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Primary Prevention of Atherosclerotic Cardiovascular Disease


The atherosclerotic process begins in childhood and manifests clinically in adulthood as an acute atherothrombotic event (acute coronary syndrome or stroke) or as symptomatic obstructive disease (angina or claudication) ( Fig. 28.1 ). The major risk factors for atherosclerotic cardiovascular disease (ASCVD) are well characterized in populations around the world (advancing age, male sex, increased total and low-density lipoprotein cholesterol [LDL-C], low high-density lipoprotein cholesterol [HDL-C], smoking, elevated blood pressure, and diabetes mellitus) and are largely driven by unhealthy lifestyle habits over the life course.

FIG. 28.1
Progression of atherosclerosis throughout the lifespan, which can manifest clinically as acute or chronic cardiovascular events.

(From Libby P. Circulation. 2001;104:365–372. FIG. 1.)

Adherence to healthy lifestyle habits should be encouraged for all children and adults. Avoidance of smoking, a Mediterranean-type diet, regular physical activity, and avoidance of obesity are all associated with a lower risk of ASCVD events. Drug treatment is recommended to reduce an increased risk of ASCVD events in many higher-risk individuals with advancing age and in those with familial or genetic hypercholesterolemia. After age 75, trajectories of comorbidity begin to widely differ among individuals, and preventive efforts may be of less importance for some patients.Thus, the priorities for clinical intervention shift throughout the lifespan ( Table 28.1 ).

TABLE 28.1
Lifestyle and Drug Therapy Recommendations for Prevention. The Strongest Randomized Trial Evidence for Drug Therapy Is Highlighted in Bold
20–49 Years 50–75 Years > 75 Years
HEALTHY LIFESTYLE HABITS
Avoid smoking – Healthy diet – Regular physical activity – Control obesity
Moderate sodium intake – Alcohol in moderation
Statins

  • –

    LDL-C ≥ 190 mg/dL

  • –

    Diabetes 40–79 years

  • –

    Consider in selected other high-risk patients

Statins

  • –

    LDL-C ≥ 190 mg/dL

  • –

    Diabetes age 50–75 years

  • –

    ≥ 7.5% 10-year ASCVD risk

  • –

    Consider 5–< 7.5% 10-year ASCVD risk

  • in selected lower-risk patients

Statins

  • –

    Consider in selected primary prevention patients

Antihypertensive drugs

  • –

    Consider in selected patients with BP ≥ 140/or ≥ 90 mm Hg

Antihypertensive drugs

  • –

    Goal BP < 140/90 mm Hg

  • –

    Consider SBP goal < 120 mm Hg in selected patients

Antihypertensive drugs

  • –

    Goal < 150/90 mm Hg unless frail or orthostatic

  • –

    Goal SBP < 140 mm Hg is reasonable

  • –

    Consider goal SBP < 120 mm Hg in selected patients

Aspirin
50–59 years: Low-dose aspirin if ≥ 10-year ASCVD risk at low risk for bleeding
60–69 years: Consider in selected patients with ≥ 10 year ASCVD risk at low risk for bleeding
EMPHASIZE ADHERENCE TO LIFESTYLE AND DRUG THERAPY
ASCVD , Atherosclerotic cardiovascular disease; BP , blood pressure; LDL-C , low-density lipoprotein cholesterol; SBP , systolic blood pressure.

This chapter will focus on the primary prevention of ASCVD in adults of 20 years of age or older. Recommendations from the 2013 prevention guidelines from the American College of Cardiology (ACC)/American Heart Association (AHA) are the focus because they were based on a rigorous systematic evidence review performed under the direction of the National Heart, Lung, and Blood Institute (NHLBI). A similar approach to statin initiation is recommended by current cholesterol treatment guidelines from the American Diabetes Association and the United Kingdom National Institute for Health and Care Excellence. The 2013 ACC/AHA recommendations are contrasted with the 2016 European Society of Cardiology (ESC)/ European Atherosclerosis Society (EAS), which are similar to the previous 2012 ESC/EAS prevention guidelines. Additional recommendations from other groups are also discussed, including recent guidelines from the Centers for Disease Control and Prevention (CDC) and the US Preventive Services Task Force.

Those interested in ASCVD prevention in children and adolescents are referred to the NHLBI pediatric guidelines. However, clinicians should be aware that if a parent has an LDL-C of 190 mg/dL or higher, the offspring, as well as other first-degree relatives, should be screened for familial hypercholesterolemia.

Encourage Long-Term Adherence

As part of an ongoing therapeutic relationship with the patient, adherence to lifestyle and drug therapy should be reinforced at each visit. Blood pressure and body mass index (BMI) should be assessed regularly. A fasting lipid panel should be performed at the initial visit, every 4–6 years as part of ASCVD risk assessment in patients who are not receiving statins, and annually in those receiving statins, or more frequently as needed.

Barriers to adherence should be addressed. Adverse effects during drug therapy often occur and should be addressed in a systematic fashion as outlined in Box 28.1 .

BOX 28.1
Management of Symptoms During Statin Therapy (2013 ACC/AHA Cholesterol Guideline)
From Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol . 2014;63:2889-2934.

Choice of statin and dose

To maximize the safety of statins, selection of the appropriate statin and dose in men and nonpregnant/nonnursing women should be based on patient characteristics, level of ASCVD∗ risk, and potential for adverse effects. Moderate-intensity statin therapy should be used in individuals in whom high-intensity statin therapy would otherwise be recommended when characteristics predisposing them to statin-associated adverse effects are present.

Characteristics predisposing individuals to statin adverse effects include but are not limited to:

  • Multiple or serious comorbidities, including impaired renal or hepatic function.

  • History of previous statin intolerance or muscle disorders.

  • Unexplained ALT elevations > 3 times ULN.

  • Patient characteristics or concomitant use of drugs affecting statin metabolism.

  • Age >75 years.

Additional characteristics that could modify the decision to use higher statin intensities might include but are not limited to:

  • History of hemorrhagic stroke.

  • Asian ancestry

Management of symptoms

The large majority of patients with symptoms during statin therapy can be successfully rechallenged with statin therapy. It is reasonable to evaluate and treat muscle symptoms, including pain, tenderness, stiffness, cramping, weakness, or fatigue, in statin-treated patients according to the following management algorithm:

  • To avoid unnecessary discontinuation of statins, obtain a history of prior or current muscle symptoms to establish a baseline before initiation of statin therapy.

  • If unexplained severe muscle symptoms or fatigue develop during statin therapy, promptly discontinue the statin and address the possibility of rhabdomyolysis by evaluating CK and creatinine and performing urinalysis for myoglobinuria.

  • If mild to moderate muscle symptoms develop during statin therapy:

    • Discontinue the statin until the symptoms can be evaluated.

    • Evaluate the patient for other conditions that might increase the risk for muscle symptoms (e.g., hypothyroidism, reduced renal or hepatic function, rheumatologic disorders such as polymyalgia rheumatica, steroid myopathy, vitamin D deficiency, or primary muscle diseases).

    • If muscle symptoms resolve, and if no contraindication exists, give the patient the original or a lower dose of the same statin to establish a causal relationship between the muscle symptoms and statin therapy.

    • If a causal relationship exists, discontinue the original statin. Once muscle symptoms resolve, use a low dose of a different statin.

    • Once a low dose of a statin is tolerated, gradually increase the dose as tolerated.

    • If, after 2 months without statin treatment, muscle symptoms or elevated CK levels do not resolve completely, consider other causes of muscle symptoms listed above.

    • If persistent muscle symptoms are determined to arise from a condition unrelated to statin therapy, or if the predisposing condition has been treated, resume statin therapy at the original dose.

Other symptoms are very unlikely to be due to statin therapy and can be managed using a similar strategy of discontinuation and rechallenge.

Monitoring

  • Creatine kinase

Do not routinely measure creatine kinase levels (although baseline levels may be helpful in patients with a history of statin intolerance, or if muscle symptoms develop)

  • Hepatic transaminases

Do not routinely measure hepatic transaminases (unless baseline alanine aminotransferase (ALT) is elevated or symptoms of hepatoxoicity develop)

  • Glucose and hemoglobin A1c

Do not routinely monitor glycemic parameters. Patients should be monitored as recommended by expert guidelines.

Overview of Primary Prevention Priorities by Age Group

Lifestyle and drug treatment priorities may be different in those 20–49 years, 50–75 years, and over age 75 years (see Table 28.1 ). Therefore, the main recommendations from the US and European guidelines are summarized by age. Guideline recommendations and randomized trial evidence are discussed in more detail in the respective sections on cholesterol, blood pressure, and aspirin therapy. ASCVD risk prediction is discussed in more detail in the cholesterol section, and links to online resources are provided.

Before Age 50

Lifestyle

Adherence to healthy lifestyle habits should be strongly encouraged as the foundation for ASCVD prevention. Changes in lifestyle habits have been shown to slow progression of atherosclerosis in this age group. Smoking cessation is a necessity and should be addressed at every visit.

Cholesterol

Statin therapy is recommended for primary prevention in high-risk patients older than 50 years if they have:

  • Familial or other genetic hypercholesterolemia (cut-off in the United States, LDL-C ≥ 190 mg/dL; in Europe, total cholesterol > 8 mmol/L or 310 mg/dL).

  • Diabetes (in the United States, age ≥ 40 years; in Europe, depends on LDL-C level).

  • Multiple or severe risk factor elevations (in Europe, this includes moderate chronic kidney disease).

For lower-risk primary prevention patients, 10-year cardiovascular risk should be estimated using calculators appropriate to the population under treatment. In the United States, the 2013 ACC/AHA Pooled Cohort Equations should be used as the starting point for estimating 10-year ASCVD risk for those aged 40–75 years if LDL-C is greater than 190 mg/dL. Statin therapy should be considered for those with a 7.5% or higher 10-year ASCVD risk and may be reasonable for those with a 5% to < 7.5% 10-year ASCVD risk. Selected lower-risk patients may also benefit from statin therapy.

In Europe, the Systematic Coronary Risk Estimation (SCORE) equations should be the starting point for estimating 10-year risk of fatal ASCVD in Caucasians who are not otherwise characterized as high risk. The calculated SCORE 10-year fatal ASCVD risk can then characterize patient risk in individuals aged 40–65 years and be used to identify an LDL-C treatment goal: very high risk (≥ 10%; LDL-C goal < 1.8 mmol/L or 70 mg/dL), high risk (5 to < 10%; LDL-C goal < 2.6 mmol/L or 100 mg/dL), moderate (≥ 1% to < 5%; LDL-C goal < 3.0 mmol/L or 115 mg/dL), or low (< 1%; LDL-C goal < 3.0 mmol/L or 115 mg/dL).

Race/ethnic-specific equations (QRISK2) for major cardiovascular disease have been developed for the United Kingdom.

Blood Pressure

Elevated blood pressure should first be addressed through lifestyle modification, including weight loss, increasing regular physical activity, and reducing sodium intake. Although there is little clinical trial evidence in individuals under 50 years of age, antihypertensive drug therapy can be considered if systolic blood pressure remains greater than 140 mm Hg or diastolic blood pressure remains higher than 90 mm Hg on multiple occasions both in and outside the office, especially if other risk factors are present.

Aspirin

There is no indication for aspirin therapy in individuals under 50 years of age.

Age 50-75 Years

Lifestyle

Smoking avoidance and healthy lifestyle habits should continue to be encouraged. However, the primary clinical focus should turn to consideration of preventive drug therapies. The largest body of evidence for preventive drug therapy comes from randomized trials in those aged 50–75 years.

In this age group, atherosclerosis is usually well advanced (see Fig. 28.1 ), with extensive fibrocalcific plaque development in most individuals. The risk of clinical events is significantly increased, and more aggressive risk factor reduction is needed. The randomized trials of drug therapy were all performed on a background of advice to maintain a healthy diet and regular physical activity. However, the modest changes in risk factor levels associated with these lifestyle interventions have not been shown to reduce ASCVD events in this age group.

Cholesterol

Statin therapy is strongly recommended for individuals aged 50–75 years with:

  • Familial or other genetic hypercholesterolemia (cut-off in the United States, LDL-C ≥ 190 mg/dL; in Europe, total cholesterol > 8 mmol/L or 310 mg/dL).

  • Diabetes (in the United States, age ≥ 40 years; in Europe, depends on LDL-C level).

  • Multiple or severe risk factor elevations (in Europe, this includes moderate chronic kidney disease).

  • Increased ASCVD risk based on risk prediction equations.

In the United States, statins should be considered in individuals up to age 75 years with a 7.5% or greater 10-year ASCVD risk and may be reasonable in those with 5% to < 7.5% 10-year ASCVD risk. Lower-risk patients in the 50–75-year age group may also benefit from statin therapy.

In Europe, SCORE charts can be used for estimating 10-year risk of fatal ASCVD in Caucasians aged 40–65 years who are not otherwise characterized as high risk. The calculated SCORE 10-year fatal ASCVD risk can then characterize patient risk in individuals aged 40–65 years and be used to identify an LDL-C treatment goal: very high risk (≥ 10%; LDL-C goal < 1.8 mmol/L or 70 mg/dL), high risk (5 to < 10%; LDL-C goal < 2.6 mmol/L or 100 mg/dL), moderate (≥ 1% to < 5%; LDL-C goal < 3.0 mmol/L or 115 mg/dL), or low (< 1%; LDL-C goal < 3.0 mmol/L or 115 mg/dL).

Blood Pressure

Antihypertensive drug therapy is recommended in those aged 50 or older if systolic blood pressure remains at 140 mm Hg or higher or diastolic blood pressure remains at 90 mm Hg or higher on multiple occasions both in and outside the office. Greater absolute risk reduction occurs from antihypertensive therapy in higher-risk individuals, and there are little data for those without cardiovascular risk factors less than 80 years of age. In selected high-risk individuals tolerating the current drug regimen, another antihypertensive drug could be considered if systolic blood pressure remains greater than 120 mm Hg.

Aspirin

Aspirin therapy can be considered for those aged 50–59 years at low risk of bleeding and is reasonable to consider in those 60–69 years, with a 10-year or greater ASCVD risk at low risk of bleeding.

Age over 75 Years

Lifestyle

Smoking avoidance and healthy lifestyle habits should continue to be encouraged. Observational evidence suggests health benefits occur from smoking cessation at any age. Regular physical activity, although not shown to reduce ASCVD events or mortality, may be beneficial for improving quality of life.

Cholesterol

Persons in good to excellent health at age 75 are likely to live at least another 10–15 years and so may benefit from preventive drug therapy. Less evidence for primary prevention with statins is available for individuals greater than 75 years, and the randomized trials that are available have conflicting results. The absolute risk of ASCVD events is highest after age 75, but high rates of competing causes of mortality and morbidity may alter the potential net benefit from statin therapy.

In the United States, after age 75 years, there are no strong recommendations for primary prevention statin therapy. Patient preferences for prevention, and concerns about safety, should contribute to the decision to initiate (or continue) statin therapy.

In Europe, age over 75 years is not mentioned as a factor in the decision to initiate statin therapy. The SCORE charts do not estimate 10-year fatal ASCVD risk after age 65 years.

Blood Pressure

Numerous randomized trials have evaluated the effect of antihypertensive therapy on ASCVD outcomes, heart failure, and mortality in generally healthy persons over 75 years. The strongest evidence for those over 75 years supports treating blood pressure greater than 150/or greater than 90 mm Hg, but recent evidence suggests a benefit from treating to blood pressure levels less than 140/<90 mm Hg in persons 75 years of age or older.

Aspirin

Few randomized trial data are available for aspirin in persons over 75 years of age, and aspirin therapy is generally not recommended for primary prevention in this age group due to the excess risk of bleeding in older individuals.

Lifestyle Recommendations

A healthy lifestyle is the foundation of health promotion and disease prevention efforts and should be addressed at every visit ( Table 28.2 ). Regular counseling to improve diet or increase physical activity changes health behaviors and is associated with small improvements in adiposity, blood pressure, and lipid levels. Smoking cessation is discussed in Chapter 18 .

TABLE 28.2
Recommendations to Reduce LDL-C, Non–HDL-C, and Blood Pressure and General Physical Activity Recommendations from the 2013 ACC/AHA Lifestyle Guideline, Centers for Disease Control, and ESC/EAS Prevention Guideline
Modified from Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol . 2014;63:2960–2984; Physical Activity Guidelines Advisory Committee. Physical Activity Guidelines Advisory Committee Report, 2008. Washington, DC: US Department of Health and Human Services. 2008; Piepoli MF, Hoes AW, Agewall S, et al. 2016 European guidelines on cardiovascular disease prevention in clinical practice: Eur Heart J . 2016;37(29):2315–2381. pii: ehw106.
Diet Class/LOE
  • 1.

    Consume a dietary pattern that:

    • Emphasizes intake of vegetables, fruits, and whole grains

    • Includes low-fat dairy products, poultry, fish, legumes, non-tropical vegetable oils, and nuts

    • Limits intake of sweets, sugar-sweetened beverages, and red meats

    • Adapts appropriate calorie requirements, personal and cultural food preferences, and nutrition therapy for other medical conditions (including diabetes mellitus)

    • Follows plans such as the DASH dietary pattern, the USDA Food Pattern, or the AHA Diet

I A
  • 2.

    Aim for a dietary pattern that achieves 5% to 6% of calories from saturated fat

I A
  • 3.

    Reduce percent calories from saturated fat

I A
  • 4.

    Reduce percent calories from trans fat

I A
  • 5.

    For those who would benefit from blood pressure lowering, reduce sodium intake

I A

  • Sodium intake ≤ 2400 mg daily is advised

  • Sodium intake ≤ 1500 mg daily can result in greater blood pressure reduction

  • Reducing sodium by at least 1000 mg daily can lower blood pressure

IIa B
Physical Activity
  • 1.

    For important health benefits, adults should:

    • Engage in at least 150 minutes’ moderate aerobic activity (e.g., brisk walking) each week

    • Alternatively, engage in 75 minutes of vigorous-intensity aerobic activity (e.g., jogging or running) each week

    • Aerobic activity sessions should be at least 10 minutes in duration

    • For even greater health benefits, increase moderate-intensity physical activity to 300 minutes per week or vigorous-intensity physical activity for 150 minutes per week

    • Engage in muscle strengthening activities at least twice a week that engage all major muscle groups

CDC
  • 2.

    In general, advise adults to engage in aerobic physical activity to reduce LDL-C, non–HDL-C, and blood pressure

    • 3–4 sessions a week

    • Lasting on average 40 minutes per session

    • Involving moderate to vigorous physical activity

IIa A
LOE , Level of evidence; CDC , Centers for Disease Control and Prevention.

Lifestyle Interventions

Diet

The 2013 ACC/AHA lifestyle guideline, ESC/EAS prevention guidelines, and other guidelines recommend a dietary pattern rich in fruits, vegetables, and whole grains that includes low-fat dairy products, poultry, fish, legumes, nuts, and non-tropical vegetable oils (see Table 28.2 ). Intake of sweets, sugar-sweetened beverages, and red meats should be limited. Saturated fat intake should be limited to 5% to 6% of calories and trans fats should be avoided. The caloric content of the diet should be based on the need of the patient to lose, maintain, or gain weight. Alcohol consumption should be limited to two glasses per day (20 g/day of alcohol) for men and one glass per day for women (10 g/day). This dietary pattern can be achieved by following plans such as the Dietary Approaches to Stop Hypertension (DASH) dietary pattern, the United States Department of Agriculture (USDA) Food Pattern, or the American Heart Association Diet.

Randomized trials of the DASH dietary pattern have been shown to reduce blood pressure, and the effect of this diet is enhanced by reducing sodium intake. Restricting sodium to no more than 2400 mg daily is advised for those who would benefit from lowering blood pressure, and greater restriction may be beneficial for some patients.

Physical Activity

For important health benefits, the CDC and the ESC/EAS prevention guidelines recommend at least 150 minutes of moderate-intensity physical activity (e.g., walking) every week, along with muscle strengthening activities on two or more days a week that work all major muscle groups (legs, back, abdomen, chest, shoulders, and arms) (see Table 28.2 ). Alternatively, more vigorous activity (such as jogging or running) can be performed for 75 minutes each week. Activity can be performed throughout the day, as long as moderate to intense effort occurs for at least 10 minutes. Even greater health benefits accrue by increasing moderate-intensity physical activity to 300 minutes per week or vigorous-intensity physical activity to 150 minutes per week.

The 2013 ACC/AHA lifestyle guideline recommends that adults in general should be advised to engage in regular aerobic physical activity to reduce LDL-C, non–HDL-C, and blood pressure. The systematic review of randomized trials performed by the guideline panel found that three to four sessions of moderate-to vigorous-intensity physical activity lasting on average 40 minutes significantly reduced all three risk factors. Reducing sedentary activity, independent of physical activity levels, also appears to have benefits for cardiovascular health.

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