Comment
Cardiovascular disease risk prediction models: challenges
and perspectives
Cardiovascular disease is the leading cause of death
worldwide and a major public health concern. Therefore,
its risk assessment is crucial to many existing treatment
guidelines.1 Risk estimates are also being used to
predict the magnitude of future cardiovascular disease
mortality and morbidity at the population level and
in specific subgroups to inform policymakers and
health authorities about these risks. Additionally, risk
prediction inspires individuals to change their lifestyle
and behaviour and to adhere to medications.2
Although several risk prediction models of cardio­
vascular disease have been developed for different
populations in the past decade,3 the validity of these
models is a cause of concern. Most data for model
formation and validation have been provided from a small
set of populations, mostly from developed countries.4
There­fore, using this set for the classification of individuals
from different risk groups of other populations might lead
to risk overestimation. This, in turn, can result in increased
costs of guidelines and health interventions. These models
might also cause risk underestimation, which can lead to
missing vulnerable cases. Consequently, providing a valid
model for cardiovascular disease risk classification of each
population has become a high priority for scientists and
organisations working in this field.3
In a systematic effort to provide a population-specific
risk prediction model, WHO and the International Society
of Hypertension (ISH) released cardiovascular disease risk
prediction charts for all WHO regions in 2007.5 However,
further validation studies showed that the WHO–ISH
risk prediction charts had validity issues when used in
populations from different countries.6
In The Lancet Global Health, the WHO CVD Risk Chart
Working Group7 presented results of a study that
aimed to assess the WHO–ISH prediction models for
21 global regions, by using individual participant
data from the Emerging Risk Factors Collaboration
(376  177 individuals from 85 cohort studies, and
19 333 incident cardiovascular events recorded during
10 years of follow-up). The group recalibrated the
models for 21 global regions—using age-specific and
sex-specific incidence data from the Global Burden
of Diseases, Injuries, and Risk Factors Study and
www.thelancet.com/lancetgh Vol 7 October 2019 e1288
risk factor values from Non-Communicable Disease Published Online
September 2, 2019
(NCD) Risk Factor Collaboration—and estimated the http://dx.doi.org/10.1016/
external validity of the models using 19 cohort studies S2214-109X(19)30365-1
(1 096 061 individuals, 25 950 cardiovascular disease This online publication has
been corrected. The corrected
events) that were not used in the model derivation. version first appeared at
The group used the models for 79 countries (mostly thelancet.com/lancetgh on
Oct 1, 2019
low-income and middle-income countries) with the
See Articles page e1332
WHO STEPwise Approach to Surveillance survey. They
explored a wide range of risk predictions for a specific
risk-factor profile among different global regions,
finding substantial variation across global regions. The
group also detected a wide range in the proportion of
individuals aged 40–64 years with an estimated risk
higher than 20% in the inspected countries, ranging
from less than 1% in Uganda to more than 16% in Egypt.
The study by the WHO CVD Risk Chart Working
Group has provided new charts for 21 global regions,
which help risk prediction in clinics and public health
interventions within countries. However, as the group
correctly mentioned in the discussion, the models
might overestimate risk scores because they use
incidence at the population level, which might include
recurrent cases. Nevertheless, a growing number of
observational studies with considerable follow-up
in middle-income countries are showing promising
results on the development and validation of country-
specific prediction models or validation of existing risk
prediction models.8 Moreover, the intrinsic specification
of a 10-year risk prediction, which gives considerable
weight to the age variable, does not allow the model to
single out the long-term risk, specifically in younger age
groups. The same problem exists for women at a smaller
scale.9 A risk prediction model that is age and sex specific
might be the solution, but it would be an expensive one
because it requires substantial long-term observational
data. Lifetime risk prediction is another approach to
address the problem, which has gained attention in
cardiovascular disease literature.10
Although the effect of primary health care in
controlling NCDs has been demonstrated before,11
controversies still exist on the benefits of applying
risk prediction compared with those of the risk
factor approach in population-based interventions.12
 Comment
Furthermore, several population studies targeting
populations by age or by risk prediction models alone are
ongoing, mostly based on the polypill.13 These polypill
studies address two main concerns: effectiveness and
cost of preventive interventions.
In conclusion, risk prediction methods are clearly in
their prime, and further efforts and resources are needed
to gather more observational data with lengthy follow-
ups to be able to derive population-specific models
that address all the concerns of existing risk prediction
models. More advanced population-specific models,
based on greater data and methods, could end up being
personalised risk assessments in the future.
Farshad Farzadfar
Non-Communicable Diseases Research Center, Endocrinology and
Metabolism Population Sciences Institute, Tehran University of
Medical Sciences, Tehran 1416753955, Iran
f-farzadfar@tums.ac.ir
I declare no competing interests.
Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open
Access article under the CC BY-NC-ND 4.0 license.
1 National Institutes of Health, National Heart, Lung, and Blood Institute.
Third report of the expert panel on detection, evaluation, and treatment of
high blood cholesterol in adults (Adult Treatment Panel III). 2002.
https://www.healthypeople.gov/2020/tools-resources/evidence-based-
resource/third-report-expert-panel-detection-evaluation-and (accessed
Aug 27, 2019).
e1289 www.thelancet.com/lancetgh Vol 7 October 2019
2 WHO. Implementation tools: package of essential noncommunicable
(PEN) disease interventions for primary health care in low-resource
settings. Geneva: World Health Organization, 2013.
3 Hajifathalian K, Ueda P, Lu Y, et al. A novel risk score to predict
cardiovascular disease risk in national populations (Globorisk): a pooled
analysis of prospective cohorts and health examination surveys.
Lancet Diabetes Endocrinol 2015; 3: 339–55.
4 Lloyd-Jones DM. Cardiovascular risk prediction: basic concepts, current
status, and future directions. Circulation 2010; 121: 1768–77.
5 WHO. Prevention of cardiovascular disease: guidelines for assessment and
management of cardiovascular risk. Geneva: World Health Organization,
2007.
6 Selvarajah S, Kaur G, Haniff J, et al. Comparison of the Framingham Risk
Score, SCORE and WHO/ISH cardiovascular risk prediction models in an
Asian population. Int J Cardiol 2014; 176: 211–18.
7 The WHO CVD Risk Chart Working Group. World Health Organization
cardiovascular disease risk charts: revised models to estimate risk in
21 global regions. Lancet Glob Health 2019; published online Sept 2.
http://dx.doi.org/10.1016/S2214-109X(19)30318-3.
8 Poustchi H, Eghtesad S, Kamangar F, et al. Prospective epidemiological
research studies in Iran (the PERSIAN Cohort Study): rationale, objectives,
and design. Am J Epidemiol 2017; 187: 647–55.
9 Cavanaugh-Hussey MW, Berry JD, Lloyd-Jones DM. Who exceeds ATP-III risk
thresholds? Systematic examination of the effect of varying age and risk
factor levels in the ATP-III risk assessment tool. Prev Med 2008; 47: 619–23.
10 Tolfrey K. American Heart Association guidelines for preventing heart
disease in women: 2007 update. Phys Sportsmed 2010; 38: 162–64.
11 Farzadfar F, Murray CJ, Gakidou E, et al. Effectiveness of diabetes and
hypertension management by rural primary health-care workers (Behvarz
workers) in Iran: a nationally representative observational study. Lancet
2012; 379: 47–54.
12 Basu S, Wagner RG, Sewpaul R, Reddy P, Davies J. Implications of scaling up
cardiovascular disease treatment in South Africa: a microsimulation and
cost-effectiveness analysis. Lancet Glob Health 2019; 7: e270–80.
13 Indian Polycap Study, Yusuf S, Pais P, et al. Effects of a polypill (Polycap) on
risk factors in middle-aged individuals without cardiovascular disease
(TIPS): a phase II, double-blind, randomised trial. Lancet 2009;
373: 1341–51.