This guideline provides recommendations on the primary prevention of atherosclerotic cardiovascular disease (ASCVD/CVD) in adults aged 19 years without clinical CVD. It does not apply to patients with a known history of CVD or who currently have signs or symptoms of CVD, as this would require treatment and secondary prevention. The recommendations include how to assess a patient's risk of CVD and how to manage their CVD risk factors. Familial hypercholesterolemia (FH) and other genetic dyslipidaemias are out of scope of this guideline. Practitioners are recommended to access Canadian Cardiovascular Society guidelines that address this condition. 1 For updated guidance on secondary prevention practitioners are recommended to access the 2021 Canadian Cardiovascular Society guidelines. 2 Key Recommendations - Assess CVD risk in all asymptomatic adults 40 years of age . 2-5 - Health behaviour change (e.g., smoking cessation, healthy diet) is recommended as the first-line intervention for all risk groups in CVD primary prevention. Pharmacological management is recommended for high risk groups . 2,4,5 - Initiate statin therapy only after objectively evaluating the person's individual risks, benefits and preferences, and by having an individualized discussion with the patient. Initiate pharmaceutical management after considering the patient's overall individual risk. Treatment with a statin is expected to result in a significant reduction (30 -50%) in the elevated baseline lipid levels . 5-8 - Reducing LDL-C using statin and/or non-pharmacological management is recommended as each 1 mmol/L decrease in LDL-C results in a 20-22% relative risk reduction of major vascular events . 2,9 - The use of aspirin to reduce risk of morbidity or mortality may only be beneficial to certain individuals. . 5,10,11 - Recommendation against the use of over-the-counter omega-3 PUFA to reduce CVD risk. .# Assessment of Risk Who to Assess
Consider assessing CVD risk in: - all asymptomatic men and women 40 years to establish a baseline 4,5 (Note: Lifetime Prevention Schedule, Ministry of Health, BC, recommends screening men 40 years and women 50 years); - all patients with pre-existing risk-related conditions (e.g., HTN, DM, CKD); and - all patients with a known family history of premature CVD (defined as men aged <55 years and women aged <65 years in first degree relatives). - A patient may be reassessed in 1 to 5 years depending on their initial risk assessment or if their risk factors change significantly. For further details, refer to Appendix A: Primary Prevention of Cardiovascular Disease Algorithm.

# Risk Assessment a. Risk assessment tool:
The Framingham Risk Score (FRS) is recommended.  The FRS, or any CVD risk assessment tool, is a risk estimation only of a patient's CVD risk. Since these scores are plus or minus several percentage points, it is important to consider modifying the risk estimation based on other known risk factors (e.g., family history, ethnicity) and a practitioner's clinical judgement. For example, the Canadian Cardiovascular Society (CCS) suggests that among individuals 30 -59 years of age without diabetes, the presence of a positive history of premature CVD in first degree relatives increases a patient's FRS by approximately 2-fold. 4 b. In addition to the FRS, other risk assessment tools include Absolute CVD Risk/Benefit Calculator from James McCormack (for patients 80 years), the University of Edinburgh Cardiovascular Risk Calculator, the United Kingdom Prospective Diabetes Study (UKPDS) risk calculator that estimates the 10-year CHD and stroke risk for adults with type 2 diabetes and QRISK3 risk calculator (for patients 84 years). For additional details on the risk assessment tools, refer to Associated Document: Resource Guide for Physicians -Tools for Primary Prevention of Cardiovascular Disease. Paper-based scores use groups of measurements for the risk factors to assign points; and online calculators use the exact measurements for the risk factors.
A risk score from an online calculator allows for a more individualized estimate of risk .
- Non-modifiable risk factors include:   age -chronological and biological age,  biological sex (men)  family history of CVD or familial hyperlipidemia (1st degree relative with ASCVD -men <55 years and women <65 years)  ethnicity (First Nations, 12 South Asians (defined as Indian, Pakistani, Bangladeshi or Sri Lankan origin)) 13 For any individual, it is imperative that the health needs of that individual as it relates to their racial/ethnic background (e.g., South Asians) is critically examined to ensure culturally appropriate medical and health decisions. 14  chronic kidney disease, chronic inflammatory diseases (e.g., rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, vasculitis (polyarteritis nodosa)), HIV infection, hypertensive diseases of pregnancy, Polycystic Ovarian Syndrome, gestational diabetes. - The modifiable risk factors are listed in 

# Modifiable Risk Factors Mitigation Strategy Resources

# Smoking
Smoking cessation is probably the most important health behaviour intervention for the prevention of CVD. 15,16 A linear relation exists between number of cigarettes smoked per day and CVD risk. 17 

# QuitNow BC Smoking Cessation Program
HealthLinkBC: Quitting Smoking Unhealthy diet A diet rich in vegetables, fruits, legumes, nuts, whole grains, fish and lean proteins with inherent soluble and insoluble vegetable fiber has been consistently shown to be associated with lower all cause mortality.  HealthLinkBC: Heart Healthy Eating

# DASH diet
Canada's Food Guide

# Low physical activity/sedentary behaviour
Engaging in at least 150 minutes per week of accumulated moderate to vigorous-intensity aerobic physical activity is associated with reduced ASCVD.  HealthLinkBC: Physical Activity 

# Reduction in alcohol consumption
Reduction in alcohol intake may lower blood pressure. 29 HealthlinkBC: Low-risk drinking guidelines Canada's Low-Risk Alcohol Drinking Guidelines BCGuidelines: Problem Drinking Hypertension High blood pressure has been shown to increase cardiovascular risk.  Adapt health behaviours to reduce blood pressure levels. Pharmacological management may be needed for some patients along with healthy behaviour changes.

# BCGuidelines: Hypertension -Diagnosis and Management
HealthlinkBC: Lifestyle Steps to Lower Your High Blood Pressure Hypertension Canada: Hypertension and You

# Diabetes Mellitus
Diabetes Mellitus is associated with 2-4 fold increase in CVD. 33,34 Adherence to a healthier behaviours in those with type 2 diabetes is associated with lower CVD risk. 35 BCGuidelines: Socio-economic factors may confer a risk equivalent to traditional risk factors. 39,42 Health education, community-based programs, and behavioural counselling have all been suggested to address the impact of these factors on CVD risk.
Diabetes
Links to some clinical practice tools that can help practitioners improve their performance in identifying and taking action on the root causes of poor health. 43 Prescribed medications 44 Some medications, including thiazide diuretics, beta blockers, and oral estrogens can cause modest changes in serum lipid concentrations. Some of the atypical antipsychotic agents, in particular clozapine and olanzapine, have been associated with weight gain, obesity, hypertriglyceridemia, and development of diabetes mellitus. 

# h. Assessment Stratification
The patient can be classified as low, intermediate, or high risk for CVD based on the risk assessment. Any patient that is considered very high risk or is symptomatic (defined as secondary prevention -out of the scope of this guideline) should be treated accordingly. The FRS defines low risk as <10%, intermediate risk as 10 -19% and high risk as 20%. These groupings are an arbitrary convenience, not a scientifically validated stratification.
A patient in the intermediate risk group may warrant a secondary assessment to raise or lower their risk stratification. However, further investigations may not be appropriate if the results would not influence the decision of how to manage the risk or treat the patient.
Secondary assessment should be done on patients for whom treatment decisions are uncertain. These assessments may include carotid ultrasound, hsCRP, or coronary artery calcium (CAC) scoring. Updated guidance on the use of CAC is recommended by the CCS 2021 guidelines. 2 Conduct a shared decision-making conversation regarding healthy behaviour modifications and if necessary pharmacological interventions. Consider using cardiovascular age during the discussion. Cardiovascular (CV) age using the Cardiovascular Life Expectancy Model (CLEM) is calculated as the patient's age minus the difference between his or her estimated remaining life expectancy (adjusted for coronary and stroke risk) and the average remaining life expectancy of Canadians of the same age and sex (chiprehab.com/index.html). 4,48 

# Management of Risk Healthy Behaviour
Healthy behaviour modifications need to be strongly advocated as the first-line intervention for all risk groups. Adequate explanations and support should be provided to patients, so they clearly understand the nature and significance of CVD, and that they have the primary responsibility for adopting the healthy behaviour changes required for reducing their risk.

# Use the prevention visit code -14066 for discussions related to management of modifiable risks. Diagnostics codes that require a prevention focused advice include smoking (786), unhealthy eating and medical obesity (783), physically inactive (785).
a. Smoking: Promote smoking cessation and avoidance of second-hand smoke. Behavioral and pharmacotherapy interventions, alone or in combination, have been shown to improve rates of smoking cessation among the general adult population. 49,50 Use a Screening, Brief Intervention and Referral to Treatment (SBIRT) approach. 51 When talking to a patient about smoking: 1) Screen for use 2) Conduct a Brief Intervention by providing risks of behaviour 3) Assess for willingness to quit 4) Support behaviour change by connecting to resources or treatment.
- For support to quit, refer patients to:  QuitNow at www.quitnow.ca/  HealthLinkBC Quitting Smoking -Patients can call 8-1-1 or visit the website www.healthlinkbc.ca/mental-healthsubstance-use/quitting-smoking.  BC Smoking Cessation Program at www.gov.bc.ca/bcsmokingcessation  Smokers' Helpline at 1-866-366-3667 or online at SmokersHelpline.ca - For more information on effective pharmacological aids for smoking cessation, refer to BC Smoking Cessation program.
- Electronic cigarettes, also known as e-cigarettes, vaping (available with or without nicotine), may play a role as an aid in smoking cessation. At present time, their risk and benefits have not been clearly established  and are not included as a pharmacological aid.
b. Physical Activity: Support patient working towards 30 minutes or more of moderate to vigorous intensity physical activity on most days of the week (weekly total 150 minutes). 25,55 Behavioural interventions for healthful diet and physical activity have been shown to generally improve participants' dietary intake and physical activity levels at 6 to 12 months of followup. 56 Techniques such as motivational interviewing and brief action planning, that promote collaborative engagement with the patient, are more effective than exercise prescription alone for patients to achieve their physical activity goals.
- Exercise stress test may be warranted for previously sedentary people with additional risk factors for CVD who wish to undertake exercise more vigorous than brisk walking. 4 - For patients who are sedentary, consider a graduated exercise program using Brief Action Planning (BAP).
- Engage the patients in completing a Physical Activity Readiness Questionnaire for Everyone (PAR-Q+) and electronic Physical Activity Readiness Medical Examination (ePARmed-X+) to help them determine their readiness. Refer them to an accessible exercise program (such as healthy heart programs). - For assistance with personalized physical activity advice, refer patient to a physical activity expert at HealthLinkBC or by telephone at 8-1-1.
c. Diet: Encourage a well-balanced diet. There are many dietary pathways to achieve CV risk reduction such as the Mediterranean diet (which emphasizes fruits, vegetables, legumes, whole grains and olive oil, with moderate consumption of fish, dairy products, poultry and minimizing meats and sweets) or the Dietary Approaches to Stop Hypertension (DASH) diet. 4 - For assistance with personalized diet advice, refer patient to a dietitian at HealthLinkBC by telephone 8-1-1 or website: www.healthlinkbc.ca.

# d. Alcohol Consumption:
Screen for alcohol abuse. Use a Screening, Brief Intervention, and Referral for Treatment (SBIRT) approach.

# Follow-up to Healthy Behaviour Modifications
- Assess success of healthy behaviour intervention change at first follow-up.
- Assess cardiovascular risk using lipid profile (non-fasting)
- For those with elevated lipids from their initial risk assessment, they may be followed up with a lipid profile in 3 -6 months. If elevated lipids are still a concern, consider pharmaceutical management. - Studies consistently demonstrate a 20-22% relative risk reduction for each 1 mmol/L reduction in low-density lipoprotein cholesterol (LDL-C). 9 The absolute risk reduction is thus dependent upon the baseline risk and the baseline LDL-C, as statin treatment will provide a greater absolute LDL-C lowering in those with higher baseline values. 2 Both non-HDL-C and ApoB appear to be stronger predictors than LDL-C for major future cardiovascular events. 2,57,58 Non-HDL-C may also be a better indicator of residual risk after statin therapy than LDL-C. 59 ApoB is not available with lipid profiles unless diagnosis of complex dyslipidemia is indicated.

# Pharmaceutical Management
Acetylsalicylic Acid (ASA) Therapy ASA therapy in Primary Prevention: Evidence does not support the use of aspirin in low and intermediate risk patients. The evidence for use of aspirin in high risk patients is currently uncertain. 5,60 Use of aspirin in people >75 may further heighten the risk of clinical significant bleeding. 61 

# Statin Therapy
For those patients with DM, CKD, or Familial Hyperdyslipidemia, statin therapy is indicated along with healthy behaviour interventions. Prior to the initiation of statin therapy:
- inform the patient of adverse effects  -effects may include muscle pain/myopathy/weakness, rhabdomyolysis, cataracts, elevated blood glucose and diabetes, acute renal failure, and liver injury; - educate the patient about any possible drug interactions with other prescribed medication, over-the-counter remedies and non-pharmaceuticals -consult a pharmacist or product monograph for a complete list; and - emphasize the importance of long-term compliance -it is estimated that 75% of primary prevention patients aged >65 years old started on statins stop their therapy within 2 years. 66 Follow-up to Statin Therapy Within 3 -6 months of the initiation of statin therapy, follow-up with the patient. This may include:
- Measure lipids with a non-HDL-C or an ApoB to assess patient adherence to statin therapy and any response to statin therapy (see Controversies in Care). A full lipid profile is not indicated. If both healthy behaviour intervention and a statin intervention have not been successful and lipids are still above target in the follow-up investigation, consider any other causes of elevated lipids (e.g., hypothyroidism, non-adherence). - Inquire about any adverse effects. The risk of statin-induced serious muscle injury, including rhabdomyolysis, is 5X). 63 - Measure liver transaminase enzyme (alanine aminotransferase (ALT)) only once within the first 3 months of starting statin. If a patient has elevated liver transaminase enzymes, (greater than 3X the normal) consider secondary causes. 65 Further follow-ups as clinically needed. After the initial follow-up, routine monitoring of CK and ALT is not indicated for asymptomatic patients. More frequent routine monitoring with a full lipid profile, non-HDL-C or an ApoB is not considered necessary for the sole purpose of treat-to-target.

# When to Refer Patients to a Specialist
Consider referral to a specialist when there is:
- Difficulty reaching treatment targets despite maximum-tolerated lipid-lowering therapy.
- Intolerance to or adverse effects of statin treatment. Statin intolerance needs to be well documented prior to referral. 63 

# Controversies in Care Statin Therapy in Primary Prevention
Both the Canadian Cardiovascular Society (CCS) 4 and the American Heart Association (ACC/AHA)5 acknowledge that there is high interindividual variability in LDL-C levels attained with statin therapy. They agree that recent studies have demonstrated lower CVD event rates with moderate-intensity and high-intensity statin therapy that outweighed the observable risks. 4,5,67 The 2016 USPSTF systematic review of statin therapy in primary prevention showed a reduced risk of all-cause and cardiovascular mortality and ASCVD events and noted greater absolute benefits in those at greater baseline risk. 68 both the CCS and ACC/AHA have recommended a more aggressive approach for statin use (see 

# CKD or high risk HTN Treat with statins.
No specific recommendation.

# Statin Use for Primary Prevention in the Elderly Population
The CCS and the ACC/AHA guidelines both recommend discussion of statin use with elderly patients who are believed to be at higher risk. 2,4,5,69 There are randomized controlled trials currently underway specifically assessing statins in primary prevention in this population.

# Treatment Goals
- Both the CCS 4 and the ACC/AHA 5 acknowledge there is controversy regarding the use of lipid treatment targets. This guideline is aligned with the current CCS (2021) recommendations in that treatment with maximally tolerated statins is recommended. If thresholds are not achieved, add-on therapy should be considered.

# Management of Other Clinical Conditions 
A number of clinical conditions contribute significantly to the risk of developing CVD.

# Blood Pressure Control
Support healthy behaviour modifications, followed by the use of antihypertensive medications when appropriate, with consideration for the presence of other CVD risk factors.

# For more information, refer to BCGuidelines.ca -Hypertension -Diagnosis and Management.
Diabetes Care Support healthy behaviour modifications followed by the use of medications when appropriate to control blood glucose. DM is a major risk factor for CVD, but a patient with DM does not need to be automatically considered high risk for CVD. CCS defines a patient with DM high risk for CVD with age 40 years, >15-year duration for age 30 years (type 1 diabetes mellitus), or with the presence of microvascular disease. While the current FRS now includes diabetic status to individualize a type 2 DM patient's risk, use the United Kingdom Prospective Diabetes (UKPDS) risk calculator or table, website: www.dtu.ox.ac.uk/riskengine. For more information, refer to BCGuidelines.ca -Diabetes Care.

# CKD Management
In patients with CKD, the combination of simvastatin plus ezetimibe has shown benefit in reducing major atherosclerotic events when compared to placebo; however, no benefit on all-cause mortality has been demonstrated. 70 For more information, refer to BCGuidelines.ca -Chronic Kidney Disease -Identification, Evaluation and Management of Adult Patients.

# Methodology
These guideline recommendations are tailored to support practice in British Columbia and are based on guidance by the Canadian Cardiovascular Society (CCS) 2,4 , American Cardiology/American Heart Association (ACC/AHA) 5 , and the European of Cardiology 6 . The guideline development working group used the AGREE II tool to assess the 6 domains and the overall guideline assessment. The working group looked at the three guidelines mentioned above carefully to identify the Scope of Purpose, Stakeholder Involvement, Rigor of Development, Clarity of Presentation, Applicability, Editorial Independence and made an assessment of the overall guideline quality. The AGREE II scores of the guidelines from the working group members showed some variation in domain scoring by individual members but overall agreement of the variation in the quality of these guidelines. The team gained a significant appreciation of both the methodology behind the three guidelines as well as the content and were able to use information from all of them in the GPAC guideline development. The working group started with the draft of the previous version of the GPAC guideline and studied the recommendations from the other three groups to inform this updated version. Where available, key references are provided. In situations where there is a lack of rigorous evidence, we provide best clinical opinion to support decision making and high-quality patient care. The guideline development process included significant engagement and consultation with primary care providers, specialists and key stakeholders, including the Provincial Laboratory Medicine Services. For more information about GPAC guideline development processes, refer to the GPAC handbook available at BCGuidelines.ca. 

# Resources

# Health Data Coalition -hdcbc.ca
An online, physician-led data sharing platform that can assist you in assessing your own practice in areas such as chronic disease management or medication prescribing. HDC data can graphically represent patients in your practice with chronic kidney disease in a clear and simple fashion, allowing for reflection on practice and tracking improvements over time.
HealthLinkBC -healthlinkbc.ca HealthLinkBC provides reliable non-emergency health information and advice to patients in BC. Information and advice on managing Diabetes in several languages is available by telephone, website, a mobile app and a collection of print resources.
People can speak to a health services navigator, registered dietitian, registered nurse, qualified exercise professional, or a pharmacist by calling 8-1-1 toll-free in B.C, or 7-1-1 for the deaf and hard of hearing.

# Diagnostic Codes
Prevention visit code -14066

# Smoking -786
Unhealthy eating and medical obesity -783
Physically inactive -785

# Appendices
Undertake a patient-specific discussion regarding the potential risks and benefits of statin use Confirm adherence and barriers to use Follow-up 3-6 months: LDL-C  50% reduction or ApoB < 0.8 g/L or non-HDL-C < 2.6mmol/L

# Consider Statin Treatment
Evaluate CVD risk vs. additional side effects and cost

# Discuss add-on therapy

# Target achieved on maximally tolerated dose
Calculate risk in all adults  40 using the Framingham risk Score (FRS) or another tool of choice. Statins are associated with a dose-dependent risk of elevated liver enzymes (NNH of 96).4 Investigations are warranted if ALT >3 times the upper limit of normal.
Statin therapy was not associated with cognitive impairment in a meta-analysis of RCTs involving cognitively normal and cognitively impaired patients. 10 Management options for the above adverse effects include statin discontinuation, switching to an alternative statin, dose decreases, and alternate day dosing. 4,5 Data on efficacy of these management options is limited or missing.
Abbreviations: BID = twice daily; CrCl = creatinine clearance in milliliters per minute; G = generics available; mg = milligram; RDP = reference drug program; Tabs = tablets;
Footnotes: a Not an exhaustive list; b Consult product monograph for detailed dosing instructions, dose adjustments for unique patient populations, and drug interactions. Product monographs available from Government of Canada: Drug Product Database, Health Canada advisories, warnings and recalls available from Government of Canada: Recalls and Safety Alerts, and drug interaction software such a Lexicomp. c For normal renal and hepatic function. Consult product monograph for detailed dosing instructions and dose adjustments for unique patient populations. d Pricing is approximate as of Dec 2021 and does not include dispensing fees or additional markups. Note: Information on which products PharmaCare covers can be obtained using the B.C. PharmaCare Formulary Search *Reimbursement is subject to the rules of a patient's PharmaCare plan, including any deductibles. In all cases, coverage is subject to drug price limits set by PharmaCare: Drug Coverage.
PharmaCare

# Associated Documents
Resource Guide for Physicians -Tools for Primary Prevention of Cardiovascular Disease
The principles of the Guidelines and Protocols Advisory Committee are to: