Coronary Heart Disease Part I: Pathophysiology and Risk
., Stefanakis, M1., Douda, H2.
1Department of Life & Health Sciences, University of Nicosia, 46, Makedonitissas Avenue,
Nicosia, 1700, Cyprus
2Department of Physical Education and Sport Science, Democritus University of Thrace,
University Campus, 69100 Komotini, Greece
Cardiovascular diseases are the leading cause of disability globally and despite the
advances in clinical care and medicine, continue to be the principal cause of morbidity and
mortality. The process of this chronic inflammatory condition is initiated early in life by
various risk factors. Atherosclerosis is believed to have the main role in the pathogenesis
of cardiovascular diseases which involve large and medium sized arteries. Acute coronary
events frequently arise and the priority is the re-opening of the occluded artery which will
limit the progression of injury. Despite the advances in cardiac surgery, several
complications may occur post-surgery. The first part of this article will review the
pathophysiology and risk factors of coronary heart disease and the preoperative and
postoperative pulmonary complications. The second part will describe the role of
physiotherapy in the management of Coronary Heart Disease.
Keywords: Coronary heart disease; anatomy; pathophysiology; acute coronary
syndromes; risk factors.
Cardiovascular Diseases (CVD) are growing radically with an estimation of 12 million
people dying each year, mainly in the developing countries (World Health Organisation,
2013). As the burden of CVD growths, coronary heart disease (CHD) is becoming the
main cause of cardiac surgery worldwide (Go et al., 2013). Current understanding of the
pathophysiological basis of myocardial ischemia is derived from experimental
observations that coronary artery narrowing limits coronary blood flow (Gould, Lipscomb
& Hamilton, 1974). Understanding these profound mechanisms of disease can help health
care professionals identify and treat CVD and prevent potentially complications (Dokken,
2008). This article reviews the pathophysiology and the risk factors of CHD, thus; the preoperative and post-operative complications of coronary artery bypass graft (CABG).
2 Anatomy of coronary arteries
Coronary arteries are composed by three layers: the tunica intima, tunica media, and
tunica adventitia. The tunica intima, which is the innermost layer of the artery, is composed
of the endothelium, which acts as the interface between the artery and the blood, and the
sub-endothelial layer of connective tissue. The tunica adventitia is mainly composed of
collagen fibers, interlaced with bands of elastic fibers. The collagen fibers help to construct
a rigid sheath around the artery and restrain the volume of the vessel (Humphrey &
McCulloch 2003). The tunica media contains layers of vascular smooth muscle cells
Themistocleous, I.-C. et al.
interspersed in a network of connective tissue and its main role is to produce
vasoconstriction or vasodilation of the artery through the contraction or relaxation of the
vascular smooth muscle cells (Humphrey & McCulloch 2003).
3 Coronary heart disease
CHD is affecting the coronary arteries, which are supplying oxygenated blood to the
cardiac muscle. CHD encompasses atherosclerotic plaques within the coronary arteries,
resulting in the stenosis of the artery. Blood flow to the heart is supplied by the right and
left coronary arteries, which provide blood on the corresponding side of the heart. Each
coronary artery branches into additional arteries, which are responsible to supply with
oxygenated blood a specific area of the cardiac tissue. Stenosis and reduced blood supply
via any of these arterial segments may have harmful effects on the cardiac muscle and
lead to a myocardial infarction (MI) (Libby & Theroux, 2005).
4 Risk factors for coronary heart disease
The risk factors of CHD have been divided into non-modifiable and modifiable (Levy 1981).
The non-modifiable risk factors include: age, male sex, and family history which cannot be
altered. According to the American Heart Association [AHA] (2009), the modifiable risk
factors which can be altered by medical and lifestyle interventions are: hypertension,
hypercholesterolemia, physical inactivity, diabetes, overweight, obesity and tobacco
smoking. Mora et al. (2007) stated that changes in the modifiable risk factors account for
approximately 60% of the risk reduction.
Figure 1. Coronary heart disease risk factors (Adapted from Boudi, 2014).
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5 Pathophysiology of coronary heart disease
CHD mainly occurs due to atherosclerosis and its progression is associated with
environmental and genetic factors (Sayols-Baixeras, Lluís-Ganella, Lucas, Elosua, 2014).
Atherosclerosis is a chronic process, characterized by progressive accumulation of lipids,
fibrous elements, and inflammatory molecules in the walls of the large arteries (Glass &
Witztum, 2001; Lusis, Mar & Pajukanta, 2004; Sanz, Moreno & Fuster, 2012).
Atherosclerosis starts with the efflux of low density lipoprotein (LDL) cholesterol to the
sub-endothelial space, which can be changed and oxidized by various agents.
Oxidized/modified LDL particles are powerful chemotactic molecules that prompt
expression of vascular cell adhesion molecules and intercellular adhesion molecules at
the surface of endothelium, and stimulate monocyte adhesion and migration to the subendothelial space (Sayols-Baixeras et al., 2014). Monocytes transform into macrophages
in the intima media. Macrophages enchain oxidized LDL thru scavenger receptors to
become foam cells (Glass & Witztum, 2001) and release pro inflammatory cytokines
including interleukins and tumor necrosis factor.
The development of fatty streak which foam cells appear in the sub-endothelial space
it is the final result of this process (Sayols-Baixeras et al., 2014). Moreover, in the subendothelial space accumulate other forms of leukocytes, including lymphocytes and mast
cells (Libby, Ridker & Hansson, 2011). The interaction between monocytes, macrophages,
foam cells and T-cells induce a cellular and humoral immune response (inflammatory
cascade) with the production of several pro inflammatory molecules such as interleukin-6
(IL-6) and tumor necrosis factor (TNF-α) (Libby, 2012; Witztum & Lichtman, 2013).
Figure 2. Pathogenesis of atherosclerosis (Modified from Encyclopedia Britannica
The process continues with the migration of smooth muscle cells from the medial layer
of the artery into the intima, following of fatty streak to a more complex lesion (Glass &
Witztum, 2001). As soon as smooth muscle cells are in the intima media, they produce
Themistocleous, I.-C. et al.
extracellular matrix molecules that are developing a fibrous cap which is covering the initial
fatty streak. Inside the fibrous cap the foam cells die, therefore release lipids that collect
in the extracellular space, forming a lipid-rich pool (necrotic core) (Tabas, 2010). This
process results in the formation of the second atherosclerotic lesion, the fibrous plaque
(Sayols-Baixeras et al., 2014). Sakakura et al. (2013) stated that the thickness of the
fibrous cap is important for the integration of the atherosclerotic plaque. The extrusion of
this type of plaque into the lumen of the artery generates a limitation of flow, well known
as stenosis, which is causing ischemia to the tissue and is expressed clinically as stable
angina. Moreover, vulnerable plaques composed of a thin fibrous cap made mostly of type
I collagen along with no or few smooth muscle cells, but abun¬dant macrophages and pro
inflammatory and pro thrombotic molecules leading to atheroma (Sakakura et al., 2013;
Witztum & Lichtman, 2013).
Two types of plaque can be defined: stable and unstable or vulnerable, based on the
balance between formation and degradation of fibrous cap (Sayols-Baixeras et al., 2014).
Stable plaques have an intact, thickset fibrous cap synthesized of smooth muscle cells in
a matrix rich in type I and III collagen (Finn, Nakano, Narula, Kolodgie & Virmani, 2010).
Vulnerable plaques are likely to break, revealing the core of the plaque to circulating
coagulation proteins, causing thrombosis, sudden artery lumen occlusion and therefore
an acute coronary syndrome. Moreover, intraplaque hemorrhage is also a potential factor
for the progression of atherosclerosis, (Sakakura et al., 2013; Witztum & Lichtman, 2013),
which occur when the vasa vasorum invades the intima from the adventitia (Doyle &
Caplice, 2007). Following the diagnosis of acute coronary syndrome the priority is the reopening of the occluded artery which will limit the progression of injury.Patients can
undergo a percutaneous coronary intervention (PCI) or to a coronary artery bypass graft
surgery (CABG) (Antman et al., 2004; Hamm et al., 2011).
Despite the advances in cardiac surgery, several complications may occur postsurgery. This review will focus on the postoperative pulmonary complications (PPC).
6 Post-surgery complications
PPC such as atelectasis, bronchospasm and tracheobronchitis can adversely affect
patient’s condition and may lead to the development of respiratory failure, pulmonary
embolism, post-surgery pneumonia, empyema, pneumothorax, acute lung injury, acute
respiratory distress syndrome (ARDS), or the need for mechanical ventilation beyond 48
hours’ post-surgery (Grooms, 2012). These complications demand carefully individualized
strategies to prevent and restore the functional residual capacity (FRC) and patient’s
ability to mobilize (Grooms, 2012). Procedure related factors are more important than
patient related factors in predicting the risk of PPCs (Rudra & Das, 2006). Table 1
summarizes the related risk factors and Table 2 the perioperative pulmonary physiology
after thoracic and upper abdominal surgery.
Table 1. Related risk factors
Patient-related factors Procedure-related factors
• General health and nutritional status • Surgical site
Age >65 years Upper abdominal
Low albumin Thoracic surgery
Weight loss >10% • Surgery technique
Open versus lamparascopic
• Neurological status
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History of CVA • Other type of surgery
• Fluid status Peripheral vascular surgery
CHF history Neurosurgery
Blood Urea nitrogen • General anasthesia
• Immune status • Duration of surgery >3hours
Chronic steroid use
Alcochol use • Emergerncy surgery
• Type of nuromascular blockage
• Chronic lung disease
Presence of productive cough • Not using nuroaxial blockade
• Cigarete smoking • Pain control with peripheral
Current or within 8 weeks Narcotics vs epidural
• ASA class >2
• Nasogastric tube
Body mass index >27.5 Kgm2
• Abnormal chest radiograph
Abbreviations: CVA: Cerebrovascular accident, CHF: Chronic Heart Failure, ASA: American
Society of Anesthesiologists classification. Based on Rudra & Das, 2006.
7 Preoperative risk factors
According to Rudra and Das (2006), the pre-operative status of the patient can be a reason
for the post-operative complications. Moreover, are stated some other risk factors
regarding the operation.
7.1 Respiratory status
Patients with abnormal respiratory findings, such as: wheezing, rales, rhonchi, prolonged
expiration, and decreased breath sounds are 6 times more likely to develop a
complication, nonetheless the risk differs with the severity of the findings (Eagle et al.,
A significant preoperative risk factor is cigarette smoking, which is often reffered as
causative factor of chronic lung disease (Jayr, Matthay, Goldstone, Gold & WienerKronish, 1993; Bluman, Mosca, Newman & Simon, 1998). Reduction of smoking will
decrease bronchial irritation and eliminate the stimulus for coughing (Bluman et al., 1998).
Smoking cessation for 48 hours before surgery reduces cough and lowers airway
pathogens, decreases the levels of carboxyhemoglobin to normal, eliminates the stimulant
effect of nicotine on cardiovascular system, and improves respiratory cilliary beating
(Rudra & Das, 2006). According to Warner et al. (1989), patients who stopped smoking
for 2 months or less had 4 times higher rate of pulmonary complications, in contrast to
those who stopped for more than 2 months (57.1% versus 14.5%).
Themistocleous, I.-C. et al.
While Strandberg, Tokics, Brismar, Lundquist and Hedenstiena (1987) found a weak
correlation between obesity [calculated by Broca’s index: weight (kg)/ (height in cm-100)]
and the area of lung densities seen directly after induction of anesthesia; other authors
reported that obesity is still a concern for health care professionals. Morbidly obese
individuals have a lower FRC, increased alveolar arterial oxygenation gradient and higher
intra-abdominal pressure (Rudra & Das, 2006). Eichenberger et al. (2002), stated that in
morbidly obese individuals, atelectasis continues for at least 24 hours in contrast to nonobese individuals where atelectasis disappears. Pelosi et al. (1997) reported that the
different mechanics of the respiratory system and the hypoxia which can be found in
morbidly obese individuals can be explained by the reduced lung volume and by the
increased intra-abdominal pressure.
8 Neurological status
Patients with previous stroke and impaired sensorium who are less mobile, have higher
risk of atelectasis post-surgery. Moreover, they are unable to protect their airway leading
to risk of pneumonia and respiratory failure (Arozullah, Daley, Henderson, Khuri, &
National Veterans Administration Surgical Quality Improvement Program, 2000;
Arozullah, Conde & Lawrence, 2003).
8.1 Immune status
Alcohol within 2 weeks of surgery increases odds of pneumonia and respiratory failure by
20% (Rudra & Das, 2006). Moreover, alcohol in longer-term may be related with
diminished B-cell mediated immunity leading to a greater risk of pneumonia. In addition,
patients with diabetes mellitus have a slightly increased risk for respiratory failure
(Arozullah et al., 2003).
9 Procedure related risk factors
9.1 Surgery related
The most important factor for the prediction of the overall risk of PPCs is the site of surgery.
The rate of complication is related to the distance of the incision from the diaphragm
(Rudra & Das, 2006). A decreased post-surgery vital capacity which leads to a
ventilation/perfusion (V/Q) mismatch and leads to development of hypoxemia is detected
in patients that undergo an upper abdominal and thoracic surgery (Rudra & Das, 2006).
Moreover, several studies show thoracic surgeries have a higher rate of complications
in contrast to lower abdominal due to diaphragmatic dysfunction (Dureuil, Viires,
Cantineau, Aubier & Desmonts, 1986; Mohr & Jett, 1988; Arozullah et al., 2000). Surgical
trauma may enlarge airway reactivity, which can be explained by the exposure to airway
irritants (Rock, Freed, Nyhan & Murray, 1995).
9.2 Anesthesia related
The supine posture under anesthesia during surgery modifies the lung volumes, causing
impairment of respiratory muscles function, alterations in lung mechanics related to gas
exchange, and impairment of mucocilliary clearance mechanisms (Rudra & Das, 2006).
The duration of anesthesia also influences the outcome post-surgery. Evidence suggest
that longer surgeries lasting more than 3-4 hours are associated with a higher risk of
pulmonary complications (Celli, Rodrigue & Snider, 1984; Brooks-Brunn, 1997). Rudra
and Das (2006) stated that “after general anesthesia, residual effect of intravenous or
Journal of Physical Activity, Nutrition and Rehabilitation, 2017
inhalational anesthetics blunt the ventilatory responses to both hypercarbia and
hypoxemia. Sedatives augment depression from opioids and anesthetics and might
directly depress ventilation”. These may lead to airway obstruction, micro aspiration, and
ultimately atelectasis, bronchitis and pneumonia (Rudra & Das, 2006).
Table 2. The perioperative pulmonary physiology after thoracic surgery.
• Reduction in vital capacity by 50% to 60% and reduction in functional residual capacity by 30%
• Diaphragmatic dysfunction secondary to reflex inhibition after surgery when viscera are
handled close to the diaphragm
• Pain and splinting
• Atelectasis and pneumonia
• Impaired gas exchange and pneumonia
• Impairment of cough and mucocilliary clearance
Based on Rudra and Das (2006)
As a conclusion, our understanding of CHD has increased rapidly and current
treatments, for this common and troublesome condition is usually offered if coronary
events appear. Despite the advances in cardiac surgery, several complications may
present post operation. Understanding the multiple effects that general anesthesia and
procedure and patients related factors has on the respiratory system is essential, as these
problems extend into the postoperative period and can be a reason for complications.
These complications may affect patients’ quality of life or even cause death.
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Coronary Heart Disease Coronary Heart Disease
Coronary heart disease (CHD), also called
coronary artery disease, is the leading cause
of death in the United States for both men
and women. CHD occurs when plaque builds up
inside the coronary arteries. These arteries supply
your heart muscle with oxygen-rich blood.
Plaque is made up of fat, cholesterol, calcium, and
other substances found in the blood. Over time,
plaque hardens and narrows the arteries, reducing
blood flow to your heart muscle.
Eventually, an area of plaque can rupture, causing
a blood clot to form on the surface of the plaque.
If the clot becomes large enough, it can mostly or
completely block the flow of oxygen-rich blood
to the part of the heart muscle fed by the artery.
This can lead to angina or a heart attack.
Angina is chest pain or discomfort that occurs
when not enough oxygen-rich blood is flowing
to an area of your heart muscle. Angina may feel
like pressure or squeezing in your chest. The pain
also may occur in your shoulders, arms, neck, jaw,
A heart attack occurs when blood flow to an area
of your heart muscle is completely blocked. This
prevents oxygen-rich blood from reaching that
area of heart muscle, causing it to die. Without
quick treatment, a heart attack can lead to serious
problems or death.
Over time, CHD can weaken the heart muscle
and lead to heart failure and arrhythmias. Heart
failure is a condition in which your heart can’t
pump enough blood throughout your body.
Arrhythmias are problems with the rate or rhythm
of your heartbeat.
Causes and Risk Factors
Research suggests that CHD starts when certain
factors damage the inner layers of the coronary
arteries. These factors include smoking, high
amounts of certain fats and cholesterol in the
blood, high blood pressure, and high amounts
of sugar in the blood due to insulin resistance or
When damage occurs, your body starts a healing process. This process causes plaque to build
up where the arteries are damaged. The buildup
of plaque in the coronary arteries may start in
Certain traits, conditions, or habits raise your risk
for CHD. These conditions are known as risk factors. The major risk factors for CHD include:
• Unhealthy blood cholesterol levels
• High blood pressure
• Insulin resistance
• Overweight or obesity
• Metabolic syndrome
• Lack of physical activity
• Age (as you get older, your risk for CHD
• Family history of early heart disease
Lifestyle changes, medicines, and/or medical procedures can prevent or treat CHD in most people.
Treatment and Prevention
Taking action to control your risk factors can help
prevent or delay CHD. Your chance of developing
CHD goes up with the number of risk factors you
For some people, lifestyle changes may be the only
treatment needed. Lifestyle changes include following a heart healthy diet, doing physical activity
regularly, maintaining a healthy weight, quitting
smoking, and reducing stress.
You may need medicines to treat CHD if
lifestyle changes aren’t enough. Medicines can
help control CHD risk factors and relieve CHD
symptoms. Some people who have CHD also
need a medical procedure to treat the disease.
Angioplasty and coronary artery bypass grafting
are two procedures used to treat CHD.
If you’ve been diagnosed with CHD, see your doctor for ongoing care. Follow your treatment plan
and take all medicines as your doctor prescribes.
Call your doctor if you have new or worsening
More information about CHD is available from
the National Heart, Lung, and Blood Institute
(NHLBI) Web site at www.nhlbi.nih.gov (under
Health Information for the Public). Podcasts,
videos, and Spanish-language articles also can
be found in the online Diseases and Conditions
Index at www.nhlbi.nih.gov/health/dci.
You also can order or download information on
heart disease from the NHLBI Web site or by
calling the NHLBI Health Information Center at
301–592–8573 (TTY: 240–629–3255).
Want More Information?
These NHLBI publications will help you take charge of your heart health!
Your Guide to a Healthy Heart (#06-5269)
This booklet provides up-to-date information and
practical tips about establishing and maintaining
a heart healthy lifestyle, including understanding
the risk factors for heart disease, determining
your risk, and establishing a plan for heart
In Brief: Your Guide to a
Healthy Heart (#06-5715)
Critical messages from
“Your Guide to a Healthy
Heart” are provided in this
easy-to-read fact sheet.
Also of interest:
• Your Guide to Living Well With Heart Disease (#06-5270)
This easy-to-read booklet for people who have heart disease
suggests ways to protect and improve heart health—providing
information on heart disease screening, risk factors, and treatments.
• In Brief: Your Guide to Living Well With Heart Dise
Background, scope and purpose of the guidelines
Of an estimated 58 million deaths globally from all causes in 2005, cardiovascular disease (CVD)
accounted for 30%. This proportion is equal to that due to infectious diseases, nutritional defi ciencies,
and maternal and perinatal conditions combined (1). It is important to recognize that a substantial proportion of these deaths (46%) were of people under 70 years of age, in the more productive period of
life; in addition, 79% of the disease burden attributed to cardiovascular disease is in this age group (2).
Between 2006 and 2015, deaths due to noncommunicable diseases (half of which will be due to
cardiovascular disease) are expected to increase by 17%, while deaths from infectious diseases,
nutritional defi ciencies, and maternal and perinatal conditions combined are projected to decline
by 3% (1). Almost half the disease burden in low- and middle-income countries is already due to
noncommunicable diseases (3).
A signifi cant proportion of this morbidity and mortality could be prevented through populationbased strategies, and by making cost-effective interventions accessible and affordable, both for
people with established disease and for those at high risk of developing disease (3–5).
To address the rising burden of noncommunicable diseases, in May 2000 the 53rd World Health
Assembly adopted the WHO Global Strategy for the Prevention and Control of Noncommunicable
Diseases (6). In doing so, it placed noncommunicable diseases on the global public health agenda.
Since then, WHO has strengthened its efforts to promote population-wide primary prevention
of noncommunicable diseases, through the Framework Convention on Tobacco Control (7) and
the Global Strategy for Diet, Physical Activity and Health (8). These activities target common
risk factors that are shared by CVD, cancer, diabetes and chronic respiratory disease, and their
implementation is critical if the growing burden of noncommunicable diseases is to be controlled.
These measures should make it easier for healthy people to remain healthy, and for those with
established CVD or at high cardiovascular risk to change their behaviour. However, populationwide public health approaches alone will not have an immediate tangible impact on cardiovascular
morbidity and mortality, and will have only a modest absolute impact on the disease burden (3,
4). By themselves they cannot help the millions of individuals at high risk of developing CVD
(Table 1) or with an established CVD. A combination of population-wide strategies and strategies
targeted at high risk individuals is needed to reduce the cardiovascular disease burden. The extent
to which one strategy should be emphasized over the other depends on achievable effectiveness,
as well as cost-effectiveness and availability of resources (1–4).
Although CVD already places a signifi cant economic burden on low- and middle-income countries (9), the resources available for its management in these countries are limited because of
competing health priorities. It is, nevertheless, essential to recognize that the transition to lower
levels of infectious diseases and higher levels of noncommunicable diseases is already under way;
failure to act now will result in large increases in avoidable CVD, placing serious pressures on the
national economies (10–12). In this context, it is imperative to target the limited resources on
those who are most likely to benefi t. Thus, as envisioned in the Global Strategy for the Prevention
Effect of three preventive strategies on deaths from coronary heart disease over 10 years in
Canadians aged 20–74 years*
Strategy No. (%) of
% of treated population by 10-year
risk of death (% of risk group treated)
No of deaths avoided a
1–10% >10% Over 10
Per 100 000
12 300 000
5 160 42
1 590 000
35 800 290
1 370 000
15 500 125
Assuming 100% community effectiveness for the single risk factor and high baseline risk strategies, and a 2% total cholesterol
reduction for the Rose strategy.
* Source: ref. 4.
and Control of Noncommunicable Diseases (6), one of the major tasks for WHO and its Member
States is to scale up cost-effective, integrated approaches for prevention of CVD.
This document provides guidance to policy-makers and health care workers on how to target individuals at high risk of developing CVD, at all levels of the health system and in different resource
settings, using evidence-based and cost-effective preventive approaches. The objective is to reduce
the incidence of heart attacks, strokes, and renal failure associated with hypertension and diabetes,
as well as the need for amputation of limbs because of ischaemia, by reducing the cardiovascular
risk. The focus is prevention of disability and early deaths and improvement of quality of life. This
document should be considered as a framework, which can be adapted to suit different political,
economic, social, cultural and medical circumstances.
Interpretation and implications of
recommendations (13, 14)
The recommendations included here provide guidance on appropriate care. As far as possible,
these are based on clear evidence that allows a robust understanding of the benefi ts, tolerability, harms and costs of alternative patterns of care. They are also feasible in different health care
Recommendations can be defi ned as being strong when it is certain that their application will
do more good than harm or that the net benefi ts are worth the costs. In this guide, such recommendations include the word “recommend” or “should”. Strong recommendations apply to most
patients in most circumstances, and can be adopted as policy in most situations.
4 Prevention of cardiovascular disease
Recommendations can be defi ned as weak when it is uncertain that their application will do more
good than harm or that the net benefi ts are worth the costs. In this guide, such recommendations
include the words “suggest” or “should probably”. In applying weak recommendations, clinicians
need to take into account each individual patient’s circumstances, preferences and values. Policymaking related to weak recommendations requires substantial debate and the involvement of a
range of stakeholders.
Development of the guidelines
This guide was developed on the basis of the total risk approach to prevention of cardiovascular disease, elaborated in the World Health Report 2002 (2). Development of the risk prediction
charts started in 2003, followed by preparations for the development of this guide in 2004, using
an evidence-based methodology.
Published data related to primary prevention of cardiovascular disease were collated from existing guidelines, and by searching the Cochrane Library, Embase Medline, the trials register of the
International Society for Hypertension (ISH), and the British Medical Journal clinical effectiveness reviews. Recent papers known to members of the Guideline Development Group (GDG) (see
Annex 6), but not yet in a database or registry, were also included.
All references directly related to key issues dealt with in the guide were further evaluated for
quality, using a Scottish Intercollegiate Guideline Network (SIGN) methodology checklist (13).
Evidence-based reviews were prepared, based on data from good quality publications, and circulated to the GDG for input. They were further discussed at a consultation of the GDG in November 2005, with particular focus on the strength and applicability of the evidence to low-resource
settings. Tables were compiled, summarizing the available scientifi c evidence to address key issues
related to primary prevention. Evidence was graded and recommendations developed. SIGN and
GRADE (Grades of Recommendation, Assessment, Development and Evaluation) systems were
used to rate the evidence and grade the recommendations (13, 14).
A draft guide, prepared by the writing committee (see Annex 6), was circulated to the GDG for
feedback. A revised draft was then sent for peer review (see Annex 7 for a list of reviewers). The
present version of the guide refl ects input from peer reviewers.
PART 1 The total risk approach to prevention of cardiovascular disease 5
The total risk approach
to prevention of
6 Prevention of cardiovascular disease
Rationale for targeting high-risk groups
The debilitating and often fatal complications of cardiovascular disease (CVD) are usually seen in
middle-aged or elderly men and women. However, atherosclerosis – the main pathological process
leading to coronary artery disease, cerebral artery disease and peripheral artery disease – begins
early in life and progresses gradually through adolescence and early adulthood (15–17). It is
usually asymptomatic for a long period.
The rate of progression of atherosclerosis is infl uenced by cardiovascular risk factors: tobacco use,
an unhealthy diet and physical inactivity (which together result in obesity), elevated blood pressure (hypertension), abnormal blood lipids (dyslipidaemia) and elevated blood glucose (diabetes).
Continuing exposure to these risk factors leads to further progression of atherosclerosis, resulting
in unstable atherosclerotic plaques, narrowing of blood vessels and obstruction of blood fl ow to
vital organs, such as the heart and the brain. The clinical manifestations of these diseases include
angina, myocardial infarction, transient cerebral ischaemic attacks and strokes. Given this continuum of risk exposure and disease, the division of prevention of cardiovascular disease into
primary, secondary and tertiary prevention is arbitrary, but may be useful for development of
services by different parts of the health care system. The concept of a specifi c threshold for hypertension and hyperlipidaemia is also based on an arbitrary dichotomy.
The document provides evidence-based recommendations on how to assess and manage individuals with asymptomatic atherosclerosis, on the basis of their estimated total, or absolute, CVD
risk. Total CVD risk is defi ned as the probability of an individual’s experiencing a CVD event (e.g.
myocardial infarction or stroke) over a given period of time, for example 10 years.
Total CVD risk depends on the individual’s particular risk factor profi le, sex and age; it will be
higher for older men with several risk factors than for younger women with few risk factors. The
total risk of developing cardiovascular disease is determined by the combined effect of cardiovascular risk factors, which commonly coexist and act multiplicatively. An individual with several
mildly raised risk factors may be at a higher total risk of CVD than someone with just one elevated
Timely and sustained lifestyle interventions and, when needed, drug treatment will reduce the
risk of CVD events, such as heart attacks and strokes, in people with a high total risk of CVD, and
hence will reduce premature morbidity, mortality and disability. Many people are unaware of their
risk status; opportunistic and other forms of screening by health care providers are therefore a
potentially useful means of detecting risk factors, such as raised blood pressure, abnormal blood
lipids and blood glucose (18).
The predicted risk of an individual can be a useful guide for making clinical decisions on the
intensity of preventive interventions: when dietary advice should be strict and specifi c, when suggestions for physical activity should be intensifi ed and individualized, and when and which drugs
should be prescribed to control risk factors. Such a risk stratifi cation approach is particularly
suitable to settings with limited resources, where saving the greatest number of lives at lowest cost
becomes imperative (19).
In patients with a systolic blood pressure above 150 mmHg, or a diastolic pressure above
90 mmHg, or a blood cholesterol level over 5.0 mmol/l, drug treatment reduces the relative risk
of cardiovascular events by between one-quarter and one-third (20–27). If blood pressure was
PART 1 The total risk approach to prevention of cardiovascular disease 7
reduced by 10–15 mmHg (systolic) and 5–8 mmHg (diastolic) and blood cholesterol by about
20% through combined treatment with antihypertensives and statins, then cardiovascular disease
morbidity and mortality would be reduced by up to 50% (28). People at very high CVD risk
would benefi t more, in terms of number of events avoided, because the relative risk reduction
would be applied to a higher baseline risk (29). Therefore, targeting patients with a high risk is the
fi rst priority in a risk stratifi cation approach.
As the cost of medicines is a signifi cant component of total preventive health care costs, it is
particularly important to base drug treatment decisions on an individual’s risk level, and not on
arbitrary criteria, such as ability to pay, or on blanket preventive strategies. In addition, guidelines
based on total risk of CVD, which use risk scoring methods, have been shown to be both less
expensive and more effective than guidelines based on single risk factor levels (30). Thus the use
of guidelines based on risk stratifi cation might be expected to free up resources for other competing priorities, especially in developing countries.
It should be noted that patients who already have symptoms of atherosclerosis, such as angina or
intermittent claudication, or who have had a myocardial infarction, transient ischaemic attack, or
stroke are at very high risk of coronary, cerebral and peripheral vascular events and death. These
people are the top priority in clinical practice for prevention efforts. Risk stratifi cation charts are
unnecessary to arrive at treatment decisions for these categories of patients. They require both
lifestyle and pharmacological interventions to help them to quit using tobacco, eat a healthy
diet, increase physical activity, and manage their weight, blood pressure, blood lipids and blood
glucose, as elaborated in other WHO guidelines and documents (5, 18).
The vast majority of the evidence on the benefi ts and potential harm of interventions to reduce
CVD risk comes from high-income countries. The limited observational epidemiological data from
low- and middle-income countries, recently extended by the Interheart case-control study (31),
support the view that cardiovascular risk factors are equally predictive of CVD events in a wide
range of low-, middle- and high-income countries. Thus, it seems reasonable to assume that the
evidence related to lowering risk factors is also applicable to people in different settings.
Complementary strategies for prevention
and control of cardiovascular disease
In all populations it is essential that the high-risk approach elaborated in this document is complemented by population-wide public health strategies (Figure 1) (11). Although cardiovascular
events are less likely to occur in people with low levels of risk, no level of risk can be considered
“safe” (32). Without population-wide public health prevention efforts, CVD events will continue
to occur in people with low and moderate levels of risk, who are the majority in any population.
Furthermore, public health approaches can effectively slow down the development of atherosclerosis (and also reduce the incidence of some cancers and chronic respiratory diseases) in
young people, thereby reducing the likelihood of future epidemics of CVD, such as were seen in
1960–1990 in most high-income countries. Population-wide strategies will also support lifestyle
modifi cation in those at high risk. The extent to which one strategy is emphasized over the other
depends on achievable effectiveness, cost-effectiveness and resource considerations.
8 Prevention of cardiovascular disease
0 5 10 15 20
25 30 35 40
A combination of population-wide and high-risk strategies are required to reduce the cardiovascular
disease risk distribution of the population (to shift the cardiovascular risk distribution to the left)
source: ref. 11
Threshold for interventions
The appropriate threshold of an individual’s total risk at which intensive lifestyle interventions
and drug treatment are initiated depends on the availability of resources and the impact of specifi c
interventions. The cost-effectiveness of pharmacological treatment for high blood pressure and
blood cholesterol depends on the total cardiovascular risk of the individual before treatment
(29–33); long-term drug treatment is justifi ed only in high-risk individuals. If resources allow, the
target population can be expanded to include those with moderate levels of risk; however, lowering the threshold for treatment will increase not only the benefi ts but also the costs and potential
harm. People with low levels of risk will benefi t from population-based public health strategies
and, if resources allow, professional assistance to make behavioural changes.
Ministries of health have the diffi cult task of setting a risk threshold for treatment that balances
the health care resources in the public sector, the wishes of clinicians, and the expectations of the
public. For example, in England, a 30% risk of developing coronary heart disease over a 10-year
period was defi ned as “high risk” by the National Service Framework for coronary heart disease
(34). This threshold would apply to about 3% of men in the population aged between 45 and
75 years. When the cardiovascular risk threshold was lowered to 20% (equivalent to a coronary
heart disease risk of 15%), a further 16% of men were considered “high risk” and therefore eligible
for drug treatments.
Ministries of health or health insurance organizations may wish to set the cut-off points to match
resources, as shown below for illust
PART 1 The total risk approach to prevention of cardiovascular disease 9
10-year total CVD risk thresholds for intensive intervention:
high-resource setting: 20%
medium-resource setting: 30%
low-resource setting: 40%
As the threshold for intervention is lowered, the number of individuals eligible to benefi t increases,
but so do the costs and the number of adverse events caused by drug treatments. In a state-funded
health system, the government and its health advisers are often faced with making decisions about
the threshold at which drug and other interventions are affordable. In many health care systems,
such decisions must be made by individual patients and their medical practitioners, on the basis
of a careful appraisal of the potential benefi ts, hazards and costs involved.
Adoption of a high (40%) threshold for 10-year CVD risk in a population might seem economical;
however, this would deny most of the population the opportunity to prevent or at least delay a fi rst
cardiovascular event. Countries that use a risk stratifi cation approach have tended to reduce the
threshold of risk used to determine treatment decisions as the costs of drugs, particularly statins,
have fallen and as adequate coverage of the population at the higher risk level has been achieved.
In low-income countries, lowering the threshold below 40% may not be feasible because of
resource limitations. Nevertheless, use of risk stratifi cation approaches will ensure that treatment
decisions are transparent and logical, rather than determined by arbitrary factors or promotional
activity of pharmaceutical companies.
Table 2 shows the percentage of the population, by age and sex, with a ten-year total CVD risk of
30% or more in each of the 14 WHO subregions. The countries included in each subregion are
listed in Annex 1 (2). For data on all risk categories, see Annex 2.
Risk prediction charts: Strengths and limitations
Use of risk prediction charts to estimate total cardiovascular risk is a major advance on the
older practice of identifying and treating individual risk factors, such as raised blood pressure
(hypertension) and raised blood cholesterol (hypercholesterolemia). Since there is a continuous
relationship between these risk factors and cardiovascular risk the concept of hypertension and
hyperlipidemia introduces an arbitrary dichotomy.
The total risk approach acknowledges that many cardiovascular risk factors tend to appear in clusters; combining risk factors to predict total cardiovascular risk is consequently a logical approach to
deciding who should receive treatment. Many techniques for assessing the cardio vascular risk status
of individual patients have been described (35–40). Most of these techniques use risk prediction
equations derived from various sources, most commonly the Framingham Heart Study (35, 41–46).
The risk charts and tables produced use different age categories, duration of risk assessment
and risk factor profi les. The current New Zealand (43) and Joint British Societies charts (40, 41)
are similar in concept. The former assess the fi ve-year risk for all cardiovascular disease in eight
discrete categories, while the latter assess the ten-year risk of CVD in three age categories. Risk scores
have different accuracy in different populations, tending to overpredict in low-risk populations and
underpredict in high-risk populations. Risk scores using the Framingham equations have been widely
tested in North American and European populations of European origin (38, 45–47), and validated
10 Prevention of cardiovascular disease
in a Chinese population (48), but not in other populations. The European Guidelines on CVD prevention use a new model for total risk estimation based on the SCORE (Systematic Coronary Risk
Evaluation) system (37). The risk charts based on the SCORE study are derived from a large dataset of
prospective European studies (37). The risk estimation is based on sex, age, smoking, systolic blood
pressure, and either total cholesterol (TC) or the ratio of total cholesterol to high-density lipoprotein
cholesterol (HDL-C). SCORE predicts only the likelihood of fatal CVD events, unlike the risk scores
based on the Framingham equations. The threshold for high risk is defi ned as a risk of death of 5% or
greater, instead of the composite fatal and non-fatal coronary endpoint of 20%.
The evidence that underpins the use of risk factor scoring and management comes from a range of
sources. There is now increasing evidence that cardiovascular risk factors are associated with clinical
The percentage of the population, by age and sex, with a ten-year CVD risk of 30% or more,
14 WHO subregions
Age group (years)
Age group (years)
<50 50–59 60–69 70+ <50 50–59 60–69 70+
African Region: D 0.32% 1.98% 11.15% 13.30% 0.04% 1.10% 8.78% 24.45%
African Region: E 1.26% 1.87% 4.05% 3.84% 0.37% 1.34% 2.43% 3.93%
Region of the
0.85% 8.40% 31.77% 54.23% 0.24% 3.13% 14.38% 31.59%
Region of the
0.43% 5.42% 19.24% 23.25% 0.31% 4.23% 12.95% 25.28%
Region of the
0.08% 2.25% 5.62% 12.36% 0.28% 1.62% 4.36% 18.65%
0.13% 4.53% 25.32% 36.64% 0.09% 5.98% 24.08% 49.01%
0.19% 4.65% 18.73% 38.46% 0.16% 2.60% 15.49% 39.91%
European Region: A 0.15% 2.77% 16.13% 37.83% 0.05% 0.32% 2.79% 20.69%
European Region: B 0.88% 8.94% 28.12% 41.93% 0.46% 1.92% 10.79% 22.77%
European Region: C 1.31% 13.70% 40.29% 58.69% 0.50% 3.16% 22.48% 51.89%
0.37% 4.13% 10.23% 13.54% 0.22% 2.02% 9.32% 13.29%
0.47% 5.12% 22.23% 31.39% 0.22% 3.31% 19.23% 29.75%
Western Pacifi c
0.35% 2.63% 12.32% 26.41% 0.05% 0.61% 2.20% 8.92%
Western Pacifi c
0.16% 3.78% 15.06% 21.63% 0.10% 1.99% 6.74% 15.28%
PART 1 The total risk approach to prevention of cardiovascular disease 11
events in a similar way in a wide range of countries (31). There is also strong epidemiological evidence
that combining risk factors into scores is capable of predicting an individual’s total cardiovascular risk
with reasonable accuracy. Finally, there is strong evidence from clinical trials that reducing the levels of
risk factors has benefi cial effects. Risk factor scoring and management have now been widely taken up
in cardiovascular prevention guidelines in most high-income countries (36, 41, 43, 44).
The risk factors included in current scoring systems are drawn from those used in the original
Framingham score. There is currently debate about the inclusion of newer risk factors, such as
C-reactive protein, fi brinogen, and waist–hip ratio (49). It is possible that, as more epidemiological data become available for low- and middle-income countries, a new generation of risk scoring
systems may emerge that have greater predictive accuracy.
Older age and male sex are powerful determinants of risk; consequently, it has been argued that
the use of the risk stratifi cation approach will favour treatment of elderly people and men, at the
expense of younger people with several risk factors and women. For example, a non-smoking
40-year-old man with a systolic blood pressure of 150 mmHg and a TC/ HDL-C ratio of 6 has a
15% risk of a cardiovascular event over the next 10 years; this would classify him as low risk. A
65-year-old man with the same systolic blood pressure and TC/HDL-C ratio has a 10-year CVD
risk of over 30%, classifying him as high risk and eligible for drug treatment. If benefi t is measured in terms of potential years of life gained, rather than simply CVD events avoided, a case
can be made for starting drug treatments among younger people. However, while younger people
gain more life years if they have a non-fatal event, older people are a lot more likely to die from
an event. When discounting is taken into consideration, the quality adjusted life years gained by
preventing events in young people are very similar to those gained in old people (Table 3) (50).
Concern about the metabolic syndrome, characterized by central obesity, elevated blood pressure,
dyslipidaemia, and insulin resistance (51, 52), has raised the question of whether identifying people
with this syndrome should be a priority. While there are different defi nitions of the syndrome, proposed by WHO and other organizations (53–58), people with this combination of risk factors are at
increased risk of developing coronary heart disease, stroke, and diabetes (59, 60), and have a worse
Effect of discounting and 30-day case-fatality on life years lost after a cardiovascular disease
event in men*
Age (years) Average life
discounted at 3%
per year (years)
30-day case fatality after a major
CVD eventa (%)
life-years lost after a
CVD event, attributable to 30-day case
80 6 · 8 6 · 2 60 3 · 7
70 12 · 2 10 · 3 50 5 · 2
60 19 · 2 14 · 8 40 5 · 9
50 27 · 6 18 · 9 30 5 · 7
40 36 · 8 22 · 4 25 5 · 6
Coronary heart disease case-fatality used as a proxy for cardiovascular disease case-fatality
(note that the model does not account for morbidity after a cardiovascular disease event).
* Source: ref. 50.
12 Prevention of cardiovascular disease
prognosis after myocardial infarction (61, 62). There is, as yet, insuffi cient evidence to justify using
metabolic syndrome as an additional risk prediction tool (63, 64). However, the proposed WHO
risk prediction charts should be used for people with the syndrome, to predict their total cardiovascular risk and implement appropriate management. It has been argued recently that the CVD
risk associated with the metabolic syndrome is nothing more than the sum of the risks of its individual components. Furthermore, in constructing the metabolic syndrome, risk factors that have a
graded relation to CVD are reduced into two very broad categories using arbitrary cut-off points;
thus, much information related to the risk prediction is lost. People with metabolic syndrome
would, in any case, benefi t from weight reduction, higher levels of activity (65–71), lowering of
blood pressure, avoidance of drugs that tend to cause hyperglycaemia (72–75), lowering of cholesterol with a statin (76–80), and reduction of hyperglycaemia with metformin. There is insuffi cient
evidence from randomized trials to support more specifi c management of dyslipidaemias (81).
In summary, the great strength of the risk scoring approach is that it provides a rational means
of making decisions about intervening in a targeted way, thereby making best use of resources
available to reduce cardiovascular risk. Alternative approaches focused on single risk factors, or
concepts such as pre-hypertension or pre-diabetes, have been popular in the past, often because
they represented the interests of specifi c groups in the medical profession and professional societies. Such an approach, however, leads to a very large segment of the population being labelled as
high risk, most of them incorrectly. If health care resources were allocated to such false-positive
individuals, a large number of truly high-risk individuals would remain without medical attention.
Risk scoring moves the focus of treatment from the management of individual risk factors to the
best means of reducing an individual’s overall risk of disease. It enables the intensity of interventions to be matched to the degree of total risk (Figure 2).
Further research is required to validate existing subregional risk prediction charts for individual
populations at national and local levels, and to confi rm that the use of risk stratifi cation methods in
low- and middle-income countries results in benefi ts for both patients and the health care system.
Intensity of interventions should be proportional to the total cardiovascular risk
PART 1 The total risk approach to prevention of cardiovascular disease 13
The WHO/ISH cardiovascular risk prediction charts
Examples of WHO/ISH cardiovascular risk prediction charts, are shown in Annexes 3 and 4.
Annex 1 provides specifi c information on the countries in each WHO subregion. Risk prediction charts for each WHO subregion (and country) are available with the pocket version of these
These charts are intended to allow the introduction of the total risk stratifi cation approach for
management of cardiovascular disease, particularly where cohort data and resources are not
readily available for development of population-specifi c charts. The charts have been generated
from the best available data, using a modelling approach (Annex 5), with age, sex, smoking, blood
pressure, blood cholesterol, and presence of diabetes as clinical entry points for overall management of cardiovascular risk.
Some studies have suggested that diabetic patients have a high cardiovascular risk, similar to
that of patients with established cardiovascular disease, and so do not need to be risk-assessed.
However, some people with diabetes, particularly younger patients and those who are newly
diagnosed, have low or moderate total CVD risk. In addition, in people with diabetes, there is no
gender difference in the risk of coronary heart disease and stroke (82). Therefore, separate charts
have been developed for assessment of cardiovascular risk in patients with type 2 diabetes.
In many low-resource settings, there are no facilities for cholesterol assay, although it is often
feasible to check urine sugar as a surrogate measure for diabetes. Annex 4 therefore contains risk
prediction charts that do not use cholesterol, but only age, sex, smoking, systolic blood pressure,
and presence or absence of diabetes to predict cardiovascular risk.
Obesity, abdominal obesity (high waist–hip ratio), physical inactivity, low socioeconomic position,
and a family history of premature cardiovascular disease (cardiovascular disease in a fi rst-degree
relative before the age of 55 years for men and 65 years for women) can all modify cardiovascular
risk. These risk factors are not included in the charts, which may therefore underestimate actual
risk in people with these characteristics. The risk charts also do not include other risk factors,
such as low HDL-C, elevated triglycerides, left ventricular hypertrophy, raised serum creatinine,
albuminuria, C-reactive protein, hyperuricaemia and fi brinogen. While including these risk factors
in risk stratifi cation would improve risk prediction in most populations, the increased gain would
not usually be large, and does not warrant waiting to develop and validate further risk stratifi cation tools. Nevertheless, these (and other) risk factors may be important for risk prediction, and
some of them may be causal factors that should be managed. Clinicians should, as in any situation, use their clinical acumen to examine the individual’s lifestyle, preferences and expectations,
and use this information to tailor a management programme.
The risk prediction charts and the accompanying recommendations can be used by health care
professionals to match the intensity of risk factor management with the likelihood of cardiovascular disease events. The charts can also be used to explain to patients the likely impact of
interventions on their individual risk of developing cardiovascular disease. This approach may
motivate patients to change their behaviour. The use of charts will help health care professionals to
focus their limited time on those who stand to benefi t the most.
It should be noted that the risk predictions are based on epidemiological data from groups of
people, rather than on clinical practice. This means that the measures of blood pressure and blood
14 Prevention of cardiovascular disease
cholesterol may have been assessed only once rather than repeatedly, as is normal in clinical practice. However, these objections do not detract from their potential to bring much-needed coherence to the clinical dilemmas of how to apply evidence from randomized trials in clinical practice,
and of who to treat with a growing range of highly effective but costly interventions.
Clinical assessment of cardiovascular risk
Clinical assessment should be conducted with four aims:
● to search for all cardiovascular risk factors and clinical conditions that may infl uence prognosis
● to determine the presence of target organ damage (heart, kidneys and retina);
● to identify those at high risk and in need of urgent intervention;
● to identify those who need special investigations or referral (e.g. those with secondary
hypertension (see Table 4)).
Causes, clinical features and laboratory tests for diagnosis of secondary hypertension
Causes Clinical features and Investigations
◆ family history of renal disease (polycystic kidney),
◆ past history of renal disease, urinary tract infection, haematuria, analgesic abuse
◆ enlarged kidneys on physical examination
◆ abnormalities in urine analysis – protein, erythrocytes, leucocytes and casts
◆ raised serum creatinine
◆ abdominal bruit
◆ abnormal renal function tests
◆ narrowing of renal arteries in renal arteriography
Phaeochromocytoma ◆ episodic headache, sweating, anxiety, palpitations
◆ neurofi bromatosis
◆ raised catecholamines, metanephrines in 24-hour urine samples
Primary aldosteronism ◆ muscle weakness and tetany
◆ decreased plasma renin activity and/or elevated plasma aldosterone level
Cushing syndrome ◆ truncal obesity, rounded face, buffalo hump, thin skin, abdominal striae, etc.
◆ raised 24-hour urinary cortisol excretion
Coarctation of the
◆ precordial or chest murmurs
◆ diminished and delayed femoral pulse
◆ reduced femoral blood pressure
◆ notching of ribs on chest X ray
◆ coarctation detected in arteriography
PART 1 The total risk approach to prevention of cardiovascular disease 15
A comprehensive clinical history (83) should include:
● current symptoms of coronary heart disease, heart failure, cerebrovascular disease, peripheral
vascular disease, diabetes, and renal disease;
● information on the use of drugs known to raise blood pressure (oral contracept
dal anti-infl ammatory drugs, liquorice, cocaine, amfetamine, erythropoietin, cyclosporins and
● the family history of high blood pressure, diabetes, dyslipidaemia, coronary heart disease,
stroke and renal disease;
● the personal history of coronary heart disease, heart failure, cerebrovascular disease, peripheral
vascular disease, diabetes, gout, bronchospasm, sexual dysfunction, and renal disease;
● symptoms suggestive of secondary hypertension, i.e. hypertension caused by an underlying
condition (Table 4);
● information on behaviour, including tobacco use, physical activity and dietary intake of fat, salt
● personal, psychosocial, occupational and environmental factors that could infl uence the course
and outcome of long-term care.
A full physical examination is essential, and should include careful measurement of blood pressure, as described below. Other important elements of the physical examination include:
● measurement of height and weight, and calculation of body mass index (BMI) (weight in kilograms divided by the square of height in meters); measurement of waist and hip circumference
for calculation of waist–hip ratio;
● examination of the cardiovascular system, particularly for heart size, evidence of heart failure,
evidence of disease in the carotid, renal and peripheral arteries, and physical signs suggestive of
coarctation of the aorta, particularly in young people with hypertension;
● examination for features of secondary hypertension (phaeochromocytoma, Cushing syndrome,
etc.) (Table 4);
● examination of the lungs for congestion ;
● examination of the abdomen for bruits, enlarged kidneys and other masses;
● examination of the optic fundi and of the central and peripheral nervous system for evidence of
cerebrovascular disease and complications of diabetes.
Measuring blood pressure
Health care professionals need to be adequately trained to measure blood pressure. In addition,
blood pressure measuring devices need to be validated, maintained and regularly calibrated to
ensure that they are accurate (84). Where possible, blood pressure should be measured when the
16 Prevention of cardiovascular disease
patient is relaxed and seated with the arm outstretched and supported. Two readings should be
taken; if the average is 140/90 mmHg or more, an additional reading should be taken at the end of
the consultation for confi rmation.
Blood pressure should be measured in both arms initially, and the arm with the higher reading
used for future measurements. If the difference between the two arms is more than 20 mmHg for
systolic pressure or 10 mmHg for diastolic pressure, the patient should be referred to the next
level of care for examination for vascular stenosis. Patients with accelerated (malignant) hypertension (blood pressure ≥ 180/110 mmHg with papilloedema or retinal haemorrhages) or suspected
secondary hypertension should be referred to the next level immediately.
When can treatment decisions be made without
the use of risk prediction charts? (40, 41, 43)
Some individuals are at very high cardiovascular risk because they have already experienced a
cardiovascular event, or have very high levels of individual risk factors. Risk stratifi cation is not
necessary for making treatment decisions for these individuals as they belong to the high risk
category; all of them need intensive lifestyle interventions and appropriate drug therapy (5). Risk
prediction charts may tend to underestimate cardiovascular risk in such individuals, who include
● patients with established angina pectoris, coronary heart disease, myocardial infarction, transient ischaemic attacks, stroke, or peripheral vascular disease, or who have had coronary revascularization or carotid endarterectomy;
● those with left ventricular hypertrophy (shown on electrocardiograph) or hypertensive retinopathy (grade III or IV);
● individuals without established CVD who have a total cholesterol ≥ 8 mmol/l (320 mg/dl) or
low-density lipoprotein (LDL) cholesterol ≥ 6 mmol/l (240 mg/dl) or TC/HDL-C ratio > 8;
● individuals without established CVD who have persistent raised blood pressure
(> 160–170/100–105 mmHg) (38–41, 43, 83);
● patients with type 1 or 2 diabetes, with overt nephropathy or other signifi cant renal disease;
● patients with known renal failure or renal impairment.
Applying the WHO/ISH risk prediction charts
Individual risk charts are specifi c to the respective WHO subregion (Annex 1). Each chart has
been calculated from the mean of risk factors and the average ten-year event rates from countries
of the specifi c subregion. The charts provide only approximate estimates of CVD risk in people
who do not have symptoms of coronary heart disease (CHD) , stroke or other atherosclerotic
disease. Importantly, these estimates represent the average for the subregion and do not capture
the variation in CVD risk within each subregion or country. They are useful as tools to help identify those at high total cardiovascular risk, and to motivate patients, particularly to change behaviour and, when appropriate, to take antihypertensive and lipid-lowering drugs and aspirin.
PART 1 The total risk approach to prevention of cardiovascular disease 17
In settings where facilities for measuring cholesterol are not available, risk prediction charts that
do not include cholesterol can be used (see Annex 4).
An individual’s risk of experiencing a cardiovascular event in the next 10 years is estimated as
● Select the appropriate chart (see Annex 3), depending on whether the person has diabetes or
not. (A person who has diabetes is defi ned as someone taking insulin or oral hypoglycaemic
drugs, or with a fasting plasma glucose concentration above 7.0 mmol/l (126 mg/dl) or a
postprandial (approximately 2 hours after a main meal) plasma glucose concentration above
11.0 mmol/l (200 mg/l)on two separate occasions).
● Select the appropriate element of the chart, corresponding to the person’s sex, age (if age is
50–59 select 50, 60–69 select 60 etc) and whether he or she is a smoker. (All current smokers
and those who quit smoking less than 1 year before the assessment are considered smokers for
assessing cardiovascular risk.)
● Find the cell in the chart element that corresponds to the individual’s systolic blood pressure
and serum cholesterol. (Systolic blood pressure, taken as the mean of two readings on each of
two occasions, is suffi cient for assessing risk but not for establishing a pretreatment baseline.
The mean of two non-fasting measurements of serum cholesterol by dry chemistry, or one nonfasting laboratory measurement, is suffi cient for assessing risk.)
● The colour of the cell indicates the risk category (see key in Annexes 3 and 4).
CVD risk may be higher than indicated in the chart in people who are already on antihypertensive
therapy, in women who have undergone premature menopause, in people approaching the next
age category, and in individuals with any of the following:
● obesity (including central obesity);
● a sedentary lifestyle;
● a family history of premature CHD or stroke in a fi rst degree relative (male < 55 years,
female < 65 years);
● a raised triglyceride level (> 2.0 mmol/l or 180 mg/dl);
● a low HDL cholesterol level (< 1 mmol/l or 40mg/dl in males, < 1.3 mmol/l or 50 mg/dl in
● raised levels of C-reactive protein, fi brinogen, homocysteine, apolipoprotein B or Lp(a), or
fasting glycaemia, or impaired glucose tolerance;
● microalbuminuria (increases the 5-year risk of diabetics by about 5%) (38, 83, 85);
● those who are not yet diabetic, but have impaired fasting glycemia or impaired glucose
● a raised pulse rate.
Other risk factors not included in these risk prediction charts such as socioeconomic deprivation
and ethnicity should also be taken unto account in addressing and managing a person’s overall
18 Prevention of cardiovascular disease
Goals of applying the prevention recommendations
The purpose of applying the recommendations elaborated in these guidelines is to motivate and
assist high-risk individuals to lower their cardiovascular risk by:
● quitting tobacco use, or reducing the amount smoked, or not starting the habit;
● making healthy food choices;
● being physically active;
● reducing body mass index (to less than 25 kg/m2) and waist–hip ratio (to less than 0.8 in
women and 0.9 in men (these fi gures may be different for different ethnic groups);
● lowering blood pressure (to less than 140/90 mmHg);
● lowering blood cholesterol (to less than 5 mmol/l or 190 mg/dl);
● lowering LDL-cholesterol (to less than 3.0 mmol/l or 115 mg/dl);
● controlling glycaemia, especially in those with impaired fasting glycaemia and impaired glucose
tolerance or diabetes;
● taking aspirin (75 mg daily), once blood pressure has been controlled.
The above goals represent the minimum that should be achieved. They are given for broad guidance in managing cardiovascular risk. In some subgroups of high-risk people, particularly those
with established cardiovascular disease or diabetes, a case can be made for lower targets for blood
pressure (< 130/80 mmHg), total cholesterol and LDL-cholesterol, which may require more
intensive treatment. Similarly, in very high-risk patients, a total cholesterol of less than 4.0 mmol/l
(152 mg/dl) and LDL-cholesterol of less than 2.0 mmol/l (77 mg/dl), or a reduction of 25% in
total cholesterol and 30% in LDL-cholesterol, whichever achieves the lower absolute level, may be