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Decipher the Guidelines
2021 ESC Guidelines on Cardiovascular Disease Prevention

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Welcome to the CardioNerds Decipher the Guidelines
2021 ESC Guidelines on Cardiovascular Disease Prevention edition! 

The Decipher the Guidelines using high-impact, board-style, clinical vignette based questions to highlight core concepts relevant to your practice. We will do so by releasing several short bite-sized Pods with one question per episode.

This particular series is built around the 2021 ESC Prevention Guidelines and 2019 ACC/AHA Prevention Guidelines, was developed in collaboration with the ACC Prevention of CVD Section, the NLA, and the PCNA. Its creation reflects the passion and energy of 31 individuals spanning medical students through to lead experts from varied backgrounds including physicians, pharmacists, and nurse practitioners.  

Decipher the Guidelines - 2021 ESC CV Prevention
Graphic designed by Dr. Ahmed Gohneem

Episodes

The following question refers to Section 4.11 of the 2021 ESC CV Prevention Guidelines. The question is asked by Dr. Christian Faaborg-Andersen, answered first by UCSF resident Dr. Jessie Holtzman, and then by expert faculty Dr. Laurence Sperling.

Dr. Laurence Sperling is the Katz Professor in Preventive Cardiology at the Emory University School of Medicine and Founder of Preventive Cardiology at the Emory Clinic. Dr. Sperling was a member of the writing group for the 2018 Cholesterol Guidelines, serves as Co-Chair for the ACC’s Cardiometabolic and Diabetes working group, and is Co-Chair of the WHF Roadmap for Cardiovascular Prevention in Diabetes.

The following question refers to Section 6.1 of the 2021 ESC CV Prevention Guidelines. The question is asked by Dr. Christian Faaborg-Andersen, answered first by UCSD cardiology fellow Dr. Harpreet Bhatia, and then by expert faculty Dr. Eugenia Gianos.

Dr. Gianos specializes in preventive cardiology, lipidology, cardiovascular imaging, and women’s heart disease; she is the director of the Women’s Heart Program at Lenox Hill Hospital and director of Cardiovascular Prevention for Northwell Health.

The following question refers to Section 4.6 of the  2021 ESC CV Prevention Guidelines. The question is asked by student Dr. Shivani Reddy, answered first by NP Carol Patrick, and then by expert faculty Dr. Eileen Handberg.

Dr. Handberg is an Adult Nurse Practitioner, Professor of Medicine, and Director of the Cardiovascular Clinical Trials Program in the Division of Cardiovascular Medicine at the University of Florida. She has served as Chair of the Cardiovascular Team Section and the Board of Trustees with the ACC and is the President Elect for the PCNA.

The following question refers to Section 4.3 of the 2021 ESC CV Prevention Guidelines. The question is asked by Dr. Maryam Barkhordarian, answered first by pharmacy resident Dr. Anushka Tandon, and then by expert faculty Dr. Noreen Nazir.

Dr. Noreen Nazir is Assistant Professor of Clinical Medicine at the University of Illinois at Chicago, where she is the director of cardiac MRI and the preventive cardiology program.

This question refers to Sections 3.1 of the 2021 ESC CV Prevention Guidelines. The question is asked by CardioNerds Academy Intern, student Dr. Hirsh Elhence, answered first by internal medicine resident at Beaumont Hospital and soon to be Mayo Clinic cardiology fellow and Dr. Teodora Donisan and then by expert faculty Dr. Eugene Yang.

Dr. Yang is professor of medicine of the University of Washington where he is medical director of the Eastside Specialty Center and the co-Director of the Cardiovascular Wellness and Prevention Program. Dr. Yang is former Governor of the ACC Washington Chapter and current chair of the ACC Prevention of CVD Section.

The following question refers to Section 3.4 of the 2021 ESC CV Prevention Guidelines. The question is asked by student Dr. Adriana Mares, answered first by early career preventive cardiologist Dr. Dipika Gopal, and then by expert faculty Dr. Michael Wesley Milks.

Dr. Milks is a staff cardiologist and assistant professor of clinical medicine at the Ohio State University Wexner Medical Center where he serves as the Director of Cardiac Rehabilitation and an associate program director of the cardiovascular fellowship. He specializes in preventive cardiology and is a member of the American College of Cardiology’s Cardiovascular Disease Prevention Leadership Council.

The following question refers to Section 4.8 of the 2021 ESC CV Prevention Guidelines. The question is asked by CardioNerds Academy Intern student Dr. Christian Faaborg-Andersen, answered first by UCSF resident Dr. Jessie Holtzman, and then by expert faculty Dr. Melissa Tracy.

Dr. Tracy is a preventive cardiologist, echocardiographer, Director of Cardiac Rehabilitation, and solid organ transplant cardiologist at Rush University.

The following question refers to Section 4.10 of the 2021 ESC CV Prevention Guidelines. The question is asked by CardioNerds Academy Intern student Dr. Christian Faaborg-Andersen, answered first by UCSD fellow Dr. Patrick Azcarate, and then by expert faculty Dr. Laurence Sperling.

Dr. Larry Sperling is the Katz Professor in Preventive Cardiology at the Emory University School of Medicine and Founder of Preventive Cardiology at the Emory Clinic. Dr. Sperling was a member of the writing group for the 2018 Cholesterol Guidelines, serves as Co-Chair for the ACC’s Cardiometabolic and Diabetes working group, and is Co-Chair of the WHF Roadmap for Cardiovascular Prevention in Diabetes.

The following question refers to Section 4.7 and figure 16 of the 2021 ESC CV Prevention Guidelines. The question is asked by CardioNerds Academy Intern Student Dr. Shivani Reddy, answered first by Fellow at Johns Hopkins Dr. Rick Ferraro, and then by expert faculty Dr. Roger Blumenthal.

Dr. Roger Blumenthal is professor of medicine at Johns Hopkins where he is Director of the Ciccarone Center for the Prevention of Cardiovascular Disease. He was instrumental in developing the 2018 ACC/AHA CV Prevention Guidelines. Dr. Blumenthal has also been an incredible mentor to CardioNerds from our earliest days.

The following question refers to Section 4.3 of the 2021 ESC CV Prevention Guidelines. The question is asked by CardioNerds Academy Intern Dr. Maryam Barkhordarian, answered first by medicine resident CardioNerds Academy House Chief Dr. Ahmed Ghoneem, and then by expert faculty Dr. Kim Williams.

Dr. Williams is Chief of the Division of Cardiology and is Professor of Medicine and Cardiology at Rush University Medical Center. He has served as President of ASNC, Chairman of the Board of the Association of Black Cardiologists (ABC, 2008-2010), and President of the American College of Cardiology (ACC, 2015-2016).

The following question refers to Section 3.3 of the 2021 ESC CV Prevention Guidelines. The question is asked by CardioNerds Academy Intern student Dr. Adriana Mares, answered first by Brigham & Women’s medicine intern & Director of CardioNerds Internship Dr. Gurleen Kaur, and then by expert faculty Dr. Allison Bailey.

Dr. Bailey is an advanced heart failure and transplant cardiologist at Centennial Heart. She is the editor-in-chief of the American College of Cardiology’s Extended Learning (ACCEL) editorial board and was a member of the writing group for the 2018 American Lipid Guidelines.

This question refers to Sections 3.2 and 3.3 of the 2021 ESC CV Prevention Guidelines. The question is asked by CardioNerds Academy Intern student Dr. Hirsh Elhence, answered first by Ohio State University Cardiology Fellow Dr. Alli Bigeh, and then by expert faculty Dr. Eugene Yang.

Dr. Yang is professor of medicine of the University of Washington where he is medical director of the Eastside Specialty Center and the co-Director of the Cardiovascular Wellness and Prevention Program. Dr. Yang is former Governor of the ACC Washington Chapter and current chair of the ACC Prevention of CVD Section.

Question and Answers

A 48-year-old Pakistani woman with rheumatoid arthritis comes to your clinic asking how she can reduce her risk of ASCVD. Her mother died of an MI at age 45, her father is healthy at age 79. Her calculated 10-year risk based on SCORE2 is 3%. SBP is 120 mmHg, LDL is 120 mg/dL. What is the next best step? 

A. Order an echocardiogram 
B. Schedule a follow-up appointment in 1 year 
C. Discuss initiating a statin 
D. Repeat lipid panel in 3-5 years 

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Answer: C. Discuss Initiating a statin 

The absolute benefit derived from risk factor modification depends on the absolute risk of CVD and the absolute improvements in each risk factor category. Risk factor treatment recommendations are based on categories of CVD risk (“low-to-moderate”, “high”, and “very high”). The cut-off risk levels for these categories are numerically different for various age groups to avoid undertreatment in the young and to avoid overtreatment in the elderly. As age is a major driver of CVD risk, but lifelong risk factor treatment benefit is higher in younger people, the risk thresholds for considering treatment are lower for younger people as per the ESC guidelines. Treatment decisions should be made with shared decision-making valuing patient preference.  

Option A is INCORRECT- there is a lack of convincing evidence that echocardiography improves CVD risk reclassification, and it is NOT recommended to improve CV risk prediction. (Class III, LOE B) 

Option B is INCORRECT- simply doing nothing is not appropriate for this patient with elevated CVD risk.  

Option C is CORRECT- This patient has a seemingly low 10-year CVD risk based on SCORE 2 of 3% and her SBP is controlled; however, given her age she is considered as having high CVD risk, therefore treatment should be considered. Stepwise approach involves targeting LDL <100 (class IIa) so initiating a statin would be appropriate. This patient also carries several risk enhancing modifiers including Pakistani ethnicity, family history of premature CVD, and inflammatory comorbidity. All patients should be counseled on smoking cessation, lifestyle modifications, and target SBP <160 mmHg. 

Option D is INCORRECT- repeating a lipid panel without risk factor modification will not change treatment recommendations for this patient with elevated CVD risk.  

Main Takeaway 

In summary, when a patient <50 years old without established ASCVD has an estimated 10-year risk 2.5 to <7.5% they are considered high CVD risk and risk factor treatment should be considered. Risk modifiers should also be taken into consideration. 

*Of note- ACC/AHA guidelines recommend the ASCVD risk calculator to estimate 10-year risk and do not restructure CVD risk groups according to age groups. High risk in the ACC/AHA guidelines is considered to be >20%. 

Guideline Location

  • Table 5 and Figure 5, Page 3251
  • 3.2.3.4, Page 3253
  • 3.2.3, Figure 6 page 3252
  • 3.3, Pages 3258-3259 

Mr. Early M. Eye is a 55-year-old man with a history of GERD who is seeing you in clinic as he is concerned about his family history of early myocardial infarction and would like to discuss if he should be taking a statin for cardiovascular prevention. He has never smoked tobacco. His 10-year CVD risk is estimated to be 8%. Which imaging modality is recommended by the ESC guidelines to reclassify his CVD risk?

A. Coronary Artery Calcium (CAC) scoring
B. Echocardiography
C. Ankle brachial index
D. Contrast enhanced computed tomography coronary angiography (CCTA)
E. None of the above

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The correct answer is A.

Coronary artery calcium (CAC) scoring can reclassify CVD risk upwards and downwards and should specifically be considered in patients with calculated risk scores that are around decision thresholds. CAC scores which are high-than-expected for age and sex increase estimated future CVD risk. Notably, CAC scoring may also be used to “de-risk” if CAC is absent or lower-than-expected. The 2021 ESC Prevention Guidelines give a Class IIb (LOE B) recommendation to consider CAC scoring to improve risk classification around treatment decision thresholds. However, one limitation of CAC is that it does not provide direct information on total plaque burden or stenosis severity. In addition, there is also a Class IIb (LOE B) recommendation to use plaque detection by carotid ultrasound as an alternative when CAC scoring is unavailable or not feasible. Plaque assessed through carotid ultrasound is defined as presence of wall thickening that is >50% greater than the surrounding vessel wall or a focal region with intima-media thickness measurement >1.5mm that protrudes into the lumen.

Similar to the ESC Prevention Guidelines, the 2019 ACC/AHA guidelines on primary prevention of CVD also have a Class IIa recommendation for using CAC score, and explicitly mention its use for adults at intermediate risk (>7.5% to <20% 10-year ASCVD risk) with cut-offs including >100 Agatson units to reclassify risk upwards and CAC of 0 to reclassify risk downwards. However, the guidelines also mention that clinicians should not down-classify risk in patients who have CAC of 0 if they are current smokers, have diabetes, have a family history of ASCVD, or have chronic inflammatory conditions. Furthermore, the 2018 ACC/AHA Cholesterol guidelines have a Class IIa recommendation that if CAC is 0, it is reasonable to withhold statin therapy and reassess risk in 5 to 10 years, as long as higher risk conditions that we just discussed are absent. If CAC is 1-99, it is reasonable to initiate statin therapy for patients ≥ 55 years of age.

Choice B is incorrect. Echocardiography is not recommended to improve CV risk prediction due to lack of convincing evidence that it improves CVD risk reclassification.

Choice C is incorrect. While the 2013 ESC guidelines mentioned that ABI may be considered as a risk modifier in CVD risk estimation, the newer 2021 guidelines state that ankle brachial index has limited potential in terms of reclassification risk, though an individual patient data meta-analysis showed there may be utility for women at intermediate risk. 12-27% of middle-aged individuals can have an abnormal ankle brachial index, defined as less than 0.9, of which 50-89% may not have typical claudication symptoms. Conversely, the 2019 ACC/AHA guidelines include ABI <0.9 as a risk-enhancing factor.

Choice D is incorrect. Coronary computed tomographic angiography (CCTA) has been shown in studies such as SCOT-HEART to have utility in predicting cardiac events in patients with stable chest pain and can identify coronary stenosis. It is not currently recommended by ESC guidelines for prognostic value or risk classification in asymptomatic patients.

According to the ESC guidelines, routine vascular testing or imaging other than CAC scoring or carotid ultrasound for plaque determination are not recommended (Class III, LOE B).

In terms of this patient’s family history of premature CVD, the ESC guidelines describe that even though family history is significantly associated with CVD in studies, it only marginally improves the prediction of CVD risk beyond conventional ASCVD risk factors. However, family history should still be obtained regularly when seeing patients, and if there is a positive family history of ASCVD, a comprehensive CVD risk assessment is warranted. Importantly, family history is not binary and those with a greater “dose” of family history (more relatives affected at earlier ages) may be at greater risk.

Main Takeaway

When a patient without established ASCVD has an estimated 10-year risk around treatment decision thresholds, CAC scoring is the best-established imaging modality to improve CVD risk stratification.

Guideline Location

Section 3.3.3, page 3259

Mrs. B is a 56-year-old African American woman with a past medical history significant for type 2 diabetes (HbA1C 7.6) and hypercholesterolemia. Her calculated ASCVD risk score today is 12.5% and her BMI is 24kg/m2. She is concerned about her high cholesterol levels despite being on a statin and feels that her diet is “not healthy enough.” She is interested in making dietary changes to help reduce her ASCVD risk. Which of the following recommendations is appropriate?

A. Sodium restriction to <3g /day will be of no benefit because she is not hypertensive.
B. Isocaloric substitution of saturated fat with polyunsaturated fat is associated with reduction of CHD risk.
C. Dietary fiber intake is associated with GI benefits but has no CV risk reduction benefit.
D. Supplementing diet with vitamins A, B, C and E helps reduce ASCVD risk.

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The correct answer is B.

Risk of CHD is reduced when dietary saturated fats are replaced with other foods having similar caloric values. The greatest reduction was observed when saturated fats were isocalorically replaced with polyunsaturated fats (↓25%), followed by monounsaturated fats (↓15%) and carbohydrates from whole grains (↓9%). This is a class 1a recommendation in the ESC guidelines and a class IIa recommendation in the 2019 ACC/AHA guidelines. Conversely, increased trans fatty acid intake is associated with increased CHD risk. A regulation of the European Union (EU) Commission has set the upper limit of trans fats to 2 g per 100 g of fat. The ACC/AHA guidelines recommend that the intake of trans fats should be avoided (a class III: harm).

Choice A is incorrect because dietary sodium restriction is recommended not only for control of blood pressure, but also for reduction of ASCVD risk. In a meta-analysis, salt reduction of 2.5 g/day resulted in a 20% reduction of ASCVD events (RR 0.80). Reduction of salt intake is a class 1 recommendation in the ESC guidelines compared to a class IIa recommendation in the 2019 ACC/AHA guidelines.

Choice C is incorrect because a 10 g/day higher fiber intake was associated with a 16% lower risk of stroke (RR 0.84) and a 6% lower risk of type 2 DM (RR 0.94). A high fiber intake may reduce postprandial glucose responses after carbohydrate-rich meals and also lower triglyceride levels. The Mediterranean diet is rich in fiber (it includes high intakes of fruits, vegetables, pulses and wholegrain products) and is a class I recommendation.

Choice D is incorrect because while vitamin supplementation has been associated with reduction in ASCVD risk in observational studies, intervention trials have failed to show any benefit. 

Main Takeaway:

A healthy diet is recommended as a cornerstone of CVD prevention in all individuals, independent of their underlying co-morbidities. Replacing saturated with unsaturated fats, reducing salt intake, and choosing a more plant-based diet that is rich in fiber can lower risk of CVD.

Guideline Location
Section 4.3.2, Page 3270

Ms. K.M. is a 40-year-old woman presenting to the outpatient clinic for a routine physical exam required for her employment as an airline stewardess. She states she has been in her usual good health but does experience occasional headaches and lightheadedness while in flight. On exam her BP was noted to be 170/90. The diagnosis of hypertension is confirmed during a subsequent clinic visit. What would be the most appropriate initial therapy recommendation(s) for Ms. K.M.?

A. Initiate single drug therapy with a beta-blocker.
B. Discuss and initiate lifestyle interventions
C. Initiate two-drug combination therapy with a thiazide-like diuretic, BB, CCB, or an ARB.
D. Both B and C 

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The correct answer is D.

The correct answer is D. Both B (lifestyle interventions) and C (initial combination therapy) are appropriate at this time.

Lifestyle interventions are indicated for all patients with high-normal BP or hypertension because they can delay the need for drug treatment or complement the BP-lowering effect of drug treatment (Class 1). Moreover, most lifestyle interventions have health benefits beyond their effect on BP.

Single-drug therapy will rarely achieve optimal BP control. Therefore, initial antihypertensive therapy with a combination of two drugs, preferably as a single-pill combination, is recommended for the management of HTN (Class 1). The only exceptions would be patients with a baseline BP close to the recommended target, who might achieve that target with a single drug, or very old (>80 years) or frail patients who may better tolerate a gentler reduction of BP.

Five major classes of BP-lowering drug therapy have shown benefit in reducing CV events; angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, calcium channel blockers (CCBs), and thiazide or thiazide-like diuretics.

A combination of an ACE inhibitor or ARB with a CCB or thiazide/thiazide-like diuretic is the preferred initial therapy for most patients with hypertension (Class 1). For those in whom treatment requires escalation to three drugs, a combination of an ACE inhibitor or ARB with a CCB and a thiazide/thiazide-like diuretic should be used (Class 1).

Resistant hypertension is defined as BP being uncontrolled despite treatment with optimal or best-tolerated doses of three or more drugs including a diuretic, and confirmed by ABPM or HBPM. Spironolactone is the most effective drug for lowering BP in resistant hypertension when added to existing treatment; however, the risk of hyperkalaemia is increased in patients with CKD. When spironolactone is not tolerated, amiloride, alpha-blockers, beta-blockers, or centrally acting drugs, such as clonidine, have evidence supporting their use. Renal denervation and device-based therapy may be considered for specific cases.

Beta-blockers should be used when there is a specific indication (e.g. angina, post myocardial infarction, arrythmia, HFrEF, or as an alternative to an ACE inhibitor or ARB in women of child-bearing potential). Combinations of an ACE inhibitor and an ARB are not recommended because of no added benefit on outcomes and increased risk of harm (Class III).

The diagnosis and treatment of hypertension in women is similar to that in men, except for women of child-bearing potential or during pregnancy, because of potential adverse effects of some drugs on the fetus, especially in the first trimester. In addition, the effect of oral contraceptive pills on the risk of developing or worsening hypertension should be considered.

Main Takeaway:

Combination drug therapies are more effective in lowering BP than monotherapy. BP management in women is similar to men with the exception of child-bearing potential given potential teratogenicity of some agents.

Guideline Location:

4.7.5.1-4, Page 3288

Figure 16, pg. 3287

The European Society of Cardiology Prevention guidelines currently recommend that low-dose colchicine (0.5mg/day) may be considered for the primary prevention of cardiovascular disease.

A. True
B. False

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The correct answer is False. 

The European Society of Cardiology recommends that low-dose colchicine may be considered as an adjunctive therapy for secondary rather than primary prevention of cardiovascular disease in individuals whose risk factors are otherwise insufficiently controlled (Class IIb, LOE A). A broad evidence base currently supports that inflammation has pro-atherosclerotic effects and that reducing inflammation may reduce atherogenesis in high-risk patients.

The initial LoDoCo trial in 2013 first demonstrated a 10.7% absolute risk reduction in acute coronary syndrome, out of hospital cardiac arrest, and non-cardioembolic ischemic stroke with daily low-dose colchicine; however, results were clouded by small sample size. Subsequently, the CANTOS trial in 2017 demonstrated a 15% relative reduction in non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death with Canakinumab, an anti-inflammatory monoclonal antibody inhibitor of interleukin-1. More recently, the COLCOT trial in 2019 studying patients with recent AMI and LoDoCo2 trial in 2021 studying patients with stable chronic CAD both demonstrated reductions in myocardial infarction, cardiovascular mortality, CVA, and ischemia-driven revascularization with colchicine 0.5mg/day. In the LoDoCo2 trial, stable CAD was defined either angiographically, by coronary CT, CAC >400, or history of CABG >10 years prior with evidence of failed grafts or angioplasty since that time.

In high-risk individuals with stable ischemic heart disease, the most recent evidence suggests that once daily low dose colchicine may reduce myocardial infarction and other ischemic events. Future studies may assess the biochemical markers including the trend of lipids and inflammatory markers to identify subpopulations that may benefit most from this therapy.

Main Takeaway:

Based upon the 2021 ESC Prevention Guidelines, clinicians may consider initiating low-dose colchicine (0.5mg/day) for secondary prevention of cardiovascular disease, particularly if other risk factors are insufficiently controlled or if recurrent CVD events occur despite optimal therapy.

Guideline Location: 

Section 4.10, page 3291.

A 62-year-old man with a history of non-obstructive coronary artery disease, heart failure with reduced ejection fraction (EF 30-35%), stage III chronic kidney disease, and type II diabetes mellitus presents to your clinic to establish care. His only medications are aspirin 81 mg daily and metformin 1000 mg BID, which he has taken since being diagnosed with diabetes mellitus 5 years ago. His hemoglobin A1c is 6.8%. What changes would you recommend to his medications at this time?

A. Start glipizide
B. Start saxagliptin
C. Start empagliflozin
D. No changes

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The correct answer is C – start empagliflozin.

The Trials involving SGLT-2 inhibitors and GLP-1R agonists have shown cardiovascular benefits independent of glycemic control and metformin use.

The ADA recommends metformin as a first-line therapy for all patients with type 2 DM. The ESC also recommends metformin as first-line therapy but only in patients without ASCVD, CKD, or HF (Class I, LOE B). If a patient has ASCVD, metformin can be considered (Class IIa, LOE B). Rather, for those patients with type 2 DM and ASCVD, the ESC recommends the use of GLP-1R agonist or SGLT-2 inhibitors with proven outcome benefits to reduce CV and/or cardiorenal outcomes (Class I, LOE A). Additionally, for those with type 2 DM and either CKD or HFrEF, the ESC recommends the use of SGLT-2 inhibitor to improve outcomes (Class I, LOE A).

In contrast to the ADA, the view of the ESC is that metformin should be considered but is not mandatory first-line treatment in patients with diabetes and ASCVD or evidence of target organ damage. The initiation of metformin in such patients should not forego or delay the initiation of evidence-based SGLT2 inhibitors or GLP-1RAs.


Therefore, the next best step for our patient is to start an SGLT-2 inhibitor given his history of CAD, HF, and CKD. While this patient’s A1c goal is within the range recommended for patients with Type 2 DM and ASCVD (<7%), given his CAD, HF, and CKD an SGLT-2 inhibitor should still be added.

Saxagliptin is a DPP-4 inhibitor, a class of drugs that showed no effect of MACE but increased risk of HF hospitalization in patients with DM and existing.

Lifestyle management is a top priority for ASCVD prevention and management of DM. Lifestyle intervention lowers future microvascular and macrovascular risks as well as mortality in the longer term. Intensive lifestyle changes with low-calorie diets and mean weight losses in the region of 10 kg leads to remission of type 2 DM in around 46% of cases at 1 year and 36% by 2 years. Smoking cessation, a diet low in saturated fat and high in fiber, aerobic physical activity, strength training, and reduction in energy intake for weight optimization are all recommended for patient with diabetes mellitus (Class I).

Main Takeaway

In patients with Type 2 DM and ASCVD or end organ dysfunction, SGLT-2 inhibitors or GLP-1R agonists should be recommended regardless of background therapy or glycemic control. For patients with type 2 diabetes mellitus and CKD or HFrEF, SGLT-2 inhibitor is recommended.

Guideline Location

Section 4.8.1, Pages 3289-90.

While you are on holiday break visiting your family, your aunt pulls you aside during the family gathering to ask a few questions about your 70-year-old uncle. He has hypertension, hyperlipidemia, type 2 diabetes mellitus, and moderate chronic obstructive pulmonary disease. His medications include Fluticasone/Salmeterol, Tiotropium, Albuterol, Lisinopril, Simvastatin, and Metformin. She is very concerned about his risk for heart disease as he has never had his “heart checked out.” She asks if the presence of COPD increases his chance of having heart disease. Which of the following statements would best answer her question?

A. Systemic inflammation and oxidative stress caused by COPD promote vascular remodeling and a paradoxical ‘anticoagulant’ state affecting all vasculature types.
B. Although chronic COPD is associated with increased cardiovascular events, individual exacerbations have no impact on risk of cardiovascular events.
C. Patients with mild-moderate COPD are 8-10x more likely to die from atherosclerotic cardiovascular disease than respiratory failure.
D. Cardiovascular mortality increases proportionally with an increase in forced expiratory volume in 1 second (FEV1)

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The correct answer is C.

Patients with mild-moderate COPD are 8-10x more likely to die from atherosclerotic cardiovascular disease than respiratory failure. Patients with COPD have a 2-3-fold increased risk of CV events compared to age-matched controls even when adjusted for tobacco smoking, a shared risk factor. This can be partly explained by other common risk factors including aging, hypertension, hyperlipidemia, and low physical activity.

Interestingly, CVD mortality increases proportionally with a decrease (rather than increase) in FEV1, making answer choice D wrong (28% increase CVD mortality for every 10% decrease in FEV1). Additionally, COPD exacerbations and related infections are associated with a 4x increase in CVD events, making answer choice B incorrect.

COPD has several effects on the vasculature which creates a ‘procoagulant’ not ‘anticoagulant’ effect on all vascular beds. This is associated with increased risk of cognitive impairment due to cerebral microvascular damage as well as increased risk of ischemic and hemorrhagic stroke.

Main Takeaway

The presence of COPD (even mild to moderate) has a significant impact on the incidence of non-fatal coronary events, stroke, and cardiovascular mortality mediated by inherent disease process and progression, risk factors (smoking, aging, hypertension, and hyperlipidemia), and systemic inflammation altering vasculature creating a ‘procoagulant’ effect. The ESC gives a Class I indication (LOE C) to investigate for ASCVD and ASCVD risk factors in patients with COPD.

Guideline Location

3.4.5, Page 3264.

Please read the following patient vignettes and choose the FALSE statement.

A. A 39-year-old man who comes for a regular physical, has normal vitals and weight, denies any significant past medical or family history – does not need systematic cardiovascular disease (CVD) assessment.
B. A 39-year-old woman who comes for a regular physical, has normal vitals and weight, and has a history of radical hysterectomy (no other significant past medical or family history) – could benefit from systematic or opportunistic CVD assessment.
C. A 39-year-old woman who comes for a regular physical, has normal vitals except for a BMI of 27 kg/m2 and a family history of hypertension – requires a systematic global CVD assessment.
D. A 39-year-old man who comes for a regular physical, has normal vitals and weight, and has a personal history of type I diabetes – requires a systematic global CVD assessment.

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The correct answer is C.

Option A is an accurate statement, as systematic CVD risk assessment is not recommended in men < 40 years-old and women < 50 years-old, if they have no known cardiovascular (CV) risk factors. (Class III, level C)

Option B is an accurate statement, as this patient had a radical hysterectomy, which means the ovaries have been removed as well and she is considered postmenopausal. Systematic or opportunistic CV risk assessment can be considered in men > 40 years-old and women > 50 years-old or postmenopausal, even in the absence of known ASCVD risk factors. (Class IIb, level C)

Option C is a false statement and thus the correct answer, as the recommendations for global screening in this patient are not as strong and would require shared decision making. Opportunistic screening of blood pressure can be considered in her, as she is at risk for developing hypertension. Blood pressure screening should be considered in adults at risk for the development of hypertension, such as those who are overweight or with a known family history of hypertension. (Class IIa, level B)

Option D is an accurate statement, as systematic global CVD risk assessment is recommended in individuals with any major vascular risk factor (i.e., family history of premature CVD, familial hyperlipidemia, CVD risk factors such as smoking, arterial hypertension, DM, raised lipid level, obesity, or comorbidities increasing CVD risk). (Class I, level C)

Additional learning points:

Do you know the difference between opportunistic and systematic CVD screening?

  • Opportunistic screening refers to screening without a predefined strategy when the patient presents for different reasons. This is an effective and recommended way to screen for ASCVD risk factors, although it is unclear if it leads to benefits in clinical outcomes.
  • Systematic screening can be done following a clear strategy formally evaluating either the general population or targeted subpopulations (i.e., type 2 diabetics or patients with significant family history of CVD). Systematic screening results in improvements in risk factors but has no proven effect on CVD outcomes.

Main Takeaway

Systematic CVD risk assessment in the general population without CV risk factors does not seem to be cost effective and has unclear benefits on outcomes, although it does lead to increased detection of potentially actionable CV risk factors. Risk assessment is not a one-time event and should be repeated (e.g., every 5 years), but there is no clear data to guide intervals.

Guideline Location

Section 3.1, page 3236; Table on page 3242.

Mr. A is a 28-year-old man who works as an accountant in what he describes as a “desk job” setting. He shares that life got “a little off-track” for him in 2020 between the COVID-19 pandemic and a knee injury. His 2022 New Years’ resolution is to improve his overall cardiovascular and physical health. He has hypertension and a family history of premature ASCVD in his father, who died of a heart attack at age 50. Prior to his knee injury, he went to the gym 3 days a week for 1 hour at a time, split between running on the treadmill and weightlifting. He has not returned to the gym since his injury and has been largely sedentary, although he is trying to incorporate a 20-minute daily walk into his routine. Which of the following exercise-related recommendations is most appropriate?

A. A target of 75-150 minutes of vigorous-intensity or 150-300 minutes of moderate-intensity aerobic physical exercise weekly is recommended to reduce all-cause mortality, CV mortality, and morbidity.
B. Bouts of exercise less than 30 minutes are not associated with favorable health outcomes.
C. Exercise efforts should be focused on aerobic activity, since only this type of activity is associated with mortality and morbidity benefits.
D. Light-intensity aerobic activity like walking is expected to have limited health benefits for persons with predominantly sedentary behavior at baseline.

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The correct answer is A.

There is an inverse relationship between moderate-to-vigorous physical activity and CV morbidity/mortality, all-cause mortality, and incidence of type 2 diabetes, with additional benefits accrued for exercise beyond the minimum suggested levels. The recommendation to “strive for at least 150-300 min/week of moderate-intensity, or 75-150 min/week of vigorous-intensity aerobic physical activity, or an equivalent combination thereof” is a Class 1 recommendation per the 2021 ESC guidelines, and a very similar recommendation (at least 75 minutes of vigorous-intensity or 150 minutes of moderate-intensity activity) is also Class 1 recommendation per 2019 ACC/AHA primary prevention guidelines. Both the ESC and ACC/AHA provide examples of activities grouped by absolute intensity (the amount of energy expended per minute of activity), but the ESC guidelines also offer suggestions for measuring the relative intensity of an activity (maximum/peak associated effort) in Table 7, which allows for a more individualized, customizable approach to setting activity goals. Importantly, individuals who are unable to meet minimum weekly activity recommendations should still be encouraged to stay as active as their abilities and health conditions allow to optimize cardiovascular and overall health.

Choice B is incorrect, as data suggests physical activity episodes of any duration, including <10 min, are associated with favorable outcomes like all-cause mortality benefit. The duration of a single exercise bout is less correlated with health benefits than the total physical activity time accumulated per week.

Choice C is incorrect. Per the ESC guidelines, it is a class 1 recommendation to perform resistance exercise, in addition to aerobic activity, on 2 or more days per week to reduce all-cause mortality. Data indicate that the addition of resistance exercise to aerobic activity is associated with lower risks of total CV events and all-cause mortality, so it’s expected that a combination of weightlifting and aerobic activity may be more beneficial for than either type of activity alone. The 2019 ACC/AHA prevention guidelines do not make a formal recommendation regarding resistance exercise; they do note that it has multiple health benefits (e.g., BP-lowering, improved glycemic control) though state its association with ASCVD risk reduction is unclear. 

Choice D is incorrect: sedentary time is independently associated with greater risk for several major chronic diseases and mortality. Reducing sedentary time for inactive adults and adding in light-intensity physical activity (as little as 15 minutes daily) is a class 1 recommendation to reduce all-cause and CV mortality and morbidity. The 2019 ACC/AHA guidelines suggest that reduced sedentary behavior may be “reasonable for ASCVD risk reduction” (Class 2b). Assuming our patient has had predominantly sedentary behavior, starting with a 20-minute daily walk can provide initial health benefits while working up to more and higher-intensity activity.

Main Takeaway

Physical activity should be individually assessed and prescribed in terms of frequency, intensity, time (duration), type, and progression.

Guideline Location

Section 4.3.1, Pages 3268-3269, Table 7

Ms. DW is a 67-year-old woman with a history of coronary artery disease and prior percutaneous coronary intervention in 2019 with a drug-eluting stent to the proximal left anterior descending artery. They have transitioned to your clinic from a previous provider, and their LDL is 134 mg/dL. What would be the ESC recommended goal LDL-C level for this patient? 

A. <30 mg/dL
B. <55 mg/dL
C. <70 mg/dL
D. <100 mg/dL

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The correct answer is B.

The ESC guidelines outline a robust LDL-C reduction goal of <55mg/dL (<1.4mmol/L) and ≥50% reduction from baseline in those with known atherosclerotic cardiovascular disease, with the highest possible Class I (LOE A) recommendation for this goal. A goal LDL-C <55mg/dL with ≥50% reduction from baseline should also be considered in apparently healthy persons <70 years of age who are at very high risk (Class IIa, LOE C). 

To achieve these goals, the guidelines recommend a stepwise approach to treatment including dietary, lifestyle, and medical management. Recognizing that lower LDL-C is better, the guidelines recommend liberal intensification of treatment especially if using submaximal doses of generic or low-cost statins and side effects are not apparent. High-intensity statin is recommended to be prescribed to the highest tolerated dose to reach LDL-C goals set for each specific risk group (Class I, LOE A). If these goals are not achieved with the maximum tolerated dose of a statin, combination therapy with ezetimibe is recommended (Class I, LOE B).

Choice A is incorrect. An LDL-C <30mg/dL is a more significant reduction than that recommended by the guidelines, even for patients with known ASCVD. Notably, for patients with ASCVD who experience a second vascular event within 2 years while taking maximum tolerated statin-based therapy, an LDL-C goal of <1.0 mmol/L (40 mg/dL) may be considered.

Choice C is incorrect. The ESC prevention guidelines recommend considering a goal of <70mg/dL for patients in the primary prevention setting at high risk who are <70 years of age (Class IIa, LOE C). (Recall again that for those at very high risk the primary prevention recommendation is target LDL-C <55 mg/dL).

Choice D is incorrect. LDL-C <100mg/dL was a frequently cited goal in older iterations of various prevention and lipid guidelines. As the data has shifted to support lower LDL-C goals, this is not a noted goal within the 2021 ESC prevention guidelines for patients <70 years of age.

Main Takeaway

Lower is better when it comes to LDL-C

For those with known atherosclerotic cardiovascular disease, liberal intensification of lipid lowering treatment is recommended. 

Guideline Location

Section 4.6.2.1, page 3276-3279, Figure 6 on page 3252, Figure 7 on page 3253

A 70-year-old man with a history of hypertension, diabetes, hyperlipidemia, peptic ulcer disease with a prior upper GI bleed, as well as coronary artery disease presents to clinic. About one year ago he suffered an NSTEMI treated with percutaneous coronary intervention to the mid LAD. He is feeling well and able to walk 1 mile daily with no anginal symptoms. He is currently taking aspirin 81 mg daily, ticagrelor 90 mg BID, atorvastatin 40 mg daily, metoprolol 25 mg BID, lisinopril 5 mg daily, and lansoprazole 15mg daily. He has a preserved ejection fraction. His BP in clinic is 110/70 and HR is 65 bpm. His LDL is 50 mg/dL. What do you recommend for his further management?

A. Switch ticagrelor to clopidogrel, continue indefinitely
B. Stop ticagrelor, continue aspirin indefinitely
C. Continue aspirin + ticagrelor indefinitely
D. Stop ticagrelor, start rivaroxaban 2.5 mg BID

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The correct answer is B – stop ticagrelor, continue aspirin indefinitely.

Twelve months of DAPT is recommended for acute coronary syndromes (Class I, LOE A). Long-term secondary prevention with dual anti-thrombotic therapy (DAPT > 12 months with a P2Y12 inhibitor and low-dose aspirin or low-dose rivaroxaban 2.5mg BID with low-dose aspirin) may be considered for patients who are at high ischemic risk without high risk of bleeding (Class IIa, LOE A). However, this patient is at increased bleeding risk (peptic ulcer disease with prior GI bleeding) and has no ischemic symptoms, and so neither would be recommended.

Main Takeaway

In summary, 12 months of DAPT is recommended after ACS. Prolonged DAPT or low-dose rivaroxaban may be considered with high ischemic risk and low bleeding risk.

Guideline Location

Section 6.1, Pages 3294-3295.

Medically supervised cardiac rehabilitation programs after ASCVD events and for patient with heart failure carries a Class I recommendation. However, placement of referrals, uptake and enrollment after referral, and rigor of rehabilitation all remain inconsistent. What minimum cumulative duration of cardiac rehabilitation has been chosen as a threshold of effectiveness for cardiac rehabilitation by the European Society of Cardiology?

A. 100-300 minutes, 10 sessions
B. 300-500 minutes, 16 sessions
C. 500-700 minutes, 22 sessions
D. 700-1000 minutes, 28 sessions
E. >1000 minutes, 36 sessions

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The correct answer is E: >1000 minutes across 36 sessions.

Cardiac rehabilitation is a comprehensive, multidisciplinary intervention not just including exercise training and physical activity counselling, but also education, risk factor modification, diet/nutritional counselling, and vocational and psychosocial support.

A broad evidence base demonstrates that multidisciplinary cardiac rehabilitation and prevention programs after ASCVD events or revascularization reduce recurrent cardiovascular hospitalizations, myocardial infarction, and cardiovascular mortality. In patients with chronic HF (mainly HFrEF), exercise based cardiac rehabilitation (EBCR) may improve all-cause mortality, reduce hospital admissions, and improve exercise capacity and quality of life. Such programs include a wide array of activities including physical activity, risk factor modification, psychosocial support, nutrition counseling, and more. Despite the heterogenous design of clinical trials, cardiac rehabilitation has been shown to be a cost-effective intervention.

Based upon the available review data, the European Association of Preventive Cardiology and the European Society of Cardiology proposed minimum standards for secondary prevention cardiac rehabilitation programs. Based upon a comprehensive review of the literature, ESC recommends that cardiac rehabilitation be multidisciplinary, supervised by health professionals, and start as soon as possible after a cardiovascular event. Cardiac rehabilitation should include both aerobic and muscular resistance tailored to the fitness level of the participant, should carry a duration of >1000 minutes in total, and should exceed 36 sessions total.

While uptake remains limited, electronic prompts within the medical record and automatic referrals should be considered to enhance referral and participation. Future research should continue to explore the benefit of home-based cardiac rehabilitation with or without telemonitoring. Lastly, studies have shown that uptake remains lower among women, and targeted programs should be undertaken to address such disparities.

Main Takeaway

Current European Society of Cardiology guidelines provide a Class I (LOE A) recommendation for the participation in multidisciplinary cardiac rehabilitation programs for the secondary prevention of ASCVD events including revascularization and in individuals with heart failure (mainly HFrEF) to improve patient outcomes.

Guideline Location

Section 4.11, Page 3292.