors and the other half to advances in medical treatments10].

Second, a preventive medical treatment can be consid-red before an acute cardiovascular event occurs. However,n a low-risk population, further risk assessment using noveliomarkers is not cost-effective. Furthermore, in a high-riskopulation, pharmacological treatment is usually mandatoryor the majority of the patients and further risk assessmentill not change this strategy. Conversely, in intermediate-

isk individuals, further risk assessment by novel risk markersould refine cardiovascular risk and, in case of positivecreening, indicate preventive pharmacological treatment.he effectiveness of statin treatment for primary preven-ion in a population with cardiovascular risk factors haseen shown in large meta-analyses [11,12]. Statins reduceortality and the risk of major cardiovascular and cere-rovascular events in people without known cardiovascularisease. Similarly, the effect of blood pressure reduction byntihypertensive drugs on cardiovascular disease preventionn a population without established cardiovascular diseaseas been demonstrated extensively, irrespective of the class

f blood pressure lowering drugs used [13].

Another, more invasive, strategy could be ‘preventive’oronary revascularization. However, most acute myocardial

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infarctions evolve from mildly obstructive coronary plaques,which are not addressed by angioplasty in stable ischaemicheart disease [14]. Thus, preventive revascularization ofobstructive coronary stenosis may only have a limited effecton incident myocardial infarction and mortality comparedwith medical treatment. This has been demonstrated bytwo large trials conducted in the modern era. The ClinicalOutcomes Utilizing Revascularization and Aggressive DrugEvaluation (COURAGE) trial [15] randomized 2287 patientswith significant stable coronary artery disease and objec-tive evidence of myocardial ischaemia to optimal medicaltreatment, alone or combined with angioplasty. After amedian 4.6-year follow-up, the primary outcome of deathfrom any cause and non-fatal myocardial infarction wasnot significantly different between the two groups (haz-ard ratio [HR] 1.05, 95% confidence interval [CI] 0.87—1.27,P = 0.62). Mortality was also similar in the two groups (HR0.87, 95% CI 0.65—1.16, P = 0.38). Similarly, bypass angio-plasty revascularization investigation 2 diabetes (BARI-2D),a randomized trial in 2368 diabetic patients with stable coro-nary artery disease, showed no survival difference betweenoptimal medical treatment, alone (87.8%) or combined withangioplasty (88.3%) after a mean of 5.3 years of follow-up (P = 0.97) [16]. A recent meta-analysis on this subject,published in 2013 [17], included five randomized trialscomprised of 5286 patients with stable obstructive coro-nary artery disease, of whom 4064 had proven myocardialischaemia. In line with the previous results, there was nosignificant difference between optimal medical treatmentand angioplasty compared to optimal medical treatmentalone.

In order to clarify the benefits of coronary revas-cularization in stable coronary artery disease, a largerandomized trial of 8000 patients, the International Studyof Comparative Health Effectiveness with Medical and Inva-sive Approaches (ISCHEMIA) (ClinicalTrials.gov Identifier:NCT01471522), is currently ongoing. This study is compar-ing an initial invasive strategy with percutaneous coronaryintervention or coronary artery bypass surgery along withoptimal medical treatment to a more conservative strat-egy with optimal medical treatment alone. To meet theinclusion criteria, all patients must have at least moder-ate ischaemia (identified on an ischaemia test) and a leftventricular ejection fraction >35%. After approximately 4years of follow-up, the composite primary endpoint of car-diovascular death or myocardial infarction will be assessed.This trial may answer some of the questions that still persiston the real benefit of angioplasty in stable ischaemic heartdisease.

Cardiovascular risk prediction bytraditional risk factors

In 1948, a large, ongoing, longitudinal observational studywas started in Framingham (USA) to study cardiovascular dis-ease. Results allowed the definition of, among other things,the well-known Framingham risk score (FRS). Six easily

available items, namely sex, age, cigarette smoking, bloodpressure, lipid profile and diabetes mellitus, allow an esti-mation of the relative and absolute 10-year risk for coronaryheart disease [18].

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Cardiovascular risk is different across populations and aisk score is only applicable in the population it was val-dated in [19]. In fact, in Europe, mortality rates differrom North to South and from East to West, being highern the Northeast part of Europe. This geographical gradienteeds to be taken into account when assessing cardiovascu-ar risk for primary prevention [20]. Thus, similarly to theRS, the European Society of Cardiology (ESC) developed

risk score to predict the 10-year risk of fatal cardiovas-ular disease, stratified by high- or low-risk regions, calledCORE [21] (Fig. 1 [22]). The ESC guidelines on cardiovas-ular disease prevention in clinical practice recommend these of this score for total risk estimation in asymptomaticdults without evidence of cardiovascular disease [22]. Sim-larly, the QRISK2 score, an updated version of the QRISKcore, should be used to estimate the 10-year risk of cardio-ascular disease of the population in the United Kingdom,ecause of its good discriminative and calibration properties23].

These risk scores are not, however, perfect predictionools—the performance of the SCORE method is given by aeceiver operating curve area of 0.81 (95% CI 0.80—0.82)n high-risk regions and 0.74 (95% CI 0.72—0.76) in low-riskegions, and should be further improved. Intense effortsre therefore being made to improve their discriminativeerformance, by the inclusion of novel biomarkers or devel-ping new imaging techniques.

ew methods for the assessment ofardiovascular risk

everal new methods for risk assessment, using either imag-ng or biomarkers, have been developed over the pastecade, with variable success. We review below the evi-ence for the main methods in the context of the recentlyublished Guideline on the Assessment of Cardiovascularisk from the American College of Cardiology (ACC) and themerican Heart Association (AHA) [24].

nkle-brachial index

ne of the simplest and most cost-effective markers ofisk is the ankle-brachial index (ABI). The result is avail-ble immediately and can be interpreted at the patient’sedside. In 2008, Fowkes et al. [25] reported, in a meta-nalysis that included 16 population cohort studies with8,294 healthy individuals, that a low ABI (≤ 0.9) was asso-iated with increased 10-year cardiovascular mortality afterdjusting for FRS (HR 2.9, 95% CI 2.3—3.7 for men and HR.0, 95% CI 2.0—4.4 for women). Nevertheless, the increasen c-statistics, compared with those using FRS alone, wasnly modest and not significant in men (from 0.646 to.655), but increased from 0.605 to 0.658 in women. More-ver, a recent double-blind randomized controlled trial thatcreened 28,980 asymptomatic participants without known

ardiovascular disease on the basis of ABI for treatment withither low-dose aspirin or placebo did not find any improve-ent in outcomes after a mean follow-up of 8.2 years [26].uidelines agree that ABI has a class IIb (AHA/ACC) or class

678 P. Degrell et al.

Figure 1. SCORE chart: 10-year risk of fatal cardiovascular disease in countries at low risk based on the following risk factors: age,sex, smoking, systolic blood pressure and total cholesterol. CVD: cardiovascular disease. From Perk et al. [22] with permission. Low CVDcountries are Andorra, Austria, Belgium, Cyprus, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Israel, Italy, Luxembourg,M venia

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igh-sensitivity C-reactive protein

ne of the most studied emerging risk factors is probablyigh-sensitivity C-reactive protein (hs-CRP). A large meta-nalysis [27] has shown that CRP concentration predictedascular death in 160,039 individuals without known vascu-ar disease after adjustment for age and sex. However, itredicted non-vascular death, for example death from can-er or respiratory disease, to the same extent. Thus, thectual value of higher CRP concentrations in the individualatient setting remains unclear and the recent ESC [22] and

CC/AHA [24] guidelines did not recommend hs-CRP mea-urement in asymptomatic low- or high-risk individuals (classII, level B), but suggested it might be useful for refining theisk in intermediate-risk individuals (class IIb, level B).

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, Spain, Sweden, Switzerland, United Kingdom.

ipoprotein-associated phospholipase A2

ipoprotein-associated phospholipase A2 (Lp-PLA2),n enzyme that is expressed by inflammatory cells intherosclerotic plaques, plays a major role in the pro-ression of the disease by producing pro-inflammatorynd pro-apoptotic mediators via oxidized phospholipidsydrolysis. The result is a sustained inflammation at thelaque level with an expansion of the necrotic core. In006, Folsom et al. [28] reported a series of case-cohorttudies including 15,792 participants followed up for 5ears for incident coronary heart disease. Several noveliomarkers were assessed as well as the traditional riskactors. Although Lp-PLA2 was associated with incident

oronary heart disease after established risk factor adjust-ent (HR 1.17, P = 0.02), the c-statistic increment was onlyoderate, from 0.774 to 0.780. Another study indicated

hat Lp-PLA2 predicted survival free of coronary events in

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a population of 1077 individuals without known coronaryheart disease [29]. Similarly, Tsimikas et al. [30] published,in 2009, data from 765 subjects followed up prospectivelyfor 10 years. They showed a significant relationship betweenLp-PLA2 activity and incident cardiovascular disease, butonly a modest increase in c-statistic, from 0.717 to 0.737(P = 0.31), compared to established risk factors alone. Oneof the largest meta-analyses summarized data from 79,036individuals participating in 32 prospective studies [31]. Afteradjustment for conventional risk factors, risk ratios for inci-dent coronary heart disease were 1.09 (95% CI 1.02—1.16)for Lp-PLA2 mass and 1.03 (95% CI 0.95—1.12) for Lp-PLA2activity. Finally, a large randomized, double-blind trialassigned 15,828 patients with stable coronary heart diseaseto receive darapladib, a selective oral inhibitor of Lp-PLA2,or placebo [32]. After a median follow-up of 3.7 years,there was no significant difference in the primary endpoint,a composite of cardiovascular death, myocardial infarctionor stroke (HR 0.94, 95% CI 0.85—1.03, P = 0.199). These datameant that Lp-PLA2 assessment was only recommended forpatients at high risk for a recurrent acute atherothromboticevent in the 2012 ESC guidelines [22] (class IIb, level B),and it was not included in the 2013 AHA/ACC guideline[24].

Coronary artery calcium score

The assessment of coronary artery calcium by ultrafast com-puted tomography and its quantification by a score was firstdescribed by Agatston et al. [33] in 1990. A coronary arterycalcification was defined as a hyper-attenuating lesion >130Hounsfield units with an area ≥1 mm2. A score for eachregion of interest is calculated by multiplying the lesion area(mm2) by a density factor (between 1 and 4). The total coro-nary artery calcium score (CACS) is determined by adding upeach of these scores for 20 slices, with a slice thickness of3 mm. Since then, several other scoring systems have beenproposed: the volume score method and the calcium massscore. Two methods are used for the assessment: electronbeam computed tomography and, more recently, multide-tector computed tomography [34].

In 2005, Taylor et al. [35] published data from a non-referred cohort of 2000 healthy men and women agedbetween 40 and 50 years old and with a 3-year follow-up. Incident acute coronary syndromes and cardiac deathoccurred in 0.16% of the men without coronary calcium ver-sus 1.95% of the men with coronary calcium (P < 0.0001).This risk was incremental across increasing coronary arterycalcium tertiles (HR 4.3 per quartile, P = 0.036) after riskfactor adjustment. Likewise, Detrano et al. [36] reportedan increase in major cardiac events across different calciumscore categories, in 6722 participants of different ethnicorigins without known coronary artery disease at baseline,after a mean follow-up of 3.8 years (P < 0.001). Raggi et al.[37] studied the prognostic value of CACS in 35,388 elderlyasymptomatic participants without known coronary arterydisease and a mean of 5.8 years of follow-up. Survivaldecreased across age deciles and with higher CACS cate-

gories (P < 0.0001). These data showed a relation betweenhigh CACS values and an increasing cardiovascular diseaserisk in healthy individuals, but do not demonstrate an addedvalue of CACS over established risk factor scores.

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In 2004, Greenland et al. [38] evaluated the additionalrognostic value of CACS in 1312 asymptomatic partici-ants without known coronary heart disease or diabetesfter 7 years of follow-up. Eighty-four patients experiencedyocardial infarction or death from coronary heart disease,

nd CACS predicted these events only in individuals with anRS >10% (P < 0.001), supporting its value for risk stratifica-ion within subjects at intermediate risk. Receiver operatingurves showed an increase in area under the curve — andherefore in diagnostic performance — from 0.63 with FRSlone to 0.68 with FRS in combination with CACS (P < 0.001).imilarly, a meta-analysis that included nine studies evalu-ted the value of adding CACS to established risk factors insymptomatic subjects [39]. It showed an improvement inhe c-statistic from 0.05 to 0.13 and a net reclassificationmprovement from 14 to 25%.

The subgroup deriving the highest value for CACS reclas-ification has been evaluated in a large population-basedohort of 5878 asymptomatic participants without knownoronary heart disease or diabetes (mean follow-up of 5.8ears) [40]. The reclassification benefit after adding CACS tostablished risk factors was most evident in intermediate-isk categories (defined by a 3—10% 5-year risk of incidentoronary heart disease), because 77% of the participantsere classified in the extreme risk categories, compared

o 69% with FRS alone. These data were confirmed in theotterdam study [41] that comprised 2028 asymptomaticarticipants evaluated after a median of 9.2 years of follow-p. In this study, 52% of the patients of the intermediate-riskroup (10—20% by FRS) were reclassified after adding CACSvaluation. Finally, Erbel et al. [42] published, in 2010, theutcomes of 4129 individuals with no coronary artery dis-ase at baseline. The net reclassification improvement forhe intermediate-risk group (10—20% according to FRS) afterhe addition of CACS was 21.7% (P = 0.0002); the receiverperating curve increased from 0.681 to 0.749 (P = 0.003)ith CACS, and CACS improved prediction of coronary deathr non-fatal myocardial infarction when added to conven-ional risk scoring. A 10-year follow-up of the Multi-Ethnictudy of Atherosclerosis (MESA) cohort has shown very lowvent rates in those with zero coronary artery calcium [43].ltimately, CACS may help match statin therapy to absoluteardiovascular disease risk [44].

oronary artery calcium score limitationsACS is assessed by computed tomography, which uses X-raysnd exposes the patient to ionizing radiation. The aver-ge effective dose ranges from 0.7 to 1.8 mSv, around 10imes the effective dose of a chest X-ray, but it has recentlyeen shown that low-dose scanning (0.37 mSv) can be asffective as the standard dose [45]. However, in cardiovas-ular risk assessment, a certain proportion of the screenedndividuals are healthy and this radiation exposure muste justified. Kim et al. [46] studied, in 2009, the lifetimexcess cancer risk due to radiation exposure from a singlexamination at the age of 40 and showed that for a medianose of 2.3 mSv, this risk reached nine cancers per 100,000

en and 28 cancers per 100,000 women. Another issue con-

erns cost-effectiveness, because the cost of a computedomography examination is approximately 100 US$. A recentost-effectiveness study suggested that screening with CACS

680

Figure 2. Receiver operator characteristic curves showing areaunder the curve for A. incident coronary heart diseasea; and B.incident cardiovascular diseaseb, in intermediate-risk MESA partici-pants. From Yeboah et al. [50] with permission. aC-statistics forFRS alone, 0.623; FRS plus coronary artery calcium, 0.784 (P <0.001); FRS plus intima-media thickness, 0.652 (P = 0.01); FRS plusflow-mediated dilation, 0.639 (P = 0.06); FRS plus high-sensitivityC-reactive protein, 0.640 (P = 0.03); FRS plus family history, 0.675(P = 0.001); and FRS plus ankle-brachial index, 0.650 (P = 0.01).bC-statistics for FRS alone, 0.623; FRS plus coronary artery cal-cium, 0.784 (P < 0.001); FRS plus intima-media thickness, 0.652(P = 0.01); FRS plus flow-mediated dilation, 0.639 (P = 0.06); FRSplus high-sensitivity C-reactive protein, 0.640 (P = 0.03); FRS plusfamily history, 0.675 (P = 0.001); and FRS plus ankle-brachial index,

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n intermediate-risk men is superior to the current practice47].

The ESC prevention guidelines [22] state that CACSshould be considered’ in intermediate-risk asymptomaticndividuals for cardiovascular risk assessment (class IIa, level). To the same extent, the AHA/ACC guideline [24] indicates

class IIb, level B for CACS use in this setting.

arotid intima-media thickness

ecent evidence suggests that carotid intima-media thick-ess (CIMT) has a poor added value when combined with theRS to refine cardiovascular risk assessment in asymptomaticndividuals. A recent meta-analysis pooled data from 14opulation-based cohorts with 45,828 individuals withoutnown cardiovascular disease [48]. Overall, the net reclas-ification improvement was small (0.8%, 95% CI 0.1—1.6%),ven when considering only intermediate-risk individuals3.6%, 95% CI 2.7—4.6%). Thus, there is little reclassifica-ion benefit after adding CIMT to FRS for predicting the0-year absolute risk for myocardial infarction or stroke,ith c-statistics of 0.759 versus 0.757. Furthermore, CIMTeasurement lacks standardization and there are concerns

egarding interobserver variability [49]. As a consequence,he AHA/ACC guideline [24] advised against the use of CIMTn this setting (class III, level B).

hat is finally left of the new methods forisk assessment?

verall, the added value of emerging risk markers on topf standard risk score appears limited. A large head-to-ead comparison of six novel risk markers has included330 intermediate-risk participants without diabetes ofhe MESA cohort [50]. Intermediate risk was defined by—20% risk according to FRS, and the primary outcomeas incident coronary heart disease defined as myocardial

nfarction, angina followed by revascularization, resusci-ated cardiac arrest or death from coronary heart disease.fter a median 7.6-year follow-up, CACS, ABI, hs-CRP andamily history were independently associated with incidentoronary heart disease in multivariable analyses (HR 2.60,5% CI 1.94—3.50; HR 0.79, 95% CI 0.66—0.95; HR 1.28,5% CI 1.00—1.64 and HR 2.18, 95% CI 1.38—3.42, respec-ively). CIMT and brachial flow-mediated dilation were notssociated with incident coronary heart disease in multivari-ble analyses (HR 1.17, 95% CI 0.95—1.45 and HR 0.95, 95%I 0.78—1.14, respectively). To compare the added valuef each marker to the FRS, areas under the curve werealculated for each of them: CACS showed the biggest incre-ent in c-statistic, from 0.623 to 0.784 (P < 0.001). The five

ther markers showed only modest increments in c-statisticsFig. 2) [50].

As a consequence, their systematic use is currentlyot recommended. The AHA/ACC guideline from 2013 [24]tated that if, after quantitative risk assessment, a risk-ased treatment decision is uncertain, assessment of one

.650 (P = 0.01). MESA: Multi-Ethnic Study of Atherosclerosis; FRS:ramingham risk score.

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or more of the four markers (family history, hs-CRP, CACS,ABI) may be considered to inform treatment decision-making(class IIb, level B). Current ESC guidelines for cardiovasculardisease prevention [22] globally agree with this statementand provide a class IIa, level B recommendation for CACS,ABI and CIMT and a class IIb, level B recommendation forhs-CRP and Lp-PLA2 in this setting.

Conclusions

Preventive treatment of coronary artery disease is effec-tive and justifies screening for this frequent and potentiallylethal disease in asymptomatic individuals. The major partof cardiovascular risk assessment can be readily performedusing simple risk scoring systems based on establishedcardiovascular risk factors and requires simple biologicalmeasurements and clinical information. The added valueof new clinical (ABI), biological (hs-CRP and Lp-PLA2) andimaging (CACS and CIMT) risk markers is limited and can onlybe recommended in intermediate-risk populations in orderto further refine their cardiovascular risk and potentiallychange their treatment strategy. The most convincing datapertain to CACS, but we should keep in mind the costs andthe radiation exposure of this technique and remember thatidentification of high-risk patients should not be equatedwith an indication for revascularization in otherwise stableasymptomatic individuals.

Disclosure of interest

The authors declare that they have no competing interest.Sources of funding: none.

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