SECTION
SECTION 1 ATHEROSCLEROSIS AND ITS PREVENTION
chapter
Assessment of Cardiovascular Risk
F. D. Richard Hobbs
Summary
n Cardiovascular disease is the most important cause of mortality
in the world and by 2020 will be the most common global
cause of death and disability.
n The evidence base on what causes cardiovascular disease and
which interventions reduce cardiovascular risks is one of the
largest in medicine.
n Because cardiovascular disease is multifactorial, the risk factors
coexist in many patients, and these risk factors are variably
additive in their influence on overall risk, identification of
people at highest risk is clinically difficult.
n Identification of people with established cardiovascular
disease is an essential component of good clinical
practice and requires the accurate recording of
established disease, such as angina or peripheral arterial
disease. Such patients warrant immediate interventions.
Increasingly, guidelines advocate similar action in patients
with diabetes.
n Identification of people at risk of cardiovascular disease, but
without current disease, is more difficult and requires the
routine monitoring of blood pressure in adults, occasional
assessment of serum lipid levels, and calculation of overall
cardiovascular disease risk.
n The use of cardiovascular disease risk scores, based on the
observed cardiovascular disease event rates among
well-phenotyped population cohorts followed up for years and
expressing absolute risk during a defined period, is the most
practical method for determining which people without
established cardiovascular disease have most to gain from
interventions.
Cardiovascular disease is the world’s major cause of death,
responsible for one third of total global deaths in 2001. The
World Health Organization predicts that by 2020, with the
rise in cardiovascular disease incidence, coronary heart dis-
ease and stroke will become the most important global
causes of death and disability (Table 4.1).1 In 2001, 80% of
all cardiovascular deaths occurred in developing, low- and
middle-income countries, whereas these countries accounted
for 86% of the total global burden of cardiovascular disease.
The number of people at risk of cardiovascular disease is
rising as average life expectancy increases and social change
leading to increases in vascular risk factors continues, nota-
bly the rapid rise in obesity in children and adolescents2
due to increased calorie intake coupled with increasingly
sedentary lifestyle. Perversely, increased survival and better
secondary prevention in patients suffering cardiovascular
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1
CHAPTER
4
ATHEROSCLEROSIS AND ITS PREVENTION: Assessment of Cardiovascular Risk
events are further increasing overall prevalence of cardiovas-
cular disease.
Long-term follow-up of well-phenotyped population
cohorts provides the best data on the occurrence of cardio-
vascular disease and development of cardiovascular risk fac-
tors over time. The most widely cited of these cohorts
(Table 4.2)3-10 is the Framingham Heart Study.11 These
cohorts also provide data on which of the risk factors are
most strongly correlated with observed cardiovascular out-
comes. The widely agreed methods for assessing future car-
diovascular risk are based on these historical observed risk
and event correlations.
Risk factors for cardiovascular disease may be present in
childhood or early adulthood, but it may be decades before
clinical disease is manifested. Therefore, cardiovascular dis-
ease prevention strategies must encompass early identifica-
tion of patients with individual risk factors coupled with
formal cardiovascular risk assessment to determine the
extent of optimal risk management needed.
RISK FACTORS FOR CARDIOVASCULAR
DISEASE
Risk factors for cardiovascular disease are well established
(Table 4.3). Major nonmodifiable risk factors include family
history of premature cardiovascular disease, age, gender,
and ethnicity. Modifiable risk factors include dyslipidemia—
high levels of low-density lipoprotein (LDL) cholesterol and
triglycerides and low levels of high-density lipoprotein
(HDL) cholesterol (Fig. 4.1); hypertension, especially systolic
elevations (Fig. 4.2); cigarette smoking; and diabetes.11-14
The pivotal data on risk factors came from the Framing-
ham Heart Study,11 initiated in 1948 to identify and evaluate
factors influencing the development of cardiovascular dis-
ease in men and women free of these conditions at the out-
set. In 1971, the Framingham Offspring Study was initiated
in children and spouses of the original cohort to study family
patterns of cardiovascular disease and risk factors. In 2002,
the Third Generation Study began enrolling grandchildren
of the original enrollees. Another important cohort of
healthy men aged 40 to 59 years, the Seven Countries
Study,4 showed that cardiovascular risk is strongly related
to both serum cholesterol and the proportion of saturated
fatty acids in the diet. More recently, the INTERHEART
study10 confirmed that nine potentially modifiable risk
factors (Fig. 4.3) remain strongly associated with the
37
SECTION
TEN LEADING CAUSES OF DEATH AND DISABILITY IN THE WORLD
1
CHAPTER
1990 2020
4
Rank Cause % Rank Cause %
ATHEROSCLEROSIS AND ITS PREVENTION

1 Lower respiratory infections 8.2 1 Ischemic heart disease 5.9

2 Diarrheal diseases 7.2 2 Major depression 5.7
3 Perinatal conditions 6.7 3 Road traffic accidents 5.1
4 Major depression 3.7 4 Cerebrovascular disease 4.4
5 Ischemic heart disease 3.4 5 Chronic obstructive pulmonary disease 4.2
6 Cerebrovascular disease 2.8 6 Lower respiratory infections 3.1
7 Tuberculosis 2.8 7 Tuberculosis 3.0
8 Measles 2.7 8 War 3.0
9 Road traffic accidents 2.5 9 Diarrheal diseases 2.7
10 Congenital abnormalities 2.4 10 Human immunodeficiency virus infection 2.6

From the Global Burden of Disease Project, World Health Organization, 1996.

Table 4.1 Ten leading causes of death and disability in the world.

MAJOR POPULATION-BASED COHORT STUDIES THAT PROVIDE DATA ON THE OCCURRENCE AND DETERMINANTS OF
CARDIOVASCULAR DISEASE

Study Countries Numbers Ethnicity Diabetes Age (yr) Period

Framingham United States 2590 men Mostly white 337 30-74 1948-present
Heart Study3,11 2983 women
SCORE38 11 European 88,080 men European, NA 19-80 2003-present
countries 117,098 women mostly white
Seven Countries Italy, Finland, 11,579 men Mostly white NA 40-59 1957-present
Study4 Greece, Japan,
Netherlands,
United States,
Yugoslavia
United Kingdom United Kingdom 2643 men U.K., All 25-85 NA
Prospective 1897 women mostly white
Diabetes Study27,34
Study of men Sweden 792 men Swedish, NA 54 1963-present
born in 19135 mostly white
Whitehall Study England 17,530 men British, mostly NA 20-64 1967-1977
white
PROCAM6 Germany 10,856 men German, 1205 impaired 36-65 1978-present
mostly white fasting glucose
406 diabetes
MONICA7 Worldwide 10 million men Multiethnic NA 25-64 1980-1995
and women
Cardiovascular United States 5888 men and Mostly white NA 65þ 1989-1999
Health Study8 women
Rotterdam Study9 Netherlands 10,994 men and Mostly white NA 55þ 1990-1999
women
INTERHEART10,50 Worldwide 15,152 cases Multiethnic NA No age 1999-2002
14,820 controls restriction, but
Men and women no ranges

Table 4.2 Major population-based cohort studies that provide data on the occurrence and determinants of cardiovascular disease.

development of a first myocardial infarction by comparing
patients with a first myocardial infarction with asymptomatic
individuals from 52 countries. These risk factors, including
smoking, hypertension, diabetes, dyslipidemia, and obesity,
38 were associated with 90% of the population risk of
myocardial infarction in all ethnic groups and across all geo-
graphic regions.
These risks factors are additive but to variable degrees
(Fig. 4.4) and also cluster in individuals; 80% to 90% of
cardiovascular disease patients have at least one of these

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 SECTION
CARDIOVASCULAR RISK FACTORS
1
CHAPTER
Major Risk Factors
4
Nonmodifiable Modifiable Emerging Risk Factorsa

ATHEROSCLEROSIS AND ITS PREVENTION: Assessment of Cardiovascular Risk

Established cardiovascular diseaseb Cigarette smoking Homocysteine
Age High saturated fat diet C-reactive protein
Male gender Body mass indexc/waist Albuminuria
Family history of premature circumference Coagulation factors (e.g., fibrinogen)
coronary heart disease Physical activity Other lipid factors
Systolic and diastolic (e.g., apolipoproteins)
blood pressure Ankle-brachial index
LDL-cholesterol Carotid artery intima-media thickness (ultrasonography)
HDL-cholesterol Calcifications in the aorta or coronaries (computed
Triglycerides tomographic scanning or other imaging techniques)
Diabetes/blood glucose
Socioeconomic status
Left ventricular mass

*Does not imply direct causality.

a
Value in addition to the major risk factors; clinical practice for assessing absolute cardiovascular risk remains to be established.
b
Includes angina, myocardial infarction, angioplasty, coronary artery bypass grafting, transient ischemic attack, ischemic stroke, or peripheral arterial disease.
c
Body mass index = weight (kg) per length (m)2.

Table 4.3 Cardiovascular risk factors.

Figure 4.1 Age-adjusted coronary heart disease

(CHD) death rate and serum cholesterol in 18
361,662 U.S. men. (From Martin MJ, Hulley SB, 16
6-yr CHD death rate per

Browner WS, Kuller LH, Wentworth D. Serum

14
cholesterol, blood pressure, and mortality:
implications from a cohort of 361,662 men. 12
1000 men

Lancet 1986;2:933-936.) 10
8
6
4
2
0
140 160 180 200 220 240 260 280 300 mg/dL
4 5 6 7 mmol/L
Serum cholesterol

four risk factors (Fig. 4.5),15,16 and each risk factor has a con-
tinuous, dose-dependent impact on cardiovascular disease
risk.17 Treatment of these cardiovascular risk factors reduces
subsequent cardiovascular events, whether coronary heart
disease or stroke.18-23
ASSESSMENT OF CARDIOVASCULAR
RISK IN PEOPLE WITH ESTABLISHED
CARDIOVASCULAR DISEASE
Based on the major epidemiologic studies and intervention
trials, the level of continued risk in people with established
cardiovascular disease (acute coronary syndromes, myocar-
dial infarction, prior revascularization, angina, peripheral
arterial disease, stroke, transient ischemic attack) is suffi-
ciently high to warrant immediate access to the full range
of multiple lifestyle and therapeutic interventions to modify
continued risk. The main challenge to clinicians is the accu-
rate and early recognition of people presenting with
symptoms or signs suggestive of cardiovascular disease. This
requires the formal investigation of symptomatic disease,
such as suspected angina (by assessments such as exercise
electrocardiographic testing and cardiac imaging) and periph-
eral vascular disease (ankle–brachial plexus index), and the
validation of events, such as myocardial infarction or stroke.
Once cardiovascular disease in an individual is established,
there is no need to assess future risk. Immediate prevention
strategies are warranted to control blood pressure, lipids,
and weight to guideline targets, to cease smoking, and to
maintain recommended levels of exercise.
ASSESSMENT OF CARDIOVASCULAR
RISK IN PEOPLE WITH DIABETES
Prospective studies show that cardiovascular risk is two to
five times higher in patients with diabetes than in the popu-
lation at large, but the magnitude of this increased risk
39
depends on diabetes-related factors, notably the time since

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SECTION Figure 4.2 Adjusted relative risk of cardiovascular
1 SBP mortality by systolic blood pressure (SBP) and
CHAPTER diastolic blood pressure (DBP) in men screened for
4 the Multiple Risk Factor Intervention Trial. (From
30 5 the National High Blood Pressure Education Program
ATHEROSCLEROSIS AND ITS PREVENTION

Working Group report on primary prevention of

25

Adjusted relative risk

4 hypertension. Arch Intern Med 1993;153:186.)
20
% of men

3
15
2
10

5 1

0 0
<110 110– 120– 130– 140– 150– 160+
119 129 139 149 159
mm Hg

DBP

30 3

25 2.5

Adjusted relative risk

20 2
% of men

15 1.5

10 1

5 0.5

0 0
<70 70– 75– 80– 85– 90– 95– 100+
74 79 84 89 94 99
mm Hg

diagnosis.24 These observations that diabetes is associated

with high cardiovascular risk25 led U.S., Canadian, and
European guidelines to view diabetes as a “coronary risk
equivalent.” However, a more accurate interpretation of
the evidence is that in people who have suffered diabetes
for some time (perhaps a decade in established diabetic
populations or those with a delay in diagnosis) and in those
with additional cardiovascular risk factors, diabetes repre-
sents a coronary risk equivalent. There is therefore no need
to assess future cardiovascular disease risk formally, and
patients are eligible for secondary prevention strategies
automatically.
There are good pragmatic arguments for supporting this
viewpoint. Diabetes is much more common,26 so secondary
risks are an increasing issue, and crucially, if a cardiovascular
event occurs in a patient with diabetes, it will likely be a
more serious event, whether a stroke or myocardial infarc-
tion, than among nondiabetics. However, when this simple
policy is not supported, cardiovascular disease risk scores
can be used to estimate risk but will underestimate future
risk of events in most patients with established diabetes,
unless adjustment is made or an algorithm incorporating
glycemic levels is used, such as from the United Kingdom
40 Prospective Diabetes Study (UKPDS).27
ASSESSMENT OF CARDIOVASCULAR
RISK IN ASYMPTOMATIC INDIVIDUALS
The assessment of cardiovascular risk in the general popula-
tion is more of a problem because people will not have pre-
sented themselves to clinicians with symptoms or with
events. Cardiovascular risk estimation tools help identify
those at greatest absolute risk of disease to prioritize manage-
ment of those with most to gain. Many countries advocate that
the threshold for considering initiation of pharmacologic inter-
vention should be set, at most, at a 10-year risk of major car-
diovascular events of 20% (or coronary heart disease of
15%) or equivalent. Cardiovascular risk estimation tools are
based on a variety of biometric measures in adults, including
age, gender, smoking status, blood pressure, and lipid ratio
estimation (in all risk scores), and sometimes family history
of cardiovascular disease, glycemia levels, and socioeconomic
status (in some risk scores). The health system challenge is to
develop strategies to collect the requisite information for all
adults, commencing at a certain age and repeating at appropri-
ate intervals. Unfortunately, there are no reliable data to
determine the most cost-effective strategy as to when to start
and how to deliver this function. Methods therefore vary
across countries, although a number of steps are uniform.

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 SECTION
POTENTIALLY MODIFIABLE RISK FACTORS AND MI Men Women 1
FROM THE INTERHEART STUDY
CHAPTER
15152 Cases 14820 Controls in 262 Centers in 52 Countries on 6 Continents 4

ATHEROSCLEROSIS AND ITS PREVENTION: Assessment of Cardiovascular Risk

3
Odds ratio

+1 RF +2 RFs +1 RF +2 RFs
2
26% 25% 27% 24%
1
0
No additional +3 RFs No additional +3 RFs
60 RF 22% RF 20%
40 19% 17%
PAR (%)

20
0
+4 or more RFs +4 or more RFs
−20
8% 12%

l
oB ng

A1

DM

ss

BP

eg

t.

ho
sit

ac
re

/V
i

po

co
ok

Figure 4.5 Presence of additional risk factors (RFs) in

St

Fr

ys
Ob
/A

Al
Sm

Ph
hypertensive patients in the Framingham cohort. (From Kannel
Ap

WB. Risk stratification in hypertension: new insights from the

9 RFs associated with 90% of MI in men and 94% in women Framingham Study. Am J Hypertens 2000;13:3S-10S.)

Figure 4.3 Main risk factors associated with cardiovascular

disease in INTERHEART. BP, blood pressure; DM, diabetes mellitus;
MI, myocardial infarction; PAR, population attributable risk; RFs, risk
factors. (From Yusuf S, Hawken S, Ounpuu S, on behalf of the
INTERHEART Study Investigators. Effect of potentially modifiable risk
factors associated with myocardial infarction in 52 countries [the
INTERHEART study]: case-control study. Lancet 2004;364:937-952.)
Selecting People for Cardiovascular
Risk Assessment
Total population screening is advocated in the U.S. National
Cholesterol Education Program, Adult Treatment Panel III
guidelines,28 which recommend screening for raised blood
pressure and lipids in all adults without cardiovascular disease
every 5 years and with cardiovascular disease every 2 to 3
years. Certain population groups are more likely than others
to be at increased risk, such as older people (especially older
than 65 years), certain ethnic groups (especially South Asians),
and people with a family history of premature cardiovascular
disease. Many of the different country guideline recommenda-
tions prioritize these groups for assessment (Table 4.4). For
example, Canadian guidelines recommend screening of all
men older than 40 years and all women older than 50 years.29
The New Zealand guidelines recommend screening of Maori,
Pacific peoples, and people from the Indian subcontinent 10
years earlier than other population groups.30 The evidence
underlying most of these recommendations is poor, and their
cost-effectiveness has not been evaluated.
A less ambitious alternative is opportunistic case finding of
those at higher cardiovascular risk through formal risk esti-
mation only in all those who have the detected presence of
any single cardiovascular disease risk factor, however so
detected. The European31 and U.K.32 guidelines emphasize
such opportunistic cardiovascular risk assessment in patients
with any cardiovascular risk factor but also stress the need to
screen close relatives of patients with early cardiovascular
disease (men < 55 years, women < 65 years) and families
with inherited dyslipidemia.
Measuring Cardiovascular Risk Factors
Once a patient has been identified for assessment, a compre-
hensive risk assessment should be carried out, involving

Figure 4.4 Additive effect of

multiple risk factors from the
Framingham cohort. BP, blood 60 60.2
pressure; LVH on ECG, left
50
8-year probability

ventricular hypertrophy on
electrocardiogram. (From Anderson
(per 1000)

40
KM, Castelli WP, Levy D. Cholesterol 34.6
and mortality. 30 years of follow-up 30
from the Framingham study. JAMA 23.2
1987;257:2176-2180.) 20

10 3.9
0
Cholesterol, mg/dL 185↔335 185↔335 185↔335 185↔335
(mmol/L) (4.8↔8.7) (4.8↔8.7) (4.8↔8.7) (4.8↔8.7)
Glucose intolerance 0 + + +
Systolic BP, mm Hg 105 195 195 195
Cigarettes 0 0 + +
LVH on ECG 0 0 0 +
41

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SECTION
RECOMMENDED GUIDELINE CRITERIA FOR USE OF CARDIOVASCULAR RISK ASSESSMENT IN INDIVIDUALS WITHOUT
1 CARDIOVASCULAR DISEASE
CHAPTER
4 Subgroup Canada Europe New Zealand United States
ATHEROSCLEROSIS AND ITS PREVENTION

People without cardiovascular All >40/>50 yr — All >45/>55 yr All >20 yr

disease or known risk factors (men/women) (men/women) (men/women)
People with known All with 1þ risk factor, All with diabetes, multiple risk factors, All >35/>45 yr All >20 yr
cardiovascular risk factors diabetes, or evidence of or family history of premature (men/women) (men/women)
atherosclerosis cardiovascular disease with known risk
factors or a high
risk of diabetes
Ethnic groups Maori, Pacific — — All >35/>45 yr —
peoples, and people from the (men/women)
Indian subcontinent

The International and Australian guidelines do not provide any clearly defined guidance on selecting people for risk assessment.

Table 4.4 Recommended guideline criteria for use of cardiovascular risk assessment in individuals without cardiovascular disease.

measurement of all major risk indicators (Table 4.5), because RISK INDICATORS TYPICALLY MEASURED AND RECORDED IN
the magnitude of cardiovascular risk is determined by the ASSESSING CARDIOVASCULAR RISK
synergistic effect of the combined risk factors.
The assessment of people with diabetes differs between Age
the guidelines. For example, diabetes is not listed in the cal- Gender
culations of the American National Cholesterol Education Ethnicity*
Program and the Canadian guidelines, as people with diabe- Smoking history
tes are categorized as coronary heart disease equivalents.33 Lipid profile (note: fasting is unnecessary for total cholesterol or
Most other guidelines consider diabetes a risk factor and HDL-cholesterol level)
include it in the risk assessment. The New Zealand guide- Fasting plasma glucose concentration/diabetes
lines, for example, make a 5% 5-year cardiovascular risk
Blood pressure
adjustment to patients with diabetes diagnosed more than
Family history of premature cardiovascular disease
10 years, in addition to the weighting given to diabetes in
the Framingham-based risk score.30 Only the UKPDS risk Body mass index/waist circumference
score34 requires measurement of blood glucose concentration Presence of left ventricular hypertrophy
for inclusion in the algorithm.
*Not all guidelines take ethnicity into account in assessing risk.
Most guidelines now recognize the “metabolic syndrome,”
in which clustering of cardiovascular risk indicators is asso-
Table 4.5 Risk indicators typically measured and recorded in
ciated with increased risk of a cardiovascular event.35 Three assessing cardiovascular risk.
or more of the five risk factors (all continuous variables that
have been arbitrarily dichotomized) are required for a diag-
nosis of metabolic syndrome according to the U.S. National CLINICAL IDENTIFICATION OF THE METABOLIC SYNDROME,
Cholesterol Education Program criteria (Table 4.6). How- ACCORDING TO THE NATIONAL CHOLESTEROL EDUCATION
ever, identification of metabolic syndrome is not formally PROGRAM
incorporated into any of the risk calculators, and currently,
Risk Factor Defining Level
none of the guidelines suggest automatic adjustment for the
metabolic syndrome in the calculated cardiovascular risk. Abdominal obesity Waist circumference
Its measurement is therefore mainly as a guide to clinicians Men 102 cm*
to intensify attainment of treatment goals or to consider Women 88 cm*
intervention for individuals who would otherwise be Triglycerides 1.7 mmol/L
assessed to have intermediate risk (most likely the young). HDL-cholesterol
In addition, certain emerging risk factors and measures of Men <1.0 mmol/L
subclinical atherosclerosis (see Table 4.3) may be used as Women <1.3 mmol/L
adjuncts to the major risk factors in assessing risk, although Blood pressure 130/85 mm Hg
data on their added value in determining the absolute risk Fasting glucose 6.1 mmol/L{
of cardiovascular disease are limited. Assessment of these risk
indicators should be limited to special circumstances in which *New Zealand guidelines30 recommend levels of 100 cm and 90 cm for men
and women, respectively.
the decision to intervene is uncertain on the basis of standard {
Canadian guidelines29 recommend levels of 6.2-7.0 mmol/L.
risk factors. Only the U.S. National Cholesterol Education
Program guidelines33 advocate vascular imaging or measure- Table 4.6 Clinical identification of the metabolic syndrome,
42 ment of high-sensitivity C-reactive protein in these cases. according to the National Cholesterol Education Program.

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Assessment of Cardiovascular Risk outcome data from large population cohorts, of which the most SECTION

Level by Use of Risk Calculators widely used are based on the Framingham Heart Study (see 1
Because cardiovascular risk assessment in individual patients Table 4.1), although it may overestimate risk in some popula- CHAPTER

tions. The European Systematic Coronary Risk Evaluation 4

is complicated by the interaction of multiple risk factors, a
(SCORE) charts38 were created to address the perceived limita-

ATHEROSCLEROSIS AND ITS PREVENTION: Assessment of Cardiovascular Risk

number of risk calculators have been developed (Table 4.7)
and are recommended in guidelines. Although there is some tions of the Framingham Heart Study.39 SCORE is based on
variation between the different calculators,36,37 the majority asymptomatic individuals from 12 European cohort studies with
are based on logistic regression (or similar) equations based no evidence of preexisting cardiovascular disease. Studies across
on the observed associations between risk factors and events multiple countries enabled charts to be drawn up for high- and
in the various population cohorts. The calculators estimate low-risk countries, and because atherosclerotic cardiovascular
an individual’s risk of experiencing a cardiovascular event disease mortality was the endpoint, these charts may provide
during a given time, usually 10 or 5 years. This time period more accurate estimates of overall cardiovascular risk.
as well as the specific outcome (either fatal or the combination However, major differences in risk estimation are observed
of fatal and nonfatal coronary heart disease or cardiovascular when populations are assessed by use of different risk
disease) varies between calculators. In most guidelines, the calculators,40-42 hence the trend for more risk-scoring algo-
risk determined is categorized as high, intermediate, and rithms using data from the population in which the algorithm
low risk (Table 4.8). Higher risk demands more intensive will be used, as is the case for SCORE,38 ASSIGN,43 the Italian
intervention and stricter treatment goals. Risk Charts,44 PROCAM,45,46 and QRISK.47 Some of these
Cardiovascular risk estimation can be performed with use of more recent algorithms may benefit from the inclusion of addi-
any of the risk calculator tools that are based on observational tional risk factors into the equation. For example, the Scottish
Intercollegiate Guidelines Network (SIGN) developed its own
risk-scoring tool (ASSIGN)43 to address two risks omitted in
LIST OF RISK CALCULATORS INCORPORATED INTO
most risk-scoring algorithms—social deprivation and family his-
CARDIOVASCULAR GUIDELINES
tory. Social deprivation refers to low-income populations who
Framingham may have limited access to health care and health education
and whose cardiovascular disease risk is underestimated by the
Australia National Heart Foundation of Australia and the
Framingham Heart Study.48,49 In ASSIGN, social deprivation
Cardiac Society of Australia and New Zealand:
Lipid Management Guidelines is estimated by region with use of the Scottish Index of Multiple
Deprivation. QRISK also accounts for social deprivation,47
Canada Working Group on Hypercholesterolemia and
Other Dyslipidemias developed from a cohort of 1.28 million patients in the United
Kingdom between the ages of 35 and 74 years and who were
New Zealand The New Zealand Guidelines Group, the National
Heart Foundation of New Zealand, and the Stroke free of diabetes or cardiovascular disease at the time of enroll-
Foundation of New Zealand ment. Data on the first diagnosis of cardiovascular disease,
United States Third Report of the National Cholesterol including myocardial infarction, coronary heart disease, stroke,
Education Program and transient ischemic attack, were available for 8.2 million per-
International International Atherosclerosis Society son-years of observation. QRISK shares many common para-
meters with other risk-scoring algorithms, including age, total
SCORE cholesterol/HDL-cholesterol ratio, systolic blood pressure, body
mass index, family history of early-onset cardiovascular disease,
Europe Third Joint European Task Force
and smoking status, but includes the Townsend score, a surro-
PROCAM gate measure of social deprivation that is based on geographic
region. Cardiovascular risk calculators are available as risk
International International Atherosclerosis Society
charts (Figs. 4.6 to 4.9) and downloadable computer-assisted
Table 4.7 List of risk calculators incorporated into cardiovascular
algorithms (Table 4.9) to assist office-based assessment of
guidelines. patients.

RISK CATEGORIES ACCORDING TO DIFFERENT GUIDELINES

Risk Per Year (%)

Guideline Outcomes* High Moderate-Intermediate Low

Australia Fatal and nonfatal CVD risk >3
Canada Fatal and nonfatal CHD risk >2 1-2 <1
Europe Fatal CVD risk 0.5 <0.5
New Zealand Fatal and nonfatal CVD risk >3 2-3 <2
United States Fatal and nonfatal CHD risk >2 1-2 <1
International Fatal and nonfatal CHD risk >2 1-2 <1

*Fatal or the combination of fatal and nonfatal coronary heart disease (CHD) or cardiovascular disease (CVD). 43
Table 4.8 Risk categories according to different guidelines.

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SECTION
1 ATP III: FRAMINGHAM POINT SCORES ESTIMATE OF 10-YEAR RISK FOR MEN
CHAPTER
4
1 3 SBP If If 5 Age Age Age Age Age
ATHEROSCLEROSIS AND ITS PREVENTION

Age Points mm Hg untreated treated 20–39 40–49 50–59 60–69 70–79

20–34 –9 <120 0 0 Nonsmoker 0 0 0 0 0
35–39 –4 120–129 0 1 Smoker 8 5 3 1 1
40–44 0 130–139 1 2
45–49 3 140–159 1 2 6 Point 10-year
50–54 6 ≥160 2 3 total risk, %
55–59 8
60–64 10 4 <0 <1
65–69 11 HDL 0 1
70–74 12 mg/dL Points 1 1
75–79 13 ≥60 –1 2 1
50–59 0 3 1
40–49 1 4 1
<40 2 5 2
6 2
7 3
2 Age Age Age Age Age 8 4
TC 20–39 40–49 50–59 60–69 70–79 9 5
<160 0 0 0 0 0 10 6
160–199 4 3 2 1 0 11 8
200–239 7 5 3 1 0 12 10
240–279 9 6 4 2 1 13 12
≥280 11 8 5 3 1 14 16
15 20
HDL = high-density lipoprotein 16 25
Expert panel on detection, evaluation, and treatment of high
≥17 ≥30
blood cholesterol in adults. JAMA. 2001;285:2486–2497.

Age 30–34 35–39 40–44 45–49 50–54 55–59 60–64 65–69 70–74 Absolute Absolute Color key for
(Low-risk risk risk‡ relative risk
level)* (2%) (3%) (3%) (4%) (5%) (7%) (8%) (10%) (13%)
Green
Total Total
Points† CHD‡ CHD¶
Below
0 1.0 2% 2% average risk
1 1.5 1.0 1.0 3% 2%
2 2.0 1.3 1.3 1.0 4% 3% Blue
3 2.5 1.7 1.7 1.3 1.0 5% 4%
4 3.5 2.3 2.3 1.8 1.4 1.0 7% 5% Average risk
5 4.0 2.6 2.6 2.0 1.6 1.1 1.0 8% 6%
6 5.0 3.3 3.3 2.5 2.0 1.4 1.3 1.0 10% 7%
7 6.5 4.3 4.3 3.3 2.6 1.9 1.6 1.3 1.0 13% 9% Yellow
8 8.0 5.3 5.3 4.0 3.2 2.3 2.0 1.6 1.2 16% 13%
Moderately above
9 10.0 6.7 6.7 5.0 4.0 2.9 2.5 2.0 1.5 20% 16%
average risk
10 12.5 8.3 8.3 6.3 5.0 3.6 3.1 2.5 1.9 25% 20%
11 15.5 10.3 10.3 7.8 6.1 4.4 3.9 3.1 2.3 31% 25% Red
12 18.5 12.3 12.3 9.3 7.4 5.2 4.6 3.7 2.8 37% 30%
13 22.5 15.0 15.0 11.3 9.0 6.4 5.6 4.5 3.5 45% 35% High
> 14 26.5 > 17.7 > 17.7 > 13.3 > 10.6 > 7.6 > 6.6 > 5.3 > 4.1 > 53% > 45% risk

* Low absolute risk level = 10-year risk for total CHD endpoints for a person the same age, BP <120/<80 mm Hg, TC 160–199 mg/dL,
HDL cholesterol ≥45 mg/dL, nonsmoker, no diabetes. Percentages show 10-year absolute risk for total CHD endpoints.
† Framingham points.
‡ 10-year absolute risk for total CHD endpoints estimated from Framingham data corresponding to Framingham points.
¶ 10-year absolute risk for hard CHD endpoints approximated from Framingham data corresponding to Framingham points.

Figure 4.6 U.S. National Cholesterol Education Program Adult Treatment Panel III (ATP III) algorithm to estimate 10-year
coronary heart disease risk. CHD, coronary heart disease; SBP, systolic blood pressure; TC, total cholesterol. (From Expert Panel
on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the
National Cholesterol Education Program [NCEP] Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol
in Adults [Adult Treatment Panel III]. JAMA 2001;285:2486-2497; and Grundy SM, Pasternak R, Greenland P, Smith S Jr, Fuster V.
Assessment of cardiovascular risk by use of multiple-risk-factor assessment equations: a statement for healthcare professionals
from the American Heart Association and the American College of Cardiology. Circulation 1999;100:1481-1492.)

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 10-YEAR RISK OF FATAL CVD IN 10-YEAR RISK OF FATAL CVD IN
POPULATIONS AT HIGH CVD RISK POPULATIONS AT LOW CVD RISK

Women Men Women Men

Non-smoker Smoker Age Non-smoker Smoker Non-smoker Smoker Age Non-smoker Smoker

180 7 8 9 10 12 13 15 17 19 22 14 16 19 22 26 26 30 35 41 47 180 4 5 6 6 7 9 9 11 12 14 8 9 10 12 14 15 17 20 23 26
160 5 5 6 7 8 9 10 12 13 16 9 11 13 15 16 18 21 25 29 34 160 3 3 4 4 5 6 6 7 8 10 5 6 7 8 10 10 12 14 16 19
65 65
140 3 3 4 5 6 6 7 8 9 11 6 8 9 11 13 13 15 17 20 24 140 2 2 2 3 3 4 4 5 6 7 4 4 5 6 7 7 8 9 11 13
120 2 2 3 3 4 4 5 5 6 7 4 5 6 7 9 9 10 12 14 17 120 1 1 2 2 2 2 3 3 4 5 2 3 3 4 5 5 5 6 8 9

180 4 4 5 6 7 8 9 10 11 13 9 11 13 15 18 18 21 24 28 33 180 3 3 3 4 4 5 5 6 7 8 5 6 7 8 9 10 11 13 15 16
160 3 3 3 4 5 5 6 7 8 9 6 7 9 10 12 12 14 17 20 24 160 2 2 2 2 3 3 4 4 5 5 3 4 5 5 6 7 8 9 11 13
60 60
140 2 2 2 3 3 3 4 5 5 6 4 5 6 7 9 8 10 12 14 17 140 1 1 1 2 2 2 2 3 3 4 2 3 3 4 4 5 5 6 7 9

SCORE project. Eur Heart J 2003;24:987-1003.)

120 1 1 2 2 2 2 3 3 4 4 3 3 4 5 6 6 7 8 10 12 120 1 1 1 1 1 1 2 2 2 3 2 2 2 3 3 3 4 4 5 6

180 2 2 3 3 4 4 5 5 6 7 6 7 8 10 12 12 13 16 19 22 180 1 1 2 2 2 3 3 3 4 4 3 4 4 5 6 6 7 8 10 12
160 1 2 2 2 3 3 3 4 4 5 4 5 6 7 8 8 9 11 13 16 160 1 1 1 1 1 2 2 2 3 3 2 2 3 3 4 4 5 6 7 8
55 55
140 1 1 1 1 2 2 2 2 3 3 3 3 4 5 6 5 6 8 9 11 140 1 1 1 1 1 1 1 1 2 2 1 2 2 2 3 3 3 4 5 6
120 1 1 1 1 1 1 1 2 2 2 2 2 3 3 4 4 4 5 6 8 120 0 0 1 1 1 1 1 1 1 1 1 1 1 2 2 2 2 3 3 4

Systolic blood pressure

Systolic blood pressure
180 1 1 1 2 2 2 2 3 3 4 4 4 5 6 7 7 8 10 12 14 180 1 1 1 1 1 1 1 2 2 2 2 2 3 3 4 4 4 5 6 7
160 1 1 1 1 1 1 2 2 2 3 2 3 3 4 5 5 6 7 8 10 160 0 0 1 1 1 1 1 1 1 1 1 1 2 2 2 2 3 3 4 5
50 50
140 0 1 1 1 1 1 1 1 1 2 2 2 2 3 3 3 4 5 6 7 140 0 0 0 0 0 1 1 1 1 1 1 1 1 1 2 2 2 2 3 3
120 0 0 1 1 1 1 1 1 1 1 1 1 2 2 2 2 3 3 4 5 120 0 0 0 0 0 0 0 0 1 1 1 1 1 1 1 1 1 2 2 2

180 0 0 0 0 0 0 0 0 1 1 1 1 1 2 2 2 2 3 3 4 180 0 0 0 0 0 0 0 0 0 0 0 1 1 1 1 1 1 1 2 2
160 0 0 0 0 0 0 0 0 0 0 1 1 1 1 1 1 2 2 2 3 160 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 1 1 1 1 1
40 40
140 0 0 0 0 0 0 0 0 0 0 0 1 1 1 1 1 1 1 2 2 140 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 1 1
120 0 0 0 0 0 0 0 0 0 0 0 0 1 1 1 1 1 1 1 1 120 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1

4 5 6 7 8 4 5 6 7 8 4 5 6 7 8 4 5 6 7 8 4 5 6 7 8 4 5 6 7 8 4 5 6 7 8 4 5 6 7 8
Cholesterol mmol 150 200250300 Cholesterol mmol 150 200250300
mg/dL mg/dL

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SCORE 15% and over 10%–14% 5%–9% 3%–4% 2% 1% < 1%

(From Conroy RM, Pyorala K, Fitzgerald AP, et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the
Figure 4.7 SCORE risk charts in high-risk and low-risk regions based on total cholesterol. CVD, cardiovascular disease.
45
4
1

ATHEROSCLEROSIS AND ITS PREVENTION: Assessment of Cardiovascular Risk

SECTION

CHAPTER
SECTION Figure 4.8 Regions of Europe with low and high
1 EUROPE cardiovascular disease risk.
CHAPTER
4
ATHEROSCLEROSIS AND ITS PREVENTION

H
H
H H
H
H H
H
H H
H H
H H
L H
H H
H
L L H
H H H
H H
L H
L H
H H
L H
L

H High - risk country L Low - risk country

Whatever the limitations of scores in terms of precision,
there is strong trial evidence that patients derive significant
vascular gains from treatment of coronary heart disease
10-year risk levels down to as low as 6%. Therefore, even
if scores overestimate risk, a threshold for intervention set
at 20% 10-year risk remains well above the levels for which
evidence of benefit is established.
SUMMARY
Cardiovascular disease is the most important cause of death
and disability in the world but encompasses the strongest
evidence base on which health professionals can base their
interventions to modify risk. It is therefore essential that clin-
icians determine those who have most to gain from interven-
tion, which requires the early and accurate recognition of
those with established disease, for secondary prevention,
and the assessment of cardiovascular risk in those without
apparent disease, for primary prevention. However, for pri-
mary prevention of cardiovascular disease, although there
is considerable evidence on what to do, in terms of which
risk factors are important and how to reduce their impact,
the major limitation is how to efficiently identify those indi-
viduals who are at most risk.

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 SECTION
RISK LEVEL WOMEN 1
CHAPTER
4
No diabetes Diabetes

ATHEROSCLEROSIS AND ITS PREVENTION: Assessment of Cardiovascular Risk

Non-smoker Smoker Age Non-smoker Smoker
4 5 6 7 8 4 5 6 7 8 4 5 6 7 8 4 5 6 7 8
180/105 180/105
160/95 160/95
70
140/85 140/85
120/75 120/75

180/105 180/105
Blood pressure (mm Hg)

Blood pressure (mm Hg)

160/95 60 160/95
140/85 140/85
120/75 120/75

180/105 180/105
160/95 160/95
50
140/85 140/85
120/75 120/75

180/105 180/105
160/95 160/95
40
140/85 140/85
120/75 120/75
4 5 6 7 8 4 5 6 7 8 4 5 6 7 8 4 5 6 7 8
Total cholesterol:HDL ratio Total cholesterol:HDL ratio
Risk level (for women and men)
5-year cardiovascular disease (CVD) risk (fatal and no−fatal)

>30% High 15–20% 5–10%

Very high 25–30% Moderate 10–15% Mild 2.5–5%
20–25% <2.5%

How to use the charts

• Identify the chart relating to the person’s sex, diabetic status, smoking history, and age.
• Within the chart, choose the cell nearest to the person’s age, blood pressure (BP), and total
cholesterol (TC) :HDL ratio. When the systolic and diastolic values fall in different risk levels,
the higher category applies.
• For example, the lower left cell contains all non-smokers without diabetes who are younger than
45 years and have a TC:HDL ratio of less than 4.5 and a BP of less than 130/80 mm Hg.
People who fall exactly on a threshold between cells are placed in the cell indicating higher risk.
A
Figure 4.9 Risk assessment charts from the New Zealand guidelines, based on the Framingham
algorithm. A, Risk level in women. B, Risk level in men. (From Assessment and Management
of Cardiovascular Risk. Available at: http://www.nzgg.org.nz/index.cfm?fuseaction=fuseaction_
10&fusesubaction=docs&documentid=22. Accessed December 2007.)
(Continued)

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SECTION
1 RISK LEVEL MEN
CHAPTER
4
No diabetes Diabetes
ATHEROSCLEROSIS AND ITS PREVENTION

Non-smoker Smoker Age Non-smoker Smoker

4 5 6 7 8 4 5 6 7 8 4 5 6 7 8 4 5 6 7 8
180/105 180/105
160/95 160/95
70
140/85 140/85
120/75 120/75

180/105 180/105
Blood pressure (mm Hg)

Blood pressure (mm Hg)

160/95 60 160/95
140/85 140/85
120/75 120/75

180/105 180/105
160/95 160/95
50
140/85 140/85
120/75 120/75

180/105 180/105
160/95 160/95
40
140/85 140/85
120/75 120/75
4 5 6 7 8 4 5 6 7 8 4 5 6 7 8 4 5 6 7 8
Total cholesterol:HDL ratio Total cholesterol:HDL ratio

Risk level: Benefits: NNT for 5 years to prevent one event

5-year CVD (CVD events prevented per 100 people treated for 5 years)
risk (fatal and
nonfatal) 1 intervention 2 interventions 3 interventions
(25% risk reduction) (45% risk reduction) (55% risk reduction)

30% 13 (7.5 per 100) 7 (14 per 100) 6 (16 per 100)

20% 20 (5 per 100) 11 (9 per 100) 9 (11 per 100)

15% 27 (4 per 100) 15 (7 per 100) 12 (8 per 100)

10% 40 (2.5 per 100) 22 (4.5 per 100) 18 (5.5 per 100)

5% 80 (1.25 per 100) 44 (2.25 per 100) 36 (3 per 100)

Based on the conservative estimate that each intervention — aspirin, BP treatment (lowering systolic BP by 10 mm Hg),
or lipid modification (lowering LDL-C by 20%) — reduces cardiovascular risk by about 25% over 5 years.

Note: Cardiovascular events are defined as myocardial infarction, new angina, ischemic stroke, transient
ischemic attack (TIA), peripheral vascular disease, congestive heart failure, and cardiovascular-related death.

NNT = Number needed to treat

B
Figure 4.9—cont’d

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 SECTION
CARDIOVASCULAR RISK CALCULATORS AVAILABLE ON-LINE
1
CHAPTER
Framingham
4
Adapted by National Cholesterol Education Program, Adult

ATHEROSCLEROSIS AND ITS PREVENTION: Assessment of Cardiovascular Risk

Treatment Panel III
n Risk calculator: http://hin.nhlbi.nih.gov/atpiii/calculator.asp?
usertype=prof (on-line version)
n Risk calculator: http://hin.nhlbi.nih.gov/atpiii/riskcalc.htm
(downloadable version)
n Risk calculator spreadsheet: http://www.nhlbi.nih.gov/guide-
lines/cholesterol/risk_tbl.htm
Adapted by New Zealand Guidelines Group
n Risk tables: http://www.nzgg.org.nz/guidelines/0035/
CARDIOVASCULAR DISEASE_Risk_Chart.pdf

SCORE

n SCORE risk charts: http://www.escardio.org/initiatives/

prevention/SCOREþRiskþCharts.htm
n HeartScore: http://www.escardio.org/knowledge/decision_tools/
heartscore/ProgramþDownload.htm

PROCAM

n Risk calculator: http://chdrisk.uni-muenster.de/calculator.php?

iSprache=1&iVersion=1&iSiVersion=0
n Risk score: http://chdrisk.uni-muenster.de/risk.php?
iSprache=1&iVersion=1&iSiVersion=0
n PROCAM Neuronal Network Analysis: http://chdrisk.uni-
muenster.de/n_network.php?
iSprache=1&iVersion=1&iSiVersion=0

United Kingdom Prospective Diabetes Study

n UKPDS Risk Engine: http://www.dtu.ox.ac.uk/index.html?

maindoc=/ukpds/

Table 4.9 Cardiovascular risk calculators available on-line.

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