These recommendations are in line with those of other health organizations.S3.2-26 Shorter durations of exercise seem to be as ben- eficial as longer ones (eg, 10-minute bouts),S3.2- 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 aero- bic physical activity (>300 minutes per week of moderate-intensity aerobic physical activity or 150 minutes per week of vigorous-intensity aer- obic 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 Specific exercise recommen- dations for the prevention of heart failure may differ slightly because the dose response rela- tionship with increasing physical activity levels may be linear.S3.2-29 3. 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 physi- cal 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. 4. 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 Sedentary behavior may be most deleterious to ASCVD risk for individu- als who engage in the least amount of moder- ate 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 rec- ommended physical activity levels, may be ben- eficial 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 behav- ior with light-intensity activity (eg, slow walking, light work) is beneficial for ASCVD prevention is 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 sed- Figure 1. Hours per day spent in various states of activity. US adults spend >7 h/d on average in sedentary activities. Replacing sedentary time with other physical activity involves increasing either moderate- to vigorous-intensity physical activity or light-intensity physical activity. Data modified from Young et al.S3.2-30 Table 4. Definitions and Examples of Different Intensities of Physical Activity Intensity METs Examples Sedentary behavior* 1 1.5 Sitting, reclining, or lying; watching television Light 1.6 2.9 Walking slowly, cooking, light housework Moderate 3.0 5.9 Brisk walking (2.4 4 mph), biking (5 9 mph), ballroom dancing, active yoga, recreational swimming Vigorous 6 Jogging/running, biking ( 10 mph), singles tennis, swimming laps *Sedentary behavior is defined as any waking behavior characterized by an energy expenditure 1.5 METs while in a sitting, reclining, or lying posture. Standing is a sedentary activity in that it involves 1.5 METs, but it is not considered a component of sedentary behavior. MET indicates metabolic equivalent; and mph, miles per hour. CLINICAL STATEMENTS AND GUIDELINES 4. OTHER FACTORS AFFECTING CARDIOVASCULAR RISK 4.1. Adults With Overweight and Obesity Recommendations for Adults With Overweight and Obesity Referenced studies that support recommendations are summarized in Online Data Supplements 8 and 9. COR LOE Recommendations I B-R In individuals with overweight and obesity, weight loss is recommended to improve the ASCVD risk factor profile.0650 I B-R Counseling and comprehensive lifestyle interventions, including calorie restriction, are recommended for achieving and maintaining weight loss in adults with overweight and obesity.S4.1-1,S4.1-2 I C-EO Calculating body mass index (BMI) is recommended annually or more frequently to identify adults with overweight and obesity for weight loss considerations. IIa B-NR It is reasonable to measure waist circumference to identify those at higher Synopsis The increased availability of affordable, palatable, and high-calorie foods and the decreased physical de- mands of many jobs have fueled the epidemic of obe- sity and the consequent increases in hypertension and Adults diagnosed as obese (BMI 30 kg/m2 ) ) are at increased risk of ASCVD, heart failure, and atrial fibrillation, com- pared with those of a normal weight.S4.1-8,S4.1-9 The nu- tritional aspects of obesity revolve around the principle of balancing caloric intake with caloric expenditure. Following the 2013 Guideline for the Management of Overweight and Obesity in Adults from the AHA, ACC, and The Obesity Society (TOS), adults with overweight/ obesity are advised to participate in comprehensive life- style programs of 6 months duration that assist par- ticipants in adhering to a low-calorie diet (800 to 1500 kcal/day) and increased physical activity. Existing clinical guidance strongly recommends face-to-face or tele- phone-delivered weight-loss maintenance programs that provide regular contact (at least monthly) with a trained interventionist to help participants engage in high levels of physical activity (200 to 300 minutes/ week), monitor body weight regularly (at least weekly), and consume a reduced-calorie diet.S4.1-10 US Food and Drug Administration (FDA) approved and bariatric adjunctive to complementary lifestyle in- terventions, additionally reduce weight and may have a role in weight loss for select patients. The present guideline document focuses primarily on lifestyle inter- ventions for overweight and obesity, as outlined in the 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults.S4.1-10 Weight loss interventions should be cautiously implemented and individualized, especially in older adults, to avoid det- rimental effects, such as loss of lean body/muscle mass and nutritional deficiencies.S4.1-13 S4.1-15 Recommendation-Specific Supportive Text 1. 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 Weight loss reduces or delays the development of T2DM in persons with High-intensity ( 14 sessions in 6 months) comprehensive weight-loss interven- tions provided by a trained interventionist work However, other modalities, such as elec- tronically delivered weight-loss programs with per- sonalized feedback and some commercial-based programs, have also shown moderate results. 2. 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 main- tain 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 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 life- style 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 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 interven- tion, 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 3. Measures used to estimate body fat and quan- tify the associated health risks include BMI, waist CLINICAL STATEMENTS AND GUIDELINES 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 evi- dence 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 rec- ommend its measurement for primary screening of individuals needing weight loss. BMI should be inter- preted with caution in persons of Asian ancestry, older adults, and muscular adults.S4.1-19,S4.1-20 4. Increased waist circumference has been associ- ated with increased cardiometabolic and ASCVD 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 cir- cumference measurement is recommended in all patients with BMI <35 kg/m2 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 (cen- Definitions of elevated waist cir- cumference 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 PanelS4.1-25 and were adopted by the 2013 AHA/ACC/TOS writing 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 4.2. Adults With Type 2 Diabetes Mellitus See Figure 2 for an algorithm for treatment of T2DM for primary prevention of cardiovascular disease. Recommendations for Adults With Type 2 Diabetes Mellitus Referenced studies that support recommendations are summarized in Online Data Supplement 10. COR LOE Recommendations I A For all adults with T2DM, a tailored nutrition plan focusing on a heart-healthy dietary pattern is recommended to improve glycemic control, achieve weight loss if needed, and improve other ASCVD risk I A Adults with T2DM should perform at least 150 minutes per week of moderate-intensity physical activity or 75 minutes of vigorous- intensity physical activity to improve glycemic control, achieve weight loss if needed, and improve other ASCVD risk factors.S4.2-3,S4.2-4 IIa B-R For adults with T2DM, it is reasonable to initiate metformin as first-line therapy along with lifestyle therapies at the time of diagnosis to improve glycemic control and reduce ASCVD risk.S4.2-5 S4.2-8 IIb B-R For adults with T2DM and additional ASCVD risk factors who require glucose-lowering therapy despite initial lifestyle modifications and metformin, it may be reasonable to initiate a sodium-glucose cotransporter 2 (SGLT-2) inhibitor or a glucagon-like peptide-1 receptor (GLP-1R) agonist to improve glycemic control and reduce CVD Synopsis a metabolic disorder characterized by insulin resistance leading to hyperglycemia. Unlike type 1 diabetes mellitus (an autoimmune condition largely unrelated to lifestyle factors), the development and progression of T2DM are heavily influenced by dietary pattern, physical activity, and body weight. Approximately 12% of US adults have diabetes, 90% to 95% of whom have T2DM, with sig- nificant heterogeneity according to age, sex, race/eth- nicity, and socioeconomic status.S4.2-15 Alarmingly, more than one-third of US adults ( 80 million adults) have prediabetes and are at risk of developing T2DM.S4.2-15 * Although contemporary data have shown a sig- nificant decrease in ASCVD rates in individuals with T2DM remains a highly prevalent disease and a major ASCVD risk factor. An aggressive, com- prehensive approach to ASCVD risk factor treatment in adults with T2DM reduces ASCVD events.S4.2-16 Man- agement of cholesterol and hypertension in adults with T2DM is discussed in the relevant sections of the pres- ent guideline (see Sections 4.3. and 4.4.). Recommendation-Specific Supportive Text 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 Recommendations for Adults With Type 2 Diabetes Mellitus (Continued) COR LOE Recommendations *An HbA1c is the optimal screening method, with a level 6.5% indicating T2DM. CLINICAL STATEMENTS AND GUIDELINES lower likelihood of CVD events and CVD death in adults with T2DM who follow a healthy dietary However, an RCT targeting aggres- sive 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,redmeatconsumptionhasbeenshown 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-nutri- tionist or a diabetes education program. 2. 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% ver- sus 8.31%) in individuals assigned to an exercise program versus control groups.S4.2-22 The com- bination of aerobic and resistance training fur- ther improves glycemic control and facilitates weight loss more than either type of exercise Prospective cohort studies have pro- vided 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 indi- viduals with T2DM remains unclear. For older indi- viduals 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 exer- cise 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. 3. Metformin decreases hepatic glucose produc- tion and increases peripheral insulin sensitivity, Figure 2. Treatment of T2DM for primary prevention of cardiovascular disease. type 2 diabetes mellitus. CLINICAL STATEMENTS AND GUIDELINES 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% reduc- tion 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 glu- cose-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 pro- file 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. 4. 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 excre- tion 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, Although most patients studied had estab- lished CVD at baseline, the reduction in heart failure has been shown to extend to primary prevention 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 As opposed to a reduc- tion in heart failure with SGLT-2 inhibitors, the ben- efit of the GLP-1R agonists has been a reduction in ASCVD events though the majority of patients stud- ied had established CVD. In patients with T2DM and additional risk fac- tors for CVD, it may be reasonable to initiate these 2 classes of medications for primary prevention of CVD. 4.3. Adults With High Blood Cholesterol Recommendations from the 2018 Cholesterol Clinical are included and adapted below. Recommendations for Adults With High Blood Cholesterol Referenced studies that support recommendations are summarized in Online Data Supplements 11 and 12. COR LOE Recommendations I A In adults at intermediate risk ( 7.5% to <20% 10-year ASCVD risk), statin therapy reduces risk of ASCVD, and in the context of a risk discussion, if a decision is made for statin therapy, a moderate-intensity statin should be recommended.S4.3-2 S4.3-9 Adapted from recommendations in the 2018 Cholesterol Clinical Practice Guidelines.S4.3-1 I A ASCVD risk) patients, LDL-C levels should be reduced by 30% or more, and for optimal ASCVD risk reduction, especially in patients at high risk ( 20% 10-year ASCVD risk), levels should be reduced by 50% or more.S4.3-2,S4.3-5 S4.3-10 Adapted from recommendations in the 2018 Cholesterol Clinical Practice Guidelines.S4.3-1 I A In adults 40 to 75 years of age with diabetes, regardless of estimated 10-year ASCVD risk, moderate-intensity statin therapy is indicated.S4.3-11 S4.3-19 Included from recommendations in the 2018 Cholesterol Clinical Practice Guidelines.S4.3-1 I B-R In patients 20 to 75 years of age with an LDL-C level of 190 mg/dL ( 4.9 mmol/L) or higher, maximally tolerated statin therapy is Included from recommendations in the 2018 Cholesterol Clinical Practice Guidelines.S4.3-1 IIa B-R In adults with diabetes mellitus who have multiple ASCVD risk factors, it is reasonable to prescribe high-intensity statin therapy with the aim to reduce LDL-C levels by 50% Included from recommendations in the 2018 Cholesterol Clinical Practice Guidelines.S4.3-1 IIa B-R year ASCVD risk) adults, risk-enhancing factors favor initiation or intensification of Adapted from recommendations in the 2018 Cholesterol Clinical Practice Guidelines.S4.3-1 IIa B-NR ASCVD risk) adults or selected borderline-risk in whom a coronary artery calcium score is measured for the purpose of making a treatment decision, AND If the coronary artery calcium score is zero, it is reasonable to withhold statin therapy and reassess in 5 to 10 years, as long as higher-risk conditions are absent (eg, diabetes, family history of premature CHD, cigarette smoking); If coronary artery calcium score is 1 to 99, it is reasonable to initiate statin therapy for patients 55 years of age; If coronary artery calcium score is 100 or higher or in the 75th percentile or higher, it is reasonable to initiate statin therapy.S4.3-28,S4.3-34 Adapted from recommendations in the 2018 Cholesterol Clinical Practice Guidelines.S4.3-1 IIb B-R In patients at borderline risk (5% to <7.5% 10- year ASCVD risk), in risk discussion, the presence of risk-enhancing factors may justify initiation of moderate-intensity statin therapy.S4.3-28,S4.3-35 Adapted from recommendations in the 2018 Cholesterol Clinical Practice Guidelines.S4.3-1 CLINICAL STATEMENTS AND GUIDELINES Synopsis Primary ASCVD prevention requires attention to AS- CVD risk factors beginning early in life (Figure 3). This guideline addresses major issues related to cholesterol management and primary ASCVD prevention, which are also addressed in the recently published 2018 Cholesterol Clinical Practice Guidelines.S4.3-1 There- fore, the relevant subset of those recommendations is presented here, along with its accompanying sup- portive text. This writing committee agrees that for young adults (20 to 39 years of age), priority should be given to estimating lifetime risk and promoting a healthy lifestyle. Only in select patients with mod- erately high LDL-C ( 160 mg/dL) or those with very high LDL-C ( 190 mg/dL) is drug therapy indicated. In adults 40 to 75 years of age, 10-year ASCVD risk should guide therapeutic considerations. The higher the estimated risk, the more likely the patient is to benefit from statin treatment. For patients >75 years of age, assessment of risk status and a clinician pa- tient risk discussion are needed to decide whether to continue or initiate statin treatment. For a detailed discussion of statin safety and management of statin- associated side effects, please refer to Section 5 of the 2018 Cholesterol Clinical Practice Guidelines.S4.3-1 Recommendation-Specific Supportive Text 1. Large-scale RCTs in primary prevention dem- onstrated ASCVD risk reduction with moder- and high-intensity statin that outweighed the observable risks. Subsequently, a large-scale RCT in an eth- nically and racially diverse population confirmed statin benefit from a moderate-intensity statin therapy, as compared with placebo, in interme- diate-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 Figure 3. Primary prevention. Colors correspond to Class of Recommendation in Table 1. ABI indicates ankle-brachial index; apoB, apolipoprotein B; ASCVD, atherosclerotic cardiovascular disease; CAC, coronary artery calcium; CHD, coronary heart disease; HIV, human immunodeficiency virus; hs-CRP, high-sensitivity C-reactive protein; LDL-C, low- density lipoprotein cholesterol; and Lp(a), lipoprotein (a). Reproduced with permission from Grundy et al.S4.3-1 Copyright 2018, American Heart Association, Inc., and American College of Cardiology Foundation. CLINICAL STATEMENTS AND GUIDELINES group, the 10-year risk of hard ASCVD was 8.7%, and the risk of the expanded ASCVD end- point that included coronary revascularization After 5.6 years, those assigned to rosuvastatin 10 mg per day showed significant absolute risk reduction in both co-primary end- points, with an acceptable safety record. By com- parison, 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 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 2. 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, espe- cially 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 pro- tein 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 reduc- tion of 50% and a highly significant ASCVD risk Importantly, the mag- nitude of the percent LDL-C reduction achieved The USPSTF systematic review of statin therapy in primary prevention showed a reduced risk of all-cause and cardio- vascular mortality and ASCVD events and noted greater absolute benefits in those at greater base- consistent with other high-quality sys- tematic 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 3. Most patients 40 to 75 years of age with diabe- tes 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 ben- efit 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. 4. Patients with primary severe hypercholesterolemia (LDL-C 190 mg/dL [ 4.9 mmol/L]) have a high risk of ASCVDS4.3-23 and premature and recurrent coronary events. Although no randomized, pla- cebo-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 inci- dence of MI and cardiovascular death in those receiving pravastatin 40 mg daily.S4.3-24 These find- ings 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 moder- ate- 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 guidelineS4.3-1 for recommendations on the use of non-statin therapies in these patients. 5. 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 partic- ularly high premium on primary prevention in indi- viduals with diabetes in that age range. Although trials using moderate-intensity statin therapy have demonstrated significant benefit in such indi- viduals, 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). 6. Knowledge of risk-enhancing factors (Table 3 in Section 2.2.) is useful for all individuals but par- ticularly 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 CLINICAL STATEMENTS AND GUIDELINES elevated lifetime ASCVD risk and benefit from Increased ASCVD risk is seen with metabolic syndrome;S4.3-31 inflammatory diseases, including psoriasisS4.3-39 and rheumatoid arthritis; and HIV when treated with protease The presence of risk-enhancing factors may affect the threshold for statin ini- tiation or intensification. Lipoprotein (a) levels, especially in those with a family history of pre- mature 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 cho- lesterol HDL-C), and, if measured, apolipopro- tein B can improve selection of those at increased 7. In adults at intermediate risk, coronary artery calcium measurement can be effective for mean- ingfully reclassifying risk in a large proportion of 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 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 down- classify risk in patients who have coronary artery calcium scores of zero but who are persistent cigarette smokers, have diabetes, have a fam- ily 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 8. Benefit from statin therapy is also seen in lower- For those in the 5% to <7.5% risk range, available generic statins are 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 treat- ing 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 communicat- ing 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 Table 6. Selected Examples of Candidates for Coronary Artery Calcium Measurement Who Might Benefit From Knowing Their Coronary Artery Calcium Score Is Zero Coronary Artery Calcium Measurement Candidates Who Might Benefit from Knowing Their Coronary Artery Calcium Score Is Zero Patients reluctant to initiate statin who wish to understand their risk and potential for benefit more precisely Patients concerned about need to reinstitute statin therapy after discontinuation for statin-associated symptoms Older patients (men 55 80 y of age; women 60 80 y of age) with low burden of risk factorsS4.3-53 who question whether they would benefit from statin therapy Middle-aged adults (40 55 y of age) with PCE-calculated 10-year risk of ASCVD 5% to <7.5% with factors that increase their ASCVD risk, although they are in a borderline risk group. Caveats: If patient is at intermediate risk and if a risk decision is uncertain and a coronary artery calcium score is obtained, it is reasonable to withhold statin therapy unless higher-risk conditions, such as cigarette smoking, family history of premature ASCVD, or diabetes mellitus, are present and to reassess coronary artery calcium score in 5 to 10 years. Moreover, if coronary artery calcium scoring is recommended, it should be performed in facilities that have current technology and expertise to deliver the lowest radiation possible. ASCVD indicates atherosclerotic cardiovascular disease; LDL-C, low-density lipoprotein cholesterol; and PCE, pooled cohort equations. Reproduced with permission from Grundy et al.S4.3-1 Copyright 2018, American Heart Association, Inc., and American College of Cardiology Foundation. Table 5. Diabetes-Specific Risk Enhancers That Are Independent of Other Risk Factors in Diabetes Mellitus Risk Enhancers in Diabetic Patients Long duration ( 10 years for T2DMS4.3-61 or 20 years for type 1 diabetes ) Albuminuria 30 mcg albumin/mg creatinineS4.3-62 ABI indicates ankle-brachial index; eGFR, estimated glomerular filtration rate; and T2DM, type 2 diabetes mellitus. Reproduced with permission from Grundy et al.S4.3-1 Copyright 2018, American Heart Association, Inc., and American College of Cardiology Foundation. CLINICAL STATEMENTS AND GUIDELINES 4.4. Adults With High Blood Pressure or Hypertension Recommendations from the 2017 Hypertension Clinical are adapted below. Recommendations for Adults With High Blood Pressure or Hypertension Referenced studies that support recommendations are summarized in Online Data Supplements 13 and 14. COR LOE Recommendations I A In adults with elevated blood pressure (BP) or hypertension, including those requiring antihypertensive medications nonpharmacological interventions are recommended to reduce BP. These include: ; a heart-healthy dietary patternS4.4-6 S4.4-8 ; ; dietary potassium supplementationS4.4-14 S4.4-18 ; increased physical activity with a structured exercise programS4.4-3,S4.4-5,S4.4-11, ; and Adapted from recommendations in the 2017 Hypertension Clinical Practice Guidelines.S4.4-1 I SBP:A In adults with an estimated 10-year ASCVD risk* of 10% or higher and an average systolic BP (SBP) of 130 mm Hg or higher or an average diastolic BP (DBP) of 80 mm Hg or higher, use of BP-lowering medications is recommended for primary prevention of Adapted from recommendations in the 2017 Hypertension Clinical Practice Guidelines.S4.4-1 DBP:C-EO I SBP:B-RSR In adults with confirmed hypertension and a 10-year ASCVD event risk of 10% or higher, a BP target of less than 130/80 mm Hg is Adapted from recommendations in the 2017 Hypertension Clinical Practice Guidelines.S4.4-1 DBP:C-EO I SBP:B-RSR In adults with hypertension and chronic kidney disease, treatment to a BP goal of less than 130/80 mm Hg is Adapted from recommendations in the 2017 Hypertension Clinical Practice Guidelines.S4.4-1 DBP:C-EO I SBP:B-RSR In adults with T2DM and hypertension, antihypertensive drug treatment should be initiated at a BP of 130/80 mm Hg or higher, with a treatment goal of less than Adapted from recommendations in the 2017 Hypertension Clinical Practice Guidelines.S4.4-1 DBP:C-EO I C-LD In adults with an estimated 10-year ASCVD risk <10% and an SBP of 140 mm Hg or higher or a DBP of 90 mm Hg or higher, initiation and use of BP-lowering medication Adapted from recommendations in the 2017 Hypertension Clinical Practice Guidelines.S4.4-1 IIb SBP:B-NR In adults with confirmed hypertension without additional markers of increased ASCVD risk, a BP target of less than 130/80 mm Hg may be reasonable.S4.4-59 S4.4-62 Adapted from recommendations in the 2017 Hypertension Clinical Practice Guidelines.S4.4-1 DBP:C-EO *ACC/AHA pooled cohort equations to estimate 10-year risk of ASCVD. Synopsis In the United States, hypertension accounts for more ASCVD deaths than any other modifiable ASCVD risk The prevalence of hypertension (defined as systolic blood pressure [SBP] 130 mm Hg or diastolic blood pressure [DBP] 80 mm Hg) among US adults is 46%; is higher in blacks than in whites, Asians, and Hispanic Americans; and increases dramatically with In a meta-analysis of 61 prospec- tive studies, a log-linear association was observed be- tween SBP levels <115 to >180 mm Hg and DBP lev- els <75 to 105 mm Hg and risk of ASCVD.S4.4-55 In that analysis, 20 mm Hg higher SBP and 10 mm Hg higher DBP were each associated with a doubling in the risk of death from stroke, heart disease, or other vascular disease. An increased risk of ASCVD associated with higher SBP and DBP has been reported across a broad age spectrum, from 30 to >80 years of age. Although the relative risk of incident CVD associated with higher SBP and DBP is smaller at older ages, the correspond- ing high BP-related increase in absolute risk is larger in older persons ( 65 years) given the higher absolute risk of CVD at an older age.S4.4-55 See Figure 4 for the BP thresholds and treatment recommendations algorithm and refer to the 2017 Hypertension Clinical Practice Guidelines for comprehensive details.S4.4-1 Recommendation-Specific Supportive Text 1. 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 Furthermore, combining recommended nonpharmacological interven- tions has been shown to increase impact on BP Nonpharmacological interven- tion 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 nonpharmacologi- cal therapy should be assessed within 3 to 6 months. See Table 7 for recommended goals and approximate impact on SBP. 2. 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 with significant out- come reductions demonstrated in stroke, heart failure, coronary events, and death. Significant reductions CLINICAL STATEMENTS AND GUIDELINES 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 treat- ment 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 Table 7. Best Proven Nonpharmacological Interventions for Prevention and Treatment of Hypertension* Nonpharmacological Intervention Goal Approximate Impact on SBP Hypertension Normotension Reference Weight loss Weight/body fat Best goal is ideal body weight, but aim for at least a 1-kg reduction in body weight for most adults who are overweight. Expect about 1 mm Hg for every 1-kg reduction in body weight. Healthy diet DASH dietary pattern Consume a diet rich in fruits, vegetables, whole grains, and low-fat dairy products, with reduced content of saturated and total fat. Reduced intake of dietary sodium Dietary sodium Optimal goal is <1500 mg/d, but aim for at least a 1000-mg/d reduction in most adults. Enhanced intake of dietary potassium Dietary potassium Aim for 3500 5000 mg/d, preferably by consumption of a diet rich in potassium. Physical activity Aerobic 90 150 min/wk 65% 75% heart rate reserve Dynamic resistance 90 150 min/wk Isometric resistance 4 2 min (hand grip), 1 min rest between exercises, 30% 40% maximum voluntary contraction, 3 sessions/wk Moderation in alcohol intake Alcohol consumption In individuals who drink alcohol, reduce alcohol to: Men: 2 drinks daily Women: 1 drink daily *Type, dose, and expected impact on BP in adults with a normal BP and with hypertension. Detailed information about the DASH diet is available via the NHLBIS4.4-81 In the United States, 1 standard drink contains roughly 14 g of pure alcohol, which is typically found in 12 oz of regular beer (usually about 5% alcohol), 5 oz of wine (usually about 12% alcohol), and 1.5 oz of distilled spirits (usually about 40% alcohol).S4.4-80 BP indicates blood pressure; DASH, Dietary Approaches to Stop Hypertension; NHLBI, National Heart, Lung, and Blood Institute; and SBP, systolic blood pressure. Reproduced with permission from Whelton et al.S4.4-1 Copyright 2017, American College of Cardiology Foundation and the American Heart Association, Inc. Figure 4. BP thresholds and recommendations for treatment. Colors correspond to Class of Recommendation in Table 1. BP indicates blood pressure; and CVD, cardiovascular disease. Adapted with permission from Whelton Copyright 2017, American College of Cardiology Foundation and the American Heart Association, Inc. CLINICAL STATEMENTS AND GUIDELINES treatment outweighs the potential harm at thresh- old BP 130/80 mm Hg. 3. Meta-analyses and systematic reviews of trials that compare more intensive BP reduction to standard BP reduction report that more intense BP lowering sig- nificantly reduces the risk of stroke, coronary events, major cardiovascular events, and cardiovascular Achieving an addi- tional 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 4. 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 that evaluated the effect of differ- ing BP goals on CKD progression in patients with CKD demonstrated no benefit for more intensive BP reduction, although post hoc follow-up analy- ses favored lower targets in patients with more These trials were under- powered 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 More intensive BP treat- ment may result in a modest reduction in glomeru- lar 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. 5. Most adults with diabetes mellitus a 10-year ASCVD risk 10%, requiring initiation of antihy- pertensive 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 levelsS4.4-31,S4.4-71 and sup- ported lowering BP to <130/80 mm Hg among those with diabetes mellitus. Two meta-analyses addressing target BP in adults with diabetes mel- litus restricted the analysis to RCTs that random- ized 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 non- fatal major cardiovascular events and was asso- ciated 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 sig- nificant outcome benefit of stroke risk reduction in the intensive BP/standard glycemic group.S4.4-74 6. 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 rela- tive risk reduction may be similar at lower levels of absolute risk. Indirect support is also provided by evidence from trials using BP-lowering medica- tions to reduce the risk of developing higher levels 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 7. The treatment of patients with hypertension with- out elevated risk has been systematically under- studied 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 pro- gressive course of hypertension, there is no trial evi- dence 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 4.5. Treatment of Tobacco Use Recommendations for Treatment of Tobacco Use Referenced studies that support recommendations are summarized in Online Data Supplements 15 and 16. COR LOE Recommendations I A All adults should be assessed at every healthcare visit for tobacco use and their tobacco use status recorded as a vital sign to facilitate tobacco cessation.S4.5-1 I A To achieve tobacco abstinence, all adults who use tobacco should be firmly advised CLINICAL STATEMENTS AND GUIDELINES I A In adults who use tobacco, a combination of behavioral interventions plus pharmacotherapy is recommended to maximize quit rates.S4.5-2,S4.5-3 I B-NR In adults who use tobacco, tobacco abstinence is recommended to reduce IIa B-R To facilitate tobacco cessation, it is reasonable to dedicate trained staff to tobacco treatment in every healthcare III: Harm B-NR All adults and adolescents should avoid secondhand smoke exposure to reduce Synopsis Tobacco use is the leading preventable cause of disease, disability, and death in the United States.S4.5-7 Smoking and smokeless tobacco (eg, chewing tobacco) use in- creases the risk of all-cause mortality and is a cause Secondhand smoke is a cause of ASCVD and stroke,S4.5-6 and almost one-third of CHD deaths are attributable to smoking and exposure to secondhand smoke. Even low levels of smoking in- crease risks of acute MI; thus, reducing the number of cigarettes per day does not totally eliminate risk.S4.5-8 Healthy People 2020 recommends that cessation treat- ment in clinical care settings be expanded, with access to proven cessation treatment provided to all tobacco Electronic Nicotine Delivery Systems (ENDS), often called e-cigarettes,S4.5-10 are a new class of tobacco product that emit aerosol containing fine and ultrafine particulates, nicotine, and toxic gases that may increase risk of cardiovascular and pulmonary diseases.S4.5-11 Ar- rhythmias and hypertension with e-cigarette use have also been reported.S4.5-12 Chronic use is associated with persistent increases in oxidative stress and sympathetic stimulation in young, healthy subjects.S4.5-13 Recommendation-Specific Supportive Text 1. 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 rec- ommended (Grade A) in 2003 and reaffirmed in 2009 that clinicians ask all adults about tobacco 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 Office-wide screen- ing systems (eg, chart stickers, computer prompts) that expand the vital signs to include tobacco use status (current, former, never) can facilitate Because many people who use tobacco do not report it, using multiple ques- tions to assess tobacco use status may improve accuracy and disclosure. For example, clinicians should ask, Have you smoked any tobacco prod- uct 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 2. 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 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 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 3. 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 replace- ment. Note that the black box warnings about neuropsychiatric events have been removed by the The net benefit of FDA-approved tobacco-cessation pharmacotherapy and behav- ioral 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 pharmaco- therapy 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 con- tinued 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 Recommendations for Treatment of Tobacco Use (Continued) COR LOE Recommendations CLINICAL STATEMENTS AND GUIDELINES whether ENDS are useful or effective for tobacco treatment, and they may be potentially harm- ful. The evidence on the use of ENDS as a smok- ing-cessation tool in adults (including pregnant women) and adolescents is insufficientS4.5-23 or The USPSTF recommends that clini- cians direct patients who smoke tobacco to other cessation interventions with established effective- ness and safety. 4. Cigarette smoking remains a strong, indepen- dent risk factor for ASCVD events and premature Even among older adults, tobacco ces- sation is beneficial in reducing excess risk.S4.5-5 The risk of heart failure and death for most for- mer 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. 5. Tobacco use dependence is a chronic disease that requires highly skilled chronic disease man- agement. It is a reasonable expectation that every health system or practice should dedicate trained staff to tobacco treatment. Healthcare profes- sionals 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 num- ber 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 A Tobacco Treatment Specialist is a professional who possesses the skills, knowledge, and training to provide effec- tive, 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/ Table 8. Highlights of Recommended Behavioral and Pharmacotherapy Tobacco Treatment Modalities for Prescribers* Timing of Behavioral Interventions <3 min of tobacco status assessment with cessation counseling at each clinic encounter >3-10 min of tobacco status assessment with cessation counseling at each clinic encounter >10 min of tobacco status assessment with cessation counseling at each clinic encounter Treatment Dosing Precautions NRT* Patch 21 mg, 14 mg, or 7 mg Starting dose: 21 mg for 10 CPD; 14 mg for <10 CPD Local irritation possible; avoid with skin disorders; may remove for sleep if needed Gum 2 mg or 4 mg Starting dose: 4 mg if first tobacco use is 30 min after waking; 2 mg if first tobacco use is >30 min after waking; maximum of 20 lozenges or 24 pieces of gum/d. Chew and park gum* Hiccups/dyspepsia possible; avoid food or beverages 15 min before and after use Lozenge 2 mg or 4 mg Nasal spray 10 mg/mL Starting dose: maximum of 40 doses/d Local irritation possible; avoid with nasal or reactive airway disorders Oral inhaler 10-mg cartridge Starting dose: Puff for 20 min/cartridge every 1-2 h; maximum 16 cartridges/d Cough possible; avoid with reactive airway disorders Other Bupropion (Zyban [GlaxoSmithKline], Wellbutrin SR [GlaxoSmithKline]) 150 mg SR 150 mg once daily (am) for 3 d; then 150 mg twice daily; may use in combination Avoid with history/risk of seizures, eating disorders, MAO inhibitors, or CYP 2D6 inhibitor Varenicline (Chantix [Pfizer]) 0.5 mg or 1 mg 0.5 mg once daily (am) for 3 d; then 0.5 mg twice daily for 4 d; then 1 mg twice daily (use start pack followed by continuation pack) for 3-6 mo Nausea common; take with food. Renal dosing required. Very limited drug interactions; near-exclusive renal clearance. *CPD can guide dosing. 1 CPD is 1-2 mg of nicotine. Note: Use caution with all NRT products for patients with recent ( 2 wk) MI, serious arrhythmia, or angina; patients who are pregnant or breastfeeding; and adolescents. Timing of assessment relates to ICD-10 coding. Dose and duration can be titrated on the basis of response.S4.5-21 The FDA has issued a removal of black box warnings about neuropsychiatric events.S4.5-20,S4.5-21 am indicates morning; CPD, cigarettes smoked per day; FDA, US Food and Drug Administration; ICD-10, International Classification of Diseases, Tenth Revision; MAO, monoamine oxidase; NRT, nicotine replacement; and SR, sustained release. CLINICAL STATEMENTS AND GUIDELINES 6. Secondhand smoke exposure is known to cause in nonsmokers, and it can lead to immediate adverse events.S4.5-30 There is no safe lower limit of exposure to secondhand 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 41000 preventable deaths per year occur in adult nonsmokers as a result of exposure to second- The US Department of Housing and Urban Development prohibited the use of combustible tobacco products in all public hous- ing 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 pres- ent writing committee recommends that clinicians advise patients to take precautions against expo- sure 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. 4.6. Aspirin Use Recommendations for Aspirin Use Referenced studies that support recommendations are summarized in Online Data Supplements 17 and 18. COR LOE Recommendations IIb A Low-dose aspirin (75-100 mg orally daily) might be considered for the primary prevention of ASCVD among select adults 40 to 70 years of age who are at higher ASCVD risk but not at increased bleeding III: Harm B-R Low-dose aspirin (75-100 mg orally daily) should not be administered on a routine basis for the primary prevention of ASCVD among adults >70 years of age.S4.6-9 III: Harm C-LD Low-dose aspirin (75-100 mg orally daily) should not be administered for the primary prevention of ASCVD among adults of any age who are at increased risk of Synopsis For decades, aspirin has been widely administered for ASCVD prevention. By irreversibly inhibiting platelet function, aspirin reduces risk of atherothrombosis but also increases risk of bleeding, particularly in the gas- Aspirin is well established for secondary prevention of ASCVDS4.6-12 and is widely rec- ommended for this indication.S4.6-13 However, in primary prevention, aspirin use is more controversial. Because persons without prior ASCVD are inherently less likely to have future ASCVD events than are those with a prior history, it is more challenging for clinicians and patients to balance benefits and harms of prophylactic aspirin for primary prevention. This uncertainty is re- flected in international guidelines, where, for example, aspirin is not recommended in European guidelines for primary ASCVD preventionS4.6-13 but is recommended in prior US guidelines for selected primary prevention for adults who have elevated risk of ASCVD based on tradi- tional risk factors.S4.6-14,S4.6-15 Adding to this controversy are more recently conducted primary-prevention trials that, in contrast to older trials,S4.6-12 have shown less overall benefit of prophylactic aspirin alongside coad- ministration of contemporary ASCVD preventive treat- ments, such as evidence-based hypertension and cho- Recommendation-Specific Supportive Text 1. To balance the benefits and risks, prior US guide- lines 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 Meta-regression analyses of his- torical trials show that observed ASCVD risk tracks reasonably well with baseline-estimated ASCVD In contrast, observed bleeding risk on aspirin is less well correlated with baseline-esti- mated ASCVD risk.S4.6-19 (A nonexhaustive list of scenarios associated with increased risk of bleed- ing 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% esti- However, the relative benefits of aspirin, specifically in pre- venting 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 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 CLINICAL STATEMENTS AND GUIDELINES evidence for ASCVD risk [inclusive, where appro- priate, of risk-enhancing factors, such as strong family history of premature MI, inability to achieve lipid or BP or glucose targets, or significant eleva- tion in coronary artery calcium scoreS4.6-21 ] 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 conse- quences not captured by clinical trials of 5 to 10 years duration) is worth a slight excess risk of seri- ous bleeding. Recent trials show that absolute risk for ASCVD events typically exceeds that of bleed- ing and, although the gap of relative benefit to relative harm for aspirin has narrowed, the num- ber needed to treat to prevent an ASCVD event remains lower than the number needed to harm to cause bleeding. Others may feel that the ben- efit 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 nar- row overall balance between benefits and harms of prophylactic aspirin, there is limited justifica- tion to use aspirin at doses >100 mg daily for pri- mary 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 aspi- rin. Recent observational studies motivate future research on the personalization of prophylactic aspirin dose according to patient-specific factors 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 2. Prophylactic aspirin in primary-prevention adults >70 years of age is potentially harmful and, given the higher risk of bleeding in this age group, dif- ficult 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 rou- tine 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 physi- cians might discuss prophylactic aspirin with adults <40 years of age or >70 years of age in the con- text of other known ASCVD risk factors (eg, strong family history of premature MI, inability to achieve lipid or BP or glucose targets, or significant eleva- tion 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 3. The accumulated trial and observational data to date support avoiding prophylactic aspirin in the setting of known risk factors for increased bleeding 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 anti- coagulants, and warfarin.S4.6-10 5. 