Lipids and CVD management: towards a global consensus

Christie Ballantyne1, Bruce Arroll2 and James Shepherd3,*

1Arteriosclerosis and Lipoprotein Section, Baylor College of Medicine, Houston, TX, USA
2Department of General Practice and Primary Care, University of Auckland, Auckland, New Zealand
3Department of Pathological Biochemistry, Royal Infirmary, Glasgow G4 0SF, Scotland, UK

Received 13 October 2004; revised 18 April 2005; accepted 19 May 2005; online publish-ahead-of-print 21 June 2005.

* Corresponding author. Tel: +44 141 552 0689; fax: +44 141 553 1703. E-mail address: jshepherd{at}gri-biochem.org.uk


    Abstract
 Top
 Abstract
 Guideline implementation: the...
 Guidelines: the common goals
 Guidelines: areas of divergence
 Guidelines as a framework...
 Conclusion
 Acknowledgements
 References
 
Cardiovascular disease (CVD) is currently the leading cause of morbidity and mortality worldwide and its incidence is likely to increase. Multiple risk factors contribute to CVD. Elevated LDL-cholesterol (LDL-C) and triglyceride levels, low HDL-cholesterol levels, hypertension, type 2 diabetes, and smoking are key modifiable risk factors. Such risk factors are present in 80–90% of coronary heart disease (CHD) patients. For many factors, modification can significantly reduce CVD incidence. For example, statin-induced LDL-C reductions reduce cardiovascular events by 24–37% and smoking cessation reduces CHD mortality by 36%. The need to identify and treat these risk factors has led many national and local groups to develop clinical practice guidelines for management of CVD. Although the aim of such guidelines is to provide practitioners with a framework to identify, prioritize, and manage patients, the plethora of guidelines can cause confusion. In addition, research indicates that guidelines are not being optimally implemented. This review considers these practical issues, highlights the common goals shared by many guidelines, and focuses on how these can be best achieved. It also highlights areas where the guidelines differ and discusses points to consider when selecting the most appropriate recommendation.

Key Words: Guidelines • Cardiovascular disease • Cholesterol • Statin


    Guideline implementation: the clinical reality
 Top
 Abstract
 Guideline implementation: the...
 Guidelines: the common goals
 Guidelines: areas of divergence
 Guidelines as a framework...
 Conclusion
 Acknowledgements
 References
 
The effectiveness of guidelines lies in their appropriate selection and subsequent implementation. However, owing to the large number of guidelines available, this can be time consuming and confusing. Recent surveys indicate that guidelines awareness and acceptance is high among practitioners, but that implementation could be improved.1,2

In a recent survey of European primary care practitioners, 89% agreed with European societies guidelines, but only 18% believed that they were being adequately implemented.2 Studies confirm this belief. Plasma lipid levels are not screened in many at-risk patients3,4 and, in patients receiving treatment, risk factor management can be poor.1,5,6 The European Action on Secondary Prevention through Intervention to Reduce Events survey5 showed a high prevalence of uncontrolled dyslipidaemia, hypertension, obesity, and smoking in patients with established coronary heart disease (CHD) (Table 1).5 In European and American studies, most high-risk patients' cholesterol levels exceed recommended goals.1,5


View this table:
[in this window]
[in a new window]
 
Table 1 EUROASPIRE5—Prevalence of risk factors in patients with established CHD
 
Potential reasons for not reaching cholesterol targets include suboptimal therapy (inadequate drug dosage/lack of titration), underuse of statin therapy (medication not prescribed or not taken), and concerns regarding side-effects of medication.1,5,710 Practitioners cite lack of time, prescribing costs, and patient non-compliance as barriers to implementation.2 However, correct implementations of guidelines could reduce cardiovascular disease (CVD) morbidity and mortality.


    Guidelines: the common goals
 Top
 Abstract
 Guideline implementation: the...
 Guidelines: the common goals
 Guidelines: areas of divergence
 Guidelines as a framework...
 Conclusion
 Acknowledgements
 References
 
Table 2 highlights the similarities shared by some of the key CVD prevention and management guidelines.1119


View this table:
[in this window]
[in a new window]
 
Table 2 Summary of guideline characteristics: areas of convergence and divergence
 
The importance of patient screening and identification
All guidelines provide advice on screening and identifying asymptomatic patients at risk of developing CVD, thus highlighting the importance of this initial step. Opportunities to screen patients exist within daily clinical practice (Table 3).


View this table:
[in this window]
[in a new window]
 
Table 3 Opportunities to screen patients for CVD risk
 
The need to calculate total risk
All guidelines provide a system to calculate risk. The general principle is to assign points to patients according to their risk factor exposure. The sum of these points is used to calculate patients' total risk (Table 4).


View this table:
[in this window]
[in a new window]
 
Table 4 Estimating patient's risk using NCEP ATP III guidelines11
 
All the guidelines focus on multiple risk factors. They agree that risk factors increase the likelihood of a cardiovascular (CV) event and that risk is additive. The compound effect of risk factors is illustrated by data from the Framingham Study (Figure 1).20 Data from patients with type 2 diabetes and/or the metabolic syndrome (in whom CVD risk factors tend to cluster) support this concept: in a substudy of the Botnia trial, presence of the metabolic syndrome was associated with relative risks of 3.0, 2.6, and 1.8 for CHD, myocardial infarction (MI), and CVD mortalities, respectively.21 Similarly, diabetes is associated with a two- to five-fold increase in the risk of MI.22



View larger version (13K):
[in this window]
[in a new window]
 
Figure 1 Compound effect of risk factors20 For individuals with all six risk factors, the 10 year risk of CHD was more than four times greater than for those with only one risk factor. Reprinted with permission from Elsevier.

 
Tools are available to assist practitioners in an office-based assessment of patients. The Framingham risk equation and SCORE risk chart are now widely available in paper and electronic formats.

The significance of risk reduction
Once an individual's risk has been estimated, CVD prevention relies on implementing effective risk management programmes. Guidelines provide recommendations on appropriate treatment for different risk levels.

The guidelines agree that high-risk patients are a priority (Table 5). Most guidelines recommend initiating lifestyle changes and lipid-modifying drugs simultaneously in this group, and treatment goals are generally similar among guidelines (Table 2). Anti-hypertensive and anti-hyperglycaemic agents (as appropriate) are also important for these patients. All guidelines recommend regular monitoring of high-risk patients.


View this table:
[in this window]
[in a new window]
 
Table 5 Priorities of CVD prevention in clinical practice
 
There is also agreement among guidelines on treatment recommendations for low-risk patients. Lifestyle changes including diet, exercise, and weight loss should be implemented in these patients, who should receive regular follow-up (every 1–5 years).

In assessing risk and recommending preventive management, most guidelines have a relatively short-term focus, i.e. the next 5 or 10 years. Individuals with the highest short-term risk are then recommended for the most intensive interventions. However, atherosclerosis is a chronic condition that usually commences decades before it elicits a CV event. It might therefore be more beneficial to consider life-time risk and to identify and target at-risk individuals before they reach high-risk status. Early institution of intensive preventive treatment in these individuals at longer term risk has the potential to substantially reduce CV risk in later life. The presence of asymptomatic atherosclerosis may be identified by non-invasive tests such as ankle–brachial index measurement, carotid ultrasonography, or exercise stress testing.19


    Guidelines: areas of divergence
 Top
 Abstract
 Guideline implementation: the...
 Guidelines: the common goals
 Guidelines: areas of divergence
 Guidelines as a framework...
 Conclusion
 Acknowledgements
 References
 
Which factors are most important in determining total risk?
The guidelines agree on the need to assess total risk, but differ on the selection and weighting of risk factors. Many guidelines focus on LDL-cholesterol (LDL-C) as the primary target.11,13 Others, however, utilize HDL-cholesterol (HDL-C) and total cholesterol.12 Inclusion of HDL-C reflects growing recognition of the atheroprotective properties of this lipoprotein fraction.23 These differences in weighting can alter risk predictions and treatment recommendations for individual patients (Table 6), particularly in primary prevention.2426 In a recent comparison involving individuals without clinical evidence of CVD, NCEP ATP III and European guidelines recommended institution of lipid-modifying therapy in 52 and 26% of patients, respectively.25


View this table:
[in this window]
[in a new window]
 
Table 6 Risk assessment and treatment guidance
 
An alternative estimator of risk, advocated by the Canadian guidelines, is apolipoprotein B.19 This lipoprotein, which is present in all atherogenic particles and thus reflects total atherogenic load, may be particularly useful for estimating risk in individuals with hypertriglyceridaemia.19 In four recent prospective studies, apolipoprotein B was a better estimator of CV risk than LDL-C.27

Which algorithm is most appropriate for estimating risk?
Risk charts derived from Framingham data that calculate the 10 year risk of MI and CHD mortalities have been incorporated into numerous guidelines (Table 2). The Framingham algorithm estimates risk accurately in European and American populations that have an average CHD risk similar to the Framingham cohort (a US population).26 However, this algorithm over-estimates risk in populations with a lower baseline risk, such as those in France, Italy, and Spain.2831 Recalibration of the Framingham data set is possible, but may be difficult in the clinical setting.

The European guidelines12 have abandoned the Framingham risk equation in favour of the European Systematic Coronary Risk Estimation (SCORE) model. On the basis of a large data set from several European cohorts, this model has separate risk charts for low- and high-risk regions of Europe. This avoids overestimation of CHD rates in low-risk populations that can occur when using risk equations developed using data from high-risk populations, such as the Framingham cohort. The SCORE charts assess 10 year risk of total CVD mortality (CHD, peripheral arterial disease and ischaemic stroke), whereas the Framingham equation assesses fatal and non-fatal CHD. The SCORE charts can be used to project risk to 60 years and allow relative risk to be assessed, which can be useful in demonstrating the importance of risk factor management to patients, and enable countries with no cohort studies to choose the most appropriate model after calculation of baseline risk from national mortality data. National/regional charts are also in development.

What constitutes a risk threshold?
Guidelines are generally in agreement on the treatment approach for high- and low-risk patients, but there is some divergence regarding the risk level at which drug therapy is recommended. This results in a group of intermediate-risk patients for whom treatment strategies are poorly defined. Data are emerging, which support the use of additional factors such as C-reactive protein, non-HDL-C, fibrinogen, lipoprotein(a), and apolipoprotein B in determining risk. These parameters, and the other non-invasive tests discussed earlier, may prove particularly useful for stratifying intermediate-risk patients.

Who should be treated?
It is important that guidelines are based on up-to-date clinical data. The recent NCEP ATP III guidelines update13 is based on results of five major clinical trials of statin therapy conducted since the 2001 guidelines11 were released. The trials support many NCEP ATP III recommendations, including the use of LDL-lowering therapy in diabetic patients and older persons. In addition, they have shown the benefits of LDL-lowering therapy in patient groups for which ATP III could not make definitive recommendations and have demonstrated the efficacy of risk reduction in high-risk persons with relatively low LDL-C levels. As a result, the NCEP update recommends an optional therapeutic target of LDL-C<70 mg/dL (1.8 mmol/L) in very high risk patients: those with acute coronary syndrome or those with CHD plus diabetes, the metabolic syndrome, multiple-risk factors, or a poorly controlled risk factor (e.g. continued smoking).13 Studies have demonstrated benefit from lipid lowering irrespective of initial LDL-C levels, including those with average levels at baseline. Indeed, LDL-C levels as low as 1.8 mmol/L have been shown to be protective in high-risk individuals in clinical trials.13

The major recommendations for modifications to the ATP III treatment algorithm are summarized in Table 7.


View this table:
[in this window]
[in a new window]
 
Table 7 Major recommendations for modifications to the ATP III treatment algorithm13
 
The use of statins, beta-blockers, and angiotensin-converting enzyme-inhibitors is widely recommended for patients with symptomatic CHD, regardless of cholesterol or blood pressure levels.12,15,17,32 However, for patients who are already below target levels before treatment, recommending therapeutic lipid and blood pressure goals is of no value. In such situations, it may be more appropriate to recommend drug dosages rather than risk factor targets. This approach is taken by the Canadian guidelines,19 which recommend that all high-risk individuals should receive the equivalent dose of 40 mg/day simvastatin. A similar approach is taken by the Australian Practical Implementation Taskforce for the Prevention of CVD,33 which recommends that all patients with CHD should receive ramipril (10 mg) or perindopril (8 mg), regardless of blood pressure. Publication of separate recommendations for high-risk symptomatic and asymptomatic individuals might reduce the confusion generated by recommending lipid and blood pressure targets for populations that should receive treatment regardless of risk factor level.

Some guidelines highlight certain ethnic groups that have a higher CV risk (Table 8) than the general population. Advice on assessing other patient groups such as those with the type 2 diabetes and/or the metabolic syndrome is also given by most guidelines, although risk assessment and treatment recommendations may differ. The NCEP ATP III guidelines11,13 define diabetic patients as CHD equivalents, i.e. their CHD risk is considered equal to that of an individual with established CVD. The New Zealand15 and Australian14 guidelines use separate tables for assessing risk in these patients, although the European12 guidelines assume that the presence of type 2 diabetes doubles the baseline risk in men and quadruples the risk in women.


View this table:
[in this window]
[in a new window]
 
Table 8 Ethnic groups at high risk according to guidelines
 
The effect of gender on CV risk is acknowledged by all guidelines. Most recommendations for CVD prevention and treatment are similar for men and women, although gender-specific issues (e.g. use of hormone replacement therapy) do exist. The recent publication of evidence-based guidelines for CVD prevention in women provides a comprehensive summary of this topic.32

Individuals with the metabolic syndrome constitute a population whose risk is not easily quantified using standard algorithms, and therefore guidelines generally recommend that these patients' 10 year risk should be adjusted upwards. However, accurate risk assessment is further complicated by the diversity of metabolic syndrome definitions. The most widely accepted criteria are those of the World Health Organization (WHO)34 and the NCEP.11 The latter definition is more widely used.

Which therapeutic targets are the most appropriate?
Although most guidelines recommend reduction of total cholesterol and LDL-C, evidence is accruing to support the use of other therapeutic targets. The NCEP ATP III guidelines11,13 use non-HDL-C (LDL-C+VLDL-C) as a target for individuals in whom triglycerides exceed 2.3 mmol/L. This recommendation acknowledges the atherogenic potential of triglyceride-rich remnant lipoproteins, which are most readily measured as VLDL-C.8 The Canadian guidelines19 regard apolipoprotein B as an alternative therapeutic target for patients at all levels of risk.


    Guidelines as a framework for optimizing outcomes
 Top
 Abstract
 Guideline implementation: the...
 Guidelines: the common goals
 Guidelines: areas of divergence
 Guidelines as a framework...
 Conclusion
 Acknowledgements
 References
 
Guidelines are not intended to replace the judgment of practitioners, whose expertise is key to optimizing patient outcomes. Practitioners must educate and motivate patients, conduct ongoing monitoring, and choose the most effective therapies and drug dosages. However, drug dosage is a topic on which the guidelines give little guidance. The Atorvastatin Comparative Cholesterol Efficacy and Safety Study showed that most CHD patients (47–85%, depending on the statin) fail to achieve their LDL-C goal of ≤100 mg/dL (≤2.6 mmol/L) at starting statin doses.35 It is important that an optimal dose is used from the outset because, once a statin has been prescribed, titration is unlikely to occur.36 The recent ATP III update recommends that all high-risk patients should start on a statin dose that provides ≥30–40% reduction in LDL-C.13 The update provides a table to guide clinicians in selecting the appropriate dose of each statin (Table 9). This shows that statins differ widely in potency. In a study of 2431 mild to moderately hypercholesterolaemic patients, LDL-C was reduced by 46–55% with rosuvastatin (10–40 mg), 37–51% with atorvastatin (10–80 mg), 28–40% with simvastatin (10–80 mg), and 20–30% with pravastatin (10–40 mg).37 In a separate study, statins that provided greater LDL-C reductions enabled more patients to achieve European LDL-C goals: 69–86% achieved goal with rosuvastatin compared with 44–74, 20–66, and 2–22% with atorvastatin, simvastatin and pravastatin, respectively.38


View this table:
[in this window]
[in a new window]
 
Table 9 Statin dose required to attain approximate 30–40% reduction in LDL-C levels13
 
In primary care, non-compliance with statin therapy occurs commonly (15–52% of patients).10,39 Patients may discontinue treatment because of poor efficacy or adverse events.10 Myopathy is the most common and potentially the most serious adverse effect of statin therapy. It is, however, rare. In a study involving 218 892 person-years of statin mono- and combination therapy, the average incidence of hospitalized rhabdomyolysis was 0.44 per 10 000 person-years of monotherapy with atorvastatin, pravastatin, or simvastatin.40 Since statin monotherapy reduces CV risk by ~35% in individuals at low or high risk,41,42 patients with baseline 10 year risks of 5 and 20% have annual CVD risks of ~0.33 and 1.3%, respectively, if assigned to statin therapy. The risk–benefit ratio is thus firmly in favour of statin use.

Primary care practitioners can improve compliance and persistence through regular monitoring and by educating and motivating patients. Potential interventions include one-to-one discussions, written materials, telephone follow-up, and group sessions. Individual counselling and community initiatives are effective in achieving lifestyle changes and reducing LDL-C levels.4346

One of the most successful community-based programmes is the Finnish North Karelia project. Its success in reducing CVD risk factors led to the development and implementation of a national CVD prevention strategy in the 1970s. This has significantly lowered cholesterol, blood pressure, and smoking levels nationwide.46 A European-wide initiative, EUROACTION, is currently investigating whether the Second Joint European Societies guidelines on lifestyle, risk factor, and therapeutic goals for CVD can be realized in everyday practice through a multi-disciplinary team comprising cardiologists, primary care practitioners, specialist nurses, dieticians, and physiotherapists.


    Conclusion
 Top
 Abstract
 Guideline implementation: the...
 Guidelines: the common goals
 Guidelines: areas of divergence
 Guidelines as a framework...
 Conclusion
 Acknowledgements
 References
 
Primary care practitioners are in a pivotal position to improve CVD management, and guidelines can assist in meeting this challenge. The numerous guidelines available contain many similarities. All guidelines promote screening and identification of at-risk patients. They concur that risk factors increase CV risk in a compound manner, recommend systems to calculate total risk and provide advice on treatment and follow-up regimens for different risk levels. The advice provided by different guidelines is similar for secondary prevention and for high- and low-risk patients. However, there are areas in which the guidelines differ, including the selection and weighting of risk factors, risk algorithms, and treatment thresholds. Divergence of the guidelines is greatest for primary prevention in intermediate-risk patients.

Countries that have not developed their own guidelines may consider using those of the International Atherosclerosis Society.47 This document, which represents an attempt to harmonize existing guidelines, highlights the difficulties inherent in producing a ‘one size fits all’ solution to the problem of CVD prevention, and acknowledges the substantial differences among countries in baseline risk, medical expenditure, and healthcare priorities. Ultimately, physicians in each region must decide which guidelines best reflect the medical priorities and CV risk profile of the population for which they are responsible.


    Acknowledgements
 Top
 Abstract
 Guideline implementation: the...
 Guidelines: the common goals
 Guidelines: areas of divergence
 Guidelines as a framework...
 Conclusion
 Acknowledgements
 References
 
C.B. has received research grants and consulting honoraria from AstraZeneca, Pfizer, Merck, Schering-Plough, Novartis, and Kos Pharmaceuticals. B.A. has received educational sponsorship from AstraZeneca. J.S. has received educational sponsorship from AstraZeneca, Merck AG, MSD, BMS, Schering Plough and GSK. Editorial support was provided by The Future Forum Secretariat, London, UK.


    References
 Top
 Abstract
 Guideline implementation: the...
 Guidelines: the common goals
 Guidelines: areas of divergence
 Guidelines as a framework...
 Conclusion
 Acknowledgements
 References
 

  1. Pearson TA, Laurora I, Chu H, Kafonek S. The lipid treatment assessment project (L-TAP): a multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid- lowering therapy and achieving low-density lipoprotein cholesterol goals. Arch Intern Med 2000;160:459–467.[Abstract/Free Full Text]
  2. Hobbs FD, Erhardt L. Acceptance of guideline recommendations and perceived implementation of coronary heart disease prevention among primary care physicians in five European countries: the Reassessing European Attitudes about Cardiovascular Treatment (REACT) survey. Fam Pract 2002;19:596–604.[Abstract/Free Full Text]
  3. Hoerger TJ, Bala MV, Bray JW, Wilcosky TC, LaRosa J. Treatment patterns and distribution of low-density lipoprotein cholesterol levels in treatment-eligible United States adults. Am J Cardiol 1998;82:61–65.[CrossRef][ISI][Medline]
  4. McBride P, Schrott HG, Plane MB, Underbakke G, Brown RL. Primary care practice adherence to National Cholesterol Education Program guidelines for patients with coronary heart disease. Arch Intern Med 1998;158:1238–1244.[Abstract/Free Full Text]
  5. EUROASPIRE I and II Group. European Action on Secondary Prevention by Intervention to Reduce Events. Clinical reality of coronary prevention guidelines: a comparison of EUROASPIRE I and II in nine countries. Lancet 2001;357:995–1001.[CrossRef][ISI][Medline]
  6. Vale MJ, Jelinek MV, Best JD. How many patients with coronary heart disease are not achieving their risk-factor targets? Experience in Victoria 1996–1998 versus 1999–2000. Med J Aust 2002;176:211–215.[ISI][Medline]
  7. Sueta CA, Chowdhury M, Boccuzzi SJ, Smith SC Jr, Alexander CM, Londhe A, Lulla A, Simpson RJ Jr. Analysis of the degree of undertreatment of hyperlipidemia and congestive heart failure secondary to coronary artery disease. Am J Cardiol 1999;83:1303–1307.[CrossRef][ISI][Medline]
  8. Fonarow GC, French WJ, Parsons LS, Sun H, Malmgren JA. Use of lipid-lowering medication at discharge in patients with acute myocardial infarction. Circulation 2001;103:38–44.[Abstract/Free Full Text]
  9. Insull WJ. The problem of compliance to cholesterol altering therapy. J Intern Med 1997;241:317–325.[CrossRef][ISI][Medline]
  10. Andrade SE, Walker AM, Gottlieb LK, Hollenberg NK, Testa MA, Saperia GM, Platt R. Discontinuation of antihyperlipidemic drugs—do rates reported in clinical trials reflect rates in primary care settings? N Engl J Med 1995;332:1125–1131.[Abstract/Free Full Text]
  11. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP). Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001;285:2486–2497.[Free Full Text]
  12. de Backer G, Ambrosioni E, Borch-Johnsen K, Brotons C, Cifkova R, Dallongeville J, Ebrahim S, Faergeman O, Graham I, Mancia G, Manger Cats V, Orth-Gomer K, Perk J, Pyorala K, Rodicio JL, Sans S, Sansoy V, Sechtem U, Silber S, Thomsen T, Wood D. Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. European guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 2003;24:1601–1610.[Free Full Text]
  13. Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, Pasternak RC, Smith SC Jr, Stone NJ. National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004;110:227–239.[Abstract/Free Full Text]
  14. National Heart Foundation of Australia. The Cardiac Society of Australia and New Zealand. Lipid Management Guidelines–2001. Med J Austr 2001;175(Suppl):S57–S88. Addendum www.heartfoundation.com.au (October 2002)
  15. The New Zealand Guidelines Group, the National Heart Foundation of New Zealand and the Stroke Foundation of New Zealand 2003. The Assessment and Management of Cardiovascular Risk. Wellington: New Zealand Guidelines Group; 2003.
  16. Scottish Intercollegiate Guidelines Network. Lipids and the primary prevention of coronary heart disease. SIGN Publication 40, 1999.
  17. Scottish Intercollegiate Guidelines Network. Secondary prevention of coronary heart disease following myocardial infarction. SIGN Publication 41, 2000.
  18. Hata Y, Mabuchi H, Saito Y, Itakura H, Egusa G, Ito H, Teramoto T, Tsushima M, Tada N, Oikawa S, Yamada N, Yamashita S, Sakuma N, Sasaki J. Working Committee on JAS Guideline for Diagnosis and Treatment of Hyperlipidemias. Report of the Japan Atherosclerosis Society (JAS) guideline for diagnosis and treatment of hyperlipidemia in Japanese adults. J Atheroscler Thromb 2002;9:1–27.[Medline]
  19. Genest J, Frohlich J, Fodor G, McPherson R (the Working Group on Hypercholesterolemia and Other Dyslipidemias). Recommendations for the management of dyslipidaemia and the prevention of cardiovascular disease: 2003 update. CMAJ 2003;168:921–924.
  20. Kannel WB, Wilson PW. An update on coronary risk factors. Med Clin North Am 1995;79:951–971.[ISI][Medline]
  21. Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M, Taskinen MR, Groop L. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001;24:683–689.[Abstract/Free Full Text]
  22. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998;339:229–234.[Abstract/Free Full Text]
  23. Gotto AM Jr, Brinton EA. Assessing low levels of high-density lipoprotein cholesterol as a risk factor in coronary heart disease: a working group report and update. J Am Coll Cardiol 2004;43:717–724.[Abstract/Free Full Text]
  24. Haq IU, Ramsay LE, Jackson PR, Wallis EJ. Prediction of coronary risk for primary prevention of coronary heart disease: a comparison of methods. QJM 1999;92:379–385.[Abstract/Free Full Text]
  25. Broedl UC, Geiss H-C, Parhofer KG. Comparison of current guidelines for primary prevention of coronary disease. J Gen Intern Med 2003;18:190–195.[CrossRef][Medline]
  26. D'Agostino RB Sr, Grundy S, Sullivan LM, Wilson P. CHD Risk Prediction Group. Validation of the Framingham coronary heart disease prediction scores: results of a multiple ethnic groups investigation. JAMA 2001;286:180–187.[Abstract/Free Full Text]
  27. Sniderman AD, Furberg CD, Keech A, Roeters van Lennep JE, Frohlich J, Jungner I, Walldius G. Apolipoproteins versus lipids as indices of coronary risk and as targets for statin treatment. Lancet 2003;361:777–780.[CrossRef][ISI][Medline]
  28. Laurie D, Nguyen PC, Cazelles B, Segond P. Estimation of CHD risk in a French working population using a modified Framingham model. The PCV-METRA Group. J Clin Epidemiol 1994;47:1353–1364.[CrossRef][ISI][Medline]
  29. Thomsen TF, McGee D, Davidsen M, Jorgensen T. A cross-validation of risk-scores for coronary heart disease mortality based on data from the Glostrup Population Studies and Framingham Heart Study. Int J Epidemiol 2002;31:817–822.[Abstract/Free Full Text]
  30. Hense HW, Schulte H, Lowel H, Assmann G, Keil U. Framingham risk function overestimates risk of coronary heart disease in men and women from Germany—results from MONICA Augsburg and the PROCAM cohorts. Eur Heart J 2003;24:937–945.[Abstract/Free Full Text]
  31. Menotti A, Puddu PE, Lanti M. Comparison of the Framingham risk function-based coronary chart with a risk function from an Italian population study. Eur Heart J 2000;21:365–370.[Abstract/Free Full Text]
  32. Mosca L, Appel LJ, Benjamin EJ, Berra K, Chandra-Strobos N, Fabunmi RP, Grady D, Haan CK, Hayes SN, Judelson DR, Keenan NL, McBride P, Oparil S, Ouyang P, Oz MC, Mendelsohn ME, Pasternak RC, Pinn VW, Robertson RM, Schenck-Gustafsson K, Sila CA, Smith SC Jr, Sopko G, Taylor AL, Walsh BW, Wenger NK, Williams CL. American Heart Association. Evidence-based guidelines for cardiovascular disease prevention in women. Circulation 2004;109:672–693.[Free Full Text]
  33. Practical Implementation Taskforce for the Prevention of Cardiovascular Disease. Prevention of cardiovascular disease: an evidence-based clinical aid 2004. Med J Aust 2004;181:F1–F14.
  34. World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications. 1999. WHO/NCD/NCS/99.2. www.who.int.
  35. Andrews TC, Ballantyne CM, Hsia JA, Kramer JH. Achieving and maintaining National Cholesterol Education Program low-density lipoprotein cholesterol goals with five statins. Am J Med 2001;111:185–191.[CrossRef][ISI][Medline]
  36. EUROASPIRE. A European Society of Cardiology survey of secondary prevention of coronary heart disease: principal results. EUROASPIRE Study Group. European Action on Secondary Prevention through Intervention to Reduce Events. Eur Heart J 1997;18:1569–1582.[Abstract]
  37. Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, Cain VA, Blasetto JW; STELLAR Study Group. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* trial). Am J Cardiol 2003;92:152–160.[ISI][Medline]
  38. Kritharides L. Reducing low-density lipoprotein cholesterol–treating to target and meeting new European goals. Eur Heart J 2004;6(Suppl. A):A12–A18.
  39. O'Connor PJ, Rush WA, Trence DL. Relative effectiveness of niacin and lovastatin for treatment of dyslipidemias in a health maintenance organization. J Fam Pract 1997;44:462–467.[ISI][Medline]
  40. Graham DJ, Staffa JA, Shatin D, Andrade SE, Schech SD, La Grenade L, Gurwitz JH, Chan KA, Goodman MJ, Platt R. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA 2004;292:2585–2590.[Abstract/Free Full Text]
  41. Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, Langendorfer A, Stein EA, Kruyer W, Gotto AM Jr. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998;279:1615–1622.[Abstract/Free Full Text]
  42. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383–1389.[CrossRef][ISI][Medline]
  43. Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M. Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001;344:1343–1350.[Abstract/Free Full Text]
  44. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393–403.[Abstract/Free Full Text]
  45. deBusk RF, Miller NH, Superko HR, Dennis CA, Thomas RJ, Lew HT, Berger WE III, Heller RS, Rompf J, Gee D, Kraemer HC, Bandura A, Ghandour G, Clark M, Shah RV, Fisher L, Taylor CB. A case-management system for coronary risk factor modification after acute myocardial infarction. Ann Intern Med 1994;120:721–729.[Abstract/Free Full Text]
  46. Vartiainen E, Jousilahti P, Alfthan G, Sundvall J, Pietinen P, Puska P. Cardiovascular risk factor changes in Finland, 1972–1997. Int J Epidemiol 2000;29:49–56.[Abstract/Free Full Text]
  47. International Atherosclerosis Society Harmonized Guidelines on Prevention of Atherosclerotic Cardiovascular Diseases. 2003. www.athero.org.




This Article
Abstract
Full Text (PDF)
All Versions of this Article:
26/21/2224    most recent
ehi373v1
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Request Permissions
Google Scholar
Articles by Ballantyne, C.
Articles by Shepherd, J.
PubMed
PubMed Citation
Articles by Ballantyne, C.
Articles by Shepherd, J.