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

Team-based care makes use of multidisciplinary health professionals to improve the quality and maintenance of ASCVD prevention. It is a multifaceted approach that supports clinical decision-making (ie, treatment algorithms), collaboration among different clinicians, and patient and family member participation to facilitate the treatment goals of patients.^S2.1-26 RCTs and systematic reviews with meta-analyses demonstrated greater reduction of ASCVD risk with team-based care than with usual care in patients with hypertension, diabetes, and hyperlipidemia.^{S2.1-1–S2.1-14} A team-based approach to ASCVD prevention may result in significant improvements in patient outcomes^S2.1-27 and often meets patient needs better than standard care, especially in low-resource settings and among vulnerable populations. In a team-based care model that compared patients enrolled in a preventive cardiology clinic staffed by advanced practice providers with a propensity-matched cohort of patients enrolled in primary care clinics, a reduction in cardiovascular risk was demonstrated through effective risk stratification and preventive management.^S2.1-28 Other successful interventions that have used team-based care include telehealth monitoring, follow-up support aids, and patient education.^S2.1-27

Decisions about primary prevention should be collaborative between a clinician and a patient. Shared decision-making occurs when practitioners engage patients in discussions about personalized ASCVD risk estimates and their implications for the perceived benefits of preventive strategies, including lifestyle habits, goals, and medical therapies. Collaborative decisions are more likely to address potential barriers to treatment options, compared with treatment and guidance offered without patient input.^{S2.1-15–S2.1-18}

Socioeconomic inequalities are strong determinants of CVD risk internationally.^{S2.1-21,S2.1-24} Therefore, the clinician should tailor advice to a patient’s socioeconomic and educational status, as well as cultural, work, and home environments.^S2.1-23 The Centers for Medicare & Medicaid Services has developed a screening tool to assess 5 domains of non–health-related measures that affect health outcomes: housing instability, food insecurity, transportation difficulties, utility assistance needs, and interpersonal safety.^S2.1-29 ASCVD prevention could benefit from such screening. ASCVD risk begins early in life, with heightened susceptibility tied to low socioeconomic status.^S2.1-25 Examples of upstream social determinants of health that affect treatment adherence and ASCVD health outcomes include comorbid mental illness, lack of health literacy, exposure to adversity (eg, home/community violence, trauma exposures, safety concerns), financial strain, inadequate housing conditions, lack of food security (ie, access to affordable and nutritious food), and inadequate social support.^S2.1-30 Systems of care should evaluate social determinants of health that affect care delivery for the primary prevention of ASCVD (eg, transportation barriers, the availability of health services).

Important considerations related to socioeconomic disadvantage are not captured by existing CVD risk equations.^S2.1-31 Addressing unmet social needs improves management of BP and lipids,^S2.1-32 which highlights the importance of dietary counseling and encouraging physical activity.^S2.1-19 More time may be required to address ASCVD prevention with adults of low health literacy or disadvantaged educational backgrounds.

Differential cardiovascular outcomes persist by important sociodemographic characteristics that include but are not limited to age, sex, and race/ethnicity.^{S2.1-22,S2.1-33–S2.1-35} Failure to address the impact of social determinants of health impedes efficacy of proven prevention recommendations. Table 2 outlines key considerations related to social determinants of health and ASCVD prevention.

To facilitate decisions about preventive interventions, it is recommended to screen for traditional ASCVD risk factors and apply the race- and sex-specific PCE (ASCVD Risk Estimator) to estimate 10-year ASCVD risk for asymptomatic adults 40 to 75 years of age.^{S2.2.1,S2.2.2} For management of stage 1 hypertension (BP 130–139 / 80–89 mm Hg), adults should be categorized as <10% or >10% 10-year ASCVD risk for therapeutic decisions (see Section 4.4 Figure 4). For management of blood cholesterol, adults should be categorized as having low (<5%), borderline (5% to <7.5%), intermediate (≥7.5% to <20%), or high (≥20%) 10-year risk.^S2.2-4 The PCE are best validated among non-Hispanic whites and non-Hispanic blacks living in the United States.^{S2.2-1,S2.2-39,S2.2-48,S2.2-49,S2.2-52} In other racial/ethnic groups^{S2.2-53,S2.2-54} or in some non-US populations,^{S2.2-40,S2.2-41,S2.2-53,S2.2-54} the PCE may overestimate or underestimate risk. Therefore, clinicians may consider the use of another risk prediction tool as an alternative to the PCE if the tool was validated in a population with characteristics similar to those of the evaluated patient. Examples include the general Framingham CVD risk score,^S2.2-55 the Reynolds risk scores,^{S2.2-56,S2.2-57} SCORE (Systematic COronary Risk Evaluation),^S2.2-58 and the QRISK/JBS3^S2.2-59 tools. Other professional societies have incorporated some of these alternative validated risk scores into their lipid management guidelines or have considered different risk thresholds for preventive interventions.^{S2.2-58–S2.2-63} Although slight differences exist across organizational guidelines, they are all very similar in their overarching goal of matching the intensity of preventive therapies to the absolute (generally 10-year) risk of the patient.^{S2.2-58–S2.2-63}

After age 20 years, it is reasonable to measure traditional risk factors at least every 4 to 6 years.^{S2.2-1,S2.2-3} For adults 20 to 39 years of age, limited data exist on the performance and utility of 10-year risk estimation tools.^S2.2-64 Because age is a major driver of risk, most in this age range (<40 years) are unlikely to have a sufficiently elevated 10-year risk to warrant pharmacological therapy with a statin (with some exceptions, such as in familial hypercholesterolemia). Nevertheless, periodic assessment of risk factors (eg, at least every 4 to 6 years in younger adults 20 to 39 years of age) is important to guide discussions about intensity of lifestyle interventions, frequency of risk factor monitoring, treatment of nonlipid risk factors, and consideration of 30-year or lifetime risk estimation.^{S2.2-1–S2.2-3}

No single risk calculator is appropriate for all patients. In certain populations, the PCE have reasonable calibration.^{S2.2-1,S2.2-65–S2.2-67} However, some studies have found underestimation of risk (and potential for undertreatment) among individuals with chronic inflammatory conditions (eg, autoimmune disease,^S2.2-50 HIV infection^S2.2-12) or socioeconomic disadvantage^{S2.2-48,S2.2-49,S2.2-51} not captured in current risk scoring models. Patients with familial hypercholesterolemia are at significant risk of having an early ASCVD event, and the use of risk calculators is not applicable to these patients. In contrast, other studies have found overestimation of risk with the PCE, particularly among those with higher socioeconomic position and those with continual access to care and preventive services, which could lead to overtreatment of individuals less likely to receive net benefit from preventive pharmacotherapies over the next decade.^{S2.2-15,S2.2-39–S2.2-47} The PCE may be suboptimally calibrated in more modern populations as compared with the older cohorts from which they were derived.^S2.2-68 Therefore, among adults at borderline (5% to <7.5%) and intermediate (≥7.5% to <20%) risk, one may consider additional individual risk-enhancing clinical factors (Table 3) that can be used to revise the 10-year ASCVD risk estimate.^S2.2-4 These factors may include having a family history of premature ASCVD,^S2.2-5 chronic inflammatory disease [rheumatoid arthritis,^S2.2-6 lupus,^S2.2-7 or HIV infection^S2.2-12], South Asian ancestry,^S2.2-13 a history of preeclampsia^S2.2-8 or preterm delivery,^S2.2-9 early menopause,^S2.2-10 erectile dysfunction,^S2.2-11 chronic kidney disease (CKD), metabolic syndrome, persistently elevated inflammatory markers,^S2.2-14 or elevated lipid biomarkers.^S2.2-4 After these clinically available risk-enhancing factors have been considered, if there is still uncertainty about the reliability of the risk estimate for individuals in the borderline- or intermediate-risk categories, further testing to document subclinical coronary atherosclerosis is reasonable to more accurately reclassify the risk estimate upward or downward.^{S2.2-17–S2.2-19,S2.2-69}

For individuals with intermediate predicted risk (≥7.5% to <20%) by the PCE or for select adults with borderline (5% to <7.5%) predicted risk, coronary artery calcium measurement can be a useful tool in refining risk assessment for preventive interventions (eg, statin therapy).^S2.2-4 In these groups, coronary artery calcium measurement can reclassify risk upward (particularly if coronary artery calcium score is ≥100 Agatston units (AU) or ≥75th age/sex/race percentile) or downward (if coronary artery calcium is zero) in a significant proportion of individuals.^S2.2-15 The extent of reclassification is sufficient to provide confidence that borderline- or intermediate-risk patients with elevated coronary artery calcium will have event rates that clearly exceed benefit thresholds (ie, ≥7.5% in 10 years) and those with coronary artery calcium scores of zero will have event rates <7.5%, which can help guide shared decision-making about statins^{S2.2-15,S2.2-16,S2.2-21} or potentially even aspirin.^S2.2-70 In observational data, the presence and severity of coronary artery calcium have been shown to be associated with the likelihood of benefit from statin therapy for ASCVD risk reduction.^S2.2-71 Coronary artery calcium scoring has superior discrimination and risk reclassification as compared with other subclinical imaging markers or biomarkers.^{S2.2-22,S2.2-27} In the MESA (Multi-Ethnic Study of Atherosclerosis) trial, the coronary artery calcium score was strongly associated with 10-year ASCVD risk in a graded manner across age, sex, and racial/ethnic groups, independent of traditional risk factors.^S2.2-17 Coronary artery calcium may even refine ASCVD risk estimates among lower-risk women (<7.5% 10-year risk),^S2.2-7 younger adults (<45 years of age),^S2.2-20 and older adults (≥75 years of age),^S2.2-26 but more data are needed to support its use in these subgroups. A coronary artery calcium score of zero identifies individuals at lower risk of ASCVD events and death over a ≥10-year period,^{S2.2-15,S2.2-17,S2.2-25} who appear to derive little or no benefit from statins for ASCVD risk reduction.^S2.2-71 Thus, the absence of coronary artery calcium could reclassify a patient downward into a lower risk group in which preventive interventions (eg, statins) could be postponed.^S2.2-22 Note that the absence of coronary artery calcium does not rule out noncalcified plaque, and clinical judgment about risk should prevail. Coronary artery calcium might also be considered in refining risk for selected low-risk adults (<5% 10-year risk), such as those with a strong family history of premature coronary heart disease (CHD).^S2.2-23 MESA^S2.2-28 and Astro-CHARM (Astronaut Cardiovascular Health and Risk Modification)^S2.2-29 are risk estimation tools that incorporate both risk factors and coronary artery calcium for estimating 10-year CHD and ASCVD risk, respectively. Coronary artery calcium 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.

For adults 20 to 39 years of age (who are not included in the PCE) and those 40 to 59 years of age who are not already at elevated (≥7.5%) 10-year risk, estimating a lifetime or 30-year risk of ASCVD may be considered (ASCVD Risk Estimator).^S2.2-2 Younger individuals often have low estimated 10-year risk, but the presence of at least 1 major risk factor by middle age is associated with increased lifetime ASCVD risk and reduced survival free of morbidity compared with those with optimal risk factors.^{S2.2-32–S2.2-34} Calculation of lifetime risk with the ACC/AHA 30-year/lifetime risk estimator for those 20 to 59 years of age (not at high short-term risk) may be reasonable to consider as a communication strategy for reinforcing adherence to lifestyle recommendations.^S2.2-2

Plant-based and Mediterranean diets, along with increased fruit, nut, vegetable, legume, and lean vegetable or animal protein (preferably fish) consumption, with the inherent soluble and insoluble vegetable fiber, have consistently been associated with lower risk of all-cause mortality than control or standard diets^{S3.1-1–S3.1-10,S3.1-29,S3.1-30} in observational studies. The PREDIMED (Prevención con Dieta Mediterránea) trial randomized participants to a Mediterranean diet supplemented with either extra-virgin olive oil or nuts and demonstrated 30% and 28% reductions, respectively, in the combined endpoint (MI, stroke, or cardiovascular mortality), but the improved outcome was driven largely by the reduction in stroke, with no significant improvement over the control diet for mortality or MI.^S3.1-1 When the PREDIMED cohort was reanalyzed post hoc for the “provegetarian” food pattern (more vegetable consumption versus animal, egg, fish, dairy, or meat product consumption), a significant mortality rate reduction (41%) was noted in the 2 quintiles with the highest vegetarian score.^S3.1-11 A comparison of plant and animal protein from the Adventist Health Study-2 cohort^S3.1-10 similarly indicated that using meat for protein was associated with a 61% increase in mortality rate, whereas replacing meat with nuts and seeds was associated with a 40% reduction in mortality rate. Similarly, the graded risk published by Song et al. indicated that lower mortality rate was associated with replacing animal protein of different origins with plant protein.^S3.1-9 The evidence is mixed with regard to the effectiveness of dairy intake to reduce ASCVD risk factors, which is why it is not included in the listed foods for this recommendation. Although the DASH (Dietary Approaches to Stop Hypertension) diet, which includes low-fat dairy products, was shown to reduce BP,^S3.1-14 and the PURE (Prospective Urban Rural Epidemiology) study indicated that dairy intake was associated with a 23% lower mortality rate,^S3.1-31 Song et al. indicated an 11% increase in cardiovascular mortality rate with dairy consumption as compared with vegetable protein S3.1-9).

Trans and saturated fats have been associated with a higher risk of total and cause-specific death.^S3.1-12 However, observational data from the PURE trial suggested that, when used instead of refined carbohydrates, saturated and unsaturated fats were associated with reduced stroke and mortality.^S3.1-13

Dietary sodium reduction was found to reduce BP and cardiovascular events in the DASH trial and in TOHP (Trials of Hypertension Prevention).^{S3.1-14,S3.1-15} Data from NHANES (National Health and Nutrition Examination Surveys)^S3.1-16 suggest that high consumption of sodium (>2000 mg daily), red meat (>14 g/d), and sugar-sweetened beverages and processed red meat consumption were associated with cardiovascular death. A prospective cohort study of US healthcare professionals^S3.1-9 with at least 1 risk factor indicated that replacement of animal protein (sources of cholesterol, saturated fat, heme iron and precursors of trimethylamine-N-oxide) with plant protein was associated with reduced cardiovascular mortality rate. In that study, compared with plant protein, poultry and fish were associated with a 6% higher mortality rate, dairy with an 8% higher mortality rate, unprocessed red meat with a 12% higher mortality rate, eggs with a 19% higher mortality rate, and processed red meat with a 34% higher mortality rate. Overall, plant protein was associated with a reduction in mortality rate of 10% for every 3% energy increment replacement of animal protein.

Intake of several food products has been shown to be potentially harmful or increase risk of ASCVD. Sugar-sweetened and artificially sweetened beverages have been correlated with increasing the development of T2DM and with ASCVD risk, with a 20% increase in the frequency of diabetes mellitus with 1 daily serving of these sweetened beverages.^S3.1-18 In large cohort studies, consumption of added sugar at >10% of daily calories has been associated with increased mortality rate.^S3.1-19 However, adults who are habitually high consumers of sugar-sweetened beverages and utilize low calorie sweetened beverages as a replacement strategy that provides a sweet taste while reducing caloric intake may find this useful in the transition to water.^S3.1-20 In REGARDS (REasons for Geographic and Racial Differences in Stroke),^S3.1-21 the Southern dietary pattern was identified as substantially increasing health risks, including a 56% higher risk of heart disease and a 30% higher risk of stroke. This pattern consisted of more fried food, added fats, organ and processed meats, and sugar-sweetened beverages. Consuming a diet^S3.1-4 with juices and sweetened beverages, refined grains, potatoes/fries, and sweets resulted in a greater increase in coronary events than the increase seen with consumption of animal products. Given the additional risk associated with intake of these various food products, clinicians would do well to counsel individuals about their associated harm and advise them to avoid these foods when possible. Furthermore, longstanding dietary patterns that focus on low intake of carbohydrates and a high intake of animal fat and protein are associated with increased cardiac and noncardiac mortality rate.^{S3.1-22–S3.1-24} In 1 meta-analysis,^S3.1-23 low-carbohydrate diets were associated with a 31% higher risk of all-cause death, with increased cardiac mortality rate. Population data from the ARIC (Atherosclerosis Risk in Communities) study indicated an 18% increase in mortality rate with low-carbohydrate diets using animal-derived protein and fat sources (eg, lamb, beef, pork, chicken),^S3.1-22 but plant sources (eg, vegetables, nuts, peanut butter, whole-grain breads) were associated with lower mortality rate. In addition, the ARIC investigators noted a 23% increase in mortality rate associated with high-carbohydrate diets, with the optimal carbohydrate intake observed to be 50% to 55%.

Intake of trans fat has been shown to be harmful and increase risk of ASCVD. Trans fat was associated with higher all-cause mortality rate in the REGARDS US healthcare professionals cohort studies.^{S3.1-12,S3.1-17} Additionally, regulations to curb use of trans fat in the food industry have been associated with a decrease in stroke and MI.^S3.1-25 Trans fats have adverse effects on lipid and lipoproteins and promote endothelial dysfunction, insulin resistance, inflammation, and arrhythmias.^S3.1-26 Since partially hydrogenated oils are optional food additives, their elimination has been a public health priority.^S3.1-27

Physical activity assessment and counseling in the healthcare setting have important complementary roles in promoting increased physical activity.^S3.2-16 Ascertaining physical activity patterns during a standard clinical visit is the first step toward effective counseling and can be accomplished through several available simple assessment tools.^S3.2-16 The results of these tools can be recorded in the electronic health record, along with parameters such as weight and BP.^S3.2-16 Physical activity counseling by clinicians can result in modest improvements in physical activity levels, with a number needed to counsel as low as 12 for an individual to achieve recommended physical activity levels.^{S3.2-1,S3.2-2} This counseling might include an exercise prescription that consists of recommended frequency, intensity, time (duration), and type of exercise.

There is a consistent, strong, inverse dose–response relationship between the amount of moderate to vigorous physical activity and incident ASCVD events and death.^{S3.2-3–S3.2-8,S3.2-12} The shape of the dose–response relationship is curvilinear, with significant benefit observed when comparing those engaging in little or no physical activity with those performing moderate amounts.^{S3.2-5,S3.2-6,S3.2-12} All adults should engage in at least 150 minutes per week of accumulated moderate-intensity aerobic physical activity or 75 minutes per week of vigorous-intensity aerobic physical activity (or an equivalent combination of moderate and vigorous activity) to lower ASCVD risk (Table 4). These recommendations are in line with those of other health organizations.^S3.2-26 Shorter durations of exercise seem to be as beneficial as longer ones (eg, ≥10-minute bouts),^{S3.2-27,S3.2-28} and thus the focus of physical activity counseling should be on the total accumulated amount. Additional reduction in ASCVD risk is seen in those achieving higher amounts of aerobic physical activity (>300 minutes per week of moderate-intensity aerobic physical activity or 150 minutes per week of vigorous-intensity aerobic physical activity).^{S3.2-5,S3.2-6,S3.2-12,S3.2-14} There is a continued but diminishing additive benefit of further increasing physical activity to very high levels.^{S3.2-5,S3.2-6,S3.2-12} Specific exercise recommendations for the prevention of heart failure may differ slightly because the dose–response relationship with increasing physical activity levels may be linear.^S3.2-29

There is likely no lower limit on the quantity of moderate-to-vigorous physical activity at which benefits for ASCVD risk start to accrue.^S3.2-6 All efforts should be made to promote achievement of the minimum recommended amount of physical activity by all adults. However, for individuals unable to achieve this minimum, encouraging at least some moderate-to-vigorous physical activity among those who are inactive (ie, no moderate-to-vigorous physical activity) or increasing the amount in those who are insufficiently active is still likely beneficial to reduce ASCVD risk.^S3.2-6 Strategies to further increase physical activity in those achieving less than targeted amounts should be implemented.

Despite the focus on moderate- and vigorous-intensity physical activity, such activity accounts for a small proportion of individuals’ daily time as compared with other forms of activity. Other activity states that comprise a 24-hour period for an average individual include sleep, light-intensity physical activity, and sedentary behavior (Figure 1). Sedentary behavior refers to waking behavior with an energy expenditure of ≤1.5 metabolic equivalents while in a sitting or reclining posture (Table 4).^S3.2-30 Increased sedentary behavior is associated with worse health parameters, including cardiometabolic risk factors.^{S3.2-3,S3.2-9–S3.2-11} Sedentary behavior may be most deleterious to ASCVD risk for individuals who engage in the least amount of moderate to vigorous physical activity.^{S3.2-3,S3.2-10,S3.2-12} Thus, strategies to reduce sedentary behavior, particularly in those not achieving current recommended physical activity levels, may be beneficial for lowering ASCVD risk. However, data on the value of reducing or modifying sedentary behavior over time to reduce ASCVD risk are sparse, and whether replacing sedentary behavior with light-intensity activity (eg, slow walking, light work) is beneficial for ASCVD prevention is unclear.^S3.2-31 The strength and specificity of the recommendation to reduce sedentary behavior are limited by uncertainty about the appropriate limits of and optimal approach to modifying sedentary behavior.^S3.2-30

Clinically meaningful weight loss (≥5% initial weight) is associated with moderate improvement in BP, low-density lipoprotein cholesterol (LDL-C), triglyceride, and glucose levels among individuals with overweight/obesity.^S4.1-1 Weight loss reduces or delays the development of T2DM in persons with obesity.^{S4.1-1,S4.1-16,S4.1-17} High-intensity (≥14 sessions in 6 months) comprehensive weight-loss interventions provided by a trained interventionist work best.^S4.1-10 However, other modalities, such as electronically delivered weight-loss programs with personalized feedback and some commercial-based programs, have also shown moderate results.

Comprehensive lifestyle intervention consists of a structured program, which includes regular self-monitoring of food intake, physical activity, and weight. Increased physical activity, preferably aerobic physical activity (eg, brisk walking) for ≥150 minutes/week (equal to ≥30 minutes/day on most days of the week), is recommended for initial weight loss.^S4.1-10 Higher levels of physical activity, approximately 200 to 300 minutes/week, are recommended to maintain weight loss or minimize weight regain after 1 year. Adults with obesity are also typically prescribed a diet designed to reduce caloric intake by ≥500 kcal/day from baseline, which often can be attained by limiting women to 1200 to 1500 kcal/day and men to 1500 to 1800 kcal/day.^S4.1-10 A very-low-calorie diet (defined as <800 kcal/day) should be prescribed only in limited circumstances and only by trained clinicians in a medical care setting with the patient under medical supervision.^S4.1-10 Comprehensive lifestyle intervention has been shown to produce on average 8 kg of weight loss (5% to 10% of initial body weight) in the short term (≤6 months) and intermediate term (6 to 12 months), compared with usual care.^{S4.1-1,S4.1-10} However, longer interventions after 1 year are associated with gradual weight gain of 1 or 2 kg/year (on average), compared with usual care. Weight loss of 5% to 10% of initial weight, achieved through comprehensive lifestyle intervention, has been shown to improve BP, delay the onset of T2DM, improve glycemic control in T2DM, and improve lipid profile.^{S4.1-1,S4.1-2}

Measures used to estimate body fat and quantify the associated health risks include BMI, waist circumference, waist–hip ratio, bioimpedance, and dual-energy X-ray absorptiometry (DXA).^S4.1-18 BMI, waist circumference, and waist–hip ratio are easily measured and therefore are the most widely used in clinical practice. A USPSTF document found good evidence supporting the use of BMI to identify adults at increased risk of future morbidity and mortality.^S4.1-18 Because obesity/overweight defined by BMI is the most studied and standardized approach, we recommend its measurement for primary screening of individuals needing weight loss. BMI should be interpreted with caution in persons of Asian ancestry, older adults, and muscular adults.^{S4.1-19,S4.1-20}

Increased waist circumference has been associated with increased cardiometabolic and ASCVD risk.^{S4.1-3–S4.1-6} Central adiposity, captured by using waist circumference, has been associated with ASCVD risk and may be missed when BMI is used as the only measure of obesity.^{S4.1-21,S4.1-22} Waist circumference measurement is recommended in all patients with BMI <35 kg/m².^{S4.1-9,S4.1-19,S4.1-23} Ethnic differences in waist circumference thresholds associated with cardiometabolic risk have been reported. Waist circumference may be more useful than BMI in persons with abdominal obesity (central adiposity).^S4.1-24 Definitions of elevated waist circumference as ≥40 inches (≥102 cm) in men and ≥35 inches (≥88 cm) in women were recommended by the 1998 National Heart, Lung, and Blood Institute Obesity Initiative Expert Panel^S4.1-25 and were adopted by the 2013 AHA/ACC/TOS writing committee.^S4.1-1 Furthermore, waist circumference assessment is needed for the diagnosis of metabolic syndrome. Thus, combining waist circumference and BMI may be the best approach for assessing obesity-related risk. Counseling and comprehensive lifestyle interventions, including calorie restriction and adjunctive therapies (eg, FDA–approved drugs, bariatric surgery), have all been associated with significant reductions in waist circumference and improvement in cardiometabolic risk profiles.^S4.1-1

A heart-healthy dietary pattern is a key intervention in the treatment of T2DM. The Mediterranean, DASH, and vegetarian/vegan diets have all been shown to help in the achievement of weight loss and improve glycemic control in T2DM.^{S4.2-1,S4.2-2} Prospective cohorts have demonstrated a significantly lower likelihood of CVD events and CVD death in adults with T2DM who follow a healthy dietary pattern.^S4.2-17 However, an RCT targeting aggressive lifestyle interventions in T2DM was unable to show a reduction in ASCVD events despite early success in achieving weight loss.^S4.2-18

The quality of carbohydrate intake is especially important for control of T2DM, and focus should be placed on the intake of fiber-rich whole grains and avoidance of refined carbohydrates.^S4.2-19 Additionally, red meat consumption has been shown to increase the risk of T2DM, and decreasing intake of red meat can improve glycemic control.^{S4.2-20,S4.2-21} Weight loss is an essential treatment component for T2DM, and dietary recommendations should be adjusted to achieve meaningful weight loss, if needed. Establishing an appropriate nutrition plan requires time and effort and is best accomplished with assistance from a registered dietitian-nutritionist or a diabetes education program.

Initiation of an exercise program for those with T2DM has been shown to improve glycemic control, with a prior meta-analysis showing a significant reduction in mean HbA1c (7.65% versus 8.31%) in individuals assigned to an exercise program versus control groups.^S4.2-22 The combination of aerobic and resistance training further improves glycemic control and facilitates weight loss more than either type of exercise alone.^{S4.2-3,S4.2-4} Prospective cohort studies have provided supportive data for the benefits of physical activity in individuals with T2DM, with increased levels of physical activity associated with lower rates of CVD events and CVD death.^S4.2-17

How to best promote physical activity in individuals with T2DM remains unclear. For older individuals with other comorbidities, a simple walking program may be ideal, whereas for younger, healthier individuals, a variety of activities should be encouraged. In addition to a structured exercise program, a general increase in physical activity throughout the day (eg, taking the stairs, walking or biking to work, avoiding prolonged periods of sitting) should be encouraged.

Metformin decreases hepatic glucose production and increases peripheral insulin sensitivity, leading to a reduction in hyperglycemia in adults with T2DM. In a substudy of the UKPDS (United Kingdom Prospective Diabetes Study), metformin, compared with conventional therapy (ie, lifestyle modifications alone), resulted in a 32% reduction in microvascular and macrovascular diabetes-related outcomes, a 39% reduction in MI, and a 36% reduction in all-cause mortality rate.^S4.2-5 A 2016 systematic review and meta-analysis of glucose-lowering therapies for T2DM supported the use of metformin as first-line therapy for T2DM because of its beneficial effects on HbA1c, weight, and improved ASCVD outcomes (compared with sulfonylureas), as well as its acceptable safety profile and low cost. However, a separate systematic review found no evidence of reduced CVD events or CVD deaths with metformin.^S4.2-8 Metformin carries a small risk of lactic acidosis and must be used with caution in patients with CKD. For younger individuals or those with a mildly elevated HbA1c at the time of diagnosis of T2DM, clinicians can consider a trial of lifestyle therapies for 3 to 6 months before reconsideration of metformin.

Several classes of medications have been shown to effectively lower blood glucose but may or may not affect ASCVD risk.^{S4.2-23–S4.2-26} However, 2 classes of glucose-lowering medications have recently been demonstrated to reduce CVD events in adults with T2DM and high ASCVD risk. SGLT-2 inhibitors act in the proximal tubule to increase urinary excretion of glucose and sodium, leading to a reduction in HbA1c, body weight, and BP. Three RCTs have shown a significant reduction in ASCVD events and heart failure with use of an SGLT-2 inhibitor.^{S4.2-9,S4.2-10,S4.2-12} Although most patients studied had established CVD at baseline, the reduction in heart failure has been shown to extend to primary prevention populations.^{S4.2-12,S4.2-27} The GLP-1R agonists increase insulin and glucagon production in the liver, increase glucose uptake in muscle and adipose tissue, and decrease hepatic glucose production. Three GLP-1R agonists have been found to significantly reduce the risk of ASCVD in adults with T2DM who are at high ASCVD risk.^{S4.2-11,S4.2-13,S4.2-14} As opposed to a reduction in heart failure with SGLT-2 inhibitors, the benefit of the GLP-1R agonists has been a reduction in ASCVD events though the majority of patients studied had established CVD.

In patients with T2DM and additional risk factors for CVD, it may be reasonable to initiate these 2 classes of medications for primary prevention of CVD.

Large-scale RCTs in primary prevention demonstrated ASCVD risk reduction with moderate-intensity^{S4.3-6,S4.3-36} and high-intensity statin therapy^S4.3-7 that outweighed the observable risks. Subsequently, a large-scale RCT in an ethnically and racially diverse population confirmed statin benefit from a moderate-intensity statin therapy, as compared with placebo, in intermediate-risk patients. That RCT enrolled men ≥55 years of age and women ≥65 years of age with at least 1 cardiovascular risk factor. In the placebo group, the 10-year risk of “hard ASCVD” was 8.7%, and the risk of the expanded ASCVD endpoint that included coronary revascularization was 10%.^S4.3-9 After 5.6 years, those assigned to rosuvastatin 10 mg per day showed significant absolute risk reduction in both co-primary endpoints, with an acceptable safety record. By comparison, after a median follow-up of 1.9 years, those assigned to a high-intensity statin dose of rosuvastatin in the JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) RCT achieved greater LDL-C lowering and greater reductions in ASCVD outcomes.^S4.3-7 This corroborates meta-analyses demonstrating that in those at risk, net benefit of LDL-C–lowering therapy is greater with greater reductions in LDL-C.^{S4.3-2,S4.3-10}

If in the context of a risk discussion, maximal ASCVD risk reduction is desired, it is reasonable to use a high-intensity statin to lower LDL-C by ≥50%. This provides increased benefit, especially when 10-year ASCVD risk is ≥20%. JUPITER enrolled men ≥50 years of age and women ≥60 years of age with high-sensitivity C-reactive protein values ≥2.0 mg/L and LDL-C <130 mg/dL. Participants randomly assigned to 20 mg per day of rosuvastatin achieved a median LDL-C reduction of 50% and a highly significant ASCVD risk reduction at 1.9 years.^S4.3-7 Importantly, the magnitude of the percent LDL-C reduction achieved determined benefit.^S4.3-29 The USPSTF systematic review of statin therapy in primary prevention showed a reduced risk of all-cause and cardiovascular mortality and ASCVD events and noted greater absolute benefits in those at greater baseline risk,^S4.3-5 consistent with other high-quality systematic reviews and meta-analyses.^{S4.3-2,S4.3-8,S4.3-35} This underscores the need for aggressive and safe risk reduction in the highest-risk groups and the need for follow-up LDL-C testing to determine adherence and adequacy of effect of the statin prescribed.^S4.3-1

Most patients 40 to 75 years of age with diabetes are at intermediate or high risk (PCE ≥7.5% 10-year risk) of ASCVD events.^{S4.3-15,S4.3-16,S4.3-18} Three of 4 double-blinded primary-prevention RCTs of moderate statin therapy in large cohorts with diabetes in this age range showed significant reductions in ASCVD events.^{S4.3-11,S4.3-12,S4.3-14,S4.3-17} A meta-analysis of these trials found that moderate-intensity statin therapy was associated with a risk reduction of 25%,^S4.3-13 similar to people without diabetes and with no apparent difference in benefit between type 1 diabetes mellitus and T2DM. Therefore, moderate-intensity statin therapy is indicated for primary prevention in patients 40 to 75 years of age with diabetes.

Patients with primary severe hypercholesterolemia (LDL-C ≥190 mg/dL [≥4.9 mmol/L]) have a high risk of ASCVD^S4.3-23 and premature and recurrent coronary events. Although no randomized, placebo-controlled trials of statin therapy have been done exclusively in subjects with LDL-C ≥190 mg/dL, a placebo-controlled primary-prevention study performed in men with a mean baseline LDL-C of 192 ± 17 mg/dL demonstrated a reduced incidence of MI and cardiovascular death in those receiving pravastatin 40 mg daily.^S4.3-24 These findings were extended in a post hoc analysis of 2 560 exclusively primary-prevention subjects in that RCT and in a 20-year observational post-trial long-term follow-up study.^S4.3-37 Because moderate- or high-intensity statins have been shown to reduce ASCVD risk and because high-intensity statins provide greater ASCVD risk reduction than do moderate-intensity statins or placebo,^S4.3-2 maximally tolerated statin therapy should be administered to patients with LDL-C ≥190 mg/dL. Please refer to the 2018 cholesterol guideline^S4.3-1 for recommendations on the use of non-statin therapies in these patients.

The occurrence of a first ASCVD event in patients 40 to 75 years of age with diabetes is associated with increased morbidity and mortality compared with those without diabetes, which places a particularly high premium on primary prevention in individuals with diabetes in that age range. Although trials using moderate-intensity statin therapy have demonstrated significant benefit in such individuals, the residual risk in the statin treatment groups in these trials remained high. (eg, 8.5% had major cardiovascular events in 3.8 years).^S4.3-13 The benefit from statin therapy is related to both global risk and intensity of treatment,^S4.3-2 and no RCTs of high-intensity statin therapy have been carried out in cohorts of patients exclusively with diabetes. On the basis of these considerations and the fact that patients with diabetes have a higher trajectory of lifetime risk than do those without diabetes, high-intensity statin therapy is preferred in patients with diabetes as they develop risk modifiers (Table 5).

Knowledge of risk-enhancing factors (Table 3 in Section 2.2.) is useful for all individuals but particularly for those at intermediate risk (ASCVD risk of 7.5% to ≤20%). For example, in an RCT,^S4.3-38 a family history of premature ASCVD identified women ≥60 years of age with elevated hsCRP and without ASCVD who benefitted from high-intensity statin therapy. Those with primary LDL-C elevations of ≥160 mg/dL (≥4.1 mmol/L) have elevated lifetime ASCVD risk and benefit from statin therapy.^{S4.3-33,S4.3-36} Increased ASCVD risk is seen with metabolic syndrome;^S4.3-31 inflammatory diseases, including psoriasis^S4.3-39 and rheumatoid arthritis; and HIV when treated with protease inhibitors.^S4.3-40 The presence of risk-enhancing factors may affect the threshold for statin initiation or intensification. Lipoprotein (a) levels, especially in those with a family history of premature ASCVD, can increase risk.^S4.3-27 However, no available RCT evidence supports lipoprotein (a) levels as a target of therapy. Moderate primary elevations of triglycerides, non–HDL-C (total cholesterol – HDL-C), and, if measured, apolipoprotein B can improve selection of those at increased ASCVD risk.^S4.3-33

In adults at intermediate risk, coronary artery calcium measurement can be effective for meaningfully reclassifying risk in a large proportion of individuals.^{S4.3-41–S4.3-55} In such intermediate-risk adults, those with coronary artery calcium ≥100 AU or coronary artery calcium ≥75th percentile have ASCVD event rates for which initiation of statin therapy is reasonable.^S4.3-41 Those with coronary artery calcium scores of zero appear to have 10-year event rates in a lower range for which statin therapy may be of limited value. For those with coronary artery calcium scores of 1 to 99 AU, 10-year ASCVD event rates are 3.8%, 6.5%, and 8.3% for adults 45 to 54, 55 to 64, and 65 to 74 years of age, respectively,^S4.3-34 indicating that risk reclassification is modest for individuals with coronary artery calcium scores of 1 to 99. Therefore, for patients with coronary artery calcium scores of 1 to 99, it is reasonable to repeat the risk discussion. If these patients remain untreated, repeat coronary artery calcium measurement in 5 years may have some value, but data are limited.^{S4.3-56,S4.3-57} Selected examples of candidates who might benefit from knowing that their coronary artery calcium scores are zero are listed in Table 6. Clinicians should not downclassify risk in patients who have coronary artery calcium 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 coronary artery calcium of zero does not rule out risk from noncalcified plaque or increased risk of thrombosis.^S4.3-58

Benefit from statin therapy is also seen in lower-risk individuals.^S4.3-35 For those in the 5% to <7.5% risk range, available generic statins are cost-effective.^S4.3-59 Nonetheless, the challenge among those in a lower ASCVD risk category is to include those who would benefit, yet avoid casting too wide a net, to minimize treating those who would derive little benefit from statins. This risk group benefits greatly from a clinician–patient risk discussion. Clinicians should assess priorities for health care, perceived ASCVD risk, and prior risk reduction experiences and should use best practices for communicating risk to arrive at a shared risk decision. The presence of risk-enhancing factors is probably the best indicator favoring initiation of statin therapy (Table 3 in Section 2.2.).^S4.3-60 Although a coronary artery calcium score can be useful in select individuals, it will be positive less often in this lower-risk group than in those with higher levels of ASCVD risk and is not recommended routinely.^S4.3-41

Nonpharmacological interventions are effective in lowering BP and may be sufficient to prevent hypertension and to achieve goal BP in some individuals with hypertension, and they are integral in the management of those on anti hypertensive medication.^{S4.4-2,S4.4-3,S4.4-6,S4.4-7,S4.4-9–S4.4-11,S4.4-14,S4.4-15,S4.4-19,S4.4-20,S4.4-24} Furthermore, combining recommended nonpharmacological interventions has been shown to increase impact on BP reduction.^S4.4-65 Nonpharmacological intervention is the preferred therapy for adults with elevated BP and an appropriate first-line therapy for adults with stage 1 hypertension who have an estimated 10-year ASCVD risk of <10%. Adherence to and impact of nonpharmacological therapy should be assessed within 3 to 6 months. See Table 7 for recommended goals and approximate impact on SBP.

Meta-analyses and RCTs provide evidence for the benefit of BP-lowering medications on ASCVD prevention in adults with moderate to high ASCVD risk and SBP ≥130 mm Hg or DBP ≥80 mm Hg,^{S4.4-32,S4.4-33,S4.4-36,S4.4-37,S4.4-66} with significant outcome reductions demonstrated in stroke, heart failure, coronary events, and death. Significant reductions were seen in stroke and all-cause death at SBP <130 mm Hg and in stroke at DBP <80 mm Hg.^S4.4-37 SPRINT (Systolic Blood Pressure Intervention Trial) provides additional support for the use of BP-lowering medications in patients without CVD at SBP levels ≥130 mm Hg.^S4.4-34

Antihypertensive drug treatment that is based on overall ASCVD risk assessment combined with BP levels may prevent more CVD events than treatment that is based on BP levels alone.^{S4.4-67–S4.4-70} These meta-analyses are consistent in concluding that lowering of BP results in larger absolute risk reduction in higher-risk individuals, regardless of baseline treated or untreated BP ≥130/80 mm Hg and irrespective of the specific cause of elevated risk. These analyses indicate that the benefit of treatment outweighs the potential harm at threshold BP ≥130/80 mm Hg.

Meta-analyses and systematic reviews of trials that compare more intensive BP reduction to standard BP reduction report that more intense BP lowering significantly reduces the risk of stroke, coronary events, major cardiovascular events, and cardiovascular mortality.^{S4.4-33,S4.4-39,S4.4-47,S4.4-71} Achieving an additional 10–mm Hg reduction in SBP reduced CVD risk when compared with an average BP of 158/82 to 143/76 mm Hg, 144/85 to 137/81 mm Hg, and 134/79 to 125/76 mm Hg. Patients with diabetes mellitus and CKD were included in the analyses.^S4.4-39

Most patients with CKD have a 10-year ASCVD risk ≥10%, requiring initiation of antihypertensive drug therapy at BP ≥130/80 mm Hg. In SPRINT, the participants with CKD who were randomized to intensive therapy (SBP target <120 mm Hg) derived the same beneficial reduction in CVD events and all-cause mortality that was seen among in their counterparts without CKD, with no difference seen in the principal renal outcome.^S4.4-34 Other RCTs^{S4.4-43,S4.4-44} that evaluated the effect of differing BP goals on CKD progression in patients with CKD demonstrated no benefit for more intensive BP reduction, although post hoc follow-up analyses favored lower targets in patients with more severe proteinuria.^S4.4-72 These trials were underpowered to detect differences in CVD event rates. Several meta-analyses and systematic reviews support more intensive BP treatment to reduce cardiovascular events but do not demonstrate a reduction in the rate of progression of kidney disease.^{S4.4-31,S4.4-33,S4.4-39} More intensive BP treatment may result in a modest reduction in glomerular filtration rate, which is thought to be primarily attributable to a hemodynamic effect and may be reversible. Electrolyte abnormalities are also more likely during intensive BP treatment.

Most adults with diabetes mellitus a 10-year ASCVD risk ≥10%, requiring initiation of antihypertensive drug therapy at BP ≥130/80 mm Hg and a treatment goal of <130/80 mm Hg.^S4.4-73 Several meta-analyses of RCTs included all trials with a difference in BP levels^{S4.4-31,S4.4-71} and supported lowering BP to <130/80 mm Hg among those with diabetes mellitus. Two meta-analyses addressing target BP in adults with diabetes mellitus restricted the analysis to RCTs that randomized patients to different BP levels.^{S4.4-33,S4.4-47} Target BP of 133/76 mm Hg provided significant benefit compared with that of 140/81 mm Hg for major cardiovascular events, MI, stroke, albuminuria, and retinopathy progression.^S4.4-33

In the ACCORD (Action to Control Cardio vascular Risk in Diabetes) trial,^S4.4-51 lowering the BP target (SBP <120 mm Hg) did not reduce the rate of the composite outcome of fatal and nonfatal major cardiovascular events and was associated with greater risk of adverse events, such as self-reported hypotension and a reduction in estimated glomerular filtration rate. Secondary analyses of the ACCORD trial demonstrated a significant outcome benefit of stroke risk reduction in the intensive BP/standard glycemic group.^S4.4-74

The relationship of SBP with CVD risk is continuous across levels of SBP and similar across groups that differ in level of absolute risk.^S4.4-55 The relative risk reduction attributable to BP-lowering medication therapy is consistent across the range of absolute risk observed in trials,^S4.4-36 suggesting that relative risk reduction may be similar at lower levels of absolute risk. Indirect support is also provided by evidence from trials using BP-lowering medications to reduce the risk of developing higher levels of BP.^{S4.4-75,S4.4-76} In the HOPE-3 (Heart Outcomes Prevention Evaluation-3) BP Trial, there was no evidence of short-term benefit during treatment of adults (average age 66 years) with a relatively low risk of CVD (3.8% CVD event rate during 5.6 years of follow-up). However, subgroup analysis suggested benefit in those with an average SBP >140 mm Hg (and a CVD risk of 6.5% during the 5.6 years of follow-up).^S4.4-59

The treatment of patients with hypertension without elevated risk has been systematically understudied because lower-risk groups would require prolonged follow-up to have a sufficient number of clinical events to provide useful outcomes data. Although there is clinical trial evidence that both drug and nondrug therapy will interrupt the progressive course of hypertension, there is no trial evidence that this treatment decreases CVD morbidity and mortality. The clinical trial evidence is strongest for a target BP of 140/90 mm Hg in this population. However, observational studies suggest that these individuals often have a high lifetime risk and would benefit from BP control earlier in life.^S4.4-77

On the basis of on the US Public Health Service’s Clinical Practice Guideline for Treating Tobacco Use and Dependence,^{S4.5-14,S4.5-15} the USPSTF recommended (Grade A) in 2003 and reaffirmed in 2009 that clinicians ask all adults about tobacco use.^S4.5-2 Treating tobacco use status as a vital sign and recording tobacco use status in the health record at every healthcare visit not only increases the rate of tobacco treatment but also improves tobacco abstinence.^{S4.5-15,S4.5-16} Office-wide screening systems (eg, chart stickers, computer prompts) that expand the vital signs to include tobacco use status (current, former, never) can facilitate tobacco cessation.^S4.5-15 Because many people who use tobacco do not report it, using multiple questions to assess tobacco use status may improve accuracy and disclosure. For example, clinicians should ask, “Have you smoked any tobacco product in the past 30 days, even a puff?” “Have you vaped or ‘juuled’ in the past 30 days, even a puff?” “Have you used any other tobacco product in the past 30 days?” If these questions are answered with “yes,” the patient is considered a current smoker. Clinicians should avoid asking “Are you a smoker?” or “Do you smoke?” because people are less likely to report tobacco use when asked in this way.^S4.5-17

Tobacco users are more likely to quit after 6 months when clinicians strongly advise adults to quit using tobacco than when clinicians give no advice or usual care.^S4.5-2 To help patients quit, it is critically important to use language that is clear and strong, yet compassionate, nonjudgmental, and personalized, to urge every tobacco user to quit.^S4.5-15 For example, “The most important thing you can do for your health is to quit tobacco use. I (we) can help.” The ASCVD benefits of quitting are immediate.^S4.5-18 The best and most effective treatments are those that are acceptable to and feasible for an individual patient; clinicians should consider the patient’s specific medical history and preferences and offer to provide tailored strategies that work best for the patient.^{S4.5-3,S4.5-19}

In alignment with previous expert consensus regarding strategies for tobacco cessation,^S4.5-19 Table 8 summarizes recommended behavioral interventions and pharmacotherapy for tobacco treatment. There are 7 FDA-approved cessation medications, including 5 forms of nicotine replacement. Note that the black box warnings about neuropsychiatric events have been removed by the FDA.^{S4.5-20,4.5-21} The net benefit of FDA-approved tobacco-cessation pharmacotherapy and behavioral interventions (even just 3 minutes of practical advice), alone or combined, in nonpregnant adults (≥18 years of age) who smoke is substantial. The net benefit of behavioral interventions for tobacco cessation on perinatal outcomes and smoking abstinence in pregnant women who smoke is substantial. However, the evidence on pharmacotherapy for tobacco cessation in pregnant women is insufficient; the balance of benefits and harms cannot be determined. Among hospitalized adults who use tobacco, intensive counseling with continued supportive follow-up contacts for at least one month after discharge is recommended.^S4.5-22

ENDS are not recommended as a tobacco treatment method. The evidence is unclear about whether ENDS are useful or effective for tobacco treatment, and they may be potentially harmful. The evidence on the use of ENDS as a smoking-cessation tool in adults (including pregnant women) and adolescents is insufficient^S4.5-23 or limited.^S4.5-24 The USPSTF recommends that clinicians direct patients who smoke tobacco to other cessation interventions with established effectiveness and safety.

Cigarette smoking remains a strong, independent risk factor for ASCVD events and premature death.^S4.5-4 Even among older adults, tobacco cessation is beneficial in reducing excess risk.^S4.5-5 The risk of heart failure and death for most former smokers is similar to that of never smokers after >15 years of tobacco cessation.^S4.5-25 In the National Health Interview Survey, smoking was strongly associated with ASCVD in young people after adjustment for multiple risk factors,^S4.5-26 which is why abstinence from an early age is recommended.

Tobacco use dependence is a chronic disease that requires highly skilled chronic disease management. It is a reasonable expectation that every health system or practice should dedicate trained staff to tobacco treatment. Healthcare professionals who receive training in tobacco treatment are more likely to ask about tobacco use, offer advice to quit, provide behavioral interventions, follow up with individuals, and increase the number of tobacco users who quit.^S4.5-1 Participants who earn a certificate in tobacco treatment practice demonstrate a nationally recognized level of training and skill acquisition in treating tobacco dependence.^s4.5-27 A Tobacco Treatment Specialist is a professional who possesses the skills, knowledge, and training to provide effective, evidence-based interventions for tobacco dependence across a range of intensities.^S4.5-28 A list of accredited Tobacco Treatment Specialist programs is available here: http://ctttp.org/accredited-programs.^S4.5-29

Secondhand smoke exposure is known to cause CVD^S4.5-6 and stroke^S4.5-16 in nonsmokers, and it can lead to immediate adverse events.^S4.5-30 There is no safe lower limit of exposure to secondhand smoke.^S4.5-31 Even brief exposure to secondhand smoke can trigger an MI.^{S4.5-30,S4.5-32} Even though exposure to secondhand smoke has steadily decreased over time, certain subgroups remain exposed to secondhand smoke in homes, vehicles, public places, and workplaces. It is estimated that 41 000 preventable deaths per year occur in adult nonsmokers as a result of exposure to secondhand smoke.^S4.5-33 The US Department of Housing and Urban Development prohibited the use of combustible tobacco products in all public housing living units, indoor common areas, and public housing agency administrative office buildings, extending to all outdoor areas up to 25 feet from public housing buildings.^S4.5-34 Therefore, the present writing committee recommends that clinicians advise patients to take precautions against exposure to secondhand smoke and aerosol from all tobacco products, such as by instituting smoking restrictions (including ENDS) inside all homes and vehicles and within 25 feet from all entryways, windows, and building vents.

To balance the benefits and risks, prior US guidelines have recommended prophylactic aspirin only in the setting of elevated ASCVD risk (eg, as calculated by risk estimators like the PCE or based on the presence of specific ASCVD risk factors).^{S4.6-14,S4.6-18} Meta-regression analyses of historical trials show that observed ASCVD risk tracks reasonably well with baseline-estimated ASCVD risk.^S4.6-19 In contrast, observed bleeding risk on aspirin is less well correlated with baseline-estimated ASCVD risk.^S4.6-19 (A nonexhaustive list of scenarios associated with increased risk of bleeding includes: a history of previous gastrointestinal bleeding or peptic ulcer disease or bleeding from other sites, age >70 years, thrombocytopenia, coagulopathy, CKD, and concurrent use of other medications that increase bleeding risk, such as nonsteroidal anti-inflammatory drugs, steroids, direct oral anticoagulants, and warfarin.) In this context, post hoc study of older trials suggests that the benefit–risk ratio for prophylactic aspirin generally becomes more favorable at >10% estimated 10-year ASCVD risk.^{S4.6-15,S4.6-19} However, the relative benefits of aspirin, specifically in preventing nonfatal MI and perhaps stroke (with a trend to lower mortality) have been less evident in more recent trials.^{S4.6-9,S4.6-16,S4.6-17,S4.6-20} Similarly, in these recent trials, the estimated ASCVD risk has generally exceeded the actual risk observed during follow-up.^S4.6-17 These recent data are the rationale for the lower COR for prophylactic aspirin in the present guideline (Class IIb) and the removal of a specific PCE risk threshold as an inclusion criterion for aspirin consideration. These changes reflect the need to instead consider the totality of available evidence for ASCVD risk [inclusive, where appropriate, of risk-enhancing factors, such as strong family history of premature MI, inability to achieve lipid or BP or glucose targets, or significant elevation in coronary artery calcium score^S4.6-21] and to also tailor decisions about prophylactic aspirin to patient and clinician preferences. Depending on risk factors present, a given patient and his/her clinician may decide that lowering the risk of MI (which has potentially serious long-term consequences not captured by clinical trials of 5 to 10 years’ duration) is worth a slight excess risk of serious bleeding. Recent trials show that absolute risk for ASCVD events typically exceeds that of bleeding and, although the gap of relative benefit to relative harm for aspirin has narrowed, the number needed to treat to prevent an ASCVD event remains lower than the number needed to harm to cause bleeding. Others may feel that the benefit of prophylactic aspirin is comparable to the risk and may instead choose to focus on optimal control of other modifiable ASCVD risk factors. Therefore, a Class IIb recommendation remains more suitable than a Class III recommendation for adults 40 to 70 years of age. Given the narrow overall balance between benefits and harms of prophylactic aspirin, there is limited justification to use aspirin at doses >100 mg daily for primary prevention. Indeed, meta-analyses suggest that the ASCVD risk benefit for low-dose aspirin is equivalent to that for high-dose aspirin, but the bleeding risk is higher with high-dose aspirin. Recent observational studies motivate future research on the personalization of prophylactic aspirin dose according to patient-specific factors (eg, weight),^S4.6-22 though we note that, regarding weight specifically, there was no evidence low-dose aspirin was any more effective in low-weight individuals than in high-weight individuals in the more recently published ASCEND (A Study of Cardiovascular Events iN Diabetes) trial,^S4.6-16 trial. Most importantly, recent clinical trials also teach us that low-dose prophylactic aspirin may be best justified among persons at high ASCVD risk who cannot achieve optimal control of other ASCVD risk factors.^S4.6-23

Prophylactic aspirin in primary-prevention adults >70 years of age is potentially harmful and, given the higher risk of bleeding in this age group, difficult to justify for routine use.^S4.6-9 In addition, for adults <40 years of age, there is insufficient evidence to judge the risk–benefit ratio of routine aspirin for the primary prevention of ASCVD. However, one caveat is that, although routine use is not recommended in these settings, there is also insufficient evidence to comment on whether there may be select circumstances in which physicians might discuss prophylactic aspirin with adults <40 years of age or >70 years of age in the context of other known ASCVD risk factors (eg, strong family history of premature MI, inability to achieve lipid or BP or glucose targets, or significant elevation in coronary artery calcium score). As inferred from the first recommendation, there is also no justification for the routine administration of low-dose aspirin for the primary prevention of ASCVD among adults at low estimated ASCVD risk. For example, in the recent ARRIVE (A Randomized Trial of Induction Versus Expectant Management) trial, observed average 10-year ASCVD risk was <10%, and the overall benefits of prophylactic aspirin by intention-to-treat were negligible.^S4.6-17

The accumulated trial and observational data to date support avoiding prophylactic aspirin in the setting of known risk factors for increased bleeding outcomes.^S4.6-10 A nonexhaustive list of conditions associated with increased bleeding risk includes: a history of previous gastrointestinal bleeding or peptic ulcer disease or bleeding at other sites, age >70 years, thrombocytopenia, coagulopathy, CKD, and concurrent use of other medications that increase bleeding risk, such as nonsteroidal anti-inflammatory drugs, steroids, direct oral anticoagulants, and warfarin.^S4.6-10