ASCVD remains the leading cause of morbidity and mortality globally.¹ Much of this is attributable to suboptimal implementation of prevention strategies and uncontrolled ASCVD risk factors in many adults. The most important way to prevent ASCVD is to promote a healthy lifestyle throughout life. Prevention strategies must include a strong focus on lifestyle optimization (improvements in diet, physical activity, and avoidance of tobacco use and exposure to secondhand smoke) to minimize the risk of future ASCVD events. A comprehensive patient-centered approach that addresses all aspects of a patient's lifestyle habits and estimated risk of a future ASCVD event is the first step in deciding whether there may be a need for pharmacotherapy.

All individuals should be encouraged to follow a heart-healthy lifestyle, and estimating an individual's 10-year absolute ASCVD risk enables matching the intensity of preventive interventions to the patient's absolute risk to maximize anticipated benefit and minimize potential harm from overtreatment. The 10-year ASCVD risk estimate is used to guide decision-making for many preventive interventions, including lipid management and blood pressure management; it should be the start of a conversation with the patient about risk-reducing strategies. After calculation of the risk score, it is reasonable to use additional risk-enhancing factors to guide decisions about preventive interventions for borderline- or intermediate-risk adults. However, the value of preventive therapy may remain uncertain for many individuals with borderline or intermediate estimated 10-year risk, and some patients may be reluctant to take medical therapy without clearer evidence of increased ASCVD risk. For these individuals, the assessment of CAC is a reasonable tool to reclassify risk either upward or downward as part of shared decision-making. For younger adults 20-59 years of age, estimation of lifetime risk may be considered. For adults >75 years of age, the clinician and patient should engage in a discussion about the possible benefits of preventive therapies appropriate to the age group in the context of comorbidities and life expectancy.

After the age of 20, it is reasonable to measure traditional risk factors at least every 4-6 years. For adults 20-39 years of age, limited data exist on the performance and utility of 10- year risk estimation tools. It is therefore important to consider lifetime risk estimation in this population. Periodic assessment of risk factors (e.g., at least every 4-6 years in adults 20-39 years of age), discussions about intensity of lifestyle interventions, and treatment of nonlipid risk factors need to be performed.

To facilitate decisions about preventive interventions, it is recommended to screen for traditional ASCVD risk factors and apply the race- and sex-specific pooled cohort equations (such as ASCVD Risk Estimator) to estimate 10-year ASCVD risk for asymptomatic adults 40-75 years of age. Of note, the ASCVD risk estimator has been best validated in non-Hispanic whites and non-Hispanic blacks. Other risk tools can be considered in different subgroups if validated. Based on the ASCVD risk score, 4 broad groups can be recognized (Table 1).

Table 1

		10-Year Risk	Recommendations
1	Low Risk	<5%	Emphasize healthy life style changes.
2	Borderline Risk	5% to <7.5%	Emphasize healthy life style changes. Evaluate for risk enhancing factors. Consider CAC to help reclassify risk for preventive interventions.
3	Intermediate Risk	≥7.5% to <20%	Emphasize healthy life style changes. Evaluate for risk enhancing factors. Consider CAC to help reclassify risk for preventive interventions.
4	High Risk	≥20%	Consider treatment with high-intensity statin.

Top 10 Take-Home Messages for the Primary Prevention of Cardiovascular Disease

1. The most important way to prevent atherosclerotic vascular disease, heart failure, and atrial fibrillation is to promote a healthy lifestyle throughout life.
2. A team-based care approach is an effective strategy for the prevention of cardiovascular disease. Clinicians should evaluate the social determinants of health that affect individuals to inform treatment decisions.
3. Adults who are 40-75 years of age and are being evaluated for cardiovascular disease prevention should undergo 10-year atherosclerotic cardiovascular disease (ASCVD) risk estimation and have a clinician-patient risk discussion before starting on pharmacological therapy, such as antihypertensive therapy, a statin, or aspirin. In addition, assessing for other risk-enhancing factors can help guide decisions about preventive interventions in select individuals, as can coronary artery calcium (CAC) scanning.
4. All adults should consume a healthy diet that emphasizes the intake of vegetables, fruits, nuts, whole grains, lean vegetable or animal protein, and fish and minimizes the intake of trans fats, processed meats, refined carbohydrates, and sweetened beverages. For adults who are overweight or obese, counseling and caloric restriction are recommended for achieving and maintaining weight loss.
5. Adults should engage in at least 150 minutes of accumulated moderate-intensity physical activity per week or 75 minutes of vigorous-intensity physical activity per week.
6. For adults with type 2 diabetes mellitus, lifestyle changes, such as improving dietary habits and achieving exercise recommendations, are crucial. If medication is indicated, metformin is first-line therapy, followed by consideration of a sodium-glucose cotransporter 2 inhibitor or a glucagon-like peptide-1 receptor agonist.
7. All adults should be assessed at every healthcare visit for tobacco use, and those who use tobacco should be strongly advised to quit and assisted.
8. Aspirin should be used infrequently in the routine primary prevention of ASCVD because of lack of net benefit.
9. Statin therapy is first-line treatment for primary prevention of ASCVD in patients with elevated low-density lipoprotein cholesterol (LDL-C) levels (≥190 mg/dL), those with diabetes mellitus who are 40-75 years of age, and those determined to be at sufficient ASCVD risk after a clinician-patient risk discussion.
10. Nonpharmacological interventions are recommended for all adults with elevated blood pressure or hypertension. For those requiring pharmacological therapy, the target blood pressure should generally be <130/80 mmHg.

Risk-Enhancing Factors for Clinician-Patient Risk Discussion

• Family history of premature ASCVD (males aged <55 years; females aged <65 years)
• Primary hypercholesterolemia (LDL-C = 160-189 mg/dL [4.1-4.8 mmol/L]; non-high-density lipoprotein cholesterol [HDL-C] = 190-219 mg/dL [4.9-5.6 mmol/L])
• Metabolic syndrome (increased waist circumference [by ethnically appropriate cutpoints], elevated triglycerides [>150 mg/dL, nonfasting], elevated blood pressure, elevated glucose, and low HDL-C [<40 mg/dL in men; <50 mg/dL in women] are factors; a tally of 3 makes the diagnosis)
• Chronic kidney disease (estimated glomerular filtration rate = 15-59 mL/min/1.73 m2 with or without albuminuria; not treated with dialysis or kidney transplantation)
• Chronic inflammatory conditions, such as psoriasis, rheumatoid arthritis, lupus, or human immunodeficiency virus
• History of premature menopause (before age 40 years) and history of pregnancy-associated conditions that increase later ASCVD risk, such as preeclampsia
• High-risk race/ethnicity, such as South Asian ancestry
• Lipids/biomarkers associated with increased ASCVD risk:
  • Persistently elevated primary hypertriglyceridemia (≥175 mg/dL, nonfasting)
  • If measured:
    • Elevated high-sensitivity C-reactive protein (≥2.0 mg/L)
    • Elevated lipoprotein(a): A relative indication for its measurement is family history of premature ASCVD. A lipoprotein(a) ≥50 mg/dL or ≥125 nmol/L constitutes a risk-enhancing factor, especially at higher levels of lipoprotein(a).
    • Elevated apolipoprotein B (≥130 mg/dL): A relative indication for its measurement would be triglyceride ≥200 mg/dL. A level ≥130 mg/dL corresponds to an LDL-C >160 mg/dL and constitutes a risk-enhancing factor.
    • Ankle-brachial index (<0.9)

Utility of CAC in Reclassifying ASCVD Risk

For individuals with intermediate predicted risk (≥7.5% to <20%) or for select adults with borderline (5% to <7.5%) predicted risk, CAC measurement can be a useful tool in refining risk assessment for preventive interventions (e.g., statin therapy). In these groups, CAC measurement can reclassify risk upward (particularly if CAC score is ≥100 Agatston units or ≥75th age/sex/race percentile) or downward (if CAC is zero) in a significant proportion of individuals.

In adults at intermediate risk, CAC measurement can be effective for meaningfully reclassifying risk in a large proportion of individuals. In such intermediate-risk adults, those with CAC ≥100 Agatston units or CAC ≥75th percentile have ASCVD event rates for which initiation of statin therapy is reasonable. Those with CAC scores of zero appear to have 10-year event rates in a lower range for which statin therapy may be of limited value. Therefore, for patients with CAC scores of 1-99, it is reasonable to repeat the risk discussion. If these patients remain untreated, repeat CAC measurement in 5 years may have some value, but data are limited. It is important to note that the absence of CAC does not rule out noncalcified plaque, and clinical judgment about risk should prevail. Clinicians should not down-classify risk in patients who have CAC scores of zero but who are persistent cigarette smokers, have diabetes, have a family history of ASCVD, or, possibly, have chronic inflammatory conditions. In the presence of these conditions, a CAC score of zero may not rule out risk from noncalcified plaque or increased risk of thrombosis.

CAC might also be considered in refining risk for selected low-risk adults (<5%), such as those with a strong family history of premature coronary heart disease. CAC measurement is not intended as a screening test for all but rather may be used as a decision aid in select adults to facilitate the clinician-patient risk discussion. The following candidates for CAC measurement may benefit from knowing that their CAC score is zero:

• Patients reluctant to initiate statin who wish to understand their risk and potential for benefit more precisely
• Patients concerned about the need to reinstitute statin therapy after discontinuation for statin-associated symptoms
• Older patients (men 55-80 years of age; women 60-80 years of age) with low burden of risk factors who question whether they would benefit from statin therapy
• Middle-aged adults (40-55 years of age) with pooled cohort equations-calculated 10-year risk of ASCVD 5% to <7.5% with factors that increase their ASCVD risk

Figure 1: Primary Prevention¹

References

1. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2019;Mar 17:[Epub ahead of print].

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias, Advanced Lipid Testing, Homozygous Familial Hypercholesterolemia, Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Diet, Exercise, Hypertension, Smoking

Keywords: Albuminuria, Antihypertensive Agents, Caloric Restriction, Cholesterol, LDL, Comorbidity, Coronary Disease, Biomarkers, Atrial Fibrillation, Aspirin, Carbohydrates, Coronary Vessels, Decision Making, Diabetes Mellitus, Diabetes Mellitus, Type 2, Cohort Studies, Arthritis, Rheumatoid, Decision Support Techniques, Blood Pressure, Apolipoproteins, Ankle Brachial Index, Factor IX, Exercise, Glucose, Heart Failure, Hypertension, Glomerular Filtration Rate, Habits, Hypertriglyceridemia, Hypercholesterolemia, Kidney Transplantation, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Life Expectancy, Life Style, Lipids, Lipoprotein(a), Menopause, Premature, Metabolic Syndrome, Obesity, Overweight, Pregnancy, Primary Prevention, Pre-Eclampsia, Metformin, Psoriasis, Renal Insufficiency, Chronic, Renal Dialysis, Smoking, Risk Factors, Sodium-Glucose Transport Proteins, Social Determinants of Health, Sweetening Agents, Thrombosis, Risk Assessment, Tobacco, Tobacco Use, Tobacco Smoke Pollution, Triglycerides, Waist Circumference, Weight Loss

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