Commentary

The alphabet soup of primary CV prevention

New prevention guideline represents shift toward lifestyle emphasis, personalized medicine

The 2019 American College of Cardiology/American Heart Association Guideline on the Primary Prevention of Cardiovascular Disease, recently released at the ACC Scientific Session in New Orleans, emphasizes social determinants of health for healthy lifestyle behavior as a critical foundation for atherosclerotic CVD risk reduction. Currently, 1 in 3 Americans has ASCVD, with the estimated proportion to reach 1 in 2 by 2030. Although advances in prevention have played a tremendous role in reducing CV morbidity and mortality over the years, CVD rate reduction has plateaued due to the worsening obesity and diabetes epidemics.

The cumulative effects of high cholesterol, high BP, obesity, smoking, poor diet and abnormal glucose metabolism are substantial in terms of their negative impact on CV health. A large body of research emphasizes that ASCVD prevention begins in childhood — the priority is promoting a healthy lifestyle and estimating lifetime risk. Later, lifestyle intervention and aggressive medical control of comorbidities are cornerstones in risk reduction. In a typical busy clinical setting, implementing the recent guideline recommendations can be challenging. Here, we summarize the most salient points related to the 2019 guideline in a simple, ABCDE-structured approach.

Aparna Sajja

Aspirin

Recent randomized controlled trials such as the ARRIVE, ASCEND and ASPREE studies have called the role for routine use of aspirin in primary prevention into question. Aspirin should not be administered on a routine basis for primary prevention in adults older than 70 years, and at any age if there is increased risk for bleeding. Overall, the new advice is to rethink aspirin.

We are looking at a smaller, refined group of patients (such as those with multiple risk-enhancing factors) who may derive potential net benefit. Aspirin could be considered for primary prevention in select adults aged 40 to 70 years at higher ASCVD risk — perhaps those who have an ASCVD risk estimate of at least 20% after other risk factors have been adequately addressed — who are not at increased bleeding risk.

Decisions about aspirin warrant shared decision-making. The decision to start prophylactic aspirin may be further guided by coronary artery calcium, a tiebreaker in indeterminate cases. From MESA data in those without diabetes, when a patient’s CAC score was 0, aspirin use would likely result in net harm compared with possible net benefit when CAC is greater than 100.

Blood pressure

In a meta-analysis, each 20 mm Hg increase in systolic BP and 10 mm Hg increase in diastolic BP were associated with twice the risk for death from vascular disease. Currently, the 2017 multisociety Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults and the 2019 primary prevention guideline recommend lifestyle changes in low-risk adults with BP less than 140/90 mm Hg. In adults with stage 2 hypertension (> 140/90 mm Hg) and/or ASCVD 10-year risk estimate greater than 10%, lifestyle and medical therapy are recommended. The best proven lifestyle interventions for hypertension are the DASH diet, which has been shown to reduce BP by approximately 11 mm Hg, followed by weight loss, reduction in dietary sodium and aerobic exercise.

Vincent A. Pallazola

The lower threshold to treat hypertension is based on the landmark SPRINT trial, which reported significant improvements in CV morbidity and mortality in high-risk hypertensive patients with intensive BP control (< 120 mm Hg systolic) compared with the standard target of less than 140 mm Hg systolic. SPRINT has many implications and questions regarding generalizability of intensive systolic BP targets and management of intermediate ASCVD risk patients.

Cholesterol and risk discussions

The 2019 primary prevention guideline emphasizes starting early lifestyle intervention and exercise for reduction of lifetime ASCVD risk. Statin therapy should be considered if there is family history of premature CVD and a persistent LDL 160 mg/dL in those with at least a 5% 10-year estimated risk for ASCVD.

Secondary risk-enhancing factors, discussed below, should be considered in all patients to better personalize risk estimation and decisions. A major hallmark of the new guidelines is improved risk stratification for borderline (5% to 7.4%) and intermediate-risk (7.5% to 20%) adults. In adults at intermediate risk, statin therapy reduces risk for ASCVD, and the decision to initiate it should be made after a clinician-patient risk discussion. In patients at borderline risk, with risk-enhancing factors and/or substantial CAC, moderate-intensity statin therapy should be strongly considered.

The new primary prevention guideline emphasizes the importance of a shared, informed clinician-patient risk discussion of lifetime CV risk. In borderline- and intermediate-risk adults, risk-enhancing factors can be used to refine the 10-year risk estimate. Furthermore, selective use of CAC for risk stratification in intermediate-risk patients is recommended if the decision to start a statin remains unclear or if the patient is not inclined to go on a prescription medication. Studies done with the MESA and Framingham cohorts have shown CAC testing in intermediate-risk groups may significantly improve risk stratification and provide helpful guidance on therapy decisions. Specifically, a CAC score of 0 is associated with a very low rate of ASCVD events over the next decade, therefore avoiding unnecessary medical therapy. This recommendation diverges from the misguided U.S. Preventive Services Task Force recommendation, which states that there is insufficient evidence in terms of utility of CAC for risk assessment.

There are several groups who may benefit from selective use of CAC assessment:

  • intermediate risk (10-year estimated ASCVD risk between 7.5% and 20%) and borderline risk (5% to 7.5%);
  • age/risk discordance, such as young patients with high risk factor levels and patients older than 60 years without other risk factors;
  • low to intermediate risk with comorbid inflammatory disease states; and
  • those with diabetes without significant other risk factors who are reluctant to start a statin.

Current guidelines recommend adults aged 40 to 75 years with diabetes, even without other risk factors, initiate a moderate-intensity statin. In those adults with diabetes who also have multiple CV risk factors, it is reasonable to prescribe a high-intensity statin with a goal to reduce LDL by 50%. Furthermore, the following diabetes-specific risk enhancers should encourage consideration of high-intensity statin: long duration (at least 10 years for type 2 diabetes, at least 20 years for type 1 diabetes), albuminuria greater than 30 mcg/mg creatinine, estimated glomerular filtration rate less than 60 mL/min/1.73 m2, retinopathy, neuropathy and ankle-brachial index less than 0.9.

Roger S. Blumenthal

Cigarettes

Tobacco use is the leading preventable cause of disease and death in the U.S. Almost one-third of ASCVD deaths in adults are related to smoking and secondhand smoke. Even a few cigarettes per day convey substantial ASCVD risk. Use of electronic cigarettes and hookah has also increased, particularly in youth.

E-cigarettes have recently been shown to almost double the risk for MI. Quitting smoking at any age substantially decreases both ASCVD and total mortality risk. The cornerstones of clinicians guiding smoking cessation involves assertive encouragement, gentle persistence and evidence-based pharmacotherapy (Table 1). All adults should be assessed at every visit for tobacco use and those who use tobacco products should be strongly advised to quit during each visit. The guideline recommends emphasizing that smoking cessation can be the most important thing one can do to improve their health.

Diet and weight

Seth S. Martin

Adults who consume a healthy plant-based or Mediterranean diet high in fresh vegetables and fruits, nuts in moderation, legumes, whole grains, lean animal protein and vegetable fiber have a lower mortality risk compared with adults consuming a standard Western diet. The following are associated with a higher CVD risk: increased intake of sugar, refined carbohydrates, trans- and saturated-fat diets, sodium, very low-carbohydrate diets, very high-carbohydrate diets and increased processed meat intake. Processed meats are any meat preserved by smoking, curing, salting or with other chemical preservatives; examples include hot dogs, bacon, sausage, salami and ham.

Current evidence supports the cardioprotective benefits of nuts, olive oil and other mono- and poly unsaturated liquid vegetable oils, plant-based diets, and antioxidant-rich foods. Eliminating trans fats and replacing saturated fat with polyunsaturated or monounsaturated fats is encouraged. While further studies are needed, there is some evidence that vegan diets may work to alter the microbiome and reduce ASCVD risk.

In overweight individuals, loss of 3% to 10% of body weight by caloric restriction and increased physical activity are recommended as part of a comprehensive lifestyle program. Calculating BMI is recommended annually or more frequently. It is also reasonable to measure waist-to-hip circumference to identify those at higher cardiometabolic risk, as there is evidence that it is a better marker of visceral adipose tissue, which is strongly associated with CVD.

Diabetes

Adults with type 2 diabetes have a significantly increased risk for developing CVD and have a 6-year average shorter life expectancy compared to those with diabetes. All persons with diabetes should undergo dietary counseling for a heart-healthy diet and aim for at least 150 minutes per week of moderate to vigorous exercise. While metformin remains first-line in terms of medical therapy, recently several diabetes outcome trials with SGLT2 inhibitors and GLP-1 receptor agonists have demonstrated a clear CV advantage, with reduction in MI, hospitalizations for HF and CV mortality.

With respect to CV benefits, SGLT2 inhibitors had greater reduction in HF-related events while GLP-1 receptor agonists improved CV outcomes mainly by decreasing atherosclerotic events and promoting weight loss. These agents are shaping a new paradigm of improving CV risk beyond addressing the conventional risk factors (BP, weight, lipids). New research is focusing on emerging mechanisms, such as inflammatory pathways and the cardio-metabolic-renal axis, in understanding these agents’ effects.

There are various HbA1c targets indicated by different societies: the American College of Physicians has set its target HbA1c higher at 7% to 8% than recommended by the American Diabetes Association (< 7%) and the American Association of Clinical Endocrinologists (6.5%). Many clinicians feel that overtreating individuals aged 65 years or older may carry more harms than benefits; however, a wider risk-benefit calculation based on patient preferences, age, and risk-enhancing factors should be considered for personalized care.

Exercise

There is a strong inverse relationship between the amount of physical activity and incident ASCVD events and mortality. Approximately half of U.S. adults do not meet the CDC’s minimum exercise recommendations. Adults should engage in at least 150 minutes per week of moderate-intensity or 75 minutes per week of vigorous-intensity exercise (Table 2). Even reducing periods of sedentary state may lower ASCVD risk. Several lines of evidence suggest that physical activity works to reduce systemic inflammation and consequently ASCVD risk. Ongoing studies have indicated an association between ASCVD and psychosocial/stress factors. While the current evidence for meditation, tai chi and mindfulness fall short of inclusion in guidelines for ASCVD primary risk reduction, these remain to be explored in future research.

A new shift

We are seeing a new shift toward personalized medicine within preventive cardiology through entry of additional diagnostic modalities for risk assessment and various pharmacological therapies. While the issue of cost is frequently raised, the 2019 primary prevention guideline continues to emphasize early lifestyle changes and prevention of CV comorbidities. When these are not sufficient, medications should be secondary consideration. Even with the latter, there is emphasis on the process of comprehensive risk discussion and shared decision-making.

Disclosures: Blumenthal, Pallazola and Sajja report no relevant financial disclosures. Martin reports he served on scientific advisory boards for Akcea, Amgen, Esperion, Novo Nordisk and Sanofi/Regeneron.

The 2019 American College of Cardiology/American Heart Association Guideline on the Primary Prevention of Cardiovascular Disease, recently released at the ACC Scientific Session in New Orleans, emphasizes social determinants of health for healthy lifestyle behavior as a critical foundation for atherosclerotic CVD risk reduction. Currently, 1 in 3 Americans has ASCVD, with the estimated proportion to reach 1 in 2 by 2030. Although advances in prevention have played a tremendous role in reducing CV morbidity and mortality over the years, CVD rate reduction has plateaued due to the worsening obesity and diabetes epidemics.

The cumulative effects of high cholesterol, high BP, obesity, smoking, poor diet and abnormal glucose metabolism are substantial in terms of their negative impact on CV health. A large body of research emphasizes that ASCVD prevention begins in childhood — the priority is promoting a healthy lifestyle and estimating lifetime risk. Later, lifestyle intervention and aggressive medical control of comorbidities are cornerstones in risk reduction. In a typical busy clinical setting, implementing the recent guideline recommendations can be challenging. Here, we summarize the most salient points related to the 2019 guideline in a simple, ABCDE-structured approach.

Aparna Sajja

Aspirin

Recent randomized controlled trials such as the ARRIVE, ASCEND and ASPREE studies have called the role for routine use of aspirin in primary prevention into question. Aspirin should not be administered on a routine basis for primary prevention in adults older than 70 years, and at any age if there is increased risk for bleeding. Overall, the new advice is to rethink aspirin.

We are looking at a smaller, refined group of patients (such as those with multiple risk-enhancing factors) who may derive potential net benefit. Aspirin could be considered for primary prevention in select adults aged 40 to 70 years at higher ASCVD risk — perhaps those who have an ASCVD risk estimate of at least 20% after other risk factors have been adequately addressed — who are not at increased bleeding risk.

Decisions about aspirin warrant shared decision-making. The decision to start prophylactic aspirin may be further guided by coronary artery calcium, a tiebreaker in indeterminate cases. From MESA data in those without diabetes, when a patient’s CAC score was 0, aspirin use would likely result in net harm compared with possible net benefit when CAC is greater than 100.

Blood pressure

In a meta-analysis, each 20 mm Hg increase in systolic BP and 10 mm Hg increase in diastolic BP were associated with twice the risk for death from vascular disease. Currently, the 2017 multisociety Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults and the 2019 primary prevention guideline recommend lifestyle changes in low-risk adults with BP less than 140/90 mm Hg. In adults with stage 2 hypertension (> 140/90 mm Hg) and/or ASCVD 10-year risk estimate greater than 10%, lifestyle and medical therapy are recommended. The best proven lifestyle interventions for hypertension are the DASH diet, which has been shown to reduce BP by approximately 11 mm Hg, followed by weight loss, reduction in dietary sodium and aerobic exercise.

PAGE BREAK
Vincent A. Pallazola

The lower threshold to treat hypertension is based on the landmark SPRINT trial, which reported significant improvements in CV morbidity and mortality in high-risk hypertensive patients with intensive BP control (< 120 mm Hg systolic) compared with the standard target of less than 140 mm Hg systolic. SPRINT has many implications and questions regarding generalizability of intensive systolic BP targets and management of intermediate ASCVD risk patients.

Cholesterol and risk discussions

The 2019 primary prevention guideline emphasizes starting early lifestyle intervention and exercise for reduction of lifetime ASCVD risk. Statin therapy should be considered if there is family history of premature CVD and a persistent LDL 160 mg/dL in those with at least a 5% 10-year estimated risk for ASCVD.

Secondary risk-enhancing factors, discussed below, should be considered in all patients to better personalize risk estimation and decisions. A major hallmark of the new guidelines is improved risk stratification for borderline (5% to 7.4%) and intermediate-risk (7.5% to 20%) adults. In adults at intermediate risk, statin therapy reduces risk for ASCVD, and the decision to initiate it should be made after a clinician-patient risk discussion. In patients at borderline risk, with risk-enhancing factors and/or substantial CAC, moderate-intensity statin therapy should be strongly considered.

The new primary prevention guideline emphasizes the importance of a shared, informed clinician-patient risk discussion of lifetime CV risk. In borderline- and intermediate-risk adults, risk-enhancing factors can be used to refine the 10-year risk estimate. Furthermore, selective use of CAC for risk stratification in intermediate-risk patients is recommended if the decision to start a statin remains unclear or if the patient is not inclined to go on a prescription medication. Studies done with the MESA and Framingham cohorts have shown CAC testing in intermediate-risk groups may significantly improve risk stratification and provide helpful guidance on therapy decisions. Specifically, a CAC score of 0 is associated with a very low rate of ASCVD events over the next decade, therefore avoiding unnecessary medical therapy. This recommendation diverges from the misguided U.S. Preventive Services Task Force recommendation, which states that there is insufficient evidence in terms of utility of CAC for risk assessment.

There are several groups who may benefit from selective use of CAC assessment:

  • intermediate risk (10-year estimated ASCVD risk between 7.5% and 20%) and borderline risk (5% to 7.5%);
  • age/risk discordance, such as young patients with high risk factor levels and patients older than 60 years without other risk factors;
  • low to intermediate risk with comorbid inflammatory disease states; and
  • those with diabetes without significant other risk factors who are reluctant to start a statin.
PAGE BREAK

Current guidelines recommend adults aged 40 to 75 years with diabetes, even without other risk factors, initiate a moderate-intensity statin. In those adults with diabetes who also have multiple CV risk factors, it is reasonable to prescribe a high-intensity statin with a goal to reduce LDL by 50%. Furthermore, the following diabetes-specific risk enhancers should encourage consideration of high-intensity statin: long duration (at least 10 years for type 2 diabetes, at least 20 years for type 1 diabetes), albuminuria greater than 30 mcg/mg creatinine, estimated glomerular filtration rate less than 60 mL/min/1.73 m2, retinopathy, neuropathy and ankle-brachial index less than 0.9.

Roger S. Blumenthal

Cigarettes

Tobacco use is the leading preventable cause of disease and death in the U.S. Almost one-third of ASCVD deaths in adults are related to smoking and secondhand smoke. Even a few cigarettes per day convey substantial ASCVD risk. Use of electronic cigarettes and hookah has also increased, particularly in youth.

E-cigarettes have recently been shown to almost double the risk for MI. Quitting smoking at any age substantially decreases both ASCVD and total mortality risk. The cornerstones of clinicians guiding smoking cessation involves assertive encouragement, gentle persistence and evidence-based pharmacotherapy (Table 1). All adults should be assessed at every visit for tobacco use and those who use tobacco products should be strongly advised to quit during each visit. The guideline recommends emphasizing that smoking cessation can be the most important thing one can do to improve their health.

Diet and weight

Seth S. Martin

Adults who consume a healthy plant-based or Mediterranean diet high in fresh vegetables and fruits, nuts in moderation, legumes, whole grains, lean animal protein and vegetable fiber have a lower mortality risk compared with adults consuming a standard Western diet. The following are associated with a higher CVD risk: increased intake of sugar, refined carbohydrates, trans- and saturated-fat diets, sodium, very low-carbohydrate diets, very high-carbohydrate diets and increased processed meat intake. Processed meats are any meat preserved by smoking, curing, salting or with other chemical preservatives; examples include hot dogs, bacon, sausage, salami and ham.

Current evidence supports the cardioprotective benefits of nuts, olive oil and other mono- and poly unsaturated liquid vegetable oils, plant-based diets, and antioxidant-rich foods. Eliminating trans fats and replacing saturated fat with polyunsaturated or monounsaturated fats is encouraged. While further studies are needed, there is some evidence that vegan diets may work to alter the microbiome and reduce ASCVD risk.

PAGE BREAK

In overweight individuals, loss of 3% to 10% of body weight by caloric restriction and increased physical activity are recommended as part of a comprehensive lifestyle program. Calculating BMI is recommended annually or more frequently. It is also reasonable to measure waist-to-hip circumference to identify those at higher cardiometabolic risk, as there is evidence that it is a better marker of visceral adipose tissue, which is strongly associated with CVD.

Diabetes

Adults with type 2 diabetes have a significantly increased risk for developing CVD and have a 6-year average shorter life expectancy compared to those with diabetes. All persons with diabetes should undergo dietary counseling for a heart-healthy diet and aim for at least 150 minutes per week of moderate to vigorous exercise. While metformin remains first-line in terms of medical therapy, recently several diabetes outcome trials with SGLT2 inhibitors and GLP-1 receptor agonists have demonstrated a clear CV advantage, with reduction in MI, hospitalizations for HF and CV mortality.

With respect to CV benefits, SGLT2 inhibitors had greater reduction in HF-related events while GLP-1 receptor agonists improved CV outcomes mainly by decreasing atherosclerotic events and promoting weight loss. These agents are shaping a new paradigm of improving CV risk beyond addressing the conventional risk factors (BP, weight, lipids). New research is focusing on emerging mechanisms, such as inflammatory pathways and the cardio-metabolic-renal axis, in understanding these agents’ effects.

There are various HbA1c targets indicated by different societies: the American College of Physicians has set its target HbA1c higher at 7% to 8% than recommended by the American Diabetes Association (< 7%) and the American Association of Clinical Endocrinologists (6.5%). Many clinicians feel that overtreating individuals aged 65 years or older may carry more harms than benefits; however, a wider risk-benefit calculation based on patient preferences, age, and risk-enhancing factors should be considered for personalized care.

Exercise

There is a strong inverse relationship between the amount of physical activity and incident ASCVD events and mortality. Approximately half of U.S. adults do not meet the CDC’s minimum exercise recommendations. Adults should engage in at least 150 minutes per week of moderate-intensity or 75 minutes per week of vigorous-intensity exercise (Table 2). Even reducing periods of sedentary state may lower ASCVD risk. Several lines of evidence suggest that physical activity works to reduce systemic inflammation and consequently ASCVD risk. Ongoing studies have indicated an association between ASCVD and psychosocial/stress factors. While the current evidence for meditation, tai chi and mindfulness fall short of inclusion in guidelines for ASCVD primary risk reduction, these remain to be explored in future research.

PAGE BREAK

A new shift

We are seeing a new shift toward personalized medicine within preventive cardiology through entry of additional diagnostic modalities for risk assessment and various pharmacological therapies. While the issue of cost is frequently raised, the 2019 primary prevention guideline continues to emphasize early lifestyle changes and prevention of CV comorbidities. When these are not sufficient, medications should be secondary consideration. Even with the latter, there is emphasis on the process of comprehensive risk discussion and shared decision-making.

Disclosures: Blumenthal, Pallazola and Sajja report no relevant financial disclosures. Martin reports he served on scientific advisory boards for Akcea, Amgen, Esperion, Novo Nordisk and Sanofi/Regeneron.