Primary prevention of CVD

Yibeltal Assefa (MD), cardiology Fellow

April 2021
 Outline
• Introduction
• Approach of primary CVD risk assessment
• Risk assessment tools
• Pharmacologic and non pharmacologic
management of CVD risk .
 Introduction
• Cardiovascular diseases are the leading cause of death in the world, especially
because of MI and stroke.
• In 2017, IHD affects around 126 million individuals globally (1,655 per 100,000),
which is estimated to be 1.72% of the world’s population . ​
• Their beginning, however, starts many years earlier with the atherosclerotic
process due to the cardiovascular risk factors.
• The concept of CV risk and prevention comes with Framingham study 1948 .
• It introduced much of the current knowledge about the cardiovascular risk
factors:
 tobacco, lipid disorders, high blood pressure, electrocardiographic
abnormalities, menopause, atrial fibrillation, overweight, and obesity, among many
others associated to the increase of cardiovascular events and
 protective factors as physical activity and HDL-cholesterol were also
established.
 Framingham
• THE Framingham study begun in 1948 and included
5,209 men and women from Framingham.
• initial cohort was enhanced in 1971, including the
descendants (5,124 sons and daughters) of first
participants
• 2002, included also their 4,095 grandchildren.
• The research extends now to genetics and epigenetics,
describing hundreds of new genes related to main
cardiovascular diseases and their precursors or risk
factors.
 Conti..
• The risk calculators are one of the outcomes from
the Framingham study.
• The most known is the Risk Score for Prediction
of Cardiovascular Diseases .
• It estimates the 10 years risk of cardiovascular
disease or death (from 40 to 75 years of age)
• Using age, sex, smoking habits, systolic blood
pressure, diabetes mellitus, and total cholesterol
and HDL.
 Risk Estimate
• The Globorisk is an extension of Framingham
and 7 more prospective studies. It estimates the 10
years risk of fatal CVD between 20- 80-year-old people
• The ACC/AHA Task Force proposed a new
Pooled Cohort ASCVD Risk Equations (race)
• Reynolds estimator adapts the calculation formula to
women by entering age, systolic BP,, high sensitivity
CRP, TC , HDL-cholesterol, haemoglobin A1c, current
smoker, and family history of premature CVD
 Risk Estimate
Others
• PROCAM caculator. ( the international task force for CVD)
• The NICE proposes QRISK2. it estimate life time risk
• The ASSIGN score ( Scottish ).
• The Italy CUORE project.
• SCORE From ESC
All are valid
Two problems are often pointed to these calculators:
The underestimation of the risk in younger individuals and
the difficulty in the management of residual risk
 FRS
• The sensitivity of Framingham Risk Score for coronary
disease is 45.9 in males and 57.5 in females
• For stroke is 71.6 in males and 61.6 in females.
• The specificity is, respectively, 83.2 and 81.9 for
coronary disease and 81.3 and 80.8 for stroke .

• In prevention/screening, we need high sensitivity tests

for detection of true negatives, and in diagnosis, we need
high specificity tests to find the true positives.
• It is important to consider risk modifiers.
 SCORE (ESC)

• ESC developed the Systematic Coronary Risk Evaluation (SCORE) based on

a large number of European participants.
• The outcome variable is death by CVD chosen because it is a strong and
reproducible variable.
• It allows separation of the mortality by ischemic heart disease and by
stroke.
• model use the common variable in the algorithm. age, sex, and 3 major
risk factors (systolic BP, TC, and current smoker
 SCORE (ESC)

• It also comprises several other modifiers with weight in the

cardiovascular risk, allowing to lessen the error of the
calculation:
 sedentary lifestyle, central obesity, poor socioeconomic conditions, low HDL-cholesterol,
high triglycerides, fibrinogen, Apo-B, and increased lipoprotein (a), evidence of preclinical
asymptomatic atherosclerosis (such as carotid plaques),presence of chronic kidney disease
(Glomerular Filtration Rate—GFR < 60 mL/min/1.73m2), and family history of premature
cardiovascular death .
• One interesting aspect of SCORE is its transposition into
categories of risk rather than dealing with the absolute value
of the calculation
Pooled cohort equation (AHA/ACC)
Variable included
• Age , Sex, Race, Total cholesterol ,HDL-c, SBP
Antihypertensive therapy, History of DM, Current smoking
Out come predicted
• Hard ASCVD (CHD death, nonfatal MI, fatal or
nonfatal stroke).
Derivation sample
• 5 community based cohorts of white and black
participants
 Framingham general CVD risk profile

Variable included
• Age , Sex, Race, Total cholesterol ,HDL-c, SBP Antihypertensive therapy,
History of DM, Current smoking

Out come predicted

• Total CVD (CHD death,MI, coronary insufficiency,angina, ischemic stroke,hemorrhagic
stroke,transient ischemic attack,intermittent claudication,and heart failure)

Derivation sample
• Single community based cohort of 2 generations.
 Reynolds risk score

Variables
• Age, Sex ,Total cholesterol ,HDL-C, SBP, Current smoking,
hsCRP level, Parental history of MI before age 60 y
Out come predicted
• Expanded ASCVD (CHD death, nonfatal MI, fatal or nonfatal stroke,
coronary revascularization)

Derivative sample
• Largely white health professionals enrolled in clinical trials
2019 Revised WHO CVD risk CHART
The Rational For Absolute Risk Assessment
 Rationale for the use of risk prediction
tools

• Traditionally, physicians have estimated prognosis by

qualitatively integrating the patient’s risks
• Assist healthcare professionals in their clinical
decision-making process, and
• to inform individuals about their risks of developing an
outcome.
• Reduce overtreatment of low risk individuals and the
under treatment of high-risk patients .
• additional goal of promoting lifestyle changes in those
at long-term risk
Objective of risk assessment and stratification

• To reduce CVD mortality and morbidity by

1. Life style modification
2. Pharmacologic intervention , mainly with
hypertension treatment and statin
2019 Primary Prevention Guideline

Risk stratification and pharmacologic

interventions
ACC/AHA
 Table 6. Selected Examples of Candidates for CAC Measurement
Who Might Benefit from Knowing Their CAC Score is Zero
CAC Measurement Candidates Who Might Benefit from Knowing Their CAC
Score Is Zero
 Patients reluctant to initiate statin who wish to understand their risk and
potential for benefit more precisely
 Patients concerned about need to reinstitute statin therapy after
discontinuation for statin-associated symptoms
 Older patients (men 55–80 y of age; women 60–80 y of age) with low
burden of risk factors (S4.4-42) who question whether they would benefit
from statin therapy
 Middle-aged adults (40–55 y of age) with PCE-calculated 10-year risk for
ASCVD 5% to <7.5% with factors that increase their ASCVD risk, although
they are in a borderline risk group.
 Studies supporting statin as primary
prevention of CVD
Heart Protection Study (HPS).
• cholesterol lowering with simvastatin in 20,536 high-risk individuals:
• a randomised placebo-controlled trial.
• Lancet 2002 
• Simvastatin was associated with an approximately 2% absolute risk reduction in all-
cause mortality (NNT=55), which was primarily driven by fewer CVD deaths (NNT=67),
including CHD deaths (NNT=83). There were also benefits for CHD events and strokes.
• The trial was included in a meta-analysis which concluded that intensive LDL-C lowering with
statins is safe.
• Reduction by 1.0 mmol/L is associated with a reduction of major vascular events risk by 20%

Jupitor ( 2008)
• In patients with normal LDL and elevated high-sensitivity CRP (HS-CRP), does
rosuvastatin reduce the incidence of major CV events .
• The authors estimate a NNT of 25; ie, treating 25 individuals with
rosuvastatin will prevent one major CV event at 5 years. 
 Statin Use in Primary Prevention of Atherosclerotic
Cardiovascular Disease According to 5 Major Guidelines
1mmol/l= 18mg/dl

Article Copyright © 2020 Authors, Source DOI: 10.1177/2048004020949326. See content reuse guidelines at: sagepub.com/journals-permissions
Stain as primary prevention above age 75

• Cholesterol Treatment Trialists meta-analysis shows no

benefits in those older than 75 years
• The on-going STAREE study which is designed
specifically to address this question.
it looks at the effect of Atorvastatin use in those >70
years who are otherwise well, particularly with no
evidence of CVD, diabetes, kidney or liver disease and is
due to report in 2023.
 For now we need to individualize based on the life
expectancy ,comorbidity and burden of risk factors
Table 2. Hypertension treatment guidelines – a comparison between the ACC/AHA and ESC/ESH guidelines.69,70
 REMAINING UNCERTAINTIES
• The effectiveness of statins has mostly been studied in middle-aged and older
individuals during relatively short treatment periods.
• It remains unknown to what extent results from these trials can be
extrapolated to younger individuals.
• Under estimate the risk in young and over estimate in old , short term risk is
low in young
• And most of the risk stratification do not consider the life time risk and CV age
• The cost of life time medications and their impact ( psychological and
economic stress ) is undermined
• Each community need to have their own risk assessment and stratification
tools
• Recent iterations of prevention guidelines have suggested the use of long-term
(eg, 30-year) or lifetime risk estimation using traditional risk factors
Prediction of Lifetime Risk for Cardiovascular Disease by Risk Factor Burden at
50 Years of Age

Donald M. Lloyd-Jones. Circulation. Prediction of Lifetime Risk for

Cardiovascular Disease by Risk Factor Burden at 50 Years of Age,
Volume: 113, Issue: 6, Pages: 791-798, DOI:
(10.1161/CIRCULATIONAHA.105.548206)
2019 Primary Prevention Guideline

Lifestyle Factors Affecting Cardiovascular

Risk
 Nutrition and Diet
Recommendations for Nutrition and Diet

COR LOE Recommendations

1. A diet emphasizing intake of vegetables, fruits,
legumes, nuts, whole grains, and fish is
I B-R recommended to decrease ASCVD risk factors.

2. Replacement of saturated fat with dietary

monounsaturated and polyunsaturated fats can be
IIa B-NR beneficial to reduce ASCVD risk.

3. A diet containing reduced amounts of cholesterol and

sodium can be beneficial to decrease ASCVD risk.
IIa B-NR
 Nutrition and Diet (cont’d)
Recommendations for Nutrition and Diet

COR LOE Recommendations

4. As a part of a healthy diet, it is reasonable to
minimize the intake of processed meats, refined
carbohydrates, and sweetened beverages to reduce
IIa B-NR ASCVD risk.

5. As a part of a healthy diet, the intake of trans fats

III- should be avoided to reduce ASCVD risk.
B-NR
Harm
 Exercise and Physical Activity
Recommendations for Exercise and Physical Activity
COR LOE Recommendations
1. Adults should be routinely counseled in healthcare visits
I B-R to optimize a physically active lifestyle.

2. Adults should engage in at least 150 minutes per week

of accumulated moderate-intensity or 75 minutes per
week of vigorous-intensity aerobic physical activity (or
I B-NR an equivalent combination of moderate and vigorous
activity) to reduce ASCVD risk.
 Exercise and Physical Activity (cont’d)
Recommendations for Exercise and Physical Activity
COR LOE Recommendations
3. For adults unable to meet the minimum physical activity
recommendations (at least 150 minutes per week of
accumulated moderate-intensity or 75 minutes per
week of vigorous-intensity aerobic physical activity),
IIa B-NR engaging in some moderate- or vigorous-intensity
physical activity, even if less than this recommended
amount, can be beneficial to reduce ASCVD risk.

4. Decreasing sedentary behavior in adults may be

IIb C-LD reasonable to reduce ASCVD risk.
 Table 4. Definitions and Examples of Different Intensities of
Physical Activity

Intensity METs Examples

Sedentary 1–1.5 Sitting, reclining, or lying; watching
behavior* television
Light 1.6–2.9 Walking slowly, cooking, light housework

Moderate 3.0 –5.9 Brisk walking (2.4–4 mph), biking (5–9

mph), ballroom dancing, active yoga,
recreational swimming
Vigorous ≥6 Jogging/running, biking (≥10 mph),
singles tennis, swimming laps

*Sedentary behavior is defined as any waking behavior characterized by an energy expenditure

≤1.5 METs while in a sitting, reclining, or lying posture. Standing is a sedentary activity in that it
involves ≤1.5 METs, but it is not considered a component of sedentary behavior.
MET indicates metabolic equivalent; mph, miles per hour.
 Adults with Overweight and Obesity
Recommendations for Adults with Overweight and Obesity

COR LOE Recommendations

1. In individuals with overweight and obesity, weight
loss is recommended to improve the ASCVD risk
I B-R factor profile.

    2. Counseling and comprehensive lifestyle

I B-R interventions, including calorie restriction, are
recommended for achieving and maintaining weight
loss in adults with overweight and obesity.
Adults with Overweight and Obesity (cont’d)
Recommendations for Adults with Overweight and Obesity

COR LOE Recommendations

3. Calculating body mass index (BMI) is recommended

annually or more frequently to identify adults with
I C-EO overweight and obesity for weight loss
considerations.

4. It is reasonable to measure waist circumference to

identify those at higher cardiometabolic risk.
IIa B-NR
 Treatment of Tobacco Use
Recommendations for Treatment of Tobacco Use
COR LOE Recommendations
1. All adults should be assessed at every healthcare visit for
tobacco use and their tobacco use status recorded as a
I A vital sign to facilitate tobacco cessation.

2. To achieve tobacco abstinence, all adults who use

I A tobacco should be firmly advised to quit.
 Treatment of Tobacco Use (cont’d)
Recommendations for Treatment of Tobacco Use
COR LOE Recommendations
3. In adults who use tobacco, a combination of behavioral
interventions plus pharmacotherapy is recommended to
I A maximize quit rates.

4. In adults who use tobacco, tobacco abstinence is

I B-NR recommended to reduce ASCVD risk.
 Treatment of Tobacco Use (cont’d)
Recommendations for Treatment of Tobacco Use
COR LOE Recommendations
5. To facilitate tobacco cessation, it is reasonable to
dedicate trained staff to tobacco treatment in every
IIa B-R healthcare system.

6. All adults and adolescents should avoid secondhand

smoke exposure to reduce ASCVD risk.
III:
B-NR
Harm
 Table 8. Highlights of Recommended Behavioral and
Pharmacotherapy Tobacco Treatment Modalities

Timing of Behavioral Interventions†

<3 min of tobacco >3-10 min of tobacco >10 min of tobacco
status status assessment with status assessment with
assessment with cessation counseling at cessation counseling at
cessation each clinic encounter each clinic encounter
counseling at
each clinic
encounter

†Timing of assessment relates to ICD-10 coding.

 Table 8. Highlights of Recommended Behavioral and
Pharmacotherapy Tobacco Treatment Modalities (cont’d)
Treatment Dosing‡ Precautions
NRT*
21 mg, 14 Starting dose: Local irritation possible;
mg, or 7 21 mg for >10 CPD; 14 mg avoid with skin disorders;
Patch mg for <10 CPD may remove for sleep if
needed
2 mg or 4 Starting dose: Hiccups/dyspepsia
Gum mg 4 mg if first tobacco use is possible; avoid food or
≤30 min after waking; 2 beverages 15 min before
2 mg or 4 mg if first tobacco use is and after use
mg >30 min after waking;
maximum of 20 lozenges
Lozenge or 24 pieces of gum/d.
Chew and park gum*

*CPD can guide dosing. 1 CPD is ≈1-2 mg of nicotine. Note: Use caution with all NRT
products for patients with recent (≤2 wk) MI, serious arrhythmia, or angina; patients
who are pregnant or breastfeeding; and adolescents.
‡Dose and duration can be titrated on the basis of response
 Table 8. Highlights of Recommended Behavioral and
Pharmacotherapy Tobacco Treatment Modalities (cont’d)
Treatment Dosing‡ Precautions
NRT*
10 Starting dose: Local irritation possible;
mg/mL 1-2 doses/h (1 dose=2 avoid with nasal or
Nasal spray reactive airway disorders
sprays); maximum of 40
doses/d
10, Starting dose: Cough possible; avoid with
10-mg Puff for 20 min/cartridge reactive airway disorders
Oral inhaler cartridge every 1-2 h; maximum 6-
16 cartridges/d; taper
over 3-6 mo§
*CPD can guide dosing. 1 CPD is ≈1-2 mg of nicotine. Note: Use caution with all NRT
products for patients with recent (≤2 wk) MI, serious arrhythmia, or angina; patients
who are pregnant or breastfeeding; and adolescents.
‡Dose and duration can be titrated on the basis of response
 Table 8. Highlights of Recommended Behavioral and
Pharmacotherapy Tobacco Treatment Modalities (cont’d)
Treatment Dosing‡ Precautions
Other║
Bupropion 150 150 mg once daily (am) Avoid with history/risk of
(Zyban mg SR for 3 d; then 150 mg twice seizures, eating disorders,
[GlaxoSmithKline], daily; may use in MAO inhibitors, or CYP 2D6
Wellbutrin SR combination with NRT inhibitor
[GlaxoSmithKline]) (S4.5-21)

0.5 mg 0.5 mg once daily (am) for Nausea common; take with
or 1 3 d; then 0.5 mg twice food. Renal dosing required.
mg daily for 4 d; then 1 mg Very limited drug
Varenicline twice daily (use start pack interactions; near-exclusive
(Chantix [Pfizer]) followed by continuation renal clearance.
pack) for 3-6 mo

‡Dose and duration can be titrated on the basis of response

§See Rx for Change for greater detail: http://rxforchange.ucsf.edu)
║The FDA has issued a removal of black box warnings about neuropsychiatric events
am indicates morning; CPD, cigarettes smoked per day; FDA, U.S. Food and Drug Administration;
ICD-10, International Classification of Diseases, Tenth Revision; MAO, monoamine oxidase; NRT,
nicotine replacement; and SR, sustained release.
 Aspirin Use
Recommendations for Aspirin Use
COR LOE Recommendations
1. Low-dose aspirin (75-100 mg orally daily) might be
considered for the primary prevention of ASCVD
among select adults 40 to 70 years of age who are at
IIb A higher ASCVD risk but not at increased bleeding risk.

2. Low-dose aspirin (75-100 mg orally daily) should not

III: be administered on a routine basis for the primary
B-R prevention of ASCVD among adults >70 years of age.
Harm

3. Low-dose aspirin (75-100 mg orally daily) should not

III: be administered for the primary prevention of ASCVD
C-LD among adults of any age who are at increased risk of
Harm
bleeding.
 ASA related studies in primary
prevention of CVD
• ASPREE (2018), "Effect of aspirin on disability-
free survival in the healthy elderly“ >70 years
With a median follow-up of 4.7 years, rates of disability-free
survival were similar between aspirin and placebo groups. Aspirin
was associated with higher incidence of major haemorrhage

•  It was published alongside two other primary

prevention trials ASCEND (Aspirin) (2018)  and 
ARRIVE (2018),which also found no benefit of
aspirin in diabetic patients and high risk
patients without diabetes, respectively.
 How does the risk stratification works
for our community?
• The risk stratification can be affected by
diet ,life style , body mass index and genetics –
which are not part of the risk calculator.
• And cost should also come to consideration
 Examples
1) 65 years old male farmer, with BP 160/90 ,
TC 190mg/dl , HDL mg /dl 50 ,no DM , not
smoker
2. A 40 years old Banker with same risk profile
 References
• ESC guideline
• AHA/ACC guideline
• Braunward text book
• PubMed
 Special Populations
• Quantitative risk assessment with current risk scores
should not be performed for patients with
 clinical ASCVD that requires secondary prevention

 confirmed familial hypercholesterolemia or baseline low-density lipoprotein–

cholesterol of ≥190 mg/dL.

 most patients with established diabetes mellitus should be considered for statin
therapy and for antihypertensive drug therapy
(if blood pressure is elevated) regardless of predicted 10-year risk.

 10-year risk estimation may still be useful in patients with diabetes mellitus to
inform thresholds for initiation of antihypertensive drug therapy and intensity of
statin dosing.
 ???CHD risk equivalent
• clinical coronary heart disease (CHD)
• 2. symptomatic carotid artery disease
(CAD)
• 3. peripheral arterial disease (PAD)
• 4. abdominal aortic aneurysm (AAA)
• 5. diabetes mellitus