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usestrthesubremtioouHovirsimthalarevetredeefipogesthemay be quite large. Furthermore, of critical but often under-estimated clinical importance is the reality that in any low-riskpopulation, the risks (and costs) of preventing an event mayact

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082doiually exceed the risks of not intervening.8

These clinical and economic realities are precisely the reasont Canadian CVD prevention guidelines recommend some

event in the predicted time frame (most famously perhaps SirWinston Churchill), and not everyone at moderate or even lowrisk is free from atherosclerosis or events.5,18,19 The inability ofcurrent CVD risk prediction systems to adequately account forCVD susceptibility may help to explain why they still fail toidentify a significant minority of persons at risk and, poten-

eived for publication August 3, 2010. Accepted August 3, 2010.Edit

Framing Cardiovascular DisJames A. Stone, MD, PhD,

University of Calgary, Libin Cardiovascular Institute of Alberta, a

Prediction is very difficult, especially about the future.

Niels Bohr

ediction about anything, as so aptly pointed out by the famousnish physicistNiels Bohr, is not easy.Without knowledge of allvariables in an equation, their exact behaviour under all con-ions, precisely the way each variable interacts with the others,d all of the plausible, potential outcomes of those interactions,dicting the outcomes of a system or (patho)physiological pro-s involves as much art as science. Add to this already headyxture of uncertainty the frequently chaotic (ie, nonlinear) be-viour of biological systems,1 and the prediction of clinical out-es becomes very difficult indeed!And yet, a thing does not have to be perfect to be quiteful. Most current cardiovascular disease (CVD) preventionategies and therapeutic interventions are far from perfect inoutcomes they deliver. However, their clinical utility instantially reducing (recurrent) events and delaying deathains undeniably useful.2-4 With any therapeutic interven-

n, it is axiomatic that the greatest absolute improvements intcomes are seen in those at the greatest risk of adverse events.wever, the total number of adverse events prevented willtually always accrue in lesser-risk populations, based on theple reality of population demographics and the observationt the number of low-risk persons is usually comparativelyge. Thus, any intervention or treatment aimed at reducingnt rates within these lower-risk populations will requireating the largest proportion of the population at risk. Andspite the clinical information clearly demonstrating the ben-ts of preventing individual CVD events in these lesser-riskpulations,5,6 the relatively low overall population risk sug-ts that the number of individuals who must be treated, andcosts incurred in order to prevent a single adverse outcome,

7

Canadian Journal of Cardtia

un

Corresponding author: Dr James A. Stone, Suite 802, 3031 Hospital Dr, Calgary Alberta, 2N T8, Canada.E-mail: jastone@shaw.caSee page 172 for disclosure information.

8-282X/$ see front matter 2011 Canadian Cardiovascular Society. Published by:10.1016/j.cjca.2010.12.041l

se Event Risk PredictionPC, FAACVPR, FACCiac Wellness Institute of Calgary, Calgary, Alberta, Canada

m of cardiovascular disease event prediction or risk stratifi-ion (Framingham,9 SCORE,10 Reynolds Risk Score,11,12

ISK213) as a critical, arguably first, step in planning anividuals health maintenance or disease care program.14-16

is process of determining event risk helps to ensure thatse at the greatest risk will receive the highest level of inter-tion (usually pharmacologic), in addition to the samealth behaviour recommendations (smoking cessation, re-ced caloric intake, healthy weight, regular physical activity,per sleep hygiene, good mental health) that should be ap-ed to individuals and populations of lesser risk. Indeed, fail-to risk stratify individuals when initiating or perpetuating

y form of CVD prevention or treatment simply introduces aferent risk: that of substantially overtreating those at low riskd undertreating those at the highest risk.It is important, however, that what CVD event risk predic-n systems do not predict is the presence (or absence) oferosclerosis. They examine an individuals exposure to thevers of atherosclerosis, ie, traditional CVD risk factors, andsed on the level of those drivers, in conjunction with the totale of exposure, ie, age, they calculate a probable adverse evente. However, exposure to the drivers of atherosclerosis is onlylf of the event determination equation. The other half of theuation is event susceptibility.17 If CVD event exposure can benceptualized as the cumulative burden of atherosclerosisvers, event susceptibility can be conceptualized as the totaldisposition to atherosclerosis (ie, age, gender, family his-y, and vascular phenotypical expression). It is CVD risktor exposure plus risk factor susceptibility that determinesprobability of developing atherosclerosis and suffering an

verse event. It is not just exposure in isolation, as suggestedmost current equations predicting the risk of CVD events.

7 (2011) 171173lly, why they still remain underused.20

In this issue of CJC, Armstrong and colleagues21 provide aique perspective on how their use of the current Framing-

Elsevier Inc. All rights reserved.

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172 Canadian Journal of CardiologyVolume 27 2011m risk score (FRS) incorporated into the 2009 Canadianid Guidelines22 changed pharmacologic treatment thresh-s within their clinic. In a retrospective analysis of their pa-nt database, they demonstrated that application of the moremprehensive FRS CVD event prediction tool promoted in2009 Lipid Guidelines resulted in a significant upward

lassification of patients into moderate- or high-risk groups.mpared with the previous FRS version in the 2006 Cana-n Lipid Guidelines,23 which predicted only death or nonfa-myocardial infarction, use of the more comprehensive FRSdel (coronary artery disease-fatal and non-fatal myocardialarction, congestive heart failure, stroke, and peripheral arte-l disease) increased the combined percentage of moderate-d high-risk patients in their clinic from 24.7% to 52.2%.e authours correctly point out that this change results in are than 2-fold increase in the numbers of patients qualifyingpharmacologic therapy and that the change to a more com-hensive FRS was, in their view, not well highlighted or pro-ted and, therefore, was likely missed by many clinicians.st, they further highlight that the more comprehensive FRSsion in the 2009 Lipid Guidelines also includes risk pointsdiabetes but fewer risk points for age and smoking.Even a cursory examination of the nuances and numeroussions of FRS prediction algorithms is far beyond the scopethis limited discussion, and interested readers are directedewhere.24,25 However, incorporation of a broader system fordicting CVD event risk into the 2009 Lipid Guidelines ismpletely consistent with contemporary thinking within therld of CVD event prediction.26 Atherosclerosis is a systemicease process, and as such, adverse event risk prediction sys-s should predict events in as many vascular beds as possible.e apparent downgrading of age and smoking (fewer riskints) is a simple reflection of the fact that changing the out-mes of risk prediction algorithms also changes the influencet any particular risk variable will have on those outcomes.e reinclusion of diabetes as a risk factor (it was present in-1998 Framingham risk models27) is also a reflection ofre contemporary thought suggesting that not all personsth diabetes are at high or proximate risk of CVD events.28

erefore, diabetes should properly be considered a CVD risktor rather than a CVD equivalent.These qualifications aside, Armstrong and coworkers are tocongratulated for highlighting the potential impact of the09 Canadian Lipid Guidelines on patient care. Their obser-ions on risk estimation within their own patient practicevide further evidence of the importance of clearly and con-tently highlighting when important changes to clinical prac-e guidelines (CPGs) are made that carry the potential toaningfully impact clinical practice.29 In addition, their anal-s serves to emphasize that CPG developers should at leastempt to provide an estimate of the clinical and economicpact of their CPGs, as suggested by the AGREE (AppraisalGuidelines for Research and Evaluation) instrument,30 rec-nizing that the data may be poor and that good decisionsrticularly government and public health policy decisionsere millions of people may be impacted) are unlikely to berived from poor quality data. Although most CPG develop-have shied away from producing this information, usually asirect consequence of the dearth of good quality informationeady alluded to, when significant changes to CPGs may re-t in substantive changes in the numbers of patients treated,G developers should at least attempt to address this issueectly. In this manner, health care payers and providers, pub-policy architects, and patients can enter into a meaningfullogue with respect to who should be insured, who should beated, and who is unlikely to benefit from, or even potentiallyharmed by, the widespread, clinically indiscriminate appli-ion of any CPG or evidence-informed clinical practice rec-mendation.The clinically appropriate prevention and treatment ofD events demands the establishment of an individuals

seline risk. The fact thatmost current CVD risk stratificationevent prediction systems estimate only risk factor exposured fail to account for individual susceptibility renders thems than perfect, but still quite useful. However, inclusion ofD susceptibility markers such as coronary artery calciumres31 or carotid intima media thickness32 may help to im-ve adverse event prediction.33 And greater fidelity in ad-se event prediction may increase the clinical use of risk pre-tion tools, increase event riskappropriate interventions,d, similar to CVDCPGharmonization and integration,mayprove clinical outcomes by reducing barriers to implemen-ion.34 These collective considerations notwithstanding, theper by Armstrong and colleagues should remind each of ust CPGs are the collective responsibility of all health carefessionals, not just CPG developers, and as such should becussed, constructively criticized, and then amended in sub-uent versions to reflect both the scientific evidence and theportant feedback from stakeholders.

sclosuresDr Stone has received consulting and/or presentation hon-rium from Astra-Zeneca, Merck, Novartis, Pfizer, Servier,d Sanofi-Aventis.

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