Overview of primary prevention of cardiovascular disease in adults

INTRODUCTION — 

Cardiovascular disease (CVD), predominantly atherosclerotic cardiovascular disease (ASCVD), is the leading cause of global mortality and a major cause of morbidity [1-3]. CVD encompasses a wide variety of acquired and congenital conditions, including heart disease, cerebrovascular disease, disease of the aorta, and peripheral artery disease [1]. ASCVD is a subset of CVD caused by atherosclerosis, including coronary heart disease as well as atherosclerotic cerebrovascular, aortic, and peripheral artery disease.

This topic reviews the primary prevention of ASCVD, with a focus on modifiable risk factors and their management.

Secondary prevention of CVD, a detailed discussion of ASCVD risk assessment, and other established and possible CVD risk factors are discussed separately.

●(See "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults".)

●(See "Overview of established risk factors for cardiovascular disease".)

●(See "Overview of possible risk factors for cardiovascular disease".)

●(See "Prevention of cardiovascular disease events in those with established disease (secondary prevention)".)

CARDIOVASCULAR RISK ASSESSMENT

Identify risk factors — The primary prevention of CVD starts with identifying risk factors to help target therapeutic lifestyle changes and adjunctive pharmacotherapies.

●History – All adults age ≥20 years should have an assessment of their diet, level of physical activity and sedentary lifestyle, alcohol intake, and tobacco use during routine annual visits. We also ask about family history of premature atherosclerotic cardiovascular disease (ASCVD; males, age <55 years; females, age <65 years) and medical conditions that increase ASCVD risk, such as diabetes mellitus and hypertension.

●Physical examination – Physical examination includes measurements of blood pressure and body mass index (BMI) to screen for hypertension and overweight/obesity, respectively.

●Laboratory testing – This includes lipid screening for all patients and, for those at increased risk of developing diabetes, screening for diabetes (table 1).

Details regarding risk factor assessment are discussed below. (See 'Promoting a healthy lifestyle' below and 'Identifying and addressing key risk factors' below.)

Role of modifiable risk factors

●Impact of modifiable risk factors – Modifiable risk factors account for approximately 50 to 70 percent of CVD events and deaths worldwide [4-6]. They may also account for up to 90 percent of the population attributable risk of first acute myocardial infarction (MI) and stroke [3,7-9]. The presence of multiple risk factors and risk factors of longer duration and greater severity confers greater CVD risk in a dose-response relationship that is at least additive (figure 1).

The relationship between modifiable risk factors and increased risk of CVD has been consistently observed across a wide range of populations, as illustrated by the following studies:

•An analysis of 112 cohorts from eight geographic regions worldwide compiled data from over 1.5 million participants to estimate the population-attributable risk of incident CVD from five modifiable risk factors: non-high-density lipoprotein cholesterol, current smoking, diabetes, systolic blood pressure and BMI [5]. Investigators estimated that these five risk factors were responsible for 57 and 53 percent of incident CVD events and 22 and 19 percent of overall deaths for females and males, respectively. An earlier study of United States adults found similar results [4].

•In a prospective cohort of over 155,000 participants from 21 high-, middle-, and low-income countries, over 70 percent of CVD events and deaths were attributable to 12 potentially modifiable risk factors [6]. These included behavioral (diet, physical activity, sodium intake, tobacco and alcohol use) and metabolic risk factors (hypertension, diabetes, dyslipidemia, and obesity) as well as psychosocial variables (low education, household pollution).

●Benefits of risk reduction – Identifying and modifying risk factors is the cornerstone of primary CVD prevention [10]. Deaths due to CVD have declined over the past 40 years in the United States and worldwide. This has been attributed to earlier diagnosis and more aggressive treatment of modifiable risk factors, particularly increased rates of smoking cessation and drug treatment of dyslipidemia and hypertension [11,12]. However, the rate of decline has decelerated since 2011; this may be due in part to increases in obesity and sedentary lifestyles [13,14].

●Importance of early intervention – We encourage early intervention to address modifiable risk factors, where possible [15]. More precise risk assessment and stratification can assist clinicians with targeting preventive strategies for those at the greatest risk of future events. Atherosclerosis begins early in life, and early intervention is the most effective way to reduce the total population burden of atherosclerotic disease and incidence of CVD events [16]. Unfortunately, it is expensive and methodologically challenging to conduct large-scale, randomized trials with sufficient power and length of follow-up to determine the benefits and risks of early intervention strategies.

Assess ASCVD risk — We engage all patients between ages 20 years and older in atherosclerotic cardiovascular disease (ASCVD) risk assessment discussions. We initiate risk discussions with patients 20 years and older during their first encounter with the health care system. The frequency of subsequent assessments depends on the individual's baseline risk of cardiovascular events (eg, absolute risk).

We use the results of risk factor assessments to develop an overall picture of the patient's risk for ASCVD events and determine whether additional risk stratification is needed (see 'Identify risk factors' above). Additional risk stratification depends primarily on the patient's age and cardiovascular risk factors, and it typically includes quantitative estimation of the patient's ASCVD risk using a calculator.

An approach to ASCVD risk assessment as part of primary prevention is described separately. (See "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults".)

SHARED DECISION-MAKING — 

After assessing risk factors and estimating atherosclerotic cardiovascular disease (ASCVD) risk, clinicians and patients should discuss specific modifiable risk factors and decide which of these to address. We start by informing patients of their level of risk and which strategies are most effective to reduce that risk.

Shared decision-making interventions and motivational interviewing can help guide and prioritize cardiovascular risk reduction strategies. Shared decision-making tools may improve the content and outcomes of conversations about CVD risk reduction [17,18]. Such tools include tailored information about cardiovascular risks and strategies for risk reduction. We typically use principles and techniques of motivational interviewing to develop therapeutic rapport; understand the patient's perspective; and elicit patient priorities, readiness, motivations, and barriers to change. Motivational interviewing, which has demonstrated efficacy in the treatment of tobacco and other substance use disorders, is also applicable to behavior change for cardiovascular risk reduction. (See "Substance use disorders: Motivational interviewing".)

Although we encourage individuals with high ASCVD risk to prioritize therapeutic lifestyle changes (TLCs) and address multiple risk factors, many patients are not able to modify multiple behaviors simultaneously. For these patients, it is important to use shared decision-making to identify which risk reduction strategies to target. Some patients wish above all else to prioritize avoiding medications and are more open to TLCs. Others prefer reducing cardiovascular risk by taking a statin or antihypertensive agent, if indicated. For patients who smoke cigarettes, tobacco cessation may offer the biggest opportunity for CVD risk reduction; however, for individuals who are not ready or able to stop smoking, it may make sense to target other more easily modifiable risk factors.

PROMOTING A HEALTHY LIFESTYLE — 

We suggest that all individuals engage in the following measures to reduce the risk of CVD: avoiding smoking, minimizing weight gain, adopting a healthy diet, ensuring adequate sleep duration, and engaging in regular physical activity. Assessing a patient's level of physical activity, dietary intake, and use of tobacco and alcohol are key components in the primary prevention of CVD. We support more frequent and intensive interventions for those individuals at the highest baseline (absolute) risk of CVD events.

Smoking cessation — We assess tobacco use, including the use of smokeless tobacco and electronic cigarettes, at annual preventive health visits. Those who do not currently smoke should be encouraged not to start. Individuals who smoke should receive clear, nonjudgmental advice to quit smoking entirely. Clinicians should discuss the cardiovascular and other benefits of smoking cessation and engage patients who want to quit or cut down in a discussion of the behavioral and pharmacologic options to help with smoking cessation [19-21]. Patients should also be counseled to minimize exposure to secondhand smoke.

An approach to smoking cessation and specific behavioral and pharmacotherapies for smoking cessation are discussed separately. (See "Overview of smoking cessation management in adults" and "Pharmacotherapy for smoking cessation in adults" and "Behavioral approaches to smoking cessation".)

●Cardiovascular risks of smoking – Cigarette smoking remains a leading contributor to cardiovascular morbidity and mortality worldwide [22]. In United States adults, smoking accounts for approximately 20 percent of cardiovascular deaths and almost one-third of deaths from coronary heart disease (CHD) [19,21]. Smoking is associated with an increased risk of death from heart disease across all age groups, including adults aged 45 and younger [21,23]. Smoking even a few cigarettes daily is associated with an increased risk of stroke and myocardial infarction (MI) [19]. The cardiovascular risks of smoking are discussed separately. (See "Cardiovascular risk of smoking and benefits of smoking cessation".)

●Cardiovascular benefits of quitting – The cardiovascular benefits of stopping smoking accrue almost immediately after quitting and increase over time. After one year of not smoking, the excess risk for CHD falls to 50 percent of that of current smokers. After 15 years, the risks of heart failure, CHD, and stroke resemble those of a nonsmoker [19,21]. Although the greatest benefits of quitting smoking occur in those who stop by age 40, even quitting after age 70 can reduce the rate of all-cause death [21,24,25]. The cardiovascular benefits of smoking cessation are discussed separately. (See "Cardiovascular risk of smoking and benefits of smoking cessation", section on 'Cardiovascular benefits of smoking cessation'.)

●Secondhand smoke exposure – Over 8 percent of all smoking-related deaths are due to secondhand smoke exposure [26]. Secondhand smoke exposure is associated with an increased risk of strokes and CHD events [21]. Conversely, comprehensive smoke-free laws are associated with reductions in cardiovascular deaths [21]. Secondhand smoke exposure is discussed separately. (See "Secondhand smoke exposure: Effects in adults", section on 'Health consequences of secondhand smoke'.)

Healthy diet — We start discussions of a healthy diet by doing a brief dietary assessment (see "Dietary assessment in adults"). We ask patients to identify both dietary strengths and areas for improvement (table 2).

We encourage all individuals to adopt a healthy diet to reduce their risk of CVD. Adherence to Mediterranean-style or plant-based diets offers optimal cardiovascular benefit. Because food choices depend on a complex interplay of cultural, socioeconomic, and societal factors, some individuals may be unwilling or unable to adopt a specific dietary pattern. Socioeconomic factors that can contribute to poor diet include food insecurity or lack of availability, time scarcity, and eating out or buying preprepared food [27].

However, most people can improve their diets by incorporating foods that have been associated with cardiovascular benefit and reducing unhealthy foods. Components of a healthy diet include the following:

●High intake of vegetables and fruits

●Intake of fiber and whole grains (table 3)

●Intake of legumes and nuts

●Intake of non-fried fish [28], particularly fatty fish such as salmon [29]

●Limited animal protein, with substitution of fish or lean poultry for red meat

●Oils that contain monounsaturated or polyunsaturated fats (olive, canola, safflower) (table 4)

Foods that may increase cardiovascular risk include:

●Sugar and artificially sweetened beverages

●Ultraprocessed foods, including processed meats, sweets, and other refined carbohydrates

●Red meat

●Foods high in cholesterol

●Foods with a high sodium content (fast foods, preprepared foods, canned soups)

●Foods containing trans fatty acids (table 4)

●Foods containing animal fats (eg, butter, lard) or tropical oils (eg, palm or coconut oil)

●Foods with a high glycemic index (table 5)

These recommendations are consistent with guidelines from the American Heart Association (AHA)/American College of Cardiology, AHA, European Society of Cardiology, and United States Preventive Services Task Force [19,30-33]. How to assess dietary intake and the benefits of specific dietary patterns and components are discussed separately. (See "Dietary assessment in adults" and "Healthy diet in adults".)

Individuals who adopt a healthy diet have significantly lower risks of CVD, including both CHD and stroke. Data from observational studies suggest that adherence to a healthy diet is associated with approximately a 20 percent reduction in all-cause mortality and 30 percent reduction in CVD risk [34,35]. Mediterranean-style diets and plant-based diets have been associated with lower rates of cardiovascular and all-cause mortality in multiple observational studies. (See "Healthy diet in adults", section on 'Dietary guidelines: Recommended dietary patterns'.)

Physical activity — We assess patients' level of physical activity by asking about formal exercise and routine activities, such as walking, housework, and gardening. We use the "FITT" mnemonic to quantify physical activity: frequency, intensity, time, and type of activity.

We counsel patients to engage in regular physical activity throughout life. Common exercise parameters for reducing CVD risk include engaging in at least 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity exercise per week, combined with muscle strengthening activities at least twice weekly [31]. Adults with limited exercise capacity due to comorbidities should stay as physically active as their condition allows [36,37]. Even modest amounts of regular physical activity, such as brisk walking for 20 minutes daily, are associated with significant reductions in the risk of CHD [38].

Individuals who engage in increased physical activity have lower morbidity and mortality from CHD (figure 2). Nonetheless, in the United States, only 21 percent reach the daily minimum requirement for physical activity [36-38].

The role of increased physical activity for primary prevention is discussed in detail separately. (See "Exercise and fitness in the prevention of atherosclerotic cardiovascular disease".)

Limit alcohol use — We routinely ask individuals if they drink alcohol and to quantify their alcohol use. For individuals who drink any alcohol, we use the following question to screen for unhealthy alcohol use: "How many times in the past year have you had five (four for females) or more drinks in a day?" Screening for unhealthy alcohol use is discussed separately. (See "Screening for unhealthy use of alcohol and other drugs in primary care", section on 'Screening tests'.)

We encourage individuals who drink alcohol to limit their intake to ≤1 drink/day for nonpregnant females and males aged 65 years and older and to ≤2 drinks/day for males under age 64 years. Individuals who do not currently drink should not begin drinking to reduce their cardiovascular risk. Heavy alcohol consumption is associated with an increased risk of CVD and overall mortality. It is uncertain whether lower levels of alcohol consumption improve or worsen cardiovascular outcomes, and alcohol has proven harmful effects on other outcomes, such as traumatic injuries, cancer, liver disease, and pancreatic disease. (See "Overview of the risks and benefits of alcohol consumption", section on 'Alcohol effect on specific conditions'.)

Although large observational studies have suggested a J-shaped curve for the relationship between alcohol intake and the risk of CHD, rigorous controlling for confounding attenuates the apparent cardioprotective effect of light alcohol intake [39].

Heavy alcohol consumption is associated with an increased risk of all-cause mortality and several cardiovascular conditions, including hypertension, atrial fibrillation, hemorrhagic and ischemic stroke, heart failure, and sudden cardiac death. Cardiovascular and general risks and benefits of alcohol are discussed separately. (See "Cardiovascular benefits and risks of moderate alcohol consumption" and "Overview of the risks and benefits of alcohol consumption".)

Adequate sleep — We ask patients about the usual duration of their sleep because inadequate sleep is an independent risk factor for CVD events. We typically advise individuals to aim for a habitual sleep duration of seven to eight hours nightly. Inappropriate sleep duration has been associated with an increased risk of MI and increased incidence of CVD risk factors and subclinical noncoronary atherosclerotic plaque burden, although limited evidence exists to confirm that improving sleep duration or quality reduces CVD events [40]. The role of short sleep duration on cardiovascular morbidity is discussed separately. (See "Insufficient sleep: Definition, epidemiology, and adverse outcomes", section on 'Cardiovascular morbidity'.)

This approach is consistent with recommendations from the AHA [40].

Benefits of maintaining multiple healthy behaviors — Multiple large cohort studies document that maintaining a healthy lifestyle is associated with cardiovascular risk reduction. The benefits of maintaining multiple healthy habits over time are at least additive [41].

●Lower rates of cardiovascular and all-cause mortality – Observational studies show an association between maintaining a healthy lifestyle and reduced rates of CVD and overall deaths [42]. As an example, in a prospective European cohort of 2339 older individuals (ages 70 to 90 years) without CVD at baseline, maintaining four lifestyle changes (eating a Mediterranean diet, being physically active, not smoking, and drinking small amounts of alcohol daily) was associated with a 65 and 67 percent lower risk of all-cause and CVD mortality, respectively, compared with the effect of zero to one lifestyle changes [43].

●Lower rates of CVD events – In the Nurses' Health Study of over 121,700 United States females followed for 14 years, females who adhered to a healthy diet, engaged in daily exercise, maintained a normal weight, and avoided smoking had an 85 percent reduction in the relative risk of CVD events compared with all other females [44]. Similarly, in a prospective cohort of over 20,000 Swedish males aged 45 to 79 years without established CVD or CVD risk factors, maintaining a healthy lifestyle was associated with an 86 percent relative risk reduction of MI [45]. The study defined a healthy lifestyle as not smoking, being physically active, having no abdominal adiposity, and engaging in a healthy diet and moderate alcohol consumption. Other studies have reported similar reductions in stroke risks in those who maintain a healthy lifestyle [46,47].

IDENTIFYING AND ADDRESSING KEY RISK FACTORS

Hypertension — All adults should undergo blood pressure screening at least once annually to identify hypertension [48]. Those identified by screening should undergo home or ambulatory blood pressure monitoring to confirm the diagnosis (algorithm 1) [48]. All individuals with hypertension should undergo risk stratification to determine their goal blood pressure and management with nonpharmacologic measures and, for most patients, antihypertensive medications.

Hypertension is a well-established risk factor for CVD. At the population level, hypertension causes more cardiovascular deaths than any other modifiable cardiovascular risk factor, both in the United States and worldwide [5,49]. Hypertension accounts for approximately 58 percent of hemorrhagic and 50 percent of ischemic stroke, 55 percent of ischemic heart disease, and 58 percent of other CVD [50,51]. Conversely, reducing blood pressure to normal levels reduces the risk for CVD events and all-cause mortality by 20 to 40 percent [50,52]. The cardiovascular risks of hypertension are detailed elsewhere. (See "Cardiovascular risks of hypertension".)

●Definition – Guidelines from the American Heart Association/American College of Cardiology define hypertension as a systolic pressure ≥130 mmHg or a diastolic pressure ≥80 mmHg [53]. Guidelines from Europe and the United Kingdom set higher diagnostic thresholds [54,55]. A linear relationship exists between increasing blood pressure and cardiovascular risk, with a doubling of cardiovascular risk for each 20 mmHg increase in systolic and 10 mmHg increase in diastolic blood pressure above levels of 115 systolic and 75 diastolic [56]. The relationship between blood pressure and increased risk of cardiovascular events begins as early as adolescence, underscoring the importance of early intervention strategies [57]. Definitions of hypertension and our approach to diagnosing hypertension are discussed separately (table 6 and algorithm 1). (See "Overview of hypertension in adults" and "Hypertension in adults: Blood pressure measurement and diagnosis".)

●Management

•Goal blood pressure – For individuals without cardiovascular risk factors, we target a blood pressure goal of ≤130/80. Individuals at higher cardiovascular risk may benefit from more intensive blood pressure reduction. Risk stratification to determine goal blood pressure should identify comorbidities relevant to CVD risk (eg, diabetes, chronic kidney disease) and, for patients who are candidates for formal atherosclerotic cardiovascular disease (ASCVD) risk calculation, the patient's 10-year estimated risk of ASCVD events. Goal blood pressures, how to assess ASCVD risk, and specific risk calculators are discussed separately. (See "Goal blood pressure in adults with hypertension" and "Cardiovascular disease risk assessment for primary prevention: Risk calculators" and "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults", section on 'ASCVD risk assessment'.)

•Therapeutic lifestyle changes – Patients with hypertension or elevated blood pressure should practice therapeutic lifestyle changes (TLCs), whether or not they are taking antihypertensive agents. In addition to lifestyle modifications that apply to all patients (see 'Promoting a healthy lifestyle' above), individuals with hypertension should reduce sodium intake and ensure adequate intake of potassium. These interventions are summarized in a table and discussed separately (table 7). (See "Overview of hypertension in adults", section on 'Nonpharmacologic therapy'.)

Nonpharmacologic measures can enhance the effectiveness of antihypertensive medications and enable some individuals to attain goal blood pressure. Combining multiple TLCs further augments blood pressure reduction [19].

•Pharmacologic therapy – Most individuals with hypertension will need medication to achieve their goal blood pressure, and many will require multiple agents. When to start pharmacologic therapy and the choice of a specific agent are discussed separately. (See "Overview of hypertension in adults", section on 'Pharmacologic therapy' and "Hypertension in adults: Initial drug therapy".)

Overweight and obesity — All adults should be screened for overweight and obesity at least once annually. Individuals with obesity or overweight should receive behavioral counseling that includes discussion of weight loss goals and lifestyle interventions [58]. Individuals at higher cardiovascular risk may benefit from antiobesity medications or metabolic (bariatric) surgery. (See "Obesity in adults: Overview of management".)

Overweight and obesity are important modifiable cardiovascular risk factors that are increasing globally [1,59]. A linear relationship exists between increasing body weight and higher rates of coronary heart disease (CHD)-related morbidity and mortality. Obesity increases the risk of developing of CHD, heart failure (especially heart failure with preserved ejection fraction), atrial fibrillation, and sudden cardiac death. Overweight and obesity contribute to the development of hypertension, dyslipidemia, and insulin resistance. Conversely, weight loss can resolve or improve them [60-62]. (See "Overweight and obesity in adults: Health consequences" and "Obesity: Association with cardiovascular disease".)

●Definition and detection – Overweight (body mass index [BMI] of 25 to 29.9 kg/m²) and obesity (BMI of ≥30 kg/m²) are chronic conditions that are commonly defined in terms of BMI. In those with BMI between 25 and 35 kg/m², we additionally measure waist circumference to identify those who are at higher risk for developing CVD. This is consistent with guidelines for the screening and evaluation of overweight and obesity [58,60,63-66]. Screening for and evaluation of obesity are discussed separately. (See "Obesity in adults: Prevalence, screening, and evaluation".)

●Weight loss goals – Patients and clinicians can work together to develop individualized weight loss goals that incorporate the patient's baseline cardiovascular risk, health goals, and preferred interventions for weight loss. Even a weight loss of 5 percent can reduce cardiovascular risk. Goals of treatment for individuals with overweight and obesity are discussed separately. (See "Obesity in adults: Overview of management", section on 'Goals of treatment'.)

●Therapeutic lifestyle changes – Individuals with overweight or obesity should be assessed for their willingness make lifestyle changes. Those who are ready should work with their clinicians to develop a plan for behavior modification, dietary changes, and increased physical activity. TLCs alone typically result in a 5 to 7 percent reduction in body weight. These topics are discussed separately. (See "Obesity in adults: Behavioral therapy" and "Obesity in adults: Dietary therapy" and "Obesity in adults: Role of physical activity and exercise".)

●Antiobesity medications and metabolic (bariatric) surgery – Individuals at moderate to high cardiovascular risk who are not able to attain weight loss goals through TLCs may benefit from antiobesity medications or metabolic surgery. (See "Obesity in adults: Drug therapy" and "Obesity in adults: Overview of management", section on 'Bariatric surgery'.)

Type 2 diabetes mellitus — Because early intervention in individuals with type 2 diabetes mellitus can reduce cardiovascular risk, we screen for diabetes mellitus in adults ages 35 to 70 years with overweight, obesity, or other factors that increase the risk of diabetes (table 1) [67] (see "Screening for type 2 diabetes mellitus and prediabetes"). Those who meet diagnostic criteria for diabetes or prediabetes should receive intensive lifestyle counseling and CVD risk factor management. Many individuals with newly diagnosed type 2 diabetes benefit from pharmacotherapy to improve glycemic control and reduce cardiovascular risk.

Diabetes mellitus is a major cardiovascular risk factor whose prevalence is increasing worldwide [1,68]. Approximately 90 percent of individuals with diabetes mellitus have type 2 diabetes. Cardiovascular (eg, "macrovascular") complications of CHD, stroke, and peripheral artery disease pose the primary threat to mortality for those with type 2 diabetes mellitus. Chronic hyperglycemia is associated with increased rates of cardiovascular events, and tight glycemic control has been linked to a reduction in events in those with type 1 diabetes [69].

Although results from early trials of intensive glycemic control on cardiovascular macrovascular outcomes in those with type 2 diabetes were mixed [70,71], emerging evidence suggests that glycemic control and intensive risk factor modification decrease cardiovascular complications [49,72]. Aggressive risk factor modification can reduce cardiovascular risk and mortality in these patients, particularly if they begin TLCs early in the course of the disease.

●Definition and detection – In individuals without symptoms of hyperglycemia, a fasting plasma glucose of ≥126 mg/dL (7 mmol/L) or a hemoglobin A1C of ≥6.5 percent on two separate occasions establishes a diagnosis of diabetes (table 8). Additional recommendations on screening and diagnosis are discussed separately. (See "Screening for type 2 diabetes mellitus and prediabetes".)

●Management – Multifactorial interventions should include smoking cessation, increased physical activity, weight reduction, aggressive glycemic and blood pressure control, and lipid-lowering therapy. The role of glycemic control in CVD risk reduction and specific interventions to reduce macrovascular disease are discussed separately. (See "Overview of general medical care in nonpregnant adults with diabetes mellitus", section on 'Reducing the risk of macrovascular disease' and "Glycemic management and vascular complications in type 1 diabetes mellitus" and "Glycemic management and vascular complications in type 2 diabetes mellitus".)

•Therapeutic lifestyle changes – TLCs for patients with diabetes include smoking cessation, weight reduction, and increased physical activity. (See 'Overweight and obesity' above and "Overview of general medical care in nonpregnant adults with diabetes mellitus", section on 'Reducing the risk of macrovascular disease'.)

•Medications for glycemic control and cardiovascular risk reduction – Goals for glycemic control should be individually tailored and consider the patient's age, duration of diabetes, and medical comorbidities. Most individuals with type 2 diabetes will ultimately require pharmacotherapy, such as metformin, to achieve glycemic control. Although some newer classes of medications, such as the glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, have demonstrated reductions in CVD mortality in patients with established CVD, their role in primary prevention remains uncertain [73].

-Glycemic control – Pharmacotherapy for glycemic control and CVD risk reduction in individuals with type 2 diabetes mellitus is discussed separately (table 9). (See "Initial management of hyperglycemia in adults with type 2 diabetes mellitus", section on 'Initial pharmacologic therapy' and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects'.)

-Statin therapy – Individuals with diabetes ages 40 to 75 years should receive statin therapy for cardiovascular risk reduction (see 'Dyslipidemia' below). It is less clear whether statin therapy benefits those with diabetes who are aged 20 to 39 years or over 75. (See "Overview of general medical care in nonpregnant adults with diabetes mellitus", section on 'Lipid management'.)

-Aspirin – The role of low-dose aspirin in the primary prevention of CVD among those with type 2 diabetes is uncertain. (See "Overview of general medical care in nonpregnant adults with diabetes mellitus", section on 'Aspirin'.)

Dyslipidemia — We perform lipid screening as part of ASCVD risk assessment for all adults ≥20 years old (see "Screening for lipid disorders in adults"). Those with elevated low-density lipoprotein cholesterol (LDL-C) should engage in risk modification through diet and, if indicated, pharmacotherapy with a statin.

Elevated LDL-C levels are correlated with ASCVD risk. Meta-analyses of randomized trials demonstrate that statin therapy lowers LDL-C and decreases ASCVD-related morbidity and mortality across a wide range of patients and LDL-C levels. (See "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease".)

●General management of LDL-C elevation

•Therapeutic lifestyle changes – In addition to maintaining a healthy lifestyle, individuals with an elevated LDL-C should follow a low-cholesterol diet (see 'Promoting a healthy lifestyle' above). Specific dietary changes to reduce cholesterol are discussed separately. (See "Lipid management with diet or dietary supplements".)

•Medications and target LDL-C reductions – The decision to initiate pharmacotherapy depends on the LDL-C level and the patient's estimated 10-year risk of ASCVD. Individuals who cannot achieve their target LDL-C with TLCs should start a medication for LDL-C reduction, typically a statin. Adults ages 30 to 79 years with a 10-year ASCVD risk of ≥10 percent should receive statin therapy. Those ages 30 to 79 years with a 10-year ASCVD risk between 7.5 and 10 percent may also benefit from statin therapy, particularly if they have factors that increase their cardiovascular risk ("risk-enhancing factors") (table 10). (See "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease".)

Target LDL-C levels vary depending on the patient's age, cardiovascular risk factors, and 10-year ASCVD risk. Except for patients with familial dyslipidemias and/or an LDL-C ≥190, most individuals can attain their goal LDL-C with a statin.

Statin therapy is categorized based on the expected degree of LDL-C lowering, with LDL-C decreases of >50 percent, 30 to 50 percent, and <30 percent defined as high-, moderate-, and low-intensity statin therapy, respectively (table 11). The individual's overall ASCVD risk generally dictates the intensity (dose and type) of statin therapy. Patients at higher cardiovascular risk generally benefit from higher-intensity statin therapy. Those with an LDL-C ≥190 mg/dL (≥4.9 mmol/L) are at high risk of ASCVD, should generally receive high-intensity statin therapy, and may require additional low-density lipoprotein-lowering agents. (See "Familial hypercholesterolemia in adults: Treatment".)

Patients with diabetes between the ages of 40 and 75 typically require moderate- to high-intensity statin therapy. The utility of statin therapy for individuals aged 76 or older is unclear.

Specific indications for statin therapy, its initiation and management, adherence to therapy, and potencies and side effects of specific statins are discussed separately (algorithm 2 and table 11). (See "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease" and "Adherence to lipid-altering medications and recommended lifestyle changes" and "Statins: Actions, side effects, and administration".)

Meta-analyses of statin therapy for primary ASCVD prevention in high-, moderate-, and low-risk individuals demonstrate that statin therapy reduces rates of clinical cardiovascular outcomes, including myocardial infarction, stroke, CVD death, and total mortality [74].

INTERVENTIONS OF UNCLEAR BENEFIT

Aspirin — The use of low-dose aspirin (75 to 100 mg daily) can be considered for the primary prevention of CVD. Aspirin use is not routine; rather, we encourage clinicians and patients to engage in individualized decision making that weighs the benefits and harms of low-dose aspirin and includes an assessment of the patient's risk of cardiovascular events and major bleeding as well as patient values pertaining to preventing specific outcomes (table 12). Aspirin should be considered only after implementation of therapeutic lifestyle changes and other drugs of proven benefit such as statins. Individualized risk assessment and decision making about aspirin for primary prevention is discussed separately. (See "Aspirin in the primary prevention of cardiovascular disease and cancer", section on 'Assessing benefits and risks'.)

Single-pill combination medications — The need for multicomponent CVD risk factor reduction has generated interest in fixed-dose combination medications (ie, "polypills," single-pill combinations, or SPCs) as potentially effective strategies for primary atherosclerotic cardiovascular disease (ASCVD) prevention. Single-pill combination medications contain multiple agents, such as statins and antihypertensive medications [75]. Although these agents can potentially improve medication adherence and decrease costs, the use of multiple drugs in one pill can also increase rates of adverse effects and complicate dose titration [76,77]. Examples of these agents appear in a table (table 13), and their use in patients with hypertension and established CVD are discussed separately. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention)", section on 'Polypill' and "Hypertension in adults: Initial drug therapy", section on 'Combination therapy for most patients'.)

Primary prevention trials of fixed-dose combination pills suggest that they may confer a small absolute risk reduction in cardiovascular events [78]. A 2021 meta-analysis of three randomized trials of 18,162 individuals compared fixed-dose polypills (two antihypertensives and a low-dose statin, with or without aspirin) with placebo for primary ASCVD prevention [79]. During a median follow-up of five years, the primary outcome (a composite of cardiovascular death, myocardial infarction (MI), stroke, or revascularization) occurred in 3 percent of the polypill group compared with 4.9 percent in the placebo group (hazard ratio [HR] 0.62, 95% CI 0.53-0.73). Gastrointestinal side effects were more common in those taking aspirin. In some trials, polypills increase adherence and decrease surrogate outcomes (blood pressure and cholesterol) [77,80-86]. In contrast, an earlier systematic review of 13 trials (which included only one of the trials in the 2021 meta-analysis) found that polypills did not reduce fatal or nonfatal cardiovascular events or mortality [80].

Omega-3 fatty acids — The role of omega-3 fatty acids in the primary prevention of CVD is uncertain. Omega-3 fatty acids significantly reduce triglycerides in a dose-dependent manner [87], but their impact on clinical cardiovascular outcomes is less clear, especially in those already treated with evidence-based doses of statins [88]. Large trials have found mixed results as to whether omega-3 fatty acids reduce cardiovascular events in populations without established CVD.

●Patients with hypertriglyceridemia – Several large, randomized trials have yielded mixed results regarding the efficacy of omega-3 fatty acids in reducing cardiovascular events in individuals with hypertriglyceridemia, both in settings of primary and secondary prevention. These data and the use of omega-3 fatty acids for managing hypertriglyceridemia are discussed separately. (See "Hypertriglyceridemia in adults: Management", section on 'Marine omega-3 fatty acids'.)

●Patients without hypertriglyceridemia – For individuals without hypertriglyceridemia, it is unclear whether omega-3 fatty acid supplementation is effective for primary CVD prevention. In a randomized trial of 25,871 adults without known CVD (VITamin D and OmegA-3 TriaL [VITAL]), low-dose n-3 polyunsaturated fatty acid (1 g/day) did not reduce the primary endpoint of major cardiovascular events after a median follow-up of 5.3 years (HR 0.92, 95% CI 0.80-1.06) [89]. Although the trial found reductions in MI (HR 0.72, 95% CI 0.59-0.90), percutaneous coronary intervention (HR 0.78, 95% CI 0.63-0.95), total coronary heart disease (HR 0.83, 95% CI 0.71-0.97), and death from MI (HR 0.50, 95% CI 0.26-0.97), no significant reduction was observed in cardiovascular or all-cause mortality. The dose of omega-3 fatty acid used was comparable to that in many nonprescription supplements but lower than that recommended for treating hypertriglyceridemia (4 g/day).

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Assessment of cardiovascular risk" and "Society guideline links: Primary prevention of cardiovascular disease".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Lowering your risk of heart disease (The Basics)" and "Patient education: Atherosclerosis (The Basics)" and "Patient education: Heart-healthy diet (The Basics)" and "Patient education: Exercise and movement (The Basics)" and "Patient education: Controlling your blood pressure through lifestyle (The Basics)" and "Patient education: High blood pressure in adults (The Basics)" and "Patient education: High cholesterol (The Basics)")

●Beyond the Basics topics (see "Patient education: High cholesterol and lipids (Beyond the Basics)" and "Patient education: Diet and health (Beyond the Basics)" and "Patient education: Quitting smoking (Beyond the Basics)" and "Patient education: Losing weight (Beyond the Basics)" and "Patient education: Aspirin in the primary prevention of cardiovascular disease and cancer (Beyond the Basics)" and "Patient education: High blood pressure in adults (Beyond the Basics)" and "Patient education: Type 2 diabetes: Overview (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Assessment of cardiovascular risk factors – All adult patients should routinely undergo evaluation to identify modifiable atherosclerotic cardiovascular disease (ASCVD) risk factors, including an assessment of their level of physical activity, sleep, dietary intake, and use of tobacco and alcohol. They should also be screened for family history of early ASCVD; hypertension; dyslipidemia; overweight/obesity; and, for selected individuals, diabetes mellitus. (See 'Identify risk factors' above.)

●Estimating ASCVD risk – Quantifying an individual's ASCVD risk can identify patients at higher cardiovascular risk and who may benefit from more intensive risk factor reduction. Risk quantification using a calculator can help guide the intensity of therapy for dyslipidemia and hypertension and inform a decision about whether to use low-dose aspirin (algorithm 3). We use patient age to guide when to quantify an individual's ASCVD risk. (See "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults" and 'Assess ASCVD risk' above.)

●Maintaining a healthy lifestyle – We encourage all individuals to engage in the following measures to reduce the risk of cardiovascular disease (CVD): avoiding smoking, minimizing weight gain, adopting a healthy diet, and engaging in regular physical activity. Maintaining a healthy lifestyle across multiple domains of risk can substantially reduce the risk of myocardial infarction, stroke, and cardiovascular and overall mortality. (See 'Promoting a healthy lifestyle' above and "Exercise and fitness in the prevention of atherosclerotic cardiovascular disease" and "Healthy diet in adults" and "Overview of smoking cessation management in adults" and "Cardiovascular benefits and risks of moderate alcohol consumption".)

●Addressing modifiable metabolic risk factors – Identifying and treating hypertension, overweight and obesity, dyslipidemia, and diabetes are the cornerstones of primary CVD prevention. Reductions of multiple risk factors, through therapeutic lifestyle changes (TLCs) and adjunctive drug therapies of proven benefit, are likely to have at least additive benefits in the primary prevention of CVD. (See 'Identifying and addressing key risk factors' above and "Overview of hypertension in adults", section on 'Treatment' and "Obesity in adults: Overview of management" and "Overview of general medical care in nonpregnant adults with diabetes mellitus".)

●Role of aspirin – We individualize decision making regarding the use of aspirin for primary prevention. Aspirin should be considered only after implementation of TLCs and other drugs of proven benefit, such as statins. (See "Aspirin in the primary prevention of cardiovascular disease and cancer".)