Robert Schlosser, MD, FRCPC
The 2009 Canadian guidelines for the diagnosis and treatment of dyslipidemia and the prevention of cardiovascular disease in the adult were published in the October 2009 issue of the Canadian Journal of Cardiology (1). They provide the latest evidence-based recommendations and standards for identifying patients at risk, lipid modification and CVD prevention.
The recommended screening strategy for adult patients is a full lipid profile every 1 to 3 years. This strategy encompasses men aged 40 or over and women aged 50 or over, but also a patient of any age with the traditional risk factors listed above or evidence of atherosclerosis in any vascular bed. Several other medical conditions suggest the need for early screening, including HIV infection treated with antiretroviral therapy, erectile dysfunction, chronic renal disease, and autoimmune disorders associated with chronic inflammation, such as rheumatoid arthritis, systemic lupus and psoriasis.
The Framingham Risk Score (FRS) has been utilized for many years as a reliable risk calculator. It provides a reasonable estimate of the 10-year risk of a major CV event for a large portion of the Canadian population. However, the FRS does not account for family history of premature coronary artery disease which increases risk 1.7-fold in women and 2.0-fold in men.
Also pertinent is that risk evolves with time. In fact, patient age is the single most powerful driver of CV risk. Accordingly, a patient’s risk for CVD should be reassessed every 3 to 5 years.
The 2009 guidelines acknowledge the limitations of the Framingham Risk Score for coronary artery disease. The consensus panel now recommends the modified FRS for total CVD (includes stroke), which is in line with the recommendations put forth by the Canadian Hypertension Education Program (CHEP) and the Canadian Diabetes Association (CDA). The panel also suggests the Reynolds Risk Score as an alternative tool that takes into account both hsCRP and family history.
The 2009 lipid guidelines retain the high, moderate and low-risk categories according to the modified Framingham Risk Score. High-risk patients are defined by having a calculated 10-year risk of at least 20% or established atherosclerotic disease or diabetes (most patients) and generally require immediate treatment (lifestyle behaviors and drug therapy). Treatment should be considered for moderate-risk patients (FRS 10-year risk 10-19%) who fit certain criteria such as: LDL-C > 3.5 mmol/L, TC/ HDL-C ratio > 5 or hsCRP > 2 mg/L for men > 50 and women > 60 years of age.
An important change is that for both high-risk and moderate-risk patients, the LDL-C goal is < 2 mmol/L OR at least a 50% reduction from baseline. Low-risk patients (FRS < 10%) for whom lipid-lowering therapy is deemed appropriate should seek to lower their LDL-C by at least 50% from baseline.
A hsCRP level should not be measured in high risk individuals since treatment is already indicated on the basis of clinical risk. This test is typically only required in men > 50 years and in women > 60 years who are at moderate risk for CVD (by FRS) and whose level of LDL-C is < 3.5 mmol/L, because these individuals—if they also have elevated hsCRP—have been shown to benefit from statin therapy in the JUPITER study (2). The lower of 2 hsCRP values taken at least 2 weeks apart in the absence of acute inflammatory illness should be used.
The JUPITER study demonstrated that moderate-risk patients > age 50 (men) or > age 60 (women) with no history of CVD or diabetes and baseline CRP > 2mg/L who were treated with rosuvastatin 20mg/day were significantly less likely to experience the primary composite CV endpoint as well as mortality. At the time of the JUPITER study termination (median follow-up 1.9 years), 142 first major CV events had occurred in the rosuvastatin group and 251 in the placebo group. This represented a 44% relative risk reduction and an absolute risk reduction of 1.2% (HR: 0.56; 95% CI: 0.46 to 0.69; p<0.00001). The number needed to treat (NNT) was 95. If projected out to 5 years, the NNT would be 25.
In a recent retrospective substudy (3), application of the 2009 Canadian lipid guidelines was examined in the JUPITER trial population consisting of 6091 participants with baseline estimated 10-year Framingham risks of 5% to 10% and 7340 participants with baseline estimated Framingham risk of 11% to 20%. In these 2 “intermediate risk” subgroups, relative risk reductions consistent with the overall trial treatment effect were observed: 49% risk reduction with FRS 10-20% (5 year NNT estimate = 18) and 45% risk reduction with FRS 5-10% (5 year NNT estimate = 40). Use of the Reynolds Risk Score to stratify the study population gave similar results.
A meta-analysis by Robinson et al (4) examined the relationship between percent relative reduction of LDL-C and the resulting absolute reduction of nonfatal MI and CHD mortality. There appears to be a linear relationship between % LDL-C reduction and reduction of CHD events (approximately 1% CVD risk reduction for every 1% LDL-C reduction) irrespective of the method of cholesterol reduction, although statin trials show the most benefit presumably due to their more potent LDL-C reducing efficacy. Therefore, a 50% reduction in LDL-C is recommended as an alternative target.
Most patients will be able to achieve their LDL-C target with statin monotherapy. Some may require combination therapy – a statin plus a cholesterol absorption inhibitor (ezetimibe) or bile acid binder (cholestyramine, colestipol); or a statin plus niacin or a fibrate. These combinations are generally safe and can decrease LDL-C by an additional 10% to 30%. Data is still lacking on the clinical benefits of combination therapy, but clinical endpoint trials are now in progress. In the recently published ACCORD-LIPID trial (5), combination therapy with fenofibrate and simvastatin failed to reduce the risk of cardiovascular events, in patients with type 2 diabetes who were at high risk. However, there was a suggestion of benefit observed among patients with higher triglyceride and lower HDL-cholesterol levels.
In summary, the 2009 Canadian Lipid Guidelines represent a significant evolutionary step in the management of patients with dyslipidemia. The main changes include more precise estimation of global cardiovascular risk, as well as simplified but still aggressive targets for high and moderate risk patients, incorporating the most recent clinical trial evidence.
1. Genest J et al. 2009 Canadian Cardiovascular Society: Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult. Can J Cardiol 2009;25(10):567-79
2. Ridker P et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;359:2195-207.
3. Ridker PM et al, Rosuvastatin for primary prevention among individuals with elevated high-sensitivity C-reactive protein and 5% to 10% and 10% to 20% 10-year risk in the JUPITER trial. Circ Cardiovasc Qual Outcomes. 2010;3:5 447-452
4. Robinson JG, Smith B, Maheshwari N, et al. Pleiotropic effects of statins: benefit beyond cholesterol reduction? A meta-regression analysis. J Am Coll Cardiol 2005; 46(10):1855-62.
5. The ACCORD Study Group. Effects of Combination Lipid Therapy in Type 2 Diabetes Melitus.N Engl J Med 2010; 362:1563-1574