Primary Prevention of Atherosclerotic Cardiovascular Disease

Primary prevention of atherosclerotic cardiovascular disease (ASCVD) is the systematic identification and treatment of cardiovascular risk factors in a patient who has not yet had a myocardial infarction, stroke, transient ischemic attack, or other clinical manifestation of atherosclerosis — as distinct from secondary prevention, which treats a patient who already has established disease and therefore starts from a much higher baseline risk.^[1] ASCVD develops silently over decades as plaque accumulates in the coronary, cerebral, and peripheral arteries; the goal of primary prevention is to intervene early enough, and intensively enough, to prevent that plaque from ever causing a clinical event.

Because a primary-prevention patient is by definition asymptomatic, the absolute benefit of any single intervention is smaller than the same intervention would provide in secondary prevention, and the balance of benefit against harm is closer — nowhere more so than for aspirin, where the evidence base has shifted substantially in the past decade (see Choose Initial Treatment). This chapter covers the whole-person risk-assessment framework Canadian guidelines use to match treatment intensity to a patient's actual risk — validated risk calculators, the risk-enhancing factors that refine a borderline decision, statin therapy by risk category, and the foundational role of lifestyle change — while cross-referencing the Hypertension and Diabetes Mellitus chapters for the detailed management of those individual risk factors rather than duplicating it here. Pharmacists are well positioned to run this whole process: identifying unscreened risk factors, calculating and explaining a risk score, supporting lifestyle change, and reassessing whether a long-standing prescription — aspirin, in particular — still matches current evidence.

Who this applies to

A primary-prevention patient has no diagnosed coronary artery disease, cerebrovascular disease, peripheral arterial disease, or abdominal aortic aneurysm.^[1] The first task in any risk assessment is confirming this is genuinely true — a patient with any of these conditions is a secondary-prevention patient by definition, already at a level of risk that places them in the highest treatment-intensity category regardless of any calculated score (see Assessment & Diagnosis).

History and exam findings that reclassify a patient before formal risk scoring

Any of the following findings mean atherosclerosis is already clinically or subclinically established, and the patient should be managed at the high-risk/statin-indicated intensity described in Treatment Targets rather than proceeding to a Framingham Risk Score calculation:

• A diminished or absent peripheral pulse, or a carotid, femoral, or abdominal bruit on examination.
• An ankle-brachial index below 0.9, suggesting peripheral arterial disease.
• A documented coronary or carotid stenosis of any degree on prior imaging, even if asymptomatic.
• A palpable pulsatile abdominal mass, or an abdominal aorta measuring more than 3 cm on any prior imaging (abdominal aortic aneurysm).
• A history of a coronary or peripheral revascularization procedure, however remote.

Outside of these specific findings, primary prevention itself is clinically silent — most patients feel entirely well, which is exactly why systematic, scheduled risk assessment, rather than waiting for a symptom to prompt it, is the basis of this chapter.

Modifiable

• Tobacco use, including secondhand smoke exposure.
• Hypertension.
• Dyslipidemia.
• Diabetes mellitus and prediabetes.
• Physical inactivity.
• An unhealthy dietary pattern.
• Obesity, particularly abdominal/visceral obesity.

Nonmodifiable

• Age (men over 45, women over 50).
• Male sex.
• Family history of premature cardiovascular disease — a myocardial infarction, stroke, or revascularization in a first-degree relative before age 55 in a man or age 65 in a woman.

Other risk factors and risk-modifying considerations

• Chronic inflammatory disease — rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, inflammatory bowel disease, ankylosing spondylitis.
• Metabolic syndrome.
• HIV infection.
• Chronic kidney disease.
• Poor sleep duration or quality.
• Socioeconomic and structural determinants of health — income, food security, housing, and access to care all independently affect cardiovascular risk and the ability to act on risk-reduction counselling.
• Obstetric and gynecological history — a hypertensive disorder of pregnancy, gestational diabetes, or premature menopause each independently raise future cardiovascular risk and should prompt earlier screening.
• Race and ethnicity — some risk calculators and guidelines include ethnicity (for example, South Asian or Indigenous ancestry) as an independent risk-modifying factor. This reflects real epidemiologic data, but it may also reflect structural inequities in access to the social determinants of health rather than biology alone — either way, using it to prompt earlier or more attentive screening in these populations can improve outcomes, and a reassuringly low calculated risk score should not be taken entirely at face value in these groups (see Assessment & Diagnosis).

Who and when to screen

Perform a global cardiovascular risk assessment in every adult 40-75 years of age, repeated every 5 years or sooner if risk status changes; begin earlier, or screen more frequently, in a patient who already has a risk factor listed above.^[1] Consider starting risk assessment earlier in patients who are South Asian, Indigenous, or recent immigrants from a population with elevated cardiovascular risk, since standard risk calculators have not been validated in these groups and may understate true risk (see Risk-Enhancing Factors below).

• Blood pressure — measured at every appropriate visit in every adult.
• Lipid panel — every 5 years starting at age 40 (men and women), or at any age if a risk factor is present; a nonfasting sample is acceptable for routine screening.
• Diabetes screening (HbA1c or fasting glucose) — every 3 years starting at age 40, or at any age with an additional risk factor.
• Height, weight, BMI, and waist circumference — at every appropriate visit.
• Tobacco use status — at every appropriate visit.

History

• Personal history of hypertension, dyslipidemia, diabetes, or tobacco use, and how well each is currently controlled.
• Family history of premature cardiovascular disease (first-degree relative: before 55 years in a man, before 65 years in a woman).
• Diet, physical activity level, and alcohol use.
• Obstetric history — hypertensive disorders of pregnancy, gestational diabetes.
• Menopausal status and age at menopause.
• Erectile dysfunction — a marker of vascular disease that can precede a coronary event.
• Symptoms suggesting existing cardiovascular disease — exertional chest discomfort, dyspnea, claudication, or a prior stroke/TIA — which would reclassify the patient to secondary prevention (see Recognize the Condition).

Physical examination

• Blood pressure, measured in both arms at the initial assessment.
• Height, weight, BMI, and waist circumference.
• Peripheral pulses and auscultation for carotid, femoral, and abdominal bruits.
• Fundoscopy for hypertensive or diabetic retinopathy where relevant.

Laboratory testing

See Dyslipidemias for the complete lipid-panel interpretation and secondary-cause work-up, and Diabetes Mellitus for glycemic diagnostic criteria — the tests below are the minimum panel for a global risk assessment.

• Lipid panel: total cholesterol, HDL-C, and calculated or directly measured LDL-C.
• Fasting glucose or HbA1c.
• Serum creatinine with estimated GFR.

Cardiovascular risk assessment tools

Once modifiable and nonmodifiable risk factors have been identified, use a validated multivariable risk calculator to translate them into a single absolute risk estimate — this individualizes the assessment, supports shared decision-making with the patient, and has been shown to improve uptake of risk-factor-modification advice compared with an unstructured discussion of individual risk factors.^[1]

The Framingham Risk Score (FRS) is the tool recommended by the Canadian Cardiovascular Society and used throughout Canadian primary-care practice. It combines age, sex, total cholesterol, HDL-C, systolic blood pressure (with separate point values depending on whether the patient is being treated for hypertension), and current smoking status into an estimated 10-year risk of a first major cardiovascular event.^[2] The complete point-by-point worksheet for calculating an FRS score by hand is presented in the Dyslipidemias chapter; this chapter focuses on how the resulting score is used to make a treatment decision.

In the United States, the equivalent tool has recently changed: the older Pooled Cohort Equations^[3] have been superseded by the newer AHA PREVENT equations, which extend the age range down to 30 years, remove race as an input, and add kidney function (eGFR) and BMI as core variables.^[4]

Risk stratification and treatment thresholds

Before calculating a score, confirm the patient does not already have a condition that places them in the high-risk category automatically: established ASCVD, an abdominal aortic aneurysm, diabetes mellitus meeting age/duration criteria, chronic kidney disease meeting age/eGFR/albuminuria criteria, or LDL-C 5 mmol/L or higher (or documented familial hypercholesterolemia) — see Dyslipidemias for the exact criteria for each. Any of these bypasses score calculation entirely; the patient is high-risk by definition.

A family history of premature cardiovascular disease doubles the calculated 10-year risk percentage for patients 30-59 years of age without diabetes — apply this "modified FRS" adjustment before assigning the risk category.^[2]

Risk-enhancing factors that refine an intermediate-risk decision

An FRS in the intermediate range does not, by itself, answer whether to start a statin — the following risk-enhancing factors are used to decide which intermediate-risk patients benefit most from earlier pharmacotherapy and which can reasonably continue with lifestyle measures alone:^[5]

• Family history of premature coronary artery disease in a first-degree relative (before 55 years in a man, before 65 years in a woman) — beyond its role in the modified FRS above, its presence alongside other risk-enhancing factors further supports earlier treatment.
• Ethnicity — South Asian or Indigenous ancestry is associated with higher cardiovascular risk than standard calculators capture; treat a reassuringly low score with caution in these populations and weigh other risk-enhancing factors more heavily.
• High-sensitivity C-reactive protein (hsCRP) 2.0 mg/L or higher — a marker of vascular inflammation independently associated with cardiovascular risk.
• Lipoprotein(a) [Lp(a)] 100 nmol/L or higher (approximately 50 mg/dL or higher) — measured once in a patient's lifetime as part of an initial lipid panel; an elevated result is a genetic, largely non-modifiable risk factor that argues for earlier statin therapy.
• Coronary artery calcium (CAC) score — a non-contrast CT scan that directly quantifies calcified plaque in the coronary arteries, reported as an Agatston score. It is the most direct way to "see" a patient's actual atherosclerotic burden rather than infer it from risk factors, and is specifically useful for reclassifying an intermediate-risk patient up or down.

Assessing bleeding risk before any aspirin discussion

Because aspirin's bleeding risk is what has shifted the evidence away from routine primary-prevention use (see Choose Initial Treatment), assess these factors in any patient for whom aspirin is even being discussed, and in any patient already taking it for this indication:

• History of gastrointestinal bleeding or peptic ulcer disease.
• Bleeding from any other site.
• Age over 70 years.
• Thrombocytopenia.
• Coagulopathy.
• Chronic kidney disease.
• Concurrent use of an NSAID, a COX-2 inhibitor, a corticosteroid, or an anticoagulant.
• Uncontrolled hypertension.

• Reduce the lifetime risk of myocardial infarction, stroke, and peripheral arterial disease/amputation.
• Reduce cardiovascular and all-cause mortality.
• Achieve blood pressure control per the current Hypertension chapter target (systolic BP under 130 mmHg for most adults, with drug therapy started at 140/90 mmHg or higher generally, or at systolic BP 130-139 mmHg in a patient already at high cardiovascular risk).
• Achieve the individualized glycemic target for a patient with diabetes, per the Diabetes Mellitus chapter (HbA1c 7.0% or lower for most adults).
• Reach the LDL-C/ApoB/non-HDL-C target for the patient's risk category once a statin is indicated — see Dyslipidemias for the complete target table.
• Achieve a BMI of 18.5-24.9 kg/m² and a waist circumference under 102 cm (men) or 88 cm (women).
• Complete tobacco cessation.
• Minimize adverse effects from any drug therapy started for risk reduction.

Lifestyle intervention is the foundation of primary prevention at every risk level, and is never replaced by drug therapy once it starts — reinforce it at every visit regardless of what medications are also prescribed.^[1]

Diet

Any of the following dietary patterns is associated with reduced cardiovascular risk; recommend whichever fits the patient's preferences and cultural context rather than defaulting to one:^[1]

• Mediterranean dietary pattern.
• Portfolio dietary pattern.
• DASH (Dietary Approaches to Stop Hypertension) pattern.
• Low glycemic-index or low glycemic-load pattern.
• A plant-based dietary pattern.

Within any pattern, encourage: nuts (at least 30 g/day), legumes (at least 4 servings/week), olive oil (at least 60 mL/day), fruits and vegetables (at least 5 servings/day), and total dietary fibre (at least 30 g/day, including at least 3 servings/day of whole grains).

Sodium and potassium

Reduce sodium intake toward 2 g/day (5 g of salt, or 87 mmol of sodium).^[1] Increase dietary potassium (fresh fruits, vegetables, legumes) to support blood pressure control, with caution in chronic kidney disease (eGFR under 45 mL/min/1.73 m²), heart failure, concurrent use of a potassium-sparing diuretic or an ACE inhibitor/ARB, or a baseline potassium above 4.5 mmol/L.

Physical activity

At least 150 minutes/week of moderate-to-vigorous aerobic activity, accumulated in bouts of 10 minutes or more, plus muscle- and bone-strengthening activity using major muscle groups at least 2 days/week.^[8]

Body weight

Target a BMI of 18.5-24.9 kg/m² and a waist circumference under 102 cm (men) or under 88 cm (women). Offer a comprehensive lifestyle intervention program (diet, physical activity, and behavioural support together) to any patient who is overweight or obese. Pharmacotherapy for obesity may be considered when lifestyle measures alone do not achieve clinically meaningful weight loss — see Diabetes Mellitus for antihyperglycemic agents that combine glycemic and weight benefit in a patient who also has diabetes. Bariatric surgery is an option for a BMI of 40 kg/m² or higher, or 35-39.9 kg/m² with an obesity-related comorbidity.

Alcohol

Recommend reducing alcohol intake — current Canadian guidance frames risk to health as increasing with the amount consumed, with no level of drinking shown to improve cardiovascular outcomes. For a patient who chooses to continue drinking, more than 2 standard drinks/week meaningfully increases health risk, and more than 6 standard drinks/week is high-risk drinking.^[9] One standard drink contains about 13.6 g of alcohol (45 mL of spirits, 150 mL of table wine, or 360 mL of beer).

Smoking cessation

Advise complete cessation and minimize secondhand smoke exposure at every visit.^[1] Combine behavioural support (in person or by telephone) with pharmacotherapy — varenicline, bupropion, or nicotine replacement therapy — rather than relying on either alone; the combination consistently outperforms either approach used in isolation (see Pharmacologic Treatment Options). Do not recommend e-cigarettes as a cessation aid — evidence for their efficacy and long-term safety is insufficient, and Health Canada has warned of a risk of vaping-associated pulmonary illness.

Nutritional supplements — what the evidence does and does not support

Antioxidant supplements (selenium, beta-carotene, vitamin A, vitamin C, vitamin E), homocysteine-lowering vitamins (B6, folic acid, B12), multivitamin tablets, and vitamin D have not been shown to reduce cardiovascular risk in primary prevention, and some have shown evidence of harm in trials — do not recommend any of these specifically for cardiovascular risk reduction.^[1] Nonprescription omega-3 fatty acid supplementation has not been shown to reduce cardiovascular risk in primary prevention on its own — this is a distinct claim from the cardiovascular-outcome evidence behind the prescription product icosapent ethyl, which is used for a different, triglyceride-driven indication (see Dyslipidemias).

Pregnancy

Primary ASCVD prevention as described in this chapter does not itself apply during pregnancy, but a hypertensive disorder of pregnancy or gestational diabetes independently raises a patient's future cardiovascular risk — screen the lipid profile and blood pressure in the postpartum period and begin ongoing primary-prevention risk assessment on the usual schedule once postpartum/breastfeeding considerations resolve.

Low-dose aspirin is used in pregnancy for an entirely different indication — preeclampsia prevention in a patient at high risk — and that recommendation is unrelated to, and unaffected by, the primary-prevention aspirin guidance in this chapter; see Hypertension for the preeclampsia-prevention dosing and timing.

Statins are contraindicated in pregnancy — see Dyslipidemias.

Breastfeeding

Statins are not recommended during breastfeeding given a lack of safety data — see Dyslipidemias. Varenicline and bupropion are not well studied in lactation; nicotine replacement therapy is generally preferred if pharmacotherapy for smoking cessation is needed while breastfeeding.

Older adults

Age itself raises calculated cardiovascular risk, but it also raises bleeding risk from aspirin more than it raises aspirin's ischemic benefit — this is the single biggest driver of the current recommendation against routine aspirin use in primary prevention, and the effect is strongest in patients age 60 and older.^[7] Statin therapy continues to provide benefit in most older adults who otherwise meet a treatment indication.

Renal impairment

Chronic kidney disease meeting age/eGFR/albuminuria criteria is itself a statin-indicated condition (see Assessment & Diagnosis) — see Dyslipidemias for statin dose adjustment in renal impairment. Chronic kidney disease is also a bleeding-risk factor that weighs against any aspirin discussion (see Assessment & Diagnosis).

Ethnicity and structural determinants of health

South Asian, Indigenous, and recent-immigrant patients carry elevated cardiovascular risk that standard calculators may understate — apply earlier or more attentive screening rather than relying on a reassuringly low score alone (see Assessment & Diagnosis). Assess and address socioeconomic and structural barriers to acting on risk-reduction advice (food security, income, access to care) as part of the same visit, not as a separate problem.

• Repeat the global cardiovascular risk assessment every 5 years in adults 40-75 years of age who are not already in a statin-indicated/high-risk category, or sooner if a new risk factor develops.
• Reinforce lifestyle measures at every visit, regardless of whether drug therapy has also been started.
• Recheck the lipid panel roughly 6-12 weeks after starting or changing statin therapy — see Dyslipidemias for the complete monitoring schedule.
• Recheck blood pressure and glycemic control per the schedules in Hypertension and Diabetes Mellitus.
• Reassess tobacco use and offer cessation support at every visit until the patient has fully quit.
• For the rare patient who starts aspirin after individualized shared decision-making, monitor for signs of GI or other bleeding at every visit and re-evaluate whether the bleeding-risk-factor profile has changed.
• For a patient already on long-standing aspirin for primary prevention, revisit the indication at least annually rather than continuing it indefinitely by default.

1. Confirm adherence to lifestyle measures and any prescribed medication before assuming a risk-reduction plan has failed.
2. If a new statin-indicated condition has developed since the last assessment (a cardiovascular event, new diabetes diagnosis, new chronic kidney disease, or a markedly elevated LDL-C), reclassify the patient to high-risk-intensity management immediately rather than waiting for the next scheduled reassessment.
3. If blood pressure or glycemic targets are not met despite lifestyle counselling, escalate pharmacotherapy per Hypertension or Diabetes Mellitus rather than treating this as a primary-prevention-specific failure.
4. If risk remains in the intermediate category after standard assessment and the treatment decision is still unclear, obtain a coronary artery calcium score to reclassify the patient up or down (see Assessment & Diagnosis).
5. If a patient is still taking aspirin for primary prevention from older prescribing practice, have the deprescribing conversation directly — explain the current evidence, assess bleeding-risk factors, and stop it in essentially all patients without a compelling individual reason to continue.
6. If a patient's calculated risk remains high despite an optimized statin, blood pressure, and lifestyle plan, refer to preventive cardiology for consideration of additional risk-enhancing-factor testing or emerging therapies.

• Starting or continuing aspirin routinely for primary prevention "just in case" — current Canadian guidance recommends against this regardless of age, sex, diabetes status, or calculated risk.
• Never revisiting a long-standing aspirin prescription that was started under older guidance.
• Treating a patient with known ASCVD, peripheral arterial disease, a low ankle-brachial index, or a documented coronary/carotid stenosis as if they were still a primary-prevention candidate — once atherosclerosis is established, secondary-prevention-intensity therapy applies.
• Trusting a reassuringly low Framingham Risk Score in a South Asian, Indigenous, or recent-immigrant patient without accounting for the calculator's validation limitations in these populations.
• Missing a risk-enhancing factor (family history, elevated hsCRP, elevated Lp(a), or a coronary artery calcium score above 0) that should push an intermediate-risk patient toward statin therapy.
• Withholding lifestyle counselling once a statin is started, as though medication has made it unnecessary.
• Recommending an antioxidant vitamin, a multivitamin, or routine omega-3 supplementation as if it reduces cardiovascular risk — the evidence does not support this in primary prevention.
• Recommending e-cigarettes as a smoking-cessation aid.
• Waiting for a dietary trial to run its course in a high-risk or statin-indicated patient rather than starting statin therapy at the same visit as lifestyle counselling.

How to use this table: Doses are adult doses unless otherwise noted, and require patient-specific confirmation, including renal/hepatic adjustment. Select any drug name to open its complete Pharmasist Drug Database page.

Antiplatelet Agent

Aspirin is included here for completeness of the drug-class reference, not as a routine recommendation — see Choose Initial Treatment for the current, substantially narrowed indication.

Statins (summary — see Dyslipidemias for the complete class table)

Full statin selection, intensity classification, and add-on-therapy escalation is covered in Dyslipidemias; the 2 high-intensity agents most relevant to starting statin therapy for primary prevention are summarized here.

Smoking-Cessation Pharmacotherapy

Combine any of these with behavioural support (in person or by telephone) for the best chance of a successful quit attempt.

Evidence note: The aspirin-in-primary-prevention entry above reflects a genuine, substantial shift in the evidence base away from routine use, cross-checked against current Canadian guidance.^[6]