Cardiometabolic Risk in Canada: A Detailed Analysis and ... · Ruth McPherson, MD, PhD, FRCPC,n Paul Poirier, MD, PhD, FRCPC, FACC, FAHA,h Shaﬁq Qaadri, MD, MPP,o ... factors increases

Canadian Journal of Cardiology 27 (2011) e1–e33

Position Statement

Cardiometabolic Risk in Canada: A Detailed Analysis andPosition Paper by the Cardiometabolic Risk Working Group

Cardiometabolic Risk Working Group: Executive Committee:

Lawrence A. Leiter (Chair), MD, FRCPC, FACP,a,b David H. Fitchett, MD, FRCPC,a,b

Richard E. Gilbert, MD, PhD, FRCPC, FRACP,a,b Milan Gupta, MD, FRCPC,a,b,c,d

G. B. John Mancini, MD, FRCPC, FACC,e Philip A. McFarlane, MD, PhD, FRCPC,a,b Robert Ross, PhD,f

Hwee Teoh, PhD,a Subodh Verma, MD, PhD, FRCSC, FAHA,a,b Working Group: Sonia Anand, MD, PhD, FRCPC,d

Kathryn Camelon, RD, CDE,g Chi-Ming Chow, MDCM, MSc, FRCPC, FACC,a,b

Jafna L. Cox, BA, MD, FRCPC, FACC,h Jean-Pierre Després, PhD, FAHA,i Jacques Genest, MD, FRCPC,j

Stewart B. Harris, MD, MPH, FCFP, FACPM,k David C. W. Lau, MD, PhD, FRCPC,l

Richard Lewanczuk, MD, PhD,m Peter P. Liu, MD, MSc, FRCPC,b,e Eva M. Lonn, MD, MSc, FRCPC, FACC,e

Ruth McPherson, MD, PhD, FRCPC,n Paul Poirier, MD, PhD, FRCPC, FACC, FAHA,h Shafiq Qaadri, MD, MPP,o

Rémi Rabasa-Lhoret, MD, PhD,p Simon W. Rabkin, MD, FRCPC, FACC,e Arya M. Sharma, MD, PhD, FRCPC,m

Andrew W. Steele, MD, FRCPC,q James A. Stone, MD, PhD, FRCPC, FAACVPR, FACC,l

Jean-Claude Tardif, MD, FRCPC, FACC,r Sheldon Tobe, MD, FRCPC,b,s Ehud Ur, MB, FRCPe

a From the Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, Ontario, Canada;b University of Toronto, Toronto, Ontario, Canada; c Brampton Civic Hospital, Brampton, Ontario, Canada; d McMaster University,Hamilton, Ontario, Canada; e University of British Columbia, Vancouver, British Columbia, Canada; f Queen’s University, Kingston,

Ontario, Canada; g University Health Network, Toronto, Ontario, Canada; h Dalhousie University, Halifax, Nova Scotia, Canada; i UniversitéLaval, Québec City, Québec, Canada; j McGill University, Montreal, Québec, Canada; k University of Western Ontario, London, Ontario,Canada; l University of Calgary, Calgary, Alberta, Canada; m University of Alberta, Edmonton, Alberta, Canada; n University ofOttawa, Ottawa, Ontario, Canada o Etobicoke, Ontario, Canada; p Institut de Recherches Cliniques de Montréal, Montreal, Québec,

q r s
Canada; Lakeridge Health Corporation, Oshawa, Ontario, Canada; Université de Montréal, Montreal, Québec, Canada; SunnybrookHealth Sciences Centre, Toronto, Ontario, Canada
ABSTRACTThe concepts of “cardiometabolic risk,” “metabolic syndrome,” and“risk stratification” overlap and relate to the atherogenic process anddevelopment of type 2 diabetes. There is confusion about what theseterms mean and how they can best be used to improve our under-
standing of cardiovascular disease treatment and prevention. With the
Toronto, Ontario M5C 2T2, Canada. Tel.: �1-416-867-7441; fax: �1-

0828-282X/$ – see front matter © 2011 Elsevier Inc. All rights reserved.doi:10.1016/j.cjca.2010.12.054

RÉSUMÉLes concepts de « risque cardiométabolique », de « syndrome métabolique »et de « stratification du risque » s’entrecoupent et s’apparentent auprocessus et au développement de l’athérogénèse du diabète de type 2.Il y a confusion sur ce que ces termes signifient et sur la manière de mieux
les utiliser pour améliorer notre compréhension du traitement et de la
Received for publication September 17, 2010. Accepted October 5, 2010.

Corresponding author: Dr Lawrence A. Leiter, Division of Endocrinol-ogy & Metabolism, St Michael’s Hospital, 61 Queen Street East #6121,

416-867-3696.E-mail: [email protected]

See page e24 for disclosure information.

mailto:[email protected]

e2 Canadian Journal of CardiologyVolume 27 2011

objectives of clarifying these concepts and presenting practical strat-egies to identify and reduce cardiovascular risk in multiethnic patientpopulations, the Cardiometabolic Working Group reviewed the evi-dence related to emerging cardiovascular risk factors and Canadianguideline recommendations in order to present a detailed analysis andconsolidated approach to the identification and management of car-diometabolic risk. The concepts related to cardiometabolic risk, patho-physiology, and strategies for identification and management (includ-ing health behaviours, pharmacotherapy, and surgery) in themultiethnic Canadian population are presented. “Global cardiometa-bolic risk” is proposed as an umbrella term for a comprehensive list ofexisting and emerging factors that predict cardiovascular diseaseand/or type 2 diabetes. Health behaviour interventions (weight loss,physical activity, diet, smoking cessation) in people identified at highcardiometabolic risk are of critical importance given the emergingcrisis of obesity and the consequent epidemic of type 2 diabetes.Vascular protective measures (health behaviours for all patients andpharmacotherapy in appropriate patients) are essential to reduce car-diometabolic risk, and there is growing consensus that a multidisci-plinary approach is needed to adequately address cardiometabolicrisk factors. Health care professionals must also consider risk factorsrelated to ethnicity in order to appropriately evaluate everyone in theirdiverse patient populations.

prévention de la maladie cardiovasculaire. Avec l’objectif de clarifierces concepts et de présenter des stratégies pratiques pour identifier etréduire le risque cardiovasculaire chez les patients de populationsmultiethniques, le groupe de travail sur le métabolisme cardiaque apassé en revue les preuves liées aux nouveaux facteurs de risquecardiovasculaire et les recommandations des lignes directrices cana-diennes pour présenter une analyse détaillée et une approche consoli-dée dans l’identification et la gestion du risque cardiométabolique. Lesconcepts liés au risque cardiométabolique et à la pathophysiologie, etles stratégies pour l’identification et la gestion (incluant les comporte-ments de santé, la pharmacothérapie et la chirurgie) dans la popula-tion multiethnique canadienne sont présentés. Le « risque cardiomé-tabolique global » est proposé comme terme générique dans une listeexhaustive de nouveaux facteurs et de facteurs existants qui prédisentla maladie cardiovasculaire et/ou le diabète de type 2. Les interven-tions sur les comportements de santé (perte de poids, activité phy-sique, diète, désaccoutumance du tabac) chez les personnes à risquecardiométabolique élevé sont d’une importance critique étant donnéla crise émergente associée à la croissance de l’obésité et les con-séquences épidémiques du diabète de type 2. Les mesures de protectionvasculaire (les comportements de santé chez tous les patients et la pharma-cothérapie chez les patients appropriés) sont essentielles pour réduire lerisque cardiométabolique, et il y a un consensus grandissant sur la nécessitéd’une approche multidisciplinaire pour répondre adéquatement au risquecardiométabolique. Les professionnels de la santé doivent aussi considérerles facteurs de risque liés à l’ethnicité pour évaluer convenablement chacundes patients selon la diversité des populations.

TABLE OF CONTENTS

Abstract e1

Objectives and Methods e2

Introduction to the Concepts ofCardiometabolic Risk, Metabolic Syndrome,and Risk Stratification: Finding the ForestAmong the Trees e2

Pathophysiology of Cardiometabolic Risk e8

Identification of Cardiometabolic Risk e9

In cases in which guidelines did not exist, literature searches

Health Behaviour Interventions to ReduceCardiometabolic Risk e12

Pharmacologic and Surgical Interventions toReduce Cardiometabolic Risk e16

Cardiometabolic Risk in SusceptibleCanadian Populations e20

Disclosures e24

References e25

Objectives and MethodsThe Cardiometabolic Risk Working Group is a national group

of individuals with special interest in cardiometabolic risk andrepresentative of the various related societies. In 2009, the Cardio-metabolic Risk Working Group conceptualized the idea of orga-nizing a consensus meeting that would be coupled with the pub-lication of a position paper conceived with Canadian expertise andwith direct and practical relevance for the diverse Canadian pop-ulation and Canadian clinicians. In addition to providing readerswith an introduction to the concept of cardiometabolic risk andthe evidence surrounding emerging risk factors not captured intraditional risk engines, key literature and existing guideline rec-ommendations for the identification and management of cardio-vascular (CV) risk factors are summarized. An executive summaryof the position paper was also developed to highlight key messagesin an abbreviated format.1

To consolidate relevant approaches, existing Canadian evi-dence-based guidelines were used to inform this position paper.

were performed to locate high-quality primary studies and re-view articles. In addition, personal files and reference lists weresearched for relevant studies. Formal searches were restricted tohuman studies published in the English-language literaturefrom 2004 onwards and listed in PubMed, EMBASE, and theCochrane Library. A close-to-final version of the document wasreviewed by representatives of supporting organizations.

Introduction to the Concepts of CardiometabolicRisk, Metabolic Syndrome, and Risk Stratification:Finding the Forest Among the Trees

G.B.J. Mancini, R. Ross, J. Cox, J.-P. Després, J. Genest, P.P.Liu, E.M. Lonn, S.W. Rabkin, J.A. Stone, and E. Ur

Atherogenesis is a complicated process. A panoply of mech-anisms are at play, all of which are influenced by multiplefactors, such as genetic predisposition or susceptibility, dyslip-idemia, and oxidant state. Similarly, the genesis of type 2 dia-betes is a complicated process. While many of the features and
processes involved in the development of this disease overlap

Leiter et al.Cardiometabolic Risk in Canada

e3

with the factors affecting atherogenesis, others are distinct. Thefact that type 2 diabetes is often complicated by atherosclerosisfurther complicates the interplay of processes affecting one orthe other or both conditions. Bench research continues to cre-ate an ever more comprehensive and detailed understanding ofatherogenesis and diabetes, but translation of this informationinto the clinical arena is difficult. It is dependent on howimportant a particular pathway might be in causing clinicaldisease, how well we can gauge such underlying processes,and whether we can actually offer treatments. For example,it is relatively easy to measure and treat blood pressure (BP)and to measure and treat lipid status. However, it is not easy,and perhaps not even currently important, to assess factorsthat may be implicated in both atherogenesis and develop-ment of type 2 diabetes but for which there are no specific orproven therapies.

The objective of this broad introduction is to put into con-text the purpose and value of the concepts of “cardiometabolicrisk” and “metabolic syndrome” and the process of “risk strat-ification.” All these concepts overlap, and all relate to theatherogenic process, as well as the resultant morbidity and mor-tality. Additionally, in response to secular trends in the fre-quency of obesity and diabetes, the terms are intimately linkedto the risk for development of type 2 diabetes, an important CVrisk factor per se. This situation has led to confusion aboutwhat these terms and concepts really mean and how they canbest be used to improve our understanding of cardiovasculardisease (CVD) treatment and prevention. Accordingly, we of-fer the following proposals:

1. That the term “cardiometabolic risk” or “global cardio-metabolic risk” be considered to represent the compre-hensive catalogue of factors that contribute to bothCVD and development of type 2 diabetes. Each of thesefactors increases the risk of CV morbidity and mortalityto some extent, but the term “global cardiometabolicrisk” is mainly intended to encourage consideration offactors that go beyond the set of traditional risk factorsand that include novel or emerging risk factors. Theterm is intended to catalogue the sources of risk but notto quantify risk in either absolute or relative terms.

2. That the term “metabolic syndrome” be considered to bea specific subset of cardiometabolic risks. This subset offactors has been the focus of numerous studies that havedemonstrated that when they are clustered together,they impart a relative increase in risk of CVD and devel-opment of type 2 diabetes.

3. That the term “risk assessment” or “global risk assess-ment” be used to describe a process that mathematicallyweighs the presence or absence of risk factors, as well astheir severity, to calculate an absolute CV risk using val-idated algorithms derived from long-term observationalstudies in large patient cohorts.

What is meant by cardiometabolic risk?

The term “cardiometabolic risk” was first employed by theAmerican Diabetes Association2 as an umbrella term to includeall the risk factors for diabetes and CVD. The term was gener-ated to acknowledge that a circumscribed focus on the cluster-ing of risk factors known as metabolic syndrome (see below)
was not an optimal strategy for determining individual risk for
diabetes and CVD.3 Rather, it was suggested that cliniciansshould evaluate and treat all CVD risk factors. A definition ofthe term “global cardiometabolic risk” and its application inclinical practice was also described by Després and Lemieux in2006.4 They also encompassed traditional risk factors, as wellas more novel or emerging risk factors (eg, prothrombotic pro-file, inflammatory state; see Fig. 1).5 Thus, a main goal of thisconcept or approach is to emphasize everything known clini-cally to affect CVD, including the emergence of type 2 diabetes,in a fashion analogous to the bench researcher’s goal of ac-counting for all known mechanisms when studying the athero-sclerotic process. Thus, the notion of “global” risk assessment,meaning “comprehensive” risk assessment, is implied by thosewho use the term “cardiometabolic risk” or “global cardiometa-bolic risk.” Even so, the term “global” is perhaps not compre-hensive enough insofar as its main genesis was to amalgamaterisks for both coronary diseases with those for the developmentof type 2 diabetes. One might argue, for example, that both thepostmenopausal state in women and the presence of erectiledysfunction in men are cardiometabolic risks for atherosclero-sis and associated morbidity and mortality, but they are notgenerally included in discussions of global cardiometabolicrisk. Even so, if one accepts the value of the concept as anall-encompassing term, then the term becomes broad enoughto envelop both established and emerging risk factors. And oneshould anticipate that the catalogue of factors contributing toglobal cardiometabolic risk will continue to expand as researchcontinues.

What is meant by metabolic syndrome?

The central tenet of the global cardiometabolic risk conceptis that it captures the risk of CVD and type 2 diabetes (see Fig.1). Metabolic syndrome also does this to some degree, but itencompasses a more limited cluster of metabolic abnormali-ties6 linked to insulin resistance, which is often associated withabdominal obesity, the high-risk form of overweight and obe-sity.7 This more circumscribed set of clinical parameters de-scribes a constellation of features originally known as “syn-drome X.”8 This pattern recognition process was linkedtogether mechanistically by emphasizing insulin resistance orhyperinsulinemia in association with excessive visceral and ec-topic fat deposition and manifested by sometimes subtle ab-normalities of blood glucose, BP, triglycerides (TGs), and/orlow high-density lipoprotein cholesterol (HDL-C). The un-derlying mechanism leading to this clustering of features ap-pears more complicated than merely insulin resistance orhyperinsulinemia and is now felt to encompass both prothrom-botic and proinflammatory mechanisms as well. (See the sec-tion titled Pathophysiology of Cardiometabolic Risk.) In spiteof the uncertainty regarding the precise reason for clustering offeatures of metabolic syndrome, the clinical reality is that thisconstellation is a common and important determinant of thedevelopment of both cardiac disease and diabetes.

The intense research interest in this specific constellationof findings has prompted attempts to define the syndromeexplicitly. The diversity of criteria for metabolic syndromehas contributed to confusion pertaining to this concept. Inmany respects, the concept is an exercise in the counting ofrisk factors, some of which are “classical” and some of whichare more novel (eg, waist circumference). Moreover, the risk
factors may be present at subtle levels (eg, impaired fasting


glucose [IFG]) or at levels that define a disease state (eg, type2 diabetes or “treated diabetes” or “treated hypertension”).However, excluding the early World Health Organizationcriteria that included consideration of renal dysfunction,9

there has emerged a general consensus that the key featuresof metabolic syndrome include visceral obesity, dysglyce-mia, BP abnormalities, elevated TGs, and low HDL-C.10-12

The variance in the definitions proposed by different groupspertains mainly to the thresholds used to designate presenceor absence of a given feature in a specific patient of a specificethnic background (see Table 1). While it is important tokeep these differences in mind when evaluating any givenpublication in this arena, it is perhaps more important toemphasize that it is generally accepted that metabolic syn-drome increases overall lifetime CVD risk13-16 about 1.5- to2-fold.17,18 It has also been shown in some studies to beassociated with increased CVD risk independently of itsassociation with dysglycemia and diabetes13,19-21 and withobesity.13,22

Recently, a harmonized set of criteria was agreed on by theInternational Diabetes Federation Task Force on Epidemiol-ogy and Prevention, the National Heart, Lung and Blood In-stitute, the American Heart Association, the World Heart Fed-eration, the International Atherosclerosis Society, and theInternational Association for the Study of Obesity (see Table1).23 Although high waist circumference was a prerequisite fordefining the syndrome, as in the older International DiabetesFederation criteria,12 it is not a requirement of the harmonizeddefinition. An analysis by Arnlov and colleagues22 appears to

Figure 1. Traditional and emerging CVD risk markers that contribucardiovascular disease—including obesity (particularly central), insuliThese conditions can also occur in isolation, and they are exaggeratethe risk of CVD, the concept of global cardiometabolic risk is usefnumbers of small, dense LDL particles, are also common findingspressure; CVD, cardiovascular disease; HDL-C, high-density lipoproteAdapted and reprinted with permission from the American Diabetes Athe American Diabetes Association.

justify this shift, at least with respect to risk of CVD and mor-

tality in middle-aged men, but perhaps it renders the clusteringless useful for the prediction of diabetes. At any rate, the syn-drome is currently based on the presence of at least 3 abnormalvalues out of 5 criteria (waist circumference, BP, fasting plasmaglucose [FPG], HDL-C, and TGs), without regard for severityor duration. Thus, while this yes-or-no, or dichotomous, as-sessment of the presence or absence of features identifies thesyndrome, and while the presence of this syndrome imparts ahigher relative risk of both CVD and diabetes, the assessment isnot designed to establish an absolute risk and should not beused for this purpose. Determining the absence or presence ofmetabolic syndrome does, however, ensure that the compo-nent risk factors are assessed in clinical practice, allowing theclinician to see the “big picture” and to recognize a patternfrom a variety of risk factor measures.15,16,24 Perhaps the mostimportant contribution is that it allows one to consider thesecardiometabolic risk factors irrespective of whether they are yetsevere.

How are metabolic syndrome and risk assessmentalgorithms used to predict individual CVD risk?

The assessment of absolute risk requires validated, math-ematical algorithms25 such as the Framingham Risk Score(FRS) or others. These algorithms include some of the fac-tors that are a part of the assessment required to determinepresence of metabolic syndrome, but not all of them. Forexample, the FRS does not incorporate waist circumferenceor TG level, whereas assessment of these factors is essential

global cardiometabolic risk.5 Risk factors for type 2 diabetes andance, hyperglycemia, dyslipidemia, and hypertension—often cluster.ysical inactivity and smoking. Since each of these factors increases

d abnormalities, including elevated TGs, low HDL-C, and increasedents with cardiometabolic risk. Apo B, apolipoprotein B; BP, bloodesterol; LDL-C, low-density lipoprotein cholesterol; TGs, triglycerides.ion from Brunzell JD, Davidson M, Furberg CD, et al.5 Copyright 2008

te ton resistd by phul. Lipiin patiin cholssociat

in attempting to identify the presence of metabolic syn-

mi:2008


e5

drome. Moreover, the risk algorithms attempt, when feasi-ble, to weigh the severity of a risk factor (eg, treated vsuntreated hypertension, ambient level of systolic BP, level ofHDL-C, age) to calculate an absolute risk. In contrast, forexample, mild abnormalities of TGs or BP are consideredthe same as treated hypertriglyceridemia or treated hyper-tension, when determining the presence of metabolic syn-drome and for implying that relative risks are augmented,no matter the degree of severity in either case.

Thus, the clinical diagnosis of the presence of metabolic

Table 1. Definitions of metabolic syndrome

WHO9

NCEP A

200110

Diagnostic criteria Diabetes, IFG, IGT, orinsulin resistance(assessed by clampstudies) plus �2other riskdeterminants arepresent

�3 risk determinants ar

BG Diabetes, IFG, IGT orinsulin resistance

FPG � 6.1 mmol/L

BP �140/90 mm Hg �130/85 mm Hg

TGs �1.7 mmol/L �1.7 mmol/L

HDL-C �0.9 mmol/L (men)�1.0 mmol/L

(women)

�1.0 mmol/L (men)�1.3 mmol/L (women)

Abdominalobesity

Waist-to-hip ratio:�0.90 (men)�0.85 (women)

WC:�102 cm (men)�88 cm (women)

Kidney function Urinary albuminexcretion rate � 20�g/min

or ACR � 30 mg/g

NA

ACR, albumin to creatinine ratio; AHA, American Heart Association; Bglucose; HDL-C, high-density lipoprotein cholesterol; IAS, International AthInternational Diabetes Federation; IFG, impaired fasting glucose; IGT, impEducation Program Adult Treatment Panel III; NHLBI, National Heart, LuHeart Federation; WHO, World Health Organization.

syndrome is certainly not sufficient to quantify risk in absolute

terms.4 The presence of metabolic syndrome leads to a 1.5- to2-fold increase in relative CVD risk.17 Accordingly, consider-ation of this syndrome may help to identify patients in whomavailable risk algorithms may underestimate true risk.

The difference and interdigitation between the 2 ap-proaches can be illustrated by several simple considerations.For example, let us consider a patient with systolic BP of 135mm Hg, an HDL-C of 0.9 mmol/L, and a TG of 1.8 mmol/Lwho, by virtue of fulfilling 3 of the 5 criteria, can be said to havemetabolic syndrome. Such a patient is perceived to have a rel-

IDF12

Harmonized definition ofthe IDF, NHLBI, AHA,WHF, IAS, and IASO23200411

t Central obesity (usingethnic-specificvalues) plus �2other riskdeterminants arepresent

(if BMI � 30 kg/m2,central obesity canbe assumed, andWC does not needto be measured)

�3 risk determinants arepresent

� 5.6 mmol/L FPG � 5.6 mmol/L (orpreviouslydiagnosed type 2diabetes)

FPG � 5.6 mmol/L (orreceiving treatment ofelevated glucose)

�130/85 mm Hg (orreceiving treatmentof previouslydiagnosedhypertension)

�130/85 mm Hg (orreceiving treatment ofpreviously diagnosedhypertension)

�1.7 mmol/L (orreceiving treatment)

�1.7 mmol/L (orreceiving treatment)

�1.0 mmol/L (men)�1.3 mmol/L (women)(or receiving treatment)

�1.0 mmol/L (men)�1.3 mmol/L (women)(or receiving treatment)

Europids, Sub-SaharanAfricans, EasternMediterranean, andMiddle East (Arab)populations:

WC � 94 cm (men)WC � 80 cm (women)South Asian,

Malaysian, Asian,Indian, Chinese,Japanese, ethnicSouth and CentralAmericanpopulations:

WC � 90 cm (men)WC � 80 cm (women)

Europids, whites, Sub-Saharan Africans,Mediterranean, andMiddle East (Arab)populations:

WC � 94 cm (men)WC � 80 cm (women)Asian (including

Japanese), Asian,Chinese, Japanese,ethnic South andCentral Americanpopulations:

WC � 90 cm (men)WC � 80 cm (women)Canada, US, European

populations:WC �102 cm (men)WC �88 cm (women)

NA NA

d glucose; BMI, body mass index; BP, blood pressure; FPG, fasting plasmaosis Society; IASO, International Association for the Study of Obesity; IDF,

lucose tolerance; NA, not applicable; NCEP ATP III, National CholesterolBlood Institute; TGs, triglycerides; WC, waist circumference; WHF, World

TP III

e presen

FPG

G, blooeroscleraired gng, and

ative 1.5- to 2-fold increase of CV risk. But what is the absolute


CV risk to begin with? In order to calculate absolute risk, weneed a validated algorithm. Irrespective of the algorithm se-lected, all of them would yield a higher absolute risk for a manthan for a woman for the identical constellation of findingsnoted above. Similarly, all else being equal, a younger patient ofeither gender will have a lower absolute risk than will an olderpatient of the same gender. Of the algorithms available, onlythe Prospective Cardiovascular Munster Study algorithmwould have incorporated a factor weighing TGs,26 an elementof the patient profile also required to assess presence or absenceof metabolic syndrome. In contrast, the algorithms more com-monly used in North America (FRS and Reynolds Risk algo-rithms) would not incorporate the impact of a TG abnormal-ity.

The individual described in the clinical case above does nothave abdominal obesity. Consider, therefore, a case with com-pletely normal TGs but with the same BP and HDL-C, as wellas a high waist circumference (specific to gender and ethnicbackground – see Table 1). None of the formal algorithms takewaist circumference into account. Accordingly, the implicationis that whatever absolute risk is computed by the chosen algo-rithm, the presence of the constellation of findings confirmingpresence of metabolic syndrome would cause one to reconsideror to question the calculated absolute risk and perhaps to read-just it higher by a relative factor of about 1.5 to 2. While thisimplication is not fully accepted or fully validated, the practicalimportance is likely to be most critical in patients who might beconsidered to have only low or moderate risk by the traditionalrisk assessment algorithms. Figure 2 shows an example thatillustrates this issue.

Thus, in clinical practice, it is prudent to first calculate anabsolute CV risk using a well-validated algorithm. To morefully capture the global cardiometabolic risk, and hence thepossibility of additional CVD risk, the construct of metabolicsyndrome should be weighed if the patient fulfils those criteria.Given the emerging crisis of obesity in Westernized countriesand the consequent epidemic of type 2 diabetes, the concept ofcardiometabolic risk serves mainly to allow practitioners to rec-ognize early stages of CVD risk from a more comprehensive listof factors than represented in risk-calculation algorithms andthat, in concert, warrant therapeutic health behaviour changesdesigned to promote weight loss.

Although the current consensus definition23 does not re-quire elevated waist circumference to be present to identifymetabolic syndrome, the importance of obesity, particularlyabdominal obesity and the potential importance of hyperinsu-linemia in many of these patients, still deserves major consid-eration (see the Pathophysiology of Cardiometabolic Risk sec-tion below).

What are the limitations of current approaches toassessing CVD risk?

Després and colleagues have outlined the advantages anddisadvantages of the cardiometabolic risk concept in the con-text of risk assessment using traditional factors (see Table 2).6

The concept of a metabolic “syndrome” is controversial, and itsapplication in clinical practice has proven to be problem-atic.27,28 The prevalence of metabolic syndrome within indi-vidual cohorts varies with the definition used, and within eachdefinition it increases with age and varies with gender and eth-
nicity.29 It is unclear whether each definition is equally pre-
dictive of CVD, whether all possible combinations of riskfactors within each definition are equally predictive, andwhether the presence of the clinical criteria for metabolicsyndrome truly increases the risk of CVD beyond tradi-tional risk factors.4,6,15,16,30,31 Furthermore, meeting the clin-ical criteria for metabolic syndrome does not necessarily confera very high absolute risk of CVD, as illustrated in the clinicalexample above and in Figure 2.4 Also, in a population-basedcohort study comparing prevalence rates and the prediction ofCVD using different definitions of metabolic syndrome, singlerisk factors such as smoking had a predictive ability equal tothat of metabolic syndrome.15,16 Differing definitions havebeen shown to be associated with measures of subclinical ca-rotid atherosclerosis, but the associations were entirely medi-ated by the individual criteria of metabolic syndrome.24 Con-sequently, the diagnosis of metabolic syndrome (irrespective ofthe definition chosen) may not provide any additional infor-mation beyond the component risk factors with respect to sub-clinical atherosclerosis, suggesting that the CV risk associatedwith metabolic syndrome is derived mainly from its key com-

Figure 2. Assessment of global coronary artery disease risk. Thechart illustrates how meeting the clinical criteria for metabolic syn-drome does not necessarily equal a very high absolute risk of car-diovascular disease (CVD). Case 1 is a 30-year-old man who does nothave diabetes, has normal blood pressure and low-density lipoproteincholesterol (LDL-C) of 3.0 mmol/L, and has never smoked. Accordingto a risk assessment algorithm such as the Framingham Risk Score,he has only a 4% 10-year coronary artery disease (CAD) risk on thebasis of his traditional risk factors. Since he has metabolic syndrome(elevated waist circumference, high fasting plasma triglycerides, andlow high-density lipoprotein cholesterol levels), his risk increases by2-fold, bringing his absolute CAD risk to 8%. Case 2 is a 55-year-oldmale smoker with untreated hypertension (170/95 mm Hg) andLDL-C of 4.1 mmol/L. According to Framingham, he has a 10-yearCAD risk of 33%. He also meets exactly the same National Choles-terol Education Program Adult Treatment Panel III metabolic syn-drome criteria as Case 1, which therefore increases his risk by 2-fold,bringing his absolute CAD risk to 66%. Using the Framingham model,Case 2 is at higher 10-year risk of CAD than Case 1 (33% vs 4%),irrespective of metabolic syndrome. Thus, the same theoretical2-fold increase in CAD risk due to metabolic syndrome generatesa much higher absolute CAD risk for Case 2 (66%) than for Case1 (8%). Adapted and reprinted with permission from Després JP,Lemieux I.4

ponents, namely, abdominal obesity, BP, and blood glucose.24


e7

As discussed earlier, metabolic risk factor criteria are dichot-omous (either you meet the criteria or you don’t) and as suchdo not reflect the continuous nature of risk.30 Thus, variousindividuals with borderline and elevated risk factors could allbe said to have metabolic syndrome, but each individual’s riskwould be very different.24

But formal risk-assessment algorithms are also not withoutproblems. Different risk-assessment methods sometimes leadto differences in risk estimates. While these may be useful toolsfor evaluating an individual’s coronary artery disease (CAD)risk, several limitations need to be considered32:

● The prediction model may not be similarly applicable toall populations.33-35

● Risk prediction algorithms may not be equally predictivein men and women.36,37

● These assessment methods may not be equally predictivefor people with type 2 diabetes.38

● There may be differences in the CVD and CAD end-points considered.32

● The risk prediction models may consider only a limitednumber of risk factors or markers. A number of otherfactors that appear to predict risk and/or refine risk strat-ification are not always included, eg, subclinical athero-sclerosis,39 apolipoprotein (apo) B,40 apo B-to-AI ra-tio,41 high-sensitivity C-reactive protein (hs-CRP),42,43

Lp(a),44 coronary artery calcification score,16,45 ankle-brachial index,46 carotid plaque,47 carotid atherosclero-sis,48 carotid artery intima-media thickness,49,50 A1C(glycated hemoglobin),51 lipoprotein-associated phos-pholipase A2,52 abdominal obesity,4,32 health behaviour

Table 2. Advantages and limitations of the clinical diagnosis ofmetabolic syndrome*

Advantages Disadvantages

Independently from the clinicalcriteria used, metabolicsyndrome is associated with a1.5- to 2-fold increase in CVDrisk

Clinical diagnosis of metabolicsyndrome does not assessglobal risk of CVD

Improves CVD risk prediction ontop of currently available riskfactors

Diagnosis of metabolic syndromedoes not appear to predictCVD risk beyond the sum ofits individual components

Identifies high-risk subjects who arenot necessarily identified bycurrently available riskalgorithms

Treatment of metabolicsyndrome does not appear tobe different than treatment ofindividual abnormalities

Independently from etiology, there isclear pathophysiological evidencelinking features of metabolicsyndrome to atherogenesis

Etiology of metabolic syndromeis still unclear (debatebetween abdominal obesityand insulin resistance)

Health behaviour interventionsimprove features of metabolicsyndrome and decrease CVDand diabetes risk

No clear rationale for cutoffvalues of proposed clinicalcriteria for its diagnosis

Severity of the syndrome notassessed by currentapproaches

Added value questioned inclinical practice

CVD, cardiovascular disease.*Modified with permission from Després JP, Cartier A, Côté M, Ar-

senault BJ.6

risk factors (lack of fruit and vegetable intake, lack of

regular exercise, and lack of mild to moderate alcoholconsumption),53 and brain natriuretic peptide (or N-ter-minal prohormone brain natriuretic peptide).54 Identifi-cation and weighting of these factors may allow moreprecise risk stratification and perhaps earlier diagnosisand intervention in patients at risk for or with occultCVD.55

● Most equations do not optimally assess lifetime risk.32,56

● Risk assessment methods are not applicable to childrenand adolescents.57

● Socioeconomic status may be an important confounderin the association of metabolic syndrome with CADrisk.58

● They may predict risk but not progression of atheroscle-rosis.14

● Although risk factors such as age, cholesterol, and BP areincluded as continuous variables in the various risk as-sessment algorithms, other risk factors, such as smoking,diabetes, and, for some risk engines, family history, areconsidered only as dichotomous variables (present or ab-sent), although extensive data suggest that the relation-ship of these risk factors to CVD risk is more complexand dependent not only on the presence or absence ofthese risk factors but also on quantitative exposure to therespective risk factor.

● Classical CVD risk assessment algorithms focus on therelatively short-term horizon (5 to 10 years), whereas life-long risk may be more relevant, especially in terms ofprimary prevention.

● There is controversy about “biochemical” risk factorsand subclinical atherosclerosis (coronary artery cal-cium, carotid artery intima-media thickness, and ca-rotid plaque).49 Subclinical atherosclerosis is not a riskfactor but rather a structural change of the vascular wallin response to the long-term exposure to various riskfactors modulated by genetically determined response(susceptibility) of the individual; many would considersubclinical atherosclerosis as evidence of vascular diseaseand not a CVD risk factor.

Summary

We have attempted to clarify several terms and processesthat overlap and cause confusion. We propose that “globalcardiometabolic risk” is an umbrella term for a comprehensivelist of existing and emerging factors that predict CVD and/ortype 2 diabetes, and we furthermore suggest that this catalogueof factors will continue to expand. Secondly, we highlight thatthe term “metabolic syndrome” pertains to a subset of thiscomprehensive list for which explicit criteria have been pro-posed. These criteria help to provide some clarity for ongoingstudies and interpretation of the explosion of research reportspertaining to metabolic syndrome. And of practical clinicalimportance, patients who meet criteria for metabolic syndromeappear to have a relative increase in CV risk by a factor of about1.5 to 2. We stress, however, that the components of the defi-nition of metabolic syndrome may not be equally weighted interms of leading to the increased relative CV risk. Furthermore,we narrowly limit the concept of absolute risk assessment as aprocess requiring the use of validated algorithms derived fromlarge cohorts of patients followed for long periods of time.25

Finally, we suggest that the calculation of an absolute risk fol-

-�, tum


lowed by a reappraisal based on the presence or absence ofmetabolic syndrome may help to identify patients whose riskmay be underestimated through sole consideration of tradi-tional risk factors and who may warrant more comprehensiveor more intensive intervention, including prompt initiation ofhealth behaviour changes (see Health Behaviour Interventionsbelow). The latter is of critical importance given the emergingcrisis of obesity in Westernized countries and the consequentepidemic of type 2 diabetes.6,30,59-62

Pathophysiology of Cardiometabolic RiskS. Verma, R.E. Gilbert, R. Rabasa-Lhoret, and H. TeohThe pathophysiological basis of cardiometabolic risk is

complex. Although various mechanisms have been pro-posed, insulin resistance, particularly at the level of the fat,liver, and muscle coupled with visceral adiposity, and al-tered adipokine kinetics, appear to be closely associated withthe clustering of abnormalities associated with increased

Figure 3. Proposed mechanisms by which visceral obesity couldresistance. (A) The hyperlipolytic and insulin-resistant state of the omin turn impairs several hepatic metabolic processes, leading to hyincreased hepatic glucose production), and hypertriglyceridemia (via iserves as a powerful source of local and systemic inflammatory moland also cause systemic endothelial injury and promote atherosclerofat deposition in undesired sites such as the liver, the heart, theabnormalities that increase risk for CVD and type 2 diabetes.4,59 AdaJ, et al.4 FFA, free fatty acid; IL-6, interleukin-6; TG, triglyceride; TNF

cardiometabolic risk.

What is the contribution of visceral adiposity tocardiometabolic risk?

The association between increased visceral/ectopic adipos-ity and insulin resistance has been demonstrated by Desprésand colleagues4,59 (see Fig. 3). The hyperlipolytic and insulin-resistant state of the omental adipose tissue exposes the liver tohigh concentrations of free fatty acids (FFAs), which impairsseveral hepatic metabolic processes, leading to hyperinsulin-emia, glucose intolerance, and hypertriglyceridemia. The vis-ceral adipose tissue is additionally an important source of localand systemic inflammatory molecules, cytokines, and adipo-kines, which potentiate tissue insulin resistance and cause sys-temic endothelial injury and promote atherosclerosis.

What is the contribution of insulin resistance tocardiometabolic risk?

In order to maintain normoglycemia, hyperinsulinemia de-velops in response to insulin resistance. Insulin regulates over700 genes, so the implications of hyperinsulinemia are signifi-cant and far reaching.63,64 While the direct contribution of

ed to the athero-thrombotic-inflammatory abnormalities of insulinadipose tissue exposes the liver to high concentrations of FFAs. Thislinemia (via decreased insulin clearance), glucose intolerance (viaed VLDL–apolipoprotein B secretion). (B) The visceral adipose tissue

cytokines and adipokines that potentiate tissue insulin resistance) Excessive visceral fat accumulation is also associated with ectopicl muscle, and the pancreas, further contributing to the metabolicd reproduced with permission from Després JP, Lemieux I, Bergeronour necrosis factor-�; VLDL, very low-density lipoprotein.

be linkental

perinsuncreasecules—sis. (Cskeletapted an

insulin resistance to global cardiometabolic risk is the subject of


e9

ongoing debate,3 insulin resistance has been shown to bestrongly associated with components of the atherogenic, pro-thrombotic, and inflammatory profile seen in individuals withcardiometabolic risk factors.

Adipose insulin resistance has been implicated as a key com-ponent of cardiometabolic risk, with heightened release ofFFAs secondary to increased lipolysis.63,65 In the liver, in-creased FFA flux results in the increased production of glucoseand TGs and secretion of very low-density lipoprotein. Asso-ciated lipid and lipoprotein abnormalities include reductionsin HDL-C and increased density of low-density lipoprotein(LDL). FFAs also reduce insulin sensitivity in muscle and con-tribute to increased pancreatic insulin secretion, resulting inhyperinsulinemia. Hyperinsulinemia (and possibly increasedFFA levels) may result in enhanced sodium reabsorption andincreased sympathetic nervous system activity and may con-tribute to the development of hypertension.63,65

In addition, there are paracrine and endocrine effects of theproinflammatory state.63,65 A variety of cells in adipose tissue(eg, adipocytes and monocyte-derived macrophages) enhancesecretion of interleukin-6 and tumour necrosis factor-�, result-ing in more insulin resistance and lipolysis of adipose tissue TGstores, resulting in further increased circulating FFAs. Cyto-kines and FFAs increase the production of fibrinogen, CRP,and plasminogen activator inhibitor-1 (PAI-1) by the liver,complementing the overproduction of plasminogen activatorinhibitor-1 by adipose tissue. This process results in a pro-thrombotic state.63,65

What are the contributions of adipokines to insulinresistance and endothelial dysfunction?

Mature adipocytes are active endocrine and paracrine or-gans secreting numerous mediators that participate in diversemetabolic processes. Fat-derived molecules (eg, lipoproteinlipase and cholesterol ester transfer protein) act via endocrine,paracrine, autocrine, and/or juxatacrine modes of action tomodulate fat depot size and body fat redistribution and ulti-mately influence the levels of secretory proteins. More recently,adipose tissue has been recognized as a rich source of pro-inflammatory mediators (adipokines) that may directly contrib-ute to vascular injury, insulin resistance, and atherogenesis. It isalso the source of adiponectin, a potent insulin-sensitizing, anti-inflammatory, and antiatherosclerotic protein, the levels ofwhich are reduced in states of insulin resistance, obesity, anddiabetes.66,67

Both FFAs and hyperglycemia contribute to mechanismsknown to promote atherosclerosis.68-72 Even short excursionsof these 2 metabolites have profound consequences,73 andcombined excursions mainly observed in the postprandial stateare believed to be synergetic for the toxic effect.74

Summary

The clustering of risk factors that constitute cardiometa-bolic risk—dyslipidemia, elevated BP, dysglycemia, pro-thrombotic state, and inflammatory state59—might be theconsequence of a complex interplay between various tissues(mainly adipose tissue and liver). The phenotype of the personwith high cardiometabolic risk is characterized by overweightor obesity with preferential android fat accumulation,63,75,76

sedentary lifestyle,63,77 and diet high in total or saturated fats.63,78

Interestingly, some obese patients remain insulin sensitive despite

enlarged fat mass but low visceral adipose tissue accumulation,79

while some normal-weight subjects display significant insu-lin resistance despite apparently normal weight but excessiveabdominal obesity.80 This suggests that factors in additionto excessive fat mass affect adipose tissue functionality.

Identification of Cardiometabolic RiskP.A. McFarlane, R. Lewanczuk, R. McPherson, and P.

PoirierCardiometabolic risk refers to the sum of risk factors that

increase an individual’s risk of having a CV event or developingmetabolic abnormalities such as type 2 diabetes (see Fig. 1).This risk is generated by traditional CV risk factors such ashypertension or smoking, by nontraditional risk factors such asinsulin resistance, and by other genetic and clinical factors thatare not fully understood. There is interplay between the variousrisk factors (eg, hyperglycemia can exacerbate hypertriglyceri-demia), and there is overlap between the main outcomes (eg,people who develop type 2 diabetes are at higher risk for CVevents). The goal of screening is to develop, through identifi-cation of the significant traditional and nontraditional risk fac-tors, a comprehensive understanding of a patient’s risk for car-diometabolic events, thereby enabling appropriate individualpreventive measures to be taken.

Who should undergo cardiometabolic risk assessment?

An assessment should occur when any traditional CV riskfactor, such as hypertension or dyslipidemia, is first identifiedor in patients who are overweight or obese, especially those whoare abdominally obese.30,59,81-85 Figure 4 describes the generalapproach to assessing cardiometabolic risk.

How should cardiometabolic risk be assessed?

Height, weight, body mass index and waist circumference.Height, weight, body mass index (BMI; see Table 3),86,87 andwaist circumference should be measured (with the use of the eth-nic-specific cutoffs in Table 1) as part of an assessment of cardio-metabolic risk. Ideally, height is measured by a stadiometer.Weight should be measured by an accurately calibrated scale.

Various methods for measuring waist circumference havebeen proposed.88 A recent expert consensus panel88 recognizedthat the method described in Table 4 for measuring waist cir-cumference81,89 might be more readily adopted by physicians(and by the general public for self-measurement) as it requires asingle palpation to locate the iliac crest. The “spin” or “orbit”techniques are alternate methods that can be considered to facili-tate encircling the abdomen with the measuring tape (see Table 5)and provide the patient with choice. However, the differencesbetween commonly used waist circumference measurement pro-tocols have no substantial influence on the association betweenwaist circumference and morbidity of CVD and diabetes and all-cause mortality and CVD mortality.88 Patient preference and levelof comfort with being measured should therefore be consideredwhen choosing a measurement technique.

BP. Hypertension is an important element of cardiometabolicrisk. Patients should have their BP accurately assessed at thetime of screening for cardiometabolic risk. Ideally, BP should
be measured using the technique described in Table 6.90


It is important to note that half of overweight individualswith high normal BP will develop hypertension within the next2 years.91 These individuals should be monitored periodicallyfor the development of hypertension.

Renal disease. In Canada, the most common cause of chronickidney disease is diabetes, followed by ischemic nephropathyfrom causes such as renovascular disease and hypertensivenephrosclerosis.92 As many as half of people with diabetes willdevelop chronic kidney disease, and the risk for end-stage renaldisease is between 2.5 and 4.25 times higher in people withhypertension than in normotensive individuals.93,94 The pop-ulation of people with elevated cardiometabolic risk will have ahigh prevalence of conditions such as diabetes, hypertension,

Figure 4. General approach to assessing cardiometabolic risk. A1C,glycated hemoglobin; apo B, apolipoprotein B; BMI, body mass index;BP, blood pressure; CV, cardiovascular; ECG, electrocardiogram; HDL-C,high-density lipoprotein cholesterol; hs-CRP, high-sensitivity C-reactiveprotein; LDL-C, low-density lipoprotein cholesterol; TC, total cholesterol;TGs, triglycerides; WC, waist circumference. �Annually in those aged�40 years and opportunistically in those aged 18 to 39 years.

or general vascular disease, all of which are conditions that

place an individual at high risk for chronic kidney disease. Forthis reason, people with elevated cardiometabolic risk shouldbe screened for signs of kidney disease, including persistentproteinuria or an inappropriately low glomerular filtration rate(as estimated using the serum creatinine). As blockers of therenin-angiotensin-aldosterone system (RAAS) such as angio-tensin-converting enzyme (ACE) inhibitors or angiotensin re-ceptor blockers (ARBs) are frequently indicated in this popu-lation, and these medications can raise serum creatinine andpotassium levels,95,96 measuring serum electrolytes and creati-nine in this population is indicated in order to determine abaseline for medication safety monitoring. Finally, patientswith generalized vascular disease are at higher risk for the de-velopment of secondary hypertension in the form of renal vas-cular disease. Suspicion for a hyperaldosterone state is increasedin those with unexplained hypokalemia.97

Laboratory tests. If the patient has a known traditional CVrisk factor or is overweight or obese or has a large waist circum-ference, then an FPG and fasting lipid profile (total cholesterol,HDL-C, LDL cholesterol [LDL-C], and TGs) should be ob-tained. Apo B can be used in place of LDL-C (see the sectiontitled Pharmacologic and Surgical Interventions to ReduceCardiometabolic Risk). These tests should be obtained in in-dividuals who reach either the Canadian Diabetes Associa-tion98 or the Canadian Cardiovascular Society (CCS)99 screen-ing thresholds according to the criteria summarized in Table 7.

The BP, glycemia, and lipid diagnostic thresholds andthresholds for initiation of treatment are listed in Table 8. Forthe purpose of interpreting the lipid tests, the FRS can be used.Those with a 10-year CV risk �20% or with diabetes are con-sidered at high risk for CV events, those with a 10-year CV riskof 10% to 19% are at moderate risk, and those with a 10-yearCV risk �10% are considered at low risk. Treatment targetsare summarized in Table 9.

Table 3. Body weight classification by BMI in adults86

BMI (kg/m2)* Category

�18.5 Underweight18.5-24.9 Normal25.0-29.9 Overweight30.0-34.9 Obese (class I)35.0-39.9 Obese (class II)�40.0 Obese (class III)

In a recent advisory statement, the American Heart Association87 recom-mended further subdividing obesity (BMI � 30.0 kg/m2) into 5 categories byadding class IV (�50.0 kg/m2) and class V (�60.0 kg/m2) obesity.

BMI, body mass index (weight in kilograms � height in metres2).*BMI values are age and gender independent and may not be correct for all

ethnic populations.

Table 4. Recommended technique to measure waist circumference

1. Locate the upper hipbone and the top of the right iliac crest.2. Position the measuring tape in a horizontal plane around the abdomen

at the top of the iliac crest.3. Fit the measuring tape snugly (but not compressing the skin) around

the person, with the tape horizontal to the ground.4. Measure at the end of a normal expiration with the person’s

abdominal muscles relaxed.


e11

Synthesis of assessment finding and possible otherassessments

After the initial assessment of cardiometabolic risk, thoseindividuals who are believed to have an elevated cardiometa-bolic risk should undergo further assessment, receive intensivehealth behaviour intervention (physical activity and dietarymodification), and be considered for pharmacologic or surgicalinterventions (see the section titled Pharmacologic and Surgi-cal Interventions to Reduce Cardiometabolic Risk). Some ad-ditional tests and assessments that may be considered in thosewith elevated cardiometabolic risk include:

1. Electrolytes, serum creatinine2. Random urine dipstick

Table 5. Alternate techniques to measure waist circumference

Spin technique1. Ask the patient to hold one end of the measuring tape against the

midline of his or her abdomen.2. The patient carefully spins 360 degrees while the clinician holds the

other end of the measuring tape.3. Once the patient has completed the spin, the tape should be wrapped

around his or her abdomen.4. Adjust the position of the tape, so it fits snugly (but not compressing

the skin) around the patient, with the tape horizontal to the ground.5. Measure at the end of a normal expiration with the patient’s

abdominal muscles relaxed.Orbit technique

1. For patients in whom performing the spin is unsafe or not possible, the“orbit” technique can be used.

2. Ask the patient to hold one end of the measuring tape against themidline of his or her abdomen.

3. While holding the other end of the tape, the clinician then walksaround the patient, wrapping the tape around the abdomen in theprocess.

4. Adjust the position of the tape, so it fits snugly (but not compressingthe skin) around the patient, with the tape horizontal to the ground.

5. Measure at the end of a normal expiration with the patient’sabdominal muscles relaxed.

Table 6. Recommended technique for measuring blood pressure90

1. The patient should be seated comfortably in a chair with both feet onthe floor.

2. A calibrated sphygmomanometer or automated monitor should beused.

a) If an automated monitor is used, the monitor should be placed atapproximately the same height as the heart, and the arm that isbeing assessed should be comfortably supported at the same height.

b) If a sphygmomanometer is used, the valve should be opened suchthat the mercury does not fall more than 5 mm Hg per second, andthe systolic and diastolic values should not be rounded off.

3. If the arm circumference is �31 cm (�12.2 inches), a regular-sizedcuff can be used; otherwise, a large cuff should be used.

4. No talking or other distractions should occur during the reading.5. Ideally, at least 3 readings should be performed. The first reading should

be discarded, and the average of the subsequent readings should betaken.

6. Blood pressure should be taken in both arms. The arm showing thehigher readings is likely to be the most accurate, and subsequentreadings should be performed in that arm.

7. Unattended blood pressure readings (ie, those done by an automateddevice while the patient is alone in the examination room) may bemore accurate.

8. Acceptable alternatives are 24-hour ambulatory blood pressure
monitoring or proper self-measurements.
3. A 75-g oral glucose tolerance test (in those with an FPGof 6.1 to 6.9 mmol/L or in those with an FPG of 5.6 to6.0 mmol/L plus 1 or more risk factors)

4. A 12-lead resting electrocardiogram and/or exercisestress test if indicated

5. Complete CV examination and investigations whenwarranted (eg, in the presence of dyspnea, reducedpulses, bruits, sleep apnea, erectile dysfunction)

6. Liver enzyme tests in obese individuals7. Screening for depression as appropriate

Summary

Screening for traditional and nontraditional risk factorsprovides a comprehensive picture of a patient’s risk for cardio-metabolic events. Screening should occur when any traditionalrisk factor is first identified or if a patient is overweight or obese,and it should include physical examination, history, and labo-ratory and other tests as indicated by patient age, existing riskfactors, or guideline-recommended criteria.

Health Behaviour Interventions to ReduceCardiometabolic Risk

R. Ross, K. Camelon, J.-P. Després, D.W.C. Lau, and A.Y. SharmaCardiometabolic risk represents global CVD risk related to

well-established risk factors (age, sex, family history, smoking,BP, LDL-C, HDL-C, diabetes) and emerging factors such as

Table 7. Thresholds and criteria for screening for dyslipidemia anddysglycemia98,99

Factor Screen with fasting lipid profile and FPG ifany of the following factors are present.

Age FPG in those aged �40 years, or earlier inthose with risk factors listed below

Fasting lipid profile in men aged �40 yearsand women aged �50 years (orpostmenopausal), or earlier in those withrisk factors listed below

Hypertension Known to be hypertensiveDyslipidemia Known to have dyslipidemiaGlycemia Known to have diabetes, IFG, or IGTFamily history Early CAD (first-degree relative aged �60

years)Type 2 diabetesFamilial dyslipidemia

Ethnicity AboriginalSouth AsianAsianAfricanHispanic

Smoking Current or former (within 1 year) smokerOther medical conditions Chronic kidney disease

Systemic lupus erythematosusPolycystic ovary syndromeAcanthosis nigricansSchizophrenia

Size Overweight and/or abdominal obesityComplications Manifestations of dyslipidemia or

complications of diabetesPregnancy History of delivery of macrosomic infant and/

or gestational diabetes mellitusVascular history Vascular disease (coronary, cerebral, vascular)

or symptoms (exertional chest discomfort,dyspnea, erectile dysfunction)

CAD, coronary artery disease; FPG, fasting plasma glucose; IFG, impaired
fasting glucose; IGT, impaired glucose tolerance.


abdominal obesity and related metabolic abnormalities oftenreferred to as metabolic syndrome. On that basis, traditionalCVD risk factors should be managed by following currentguidelines.11,12,90,98-101

Health behaviour modification is recommended as the pri-mary treatment strategy for management of cardiometabolicrisk.11,12,90,98-101 Attempts to modify health behaviour should in-clude simultaneous counselling regarding physical activity, caloricintake, and diet composition, as well as smoking cessation (seepage e19).

Abdominal obesity

What is the effect of exercise on abdominal obesity?Chronic exercise is generally associated with reduction in abdom-

Table 8. Tests and diagnostic criteria and thresholds for treatment

Test

Blood glucose98

FPG every 3 years in those aged �40 yearsMore frequent and/or earlier testing with an FPG or

75-g OGTT in those with additional risk factors75-g OGTT in those with an FPG of 6.1-6.9 mmol/L75-g OGTT in those with an FPG of 5.6-6.0 mmol/L

and one or more risk factorsBlood pressure90,98

Diagnosis of HT requires multiple readings at separatescreening visits to rule out “white coat” HT. Thenumber of readings and screening visitsrecommended by CHEP vary according to the BPmeasurements, and presence of diabetes, CKDand/or end-organ damage.

Fasting plasma lipid profile99

BP, blood pressure; CHEP, Canadian Hypertension Education Programpressure; FPG, fasting plasma glucose; HDL-C, high-density lipoprotein cholefasting glucose; IGT, impaired glucose tolerance; LDL-C, low-density lipoprototal cholesterol.

Table 9. Treatment targets

Parameter

Blood glucose98

BP90

Lipids99 Risk level

High

Moderate

Low

A1C, glycated hemoglobin; apo B, apolipoprotein B; BP, blood pressure;applicable.

*When setting treatment goals and strategies, consideration should be g
comorbidities.
inal obesity as measured by waist circumference, and the degree ofwaist circumference reduction achieved is linearly related to themagnitude of weight loss.102 Not surprisingly, a considerable in-terindividual variation (�40%) in the magnitude of change inwaist circumference is reported.103 In general, those studies thatprescribe the greatest amount of moderate physical activity (�60minutes per day), and thus induce the greatest negative energybalance and weight reduction (�8.0 kg), generally report the larg-est reductions in waist circumference (�7.0 cm), independent ofgender.103,104 More modest exercise prescriptions (�30 minutesper day) often lead to smaller reductions in waist circumference(1.0-3.0 cm).105,106

Regular exercise is also consistently associated with reduc-tions in visceral fat.102,107 As expected, the greatest exercise

Diagnostic criteria or thresholds for treatment

g �6.1 and 2h 7.8-11.0 mmol/L � isolated IGTg 6.1-6.9 mmol/L and 2h �7.8 mmol/L � isolated IFGg 6.1-6.9 mmol/L and 2h 7.8-11.0 mmol/L � IFG and IGTg �7.0 mmol/L or 2h �11.1 mmol/L � diabetes

tes or CKD �130 mm Hg SBP or �80 mm Hg DBPabetes or chronic kidney disease:fice readings: �160 mm Hg SBP or �100 mm Hg DBP averaged over 3ts or �140 mm Hg or �90 mm Hg averaged over 5 visitsme readings �135 mm Hg SBP or �85 mm Hg DBPhour BP monitor daytime average �135 mm Hg SBP or �85 mm HgP orhour BP monitor average �130 mm Hg SBP or �80 mm Hg DBPattended automated office BP �135 mm Hg SBP or �85 mm Hg DBPrisk for CVD Consider treatment in all patientsrate risk for CVD Treat if:

LDL-C � 3.5 mmol/L TC/HDL-C � 5

hs-CRP � 2 mg/L (in men aged�50 years or women aged�60 years)

Family history and hs-CRPmodulates risk

isk for CVD Treat if:LDL-C � 5.0 mmol/L

, chronic kidney disease; CVD, cardiovascular disease; DBP, diastolic bloods-CRP, high-sensitivity C-reactive protein; HT, hypertension; IFG, impairedlesterol; OGTT, oral glucose tolerance test; SBP, systolic blood pressure; TC,

Target

A1C* � 7.0%KD or diabetes: �130/80 mm Hg

Otherwise: �140/90 mm HgPrimary target Alternate primary target

� 2.0 mmol/L0% reduction in LDL-C)

Apo B � 0.80 g/L

� 2.0 mmol/L0% reduction in LDL-C)

Apo B � 0.80 g/L

reduction in LDL-C NA

chronic kidney disease; LDL-C, low-density lipoprotein cholesterol; NA, not

individuals’ risk factors such as age, prognosis, presence of risk factors, and

FastinFastinFastinFastin

DiabeNo di● Of

visi● Ho● 24-

DB● 24-● UnHighMode

Low r

; CKDsterol; htein cho

C

LDL-C(or �5LDL-C(or �5�50%

CKD,

iven to


e13

dose induces the greatest energy deficit, leading to greaterweight loss and, accordingly, greater reduction in visceral fat.For example, approximately 60 minutes of daily exercise over 3months is associated with a 1.0-kg reduction (�30%) in vis-ceral fat and a 7.0-cm reduction in waist circumference con-current with an 8.0-kg weight loss in obese men andwomen.103,104 However, the visceral fat changes reportedacross physical activity studies are inconsistent (�3.1% to�30.2% change).106

Although exercisers who lose weight generally have greaterreductions in waist circumference and visceral fat comparedwith exercisers who maintain body weight,103,104 it is notewor-thy that regular exercise can lead to marked reduction in bothwaist circumference and visceral fat even when body weight isunchanged.104,108,109

What is the effect of caloric restriction on abdominalobesity? Caloric restriction is consistently reported to decreasewaist circumference in obese men and women.103-105,110-113

For example, reducing caloric intake by 700 kcal per day for 3months resulted in a 7.0-cm reduction in waist circumferenceconcurrent with a 7.5-kg weight loss in obese men.104 Similarresults were also reported in a sample of obese, premenopausalwomen.103 Combined evidence from several studies suggeststhat each kilogram of weight lost because of caloric restrictionalone is associated with an approximately 1.0-cm decrease inwaist circumference.104,111,112

With regard to visceral fat, the strictest diets (very low cal-orie diets [VLCDs] with energy intake of 800-1200 kcal perday) of 3 to 6 months’ duration, tend to result in the greatestreductions in weight (10-18 kg) and visceral fat (24%-47%).114-116 However, it should be noted that in 1998, a USNational Heart, Lung, and Blood Institute expert panel recom-mended against the use of VLCDs based on studies that dem-onstrated no difference in long-term weight reduction betweenVLCDs and low-calorie diets, as there was greater weight re-gain with VLCDs.117

Glucose metabolism

What is the effect of exercise on glucose metabolism?Significant reductions in FPG levels are consistently observedin people with type 2 diabetes in response to a single exercisesession.118-120 This effect, however, is exclusive to those withsignificantly elevated plasma glucose values as an acute exercisebout in individuals without diabetes (with relatively normalblood glucose levels) has no appreciable effect on plasma glu-cose values.120

Significant improvements in insulin resistance, as measured bythe rate of glucose clearance during a euglycemic-hyperinsuline-mic clamp, have been achieved after approximately 1 hour ofmoderate-intensity exercise in obese people with type 2 diabetesand in normoglycemic individuals,121 insulin-resistant individu-als,122 people with type 2 diabetes,123 and healthy individuals.124

(In contrast, most clinical trials have not demonstrated a beneficialeffect of glycemic control in people with type 1 diabetes.125 Theeffects of physical activity on glycemic control in this populationare beyond the scope of this document.) The magnitude of im-provement in insulin sensitivity after a single exercise bout ranges
from 15%124 to 24%121—improvements that are equivalent in
magnitude to those achieved through chronic pharmacologic in-tervention.126-128

What is the effect of caloric restriction on glucosemetabolism? A meta-analysis of 10 intervention studies inpeople with type 2 diabetes concluded that VLCDs (800 kcalper day) of at least 3 months’ duration resulted in a 25% to30% reduction in FPG levels, with the degree of plasma glu-cose reduction linearly related to the amount of weight lost.128

However, as with exercise, caloric restriction does not appear toaffect FPG levels in subjects with normal baseline values.103,104

Caloric restriction of 3 to 4 months’ duration is associatedwith improvements in insulin resistance of 17% to72%,104,114,129 with VLCDs associated with improvements inthe upper range (eg, 72%),129 and more modest caloric restric-tion (700-kcal reduction per day) associated with improve-ments of approximately 43% in 1 study.104 VLCDs, however,are generally not recommended for obesity-managementprograms.

Three large randomized controlled trials (RCTs), the USDiabetes Prevention Program,126 the Finnish Diabetes Preven-tion Study,127 and the Chinese Da Qing Study,130 providecompelling evidence that intensive health behaviour interven-tion can prevent or delay the development of diabetes in indi-viduals with impaired glucose tolerance (IGT).126,127,130 In theDiabetes Prevention Program and Diabetes Prevention Study,the independent effects of physical activity vs dietary modifi-cation were unclear; thus in Table 10, we describe the overalleffects of health behaviour change. Comprehensive interven-tion programs based on health behaviours can reduce risk ofprogression to diabetes to a greater degree than can be achievedwith some pharmacologic interventions.126,127,130-135 (See Ta-bles 10 and 11.) Based on these trials, the Canadian DiabetesAssociation recommends that a structured program of healthbehaviour modification that includes moderate weight loss andregular physical activity be implemented to reduce the risk oftype 2 diabetes in people with IGT.98

Intensive health behaviour intervention has also beenshown to be highly effective in improving diabetes controland CV risk factors in overweight or obese people with type2 diabetes. The ongoing, multicentre, Look AHEAD (Ac-tion for Health in Diabetes) trial, sponsored by the USNational Institutes of Health, is designed to determinewhether CV morbidity and mortality in individuals withtype 2 diabetes can be reduced through intensive healthbehaviour modification. The 1-year results from the trialdemonstrated that a mean weight loss of 8.6% resulted insignificant improvement in glycemic control (0.7% absolutelowering in A1C), TGs, and HDL-C levels, as well as de-creased systolic and diastolic BP values and reductions indiabetes, hypertension, and lipid-lowering medications.136

Dyslipidemia

The atherogenic lipid profile consists of hypertriglyceride-mia, low levels of HDL-C, and high levels of LDL-C, in par-ticular small and dense LDL particles.

What is the effect of exercise on dyslipidemia? The evi-dence for beneficial lipid changes due to chronic physical ac-
tivity is strongest for HDL-C and TGs.137-141 Results of several


interventions reveal that overall, 30 to 60 minutes of aerobicphysical activity, 3 to 5 times per week, at a moderate intensityresults in a mean increase in HDL-C levels of �4% (0.05mmol/L), predominantly as a result of increases in theHDL2-C subfraction,140,142,143 and a decrease in TG levels of�12% (0.21 mmol/L).140 Others have concluded that physicalactivity that induces an energy expenditure of 1200 to 2200kcal per week may bring about a 4% to 22% (0.05-0.21mmol/L) increase in HDL-C levels and a 4% to 37% (0.01-0.43 mmol/L) decrease in TG levels.138 A recent meta-analysissuggested that a minimal weekly aerobic exercise volume of�900 kcal or 120 minutes per week is required to increaseHDL-C levels by 0.065 mmol/L.144

In contrast to the consistent findings for HDL-C and TGs,the available evidence suggests that chronic physical activitydoes not significantly alter the levels of LDL-C.138,140 Dailyaerobic activity of at least 25 minutes’ duration can, however,increase the mean LDL particle size.139 It appears that LDLparticle size is as important as total LDL-C levels in predictingcardiometabolic risk. For example, analyses from the QuébecCardiovascular Study demonstrated that a higher proportionof small LDL particles predicted incidence of ischemic heartdisease, independent of total LDL-C levels.145

While some suggest that exercise-induced weight loss mustbe achieved in order to observe improvements in lipid pro-file,137 others have shown that improvements in HDL-C andTGs are observed even when weight remains un-changed.138,140,146 Changes may be mediated by improve-ments in body composition, such as increases in skeletal musclemass or reductions in visceral fat.104,105

What is the effect of caloric restriction on dyslipidemia?A meta-analysis based on evidence from 64 individual studies

Table 10. Summary of health behaviour intervention trials to prevent

Study N Intervention

Da Qing130 577 DietExerciseDiet � exercise

DPS127 3234 Intensive health behaviour modificatioweight reduction goal of 7% of in150 minutes per week of moderatactivity)

DPP126 522 Intensive health behaviour modificatioweight loss, �30% of total energytotal energy from saturated fat, �1day; moderate-intensity exercise fo

DPP, Diabetes Prevention Program; DPS,Diabetes Prevention Study.

Table 11. Summary of pharmacologic intervention trials to prevent p

Study N Interve

DPP126 3234 Metformin (GlucophSTOP-NIDDM131 1429 Acarbose (Glucobay)XENDOS135 3305 Xenical (orlistat)DREAM132 5269 Rosiglitazone (AvandiCANOE133 207 Rosiglitazone � metf

CANOE, Canadian Normoglycemia Outcomes Evaluation; DPP, Diabet
Rosiglitazone Medication; STOP-NIDDM, Study to Prevent Non Insulin Dependent
revealed that TG levels are reduced by �32% (0.66 mmol/L)in response to various calorie-restriction protocols that resultedin an average 16.6-kg weight loss.147 Caloric restriction is alsoassociated with modest increases in HDL-C levels, althoughthe relationship is not as straightforward as that observed forTG levels. Specifically, caloric restriction results in a transientdecrease in HDL-C levels,147,148 but once body weight has sta-bilized and a new energy balance has been achieved, HDL-Clevels increase above baseline.147 Active weight loss reducesHDL-C by an average of 8%, followed by a 12% increase abovebaseline once weight had stabilized.147 The effects of caloricrestriction on LDL-C are well established, with an 11% reduc-tion reported after mean weight loss of 16.6 kg.147

Elevated BP

What is the effect of exercise on elevated BP? It is welldocumented that regular aerobic physical activity reduces systolicand diastolic BP149-155 in lean,149,154 obese,149,154 hyperten-sive,149,152,153 and normotensive149,150,152 individuals. The re-sults of various reviews and meta-analyses suggest that indepen-dent of age and BMI, 40 minutes of moderate-intensity physicalactivity performed 3 times per week reduces systolic BP by 3 to 11mm Hg and diastolic BP by 3 to 8 mm Hg.149-155 Further, the BPreductions are significantly greater among hypertensive vs normo-tensive individuals (7 and 5 mm Hg vs 2 and 2 mm Hg reductionsin systolic BP and diastolic BP, respectively).155 Exercise-inducedBP reductions do not appear to be related to alterations in bodyweight or abdominal obesity.155

What is the effect of caloric restriction on elevated BP?Caloric restriction modestly decreases BP in men and women.A meta-analysis of 25 RCTs involving 4874 subjects showed

ssion from impaired glucose tolerance to type 2 diabetes

Mean follow-up(years)

Risk reduction fortype 2 diabetes (%)

6 314642

ry modification,y weight, andity physical

2.8 58

s were 7%t, �10% ofe/1000 kcal/inutes per day)

3.2 58

ion from impaired glucose tolerance to type 2 diabetes

Follow-up(years)

Risk reduction fortype 2 diabetes (%)

3.2 (mean) 313.9 (median) 32

4 453 (median) 60

vandamet) 3.9 (median) 66

ntion Program; DREAM, Diabetes Reduction Assessment with Ramipril and

progre

n (dietaitial bode-intens

n (goalfrom fa5 g fibrr �30 m

rogress

ntion

age)

a)ormin (A

es Preve
Diabetes; XENDOS, Xenical in the Prevention of Diabetes in Obese Subjects.
mi:3234

mi:1000

mi:3234

mi:1429

mi:3305

mi:5269


e15

that caloric restriction that induced a mean weight loss of 6.7kg was associated with a 5- and 4-mm Hg reduction in systolicand diastolic BP, respectively.156 A later meta-analysis of 11trials reported similar diet-induced BP reductions.157

Exercise- and diet-induced reductions in BP are thus mod-est and rarely of sufficient magnitude to achieve normoten-sion.158 Significant decrements in health risk are expected,however, even with marginal reductions in BP.159

What is the impact of dietary composition oncardiometabolic risk?

Although a detailed consideration of the effects of diet com-position on the components of cardiometabolic risk is beyondthe scope of this review, a number of excellent reviews160-162areavailable. Dietary modification is recommended by HealthCanada163 and others98,164as one of the key health behaviour–based strategies to reduce CV risk (see Table 12).98,164,165 Fur-thermore, the 2006 Canadian Clinical Practice Guidelines on theManagement and Prevention of Obesity101 present dietary inter-vention recommendations appropriate for weight loss and man-agement. Regardless of the macronutrient composition, the mostimportant nutritional consideration in improving cardiometa-bolic risk appears to be calorie reduction.101 Sugar-sweetened bev-erages are the greatest contributor to added-sugar intake in theUnited States and may promote weight gain because caloric intakeat subsequent meals is not reduced to compensate for these liquidcalories. As these beverages provide little nutritional value and mayalso increase the risk of type 2 diabetes and CVD independently ofobesity, intake should be limited and should be replaced byhealthy alternatives such as water.166 Limiting dietary sodium in-take to a maximum of 1500 mg per day for those aged �50 years,1300 mg per day for those aged 51 to 70 years, and 1200 mg perday for those aged �71 years is recommended for all adult Cana-

Table 12. Summary of nutritional and physical activityconsiderations

Follow Eating Well with Canada’s Food Guide163

Eat at least 1 dark green and 1 orange vegetable each day.Choose vegetables and fruit prepared with little or no added fat, sugar, or

salt.Have vegetables and fruit more often than juice.Make at least half of grain products whole grain each day.Choose grain products that are lower in fat, sugar, or salt.Drink skim, 1%, or 2% milk or fortified soy beverages each day.Select lower-fat milk alternatives.Have meat alternatives such as beans, lentils, and tofu often.Eat at least 2 Food Guide servings of fish each week.Select lean meats and alternatives prepared with little or no added fat or salt.Include a small amount of unsaturated fat each day.Satisfy thirst with water.Limit foods and beverages high in calories, fat, sugar, or salt.Limit alcohol intake to fewer than 2 drinks per day (fewer than 14 standard

drinks per week for men and fewer than 9 per week for women).98,99

Physical activityDo a minimum of 30 minutes per day most days of the week in addition to

the routine activities of daily living.98,99,101 Recently, an independentCanadian panel recommended adults should accumulate 150 minutesper week of moderate-intensity physical activity or 90 minutes per weekof vigorous activity in periods of at least 10 minutes each.165

Caloric restriction for weight lossDaily caloric deficit of 500-600 kcal, with a goal of no more than a 0.5-kg

(�0.5-1 lb) weight loss per week.101

dians to prevent and control hypertension.90

Brief interactive dietary assessment tools are available fromHealth Canada (http://www.canadasfoodguide.org)163 andDietitians of Canada (http://www.eatracker.ca).167 These toolsprovide information suitable for the general public regardinghow their eating habits compare with Health Canada recom-mendations. In addition, tools and resources for health careprofessionals and the general public regarding dietary sodiumare available from the Canadian Hypertension Education Pro-gram (CHEP; http://hypertension.ca/chep/).90

How can physicians help their patients adopt andmaintain healthy lifestyle behaviours?

Family physicians have described many barriers to incorpo-rating health behaviour counselling into primary care. Theseinclude lack of time, lack of counselling expertise, limited clin-ical resources, lack of support from the health care system, andthe perception that patients are uninterested in changing healthbehaviour habits.168

Until recently, the effectiveness of health behaviour coun-selling interventions delivered by primary care providers onhealth outcomes was unclear. Fleming and Godwin169 con-cluded that primary care–based counselling of adults at lowCV risk had modest benefit on metabolic risk factors includingBP, lipids, CV risk scores, and body weight, even in tightlycontrolled RCTs. Other literature reviews have reached similarconclusions.169,170

Recent evidence, however, suggests that health behaviour–based counselling by primary care providers (nurses and kine-siologists) can promote long-term increased physical activityamong formerly sedentary women171 and long-term weightmaintenance among overweight women.172 Although reasonsfor success were not examined in those trials, other studies haveconsistently identified factors that can reinforce messages andsustain health behaviour changes, including frequent or ongo-ing telephone support, follow-up of missed appointments,work with peer or family members to support health behaviourchanges, and self-monitoring of body weight.173,174 Also, itappears that walking is as effective as expensive centre-basedexercise classes, especially for older adults.173

Nutrition therapy, including counselling by registered di-etitians, has been demonstrated to effectively decrease bodyweight and several metabolic measures (eg, blood lipids, A1C,BP) in individuals who are overweight or have diabetes, dyslip-idemia, and/or hypertension.175

There is a growing consensus that counselling in primarycare requires a multidisciplinary approach.98,101 It is clear thatalthough family physicians have a very important role in iden-tifying people with increased cardiometabolic risk, they do nothave the time or resources to deliver evidence-based, cost-effec-tive interventions that promote sustainable health behaviourchange among their patients. Primary health care reform offersopportunities for inclusion of exercise specialists (kinesiolo-gists) and nutrition specialists (registered dietitians) in primaryhealth care teams.

Summary

The weighted evidence shows that modifications in healthbehaviours (specifically, moderate-intensity exercise for 30 to60 minutes on most days of the week, together with a moderatereduction in caloric intake [�500 kcal per day]) will result in
significant reductions in cardiometabolic risk (see Table 13).
http://www.canadasfoodguide.org

http://www.eatracker.ca

http://hypertension.ca/chep/


Regular exercise is associated with improvements in abdominalobesity, visceral fat, FPG, insulin resistance, TGs, HDL-C, andsystolic and diastolic BP. Caloric restriction is associated withimprovements in abdominal obesity, visceral fat, FPG, insulinresistance, LDL-C, TGs, and HDL-C, and with modest im-provements in BP. Comprehensive and sustained modifica-tions in health behaviours can also significantly reduce the riskfor type 2 diabetes and improve metabolic control and CVDrisk factors in people with type 2 diabetes. The magnitude ofimprovement in these variables appears to be dependent onbaseline values, with greater improvements reported amongthose with the greatest disturbances in metabolic status. Al-though the improvements in cardiometabolic risk factors tendto be more pronounced when a modest reduction in bodyweight is achieved, significant improvements are also observedin the absence of significant weight change.

Despite some evidence of a carry-forward effect of short-term health behaviour interventions, the long-term benefit ofhealth behaviour interventions requires sustained efforts incompliance and adherence. Despite the expected benefits andsignificant reductions in morbidity associated with health be-haviour change, the positive impact of health behaviour inter-ventions on mortality has yet to be demonstrated. Further, theeffect of health behaviour interventions on CV events is not yetknown. The Look AHEAD trial may provide much-neededinsight into the potential association.176 Short-term effects ofhealth behaviour modification on glucose and metabolic riskfactors are promising,136 but long-term data are required inorder to elucidate the effects on the microvascular complica-tions of diabetes and CVD.

Pharmacologic and Surgical Interventions toReduce Cardiometabolic Risk

D.H. Fitchett, M. Gupta, L.A. Leiter, P.A. McFarlane, P.Poirier, J.-C. Tardif, A.W. Steele, and S. Tobe

The adoption of healthy behaviour is the most fundamentaltherapeutic strategy for the individual at increased cardiometa-bolic risk. Clinical trial evidence shows that weight loss andincreased physical activity are very effective in reversing cardio-metabolic risk. However, these health behaviour modifications

Table 13. Effects of health behaviour modification on cardiometabol

Cardiometabolic risk factor Effect of

WC �3.0 to �TGs �0.21 mmHDL-C �0.05 mmLDL-C IncreasedFPG

Person without diabetes NegligiblePerson with diabetes �1.5 mm

Insulin resistance �32% toType 2 diabetes CombinaBP

Systolic �4 mm HDiastolic �3 mm H

BP, blood pressure; FPG, fasting plasma glucose; HDL-C, high-density lipWC, waist circumference.

*Moderate-intensity exercise � 3-5 d/wk; 30-60 min/d.**500- to 700-kcal daily caloric restriction.

are often difficult to achieve and sustain long-term. Thus, phar-

macologic therapy or surgery may be required as an adjunct tohealth behaviour intervention to optimally reduce cardiometa-bolic risk.

The majority of pharmacologic interventions to reduce car-diometabolic risk also apply to the patient with diabetes, sincemost patients with diabetes have increased cardiometabolicrisk.177 Yet there are very few clinical trials that evaluate treat-ment for individuals with cardiometabolic risk without eitherconcomitant diabetes or established CVD.

Who should receive weight loss medications?

In addition to health behaviour modification, pharmaco-logic approaches may be required to manage obesity. Sinceobesity, especially abdominal obesity, is a key component ofcardiometabolic risk,7 reductions in body weight and waistcircumference103,104 are important first steps in any manage-ment strategy, to be achieved primarily through diet and in-creased physical activity.178,179 Of note, visceral fat depot willbe the first fat depot to be mobilized through these ap-proaches.180,181

Weight-loss medications should be used only in associationwith a weight-reducing diet and increased physical activity.182

For patients with a BMI � 30 kg/m2, or those with a BMI �27 kg/m2 plus CV risk factors and/or IGT, guidelines recom-mend that weight-loss medications can be considered if weightloss is �0.5 kg (1 lb) per week after health behaviour changeshave been attempted for 3 to 6 months.182 (See Table 3.) Thereare currently no data to show that weight reduction induced bymedications results in improved clinical outcomes. This is incontrast to the reduced event rates consequent to weight reduc-tion resulting from bariatric surgery.183,184

In Canada, 2 prescription drugs are approved for weightloss, the gastrointestinal lipase inhibitor orlistat and the sero-tonin and norepinephrine reuptake inhibitor sibutramine.Clinical trials using either agent have demonstrated weight lossof approximately 6 to 7 kg during 1 to 2 years, compared with2 to 3 kg with diet alone.182 Studies of clinical outcomes forboth agents are as yet limited. However, weight-loss medica-tions appear to have beneficial effects on the CV system.185 TheXenical in the Prevention of Diabetes in Obese Subjects trial

exercise*Effect of chronic caloric

restriction**

(�6%) �4 to �7 cm (�6%)12%) �0.12 mmol/L (�6%)4%) �0.07 mmol/L (�6%)

rticle size �0.39 mmol/L (�11%)

Negligible15%) �1.2 mmol/L (�15%)

�17% to �72%hysical activity and diet: 31% to 58% relative risk reduction

�5 mm Hg�4 mm Hg

n cholesterol; LDL-C, low-density lipoprotein cholesterol; TGs, triglycerides;

ic risk

chronic

0.7 cmol/L (�ol/L (�

LDL pa

ol/L (��85%

tion of p

gg

oprotei

showed that orlistat treatment for 4 years decreased the risk of


e17

developing type 2 diabetes in patients with IGT, yet in indi-viduals with normal baseline glucose tolerance, new IGT anddiabetes were not prevented.135 A meta-analysis indicates thatsibutramine-induced weight loss is also associated with im-proved glycemic control.186 The Sibutramine CardiovascularOutcomes trial assessed the impact of sibutramine on morbid-ity and mortality in obese patients with established CV disease,diabetes, or both187 and showed increased CV events in thosesubjects randomly assigned to sibutramine vs placebo (11.4%of patients vs 10%). Further analyses indicate the increased riskfor CV events occurred in patients with a history of CVD,leading the US Food and Drug Administration to contraindi-cate the use of the drug in patients with a history of CVD.Subsequently, the Food and Drug Administration concludedthat the CV risks posed by sibutramine outweighed the modestweight loss observed with the drug and asked the manufacturer(Abbott Laboratories) to pull the drug from the market.188

There is insufficient evidence to recommend in favour of oragainst the use of herbal remedies, dietary supplements, or ho-meopathy for weight management in the obese person.101,189

Who should be considered for bariatric surgery?

Bariatric surgery has been shown to lower all-cause mortalityby 24% to 40%.183,184 because of a reduction in deaths frommyocardial infarction (MI), diabetes, and cancer and to preventthe development of diabetes in patients with severe obesity.190

Currently, bariatric surgery can be considered in individuals withclass III or above obesity (ie, BMI � 40 kg/m2)87 or those withclass II obesity (ie, BMI � 35 kg/m2) plus comorbid condi-tions.101,189 Bariatric surgery has a low operative mortality (�1%)if performed by an experienced team.191 Surgical intervention re-sults in sustained weight loss, improvement in comorbidities, andincreased survival. However, late complications may arise fromboth nutritional deficiencies and behavioural changes. The bestoutcomes are achieved in high-volume, comprehensive bariatriccentres, with an interdisciplinary team dedicated to long-term fol-low-up. Bariatric surgery is indicated for patients who have severeobesity, in whom efforts at medical therapy have failed, and whohave an acceptable operative risk. Following bariatric surgery, pa-tients report improvements in their quality of life, social interac-tions, psychological well-being, employment opportunities, andeconomic condition.

Lipid control

Statin therapy reduces adverse CV risk in persons with dia-betes, irrespective of the baseline LDL-C.192 The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) showed that lovastatin 20 to 40 mg reduced majorCV events by 37% in subjects with no history of vascular dis-ease and average LDL-C levels, yet lower than average HDL-C(35% had HDL-C � 0.91 mmol/L).193 The population meanBMI was 26 to 27 kg/m2, and the median hs-CRP was 1.6mg/L. Hence, it is likely that a significant proportion of thepopulation had cardiometabolic risk factors. A post hoc analy-sis indicated that in individuals with LDL-C below the medianLDL-C, the benefit of statin treatment was limited to thosewith an elevated hs-CRP level. The randomized trial of rosuv-astatin in the primary prevention of cardiovascular eventsamong individuals with low levels of LDL-C and elevated levelsof CRP (Justification for the Use of Statins in Prevention: An
Intervention Trial Evaluating Rosuvastatin [JUPITER])
showed that women aged �60 years and men aged �50 yearswith LDL-C � 3.4 mmol/L and hs-CRP � 2 mg/L benefitedfrom rosuvastatin 20 mg daily (44% reduction in the primaryendpoint [MI, stroke, arterial revascularization, hospitalizationfor unstable angina, or death from CV causes] and 37% reduc-tion in the combined endpoint of nonfatal MI, nonfatal stroke,or death from CV causes).42 Subgroup analysis showed similarrelative hazard ratio reductions in the rosuvastatin group inevery subgroup analysis, including those with or without met-abolic syndrome and those with or without a BMI � 25 kg/m2

or BMI �30 kg/m2. (Over 40% of individuals were noted tomeet the most recent criteria of the National Cholesterol Edu-cation Program Adult Treatment Panel III for metabolic syn-drome, and the median BMI was 28.1 kg/m2.42) The Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm,in patients with hypertension and 3 additional CV risk factors,demonstrated that atorvastatin 10 mg daily reduced CV eventsby 36% during approximately 3 years.194 Many individualswith cardiometabolic risk have hypertension with additionalCV risk factors and will consequently benefit from statin ther-apy. (See Tables 8 and 9.)

Which patients with cardiometabolic risk should receivestatin therapy? Current CCS dyslipidemia guidelines99 indi-cate that the decision to institute statin therapy should be basedon an estimate of 10-year total CV risk determined by the FRS.Patients at high risk should be treated with statin therapy in-dependent of baseline LDL-C, whereas health behaviour inter-vention alone may suffice for those with a low risk score. Forindividuals with a moderate risk score, recognition of cardio-metabolic risk may justify managing the patient as if he or shewere at high risk. The American Diabetes Association/Ameri-can College of Cardiology consensus statement5 on lipoproteinmanagement in patients with cardiometabolic risk suggeststhat individuals with an FRS of 10% to 19% be consideredhigh risk if they have 2 or more cardiometabolic risk factors.The CHEP guidelines90 recommend statin therapy for individ-uals with systemic hypertension and 3 or more CV risk factors.However, the current CCS dyslipidemia guidelines99 state thata moderate-risk patient with apo B � 1.0 g/L does not requiretreatment with a statin just to achieve the apo B target of �0.8g/L. In men aged �50 years and women aged �60 years withmoderate FRS (10%-19%), hs-CRP � 2 mg/L identifies agroup of patients who benefit from aggressive LDL-C reduc-tion. Many of these patients will have cardiometabolic risk.

The CCS dyslipidemia guidelines99 recommend an apoB lipoprotein � 0.8 g/L as an alternative primary treatmenttarget in high- and moderate-risk patients. In patients withcardiometabolic risk and relatively low baseline LDL-C, apo Bis likely to be a more useful measurement than LDL-C. Apo Blipoprotein measurement is valuable in the identification ofhigh CAD risk in individuals with cardiometabolic risk. Addi-tional investigations may help to better stratify risk and mayinclude measurement of hs-CRP, noninvasive imaging of thecarotid arteries for atherosclerosis, measurement of the ankle-brachial index, and an assessment of cardiorespiratory fitness.

What are the treatment goals of lipid therapy? Individualswith IGT have a risk of CAD close to that of people with
diabetes. Consequently, there is justification to recommend


that they receive statin therapy to achieve LDL-C targets sim-ilar to those for patients with established diabetes. The currentCCS dyslipidemia guidelines99 recommend a �50% reductionof LDL-C or target level of �2.0 mmol/L in subjects consid-ered to be at high risk. Similar treatment goals should be soughtin the patient with a moderate FRS and multiple cardiometa-bolic risk factors. In subjects with isolated IFG (ie, with aknown normal 2-hour 75-g oral glucose tolerance test value),CAD risk is lower than in those with IGT. In the absence ofmultiple cardiometabolic risk factors, these subjects shouldlikely be managed according to their FRS, LDL-C, or apo Blevels. Apo B may be helpful in achieving an optimal reductionof cardiometabolic risk, especially in individuals with hypertri-glyceridemia and low HDL-C. (See Tables 7 and 8.)

Can we reduce residual risk by managing other lipidtargets? There is a large residual risk for patients at high risk forCVD, despite LDL-C reduction with high-dose statins. Mostpatients with cardiometabolic risk have an acquired combinedhyperlipidemia, associated with increased TGs, a modest in-crease in LDL-C, and low HDL-C. LDL particle numbers areincreased, as reflected by the increased levels of apo B100.

Beyond LDL-C lowering, other strategies that might reducethe residual risk include the optional secondary targets dis-cussed in the most recent CCS dyslipidemia guidelines.99

These include reducing the total cholesterol–to–HDL-C ratio,hs-CRP, and TGs, although there are no clinical trial data tosupport such strategies. In the patient with diabetes, optimiza-tion of glycemic control and health behaviour modificationshould be attempted prior to the addition of another agent,such as a fibrate. In the Action to Control Cardiovascular Riskin Diabetes trial,195 the addition of fenofibrate to simvastatinin patients with type 2 diabetes failed to show any reduction ofCV events, although there may have been benefit in individualswith high TGs and/or low HDL-C, as had been shown inpatients with the same lipid profile features in the FenofibrateIntervention in Event Lowering in Diabetes trial,196 the Beza-fibrate Infarction Prevention study,197 and the Veterans AffairsHigh-density Lipoprotein Trial.198 We await the results of on-going clinical trials such as the Atherothrombosis Interventionin Metabolic Syndrome With Low HDL/High Triglyceridesand Impact on Global Health Outcomes,199 the Treatment ofHDL to Reduce the Incidence of Vascular Events,200 and theStudy of RO4607381 [dalcetrapib] in Stable Coronary HeartDisease Patients With Recent Acute Coronary Syndrome,201

which are assessing whether the addition of other second lipid-modifying agents to a statin will be associated with additionalCV risk reduction.

Hypertension control

Over 30% of people with metabolic syndrome have sys-temic hypertension. In addition, approximately 20% of peoplewith hypertension have IGT.202 These individuals are at higherrisk of developing diabetes and CVD. Furthermore, chronicrenal insufficiency (glomerular filtration rate � 60 mL perminute) is approximately 2.5 times more common in peoplewith metabolic syndrome.

Who should receive antihypertensive treatment and towhat goals? The CHEP guidelines90 recommend health be-
haviour changes for people at risk for developing hypertension,
specifically physical exercise, weight reduction, maintenance ofa healthy BMI and waist circumference, and moderation ofalcohol and sodium intake. The CHEP guidelines90 recom-mend people with cardiometabolic risk should be treated to aBP � 140/90 mm Hg, unless they have diabetes or chronickidney disease, in which case a lower target of �130/80 mmHg should be used. Yet the recently reported Action to ControlCardiovascular Risk in Diabetes BP trial203 in patients withdiabetes failed to show benefit of systolic BP lowering to 120mm Hg compared with 140 mm Hg. (See Tables 7 and 8.)

Should specific antihypertensive agents be chosen oravoided in individuals with cardiometabolic risk? Clinicaltrials have not specifically evaluated BP lowering in individualswith cardiometabolic risk. However, RAAS inhibitors havebeen prospectively tested in individuals with prediabetes for theprevention of new-onset diabetes. In the Nateglinide and Val-sartan in Impaired Glucose Tolerance Outcomes Researchstudy,204 valsartan was shown to reduce the incidence of dia-betes by 14% in individuals with IGT and heightened CV risk.In the Diabetes Reduction Assessment With Ramipril andRosiglitazone Medication, ramipril was found to have asmaller, nonsignificant effect on the prevention of diabetes inindividuals with either IFG or IGT.205 In a systematic over-view of 3 large trials of ACE inhibition in individuals withCVD, but without diabetes, a reduction in diabetes of similarmagnitude was observed.206 Therefore, in individuals with car-diometabolic risk associated with dysglycemia, it may be advis-able to use antihypertensive drugs that may be associated withimprovement of glucose metabolism (ie, RAAS inhibitors) oragents that are metabolically neutral (ie, calcium channelblockers [CCBs]). Thiazide diuretics are associated with anincreased risk for development of new diabetes. In the Antihy-pertensive and Lipid-Lowering Treatment to Prevent HeartAttack Trial,207 chlorthalidone treatment was associated with agreater incidence of new diabetes than in patients treated witheither amlodipine or lisinopril. Yet prevention of MI was sim-ilar with all 3 agents during the study’s relatively short period ofobservation. In a long-term cohort study of newly treated hy-pertensive patients, with follow-up 1 to 16 years (median, 6years), the development of new diabetes was associated with arisk of CV events that was similar to that of individuals withpreviously known diabetes.208 Combinations of an ACE inhib-itor and CCB, compared with therapy that includes a thiazidediuretic, are associated with a reduced incidence of new-onsetdiabetes209 and improved CV outcomes related to differencesin blood glucose level and body weight.210 Consequently, inpatients with cardiometabolic risk, it may be preferable to useantihypertensive therapies that are metabolically neutral (ie,CCBs). In patients with cardiometabolic risk who require BPlowering with multiple agents, combining an ACE inhibitorand a CCB may be preferred to combining an ACE inhibitorand a diuretic.211

How can the risk for diabetes be reduced in thepatient with cardiometabolic risk?

Individuals with cardiometabolic risk are at a substantiallygreater risk of developing type 2 diabetes, with its associatedincremental risks for CVD and renal disease. For patients withIFG, IGT or metabolic syndrome, health behaviour modifica-
tion with weight loss and increased physical activity are the


e19

most effective210 (See the section titled Health Behaviour In-terventions to Reduce Cardiometabolic Risk). While healthbehaviour change is most effective, metformin,126 acarbose,131

rosiglitazone,132 pioglitazone,134 combination therapy withmetformin and rosiglitazone,133 and orlistat135 have all beenshown to reduce progression to type 2 diabetes. In the DiabetesPrevention Program, metformin reduced progression fromIGT to diabetes126 Rosiglitazone was shown in the DiabetesReduction Assessment with Ramipril and Rosiglitazone Med-ication trial to reduce the development of diabetes in subjectswith either IGT or IFG, yet the study was not powered toexamine CV outcomes.132 The Study to Prevent Non-Insulin-Dependent Diabetes suggested that a reduction of the inci-dence of new diabetes with acarbose was associated with a re-duction of CV events.131 In the Xenical in the Prevention ofDiabetes in Obese Subjects study, orlistat treatment was asso-ciated with a reduction in weight and in the incidence of dia-betes.135 The recently published Nateglinide and Valsartan inImpaired Glucose Tolerance Outcomes Research showed thatvalsartan exerted a modest reduction in the development ofnew diabetes (hazard ratio, 0.86; 95% CI, 0.8-0.92; P � .001)in patients with both IGT and either CVD or CV risk fac-tors.204 However, neither valsartan212 nor the antihyperglyce-mic agent nateglinide204 had any impact on CV events (CVdeath, nonfatal MI, nonfatal stroke, hospitalization for unsta-ble angina, heart failure, or arterial revascularization; see Tables7 and 8). While health behaviour modifications are the pre-ferred strategy to prevent diabetes, if pharmacologic interven-tions are added to health behaviour, metformin is indicated asfirst-line therapy, based on its efficacy, safety, and cost.

Antiplatelet therapy

Enhanced platelet activity plays a role in the increased riskof atherothrombosis in individuals with metabolic syndrome.Antiplatelet therapy with acetylsalicylic acid (ASA) is an estab-lished treatment for the secondary prevention of coronaryevents in high-risk patients with acute or chronic CAD.213

However, a meta-analysis of ASA trials for the primary preven-tion of CVD showed no mortality benefit, a small absolutereduction of CAD in men (8/1000 treated over 6.4 years), butnot women, and a reduction of stroke in women (3/1000), butnot men.214 For individuals with hypertension and increasedvascular risk with metabolic syndrome or dysglycemia, the Hy-pertension Optimal Treatment trial215 also showed a verysmall absolute reduction (0.16%) using ASA in patients withmultiple CV risk factors and hypertension, once BP is ade-quately controlled. Furthermore, for patients with diabetes andno clinical evidence of vascular disease, a recent meta-analysisfailed to show evidence that ASA provides any protective ben-efit.216 Hence, the benefits of ASA for primary prevention arevery small and offset by bleeding risk, even when used in pa-tients with risk factors such as diabetes.

Should patients with cardiometabolic risk receive ASA?Although a recent US Preventive Services Task Force Recom-mendation Statement217 recommends ASA for primary pre-vention in men aged 45 to 79 years and women aged 55 to 79years, current clinical trial evidence is not supportive of thisadvice. In the absence of a clinical history of CAD (MI or
angina), stroke or peripheral arterial disease, or vascular imag-
ing showing atherosclerosis, there is no evidence to support theuse of ASA in patients with cardiometabolic risk.

Antismoking therapy

Clinician counselling218 with pharmacologic assistance in amotivated patient is most likely to result in long-term absti-nence than either strategy alone. Nicotine replacement (gum orpatch), bupropion, and varenicline are pharmacologic agentsthat have been shown to improve the success of smoking ces-sation by successfully treating the addiction component ofsmoking.219

Which patients should receive pharmacologic agents tohelp increase the success of smoking cessation? All pa-tients who are motivated to stop smoking should be offeredboth medication and counselling, as well as follow-up contactsto prevent relapse.220 Combinations of medications should beconsidered. Motivated patients should be managed through amultidisciplinary smoking cessation program when one isavailable locally.

Summary

Vascular protective measures are essential for all patientswith cardiometabolic risk.

Health behaviour modification: As discussed in the sectiontitled Health Behaviour Interventions to Reduce Cardiometa-bolic Risk.

Optimizing BP levels: In hypertensive patients, BP controlshould be achieved. In individuals with cardiometabolic riskassociated with dysglycemia, it may be advisable to use antihy-pertensive agents associated with improved glucose metabo-lism or agents that are metabolically neutral.

Optimizing lipid levels: In patients with cardiometabolicrisk with a moderate or high FRS, treatment should be initiatedwith a statin to reduce LDL-C by at least 50% and to �2.0mmol/L. Apo B levels are a better measurement of lipid-relatedrisk in these patients and the target level for treatment is �0.80g/L in high-risk and moderate-risk individuals.

Optimizing blood glucose levels, preventing progressionto diabetes and managing hyperglycemia: In patients withcardiometabolic risk, weight loss and increased physical activityare recommended to reduce risk. Pharmacotherapy can also beconsidered as per the Canadian Diabetes Association 2008guidelines.

Antiplatelet therapy: The benefits of ASA for primary pre-vention are very small and offset by the bleeding risks, evenwhen used in patients with risk factors for vascular disease suchas diabetes. In patients with cardiometabolic risk, in the ab-sence of a clinical history of coronary heart disease (MI orangina), stroke, or peripheral vascular disease, or of vascularimaging showing atherosclerosis, there is no evidence to sup-port the use of ASA.

Smoking cessation: In addition to counselling, medica-
tions (nicotine replacement, buproprion, or varenicline)


should be offered to most patients who are motivated to stopsmoking.

Cardiometabolic Risk in Susceptible CanadianPopulations

M. Gupta, S. Anand, C.-M. Chow, S.B. Harris, S. Qaadri,and H. Teoh

How do ethnicity and culture impact oncardiometabolic risk?

Canada is one of the world’s most ethnically diverse coun-tries. It has been recognized that ethnicity may impact onhealth outcomes, including the risk for cardiometabolic dis-eases. Accordingly, in order to appropriately assess and screenindividuals in Canada’s diverse patient populations, Canadianhealth care professionals must be aware that risk factors vary infrequency among certain ethnic populations. This section fo-cuses on the prevalence of cardiometabolic risk factors in 3 ofCanada’s susceptible populations: South Asians, Chinese, andAboriginals. It is important to note that research and data arelacking for certain susceptible populations entirely, and for riskfactors in a given population. In Canada, this particularly ap-plies to the Afro-Caribbean population. As there are noagreed-on terms in the literature to describe each population,

Table 14. Cultural and clinical considerations regarding cardiometab

Population (originating from) Cultural consid

South Asian (India, Pakistan, Sri Lanka,Bangladesh, and Nepal)

An extremely heterogeneowide variations in apphealth behaviour, diet,consumption234

Chinese (Mainland China, Hong Kong,Malaysia, Singapore, and Taiwan)

Recent change in the demimmigrants: now fromand speaking mainly Mtraditional immigratiospeaking regions of sounamely Hong Kong)28

Aboriginal (Canada) Rapid cultural transition ogenerations, highlightefrom traditional healthmore sedentary livinghas translated into a hchronic disease

BMI, body mass index; BP, blood pressure; HT, hypertension; IGT, imglucose tolerance test; WC, waist circumference.

or even agreement on the inclusion criteria for each population,

the terms used in this section reflect the language used by theauthors of the relevant studies.

CVD rates vary considerably among Canadians of differingethnic origins, but the reasons for this variation have not beenfully elucidated.221 For example, the Study of Health Assess-ment and Risk in Ethnic Groups (SHARE) found differencesin the prevalence of conventional and emerging risk factorsamong South Asians, Chinese, and individuals whose ancestorsoriginated from Europe, all residing in Canada, but this varia-tion did not fully explain the higher rates of CVD noted amongSouth Asians. It is important that SHARE suggested that find-ings from studies carried out in European populations cannotbe fully extrapolated to other ethnocultural populations.222

Table 14 provides a brief description of South Asian, Chi-nese, and Aboriginal/First Nations populations and highlightsclinical issues that should be considered in the management ofpatients in these populations. The text expands on issues ofparticular importance in each population. It is important tonote that the relationship between percentage body fat andBMI is ethnic specific.223-225 Therefore, ethnic-specific thresh-olds for the definition of overweight and central adiposity arerecommended (see Table 1). Despite the differences amongpopulations, it is important to note that the INTERHEARTstudy (which evaluated modifiable risk factors associated with

and assessment in select at-risk populations

s Clinical considerations

lation, withto health,acco

BMI and WC:● Increased cardiometabolic risk at BMI or WC

levels traditionally considered “normal.”● Use ethnic-specific WC and BMI cutoffs (see

Table 1)BP:● Three times more likely to have HT than people of

European descent236

Lipids:● Higher LDL-C than Europeans and Chinese222

Diabetes:● High prevalence of diabetes98

cs of thend Chinan (vsCantonese-hina,

BMI and WC:● Increased cardiometabolic risk at BMI or WC

levels traditionally considered “normal”● Use ethnic-specific WC (see; Table 1) and BMI

cutoffs223

past 2 or 3hift awayours towardstern diets,d risk for

BMI and WC:● With high rates of obesity, focus on physical

activity and other healthy behaviours.Diabetes:● High rates of diabetes● Screening for diabetes should be considered every 1

to 2 years in individuals with more than 1 riskfactor98

● Individuals with normal results, but with riskfactors, should receive health behaviour counselling

● Annual OGTT testing should be encouraged inindividuals with IGT98

Smoking:● Among the highest rates of smoking in the

world266

● Smoking prevention and cessation should be apriority

glucose tolerance; LDL-C, low-density lipoprotein cholesterol; OGTT, oral

olic risk

eration

us popuroachesand tob

ographimainlaandari

n fromthern C

2

ver thed by a sbehavi

and Weeightene

paired

MI in 27,000 people from 52 countries) found that, collec-


e21

tively, the following 9 risk factors account for 90% of the pop-ulation-attributable risk of MI in men and 94% in women:abnormal lipids, smoking, hypertension, diabetes, abdominalobesity, psychosocial stress, lack of consumption of fruits andvegetables, lack of moderate alcohol consumption, and lack ofphysical activity. The proportional contribution of these riskfactors to risk of first MI was consistent across all ethnicgroups.53 These findings stress the importance of addressingthese risk factors (through prevention and treatment) in allpopulations, regardless of ethnic origin.

What is known about cardiometabolic risk in SouthAsians?

South Asian ethnicity has been suggested to be an indepen-dent risk factor for CVD.222,226 People of South Asian originare at increased risk for premature CAD,227 with an approxi-mately 3- to 5-fold increased risk for MI and CV death com-pared with other ethnic groups.228 In addition, in an analysis ofage-standardized mortality in Canada over 15 years, SouthAsians had the highest CAD mortality compared with individ-uals of European or Chinese descent.229

In the SHARE study, South Asians had the highest preva-lence of CVD and an increased prevalence of glucose intoler-ance and dyslipidemia, as well as more abnormalities of novelrisk factors (such as increased fibrinogen, homocysteine, lipo-protein (a), and plasminogen activator inhibitor-1.222 Com-pared with matched controls of various ethnic descents, SouthAsian Canadians have been found to present to the hospitallater in the course of acute MI; be more likely to have ananterior infarction230; be younger at the first hospitalization forheart failure226,231; and at the time of catheterization,232 havemore significant left main, multivessel, and distal CAD232;have poorer outcomes and survival from coronary artery bypasssurgery (CABG)233; have CAD at lower BMI (actually withinthe “reference range”)226,230; be more likely to have diabe-tes234; and be more likely to have evidence of CAD, even in theabsence of symptoms or clinical findings.234 A recent analysisof CV risk profiles of major ethnic groups in Ontario demon-strated that South Asians have a higher prevalence of heartdisease and strokes than does the white population.235

In the INTERHEART study,231 the average age of first MIin South Asians was approximately 10 years younger than inthe rest of the study population. However, after adjusting forthe major INTERHEART risk factors, particularly smoking,high ratio of apo B100 to apo A1, hypertension, and diabetes,this age difference became insignificant, suggesting that SouthAsians do not necessarily have “unexplained CAD risk factors”;rather they accrue known risk factors at a younger age, thusexplaining the premature onset of CAD. Possible explanationsfor South Asians’ development of risk factors at younger agesinclude genetic predisposition, unique health behaviours,and/or an interaction between the two.

Compared with other populations, South Asians have beenfound to have higher LDL-C, lower HDL-C, and higherTGs.222,232,234 South Asian men have been shown to havehigher concentrations of small HDL particles (the cardiopro-tective properties of HDL are likely restricted to the largerparticles), and some studies have shown higher levels of small,dense LDL particles, which may be more atherogenic.222,234

In a recent Ontario survey on the prevalence and control of
hypertension, South Asians were 3 times more likely than
white people to have hypertension.236 Ontario data on CV riskfactors also revealed that smoking and obesity are less prevalentin South Asian than in white populations.237

The prevalence of diabetes is uniformly higher amongSouth Asians than in most comparative populations. In On-tario, compared with immigrants from western Europe andNorth America, those from South Asia have the highest prev-alence of diabetes, followed by those from Latin America, theCaribbean, and sub-Saharan Africa.237 In SHARE, SouthAsians had almost 3 times the prevalence of treated diabetes aspeople of European descent. Testing with a 2-hour oral glucosetolerance test revealed that one-third of South Asians withoutknown diabetes had either IGT or type 2 diabetes (despitehaving a lower BMI compared with people of European de-scent).222 A well-documented pattern of type 2 diabetes orglucose intolerance, often associated with reduced HDL-C andincreased TGs, in South Asians suggests that insulin resistancemay partially explain the excess CAD risk in this population.234

When obesity is defined by standard criteria, such as BMI� 30 kg/m2, South Asians have a low prevalence of obesitycompared with other populations.228 However, abdominalobesity, as suggested by increased waist circumference, seems tobe highly prevalent in this population and is independentlyassociated with both diabetes and CVD. Thus, South Asiansmay exhibit considerable cardiometabolic risk at BMI or waistcircumference levels traditionally considered “normal”.238 Ac-cordingly, lower BMI and waist circumference thresholds havebeen advocated in South Asians. In fact, some studies suggestthat the ideal BMI in a South Asian individual may be between19 and 21 kg/m2.225

South Asians are more likely to have visceral fat across theBMI spectrum. This is accompanied by a higher degree ofinsulin resistance for the same BMI, even in individuals whoare not obese.225,234 The hyperinsulinemia that accompaniesinsulin resistance is associated with premature CAD. SouthAsians, therefore, appear to have higher CAD risk at lower BMIcompared with European populations. Accordingly, the WorldHealth Organization223 has recommended lower BMI cutoffsfor overweight (23 kg/m2) and obesity (25 kg/m2) in all Asians,including South Asians. The increased prevalence of abdomi-nal obesity, metabolic syndrome, glucose intolerance, or acombination may mediate the excess CAD risk. Furthermore,South Asians have the least favourable adipokine profile, andlike the Aboriginal people, they display a greater increase ininsulin resistance with decreasing levels of adiponectin.239

What is known about cardiometabolic risk in Chinese?

Lipid levels in general are similar between Chinese and Eu-ropeans, but Chinese are more susceptible to the low HDL-Cassociated with metabolic syndrome and insulin resistance.222

Noteworthy is the high prevalence of dyslipidemia at low BMIvalues among Chinese adults from Singapore224,240 and Tai-wan.241

Hypertension is the leading preventable risk factor for CVDand all-cause mortality in the developing world, and there is astrong linear association between BP levels and CVD in theChinese.242 Chinese seem to be prone to elevated BP, with therisk increasing at a BMI of about 23 kg/m2.243 In the CanadianSHARE study, the Chinese group had the highest rate of hy-pertension requiring medication.222 In an Ontario BP survey,
East Asians, a heterogeneous ethnic group including Chinese,


had a prevalence of hypertension similar to that of white peo-ple.236 Chinese in Ontario were found to have a lower preva-lence of obesity, lower rates of smoking, similar prevalence ofdiabetes, and a relatively low prevalence of CVD comparedwith the white population.235

In the SHARE study, if subjects with diabetes at baseline(2.6%) were excluded, the prevalence of newly diagnosed IGTor diabetes in the Chinese was 20%, compared with 18% ofEuropeans and 28% of South Asians.222 This is an importantfinding, as the Chinese had significantly lower BMI than didEuropeans, yet had intermediate rates of dysglycemia.

For the same BMI, Chinese persons have been shown tohave a higher percentage of body fat than white peopledo,244,245 which may explain the high prevalence of CVD riskfactors at low BMI and waist-to-hip ratios, as well as the highmorbidity and mortality from CVD even in the presence of lowpopulation-mean BMI and obesity rates. In an analysis ofSHARE,225 among Chinese with a BMI � 23 kg/m2, BP,glucose, and lipids became abnormal. Hence, universal BMIcutoff points are not appropriate,244,245 and the use of valuesextrapolated from those of white people may significantly un-derestimate risk.

In INTERHEART, the Chinese had a more favourablelipid profile than did people in other regions of the world. Theassociations between first MI and diabetes, depression, andstress were stronger for the Chinese than for other participants,whereas the association between first MI and abdominal obe-sity was significantly lower.246

Identifying those with hypoadiponectinemia and elevatedwaist circumference has been shown to increase the sensitivityof identifying Chinese subjects at particular risk of glucoseintolerance and clustering of other risk factors.247,248 It is,however, recognized that the measurement of adiponectin can-not be readily performed at the present time.

What is known about cardiometabolic risk inAboriginal people?

Compared with Canadians of European descent, Canada’sAboriginal people have a higher prevalence of carotid athero-sclerosis and CVD and significantly higher rates of smoking,glucose intolerance, obesity, and abdominal obesity.222,249-251

In one community, a tripling in admission rates for ischemicheart disease was observed during a 15-year period.252

Despite a rich variation in location, language, history, andculture, increased rates of type 2 diabetes in comparison withthe nonindigenous general population seem to be a shared phe-nomenon.253 Type 2 diabetes has reached epidemic propor-tions among Canadian Aboriginals/First Nations peoples. Theage-adjusted national prevalence is 2.5 to 5 times higher inFirst Nations people than in the general population,254,255

with prevalence rates as high as 26% in some communities.256

First Nations peoples are also diagnosed with type 2 diabetes ata much younger age.254,257 Recent data indicate that the inci-dence of type 2 diabetes is increasing among children andyouth aged �18 years and disproportionately among Aborigi-nal youth.258 In the 2004 Canadian Community Health Sur-vey, the prevalence of obesity in adults was 37.8% among Ab-originals, compared with 22.6% in non-Aboriginals, and inchildren and youth, the respective rates were 15.8% vs8.2%.257 In the Canadian First Nations Diabetes Clinical
Management Epidemiologic (CIRCLE) study carried out in
partnership with 19 First Nations communities across Can-ada, 25.7% of adults were obese (BMI 30.0-34.9 kg/m2),and 30.3% were classified as morbidly obese (BMI � 35.0kg/m2).257

A number of other factors may contribute to the high ratesof disease. These include genetic susceptibility, high-fat andhigh-glycemic-load diets, low levels of physical activity (partlydue to environments not conducive to physical activity), smok-ing, geographic isolation, and remoteness (leading to inade-quate access to care). In addition, social factors such as highrates of poverty, inferior health care and social service infra-structure, educational disadvantage, and high unemploymentrates may be implicated.259-262 Aboriginal peoples in Canadaare more socially disadvantaged than populations of European,South Asian, or Chinese ancestry.263 Worldwide, Aboriginalpeoples have unemployment and poverty rates almost 2 to 4times higher than national benchmarks.264 In Canada, diabetesrates have been shown to be inversely correlated with house-hold income level.265 For any given income level, Aboriginalpeople have a higher prevalence of risk factors and CVD thando Europeans.249

Aboriginal Canadians have among the highest rates ofsmoking in the world (First Nations, 56%; Métis, 57%; Inuit,72%).266 In the Ojii-Cree community of Sandy Lake, 50% ofthe participants overall and 82% of the adolescent participants(aged 15-19 years) were current smokers. An independentdose-response relation was found between current smoking ex-posure and both traditional (systolic BP) and nontraditional(homocysteine level) CVD risk factors. The relationship be-tween smoking and increased CV risk at an early age may be acontributing factor to the high prevalence of CVD in this pop-ulation.267 Together, these factors result in the marginalizationof Aboriginal peoples and may produce stressful environmentsthat impact health and cardiometabolic disease through bothpsychosocial and behavioural pathways.268

What do we know about cardiometabolic risk inAfro-Caribbeans?

Recent Canadian Census data indicate that of immigrantsto Canada from 2001 to 2006, 11% were from Central orSouth America, and 10.6% were from Africa. Unfortunately,there is a lack of studies among Afro-Caribbeans in Canada.Although there is a wider American literature on health serviceuse and outcomes in African Americans, it is unknown whetherfindings in that population would apply to the Canadian Afro-Caribbean population. Canadian guidelines include Africandescent as a risk factor for type 2 diabetes.269 In addition, anOntario BP survey found that black people (primarily of Ca-ribbean origin) had the highest prevalence of hypertensionamong the 4 ethnic groups studied, with a 3.3-fold increase inthe prevalence of hypertension compared with the referencewhite population. In addition, they developed hypertension ata much earlier age; by age 60, 50% of this population hadhypertension.236

A recent Ontario study revealed a paradox among Ontariansof black ethnicity: While they had least favourable overall CVrisk profile compared with Ontarians of white, Chinese, orSouth Asian ethnicity, they had a relatively low prevalence of
heart disease.235


e23

What is known about emerging risk factors insusceptible populations?

Several studies have shown higher levels of hs-CRP in SouthAsians compared with Caucasians, a difference that persistseven after adjusting for total body fat and waist circumference,suggesting that South Asians may have an underlying proin-flammatory state linked to excess visceral adiposity that maycontribute to their increased risk of diabetes and CAD.234,270

CRP levels have been shown to vary significantly among ethnicpopulations and to be influenced by the differences in meta-bolic factors in these populations. However, prospective vali-dation of the predictive value of CRP for CVD among non-Europid populations is needed.270 In addition, it has beenshown that the nonfasting ratio of apo B to apo A1 is superiorto any of the cholesterol ratios for estimation of the risk of acuteMI in all ethnic groups, in both sexes and at all ages.271 How-ever, this test is not routinely available in Canada, and there areno current guideline recommendations regarding this ratio,either for screening or as a target of therapy. Given that SouthAsians have proportionately more visceral fat (across the BMIrange) than do other populations, altered levels of adipokines(adiponectin, resistin, and leptin) have been implicated in thepathogenesis of insulin resistance in this population.234

Many emerging risk markers are under investigation andmay vary among ethnic groups, but none has yet been shown tosubstantially aid in risk stratification beyond traditional riskfactors, nor has any been shown to specifically improve riskstratification in particular ethnic groups. Noninvasive imagingof atherosclerosis, such as with carotid intima-media thicknessmeasurement, has potential screening utility in the future, butfurther studies are required. The SHARE study revealed thatcarotid atherosclerosis in healthy middle-aged Canadians wasfairly common (23% prevalence) and occurred with similarprevalence among white Europeans (25%), Chinese (24%),Aboriginals (20%), and South Asians (22%).272

Does socioeconomic status impact on cardiometabolicrisk?

Anand and colleagues studied the relationship between so-cioeconomic status, CV risk factors, and CVD among men andwomen from diverse ethnic populations. The most socially dis-advantaged were more likely to be older, women, smokers, andhave higher body weight, abdominal obesity, glucose, and in-flammatory marker elevation compared with less socially dis-advantaged individuals. Indeed, for every 1-point increase inthe index used to calculate social disadvantage, the relative in-crease in CVD was 25% (range, 6%-47%).263 People of Euro-pean origin were the least socially disadvantaged, comparedwith Aboriginal people (who were the most socially disadvan-taged), with Chinese and South Asians having intermediatelevels of social disadvantage.263 Independent of age, social dis-advantage is associated with an increase in some, but not all,CV risk factors and has been shown to be a significant predictorof CVD.263

The highest rates of diabetes are seen in the lower-incomequintiles.273 In the 1998-1999 National Population HealthSurvey,267 21.4% of people with diabetes reported low income(vs 12.8% in the general population), and 42.7% reported notfinishing secondary school (vs 22.5% in the general popula-
tion). People in lower income brackets and with fewer years of
formal education also reported higher rates of smoking, lessphysical activity, and higher rates of overweight.274 Smokingprevalence is twice as high for the lowest family-income cate-gory as for the highest (37% vs 20% for men and 30% vs 16%for women).275

Household food insecurity has also been shown be associ-ated with poorer health. The prevalence of household foodinsecurity is higher among Canadians with diabetes and is as-sociated with an increased likelihood of unhealthy behavioursthat would impact on cardiometabolic risk (including physicalinactivity, lower fruit and vegetable consumption, and currentsmoking).276 Research in the United States has demonstratedthe association between food insecurity among low-income in-dividuals and hypertension and hyperlipidemia.277

Due to the paucity of Canadian research on the impact andimplications of low socioeconomic status on cardiometabolicrisk, recommendations on specific management of this popu-lation cannot be made. More research on the social determi-nants of heath, specifically in the area of cardiometabolic dis-eases, will help clarify therapeutic strategies and the healthpolicies needed to minimize risk in this population.

Therapeutic implications

Traditional risk factors explain the majority of CV events inall populations, including the specific populations discussed inthis chapter.53 Thus, health behaviour and pharmacologic in-terventions to reduce cardiometabolic risk should be optimallyapplied to all patient populations as per national guidelines,and as per the suggestions outlined earlier in this document (seethe section titled Health Behaviour Interventions to ReduceCardiometabolic Risk and the section titled Pharmacologicand Surgical Interventions to Reduce Cardiometabolic Risk).

Whether specific ethnic groups would benefit from thera-pies different from those recommended in guidelines or fromdifferential treatment targets remains unclear. However, it iswidely known that certain groups, such as blacks, may have areduced BP-lowering response to RAAS blockers, and thusthese agents may not be ideal as first-line drugs for the man-agement of hypertension.207 Similarly, antihypertensive agentsthat improve glucose metabolism (ie, RAAS inhibitors) or thatare metabolically neutral (ie, CCBs) may be preferable as first-line therapy in populations prone to diabetes, such as SouthAsians. Differences in statin efficacy among ethnic groups maybe attributable to differences in pharmacokinetic and pharma-codynamic effects or to polymorphisms of genes critical to drugmetabolism.278 Asians have historically been considered to bemore responsive than white populations to the lipid-loweringeffects of statins. As such, Health Canada and the US Food andDrug Administration recommend lower starting doses of cer-tain statins in Asian patients.279,280 Recent data, however, sug-gest that people of South Asian origin derive similar lipid ef-fects from atorvastatin and simvastatin as white populationsand that dose adjustment in South Asians may not be neces-sary.281

Summary and implications

Evidence-based prevention strategies and therapies recom-mended by major national guidelines should be optimally em-ployed in the management of cardiometabolic risk in all pop-ulations, including increased and regular physical activity to
prevent weight gain or promote weight loss, healthy dietary


practices, control of risk factors with therapies proven in ran-domized trials, and aggressive secondary prevention strategieswhen vascular disease is established. However, as the culturaldynamics of chronic illnesses and their management arecomplex and often deeply rooted in cultural traditions,community-based prevention and management programsshould be developed and delivered in partnership with targetcommunities, should reflect the ethnocultural representation,should be culturally sensitive, and when possible should bedelivered in the patient’s language of choice.269

Research is needed to develop reference data that are basedon health-related criteria or outcomes (rather than beingmerely representative of the population), and population-based research is needed to help establish ethnic-specific cutoffvalues for waist circumference with sensitivity and specificity todiscriminate clinical events.101 It is important to note that toour knowledge there are no data on youth in Canada’s ethn-ocultural communities—a situation that must be addressed ifsuccessful prevention strategies are to be implemented.

In conclusion, Canadian health care professionals must beaware of ethnicity-related risk factors in order to appropriatelyassess and screen individuals in their diverse patient popula-tions. As the relationship between percentage body fat andBMI is ethnic specific, ethnic-specific cutoff for measurementsof overweight and central adiposity are recommended. Com-munity-based prevention and management programs shouldbe developed and delivered in partnership with target commu-nities, should reflect the ethnocultural representation, shouldbe culturally sensitive, and when possible should be delivered inthe patient’s language of choice. Evidence-based preventionstrategies and therapies recommended by major nationalguidelines should be optimally employed in the managementof cardiometabolic risk in all populations.

AcknowledgementsThe authors thank medical writer and editor Cynthia N.

Lank, Halifax, Nova Scotia, for her assistance in the develop-ment of the position paper, as well as the individual reviewersfrom each of the endorsing organizations, including Dr Vin-cent Woo from the Canadian Diabetes Association; Dr Rich-ard Birtwhistle, Dr Peter J. Lin, Dr Kevin Saunders, and DrRichard Ward from the College of Family Physicians of Can-ada; May Yee Jung, RD, CDE, and Daphna Steinberg, RD,from the Dietitians of Canada; and Dr David C. W. Lau fromObesity Canada.

Funding SourcesFunding for this project was provided by the following or-

ganizations in the form of unrestricted educational grants:AstraZeneca Canada Inc, Boehringer Ingelheim (Canada) Ltd,Bristol-Myers Squibb Canada, Eli Lilly Canada Inc, Glaxo-SmithKline Canada, Hoffmann-La Roche Ltd, Merck FrosstCanada Ltd, Merck Frosst/Schering Pharmaceuticals, NovartisPharmaceuticals, Novo Nordisk Canada, Pfizer Canada Inc,Sanofi-Aventis Canada Inc, and Servier Canada Inc. Corporatesponsors were not involved in the decision to publish this po-sition paper, the review of the literature, or the development or
review of any of the drafts.
DisclosuresAll authors completed and signed a duality of interest dis-

closure detailing relevant financial interests, honouraria forCME, research funding, and consultant or advisory boardmembership for the past 12 months. Authors received an hon-ourarium and were reimbursed for their travel and accommo-dation expenses to attend a Cardiometabolic Risk WorkingGroup meeting in Toronto, Ontario. In addition, a token hon-ourarium was offered to each author for his or her participationin the overall project and was either accepted or declined ateach author’s discretion.

Cardiometabolic Risk Working Group, executive commit-tee: Lawrence A. Leiter: honouraria for CME: AstraZeneca,Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Merck,Merck/Schering Plough, Novartis, Novo Nordisk, Pfizer,Roche, sanofi-aventis, Servier; research funding: AstraZeneca,Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Merck,Merck/Schering Plough, Novartis, Novo Nordisk, Pfizer,Roche, sanofi-aventis, Servier; consultant/advisory board:AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmith-Kline, Merck, Merck/Schering Plough, Novartis, Novo Nor-disk, Pfizer, Roche, sanofi-aventis, Servier. David H. Fitchett:honouraria for CME: AstraZeneca, Biovail, GlaxoSmithKline,Merck, Novartis, Pfizer, sanofi-aventis, Schering; researchfunding: sanofi-aventis; consultant/advisory board: AstraZen-eca, Biovail, GlaxoSmithKline, Merck, Novartis, Pfizer, sanofi-aventis, Schering. Richard E. Gilbert: honouraria for CME:Bristol-Myers Squibb, Novartis, sanofi-aventis; research fund-ing: Bristol-Myers Squibb, sanofi-aventis; consultant/advisoryboard: Bristol-Myers Squibb, Novartis, sanofi-aventis. MilanGupta: honouraria for CME: Abbott, AstraZeneca, Bayer,Boehringer Ingleheim, Bristol Meyers Squibb, GlaxoSmith-Kline, Eli Lilly, Merck Frosst Schering, Novartis, Pfizer, Ser-vier, sanofi-aventis; research funding: AstraZeneca, Glaxo-SmithKline, Merck, Novartis, Pfizer; consultant/advisoryboard: Abbott, AstraZeneca, Bayer, Boehringer Ingleheim,Bristol Meyers Squibb, Eli Lilly, GlaxoSmithKline, MerckFrosst Schering, Novartis, Pfizer, sanofi-aventis, Servier. G. B.John Mancini: honouraria for CME: AstraZeneca, Glaxo-SmithKline, Merck Frosst, Pfizer, sanofi-aventis; researchfunding: Cordis; consultant/advisory board: AstraZeneca,Pfizer, sanofi-aventis, Schering Plough. Philip A. McFarlane:honouraria for CME: Biovail, BMS, Boehringer Ingleheim,GlaxoSmithKline, Merck, Novartis, sanofi-aventis; researchfunding: Amgen Inc, AstraZeneca, Biovail, Boehringer Ingel-heim, GlaxoSmithKline, Novo Nordisk, Ortho-Biotech,sanofi-aventis; consultant/advisory board: Amgen Inc, Biovail,BMS, Boehringer Ingelheim, Novartis, Ortho-Biotech, sanofi-aventis, Schering. Robert Ross: honouraria for CME: Glaxo-SmithKline, Merck Pharmaceuticals, sanofi-aventis, Therat-echnologies; research funding: sanofi-aventis; consultant/advisory board: sanofi-aventis; other: royalties received fromHuman Kinetics. Hwee Teoh: No conflicts of interest to de-clare. Subodh Verma: honouraria for CME: AstraZeneca,GlaxoSmithKline, Novartis, Pfizer; research funding: Astra-Zeneca; consultant/advisory board: AstraZeneca, GlaxoSmith-Kline, Novartis, Pfizer. Working Group: Sonia Anand: honou-raria for CME: AstraZeneca, Boehringer Ingelheim,GlaxoSmithKline, Merck-Frosst, Pfizer, sanofi-aventis; re-search funding: AstraZeneca, GlaxoSmithKline, sanofi-aven-
tis. Kathryn Camelon: consultant/advisory board: Abbott.


e25

Chi-Ming Chow: honouraria for CME: AstraZeneca, Merck,Novartis; research funding: Pfizer; consultant/advisory board:Mechanisms in Medicine. Jafna L. Cox: research funding:Pfizer; consultant/advisory board: Boehringer Ingleheim,sanofi-aventis; Jean-Pierre Després: honouraria for CME:Abbott Laboratories, AstraZeneca, Solvay Pharma, Glaxo-SmithKline, Pfizer Canada Inc; research funding: Eli Lilly;consultant/advisory board: Theratechnologies, Torrent Phar-maceuticals Inc, Novartis, sanofi-aventis. Jacques Genest: hon-ouraria for CME: AstraZeneca, Merck; research funding:AstraZeneca, Merck; consultant/advisory board: Amgen, As-traZeneca, Merck. Stewart B. Harris: honouraria for CME:AstraZeneca, BMS, GlaxoSmithKline, Merck, Novo Nordisk,Pfizer, sanofi-aventis, Roche; research funding: GlaxoSmith-Kline, Merck, Novo Nordisk, sanofi-aventis; consultant/advi-sory board: AstraZeneca, BMS, Eli Lilly, GlaxoSmithKline,Merck, Novo Nordisk, Pfizer, Roche, sanofi-aventis. DavidC. W. Lau: honouraria for CME: AstraZeneca, BoehringerIngelheim, BMS; research funding: AstraZeneca, BMS, EliLilly, GlaxoSmithKline, Pfizer, sanofi-aventis; consultant/ad-visory board: Abbott, Allergan, AstraZeneca, Boehringer Ingel-heim, Eli Lilly, GlaxoSmithKline, Merck, Novo Nordisk,Pfizer, Roche, sanofi-aventis, Sepracor. Richard Lewanczuk:honouraria for CME: Merck, Novartis, Pfizer, sanofi-aventis,Servier; consultant/advisory board: Novartis, Merck, Pfizer.Peter P. Liu: No conflicts of interest to declare. Eva M. Lonn:honouraria for CME: AstraZeneca, GlaxoSmithKline, Merck,Pfizer, sanofi-aventis, Schering Plough; research funding: As-traZeneca, GlaxoSmithKline, Roche; consultant/advisoryboard: sanofi-aventis. Ruth McPherson: honouraria for CME:AstraZeneca, Merck Frosst Canada, Pfizer Canada; consultant/advisory board: AstraZeneca, Merck Frosst, Pfizer, Roche. PaulPoirier: No conflicts of interest to declare. Shafiq Qaadri: hon-ouraria for CME: Abbott, Boehringer Ingelheim, CanadianHeart Research Centre, Merck, Novartis, Pangaea Group.Rémi Rabasa-Lhoret: honouraria for CME: AstraZeneca, EliLilly, GlaxoSmithKline, Medtronic, Merck, Novo Nordisk,sanofi-aventis; research funding: Merck, Novo Nordisk,sanofi-aventis; consultant/advisory board: GlaxoSmithKline,Medtronic, Merck, Novartis, Novo Nordisk, sanofi-aventis.Simon W. Rabkin: honouraria for CME: Abbott, Schering;consultant/advisory board: Bayer. Arya M. Sharma: honoura-ria for CME: Abbott, Boehringer Ingleheim; research funding:Abbott, Allergan, Covidien, Johnson & Johnson; consultant/advisory board: Abbott, Boehringer Ingleheim, Novo Nordisk.Andrew W. Steele: honouraria for CME: AstraZeneca, Boehr-inger Ingelheim, Merck, Novartis, Pfizer; research funding: As-traZeneca, Novartis; consultant/advisory board: AstraZeneca,Novartis, sanofi-aventis. James A. Stone: honouraria for CME:AstraZeneca, Novartis, Pfizer; consultant/advisory board: As-tra-Zeneca, Merck, Novartis, sanofi-aventis, Schering-Plough.Jean-Claude Tardif: honouraria for CME: AstraZeneca, Pfizer;research funding: Pfizer, Roche. Sheldon Tobe: honouraria forCME: Abbott, Amgen, AstraZeneca, Bayer, Boehringer, Bris-tol Myers Squibb, Merck Frosst, Pfizer; research funding: Am-gen, Bayer, Bristol Myers, Novartis, Ortho Biotech, sanofi-aventis, Roche; consultant/advisory board: Abbott, Bayer,BMS/sanofi, Merck Frostt, Ortho Biotech, Pfizer. Ehud Ur:honouraria for CME: Abbott; consultant/advisory board: Ab-
bott, sanofi-aventis.
Supporting OrganizationsC-CHANGE, Canadian Cardiovascular Society, Canadian

Diabetes Association, Canadian Institutes of Health Research,Canadian Obesity Network, The College of Family Physiciansof Canada, Dietitians of Canada, Obesity Canada.

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http://www.hc-sc.gc.ca/fniah-spnia/pubs/finance/_agree-accord/10_years_ans_trans/5_agreement-entente-eng.php



http://www.smoke-free.ca/documents/backgroundhealth.htm

http://www.smoke-free.ca/documents/backgroundhealth.htm

http://www.ices.on.ca/WebBuild/site/ices-internet-upload/file_collection/DM_Chapter1.pdf

http://www.ices.on.ca/WebBuild/site/ices-internet-upload/file_collection/DM_Chapter1.pdf

http://www.statcan.gc.ca/cgi-bin/imdb/p2SV.pl?Function=getSurvey%26SurvId=3225%26SurvVer=0%26InstaId=15280%26InstaVer=3%26SDDS=3225%26lang=en%26db=imdb%26adm=8%26dis=2



http://www.smoke-free.ca/pdf_1/SmokinginCanada-2005.pdf

http://www.smoke-free.ca/pdf_1/SmokinginCanada-2005.pdf

http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/PublicHealthAdvisories/ucm051756.htm




http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/public/_2005/crestor_2_pa-ap-eng.php



http://www.statcan.gc.ca/daily-quotidien/080402/dq080402a-eng.htm

http://www.statcan.gc.ca/daily-quotidien/080402/dq080402a-eng.htm

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