Atherosclerosis, dyslipidemia & hypertension:

from risk factors to CVD events

Faris Basalamah, MD FIHA FAPSIC

Disclosure
Nothing to declare…..
Cardiovascular Disease Facts:
WHO 2012 United States Worldwide
Number Percent Number Percent
millions millions
CVD Prevalence 85.6 35
CVD Mortality .801 30.8 17.5 31
CHD Mortality .370 14.2 7.4 12.2
Stroke Mortality .129 5 6.7 11.8

WHO Key Facts:

 Number one cause of death globally
 ~80% die of MI or stroke
 >75%% of CVD deaths in low and middle income countries
 By 2030 almost 23.6 million will die from CVD
 Most CV diseases can be prevented by addressing behavioral factors
 Those at high CVD risk need early detection and management using
counselling and medications
American Heart Association. 2016 Heart and Stroke Statistical Update WHO. 2008,02012

3 CVD Primary Prevention

Mortality Projections by Disease: WHO

Graph showing the projected mortality trends from 2008

to 2030 for NCDs, CVDs and communicable disease
24%
22%
20%
18%
16%
14%
12%
10%
8%
6%
4%
2%
0%
2008 2015 2030

Cardiovascular diseases Cancer Diabetes Perinatal conditions Maternal conditions

Chronic respiratory diseases Tuberculosis Malaria HIV/AIDS

Source: WHO Global Atlas on CVD prevention and control estimates 2011

4 CVD Primary Prevention

Cardiovascular Disease Mortality Projected: WHO

Projected CVD deaths 2015-2030 by WHO region

20 000
Number of deaths (in thousands)

18 000

16 000

14 000

12 000

10 000
Cardiovascular diseases

8 000 All causes except CVD

6 000

4 000

2 000

0
2015 2030 2015 2030 2015 2030 2015 2030 2015 2030 2015 2030
AFR AMR EMR EUR SEAR WPR

AFR, African Region; AMR, Region of the Americas; EMR, Eastern Mediterranean
Region; SEAR, South-East Asia Region; WPR, Western Pacific Region

Source: WHO Global health estimates 2014

5 CVD Primary Prevention

 Age-Standardized Stroke and CHD
Death Rates by Country, 2002
Stroke death rate per 100,000 person-years CHD death rate per 100,000 person-years

6
Ueshima H et al. Circulation. 2008;118:2702-2709.
 Indonesia is rank #1
worldwide in terms of
the highest death rate
caused by Stroke Indonesia is rank #5 for the most country
with Diabetes prevalence

International Diabetes Federation 2014

Data Source: Published By WHO May 2014 .
(http://www.worldlifeexpectancy.com/),
(http://www.worldlifeexpectancy.com/countr
y-health-profile/indonesia)
 CHD risk increases with increasing levels of LDL-C

3.7

Relative risk for CHD

2.9

(log scale)
2.2

1.7
1.3

1.0

40 70 100 130 160 190

LDL-C (mg/dL)
 For every 30 mg/dL increase in LDL-C, the relative risk for CHD
increases by about 30%
 Elevated LDL-C or total cholesterol levels increase the risk of CHD,
independent of other risk factors
Grundy SM, et al. Circulation 2004;110:227–239
CHD, coronary heart disease Figure available for electronic presentation per Wolters Kluwer Health.
LDL-C, low-density lipoprotein-cholesterol Contact AHA 214-706-1131 for print permissions
Need for optimization of treatment dyslipidemia
to maximize benefit and improve outcome
Hyperlipidemia Facts:
• WHO estimates that dyslipidemia accounts for 39% of the worldwide
burden of CVD
• 4th in rank among leading risks
• Inadequate control of dyslipidemia is responsible for >4 million yearly
deaths worldwide and 350,000 in the US

Lancet 2016;388:1659-724 WHO 2008

10 CVD Primary Prevention

Hyperlipidemia: WHO

11 CVD Primary Prevention

 Diabetes and Cardiovascular Disease
• Framingham Heart Study – Risk for CHD 2x in men and 3x in women
• MRFIT study – 12-year risk for CVD death 9.7% versus 2.6%
• 65 to 75% of all diabetic mortality is due to CVD
• 75% from coronary atherosclerosis
• On average mortality 14.6 years earlier
• Accelerated atherosclerosis is multifactorial and begins
years/decades prior to diagnosis of type 2 diabetes
• >50% of patients with newly diagnosed type 2 DM have CHD
• Increased atherosclerotic burden
• Diffuse disease/Multi-vessel involvement
• Increased disease progression
• Increased risk for acute MI/death and heart failure
• Poor response to medical and revascularization therapies
• Risk factors are synergistic rather than additive for risk of ASCVD
• 14.3% US adults with DM2 at targets for HBA1C, LDL and BP
• A single risk factor confers a high risk (80% lifetime risk)
Kannel WB, et al. Circulation. 1979;59(1):8-13. Stamler J, et al. Diabetes Care. 1993;16(2):434-444.
ERFC. Lancet. 2010;375(9733):2215-2222. Booth GL, et al. Lancet. 2006;368(9529):29-36.

12 CVD Primary Prevention

 Diabetes and High Glucose: WHO
Worldwide Prevalence of Diabetes Change in Prevalence of Diabetes
Fasting BS >7.0 mmol/L 1980 to 2014
WHO Region Prevalence (%) Number
(millions)
1980 2014 1980 2014

African Region 3.1% 7.1% 4 25

Region of the Americas 5% 8.3% 18 62

Eastern Mediterranean 5.9% 13.7% 6 43

Region
European Region 5.3% 7.3% 33 64

South-East Asia Region 4.1% 8.6% 17 96

Western Pacific Region 4.4% 8.4% 29 131

Total a 4.7% 8.5% 108 422

• Number of adults worldwide with diabetes nearly quadrupled from 108 million
in 1980 to 422 million in 2014
• Largest number in SE Asia and W Pacific regions
• Prevalence nearly doubled from 4.7% to 8.5%
WHO 2016

13 CVD Primary Prevention

Diabetes and Mortality: WHO
• DM and elevated blood sugar responsible for 3.7 million deaths a year
• 80% of diabetes deaths in low and middle income countries
• Almost half occur before age 70
• By 2030 deaths will be doubled compared with 2005 and the 7th leading
cause of death
• Direct annual worldwide cost of 827 billion dollars

12%
% of total deaths attributable to high blood glucose

10%

8%

6%

4%

2%

0%

African Region of Eastern European South- Western

Region the Americas Mediterranean Region East Asia Pacific
Region Region Region

MEN: 2000 2012 WOMEN: 2000 2012

WHO 2016

14 CVD Primary Prevention

Diabetes and Cardiovascular Disease

Myocardial Infarction Heart Failure

DM + Prior MI
HF and no DM

Prior MI
HF and DM
DM

No DM
No Prior MI

AGE

Burger AJ , et al. Am J Cardiol. 2005,95(9):1117-1119.

Schramm TK, et al. Circulation. 2008;117(15):1945-1954.

15 CVD Primary Prevention

 Glucose Levels and Cardiovascular Events

3 3
2 h Glucose Fasting Glucose
2.5 2.5

2
RR 2 RR

1.5 1.5

1 1
72 108 144 180 198 72 90 108 126 144

2hPG = 140 mg/dL; RR = 1.58 (1.19-2.10)

2hPG=2-hour plasma glucose; FPG=fasting plasma glucose; RR=risk ratio

Blue lines are 95% Confidence Intervals

Coutinho MS, et al. Diabetes Care. 1999;22(2):233-240.

16 CVD Primary Prevention

The Framingham Study: increased level of
total cholesterol is associated with incidence of
coronary heart disease (CHD)
150
CHD incidence per 1000
125

100

75

50

25

0
<204 205-234 235-264 265-294 >295
(<5.3) (5.3–6.1) (6.1–6.8) (6.8–7.6) (>7.6)

Serum total cholesterol, mg/dL (mmol/L)

Adapted from Castelli WP. Am J Med 1984;76:4–12

CV Risk Factors (Dyslipidemia, Hypertension,
diabetes,Smoking) associated with CV disease

LDL-C BP Risk factors Diabetes Smoking Heart failure

Oxidative stress

Endothelial dysfunction

NO Local mediators Tissue ACE-Ang II

PAI-1 VCAM Endothelium Growth factors Proteolysis

matrix
ICAM cytokines

Thrombosis Inflammation Vasoconstriction Vascular lesion Plaque rupture

and remodelling

Clinical endpoints
NO = nitric oxide

Adapted from Gibbons GH, Dzau VJ. N Engl J Med 1994;330;1431–1438

 Target Organ Damage due to Hypertension
 Heart
Left ventricular hypertrophy
Angina or prior myocardial
infarction, heart failure

Brain
Stroke or transient ischemic
attack

Chronic kidney disease

Peripheral arterial disease

 Retinopathy
The link between Hypertension and Coronary Heart
Disease
From: Systolic Blood Pressure Levels Among Adults With Hypertension and Incident Cardiovascular
EventsThe Atherosclerosis Risk in Communities Study
JAMA Intern Med. 2014;174(8):1252-1261. doi:10.1001/jamainternmed.2014.2482

Figure
Legend:
Adjusted Hazard Ratios (HRs) of Incident Cardiovascular Events by Time-Varying Systolic Blood Pressure (SBP) Level Category Among Participants With
HypertensionThe Atherosclerosis Risk in Communities Study (1987-2010) stratified by composite event (heart failure, ischemic stroke, or combination measure
myocardial infarction/incidence of coronary heart disease Copyright
death [MI/CHD]) (A),American
© 2017 heart failure (B), ischemic stroke (C), and MI/CHD (D). Elevated BP is defined
Medical
Date
as an of
SBPdownload:
of 140 mm3/18/2017
Hg or higher; standard BP, an SBP ofAssociation.
120 to 139 mm Hg; and low BP, an SBP of lower than 120 mm Hg. The vertical lines through the
All rights reserved.
HRs represent 95% CIs.
From: Systolic Blood Pressure Levels Among Adults With Hypertension and Incident Cardiovascular
EventsThe Atherosclerosis Risk in Communities Study
JAMA Intern Med. 2014;174(8):1252-1261. doi:10.1001/jamainternmed.2014.2482

Figure Legend:
Unadjusted Cardiovascular Event-Free Survival Among Participants With Hypertension by Systolic Blood Pressure (SBP)
CategoryThe Atherosclerosis Risk in Communities Study (1987-2010) stratified by composite event (heart failure, ischemic stroke,
or combination measure myocardial infarction/incidence of coronary heart disease death [MI/CHD]) (A), heart failure (B), ischemic
stroke (C), and MI/CHD (D). Elevated BP is defined as an SBP of 140 mm Hg or higher; standard BP, an SBP of 120 to 139 mm Hg;
and low BP, an SBP of lower than 120 mm Hg. Copyright © 2017 American Medical
Date of download: 3/18/2017
Association. All rights reserved.
Progress of Atherogenesis

Threshold

Decades Years-Months Months-Days

healthy subclinical symptomatic

Thrombus
Intima
Lumen
Media

Plaque

Adapted from Gibbons GH, Dzau VJ. N Engl J Med 1994;330;1431–1438

Rationale For Primary Prevention
Plaque
Occlusive Rupture/
Fatty Fibrous Atherosclerotic Fissure &
Normal Streak Plaque Plaque Thrombosis Unstable
Angina

MI

Coronary
Death

Stroke

Critical Leg
Effort Angina Ischemia
Clinically Silent
Claudication

Increasing Age

25 CVD Primary Prevention

Rationale For Primary Prevention

8
68%
0

6
0

4
0
18%
2 14%
0

0
<50 50%–70% >70
% %
% Stenosis

Adapted from Falk et al. Circulation. 1995;92:657–671. Rioufol G, et al. Circulation 2002;106:804-8

26 CVD Primary Prevention

Rationale For Primary Prevention
• Of those experiencing a MI, ~25% die within 1 hr
• 50%/64% male/female who die suddenly of CHD have no previous
symptoms
• Coronary atherosclerosis begins early in life and progresses with age
• Asymptomatic coronary stenoses are more likely to be the culprit lesions
for MI
• The dominant risk factors are known
• INTERHEART: 90% of risk explainable by 9 modifiable RF’s: smoking,
lipid abnormalities, HTN, DM, lack of physical activity, nutrition, over
use of alcohol and psychosocial factors
• Clinical tools and diagnostic testing available to identify the at risk population
• Effective and safe interventions supported by clinical trials
– Identification of the at risk patient and early aggressive treatment appears
to reduce the risk of MI and death
Lancet 2004;364(9438):937-952

27 CVD Primary Prevention

Who is at Risk For Cardiovascular Disease?
• Known CHD: Prior heart attack, abnormal stress test or cath,
angina
• Other vascular disease such as carotid artery disease, stroke,
aortic aneurysm, PAD
• Diabetes, particularly with at least one additional risk factor

• Multiple risk factors associated with high risk of > 20%

10-year risk
• Intermediate risk (10 to 20% 10-year risk) with other risk
factors such as strong family history of premature CHD,
metabolic syndrome, elevation of other markers of risk or
inflammation: e.g. hs-CRP, LP(a), carotid IMT (intimal
medial thickness), coronary calcification score, ABI
(ankle-brachial index)
• Chronic inflammatory diseases: SLE, Rheumatoid arthritis
28 CVD Primary Prevention
Risk-Based Management
• CVD risk stratification consists of the categorization and management of
people according to their likelihood or chance for a cardiovascular event
• Level of risk is determined with simple risk-scoring tools and calculated as
the combined effect of multiple risk factors, including age, gender,
smoking, blood pressure, cholesterol and body mass index and expressed
as the probability of developing CVD over a period such as 10 years
• Comprehensive risk assessment in adults with no known CVD using
simple risk-scoring tools can help identify those at high risk and initiate
early preventive interventions
• Clinical trials have shown that modification of CVD risk factors, including
high blood cholesterol and blood pressure, reduces the number of clinical
events and premature deaths in people with established CVD and in those
at high or intermediate risk for CVD due to one or more factors
• Generally established 10-year risk levels;
• Low risk: <5 to 10%
• Intermediate risk: 10-20% yearly risk
• High risk: >20% yearly risk
• Very high risk: >30%

29 CVD Primary Prevention

Assessing Risk For Primary Prevention

Evaluation Tools
• Framingham risk score (FRS)
• ACC/AHA ASCVD algorithm
• Reynolds risk score Population
• PROCAM Score
• MESA
• Systematic Coronary Risk Evaluation (SCORE)
• QRISK
• WHO

Considerations for Risk Assessment Individual

• Age
• Gender
• Smoking status
• Systolic blood pressure Other Markers
• Total cholesterol Including
• Comorbid conditions imaging

30 CVD Primary Prevention

Stepwise Selection of Risk Factors* in 2693 White Patients
With Type 2 Diabetes - Time to First Event: UKPDS

Coronary Artery Disease (n=280)

Position in Model Variable P-Value

First Low-density lipoprotein <0.0001
Second High-density lipoprotein 0.0001
Third Hemoglobin A1c 0.0022
Fourth Systolic Blood Pressure 0.0065
Fifth Smoking 0.056
*Adjusted for age and sex

Turner RC, et al. BMJ. 1998;316:823-8.

31 CVD Primary Prevention

An Analysis of Calibration and Discrimination Among Multiple
Cardiovascular Risk Scores in a Modern Multiethnic Cohort Calibration
and Discrimination Among CVD Risk Scores: Men

DeFilippis AP et al Ann Intern Med. 2015 Feb 17;162(4):266-75

FRS-CHD, FRS-CVD, ATPIII-FRS-CHD and AHA-ACC-ASCVD overestimate risk by
53%, 37%, 154% and 86%. RRS had the best calibration for men with 9% overestimation.
Risk score–specific predicted and observed events by decile of calculated risk.
Hosmer–Lemeshow calibration plots for women (n = 2266). ACC = American College of Cardiology; AHA = American Heart
Association; ASCVD = atherosclerotic cardiovascular disease; ATPIII = Adult Treatment Panel III; CHD = coronary heart disease;
CVD = cardiovascular disease; FRS = Framingham risk score; RRS = Reynolds Risk Score.

32 CVD Primary Prevention

Other Markers of Risk That May Influence Decision to Treat
• Lipoprotein (a)
• Us CRP
• TMAO
• Myeloperoxidase

• Pre-clinical disease
• Coronary calcification score
• Carotid IMT
• Inflammatory diseases associated with high CVD risk
• Rheumatoid arthritis
• Psoriatic arthritis
• Systemic lupus

33 CVD Primary Prevention

Incorporating CAC into Risk Assessment

MESA Online Reference Calculator:

https://www.mesa-nhlbi.org/CACReference.aspx
MESA 10-Year CHD Risk with Coronary Artery Calcification

The estimated 10-year risk of a

CHD event for a person with this
risk factor profile including
coronary calcium is 10.9%. The
estimated 10-year risk of a CHD
event for a person with this risk
factor profile if we did not factor
in their coronary calcium score
would be 4.5%

FRS: 4%
ACC/AHA: 2.3%
PROCAM: <10%
Reynolds: 4.5%

34 CVD Primary Prevention

 How to Estimate CVD Risk: ESC
Framingham44
Data Prospective studies:
Framingham Heart Study and
Framingham offspring study.
Latest version includes both
Population General population,
Framingham, Massachusetts,
USA. Baselines: 1968–1971,
1971–1975, 1984–1987
Sample size 3969 men and
4522 women
Calculates 10-year risk of CAD
eventsoriginally.
Latest version:
10-year risk of CVD events
NCEP ATP III version: 10-year
risk of hard coronary events
Age range (years)
30–75
Variables Sex, age, total cholesterol,
HDL-C, SBP,
smoking status, DM,
hypertensive treatment
Framingham44
Comments/ Latest version includes National, updated
developments version based on recalibrations
non-laboratory values
only,
substituting BMI from lipid
measurements
Recommended NCEP guidelines,54
by guidelines Canadian CV guidelines,55
other national guidelines
recommend adapted
versions including New
Zealand56
SCORE30 ASSIGN – SCORE45 QRISK146& QRISK247 PROCAM48 Pooled Cohort Studies CUORE49 Globorisk52
Equations50
12 pooled prospective SHHEC Prospective study QRESEARCH database Prospective study 4 Pooled prospective studies CUORE Derivation cohort: 8 pooled prospective studies
studies ARIC CHS CARDIA - Atherosclerosis Risk in Communities,
Framingham (original and Cardiovascular Health Study, Framingham Heart
offspring studies) Study original cohort and offspring cohort,
Honolulu Program, Multiple Risk Factor
Intervention Trial, Puerto Rico Heart Health
Program, and Women’s Health Initiative Clinical
Trial
12 prospective studies Random sample from Data collected from 1993– Healthy employees. Baselines 1987–89 1980s and 1990s 8 prospective studies from North America.
from 11 European countries. general population 2008 from GP Baseline: 1978–1995 (ARIC), 1990 and Baselines: 1948–1993
Baselines: 1972–1991 in Scotland, baseline: 1984– databases – imputation of 1992–3 (CHS), 1985–6
1987 missing data (CARDIA), 1968–1971,
1971–1975, 1984–1987
(Framingham)
117 098 men and 6540 men and 6757 women 1.28 million (QRISK1) 18 460 men and 11 240 white women, 7520 men and 13 127 33 323 men and 16 806 women
88 080 women 8515 women 9098 white men, 2641 women
2.29 million (QRISK2)
African-American women and
1647 African-American men
10-year risk of CVD 10-year risk of CVD 10-year risk of CVD Two separate scores 10-year risk for a first 10-year probability of 10 year risk of fatal cardiovascular disease
mortality events events. calculate 10-year risks of atherosclerotic CVD developing a first major
major coronary events event. CV event (myocardial
Lifetime risk
and cerebral ischaemic infarction or stroke)
events Lifetime risk
40–65 30–74 35–74 20–75 20–79 35–69 40–84
Sex, age, total cholesterol Sex, age, total cholesterol, QRISK1 - sex, age, total Age, sex, LDL-C, HDL-C, Age, sex, race (white or Age, sex, SBP, total Age, sex, smoking, total cholesterol, DM, systolic
or total cholesterol/ HDL-C HDL-C, SBP, smoking – no. cholesterol to HDL-C ratio, DM, other/African American), cholesterol, HDL-C, BP
ratio, SBP, smoking status. cigs, DM, area based index SBP, smoking status, DM, area smoking, SBP total cholesterol, HDL-C, antihypertensive therapy
Versions for use in high and of deprivation, family based index of deprivation, SBP, antihypertensive and smoking habit
low-risk countries history family history, BMI, BP treatment, DM, smoking
treatment, ethnicity and
chronic diseases
SCORE30 ASSIGN – SCORE45 QRISK146& QRISK247 PROCAM48 Pooled Cohort CUORE49 Globorisk52
Studies Equations50
QRISK2 includes Recent change in the Race specific beta Recalibrations have been undertaken for
interaction terms to methods (Weibull) coefficients for risk 11 countries
adjust for the allows extension of risk factors have
interactions between age estimation to women been incorporated.
and some of the and broader age range Calculator shown to
variables overestimate risk in
external validations –
this may indicate the
need for recalibration in
certain populations
European Guidelines on SIGN37 NICE guidelines on lipid International Task 2013 AHA ACC
CVD Prevention29 modification,57 Force for Prevention of Guideline on the
QRISK Lifetime Coronary Disease assessment of CVD
recommended by JBS3 Guidelines risk50
guidelines58
35 CVD Primary Prevention
How to Estimate CVD Risk: ESC

European Heart Journal 2012;33:1635-1701

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the image, or the image may hav e been corrupted. Restart y our computer, and then
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Figure 1 SCORE chart: 10-year risk of fatal cardiovascular disease in populations of countries at Figure 2 SCORE chart: 10-year risk of fatal cardiovascular disease in populations of
high cardiovascular risk based on the following risk factors: age, sex, smoking, systolic blood countries at low cardiovascular risk based on the following risk factors: age, sex, smoking,
pressure, total cholesterol. CVD ¼ cardiovascular disease; SCORE ¼ Systematic Coronary Risk systolic blood pressure, total cholesterol. CVD ¼ cardiovascular disease; SCORE ¼
Estimation. Systematic Coronary Risk Estimation.

36 CVD Primary Prevention

How to Estimate CVD Risk: ESC
Table 5 Risk categories

Very high-risk Subjects with any of the following:
•Documented CVD, clinical or unequivocal on
imaging. Documented clinical CVD includes
previous AMI,ACS, coronary revascularization
and other arterial revascularization procedures,
stroke and TIA, aortic aneurysm and PAD.
Unequivocally documented CVD on imaging
includes plaque on coronary angiography or
carotid ultrasound. It does NOT include some
increase in continuous imaging parameters such
as intima–media thickness of the carotid artery.
•DM with target organ damage such as
proteinuria or with a major risk factor such as
smoking or marked hypercholesterolaemia or
marked hypertension.
•Severe CKD (GFR <30 mL/min/1.73 m2).
•A calculated SCORE 10%.
Risk factor goals and target levels for
important cardiovascular risk factors
Smoking No exposure to tobacco in any form.
Diet Low in saturated fat with a focus on wholegrain
products, vegetables, fruit and fish.
Physical At least 150 minutes a week of moderate aerobic PA
activity (30 minutes for 5 days/week) or 75 minutes
a week of vigorous aerobic PA (15 minutes for 5
days/week) or a combination thereof.
Body weight BMI 20–25 kg/m2.Waist circumference <94 cm (men) or
<80 cm (women).
Blood pressure <140/90 mmHga

European Heart Journal 2012;33:1635-1701

High-risk Subjects with:
•Markedly elevated single risk factors, in
particular cholesterol >8 mmol/L (>310 mg/dL)
(e.g. in familial hypercholesterolaemia) or
BP 180/110 mmHg.
•Most other people with DM (with the exception
of young people with type 1 DM and without
major risk factors that may be at low or
moderate risk).
•Moderate CKD (GFR 30–59 mL/min/1.73 m2).
•A calculated SCORE 5% and <10%.
Moderate-risk SCORE is 1% and <5% at 10 years. Many
middle- aged subjects belong to this category.
Low-risk SCORE <1%.
Lipidsb Very high-risk: <1.8 mmol/L (<70 mg/dL), or a
LDLc is the reduction of at least 50% if the baseline is between
primary target 1.8 and 3.5 mmol/L (70 and 135 mg/dL)d
High-risk: <2.6mmol/L (<100 mg/dL), or a
reduction of at least 50% if the baseline is between
2.6 and 5.1 mmol/L (100 and 200 mg/dL)
Low to moderate risk: <3.0 mmol/L (<115
mg/dL).
HDL-C No target but >1.0 mmol/L (>40mg/dL) in men and
>1.2 mmol/L (>45 mg/dL) in women indicate lower risk.
Triglycerides No target but <1.7 mmol/L (<150 mg/dL) indicates
lower risk and higher levels indicate a need to look for
other risk factors.
Diabetes HbA1c <7%. (<53 mmol/mol)

ACS ¼ acute coronary syndrome; AMI ¼ acute myocardial infarction; BP ¼

blood
pressure; CKD ¼ chronic kidney disease; DM ¼ diabetes mellitus; GFR
¼
glomerular filtration rate; PAD ¼ peripheral artery disease; SCORE ¼
systematic
coronary risk estimation; TIA ¼ transient ischaemic
attack.

37 CVD Primary Prevention

WHO: HEARTS Program

• H: Healthy Lifestyle
• E: Evidence-Based Treatment Protocols
• A: Access to Essential Medicines and Technology
• R: Risk-Based management
• T: Team Care and Task-Sharing
• S: Systems for Monitoring

Hearts: technical package for cardiovascular disease management in primary health care.
World Health Organization 2016

38 CVD Primary Prevention

CVD Facts: WHO

Flow chart of CVD risk assessment and management

Total CVD risk greater than History of diabetes

20-30% based on CVD risk or chronic kidney
stratification charts disease

HIGH RISK
for heart
attacks and
strokes

Systolic blood pressure ≥ 160

History of heart attack or mmHg or total cholesterol ≥
stroke 8 mmol/L

WHO Country Specific Risk Charts

39 CVD Primary Prevention

WHO Cardiovascular Risk Assessment

Risk Level <10% 10% to <20% 20% to <30% 30% to <40% ≥40%

AFR D People with Diabetes Mellitus

WHO and International Society of Hypertension (ISH) cardiovascular risk prediction chart
(Shows the 10 year risk of a fatal or nonfatal cardiovascular event by gender, age, smoking
status, systolic blood pressure, blood cholesterol and presence or absence of diabetes.
Different charts are available for all WHO subregions).

CVD Primary Prevention

WHO: Distribution of Cardiovascular Risk
Americas Region A (Males) Americas Region A (Females)
0.85% 0.24%
100 0.51% 8.40%
100 0.40% 3.13%
2.63% 1.18% 3.51% 14.38%
90 5.14% 90 6.45%
31.59%
31.77%
8.50%
80 17.18% 80
54.23%
70 70
13.69% 27.03%
20.47%
60 60
96.00% 98.18%
50 50 86.91%

40 35.27% 40
23.86%
32.09%
30 69.27% 30
50.09%
20 20

10 19.27%
18.76%
10 15.84%
Risk categories:
■ <10%
3.15%
0 0
<50 50–59 60– 70+ <50 50–59 60– 70+
South-East Asia Region C (Males) 69 South-East Asia Region C (Females)69 ■ 10–19.9%
0.47% 0.22%
100 0.25%
1.30%
5.12%
4.41%
100 0.74%
0.65%
3.31%
3.39% ■ 20–29.9%
90 7.45%
22.23%
31.39%
90 8.72% 19.23%
29.75% ■ ≥30%
80 80
12.45%
70 14.32% 70
14.42% 22.95%
60 60
97.99% 98.39%
27.48%
50 50 38.52%

40 83.02% 44.02% 40 84.58%

30 30 40.66%

20 20
35.97%
29.80%
10Riskcategories: ■ <10% ■ 10–19.9% ■ 20–29.9% ■ 10Riskcategories: ■ <10% ■ 10–19.9% ■ 20–29.9% ■
≥30% 10.17% ≥30% 6.64%
0 0
<50 50–59 60– 70+ <50 50–59 60– 70+
69 69
Age Group Age Group
(years) (years)

CVD Primary Prevention

Issues with Risk Scores
• Accurate cardiac risk estimation is essential to balancing the risks and
benefits of preventive therapies.
• Overestimation of risk may result in increased use of preventive
medications, potentially exposing some patients to the unnecessary risks
of these drugs. Need to balance overprescribing with drug risk.
• Implications for public health planning with financial ramifications for a
heavily burdened health care system. Statins, for example, are clearly
cost-effective in secondary prevention or high risk primary prevention
patients, become less cost effective for low-risk patients
• They should only be used as a starting point for clinicians to begin
discussions of the risk and benefits of treatment and not a mandate to
write a Rx.
• Low risk score does not preclude treatment. Need to individualize for the
patient. Other risk markers and measures of preclinical atherosclerotic
disease may help better determine risk level in individual patients.
• Many risk scores have been proposed but all have limitations.

42 CVD Primary Prevention

Estimating CVD Risk
• Assessing a patients future risk for developing CVD is the key to many decisions
regarding institution of and intensity of preventive therapies
• In apparently healthy persons, CV risk in general is the result of multiple,
interacting risk factors and basis for the total CV risk approach to prevention
• Risk scores estimates the 10 year risk of fatal CVD and can assist in making
logical management decisions to avoid both under- and overtreatment. Validated
local risk estimation systems are preferred
• Individuals automatically at high to very high CV risk do not need the use of a risk
score and require immediate attention to risk factors. These include those with
clinical atherosclerotic disease, diabetes, familial hypercholesterolemia
• In younger persons, a low absolute risk may conceal a very high lifetime relative
risk and use of the relative risk chart, calculation of their “risk age” or other risk
markers may help in advising them of the need for intensive preventive efforts
• Whether to initiate preventive interventions and treatment intensity are guided by
the level of risk. Those at higher risk for CVD events require more intensive
management. Conversely, low-risk individuals who might not benefit sufficiently
from are spared the harms and cost of treatment
• CVD risk and risk factors may vary considerably by region globally

43 CVD Primary Prevention

CVD Primary Prevention
t hanks
44
CASE STUDY
 Case 1. Bpk. X (57 years)
• LDL-C 170 mg/dL
• HDL-C 35 mg/dL
• Fasting blood glucose 130 mg/dL, no medication
• Total cholesterol 250 mg/dL (≈6.5 mmol/L)
• SBP 140 mmHg; DBP 90 mmHg
– Receiving 10 mg/day amlodipine
• BMI 27 kg/m2
• Family history: father had an MI aged 45 years
• Non-smoker
 Case 1. Bpk. X (57 years)
• What is the risk of CV in this patients?
• What things should be considered?
• What would be the target? (BP, LDL level, etc)
 Case 2. Ny. Y (60 years)
• Woman, aged 55 years
• Does little exercise
• Smoker
• LDL-C 150 mg/dL
• HDL-C 48 mg/dL
• Total-C 250 mg/dL
• Takes antihypertensive therapy
(amlodipine 10 mg/day, olmesartan 40 mg/day, HCTZ 25
mg/day)
• Treated blood pressure 130/85 mmHg
(at time of antihypertensive initiation: 180/120 mmHg)
• BMI 28 kg/m2
 Case 2. Ny. Y (60 years)
• What is the risk of CV in this patients?
• What things should be considered?
• What would be the target? (BP, LDL level, etc)
Novel Risk Model: Lancet
Men Women
South Korea Spain
Spain South Korea
Denmark Japan
England Denmark
Japan England

40–64 years
USA USA
Mexico Mexico
Malawi Czech Republic
China Malawi
Distributions of 10-year risk of fatal
Czech Republic Iran cardiovascular disease by country,
Iran China sex, and age group

Spain Japan Results for Czech Republic, Iran, and

Japan Spain Malawi are shown only for people
South Korea Denmark
aged 40–64 years because older

65–84 years
Denmark England
individuals were not enrolled in the
England South Korea
national health examination surveys
USA USA

Mexico Mexico
in these countries. Raw data are
China China
shown in the appendix.

South Korea South Korea

Spain Spain

Denmark Denmark

40–84 years
England England

USA Japan

Mexico USA

Japan Mexico

China China

0 20 40 60 80 100 0 20 40 60 80 100
Population in risk category (%) Population in risk category (%)

<3% 3–6% 7–9% 10–14% ≥15%

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CVD Primary Prevention 53 2015
 Risk Models: BMJ

Table 4 | Description of study populations and design characteristics used to validate seven most often (>10 times, see table 3) validated models. Values are numbers (percentages) unless stated otherwise

Framingham Framingham
SCORE: Conroy 20036 D’Agostino 200836 QRISK: Hippisley-Cox 20078
Wilson 19985 (n=89)† Anderson 19913 (n=73) (n=63) (n=44) ATP III 200237 (n=31) Anderson 19914 (n=30) (n=12)

Characteristics
Location: 9 (10) 3 (4) 2 (3) 8 (18) 2 (6) 2 (7) 0 (0)
Asia 0 (0) 12 (16) 4 (6) 2 (5) 1 (3) 2 (7) 0 (0)
Australa 34 (38) 52 (71) 47 (75) 20 (45) 6 (19) 18 (60) 12 (100)
Europe 46 (52) 6 (8) 10 (16) 14 (32) 22 (71) 8 (27) 0 (0)
North Ameria
Age:
Same age range as development 2 (3) 21 (29) 4 (6) 5 (11) 0 (0) 0 (0) 12 (100)
study*
3 (3) 6 (8) 4 (6) 3 (7) 3 (10) 1 (3) 0 (0)
Young people (<50 years)
5 (6) 7 (10) 4 (6) 3 (7) 10 (32) 0 (0) 0 (0)
Older people (>60 years)
Other 79 (89) 39 (53) 51 (81) 33 (25) 18 (58) 29 (97) 0 (0)
Sex:
Men 38 (43) 30 (41) 23 (37) 11 (25) 10 (32) 16 (53) 6 (50)
Womn 29 (33) 25 (34) 23 (37) 11 (25) 10 (32) 13 (43) 6 (50)
Men and women 22 (25) 18 (25) 17 (27) 22 (50) 11 (35) 1 (3) 0 (0)
Median (range) No of participants 2716 (100-163627), n=87 2423 (262-797373), n=71 8025 (262-44649), n=63 2661 (272-542987), n=44 3029 (534-36517), n=31 3573 (331-542783), n=30 536,400 (301,622-797373), n=12
Median (range) No of events 146 (8-24 659), n=65 128 (1-42 408), n=59 224 (16-1722), n=54 164 (15-26 202), n=35 415 (35-2343), n=29 188 (4-26 202), n=28 29057 (18027-42408), n=6
Median (range) C statistic 0.71 (0.57-0.92), n=61 0.75 (0.53-0.99), n=46 0.75 (0.62-0.91), n=28 0.77 (0.58-0.84), n=28 0.66 (0.60-0.84), n=21 0.75 (0.63-0.78), n=6 0.79 (0.76-0.81), n=12
Median (range) observed:expected 0.59 (0.37-1.92), n=14 0.68 (0.18-2.60), n=42 0.68 (0.28-1.50), n=26 0.80 (0.62-0.96), n=3 0.47 (0.47-0.47), n=1 0.71 (0.32-3.92), n=14 0.94 (0.87-1.00), n=4

*30-74 (Framingham Wilson 1998,5 Anderson 1991,3 4 D’Agostino 2008,36 ATP III 200237 ), 40-65 (SCORE Conroy 20036 ), 35-74 (QRISK Hippisley-
Cox 20078).
†Number of times model was externally validated.
‡Number of models for which this information was reported.

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CVD Primary Prevention 54
 Risk Models: BMJ
List of the models that were validated at least three times, and their predicted outcomes (sorted by number of validations)
Reference (No of developed models) Predicted outcomes No of validations
Framingham Wilson 19985 (n=2*) Fatal or non-fatal CHD 89
Framingham Anderson 19913 (n=12) Fatal or non-fatal: CHD, CVD, 73
myocardial infarction, and stroke
SCORE Conroy 20036 (n=12) Fatal: CHD, CVD, and non-CHD 63
Framingham D'Agostino 200836 (n=4) Fatal CVD 44
Framingham ATP III 200237 (n=2) Fatal or non-fatal CHD 31
Framingham Anderson 19914 (n=4) Fatal or non-fatal CHD 30
QRISK Hippisley-Cox 20078 (n=2) Fatal CVD 12
PROCAM Assman 200238 (n=1) Fatal or non-fatal CHD 8
Framingham Wolf 199139 (n=2) Fatal or non-fatal stroke 8
Chambless 200340 (n=4) Fatal or non-fatal CHD 7
Friedland 200941 (n=7) Fatal or non-fatal: CHD, myocardial infarction, and stroke; 6
claudication; coronary artery bypass grafting;
percutaneous transluminal coronary angioplasty;
transient ischaemic attack

QRISK Hippisley-Cox 20107 (n=2) Fatal CVD 6

Keys 197242 (n=4) Fatal or non-fatal CHD 6
Leaverton 198743 (n=4) Fatal CHD 6
Asia Pacific cohort studies 200744 (n=4) Fatal CVD 4
Woodward 200745 (n=2) Fatal CVD 4
Levy 199046 (n=4) Fatal or non-fatal CHD 4
Chien 201247 (n=3) Fatal or non-fatal CHD 3
Framingham unspecified† — 32
CHD=coronary heart disease; CVD=cardiovascular disease.
*Number of models developed in this article.
†Authors stated they externally validated the Framingham model without referencing the specific model.

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