World Heart Federation Cholesterol Roadmap

Background: The World Heart Federation has undertaken an initiative to develop a series of Roadmaps.
of 24
All materials on our website are shared by users. If you have any questions about copyright issues, please report us to resolve them. We are always happy to assist you.
Related Documents
  World Heart Federation Cholesterol Roadmap Adrianna Murphy*, Jose R. Faria-Neto y , Khalid Al-Rasadi z , Dirk Blom x , Alberico Catapano k , { ,# , Ada Cuevas**,Francisco Lopez-Jimenez yy , zz , Pablo Perel xx , kk , Raul Santos {{ ,## , Allan Sniderman***, Rody Sy yyy , zzz ,Gerald F. Watts xxx , kkk , Dong Zhao {{{ , Salim Yusuf  xx ,###, **** , yyyy , David Wood xx , zzzz , xxxx London, United Kingdom; Curitiba, Brazil; Muscat, Oman; Cape Town, South Africa; Milan, Italy; Santiago,Chile; Rochester, MN, USA; Geneva, Switzerland; Sao Paulo, Brazil; Montreal, Quebec, Canada; Manila,Philippines; San Juan, Philippines; Perth, Western Australia, Australia; Beijing, China; Hamilton, Ontario,Canada; and Bethesda, MD, USA ABSTRACTBackground:  The World Heart Federation has undertaken an initiative to develop a series of Roadmaps. Objectives:  The aim of these is to promote development of national policies and health systems approachesand identify potential roadblocks on the road to effective prevention, detection and management of cardiovascular disease (CVD) in low-and middle-income countries (LMIC), and strategies for overcomingthese. This Roadmap focuses on elevated blood cholesterol, a leading risk factor for myocardial infarction,stroke, and peripheral arterial disease. Methods:  Through a review of published guidelines and research papers, and consultation with a committeecomposed of experts in clinical management of cholesterol and health systems research in LMIC, thisRoadmap identi 󿬁 es (1) key interventions for primordial, primary and secondary prevention of CVDthrough detection, treatment, and management of elevated cholesterol and familial hypercholesterolemia(FH); (2) gaps in implementation of these interventions (knowledge-practice gaps); (3) health systemroadblocks to treatment of elevated cholesterol in LMIC; and (4) potential strategies for overcoming these. Results:  Despite strong evidence of the importance of cholesterol levels in primary or secondary prevention of CVD, and the effectiveness of statin therapy for cholesterol lowering and reduction of CVD risk, gaps exist inthe detection, treatment, and management of high cholesterol globally. Some potential roadblocks includepoor access to laboratory facilities or trained professionals for cholesterol management, low awareness of FH among the general population and health professionals, unaffordability of statins for patienthouseholds, and low awareness of the importance of persistent adherence to lipid-lowering medication. Po-tential solutions include point-of-care testing, provision of free or subsidized lipid-lowering medication, andtreatment adherence support using text message reminders. Conclusions:  Known effective strategies for detection, treatment, and management of elevated cholesteroland FH exist, but there are barriers to their implementation in many low-resource settings. Priorities forhealth system intervention should be identi 󿬁 ed at the national level, and the feasibility and effectiveness of proposed solutions should be assessed in speci 󿬁 c contexts. Many solutions proposed in this Roadmapmay apply to other cardiovascular conditions and present opportunities for integration of CVD care inLMIC. In 2012, all member states of the World HealthOrganization (WHO) endorsed a historic target to reducepremature mortality from noncommunicable diseases(NCD) by 25% by 2025. This commitment was echoed by the United Nations Sustainable Development Goals in2015, which include a target to reduce premature mortality from NCD by 30%. These targets are especially relevant toatherosclerotic cardiovascular disease (CVD), which is theleading cause of death globally and is increasing in prev-alence in low- and middle-income countries (LMIC).In support of reaching these targets, the World HeartFederation (WHF) has undertaken an initiative to developa series of Roadmaps to promote development of nationalpolicies and health systems approaches; identify potentialroadblocks on the road to effective prevention, detection,and management of CVD in LMIC; and provide strategiesfor overcoming these. These Roadmaps provide guidancefor countries toward developing or updating national NCDprograms using the framework provided by the WHO ’ sGlobal Action Plan for the prevention and control of NCD Dr. Faria Neto has receivedhonoraria in the form of speaker, consultancy, advi-sory board, or committeemember fees from MSD,AstraZeneca, P 󿬁 zer, Sano 󿬁 ,Amgen, Unilever, andAegerion. Dr. Al-Rasadi hasreceived a research grantfrom Sano 󿬁 ; and served onthe speakers bureau and asan advisory board memberfor Sano 󿬁 , AstraZeneca,and P 󿬁 zer. Dr. Blom hasreceived grants for con-ducting clinical trials fromSano 󿬁 -Aventis, RegeneronPharmaceuticals, Inc.,Novartis, Eli Lilly & Com-pany, Amgen, and Aege-rion; honoraria for lecturesfrom Sano 󿬁 -Aventis,Regeneron Pharmaceuti-cals, Inc., Aegerion, Amgen,AstraZeneca, MSD, P 󿬁 zer,Servier, and Unilever; advi-sory board fees fromSano 󿬁 -Aventis, Aegerion,Amgen, AstraZeneca, andMSD; travel assistancefrom Amgen and Aegerion;a fee for chairing a steeringcommittee from Aegerion;a consultancy fee fromGemphire; and non 󿬁 nan-cial support (editorialassistance and statisticalanalysis) from Sano 󿬁 -Aventis and RegeneronPharmaceuticals, Inc. Dr.Catapano has receivedhonoraria, lecture fees, orresearch grants from Sig-maTau, Menarini, Kowa, EliLilly, Recordati, P 󿬁 zer,Sano 󿬁 , Mediolanum,Merck, Aegerion, Amgen,Genzyme, Bayer, andAstraZeneca. Dr. Cuevashas received speakers ’  feesfrom Synthon, Amgen,Abbott, Saval, Novonordisk,and Sano 󿬁 ; and has partic-ipated in advisory boardsfor Abbott, Novonordisk,and Janssen. Dr. Lopez-Jimenez has receivedspeakers ’  fees from Amgen.Dr. Santos has receivedhonoraria for consultingand/or speaker activitiesfrom Amgen, Aegerion,Akcea, AstraZeneca, Biolab,Boehringer-Ingelheim, Cer-enis, Eli-Lilly, Genzyme,Kowa, Merck, P 󿬁 zer,Sano 󿬁 /Regenron, Praxis,Procaps, Torrent, and GLOBAL HEART, VOL. - , NO. - , 2017  1 Month 2017: - - - WORLD HEART FEDERATION ROADMAP gRECS  2013 to 2020 [1,2]. Roadmaps dedicated to secondary prevention of CVD [3]; tobacco control [4]; raised blood pressure [5], rheumatic heart disease [6], and atrial  󿬁 bril-lation [7] have already been published. This Roadmap fo-cuses on blood cholesterol. While most existing global datarefer to total blood cholesterol (TC), this Roadmap willre 󿬂 ect a growing body of evidence on the risk associatedwith speci 󿬁 c subtypes of cholesterol, for example, low-density lipoprotein cholesterol (LDL-C), or the ratio of apolipoprotein B ([apo B]; the main protein in LDL-C) toapolipoprotein A1 ([apo A-I]; the main protein in high-density lipoprotein cholesterol [HDL-C]). THE RELEVANCE OF CHOLESTEROL TO THEGLOBAL BURDEN OF CVD Reducing cholesterol-related CVD risk, namely risk associ-ated with myocardial infarction, stroke, and peripheralarterial disease, plays a vital role in achieving the WHO 25   25 target for reducing premature mortality from CVD andother NCD. Worldwide, there are about 17 million deathsdue to CVD each year [8], and international studies havesuggested that elevated apo B/apo A-I is among the mostimportant risk factors for myocardial infarction (MI) [9] andfor ischemic stroke [10]. Research from 2008 suggested thatthe global average of TC showed little change in the pre-ceding 3 decades, because of opposing trends: decreases in Australasia, North America, and Europe and increases in eastand southeast Asia and Paci 󿬁 c [11]. Estimated average TCby country, for men and women, is shown in Figure 1 [12]. WHO has identi 󿬁 ed control of cholesterol, as part of aTotal Risk Approach to the prevention of CVD, as a publichealth priority  [13]. Cholesterol reduction is vital to bothprimary and secondary prevention of CVD; loweringcholesterol in those with established CVD, and those athigh risk of developing CVD, is essential to reducing CVDmorbidity and premature mortality globally. Low costmethods for identifying at-risk patients in LMIC exist[14,15], and treatment with cholesterol-lowering medica-tions in the form of statins is cost-effective in these settings[16]. Nevertheless, while the prevalence of raised choles-terol and other CVD risk factors are all lower in LMICcompared with high-income countries (HIC), mortality from CVD is higher in LMIC, suggesting that detection andmanagement of these risk factors together with the man-agement of CVD is poorer in LMIC [17].This Roadmap was developed through a review of published guidelines and research papers, and in consul-tation with an expert committee, composed of experts inclinical management of cholesterol and health systemsresearch in LMIC. In the following sections, we outlineessential strategies for measurement and management of cholesterol in the context of primordial prevention inpopulations, primary prevention in asymptomatic high-risk individuals, secondary prevention in patients withestablished CVD, and familial hypercholesterolemia (FH). We then identify potential roadblocks to implementationof evidence-based strategies in LMIC and propose solutionsfor overcoming these roadblocks. MEASUREMENT AND MANAGEMENT OFBLOOD CHOLESTEROLPrimordial prevention for the general population LDL-C contributes to the development of CVD, either onits own or in interaction with other cardiovascular riskfactors. There is clear evidence of a strong positive asso-ciation between LDL-C and coronary artery disease([CAD]; the most common CVD) [18,19]. Whereas evi-dence of the impact of many lifestyle-related factors on TCand LDL-C is inconclusive, there is general consensus thataerobic physical activity may increase HDL-C [19,20], anddiets low in saturated and trans fats, and higher in vege-tables, can reduce TC and LDL-C levels in the blood[21,22]. Among the most common sources of trans fats arehydrogenated and partially hydrogenated oils often foundin processed foods [23]. As such, a primary aim of publichealth interventions for reducing morbidity and mortality due to elevated LDL-C should be to encourage a healthy lifestyle among the general population, irrespective of in-dividual cholesterol levels [24]. Various dietary guidelinesexist, such as those from the European Society of Cardi-ology, that encourage a preference for whole grains, veg-etables, legumes, fresh or frozen fruit, lean and oily   󿬁 shand poultry, and nonfat dairy products ( Appendix 1) [19]. However, some of these have been criticized for leading tocarbohydrate-heavy diets. An in-depth review of currentevidence concluded that the strongest evidence supportsthe traditional Mediterranean-type diet as a healthy dietary pattern to reduce CVD [25]. The Mediterranean diet con-sists of 40% to 50% carbohydrates from mainly complexcarbohydrates such as vegetables, fruits, beans, and non-re 󿬁 ned cereals; 15% to 20% protein, emphasizing lean andplant protein sources; and a high nut and olive oil contentmaking up 16% to 21% monounsaturated fatty acids, 7%to 11% saturated fatty acids, and 5% to 7% poly-unsaturated fatty acids. Based on that review, expertsdeveloped guidance for adapting the Mediterranean diet toother regions. This guidance has been included in Appendix 2. National dietary guidelines for prevention of CVD should re 󿬂 ect local food availability and customs. Primary preventionRisk assessment.  Traditionally, primary prevention of CVD has focused on a  “ single-risk-factor ”  approach, whichtargets patients based on their levels of individual CVD riskfactors,suchasraisedLDL-C or highblood pressure,butthisapproach has been progressively replaced in all contempo-rary CVD prevention guidelines with the Total Risk Approach based on absolute risk of developing CVD over ade 󿬁 ned period of time [26-28]. The level of absolute riskused to de 󿬁 ne a  “ high risk individual ”  eligible for primary prevention, including the use of drug therapies, varies Unilever. Dr. Sy hasreceived honoraria for lec-tures from MSD and P 󿬁 zer;has been involved in theOdyssey Outcomes Study;and has received aresearch grant from Sano 󿬁 .Dr. Watts has receivedhonoraria for advisoryboards, lectures, or grantsfor research from Amgen,Sano 󿬁 , Regeneron, Kowa,and Gemphire. Dr. Yusuf has received researchfunding for the conduct of the HOPE 3 trial fromAstraZeneca. All other au-thors report no relation-ships that could beconstrued as a con 󿬂 ict of interest.From the *Centre forHealth and Social Change,Department of Health Ser-vices Research and Policy,London School of Hygieneand Tropical Medicine,London, United Kingdom; y School of Medicine, Pon-ti 󿬁 cia Universidade Catol-ica do Parana, Curitiba,Brazil;  z Department of Biochemistry, SultanQaboos University Hospi-tal, Muscat, Oman; x Division of Lipidology,Department of Medicine,University of Cape Town,Cape Town, South Africa; k Department of Pharma-cology, Center of Epidemi-ology and PreventivePharmacology, Universityof Milan, Milan, Italy; { Laboratory of Lipopro-teins, Immunity andAtherosclerosis, Depart-ment of Pharmacologicaland Biomolecular Sciences,University of Milan, Milan,Italy; #Center for the Studyof Atherosclerosis at Bas-sini Hospital, University of Milan, Milan, Italy;**Nutrition Department,Clinica Las Condes, San-tiago, Chile;  yy Departmentof Medicine, Mayo MedicalSchool, Division of Preven-tive Cardiology, MayoClinic, Rochester, Minne-sota, USA;  zz Departmentof Research, Dan AbrahamHealthy Living Center,Rochester, Minnesota, USA; xx World Heart Federation,Geneva, Switzerland; kk London School of Hy-giene and Tropical gRECS 2  GLOBAL HEART, VOL. - , NO. - , 2017Month 2017: - - -  betweennationalguidelinesanddependsontheabilityofthehealth system to screen and manage that proportion of thepopulationclassi 󿬁 edashighrisk,aswellasthecosts of doingso. Whereas the Total Risk Approach is appropriate for mostoftheadultpopulation,somepeoplewillbeeligibleforstatintherapy without the need to calculate absolute CVD riskbecause they are already athigh or very high risk. Inadditionto those with established CVD (discussed in the Secondary Prevention section), these patients include those with FH,those with very high LDL-C   190 mg/dl (4.9 mmol/l)[19,28], those with diabetes and target organ damage, andthose with chronic kidney disease (see Table 1 for details)[13]. The de 󿬁 nitionsofthese high-riskgroups,which vary tosome extent between national and regional guidelines, areshown in Table 1. More recent evidence supports the use of statin therapy in patients that have been prescribed life-longantihypertensive therapy  [29,30]. Children and youngpeople with obesity, insulin resistance, and type 2 diabetesrequire intensive lifestyle intervention and, if appropriate,drug therapies to reduce their lifetime risk.The Total Risk Approach recognizes that many CVDrisk factors may only be elevated to a moderate degree butbecause they occur in clusters and have a multiplicativeeffect, overall absolute CVD risk is elevated. As such,treatment of all risk factors together with healthy lifestylechanges, blood pressure, lipids, and glucose lowering [5]will produce the greatest reductions in risk of developingCVD. The Total Risk Approach relies on estimating anindividual ’ s baseline CVD risk using a risk prediction al-gorithm ideally developed from the population to which itis to be applied. Assessing risk based on the Total Risk Approach will assign a risk score to screened individuals.The decision of who to screen for CVD risk, and which riskthreshold to use to initiate treatments with statins, is amatter of national (or local) policy and available resourcesbut, for example, the National Health Service in the UnitedKingdom screens all adults without pre-existing conditionsbetween the ages of 40 and 70, every 5 years [31]. Thereare limited data suggesting that systematic risk assessment(screening-like programs with a pre-determined selectionprocess of individuals to be assessed), as opposed toopportunistic screening, may have positive effects onreducing CVD risk, and more evidence is needed [32].Patient 10-year total risk of fatal and nonfatal CVD can bestrati 󿬁 ed according to risk score charts such as the Fra-mingham [26] and SCORE (Systemic Coronary RiskEvaluation) [27], which have been validated primarily inHIC, and the WHO/International Society for Hypertension(ISH) [14] risk chart, which was developed for use in allregions of the world. The American College of Cardiology/  American Heart Association (ACC/AHA) has recently developed a pooled cohort equation for CVD risk assess-ment [33]. (As examples, the WHO/ISH and SCORE riskassessment tools are included as Appendices 3 [34] and 4). These risk score charts assign absolute risk levels based onage, sex, smoking habit, blood pressure and TC levels, andother risk factors can also be incorporated.Conventionally, cholesterol has been measured in bloodsamples obtained after 8 hours of fasting; however, recentevidence suggests that these fasting measurements areessentially indistinguishable from nonfasting measurements[35,36]. Therefore, more recent guidelines suggest thatnonfasting blood samples are suf  󿬁 cient for measurement of cholesterol levels [23,37]. Ideally, the full lipid pro 󿬁 le — totalcholesterol,HDL-C,andtriglycerides — willbemeasuredandLDL-C and non-HDL-C will be calculated. Where appro-priate laboratory facilities exist, apo B/apo A-I should bemeasuredgiventhe importanceoftheapoB e apoA-Iratioasa risk factor for MI [9] and ischemic stroke [10]. In fact, current evidence suggests that apo B is a more accuratemarkerofcardiovascularriskthanLDL-Cornon-HDL-Candthat apo B e apo A-I ratio is at least equal to, and perhapssuperior to, the cholesterol ratios (TC e HDL-C, non-HDL-C e HDL-C, LDL-C e HDL-C) as a summary index of cardiovascular risk. The measurements of apo B and apo A-Iare accurate, standardized, and can be determined usingautomated methods in any routine clinical chemistry labo-ratory at a cost similar to the cost of conventional lipoproteinlipids. Except for TC, the measurements of the conventionallipoprotein lipids — LDL-C, non-HDL-C, and triglycerides — are not standardized. The accuracy of calculated LDL-C isparticularly problematic at triglyceride levels  > 200 mg/dl(2.2 mmol/l) or LDL-C < 70 mg/dl (1.8 mmol/l). There is noevidence, however, that directly measured LDL-C is a moreaccurate measure of cardiovascular risk than calculatedLDL-C. The relative strengths of each type of cholesterolmeasure of cardiovascular risk are outlined in Appendix 5. Whereas apo B appears to be the most predictive measure,it is important to note that measurement of TC alone iscurrently more realistic for many countries, given the costand complexity of measuring apolipoproteins in resource-limited settings. Under some rare circumstances, TC mea-surements should be interpreted with caution as,for example, high TC levels may be driven by high levelsof HDL-C; furthermore, normal TC levels may disguiseinadequate nutrition. Although existing risk calculators (WHO/ISH, SCORE,Framingham, etc.) provide a good assessment of total CVDrisk, for these charts to predict risk as accurately as possiblethey must be based on epidemiological data derived fromthe populations to which they are to be applied. Alterna-tively, in the absence of such epidemiological data, it ispossible to adapt existing risk algorithms with adjustmentsfor CVD mortality and prevalence of risk factors for a givencountry  [38]. There may also be speci 󿬁 c populationswithin countries who are at higher risk of CVD, such asthose on antiretroviral treatment for HIV  [39], for whomrisk assessment tools may need to be speci 󿬁 cally tailored.Risk scores produced by existing charts may underestimateactual risk in many LMIC, where CVD mortality isincreasing [23]. There is therefore an urgent need to sup-port data collection efforts in countries where these dataare currently not available. WHO is currently in the pro-cess of revising its risk score charts to be more widely  Medicine, London, UnitedKingdom;  {{ Lipid ClinicHeart Institute, Universityof Sao Paulo MedicalSchool Hospital, Sao Paulo,Brazil; ##Preventive Medi-cine Center and CardiologyProgram, Hospital IsraelitaAlbert Einstein, Sao Paulo,Brazil; ***Division of Car-diology, McGill UniversityHealth Centre, Montreal,Quebec, Canada; yyy Section of Cardiology,Department of Medicine,University of the PhillipinesCollege of Medicine, Ma-nila, Philippines; zzz Cardiovascular Institute,Cardinal Santos MedicalCenter, San Juan,Philippines; xxx Cardiometabolic Ser-vice, Department of Cardi-ology, Royal Perth Hospital,Perth, Western Australia,Australia;  kkk School of Medicine, Faculty of Healthand Medical Sciences, Uni-versity of WesternAustralia, Perth, WesternAustralia, Australia; {{{ Beijing Institute of Heart, Lung and BloodVessel Diseases, CapitalMedical University, BeijingAnzhen Hospital, Beijing,China; ###Department of Medicine, McMaster Uni-versity, Hamilton, Ontario,Canada; ****PopulationHealth Research Institute,Hamilton, Ontario, Canada; yyyy Hamilton Health Sci-ences, McMaster Univer-sity, Hamilton, Ontario,Canada;  zzzz Departmentof Cardiovascular Medi-cine, Imperial College Lon-don, London, UnitedKingdom; and the xxxx National Heart andLung Institute, Bethesda,MD, USA.GLOBAL HEART© 2017 World HeartFederation (Geneva). Pub-lished by Elsevier Ltd. Allrights reserved.VOL. - , NO. - , 2017ISSN 2211-8160/$36.00. j.gheart.2017.03.002 gRECS GLOBAL HEART, VOL. - , NO. - , 2017  3 Month 2017: - - -  applicable. The INTERHEART risk score is anotherexample and was developed from a case-control study in52 high-, middle-, and low-income countries and wassubsequently validated in cohorts from 21 countries [40]. Another recent effort to develop an adaptable risk predic-tion equation for CVD is the Globorisk score [41]. Todevelop the Globorisk score, data from 8 prospectivecohort studies were used to estimate risk of fatal andnonfatal CVD associated with smoking, blood pressure,diabetes, and TC, allowing the effect of sex and age to vary between cohorts and countries. The resulting risk predic-tion equation can be recalibrated for application indifferent countries using locally available mortality andprevalent risk factor data. Whatever approach is used, riskscore charts are only a guide to assessment of CVD risk,and resulting scores should be interpreted in light of theclinician ’ s knowledge of the patient and his or her family history, taking account of other factors that may increaserisk such as level of social deprivation and psychosocialstress [42]. Although the Total Risk Score approach is morecomprehensive than a single risk approach, it is heavily in 󿬂 uenced by age and sex, risk factors for CVD that arenonmodi 󿬁 able, and to a much lesser extent by LDL-C,blood pressure, smoking, and diabetes, CVD risk factorsthat can be successfully modi 󿬁 ed by treatment. For <4.45 mmol/L (<172 mg/dl)4.46-4.79 mmol/L (173-185 mg/dl)4.80-5.18 mmol/L (186-200 mg/dl)>5.18 mmol/L (>200 mg/dl)Not applicable AB FIGURE 1. Mean total cholesterol (mmol/l) by country . (A) Male and (B) female subjects, 2008 (conversion to mg/dl is approximate). gRECS 4  GLOBAL HEART, VOL. - , NO. - , 2017Month 2017: - - -

Syllabus NWWP

Oct 15, 2019


Oct 15, 2019
Similar documents
View more...
Related Search
We Need Your Support
Thank you for visiting our website and your interest in our free products and services. We are nonprofit website to share and download documents. To the running of this website, we need your help to support us.

Thanks to everyone for your continued support.

No, Thanks

We need your sign to support Project to invent "SMART AND CONTROLLABLE REFLECTIVE BALLOONS" to cover the Sun and Save Our Earth.

More details...

Sign Now!

We are very appreciated for your Prompt Action!