Cardiovascular Disease Risk Factors: Epidemiology

and Risk Assessment

Björn Dahlöf, MD

Current epidemiologic predictions show that the world is heading for a vascular
tsunami of pandemic proportions. The number of people at high risk from cardio-
vascular disease is increasing; recent cohort studies suggest that only 2%–7% of the
general population have no risk factors at all, and >70% of at-risk individuals have
multiple risk factors. The recently published Ongoing Telmisartan Alone and in
Combination with Ramipril Global Endpoint Trial (ONTARGET) study, which
showed that telmisartan was as effective as ramipril in the prevention of a range of
cardiovascular outcomes, enrolled a broad cross section of high-risk patients. This
population was chosen to reflect the type of patients encountered in general practice,
and because the proportion of high-risk individuals is increasing worldwide, the
ONTARGET results will be relevant for most at-risk patients. Further analysis of the
ONTARGET results may also aid in the development of risk estimation scores
populated with real-life data and could also determine the impact of treatment on the
long-term reduction of total cardiovascular burden (ie, absolute risk reduction). This
may be a particularly useful exercise because current risk estimation charts have lim-
itations in their scope, sensitivity, and the ability to reflect changes in risk. © 2010
Elsevier Inc. All rights reserved. (Am J Cardiol 2010;105[suppl]:3A–9A)

Cardiovascular disease (CVD) can be thought of as a con-
tinuum that begins with the presence of cardiovascular risk
factors and proceeds via progressive vascular disease to
target organ damage, end-organ failure, and death.1 This
concept has led to 2 important proposals: first, that inter-
vention anywhere along the chain of events can disrupt the
pathophysiologic process and thus confer cardiovascular
protection; and second, because many cardiovascular events
share the same etiology, it is essential to assess and treat a
patient’s total cardiovascular risk rather than to consider
risk factors in isolation.
Modifiable risk factors for CVD—which include hyper-
tension, smoking, abdominal obesity, abnormal lipids, and
diabetes mellitus, as well as stress, low consumption of
fruits and vegetables, and lack of regular physical activity—
are the major contributors to cardiovascular morbidity and
mortality and account for ⬎90% of all myocardial infarc-
tions (MI).1,2 More recently, too little (⬍6 hours) or too
much (⬎9 hours) sleep has been identified as another inde-
pendent risk factor for hypertension and metabolic syn-
drome.3–5 Cardiovascular risk factors show a continuous
association with overall cardiovascular risk with no mini-
Department of Medicine, Sahlgrenska University Hospital, Göteborg,
Sweden.
This work was supported by Boehringer Ingelheim GmbH.
Statement of author disclosure: Please see the Author Disclosures
section at the end of this article.
Address for reprints: Björn Dahlöf, MD, Department of Medicine,
Sahlgrenska University Hospital/östra, SE-416 85 Gothenburg, Sweden.
E-mail address: bjorn.dahlof@a-plusscience.com.
mum threshold for disease.6,7 Risk factors rarely occur in
isolation and instead tend to cluster in individuals.8,9 Ap-
proximately 70% of all individuals at risk have multiple risk
factors, which interact synergistically to increase an indi-
vidual’s total risk of CVD; from 4-fold with 1 risk factor to
60-fold in the presence of 5 risk factors.10,11
Most cardiovascular events occur in people with modest
and therefore often unnoticed elevations in multiple risk
factors, rather than a large increase in a single factor, and
consequently for many individuals, death is the first mani-
festation of CVD.
Worldwide Prevalence of Cardiovascular Risk Factors
The worldwide prevalence of cardiovascular risk factors is
increasing. Hypertension, which was identified in a recent
World Health Organization (WHO) report as among the
most important preventable causes of premature death, af-
fected 972 million people worldwide in 2000 and is pre-
dicted to increase by around 60% to 1.56 billion people by
2025.12 Similarly, diabetes, which currently affects 151 mil-
lion people globally, is expected to increase by 46% to 221
million by 2010.13
Total global mortality estimates show that the top 3
causes of death in industrialized countries are hypertension,
tobacco use, and high levels of cholesterol—all high-profile
risk factors for CVD.14 –16 However, CVD is no longer the
preserve of affluent nations. Similar trends are now emerg-
ing in economically developing countries, where the prev-

0002-9149/10/$ – see front matter © 2010 Elsevier Inc. All rights reserved. www.AJConline.org
doi:10.1016/j.amjcard.2009.10.007
4A The American Journal of Cardiology (www.AJConline.org) Vol 105 (1A) January 4, 2010
Figure 1. Global mortality and burden of disease attributable to cardiovascular diseases and their major risk factors for people aged ⱖ30 years. The size of
each circle is proportional to the number of deaths (left) or burden of disease (right; measured in disability-adjusted life years) in millions (M). (Adapted from
PLoS Med.16)
alence of obesity and high cholesterol has been shown to
correlate strongly with increasing national income.16
The number of people with multiple cardiovascular risk
factors is increasing alarmingly. Obesity is a major driver of
cardiovascular risk, and it associates strongly with other
cardiovascular risk factors, such as hypertension, diabetes,
and high cholesterol.17 The prevalence of obesity in the
United States has increased dramatically in the last 2 de-
cades and is still climbing. Data from successive Behavioral
Risk Factor Surveillance System (BRFSS) surveys shows
that in the 10 years between 1991 and 2002, the prevalence
of obesity (defined as a body mass index ⱖ30 ) increased
from 12.0% to 20.9%, an increase of 74%.17–19 Mirroring
this increase in obesity has been a dramatic 61% increase in
the prevalence of type 2 diabetes, from 4.9% in 1990 to
7.9% in 2001.17,20 Similar increases have been seen in
metabolic syndrome, a cluster of related risk factors that
includes abdominal obesity, hypertension, dyslipidemia,
and insulin resistance. Metabolic syndrome increases the
relative risk of CVD by 70%–90%,21 and is becoming more
prevalent. In 2000, 27% of the US population or 55 million
people had metabolic syndrome, an increase of 34% in 10
years.22
Epidemiology of Cardiovascular Disease
CVD is the leading cause of death worldwide, accounting
for around 16.7 million deaths each year, mainly from heart
attacks and strokes.23 This number is predicted to increase
to approximately 25 million deaths by 2020, if current
trends continue.24 In 2004, ischemic heart disease caused an
estimated 7.2 million deaths and cerebrovascular disease
resulted in 5.5 million deaths, accounting for 22% of all
global mortality.15 Yet these fatalities represent only the tip
of the cardiovascular iceberg. A far larger proportion of
individuals have asymptomatic disease and target organ
damage secondary to undetected high blood pressure and
the presence of other risk factors. Current estimates show
that the global burden of CVD far exceeds that of its death
toll, affecting an estimated 128 million people, or nearly
8 times the number for cardiovascular mortality (Figure 1).16
In the United States alone, 71.3 million adults— or 1 in
3— have ⱖ1 types of CVD.25 Thus, the greater burden of
CVD is attributable not to mortality but to nonfatal cardio-
vascular events and their long-term consequences. Recent
US disease trends show that although cardiovascular death
rates are slowing, the number of patients surviving a car-
diovascular event and being discharged from the hospital is
increasing.25
Furthermore, the global incidence of CVD is increasing
as the world’s population ages and as lifestyles (and hence,
risk factors) in lower- and middle-income countries become
more akin to those of wealthier nations. Future cardiovas-
cular burden is likely to be exacerbated not just by the aging
population, but also by the epidemic of obesity and related
cardiovascular risk factors, both of which are increasing in
prevalence. The recently published Reduction of Athero-
thrombosis for Continued Health (REACH) Registry, which
collected global data on atherosclerosis risk factors from
67,888 patients aged ⱖ45 years in 44 countries, found that
classic cardiovascular risk factors (hypertension, high cho-
lesterol levels, diabetes, obesity, and smoking) confirm the
findings from the INTERHEART study and are consistent
and common in diverse ethnic populations, even if they do
tend to be undertreated and undercontrolled in many regions
of the world.26 So although the problem of CVD may be
pandemic, prevention can be based on the same principles
worldwide. REACH also found regional differences in the
distribution of different categories of CVD (coronary artery
disease [CAD], cerebrovascular disease, and peripheral ar-
terial disease) (Figure 2).
 Dahlöf/Cardiovascular Disease Risk Factors: Epidemiology and Risk Assessment 5A

Figure 2. Cardiovascular disease characteristics distribution by region in the Reduction of Atherothrombosis for Continued Health (REACH) registry, an
international, prospective, observational registry in outpatients aged ⱖ45 years with established coronary artery disease (CAD), cerebrovascular disease
(CVD), or peripheral arterial disease (PAD), or with ⱖ3 atherosclerosis risk factors.

The Importance of Total Cardiovascular Risk
Assessment
Because risk factors tend to cluster in individuals and in-
teract to increase cardiovascular risk, global or total cardio-
vascular risk assessment is essential. Most cardiovascular
events occur not among the small number of individuals at
high risk but among the much larger numbers of individuals
at lower risk.27 Global risk assessment can identify both the
high-risk patients who need aggressive intervention, as well
as patients who might appear to be at low risk but who are
actually at a much higher risk of CVD.28,29
Global risk assessment leads to a more effective preven-
tion of CVD than assessments based on single risk factors.
Emberson et al28 calculated the potential effectiveness of
different risk reduction strategies in the primary prevention
of CVD using prospective observational cardiovascular
study data (the British Regional Heart Study) and estimates
of relative risk reduction. They concluded that overall risk
assessment was more effective and that, furthermore, mul-
tiple interventions had considerably greater benefits than
interventions targeting single risk factors: modest 10% re-
ductions in long-term mean blood cholesterol levels and
blood pressure yielded a 45% reduction in major CVD.
Jackson and colleagues29 reached similar conclusions in a
review of randomized controlled studies and meta-analyses
evaluating the effects of blood pressure– or blood choles-
terol–lowering treatments. The investigators argued in favor
of providing treatment based on a patient’s overall absolute
cardiovascular risk (ie, the probability that a patient will
have a cardiovascular event in a defined period), rather than
on specific blood pressure or blood cholesterol levels be-
cause these measures have little clinical relevance when
considered in isolation from other risk factors. Importantly,
an individual at low relative risk of CVD can nevertheless
have a high absolute risk, depending on which risk factors
are present. Because absolute cardiovascular risk is deter-
mined by the interactions of all cardiovascular risk factors
present,10 the investigators concluded that moderate reduc-
tions in several risk factors are likely to be more effective
than major reductions in a single risk factor.29
The importance of treating global cardiovascular risk rather
than single factors has been corroborated by the Clinical Out-
comes Utilizing Revascularization and Aggressive Drug Eval-
uation (COURAGE) trial. This study, conducted in patients
with myocardial ischemia and stable CAD, showed that inten-
sive pharmaceutical treatment plus lifestyle intervention (opti-
mal medical therapy) was as effective as percutaneous coro-
nary intervention in lowering the composite cardiovascular end
point of death, MI, and stroke (19.0% in the coronary inter-
6A The American Journal of Cardiology (www.AJConline.org) Vol 105 (1A) January 4, 2010

Figure 3. Risk stratification according to European Society of Hypertension and the European Society of Cardiology (ESH-ESC) criteria. Low, moderate,
high, and very high added risk are calibrated to indicate an absolute 10-year risk of cardiovascular disease of ⬍15%, 15%–20%, 20%–30% and ⬎30%,
respectively, according to Framingham criteria, or an absolute fatal cardiovascular risk of ⬍4%, 4%–5%, 5%– 8%, and ⬎8% according to the Systematic
Coronary Risk Evaluation (SCORE) chart. ACC ⫽ associated clinical conditions; TOD ⫽ target organ damage; SBP ⫽ systolic blood pressure; DBP ⫽
diastolic blood pressure. (Reprinted with permission from J Hypertens.31)

vention group vs 18.5% in the optimal medical therapy group),
showing that systemic reduction in risk throughout the entire
vascular tree was as effective as isolated surgical treatment of
the acutely affected vessel.30
Estimating Total Cardiovascular Risk
Different algorithms exist for estimating total cardiovascular
risk, including those published by the European Society of
Hypertension and the European Society of Cardiology (ESH-
ESC),31 the National Cholesterol Education Program (NCEP),
and the Adult Treatment Panel III (ATP III).32 However, the
methods, populations, and definitions of risk used to calculate
cardiovascular risk differs between systems, and there is no
general agreement on which one to use.
FRAMINGHAM-BASED RISK CHARTS: Many risk assess-
ment charts are based on the Framingham study, which
represents the trends in risk observed in a US cohort of
about 5,000 white people, established ⬎50 years ago and
replenished by offspring of the original cohort.8,33 The ap-
plicability of these risk charts to different ethnic and socio-
economic groups is uncertain, but studies in European pop-
ulations indicate that Framingham-based charts tend to
overestimate risk in countries with lower CAD rates.34 –36
Indeed, in a recent systematic review of 27 randomized
controlled studies that compared Framingham-based predic-
tions of CAD risk with the observed 10-year risk in different
populations, CAD risk was underestimated in high-risk pop-
ulations by 0.43 (95% confidence interval [CI], 0.27– 0.67)
and overestimated in lower-risk populations by 2.87 (95%
CI, 1.91– 4.31).37
In addition to these considerations, Framingham-based
risk assessment does not incorporate all risk factors and its
end point definitions differ from those used in other studies.
Framingham-based risk scoring uses a definition of nonfatal
CAD that includes the “soft” end points of nonfatal MI,
onset of angina, and coronary insufficiency (unstable an-
gina), making it difficult to relate to the “hard” end points of
coronary death and nonfatal MI, used in other cohort studies
and in therapeutic clinical trials.38 Because evidence-based
medicine is a product of interventional clinical trials, the
utility of Framingham risk scores as a basis of evidence-
based intervention can be restrictive. Furthermore, the in-
vestigators involved in the Framingham-based ATP III
guidelines note that the equations for 10-year CAD risk
were never intended to be used for tracking changes in risk
over time.32
SYSTEMATIC CORONARY RISK EVALUATION– BASED
RISK CHARTS: The ESH-ESC guidelines incorporate the
Systematic Coronary Risk Evaluation (SCORE) system,
which was developed to provide total fatal cardiovascular
risk estimation in European countries (Figure 3).31,38 Unlike
Framingham, SCORE was based on a very large multina-
tional dataset and thus provides equations for both high- and
low-risk European regions, enabling regional estimations of
cardiovascular risk. Because the primary end point is total
cardiovascular mortality, this system provides a robust and
reproducible estimate of risk, although it is not an estima-
tion of nonfatal or total cardiovascular events. The ESH-
ESC risk chart displays 10-year risk in absolute values as
well as relative risk categories,39 although, as with the
Framingham-based charts, the ESH-ESC chart does not
adequately reflect changes in risk over time (Figure 3). For
example, a patient with associated clinical conditions whose
blood pressure is lowered from “grade 2” to “high normal”
would remain at “very high added risk” using these criteria
 Dahlöf/Cardiovascular Disease Risk Factors: Epidemiology and Risk Assessment 7A

Table 1
Key baseline characteristics of ONTARGET study participants
Characteristics (mean ⫾ SD) Ramipril (n ⫽ 8,576) Telmisartan (n ⫽ 8,542) Combination Therapy (n ⫽ 8,502)

Age (years) 66.4 ⫾ 7.2 66.4 ⫾ 7.1 66.5 ⫾ 7.3

Blood pressure (mm Hg) 141.8 ⫾ 17.4/82.1 ⫾ 10.4 141.7 ⫾ 17.2/82.1 ⫾ 10.4 141.9 ⫾ 17.6/82.1 ⫾ 10.4
Body mass index (kg/m2) 28.1 ⫾ 4.5 28.1 ⫾ 4.6 28.0 ⫾ 4.5
Current smoker (%) 12.4 12.4 12.9
Past smoker (%) 52.0 52.3 51.1
Coronary artery disease (%) 74.4 74.5 74.7
Myocardial infarction (%) 48.3 49.3 49.3
Stable angina (%) 35.4 34.6 34.8
Unstable angina (%) 14.7 15.2 14.9
Stroke/TIA (%) 21.0 20.6 20.9
Peripheral artery disease (%) 13.2 13.6 13.8
Hypertension (%) 69.0 68.6 68.5
Diabetes (%) 36.7 38.0 37.9
LVB (%) 12.7 13.1 12.7
Microalbuminuria (%) 13.1 13.2 13.3
Previous CABG (%) 21.7 22.5 22.3
Previous PTCA (%) 29.5 29.0 28.6

CABG ⫽ coronary artery bypass graft; LVH ⫽ left ventricular hypertrophy; ONTARGET ⫽ Ongoing Telmisartan Alone and in Combination with
Ramipril Global Endpoint Trial; PTCA ⫽ percutaneous transluminal coronary angioplasty; TIA ⫽ transient ischemic attack. Adapted from N Engl J Med.45

because the risk factors that determine the patient’s risk
grade form part of the patient’s history. Calculation of
absolute risk may be more relevant to assessing the cardio-
vascular benefits of lowering blood pressure.
Recently, Ridker et al40 developed a new risk estimation
algorithm for women based on an evaluation of 35 risk factors
in a cohort of 24,558 initially healthy US women. The new
model, which accounts for age, systolic blood pressure, hemo-
globin A1c if patient has diabetes, smoking, total and high-
density lipoprotein cholesterol, high-sensitivity C-reactive pro-
tein, and parental history of MI before 60 years of age, showed
greatly improved accuracy over the ATP III risk score in
cardiovascular risk prediction, and reclassified 40%–50% of
women at intermediate risk into higher- or lower-risk catego-
ries.40 Whether this refined model, which uses more variables,
delivers a better and more accurate prediction has yet to be
validated in large-scale studies.
LIMITATIONS OF CURRENT PAPER-BASED RISK CHARTS:
All paper-based charts are limited as to the variables that
can be included in risk estimation. Currently, the effects of
obesity and exercise are not accounted for, there are no
separate charts for diabetes or metabolic syndrome, and
many new risk factors (eg, plasma lipoprotein[a], coagula-
tion factors, and inflammation markers) are not included.39
No single, paper-based risk estimation system reflects the
continuous nature of cardiovascular risk, and many are also
complicated to administer. This causes confusion among
physicians and acts as a barrier to use, leading to an under-
estimation of cardiovascular risk in general practice. In a
large European survey of primary care physicians, only 13%
always used risk charts to assess a patient’s risk of devel-
oping CVD, and 40%–50% never used them.41 The low use
of risk charts means that physicians tend to base their
assessment on educated guesswork and often underestimate
cardiovascular risk, particularly in high- or very-high-risk
patients. The CONTROLRISK study, which investigated
the accuracy of cardiovascular risk stratification among
physicians in primary care and specialist settings in Spain,
found that only 55% of specialists and 48% of primary care
physicians stratified their patients correctly according to
ESC-ESH guidelines. Both specialists and general practi-
tioners strongly underestimated cardiovascular risk in their
patients, ⬎50% of whom belonged to high- or very-high-
risk groups.42 In a separate survey of cardiovascular
specialists in Italy, perceived total risk was routinely under-
estimated by 25% in high-risk patients and by 50% in
very-high-risk patients.43
Implications for the Ongoing Telmisartan Alone and in
Combination with Ramipril Global Endpoint Trial Study
The recently completed Ongoing Telmisartan Alone and
in Combination with Ramipril Global Endpoint Trial
(ONTARGET), which showed that telmisartan was as ef-
fective as ramipril in the prevention of a range of cardio-
vascular outcomes (see article elsewhere in this supplement
for detailed description of results44), enrolled a high-risk
population with multiple risk factors for CVD (Table 1).45
This population was at higher risk than populations used in
previous studies, such as the European Trial on Reduction
of Cardiac Events with Perindopril in Stable Coronary Ar-
tery Disease Investigators (EUROPA).46 Further analysis of
the ONTARGET results may aid in the development of risk
estimation scores populated with real-life data and could
also determine the impact of treatment on long-term cardio-
vascular risk reduction.
The population enrolled in ONTARGET will also have
particular relevance to the real-life setting. Recent evidence
suggests that only a very small minority of individuals
8A The American Journal of Cardiology (www.AJConline.org) Vol 105 (1A) January 4, 2010
within a population are entirely free from cardiovascular
risk factors. Findings (unpublished data, 2005) from the
Belgian Job Stress Project survey47 of 20,000 men and
women aged 35–59 years show that only 2.2% of men and
6.9% of women did not have elevated blood pressure
(⬎130/80 mm Hg), high cholesterol (⬎5 mmol/L), body
mass index ⬎25, or a history of smoking.
Conclusion
Current epidemiologic predictions suggest that CVD is
reaching pandemic proportions. It is already the number 1
killer worldwide, and the prevalence of cardiovascular risk
factors is increasing. Future cardiovascular burden is likely
to be exacerbated by the aging population, the increasing
obesity epidemic, and insufficient implementation of pre-
vention strategies. However, global surveillance studies
suggest that cardiovascular risk factors operate the same
way in all populations the world over, suggesting that pre-
vention and treatment strategies are likely to be effective
wherever they are instituted.
Accurate global risk assessment is fundamental to the
prevention of CVD if targeted treatment strategies are to be
effective. Current risk estimation charts have limitations in
their scope, sensitivity, and the ability to reflect changes
in risk. Further analysis of the ONTARGET results may aid
in the development of risk estimation scores populated with
real-life data and could also determine the impact of treat-
ment on the long-term reduction of total cardiovascular
burden (ie, absolute risk reduction). The ONTARGET find-
ings are also relevant to most at-risk patients, who are
generally seen in practices worldwide.
Acknowledgment
Writing and editorial assistance was provided by Tom Rees,
PhD, of PAREXEL MMS, which was contracted by Boehr-
inger Ingelheim for these services. The author(s) meet cri-
teria for authorship as recommended by the International
Committee of Medical Journal Editors (ICMJE) and were
fully responsible for all content and editorial decisions, and
were involved at all stages of manuscript development. The
authors received no compensation related to the develop-
ment of the manuscript.
Author Disclosures
The author who contributed to this article has disclosed the
following industry relationships:
Björn Dahlöf, MD, has been a member of the Speakers’
Bureau for Novartis, Boehringer Ingelheim, and Pfizer; and
has been a consultant for Novartis, Boehringer Ingelheim,
and Daiichi-Sankyo.
1. Dzau VJ, Antman EM, Black HR, Hayes DL, Manson JE, Plutzky J,
Popma JJ, Stevenson W. The cardiovascular disease continuum vali-
dated: clinical evidence of improved patient outcomes: part I: patho-
physiology and clinical trial evidence (risk factors through stable
coronary artery disease). Circulation 2006;114:2850 –2870.
2. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen
M, Budaj A, Pais P, Varigos J, Lisheng l, for 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.
3. Gottlieb DJ, Redline S, Nieto FJ, Baldwin CM, Newman AB, Resnick
HE, Punjabi NM. Association of usual sleep duration with hyperten-
sion: the Sleep Heart Health Study. Sleep 2006;29:1009 –1014.
4. Gangwisch JE, Heymsfield SB, Boden-Albala B, Buijs RM, Kreier F,
Pickering TG, Rundle AG, Zammit GK, Malaspina D. Short sleep
duration as a risk factor for hypertension: analyses of the first National
Health and Nutrition Examination Survey. Hypertension 2006;47:833–
839.
5. Wolk R, Somers VK. Sleep and the metabolic syndrome. Exp Physiol
2007;92:67–78.
6. Stamler J, Wentworth D, Neaton JD. Is relationship between serum
cholesterol and risk of premature death from coronary heart disease
continuous and graded? Findings in 356,222 primary screenees of the
Multiple Risk Factor Intervention Trial (MRFIT). JAMA 1986;256:
2823–2828.
7. Kannel WB. Risk stratification in hypertension: new insights from the
Framingham Study. Am J Hypertens 2000;13:3S–10S.
8. Meigs JB, D’Agostino RB Sr, Wilson PW, Cupples LA, Nathan DM,
Singer DE. Risk variable clustering in the insulin resistance syndrome:
the Framingham Offspring Study. Diabetes 1997;46:1594 –1600.
9. Zanchetti A. The hypertensive patient with multiple risk factors: is
treatment really so difficult? Am J Hypertens 1997;10:223S–229S.
10. Kannel WB. Some lessons in cardiovascular epidemiology from Fra-
mingham. Am J Cardiol 1976;37:269 –282.
11. Wilson PW, Kannel WB, Silbershatz H, D’Agostino RB. Clustering of
metabolic factors and coronary heart disease. Arch Intern Med 1999;
159:1104 –1109.
12. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J.
Global burden of hypertension: analysis of worldwide data. Lancet
2005;365:217–223.
13. Zimmet P, Alberti KG, Shaw J. Global and societal implications of the
diabetes epidemic. Nature 2001;414:782–787.
14. Ezzati M, Lopez AD, Rodgers A, Vander Hoorn S, Murray CJ, for the
Comparative Risk Assessment Collaborating Group. Selected major
risk factors and global and regional burden of disease. Lancet 2002;
360:1347–1360.
15. Ezzati M, Hoorn SV, Rodgers A, Lopez AD, Mathers CD, Murray CJ,
for the Comparative Risk Assessment Collaborating Group. Estimates
of global and regional potential health gains from reducing multiple
major risk factors. Lancet 2003;362:271–280.
16. Ezzati M, Vander Hoorn S, Lawes CM, Leach R, James WP, Lopez
AD, Rodgers A, Murray CJ. Rethinking the “diseases of affluence”
paradigm: global patterns of nutritional risks in relation to economic
development. PLoS Med 2005;2:e133.
17. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS,
Marks JS. Prevalence of obesity, diabetes, and obesity-related health
risk factors, 2001. JAMA 2003;289:76 –79.
18. Mokdad AH, Serdula MK, Dietz WH, Bowman BA, Marks JS, Koplan
JP. The spread of the obesity epidemic in the United States, 1991-
1998. JAMA 1999;282:1519 –1522.
19. Mokdad AH, Bowman BA, Ford ES, Vinicor F, Marks JS, Koplan JP.
The continuing epidemics of obesity and diabetes in the United States.
JAMA 2001;286:1195–1200.
20. Mokdad AH, Ford ES, Bowman BA, Nelson DE, Engelgau MM,
Vinicor F, Marks JS. Diabetes trends in the U.S.: 1990-1998. Diabetes
Care 2000;23:1278 –1283.
 Dahlöf/Cardiovascular Disease Risk Factors: Epidemiology and Risk Assessment
21. Ford ES. Risks for all-cause mortality, cardiovascular disease, and
diabetes associated with the metabolic syndrome. Diabetes Care 2005;
28:1769 –1778.
22. Ford ES, Giles WH, Mokdad AH. Increasing prevalence of the met-
abolic syndrome among U.S. Adults. Diabetes Care 2004;27:2444 –
2449.
23. American Heart Association. International Cardiovascular Disease
Statistics. 2007 Update. Available at: http://www.americanheart.org/
presenter.jhtml?identifier ⫽ 3001008. Accessed December 10, 2007.
24. Yach D, Hawkes C, Gould CL, Hofman KJ. The global burden of
chronic diseases: overcoming impediments to prevention and control.
JAMA 2004;291;2616 –2620.
25. Thom T, Haase N, Rosamond W, Howard VJ, Rumsfeld J, Manolio T,
Zheng ZJ, Flegal K, O’Donnell C, Kittner S, et al, for the American
Heart Association Statistics Committee and Stroke Statistics Subcom-
mittee. Heart disease and stroke statistics—2006 update: a report from
the American Heart Association Statistics Committee and Stroke Sta-
tistics Subcommittee. Circulation 2006;113:e85–151.
26. Bhatt DL, Steg PG, Ohman EM, Hirsch AT, Ikeda Y, Mas JL, Goto S,
Liau CS, Richard AJ, Röther J, Wilson PW, for the REACH Registry
Investigators. International prevalence, recognition, and treatment of
cardiovascular risk factors in outpatients with atherothrombosis. JAMA
2006;295:180 –189.
27. Rose G. Sick individuals and sick populations. Int J Epidemiol 1985;
14:32–38.
28. Emberson J, Whincup P, Morris R, Walker M, Ebrahim S. Evaluating
the impact of population and high-risk strategies for the primary
prevention of cardiovascular disease. Eur Heart J 2004;25:484 – 491.
29. Jackson R, Lawes CM, Bennett DA, Milne RJ, Rodgers A. Treatment
with drugs to lower blood pressure and blood cholesterol based on an
individual’s absolute cardiovascular risk. Lancet 2005;365:434 – 441.
30. Boden WE, O’Rourke RA, Teo KK, Hartigan PM, Maron DJ, Kostuk
WJ, Knudtson M, Dada M, Casperson P, Harris CL, et al, for the
COURAGE Trial Research Group. Optimal medical therapy with or
without PCI for stable coronary disease. N Engl J Med 2007;356:
1503–1516.
31. Guidelines Committee. 2003 European Society of Hypertension–Eu-
ropean Society of Cardiology guidelines for the management of arte-
rial hypertension. J Hypertens 2003;21:1011–1153.
32. National Cholesterol Education Program (NCEP) Expert Panel on
Detection, Evaluation, and Treatment of High Blood Cholesterol in
Adults (Adult Treatment Panel III). 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) final report. Circulation 2002;106:3143–3421.
33. Dawber TR, Kannel WB, Revotskie N, Kagan A. The epidemiology of
coronary heart disease—the Framingham Enquiry. Proc R Soc Med
1962;55:265–271.
34. Hense HW, Schulte H, Löwel H, Assmann G, Keil U. Framingham
risk function overestimates risk of coronary heart disease in men and
9A
women from Germany: results from the MONICA Augsburg cohort
and the PROCAM cohort. Eur Heart J 2003;24:937–945.
35. Thomsen TF, McGee D, Davidsen M, Jørgensen T. A cross-validation
of risk-scores for coronary heart disease mortality based on data from
the Glostrup Population Studies and Framingham Heart Study. Int J
Epidemiol 2002;31:817– 822.
36. Menotti A, Puddu PE, Lanti M. Comparison of the Framingham risk
function-based coronary chart with risk function from an Italian pop-
ulation study. Eur Heart J 2000;21:365–370.
37. Brindle P, Beswick A, Fahey T, Ebrahim, S. Accuracy and impact of
risk assessment in the primary prevention of cardiovascular disease: a
systematic review. Heart 2006;92:1752–1759.
38. Conroy RM Pyörälä K, Fitzgerald AP, Sans S, Menotti A, De Backer
G, De Bacquer D, Ducimetière P, Jousilahti P, Keil U, et al. Estimation
of ten-year risk of fatal cardiovascular disease in Europe: the SCORE
project. Eur Heart J 2003;24:987–1003.
39. Graham IM. The importance of total cardiovascular risk assessment in
clinical practice. Eur J Gen Pract 2006;12:148 –155.
40. Ridker PM, Buring JE, Rifai N, Cook NR. Development and validation
of improved algorithms for the assessment of global cardiovascular
risk in women: the Reynolds Risk Score. JAMA 2007;14;297:611–
619.
41. Hobbs FD, Erhardt L. Acceptance of guideline recommendations and
perceived implementation of coronary heart disease prevention among
primary care physicians in five European countries: the Reassessing
European Attitudes about Cardiovascular Treatment (REACT) survey.
Fam Pract 2002;19:596 – 604.
42. Barrios V, Escobar C, Calderón A, Echarri R, González-Pedel V,
Ruilope LM, for the CONTROLRISK Investigators. Cardiovascular
risk profile and risk stratification of the hypertensive population
attended by general practitioners and specialists in Spain: the
CONTROLRISK study. J Hum Hypertens 2007;21:479 – 485.
43. Mancia G, Volpe R, Boros S, Ilardi M, Giannattasio C. Cardiovascular
risk profile and blood pressure control in Italian hypertensive patients
under specialist care. J Hypertens 2004;22:51–57.
44. Weber MA. Telmisartan in high-risk cardiovascular patients. Am J
Cardiol 2009;(suppl xx): xxx–xxx.[[this issue]].
45. The ONTARGET Investigators. Telmisartan, ramipril, or both in pa-
tients at high risk for vascular events. N Engl J Med 2008;358:1547–
1559.
46. The European Trial on Reduction of Cardiac Events with Perindopril
in Stable Coronary Artery Disease Investigators. Efficacy of perindo-
pril in reduction of cardiovascular events among patients with stable
coronary artery disease: randomized, double-blind, placebo-controlled,
multicentre trial (the EUROPA study). Lancet 2003;362:782–788.
47. De Bacquer D, Pelfrene E, Clays E, Mak R, Moreau M, de Smet P,
Kornitzer M, De Backer G. Perceived job stress and incidence of
coronary events: 3-year follow-up of the Belgian Job Stress Project
cohort. Am J Epidemiol 2005;161:434 – 441.