Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study
Salim YusufPhilip JosephSumathy RangarajanShofiqul IslamAndrew MentePerry HystadMichael BräuerV. Raman KuttyRajeev GuptaAndreas WielgoszKhalid F. AlHabibAntonio DansPatricio López‐JaramilloÁlvaro AvezumFernando LaņasAytekin OğuzIolanthé M. KrugerRafael DíazKhalid YusoffPrem MonyJephat ChifambaKaren YeatesRoya KelishadiAfzalhussein YusufaliRasha KhatibOmar RahmanKatarzyna ZatońskaRomaina IqbalWei LiAnnika RosengrenManmeet KaurViswanathan MohanScott A. LearKoon TeoDarryl P. LeongMartin O’DonnellMartin McKeeGilles R. Dagenais
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Key result
Modifiable risk factors account for ~70% of global CVD cases and deaths, led by hypertension.
- n=155,722
Why the study?
Global estimates of the impact of common modifiable risk factors on cardiovascular disease and mortality are largely based on separate studies with different methodologies, lacking a unified prospective evaluation across diverse countries.
Key Points
- To prospectively evaluate the impact of 14 common modifiable risk factors on cardiovascular disease and mortality across 21 high-, middle-, and low-income countries using standardized methodology.
- Enrolled 155,722 community-dwelling adults aged 35–70 years across 21 countries (11·1% high-income, 65·9% middle-income, 23·0% low-income; 52·6% urban) with a median follow-up of 9·5 years.
- Evaluated 14 risk factors spanning behavioural, metabolic, socioeconomic/psychosocial, muscle strength, household solid fuel, and ambient PM2·5 air pollution categories.
- Calculated hazard ratios and population attributable fractions (PAFs) for incident composite cardiovascular disease (7,980 cases) and all-cause mortality (10,234 deaths).
- Modifiable risk factors accounted for over 70% of cardiovascular disease cases and deaths in the overall cohort, with individual and household factors explaining 71% of the PAF for CVD and 75% for mortality.
- Metabolic factors were the predominant contributors to cardiovascular disease (41·2% of PAF), led by hypertension (22·3% of PAF), while ambient PM2·5 accounted for 13·9% of CVD PAF.
- Behavioural risk factors contributed 26·3% of the PAF for deaths, with low education being the single largest individual risk factor (12·5% of PAF), followed closely by tobacco use, low grip strength, and poor diet.
Study Design
Type
Cohort (n=155,722)
Multicenter
Yes
Structured PICO
P
Population
155,722 community-dwelling adults aged 35-70 without prior cardiovascular disease from 21 countries, followed for a median of 9.5 years.
O
Outcome
Composite of cardiovascular disease events (defined as cardiovascular death, myocardial infarction, stroke and heart failure) and mortalitycomposite
Limitations
- Information on sodium excretion was available in only two-thirds of the study population.
- Ambient air pollution was estimated at the community level rather than the individual level, requiring different statistical methods.
- Potential for reverse causality (e.g., lower lipid values associated with some chronic diseases).
- May not be generalizable to all countries (no data from West Africa, North Africa, or Australia, and modest Middle East representation)
- Recruitment was limited to specific provinces within some countries
- Potential misclassification due to self-reported or single-measure risk factors without regression dilution correction for categorical variables
- Did not include other community-level factors such as built environment or noise pollution
- Population attributable fraction (PAF) estimates in subgroups may be prone to random error
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“While long-term CVD prevention and management strategies have proved successful in reducing the burden in HIC, a change in tack is required to alleviate the disproportionately high impact of CVD in LIC and MIC. Governments in these countries need to start by investing a greater portion of their Gross Domestic Product in preventing and managing non-communicable diseases including CVD, rather than focussing largely on infectious diseases.”
Implication
A small cluster of modifiable risk factors, particularly metabolic factors like hypertension, accounts for the vast majority of cardiovascular disease globally, emphasizing the need for global health policies targeted at these predominant drivers.
Abstract
Background: Global estimates of the impact of common modifiable risk factors on cardiovascular disease (CVD) and mortality are largely based on data from separate studies, using different methodologies. The Prospective Urban Rural Epidemiology (PURE) study overcomes these limitations by using similar methodology to prospectively evaluate the impact of modifiable risk factors on CVD and mortality across 21 countries (spanning five continents) at different economic levels. Methods: In a multi-national, prospective cohort study, we examined associations for 14 potentially modifiable risk factors with mortality and major CVD in 155,722 community-dwelling participants (ages 35–70 years at enrollment) from 21 high-, middle-, or low-income countries (HIC, MIC or LIC) followed for a median of 9·5 years. We describe the prevalence, hazard ratios, and population attributable fractions (PAFs) for CVD and mortality associated with a cluster of behavioural factors (i.e. tobacco, alcohol, diet, physical activity and sodium intake), metabolic factors (i.e. lipids, blood pressure, diabetes, obesity), socioeconomic and psychosocial factors (i.e. education, symptoms of depression), strength, household (solid fuel for cooking) and ambient PM 2·5 air pollution. Findings: Mean age of the population was 50·2 years of age, 58·3% were female, 52·6% were from urban areas, 11·1% from HIC, 65·9% from MIC, and 23·0% from LIC. Over 70% of CVD cases and deaths in the overall cohort were attributed to modifiable risk factors. Metabolic factors were the predominant risk factors for CVD (41·2% of the PAF), with hypertension being the largest (22·3% of the PAF). As a cluster, behavioural risk factors contributed most to deaths (26·3% of the PAF), although the single largest risk factor was a low education level (12.5% of the PAF). Ambient air pollution was associated with 13·9% of the PAF for CVD (although different statistical methods were used for this analysis). In MIC and LIC, the importance of household air pollution, poor diet, low education, and low grip strength were larger compared with HIC. Interpretation: The majority of CVD cases and deaths can be attributed to a small number of common, modifiable risk factors. While some factors have extensive global impacts (e.g. hypertension, education), others (e.g. household air pollution, poor diet) vary by a country’s economic level. Health policies should focus on risk factors that have the greatest effects on averting CVD and death globally, with additional emphasis on risk factors of greatest importance in specific groups of countries.
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Cite This Study
Yusuf et al. (2019) conducted a cohort in Cardiovascular disease and mortality (n=155,722). 14 modifiable risk factors (behavioral, metabolic, socioeconomic, psychosocial, strength, and environmental) vs. Unexposed or low-risk reference categories was evaluated on Composite of cardiovascular disease events (CV death, myocardial infarction, stroke, heart failure) and mortality. Fourteen modifiable risk factors accounted for over 70% of cardiovascular disease cases and deaths globally, with metabolic factors (mainly hypertension) driving CVD and behavioral factors and low education driving mortality.
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