Cardiovascular disease (CVD) causes one-third of deaths in Canada – more than any other illness (1
). The prevalence of CVD is expected to increase in Canada in the next decade, predominantly because of increasingly sedentary lifestyles and an attendant increase in the prevalence of obesity and diabetes mellitus. The economic cost of CVD represents approximately $22 billion in direct and indirect health care costs and lost productivity annually. However, mortality from coronary artery disease (CAD) in Canada has decreased by nearly 40% in the past several decades (2
). Intensive secondary prevention has resulted in a marked decrease in recurrent cardiovascular events in patients with established CAD, to a level approaching that of age- and sex-matched individuals without clinical CAD (at least in clinical trials). The decrease in cardiac mortality has been attributed to improvements in the control of CVD risk factors – especially cholesterol levels, smoking and blood pressure – and to improved medical management of patients with CVD. Despite these improvements, CVD still represents the major burden of disease in our society.
The incorporation of new data from clinical studies into clinical practice guidelines helps promote a standard of care that is current and uniform across Canada. Frequent updates are required to take this new information into account. The development of guidelines has undergone major changes to reduce bias by promoting a structured process that assesses and grades evidence, and highlights potential conflicts of interest among contributors. Duality of interest of participants of guideline development has been the focus of much attention and debate, recognizing that individuals have many potential sources of bias. In common with documents prepared in other therapeutic areas, the present guidelines were developed by volunteer experts in lipid disorders and CVD, with full and open disclosure of their relationships with the pharmaceutical industry. There was no direct financial support for this guideline development from industry, nor was there any involvement by them in the guideline writing process.
While the major principles of screening and risk stratification in the 2006 Canadian lipid guidelines (3
) have been retained, the process by which this updated version was developed took into account comments and criticisms by many stakeholders. The process changes include working under the Canadian Cardiovascular Society (CCS) guidelines process, and the establishment of primary and secondary review panels. In addition, members of the Canadian Vascular Coalition have had input in the guideline process. A systematic electronic PubMed search of original research published in the medical literature between January 1, 2006, and February 1, 2009, was performed. The following key words were used: lipid-lowering therapy (including generic names of medications), statins, fibrates, niacin, ezetimibe, diet, cardiovascular disease, prevention and clinical trials. Only blinded randomized controlled trials with cardiovascular outcome data were retained for evaluation. Meta-analyses of studies of the efficacy and safety of lipid-lowering therapies and on the predictive value of established and emerging risk factors were also reviewed. Strict criteria have been implemented for the incorporation of biomarkers of risk. Novel biomarkers (4,5) must show improved risk prediction over the previously accepted markers and improved CVD risk stratification, and demonstrate that clinical decisions and outcomes are influenced by their measurement.
The Canadian Vascular Coalition represents an informal group of stakeholders involved in CVD prevention under the banner of the Canadian Institutes of Health Research. Member organizations are listed in . (Supplementary information begins on page 576.) The recommendations for the treatment of lipoprotein disorders are harmonized with those of the major Canadian stakeholders in CVD prevention. Areas of discordance between the various stakeholders and opinion leaders are highlighted and discussed. The CCS provided oversight and logistical support for the process. The recently released recommendations of the Canadian Heart Health Strategy and Action Plan (available at http://www.chhs-scsc.ca/web/
) were also influential in writing these guidelines. The writing group used a widely accepted system to grade and assess the evidence behind the recommendations, based on consensus ().
Since the previous publication of the recommendations for the management and treatment of dyslipidemia in 2006 (3
), a number of new clinical studies have been published. When assessing interventions, the primary outcomes examined were cardiovascular death, nonfatal myocardial infarction (MI) and stroke as a combined end point, and total mortality as a secondary end point. Less emphasis was placed on the effects of biomarkers on cardiovascular risk or surrogate end points, such as invasive or noninvasive atherosclerosis assessment. The major changes in our recommendations since the 2006 guidelines are summarized in . The high-risk population has been better defined, including patients with end-stage cardiac or renal disease (ie, severe heart failure or chronic kidney disease on hemodialysis, respectively). Improved, validated CVD event risk-stratification tools are provided. This is especially relevant in subjects at intermediate CVD risk for whom the justification of treatment, other than health behaviour interventions, is often extrapolated from studies of high-risk patients.
The screening strategy is defined in . The importance of genetic factors and family history of premature CVD is taken into account in the determination of risk (6
). The importance of obesity (especially abdominal obesity) as a major modifiable CVD risk factor (8
) is emphasized by including the International Diabetes Federation (IDF) classification of the metabolic syndrome (10
) () and including overweight and obesity in the screening strategy. We have included risk stratification for several inflammatory diseases, including rheumatoid arthritis, psoriasis and systemic lupus erythematosis (SLE) (11
). Such patients require comprehensive assessment and treatment of the traditional cardiovascular risk factors. The association between inflammatory bowel diseases (which share many commonalities with other inflammatory diseases) and CVD is less well established (14
). The use of biomarkers of inflammation is now included in the guidelines based, in large part, on the epidemiology of high-sensitivity C-reactive protein (hs-CRP) and clinical trials of patients with high hs-CRP levels (4
). Similarly, recommendations for patients with chronic HIV infection who are on highly active antiretroviral therapies are included (16
Patients whose plasma lipid profile should be screened
International Diabetes Federation classification of the metabolic syndrome
We also provide simplified target lipid levels. The emphasis is once again focused on atherogenic lipoproteins, as reflected by the serum (or plasma) levels of low-density lipoprotein cholesterol (LDL-C) or apolipoprotein (apo) B. The evidence favouring LDL-C reduction for the prevention and treatment of atherosclerosis is strong and compelling, and is based on multiple randomized clinical trials (17
). Whereas a specific target level for LDL-C will remain a matter of debate, the data indicate that a lower level of LDL-C is associated with reduced CAD risk (18
). LDL-C therefore continues to constitute the primary target of therapy; the alternate primary target is apoB. A summary is provided of optional secondary therapeutic targets of potential relevance once the LDL-C (or apoB) is at target, including (in alphabetical order) the apoB to apoAI ratio, the total cholesterol (TC) to high-density lipoprotein cholesterol (HDL-C) ratio, and the hs-CRP, non-HDL-C and serum (or plasma) triglyceride levels. Increased levels of all these parameters have been found to confer additional risk. However, clinical trial evidence is lacking on the importance of intervening on these variables to further reduce risk and thus, they are considered secondary and optional targets (19
). We also provide further consideration for the noninvasive assessment of atherosclerosis in asymptomatic individuals, bearing in mind that data on cost effectiveness and outcomes are lacking.
While there is general agreement on the need for sustained, aggressive and multifactorial therapeutic interventions in the secondary prevention of CVD (18
), controversy remains about the cost effectiveness and societal impact of primary prevention strategies. However, most heart attacks occur in subjects with relatively ‘normal’ serum cholesterol levels (based on population distribution) but frequently suboptimal levels of cardiometabolic fitness in association with tobacco consumption. Many biomarkers, including levels of serum lipids, lipoproteins, apolipoproteins and various derived ratios, predict CVD risk (5
). However, it is important to keep in mind that none of the traditional CVD risk factors or biomarkers reflect the actual presence or absence of atherosclerosis. They help to establish CVD event risk rather than the risk or presence of CVD itself. The inflammatory biomarker hs-CRP also predicts risk and identifies a population that responds particularly well to statin therapy. Importantly, however, our ability to predict CVD events does not always translate into our ability to prevent subsequent events. For instance, homocysteine level predicts CVD risk, but lowering an elevated homocysteine level with folic acid and other B vitamins to prevent recurrent cardiovascular events has proven to be unsuccessful (22
). Therefore, we have focused on CVD risk factors whose measurement influences clinical decision making and for which there exists a proven effect on clinical outcomes.