Abstract
Résumé
Introduction and Process
Lipid screening for men and women 40 years of age and older Inclusion of screening for women with a history of hypertensive diseases of pregnancy |
Nonfasting lipid determination recommendation LDL-C as primary, non-HDL-C or apoB as alternative targets |
Risk assessment with modified Framingham Risk Score to determine risk category Alternate approach is use of CLEM to calculate cardiovascular age Shared decision-making |
Retention of treatment targets for those receiving therapy Broader treatment recommendations for those in the intermediate risk category New expanded definition of CKD as high risk phenotype |
Statins remain drugs of choice New recommendation for nonstatin drugs |
Nutritional guidelines that focus on dietary patterns—Mediterranean, DASH, or Portfolio diet Detailed review of the effect of nutritional components on lipids and CV events |
Definitions
Risk Assessment for Primary Prevention
- European Association for Cardiovascular Prevention and Rehabilitation
- Reiner Z.
- Catapano A.L.
- et al.
- 1.We recommend that a CV risk assessment be completed every 5 years for men and women aged 40 to 75 years using the modified FRS or CLEM to guide therapy to reduce major CV events. A risk assessment might also be completed whenever a patient's expected risk status changes (Strong Recommendation; High-Quality Evidence).
- 2.We recommend sharing the results of the risk assessment with the patient to support shared decision-making and improve the likelihood that patients will reach lipid targets (Strong Recommendation; High-Quality Evidence).
Whom to Consider for Screening

How to Screen: Fasting or Nonfasting Lipid Determination
- Nordestgaard B.G.
- Langsted A.
- Mora S.
- et al.
- 1.We recommend nonfasting lipid and lipoprotein testing can be performed in adults in whom screening is indicated as part of a comprehensive risk assessment to reduce CVD events (Strong Recommendation; High-Quality Evidence).
- 2.We suggest that for individuals with a history of triglyceride levels > 4.5 mmol/L that lipid and lipoprotein levels be measured fasting (Conditional Recommendation; Low-Quality Evidence).

Primary and Secondary Lipoprotein Determinants

When to Consider Pharmacological Treatment in Risk Management

Category | Consider initiating pharmacotherapy if | Target | NNT |
---|---|---|---|
Primary prevention | High FRS (≥ 20%) All | LDL-C < 2.0 mmol/L or > 50% ↓ Or | 35 |
Intermediate FRS (10%-19%) LDL-C ≥ 3.5 mmol/L or non-HDL-C ≥ 4.3 mmol/L or ApoB ≥ 1.2 g/L or men ≥ 50 and women ≥ 60 years and 1 additional CVD RF | ApoB < 0.8 g/L Or non-HDL-C < 2.6 mmol/L | 40 | |
Statin-indicated conditions | Clinical atherosclerosis | 20 | |
Abdominal aortic aneurysm | |||
Diabetes mellitus Age ≥ 40 years 15-Year duration for age ≥ 30 years (DM 1) Microvascular disease | |||
Chronic kidney disease (age ≥ 50 years) eGFR < 60 mL/min/1.73 m2 or ACR > 3 mg/mmol | |||
LDL-C ≥ 5.0 mmol/L | > 50% ↓ in LDL-C |
Statin-indicated conditions
Primary prevention
- 1.The low-risk category applies to individuals with a modified 10-year FRS < 10%. Most of these individuals do not require pharmacologic therapy. The exceptions are subjects with an LDL-C ≥ 5.0 mmol/L, many of whom have a genetic dyslipidemia such as familial hypercholesterolemia (see the section on Statin-indicated conditions). In individuals with a modified FRS of 5%-9%, yearly monitoring could be used to evaluate change in risk. On the basis of a consistent relative risk reduction observed in the Cholesterol Treatment Trialists' meta-analysis,39certain individuals in the low-risk category might decide to start statin therapy with a view to long-term risk reduction.
- 2.The high-risk category is the least common in the general population until age increases beyond 65 years. It is defined as an adjusted FRS 10-year risk ≥ 20%. Statin therapy is indicated for these subjects (NNT = 35).
- 3.The IR group encompasses a significant proportion of Canadians (up to 25%). Statin therapy, in addition to health behaviour interventions might be appealing to a broad group of individuals in the IR group. The strongest evidence for treatment is on the basis of the inclusion criteria from the primary prevention studies outlined in the section, Primary prevention studies.
- i.Those with an LDL-C ≥ 3.5 mmol/L, or an apoB ≥ 1.2 g/L or non-HDL-C ≥ 4.3 mmol/L as per the previous 2012 CCS dyslipidemia guidelines.
- ii.Men 50 years of age and older or women 60 years of age and older and 1 additional risk factor including low HDL-C, impaired fasting glucose, increased waist circumference, cigarette smoking, and hypertension (with additional risk factors including left ventricular hypertrophy).
- iii.Consideration could be given to subjects with other factors including subclinical atherosclerosis (coronary artery calcium [CAC] score > 100), high-sensitivity C-reactive protein ≥ 2 mmol/L, or Lp(a) ≥ 30 mg/dL. These should be considered as less well studied indications for therapy.
- i.
Primary prevention studies
- Sever P.S.
- Dahlof B.
- Poulter N.R.
- et al.
- 1.Statin-indicated conditions: We recommend management that includes statin therapy in high-risk conditions including clinical atherosclerosis, abdominal aortic aneurysm, most DM, CKD (age older than 50 years), and those with LDL-C ≥ 5.0 mmol/L to decrease the risk of CVD events and mortality (Strong Recommendation; High-Quality Evidence).
- 2.Primary prevention:
- i.We recommend management that does not include statin therapy for individuals at low risk (modified FRS < 10%) to decrease the risk of CVD events (Strong Recommendation; High-Quality Evidence).
- ii.We recommend management that includes statin therapy for individuals at high risk (modified FRS ≥ 20%) to decrease the risk of CVD events (Strong Recommendation; High-Quality Evidence).
- iii.We recommend management that includes statin therapy for individuals at IR (modified FRS 10%-19%) with LDL-C ≥ 3.5 mmol/L to decrease the risk of CVD events. Statin therapy should also be considered for IR persons with LDL-C < 3.5 mmol/L but with apoB ≥ 1.2 g/L or non-HDL-C ≥ 4.3 mmol/L or in men 50 years of age and older and women 60 years of age and older with ≥ 1 CV risk factor (Strong Recommendation; High-Quality Evidence).
- i.
CKD
- 1.We recommend treatment with a statin or a statin/ezetimibe combination to reduce CVD events in adults 50 years of age and older with CKD not treated with dialysis or a kidney transplant (Strong Recommendation; High-Quality Evidence).
- 2.We suggest that lipid-lowering therapy not be initiated in adults with dialysis-dependent CKD (Conditional Recommendation; Moderate-Quality Evidence).
- 3.We suggest that lipid-lowering therapy be continued in adults already receiving it at the time of dialysis initiation (Conditional Recommendation; Low-Quality Evidence).
- 4.We suggest the use of statin therapy in adults with kidney transplantation (Conditional Recommendation; Moderate-Quality Evidence).
Secondary Testing
CAC (Agatston score) measurement
- McClelland R.L.
- Jorgensen N.W.
- Budoff M.
- et al.
- Taylor A.J.
- Cerqueira M.
- Hodgson J.M.
- et al.
- 1.We suggest that CAC screening using computed tomography imaging might be appropriate for asymptomatic, middle-aged adults (FRS 10%-20%) for whom treatment decisions are uncertain (Conditional Recommendation; Moderate-Quality Evidence).
- 2.We suggest that CAC screening using computed tomography imaging not be undertaken for: (1) high-risk individuals; (2) patients receiving statin treatment; or (3) most asymptomatic, low-risk adults (Strong Recommendation; Moderate-Quality Evidence).
- 3.We suggest that CAC screening might be considered for a subset of low-risk middle-aged individuals with a family history of premature CHD (men younger than 55 years; women younger than 65 years) (Conditional Recommendation; Low-Quality Evidence).
- 4.We suggest that in patients who warrant risk factor management on the basis of usual criteria, CAC scoring not be undertaken. Moreover, CAC scoring (seeking a result with a value of 0) should not be used as a rationale for withholding otherwise indicated, preventive therapies (Strong Recommendation; Low-Quality Evidence).
Lp(a)
- 1.We suggest that Lp(a) might aid risk assessment in subjects with intermediate FRS or with a family history of premature coronary artery disease (Conditional Recommendation; Moderate-Quality Evidence).
Monitoring, Surveillance, and Targets
- (1)There is high interindividual variability in LDL-C levels attained with statin therapy, and evidence from in-trial achieved lipid parameters indicates that lower LDL-C levels are associated with a lower risk for CV events.56
- (2)RCTs and meta-analyses of statin trials show that the proportional reduction in major CVD events is directly related to the absolute LDL-C reduction that is achieved. In 5 trials conducted in populations targeted for secondary prevention, high-intensity statin therapy resulted in further significant reductions in major CVD events compared with moderate-intensity statin therapy. Relative risk reductions were similar across various levels of baseline risk, and if anything there was a greater relative risk reduction among lower-risk individuals (< 1% per year event rates) targeted for primary prevention. There was no evidence of any threshold within the cholesterol ranges studied.57
- (3)New evidence from the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT),61in which patients with a recent acute coronary syndrome were treated for an average of 7 years, indicates that the combination of ezetimibe with moderate-intensity statin therapy reduces LDL-C levels and CVD events. In this trial, LDL-C was decreased to < 2 mmol/L (average in-trial LDL-C level achieved with statin monotherapy and statin with ezetimibe were 1.8 mmol/L and 1.4 mmol/L, respectively). Thus, this provides further evidence for more aggressive LDL-C-lowering in high-risk patients. However, we acknowledge that more aggressive LDL-C-lowering with other nonstatin lipid-lowering therapies have not resulted in a reduction in CV events. In the Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes (AIM-HIGH)62and Heart Protection Study 2 - Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE)63trials, patients achieved an LDL-C level < 2 mmol/L with the combination of a statin (with or without ezetimibe) and niacin (with or without laropiprant), but this did not translate into a reduction in CV events. The reasons for the lack of benefit with niacin in these trials is not clear but might relate to the population studied already having optimum lipid values.
- (4)Very recently the European Society of Cardiology and American College of Cardiology have recommended the use of targets.64,
- Lloyd-Jones D.M.
- Morris P.B.
- et al.
Writing Committee
2016 ACC expert consensus decision pathway on the role of non-statin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology task force on clinical expert consensus documents.J Am Coll Cardiol. 2016; 68: 92-12565Authors/Task Force Members, Piepoli MF, Hoes AW, Agewall S, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts): Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur J Prev Cardiol 2016;23:NP1-96.
- (5)The use of lipid targets might aid clinicians in optimizing lipid-lowering therapy, and might reinforce patient adherence and provide evidence for patients of the efficacy of treatment.
- 1.We recommend a treat-to-target approach in the management of dyslipidemia to mitigate CVD risk (Strong Recommendation; Moderate-Quality Evidence).
- 1.We recommend a target LDL-C level consistently < 2.0 mmol/L or > 50% reduction of LDL-C for individuals for whom treatment is initiated to decrease the risk of CVD events and mortality (Strong Recommendation; Moderate-Quality Evidence).
- 2.We recommend a > 50% reduction of LDL-C for patients with LDL-C > 5.0 mmol/L in individuals for whom treatment is initiated to decrease the risk of CVD events and mortality (Strong Recommendation; Moderate-Quality Evidence).
- 3.We recommend a target LDL-C consistently < 2.0 mmol/L or > 50% reduction of LDL-C in individuals for whom treatment is initiated to decrease the risk of CVD events (Strong Recommendation; Moderate-Quality Evidence).
Health Behaviour Interventions
- Booth 3rd, J.N.
- Levitan E.B.
- Brown T.M.
- et al.
Smoking cessation
Nutrition therapy
Physical activity
Psychological factors
- 1.We recommend that adults who smoke should receive clinician advice to stop smoking to reduce CVD risk (Strong Recommendation; High-Quality Evidence).
- 1.We recommend that all individuals are offered advice about healthy eating and activity and adopt the Mediterranean dietary pattern to decrease their CVD risk (Strong Recommendation; High-Quality Evidence).
- 2.We recommend that omega-3 PUFAs supplements not be used to reduce CVD events (Strong Recommendation; High-Quality Evidence).
- 3.We suggest that individuals avoid the intake of trans fats and decrease the intake of saturated fats for CVD disease risk reduction (Conditional Recommendation; Moderate-Quality Evidence).
- 4.We suggest that to increase the probability of achieving a CV benefit, individuals should replace saturated fats with polyunsaturated fats (Conditional Recommendation; Moderate-Quality Evidence), emphasizing those from mixed omega-3/omega-6 PUFA sources (eg, canola and soybean oils) (Conditional Recommendation; Moderate-Quality Evidence), and target an intake of saturated fats of < 9% of total energy (Conditional Recommendation; Low-Quality Evidence). If saturated fats are replaced with MUFAs and carbohydrates, then people should choose plant sources of MUFAs (eg, olive oil, canola oil, nuts, and seeds) and high-quality sources of carbohydrates (eg, whole grains and low GI carbohydrates) (Conditional Recommendation; Low-Quality Evidence).
- 1.We suggest that all individuals be encouraged to moderate energy (caloric) intake to achieve and maintain a healthy body weight (Conditional Recommendation; Moderate-Quality Evidence) and adopt a healthy dietary pattern to lower their CVD risk:
- i.Mediterranean dietary pattern (Strong Recommendation; High-Quality Evidence);
- ii.Portfolio dietary pattern (Conditional Recommendation; Moderate-Quality Evidence);
- iii.DASH dietary pattern (Conditional Recommendation; Moderate-Quality Evidence);
- iv.Dietary patterns high in nuts (≥ 30 g/d) (Conditional Recommendation; Moderate-Quality Evidence);
- v.Dietary patterns high in legumes (≥ 4 servings per week) (Conditional Recommendation; Moderate-Quality Evidence);
- vi.Dietary patterns high in olive oil (≥ 60 mL/d) (Conditional Recommendation; Moderate-Quality Evidence);
- vii.Dietary patterns rich in fruits and vegetables (≥ 5 servings per day) (Conditional Recommendation; Moderate-Quality Evidence);
- viii.Dietary patterns high in total fibre (≥ 30 g/d) (Conditional Recommendation; Moderate-Quality Evidence), and whole grains (≥ 3 servings per day) (Conditional Recommendation; Low-Quality Evidence);
- ix.Low glycemic load (Conditional Recommendation; Moderate-Quality Evidence); or low GI (Conditional Recommendation; Low-Quality Evidence) dietary patterns;
- x.Vegetarian dietary patterns (Conditional Recommendation; Very Low-Quality Evidence).
- i.
- 1.We recommend the following dietary components for LDL-C lowering:
- i.Portfolio dietary pattern (Strong Recommendation; High-Quality Evidence);
- ii.Dietary patterns high in nuts (≥ 30 g/d) (Strong Recommendation; High-Quality Evidence);
- iii.Dietary patterns high in soy protein (≥ 30 g/d) (Strong Recommendation; High-Quality Evidence);
- iv.Dietary patterns with plant sterols/stanols (≥ 2 g/d) (Strong Recommendation; High-Quality Evidence);
- v.Dietary patterns high in viscous soluble fibre from oats, barley, psyllium, pectin, or konjac mannan (≥ 10 g/d) (Strong Recommendation; High-Quality Evidence);
- vi.US National Cholesterol Education Program Steps I and II dietary patterns (Strong Recommendation; High-Quality Evidence);
- i.
- 2.We suggest the following dietary patterns for LDL-C lowering:
- i.Dietary patterns high in dietary pulses (≥ 1 serving per day or ≥ 130 g/d) (beans, peas, chickpeas, and lentils) (Conditional Recommendation; Moderate-Quality Evidence);
- ii.Low GI dietary patterns (Conditional Recommendation; Moderate-Quality Evidence);
- iii.DASH dietary pattern (Conditional Recommendation; Moderate-Quality Evidence).
- i.
- 1.We recommend that adults should accumulate at least 150 minutes of moderate- to vigorous-intensity aerobic physical activity per week, in bouts of 10 minutes or more to reduce CVD risk (Strong Recommendation; High-Quality Evidence).
- 1.We recommend combining low-risk lifestyle behaviours that include achieving and maintaining a healthy body weight, healthy diet, regular physical activity, moderate alcohol consumption, and moderate sleep duration to achieve maximal CVD risk reduction (Strong Recommendation; High-Quality Evidence).
Nonstatin Therapy
Ezetimibe
Niacin
Fibrates
Bile acid sequestrants
Proprotein convertase subtilisin kexin 9 inhibitors
- 1.We recommend ezetimibe as second-line therapy to lower LDL-C levels in patients with clinical CVD if targets are not reached with maximally tolerated statin therapy (Strong Recommendation; High-Quality Evidence).
- 2.We recommend that niacin not be combined with statin therapy for CVD prevention in patients who have achieved LDL-C targets (Strong Recommendation; High-Quality Evidence).
- 3.We recommend that fibrates not be combined with statin therapy for CVD event prevention in patients who have achieved LDL-C targets (Strong Recommendation; High-Quality Evidence).
- 4.We suggest that BASs be considered for LDL-C lowering in high-risk patients whose levels remain above target despite statin treatment with or without ezetimibe therapy (Conditional Recommendation; Low-Quality Evidence).
- 5.We suggest the use of PCSK9 inhibitors (evolocumab, alirocumab) to lower LDL-C for patients with heterozygous familial hypercholesterolemia whose LDL-C level remains above target level despite maximally tolerated statin therapy (Conditional Recommendation; Moderate-Quality Evidence).
- 6.We suggest that PCSK9 inhibitors be considered to lower LDL-C level for patients with atherosclerotic CVD in those not at LDL-C goal despite maximally tolerated statin doses with or without ezetimibe therapy (Conditional Recommendation; Moderate-Quality Evidence).
- 7.We suggest that lomitapide and mipomersen (not approved in Canada) might be considered exclusively in patients with homozygous familial hypercholesterolemia (Conditional Recommendation; Moderate-Quality Evidence).

Potential Adverse Effects of Statins
- 1.We recommend that despite concerns about a variety of possible adverse effects, all purported statin-associated symptoms should be evaluated systematically, incorporating observation during cessation, reinitiation (same or different statin, same or lower potency, same or decreased frequency of dosing) to identify a tolerated, statin-based therapy for chronic use (Strong Recommendation; Low-Quality Evidence).
- 2.We recommend that vitamins, minerals, or supplements for symptoms of myalgia perceived to be statin-associated not be used (Strong Recommendation; Low-Quality Evidence).
Practical Approach
Conclusions
Acknowledgements
Supplementary Material
- Supplementary Material
References
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This statement was developed following a thorough consideration of medical literature and the best available evidence and clinical experience. It represents the consensus of a Canadian panel comprised of multidisciplinary experts on this topic with a mandate to formulate disease-specific recommendations. These recommendations are aimed to provide a reasonable and practical approach to care for specialists and allied health professionals obliged with the duty of bestowing optimal care to patients and families, and can be subject to change as scientific knowledge and technology advance and as practice patterns evolve. The statement is not intended to be a substitute for physicians using their individual judgement in managing clinical care in consultation with the patient, with appropriate regard to all the individual circumstances of the patient, diagnostic and treatment options available and available resources. Adherence to these recommendations will not necessarily produce successful outcomes in every case.