B P4 C25 Primary Prevention of Cardiovascular Disease

Question 1

The largest contributors to the age-adjusted decline in cardiovascular death are:

Answer 1

Lower cholesterol and blood pressure
Smoking cessation

Question 2

_____ prevention is the prevention of the development of risk factors

Answer 2

Primordial prevention

Question 3

_____ prevention aims to prevent the clinical manifestation of cardiovascular disease in individuals without clinical cardiovascular disease

Answer 3

Primary prevention

Question 4

_____ prevention focuses on social determinants of health and health inequities (e.g.,poverty and living conditions, urbanization, air pollution, education, sedentary behavior, psychosocial stress)

Answer 4

Primordial prevention

Question 5

_____ prevention focuses on controlling cardiovascular risk factors among high-risk individuals through lifestyle approaches and treatment of established risk factors.

Answer 5

Primary prevention

Question 6

_____ prevention targets patients with established disease to reduce risk of recurrent cardiovascular events and mortality.

Answer 6

Secondary prevention

Question 7

____ prevention can eliminate most cardiovascular events

Answer 7

Primordial and primary prevention

Question 8

According to the PURE (Prospective Urban Rural Epidemiology) study, the largest contributors to as to CV risk, all-cause death, and MI are:

Answer 8

CV risk: Hypertension (22%), non-HDL cholesterol (8%)

All-cause deaths: Behavioral risk factors (26%), low education (12.5%)

MI: non-HDL cholesterol, followed by hypertension, smoking, abdominal obesity, and diabetes

Question 9

The AHA introduced Life’s Simple 7 cardiovascular health metrics in 2010 to shift the focus from disease toward cardiovascular and overall health and well-being. The seven health metrics are:

Answer 9

Smoking status
Body mass index (BMI)
Physical activity
Diet
Cholesterol
Blood pressure
Glucose

Question 10

Ideal cardiovascular health is defined as the:

Answer 10

Absence of clinical cardiovascular disease

+

Ideal levels of all seven components

+

Absence of medication treatment

Question 11

AHA’s Life’s Simple 7

Answer 11

1. Get active
2. Eat better
3. Lose weight
4. Stop smoking
5. Control cholesterol
6. Manage blood pressure
7. Reduce blood sugar

Question 12

Specific AHA’s Life’s Simple 7:

Answer 12

1. At least 150 minutes moderate activity /week or at least 75 minutes vigorous activity/week
2. Eat a healthy diet (4–5 components of healthy diet score:
   1) 4.5 cups or more of fruits and vegetables per day;
   2) two or more 3.5-oz servings of fish per week;
   3) three servings per day of whole grains;
   4) less than 1500 mg of sodium per day; and
   5) 36 ounces or less of sugar-sweetened beverages per)
3. Have a normal body weight (BMI<25)
4. Never smoked or quit >1 year ago
5. Total cholesterol <200 mg/dL
6. Blood pressure <120/<80 mm Hg
7. Fasting blood glucose <100 mg/dL

Question 13

_____, that is, the number of years that a population can anticipate living in good health (commonly known also as healthy life expectancy)

Answer 13

Health-adjusted life expectancy (HALE)

Question 14

_____ risk assessment was developed to address limitations of 10-year risk assessments and has been highlighted in recent guidelines

Answer 14

Lifetime risk

Question 15

Of several imaging techniques developed over the past decade, _____ has emerged as a leading imaging tool for the preventive cardiology community.

Answer 15

Computed tomography to detect coronary artery calcification (CAC)

Question 16

The AHA/ACC guidelines suggest use of CAC among those with estimated 10-year risk between _____% in the context of shared decision-making when either the physician or patient is otherwise uncertain about use of specific preventive therapies, in particular statins

Answer 16

5-20%

Question 17

____ only detects calcified plaques (which are less likely to rupture) and does not detect the noncalcified thin-capped lesions that underlie many clinical events.

Answer 17

CAC

Question 18

CAC scores of zero do not eliminate atherosclerotic risk, particularly over long-term follow-up, and repeat testing after ___ years may be needed.

Answer 18

5 years

Question 19

An the open-label, parallel-group _____ trial of 4146 patients with stable chest pain, participants randomized to CCTA as compared to usual care

Low- to intermediate-risk patients with chest pain were randomized to evaluation with coronary CTA (n = 2,073) versus standard care (n = 2,073).

Lower rate of nonfatal myocardial infarction or coronary death at 5 years randomized to CCTA, an effect due to earlier use of coronary revascularization and more aggressive use of preventive and anti-anginal therapies

Answer 19

SCOT-HEART trial (Scottish Computed Tomography of the HEART)

Although CTA was associated with an increase in invasive therapy and revascularization in the short-term, there was no difference in invasive therapy and revascularization between treatment arms at 5 years. Since there was no difference in overall revascularization rates, long-term benefit from CTA may have been due to lifestyle modification and statin therapy. SCOT-HEART (and PROMISE) shows that coronary CTA is an alternative to standard care (including conventional stress testing) in the evaluation of patients with chest pain.

Question 20

Moreover, among patients with stable chest pain, _____ plaque burden most strongly predicted fatal or nonfatal myocardial infarction, irrespective of risk score, CAC, or coronary artery area stenosis, and nearly half of all incident infarctions occurred among those without clear obstructive disease

Answer 20

Low- attenuation noncalcified plaque burden

Question 21

The guidelines recommend assessing 10-year ASCVD risk every __ years in all asymptomatic adults age 40 to 75 years old, using the sex- and race-specific PCE.

Answer 21

5 years

Question 21

ACC/AHA Atherosclerotic Cardiovascular Disease Risk Enhancers Used in the ACC/AHA Guidelines

Answer 21

• Family history of premature ASCVD (men <55 years, women <65 years)
• Primary hypercholesterolemia (LDL-C ≥160 mg/dL [4.1 mmol/L]; non-HDL-C ≥190 mg/dL [4.9 mmol/L])
• Chronic kidney disease (eGFR 15–59 mL/min/1.73 m2, not on dialysis or kidney transplant)
• Metabolic syndrome
• Conditions specific to women (e.g., preeclampsia, premature menopause)
• Chronic inflammatory conditions (especially rheumatoid arthritis, lupus, psoriasis, HIV)
• High-risk race/ethnicity (e.g., South Asian ancestry)

Question 22

ACC/AHA Atherosclerotic Cardiovascular Disease Risk Enhancers Used in the ACC/AHA Guidelines (Biomarkers/Lipids)

Answer 22

Persistently elevated triglycerides (≥175 mg/dL [2 mmol/L], fasting or nonfasting)
In selected individuals if measured:
hsCRP ≥2 mg/L
Lipoprotein(a) ≥50 mg/dL or ≥125 nmol/L
Apolipoprotein B ≥130 mg/dL
Ankle-brachial index <0.9

Question 23

Lipid analysis for estimation of total risk of CVD. (IC)

Answer 23

Total cholesterol

Question 24

Lipid analysis for further refining risk estimation. IC

Answer 24

HDL-C

Question 25

Lipid analysis for the primary lipid analysis method for screening, diagnosis, and management. IC

Answer 25

LDL-C

Question 26

Lipid analysis recommended for risk assessment, particularly if high TGs, DM, obesity, or very low LDL-C.IC

Answer 26

Non-HDL-C

Question 27

Treatment goals for LDL-C in primary prevention

Answer 27

In individuals at very high risk, LDL-C reduction ≥50% and an LDL-C goal of <1.4 mmol/L (<55 mg/dL). IC

In individuals at high risk, LDL-C reduction ≥ 50% and LDL-C goal of <1.8 mmol/L (<70 mg/dL). IA

Question 28

As described in the 2020 Surgeon General’s report on smoking, _____ remains the single most important preventable cause of death and disability in the United States.

Answer 28

Tobacco use

Question 29

Prospective studies indicate that death from both coronary disease and stroke increases progressively from blood pressure levels as low as _____.

Answer 29

115 mm Hg systolic and 75 mm Hg diastolic

Question 30

The core strategies to prevent and treat high blood pressure are:

Answer 30

Lifestyle (weight loss,sodium reduction,potassium supple- mentation, healthy diet, increased activity, and moderation of alcohol intake)

Drug therapy

Question 31

Dietary Approaches to Stop Hypertension (DASH) intervention (low sodium combined with high fruits, vegetables, low- fat dairy, and naturally high potassium) having the largest mean effect on lowering blood pressure (up to ____ mm Hg reduction in systolic blood pressure, and ____mm Hg reduction in diastolic blood pressure), with clinically meaningful blood pressure-lowering benefits also seen for low-sodium, high-potassium, low-calorie, or Mediterranean diets

Answer 31

−7.6/4.2 mm Hg

Question 32

Physical activity protects against hypertension. In a meta-analysis of 29 studies of greater than 330,000 individuals, the risk of incident hypertension was lower by ___% for each __ metabolic equivalents (MET hour/week) increment in leisure-time physical activity, with more benefit with higher activity (e.g.,up to 33% lower risk of hypertension with 60 MET hour/week)

Answer 32

6% lower for each 10 MET increment

Question 33

Weight loss of ____ kilogram achieved through lifestyle/diet is associated with approximately 1 mm Hg systolic blood pressure reduction in a dose-response manner, with greater reductions in patients with higher blood pressures.

Answer 33

1 kg = 1 mm Hg

Question 34

Multiple randomized trials in patients with hypertension have demonstrated that blood pressure reductions as small as _____ mm Hg result in large and clinically significant reductions in risk for stroke, cardiovascular mortality, congestive heart failure, and coronary disease in middle-aged subjects, elderly persons, and specified high-risk patients such as those with diabetes and peripheral arterial disease

Answer 34

3-5 mm Hg

Question 35

The presence of diabetes confers an equivalent risk to aging _____ years

Answer 35

15 years

Question 36

Metabolic syndrome is a cluster of:

Answer 36

• Glucose intolerance and hyperinsulinemia accompanied by hypertriglyceridemia (both fasting and postprandial)
• Low-HDL cholesterol levels
• Predominance of small dense LDL particles and elevation of LDL particles and apolipoprotein B (apoB) levels
• Central obesity
• Hypofibrinolysis
• Hypertension
• Microalbuminuria
• Elevated inflammatory biomarkers such as hsCRP

Question 37

Beyond diet, exercise, and other lifestyle interventions, multiple randomized trials now demonstrate cardiovascular risk reduction among those with diabetes using new classes of glucose-lowering agents, in particular for _____, which both reduce cardiovascular events and improve glycemic control

Answer 37

Glucagon-like peptide-1 receptor agonists (GLP-1RA)
Sodium-glucose cotransporter 2 (SGLT-2) inhibitors

Question 38

The pharmaceutical grade preparation of the n-3 fatty acid eicosapentaenoic acid (EPA, icosapent ethyl) administered in high dose (2 g twice daily) to patients who met the entrance criteria for ____ (Trial) did benefit in improving CV outcomes

Eligible patients were randomized in a 1:1 fashion to either IPE (2 g twice daily with food) (n = 4,089) or matching placebo (n = 4,090). Randomization was stratified by primary vs. secondary prevention, use of ezetimibe, and geographic region

Answer 38

REDUCE-IT Trial (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial)

The results of this trial indicate that the use of IPE 2 g twice daily was superior to placebo in reducing TGs, CV events, and CV death among patients with high TGs and either known CV disease or those at high risk for developing it, and who were already on statin therapy with relatively well-controlled LDL levels. Results were consistent among patients with diabetes and those with prior MI, and across the spectrum of kidney function. Rates of revascularization and MI (all types) were lower, while atrial fibrillation/flutter and bleeding were higher with IPE. Results were maintained in the US cohort, and whether events were investigator-reported vs. CEC-adjudicated.

These are very interesting findings and come on the heels of several negative trials with n–3 fatty acid supplementation. One aspect of this medication is that it has a higher dose of purified EPA (4 g/day) than what was tested in other clinical trials. Other trials with moderate to high doses of EPA are ongoing. This is one of the first non-LDL targeted trials to show a CV benefit and will likely be featured in future guidelines.

Question 39

Low-dose aspirin may be considered for primary prevention of cardiovascular disease in patients with diabetes and increased cardiovascular risk who are not at increased risk of bleeding given the recent _____ trial showing 12% risk reduction in the primary cardiovascular endpoint, although at the cost of 30% increased risk of major bleeding, while aspirin should be used in those with diabetes and cardiovascular disease unless there is a contraindication.

The goal of the trial was to evaluate aspirin compared with placebo among diabetics with no known cardiovascular disease (CVD).

Patients with diabetes and no known CVD were randomized to aspirin 100 mg daily (n = 7,740) versus placebo (n = 7,740).

Answer 39

ASCEND Trial (A Study of Cardiovascular Events in Diabetes - Aspirin)

Among diabetic patients with no known CVD, aspirin was associated with a 12% relative reduction in major adverse cardiovascular events compared with placebo. Aspirin was associated with a 29% relative increase in major bleeding events compared with placebo. The increase in bleeding was mainly due to GI hemorrhage. The absolute risk reduction for major adverse cardiovascular events was 1.1%, while the absolute risk increase for major bleeding was 0.9%. There was no reduction in GI cancer, HF events, or dementia from the use of aspirin. The use of aspirin among diabetics with no known CVD needs to be individualized. Similarly, there was no effect of omega-3 fatty acid on HF events.

Question 40

BMI classification:

Answer 40

BMI of ≥25 kg/m2: overweight
BMI ≥30 kg/m2: obesity
BMI ≥35 kg/m2: severe obesity

Question 41

By contrast to medical intervention trials, randomized trials indicate that _____improves diabetes control, hypertension, lipid levels, sleep apnea, and osteoarthritis and show a trend toward improved mortality.

Answer 41

Metabolic surgery

Question 42

Within the _____ trial, those subjects with a family history of premature atherosclerosis experienced a 62% reduction in first vascular events associated with statin therapy as compared with a 39% reduction among those without a family history, with even greater statin-related risk reductions seen in women with family history versus men, which has led recent US guidelines to emphasize family history as a risk-enhancing factor when considering statin treatment.

Answer 42

JUPITER Trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin)

The JUPITER trial was designed to assess whether apparently healthy persons with levels of low-density lipoprotein (LDL) that do not mandate statin treatment, as per current guidelines (<130 mg/dl), but with levels of high-sensitivity C-reactive protein (hs-CRP) ≥2 mg/L, would benefit from taking rosuvastatin.

Rosuvastatin 20 mg daily or placebo

The results of the JUPITER trial indicate that rosuvastatin is associated with a significant reduction in major cardiovascular events, including death, in apparently healthy persons with LDL cholesterol <130 mg/dl, but hs-CRP ≥2 mg/L. Individuals who had the greatest percent reduction in LDL (not the absolute LDL level), experienced the greatest reduction in adverse events with rosuvastatin. Among those at risk for diabetes, rosuvastatin versus placebo was associated with an increased risk for developing diabetes. Rosuvastatin did not reduce the risk for fractures.

Question 43

In the _____ study of 154,169 participants from 20 countries, lower educational level associated strongly with 1.5- to 2-fold increased risk of cardiovascular events and mortality independent of household wealth and other risk factors, with the strongest association noted in low- and middle-income countries and to a lesser degree in high-income countries.

Answer 43

PURE study

Question 44

Notably, in the PURE study, out of 14 potentially modifiable cardiovascular risk factors, the largest contributor to death was _____ which accounted for 16% of deaths, exceeding that of smoking or hypertension (11% each), household pollution, diet, or grip strength (8% each).

Answer 44

Low education

Question 45

The ABI for lower extremities is obtained noninvasively and calculated by _____.

Answer 45

Dividing each of the ankle pressures by the higher of the brachial artery pressures

Question 46

For cardiovascular risk assessment, the _____ ABI between the two legs is used.

Answer 46

Lowest

Question 47

A normal resting ABI is greater than _____ (borderline abnormal is ABI _____). An ABI ____ is abnormal (low), diagnostic for lower extremity arterial disease, and is associated with more than doubling of the 10- year cardiovascular risk, while ABI ____ is also abnormal (high) as it represents arterial stiffening, vascular calcification, and noncompressibility, and is also associated with higher cardiovascular risk

Answer 47

Normal: 1.00 - 1.40
Borderline abnormal: 0.91 to 0.99
Abnormal (low): ≤0.9
Abnormal (high): >1.4

Question 48

The AHA/ACC guidelines consider ABI less than ____ as a risk-enhancing factor that can be useful for further risk stratification and statin decisions among individuals with borderline or intermediate risk based on the PCE equations

Answer 48

<0.9

Question 49

Cholesterol screening for children with a nonfasting sample should start early (age __ years) and be repeated every _____ years.

Answer 49

Start at 10 years

Repeated every 5 years

Question 50

If there is a family history of hypercholesterolemia or premature cardiovascular disease, cholesterol screening should start earlier at age __ and repeated every 3 to 5 years for early identification of familial hypercholesterolemia and hereditary dyslipoproteinemias, even if the initial profile is normal

Answer 50

Start at age 2

Repeated every 3-5 years

Question 51

Adults should have the traditional cardiovascular risk factors assessed at least every ___ years starting at age __, and by age 40 all adults should undergo a cardiovascular risk assessment with a global risk score to estimate the absolute 10-year risk of ASCVD to guide discussions and decisions about preventive therapies.

Answer 51

Age 20: CV risk factor assessment every 5 years

Age 40: Global risk score assessment (10 yr risk of ASCVD)

Question 52

Most guidelines, including the latest US and European guidelines, define elevated non- fasting triglycerides as ≥____mg/dL (≥___ mmol/L) based on a cut point that has been prospectively validated.

Answer 52

≥175 mg/dL

≥2 mmol/L

Question 52

On average, the lowering of LDL cholesterol by 1% corresponds to approximately a __% lower risk of cardiovascular events.

Answer 52

1% decrease in LDL-C = 1% decrease in risk of CV events

Question 53

In this trial, cholesteryl ester transfer inhibition with anacetrapib increased HDL cholesterol by twofold, but the modest clinical benefit (9% relative risk reduction) may have been due to the concomitant modest reduction in atherogenic particles.

Answer 53

REVEAL (Randomized Evaluation of the Effects of Anacetrapib Through Lipid Modification)

Large clinical trials have found no evidence that increasing HDL cholesterol reduces clinical events

Question 54

In general, observational data suggest that each 1 mg/dL higher increment in HDL cholesterol is associated with approximately _____% lower risk of total cardiovascular disease, in particular for coronary events.

Answer 54

Each 1mg/dL HDL higher increment = 2-3% lower total CVD risk

Question 54

In general, observational data suggest that each 1 mg/dL higher increment in HDL cholesterol is associated with approximately ____% lower risk of total cardiovascular disease, in particular for coronary events.

Answer 54

Each 1mg/dL higher increment in HDL = 2-3% lower total CVD risk

Question 55

In the _____ trial, cholesteryl ester transfer inhibition with anacetrapib increased HDL cholesterol by twofold, but the modest clinical benefit (9% relative risk reduction) may have been due to the concomitant modest reduction in atherogenic particles

Answer 55

Randomized Evaluation of the Effects of Anacetrapib Through Lipid Modification (REVEAL)

Question 56

In a meta-analysis of randomized trials (N = 374,358 from 25 statin trials and 24 nonstatin trials),triglyceride lowering is associated with lower cardiovascular risk (approximately ___% lower risk per 1 mmol/L reduction in triglycerides), which was somewhat lower than for LDL cholesterol (approximately ___ % lower risk per 1 mmol/L reduction in LDL cholesterol)

Answer 56

1 mmol/L dec in TG = 15% lower CV risk

1 mmol/L Dec in LDL = 20% lower CV risk

Question 57

Nonfasting triglycerides are associated equally or more strongly with cardiovascular endpoints than fasting levels. Guidelines consider nonfasting triglycerides ≥ ___ mmol/L (___ mg/dL) as abnormal, while for fasting triglycerides the corresponding level is ≥ ___ mmol/L (___ mg/dL).

Answer 57

Nonfasting TG: ≥ 2 mmol/L (175 mg/dL)

Fasting TG: ≥ 1.7 mmol/L (150 mg/dL)

Question 58

There are some differences in the guideline cut points for severe hypertriglyceridemia, defined as fasting triglycerides ≥ ___ mg/dL (___ mmol/L) in US guidelines and greater than __ mmol/L (___mg/dL) in European guidelines.

Answer 58

US: ≥ 500 mg/dL (5.7 mmol/L)
Europe: > 885 mg/dL (10 mmol/L)

Question 59

Agents for reducing triglycerides include _____, which moderately reduce triglycerides.

Answer 59

n-3 fatty acid supplements and Fibrates

Question 60

Fibrates are weak peroxisome proliferator-activated receptor (PPAR)-α agonists and reduce triglycerides by approximately ____% depending on baseline levels

Answer 60

25-50%

Question 61

____ is an apoCIII inhibitor used for familial hyperchylomicronemia syndrome as an adjunct to diet and reduces triglycerides by 70%

Answer 61

Volanesorsen

Question 62

_____ is a monoclonal anti-ANGPTL3 antibody that binds circulating ANGPTL3 to form immune complexes.This augments plasma lipase activity, reducing triglycerides (approximately 50% to 75%).

Answer 62

Evinacumab

Question 63

_____ is a novel potent SPPARM that reduces triglycerides by up to 45% in patients with diabetes and hypertriglyceridemia, in addition to reducing non-HDL cholesterol and remnant cholesterol, apoB and apoCIII, and increasing HDL cholesterol, without significant effect on LDL cholesterol

Answer 63

Pemafibrate

Question 64

_____ is an international phase 3 randomized placebo-controlled trial in approx- imately 10,000 patients (two thirds with prior cardiovascular disease) with type 2 diabetes and mild to moderate hypertriglyceridemia (2.26 to 5.64 mmol/L, or 200 to 499 mg/dL) and low HDL cholesterol (≤1.03 mmol/L or 40 mg/dL) that is evaluating efficacy of pemafibrate on a background of statin therapy in reducing cardiovascular events.

Answer 64

PROMINENT (Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients With Diabetes)

Question 65

Individuals with higher numbers of _____ repeats have lower circulating lipoprotein(a) levels.

Answer 65

kringle IV type 2

Question 66

_____ is a sulfhydryl-containing amino acid derived from the demethylation of dietary methionine

Answer 66

Homocysteine

Question 67

In patients with rare inherited defects of methionine metabolism, severe hyperhomocysteinemia (plasma levels >____ mmol/L) can develop; such patients have greatly elevated risk for premature atherothrombosis as well as venous thromboembolism.

Answer 67

> 100 mmol/L

Question 68

Inflammatory cytokines such as interleukin _____ implicated in atherogenesis and activated by the ____ inflammasome, elicit the expression of the messenger cytokine _____, which can travel from local sites of inflammation to the liver and change the program of protein synthesis to produce the acute-phase response.

Answer 68

IL-1

NLRP3

IL-6

Question 69

In clinical practice, the best-studied and most easily applied bio- marker of this inflammatory process is the downstream acute-phase reactant _____.

Answer 69

CRP

Question 70

Based on JUPITER and other studies, current US guidelines consider hsCRP ≥___ mg/L as a risk-enhancing factor that could be used in global risk evaluation, in particular when statin decision making is otherwise uncertain (borderline- or intermediate-risk individuals), while hsCRP levels of less than 1 mg/L are lower risk

Answer 70

≥2 mg/L: Risk-enhancing
<1 mg/L: Low risk

Question 71

Values of hsCRP in excess of ___ mg/L may represent an acute-phase response caused by an underlying inflammatory disease or intercurrent infection and should lead to repeat testing in approximately 2 to 3 weeks

Answer 71

> 8 mg/L

Question 72

Autopsy data support this hypothesis: elevated hsCRP levels are more common in patients with _____ plaques than in those with erosive disease or those who died of nonvascular causes.

Answer 72

Frankly ruptured

Question 73

In primary prevention, _____ are the first-line interventions for those with elevated hsCRP, as with elevated LDL cholesterol or other risk factors.

Answer 73

Diet
Exercise
Smoking cessation

Question 74

The large-scale multinational _____ trial demonstrated that statin therapy, previously shown to lower hsCRP levels independent of LDL cholesterol lowering, markedly reduces vascular event rates among apparently healthy men and women with hsCRP ≥2 mg/L and LDL cho- lesterol less than 130 mg/dL

Population: healthy persons with levels of low-density lipoprotein (LDL) that do not mandate statin treatment, as per current guidelines (<130 mg/dl), but with levels of high-sensitivity C-reactive protein (hs-CRP) ≥2 mg/L, would benefit from taking rosuvastatin

Placebo vs Rosuvastatin 20mg

Answer 74

JUPITER Trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin)

Question 75

In this trial, random allocation to rosuvastatin 20 mg daily as compared to placebo resulted in a 44% lower risk of the trial primary endpoint of all vascular events, a 54% reduction in myocardial infarction, a 48% reduction in stroke, a 46% reduction in need for arterial revascularization, and a 20% reduction in all-cause mortality.

Answer 75

JUPITER Trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin)

Question 76

JUPITER influenced clinical guidelines and resulted in much wider use of statin therapy. However, by using a statin—an LDL-lowering drug with concomitant anti-inflammatory effects—JUPITER was not a formal test of the inflammation hypothesis of atherothrombosis

That evidence arose from the____ trial which provided direct proof-of-principle that inflammation inhibition in the absence of lipid lowering can significantly reduce cardiovascular event rates.

Answer 76

Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS)

Question 77

Patients with MI and elevated hsCRP were randomized to canakinumab 50 mg (n = 2,170) vs. canakinumab 150 mg (n = 2,284) vs. canakinumab 300 mg (n = 2,263) vs. placebo (n = 3,344).

Evaluated canakinumab compared with placebo among patients with a history of myocardial infarction (MI) and elevated high-sensitivity C-reactive protein (hsCRP). Canakinumab is a monoclonal antibody targeting interleukin-1β.

This study showed that among 10,061 stable atherosclerosis patients with residual inflammatory risk who were already on statin therapy, those allocated to higher doses of canakinumab—a monoclonal antibody that binds IL-1β—experienced a 15% reduction in major adverse cardiovascular events when compared to a placebo.

Answer 77

CANTOS Trial (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study)

Among patients with a history of MI and elevated hsCRP, canakinumab was effective at preventing adverse cardiac events over a median of 3.7 years. The only dose that achieved significance after multiplicity-adjusted threshold for statistical significance was the 150 mg group. Canakinumab was not associated with a reduction in incident diabetes. Canakinumab was effective at reducing hsCRP in a dose-response relationship.

Canakinumab was effective among those with chronic kidney disease, especially those who achieved the greatest reduction in hsCRP. Residual inflammatory risk is a significant determinant of recurrent cardiovascular risk. Canakinumab was associated with an increased risk of fatal infection or sepsis despite exclusion of patients with chronic or recurrent infection.

Question 78

In contrast ,the _____ of 4786 stable atherosclerosis patients with diabetes or metabolic syndrome reported that low-dose methotrexate did not reduce major adverse cardiovascular events.

Answer 78

Cardiovascular Inflammation Reduction Trial (CIRT)

Question 79

In _____ trial, treatment with colchicine 0.5 mg daily as compared to placebo over a 2-year period among 4745 post-myocardial infarction patients resulted in a 23% relative reduction in the primary trial endpoint inclusive of myocardial infarction, stroke, resuscitated cardiac arrest, urgent hospitalization for angina leading to revascularization, and cardiovascular death. While the benefit of colchicine was significant only for the coronary revascularization and stroke components of this primary endpoint, all cardiovascular outcomes were directionally consistent, providing reassurance

Answer 79

COLCOT Trial (Colchicine Cardiovascular Outcomes Trial)

Question 80

In _____, colchicine 0.5 mg as compared to placebo among 5522 patients with stable coronary disease resulted in a similar 28% relative reduction in major recurrent adverse cardiovascular events. Rates of coronary revascularization and coronary death were also reduced although no reduction in all-cause mortality was observed

Answer 80

LoDoCo2 trial (Low-Dose Colchicine vs. Placebo in Patients With Chronic Coronary Disease)

Question 81

In cardiovascular practice, three times as many patients have “residual inflammatory risk” defined as a post-statin LDL cholesterol less than __ mg/dL but an hsCRP greater than __mg/L than have “residual cholesterol risk” defined as a post-statin LDL cholesterol greater than __ mg/dL and an hsCRP less than __mg/L.

Answer 81

Residual Inflammatory risk
Post-statin LDL: <70 mg/dL
hsCRP: >2 mg/L

Residual Cholesterol risk
Post-statin LDL
hsCRP

Question 82

The two recently added risk-enhancing factors specific for women, specifically _____, increase cardiovascular risk to a similar extent as standard risk factors.

Answer 82

Premature menopause (<40 years old)

Preeclampsia (elevated blood pressure and proteinuria after 20 weeks of gestation)

Question 83

Because of its risks, many professional organizations have recommended against (class III) the use of ____ therapy at any age to prevent coronary heart disease and other chronic diseases.

Answer 83

Hormone therapy

Women’s Health Initiative (WHI) trial provided clear evidence that postmenopausal hormone therapy did not prevent coronary disease in women who started treatment distant from menopause onset (>10 years).

Question 84

The AHA’s Life’s Simple 7 includes healthy diet as one of the simple 7 cardiovascular health metrics, with an ideal diet defined as 4 to 5 components (and poor diet one or less) of the following five diet elements:

Answer 84

(1) >/= 4.5 cups of fruits and vegetables/day
(2) 2 or more 3.5-oz servings of fish/week
(3) 3 servings per day of whole grains
(4) < 1500 mg of sodium per day
(5) 36 ounces or less of SSB/week

Question 85

The _____ was a secondary prevention trial in central, non-Mediterranean France comparing a low-fat diet with a Mediterranean diet which included a margarine high in alpha-linolenic-acid.

There were significantly fewer primary cardiovascular events in the Mediterranean diet group (8/302) compared with the control group (33/303).

Answer 85

Lyon Heart Study

Question 86

More recently, the _____ study was a large-scale primary prevention parallel-group randomized trial conducted in 7447 Spanish men and women at high cardiovascular risk recruited based on cardiovascular risk factors.The study was originally published in 2013, but because of some trial irregularities in the randomization procedures, the study was retracted and republished in 2018.

Over a follow-up period of 4.8 years, this trial found that a Mediterranean dietary intervention supplemented either with nuts or extra virgin olive oil compared with a low-fat dietary pattern significantly reduced the primary endpoint of major cardiovascular events by 30% and favorable reduction in other outcomes.

Answer 86

Prevención con Dieta Mediterránea (PREDIMED) study

Mediterranean dietary intervention supplemented either with nuts or extra virgin olive oil compared with a low-fat dietary pattern significantly reduced the primary endpoint of major cardiovascular events by 30% and favorable reduction in other outcomes.

Question 87

Though cultural norms vary widely, mild to moderate alcohol consumption is typically defined as roughly one drink-equivalent per day using as a reference a _____ for an approximate 12 to 14 g of alcohol per beverage.

Answer 87

12-ounce regular beer (5% alcohol)
5 fluid ounces of wine (12% alcohol)
1.5 fluid ounce of 80-proof distilled spirit (40% alcohol)

Question 88

Habitual heavy alcohol consumption, defined as __ or more drinks per week for women, __ or more drinks per week for men, or binge drinking for either gender, is a major cause of preventable death

Answer 88

8 or more/wk in women
15 or more/wk in men

Because of the health hazards of alcohol associated with higher intake, moderate alcohol use does not offer a population-based strategy to reduce cardiovascular risk, even for myocardial infarction where epidemiologic data remain consistent

Question 89

Among older women (mean age 72 years), as few as ____steps/day was associated with 40% risk reduction in mortality compared with 2700 steps/day, with greater benefit for more steps taken per day until approximately 7500 steps/day.

Answer 89

4400 steps/day

Question 90

The authors estimated that for every 1 hour of sitting time, there was _____% increased risk of mortality that was independent of activity levels, and that television viewing (which was worse than sitting) accounted for approximately 5% of cardiovascular mortality, 8% of all-cause mortality, and 29% of type 2 diabetes, suggesting an important burden of deaths that could be avoided with decreasing television viewing.

Answer 90

1 hour sitting time = 1-2% increased mortality risk

Question 91

Such tools could provide personalized estimates for the potential for absolute risk reduction (number needed to treat, NNT) with a medication or intervention weighed against the potential for adverse events (num- ber needed to harm,NNH),with net clinical benefit calculated as _____.

Answer 91

NNT minus NNH

Question 92

The 2019 ACC/AHA prevention guidelines gave a class _____ for shared decision-making in cardiovascular disease prevention based on data supporting that patient input and collaboration with clinicians decreases potential barriers to treatments.

Answer 92

I (LOE B-R [moderate quality evidence])

Question 93

Statins inhibit cholesterol synthesis by inhibiting the enzyme hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase and preventing the formation of _____, the rate-limiting step of sterol synthesis

Answer 93

Mevalonate

Question 94

Statins lower LDL cholesterol in a non-linear dose-response manner. Statins vary in intensity from high-intensity (average lowering of LDL cholesterol by ____%) to moderate-intensity (_____%) and low-intensity (____%)

Answer 94

High intensity: ≥50%
Moderate intensity: 30% -49%
Low intensity: <30%

Question 95

Statins do not reduce _____.

Answer 95

Lp(a)

Question 96

The major side effects of statins are muscle symptoms (statin-associated muscle symptoms [SAMS]) ranging from diffuse myalgias (normal creatine kinase without functional loss), seen in up to _____% of statin users, to myositis, defined as diffuse muscle pain with evidence of muscle inflammation and elevated creatine kinase levels, which necessitate discontinuation of use of the drug in _____% of patients. ____, statin use is associated with rhabdomyolysis, which is often associated with predisposing factors (advanced age, frailty, renal failure, shock, concomitant use of antifungal agents, antibiotics, the fibric acid derivative gemfibrozil, and hypothyroidism).

Answer 96

Diffuse myalgias: 10-15%
* Normal CK, no functional loss

Myositis: <1%
* Elevated CK, (+) Muscle pain

Rhabdomyolysis: Rarely

Question 97

In the _____ meta-analysis of 27 randomized statin trials (N = 174,149 individuals, 27% women), every 1 mmol/L (39 mg/dL) in LDL cholesterol with statin versus placebo (22 trials) or more versus less intensive statin (5 trials) was associated with 21% reduction in major vascular events over median follow-up of 4.9 years, with significant risk reductions in all-cause mortality (10%) driven by reduction in vascular mortality (12%),major coronary events (23%), coronary revascularization (24%), and stroke (15%), with no effect on incident cancer or cancer mortality.

Answer 97

Cholesterol Treatment Trialists

Each 1mmol/L = 21% RR in MVE

Question 98

Before initiation of statin therapy, either a fasting or nonfasting lipid panel should be obtained along with baseline _____.

Answer 98

ALT, Creatine kinase

Question 99

After initiation of statin therapy, the response should be checked with a repeat lipid panel (fasting or nonfasting) within the first ____ months to determine the patient’s adherence and response

Answer 99

1-3 months

Question 100

European guidelines suggest that although LDL cholesterol is the primary target of lipid-lowering therapy, _____ are secondary treatment targets, in particular for patients who also have cardiometabolic risk factors (e.g., triglycerides >175 mg/dL, obesity, metabolic syndrome, or diabetes) or low LDL cholesterol.

Answer 100

Non-HDL cholesterol or apoB

Question 101

Low-dose aspirin provides proven clinical benefit in the _____ prevention of cardiovascular disease.

Answer 101

Secondary

Question 102

In 2018, three contemporary primary prevention trials of aspirin were reported:

Answer 102

ASCEND (a trial of patients with diabetes) - statistically powered
ARRIVE (a trial intended to evaluate high-risk patients without diabetes)
ASPREE (a trial of older individuals).

Question 103

This trial randomly allocated 15,480 patients with diabetes (estimated absolute 10-year risk of cardiovascular disease 10%, i.e., intermediate risk) to aspirin 100mg daily or matching placebo. During a mean follow-up of 7.4 years, aspirin was associated with a 12% reduction in cardiovascular events, yet at a cost of a 29% increase in major bleeds.In this trial, all-cause mortality was neutral.

Answer 103

ASCEND trial (A Study of Cardiovascular Events in Diabetes)

12% reduction in CVE
29% increase in major bleed
Neutral all cause mortality

Question 104

This trial was intended to investigate the role of 100 mg aspirin daily or placebo among higher-risk primary prevention patients without diabetes.

During 5 years of follow-up among 12,456 participants, however, observed risk estimates were substantially lower than predicted and the trial was underpowered.Thus, this trial should be interpreted as a trial of borderline to intermediate risk primary prevention (estimated 10-year risk of cardiovascular disease 7%).

In this context, aspirin conferred no vascular benefit but resulted in a significant twofold increase in gastrointestinal bleeding. In this trial, all-cause mortality was again neutral.

Answer 104

ARRIVE (Aspirin to Reduce Risk of Initial Vascular Events)

*borderline to intermediate risk

No vascular benefit
2-fold increase in GIB
Neutral all cause mortality

Question 105

This trial included 19,114 participants 70 years of age and older (estimated 10-year risk of cardiovascular disease 8%) who were free of cardiovascular disease, dementia, or disability at trial entry and who were randomly allocated to 100 mg enteric coated aspirin or placebo for up to 5 years.

In this trial, aspirin as compared to placebo conferred no benefit on the primary endpoint of survival without dementia or persistent physical disability.

Answer 105

ASPREE trial (Aspirin in Reducing Events in the Elderly)

The ASPREE trial showed that aspirin did not prevent disability-free survival, but did increase major bleeding compared with placebo

Question 106

Statins in primary prevention are associated with a __% reduction in cardiovascular events for every 1 mmol/L reduction in LDL cholesterol, without the bleeding complications associated with aspirin

Answer 106

1 mmol/L LDL decrease = 25% CV event risk reduction

Question 107

In the _____ trial, a daily fixed-dose combination polypill (simvastatin, ramipril, atenolol, and hydrochlorothiazide) plus low-dose aspirin (75 mg) as compared to placebo among 5713 intermediate risk individuals (mostly Asian) resulted in a 31% relative risk reduction in the primary cardiovascular endpoint, with increases in dizziness and hypotension in the polypill arm. Notably, the combination of the polypill (which included a statin) with aspirin was more effective than the polypill alone (31% vs.21% relative risk reductions)

Answer 107

International Polycap Study-3 (TIPS-3) trial

31% RR of CVE with PP + Asa
21% RR of CVR with PP

Question 108

Major risk factors for gastrointestinal bleeding include:

Answer 108

• Male sex
• History of UGIB
• Older age (doubling with each decade, and particularly increased for age >70 years)
• Hepatic or renal disease
• Multiple cardiovascular risk factors
• Use of other medicines (e.g., non-steroidal anti-inflammatory drugs, corticosteroids, antiplatelets, antithrombotics, and selective serotonin reuptake inhibitors)

Question 109

With the exception of the _____ (for n-3 fatty acids) that was conducted in a general primary prevention American population at usual risk, the rest of the trials were conducted in patients from secondary prevention or at high cardiovascular risk.

Answer 109

VITamin D and OmegA-3 TriaL (VITAL)

Question 110

For example, a 2018 meta-analysis from the _____ examined aggregate study-level data from 10 randomized trials (EPA dose ranged from 226 to 1800 mg/day; 9 trials tested combined EPA+DHA) conducted in high-risk populations (n = 77,917 individuals; 12,001 cardiovascular events) and found no significant reduction in major cardiovascular or coronary events, with a trend toward 7% relative risk reduction in coronary deaths

Answer 110

Omega-3 Treatment Trialists’ Collaboration

Question 111

The _____ trial is the only primary prevention trial of n-3 fatty acid supplementation in a general usual-risk population selected only on age and not selected on high cardiovascular risk.

Answer 111

VITAL Trial

Question 112

This trial was a randomized, double-blind, placebo-controlled trial of marine n-3 fatty acids (1 g/day Omacor fish-oil capsule with 840 mg of n-3 FAs, including EPA+DHA (1.3:1 ratio) versus placebo (olive oil), and in a 2×2 factorial design also tested vitamin D3 (2000 IU/day) versus placebo in the primary prevention of cardiovascular disease and cancer among 25,871 US men aged ≥ 50 and women ≥ 55 with no prior cardiovascular disease.

Compared with placebo, n-3 fatty acids did not significantly reduce the primary endpoint of major cardiovascular events (a composite of myocardial infarction, stroke, and cardiovascular mortality; hazard ratio (HR)=0.92 [95% confidence interval 0.80 to 1.06]) but significantly reduced myocardial infarction (a prespecified secondary endpoint) by 28% and total coronary heart disease events by 17%.

Answer 112

VITAL Trial

Question 113

In 2018, ______ trial reported results of supplementation with 1g/day fish oil capsule (840 mg EPA+DHA, same ratio and formulation as used in the VITAL trial) versus placebo (olive oil), and in a 2×2 factorial design, which also tested low dose aspirin versus placebo in 15,480 UK patients with diabetes but without clinical evidence of cardiovascular disease.

There was no n-3 treatment-related reduction in composite vascular events over a 7.4-year follow-up period.

In this trial, there was a significant reduction in vascular death (19%), driven by coronary death, with no reduction in stroke or stroke death.

Answer 113

A Study of Cardiovascular Events in Diabetes (ASCEND)

Question 114

Subsequently, in a higher-risk patient population than ASCEND, _____ trial examined a high-risk patient population of statin-treated patients (N = 8179;90% white),with elevated triglycerides (median baseline triglycerides 216 mg/dL, LDL cholesterol 75 mg/dL) and with either known cardiovascular disease (70.7% of the study population) or high-risk patients with diabetes and one or more additional cardiovascular risk factors.

The trial tested a high-dose purified synthetic EPA (icosapent ethyl, 4 g/day) versus placebo (mineral oil). Over a 5-year follow-up, there was a significant 26%
reduction in major cardiovascular events, including significant reductions of 31%, 28%,and 20% in total myocardial infarction, total stroke, and cardiovascular death, respectively.

The n-3 intervention arm had more atrial fibrillation (5.3% vs. 3.9%) and a trend toward increased bleeding.

Answer 114

The Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) Trial

Significant reductions:
26% MACE
31% MI
28% Stroke
20% CV death

The n-3 intervention arm had more atrial fibrillation (5.3% vs. 3.9%) and a trend toward increased bleeding.

Question 115

The _____ trial tested a different high-dose purified formulation of n-3 carboxylic acids (Epanova 4 g/day, EPA+DHA, ratio 2.75:1) versus placebo (corn oil).

The trial was stopped early in 2020 for futility to reduce major cardiovascular events in 13,086 patients with hypertriglyceridemia and low HDL cholesterol on maximally tolerated statins and with established atherosclerotic disease or at high cardiovascular risk.

Answer 115

Statin Residual Risk Reduction With EpaNova in HiGh CV Risk PatienTs With Hypertriglyceridemia (STRENGTH)

Question 116

However, in the _____ trial of intermediate risk individuals (mostly Asian), a fixed-dose combination polypill plus aspirin versus double placebo resulted in 31% relative risk reduction in cardiovascular events, with greater benefit seen when aspirin was added to the polypill versus polypill alone

Answer 116

TIPS-3

Question 117

Formally, _____ medicine in cardiovascular settings has been described as an integrative approach that considers an individual’s genetics, lifestyle, and exposures as determinants of their overall cardiovascular health and disease phenotypes

Answer 117

Precision Medicine

Question 118

Give class 1 recommendations in initiating statin therapy? 3 subgroups and target LDL reduction in %
1.
2.
3.

Answer 118

1. Patients from secondary prevention with clinical ASCVD (history of acute coronary syndrome, myocardial infarction, stable or unstable angina, coronary or arterial revascularization, stroke, transient ischemic attack, or peripheral arterial disease) should be treated with maximally tolerated statin and nonstatin therapy to achieve LDL cholesterol reduction of 50% or more
2. Individuals from primary prevention with LDL cholesterol greater than or equal to 190 mg/dL, as this indicates primary hypercholesterolemia and should be treated with high-intensity statin or the highest intensity tolerated, aiming for LDL cholesterol reduction of 50% or more which can be achieved with addition of non-statin medication
3. Patients from primary prevention with diabetes, age 40 to 75 years old, and LDL cholesterol 70 to 189 with no clinical ASCVD, should be treated with moderate-intensity therapy, or high intensity if multiple ASCVD risk factors present in addition to diabetes

Question 119

Give diabetes specific risk enhancers that are independent of other risk factors

Answer 119

• Long duration of diabetes
• Nephropathy (eGFR <60 mL/min/1.73 m 2 or albuminuria ≥ 30 μg albumin/mg creatinine)
• Retinopathy
• Neuropathy
• ABI < 0.9

Question 120

The _____________, a surrogate for centripetal or abdominal obesity, independently predicts cardiovascular risk in women and older men.

Answer 120

Waist-to-hip ratio

Question 121

The AHA/ACC and ESC guidelines support screening ABI measurements particularly among individuals at increased risk of peripheral arterial disease

Factors that increase risk of PAD:

Answer 121

• Age > 65 years old
• Presence of other cardiovascular risk factors (e.g., diabetes, history of smoking, hyperlipidemia, hypertension)
• Family history of PAD
• Known atherosclerosis in another vascular bed (coronary or non-coronary)

Question 122

The US federal government issued its first-ever physical activity guidelines in 2008 and updated them in 2018, asking adults to do at least _____________ (2.5 to 5 hours) per week of moderate-intensity aerobic physical activity (e.g., brisk walking), or ____________________ of vigorous aerobic activity (e.g., jogging), or a combination of activities of both intensities that expends an equivalent amount of energy, preferably spread throughout the week.

Answer 122

Moderate intensity - 150 to 300 minutes per week
Vigorous aerobic - 75 to 150 minutes per week

Question 123

The use of statins is associated with a small but significant dose-dependent increase in new-onset ____________ of approximately 1 per 1000 person years

Answer 123

Diabetes

in particular among adults with other diabetes risk factors

The overwhelming benefits of statins in subjects at high risk for or in the secondary prevention of cardiovascular disease exceeds the small risk for development of diabetes.

Question 124

Based on the VITAL study results and previous studies, a reasonable approach would be to consider using n-3 fatty acid supplements among primary prevention adults with ________________ or among African Americans.

For secondary prevention or high-risk primary prevention patients, high-dose EPA provides additional cardiovascular benefit among maximally statin-treated patients with high triglycerides and other risk factors.

Answer 124

Low fish consumption