The Burden of Cardiovascular Events According to Cardiovascular Risk Profile in Adults From High-Income, Middle-Income, and Low-Income Countries (PURE): A Cohort Study
Comprehensive Overview
Published in The Lancet Global Health in 2025, this study asked what proportion of heart attacks, strokes, and other major cardiovascular events occur in people never flagged as high risk in the first place, since prevention efforts worldwide focus almost entirely on those already known to have cardiovascular disease or predicted to be at high risk. Researchers analyzed data from the Prospective Urban Rural Epidemiology (PURE) study, an ongoing international cohort that enrolled 128,973 adults aged 40 to 75 from households representative of their communities across 26 high-income, middle-income, and low-income countries. Participants without prior cardiovascular disease were classified as low (under 10%), intermediate (10% to under 20%), or high (20% or greater) predicted 10-year risk using validated World Health Organization risk tables based on age, sex, smoking, diabetes, blood pressure, and cholesterol, while a fourth group already had known cardiovascular disease at enrollment. All participants were then followed for a median of 12.3 years to track new fatal or non-fatal cardiovascular events. The topline result was that a large share of cardiovascular events occurred in people who had been classified as low risk at baseline, with this pattern varying substantially by a country's income level and by sex.
Outcomes and Implications
The most important finding was that 41% of all cardiovascular events in the study occurred in participants who had no history of cardiovascular disease and had been classified as low risk at baseline, even though this group's age- and sex-standardized event rate, 4.1 per 1000 person-years, was far lower than the 17.7 seen in the intermediate-risk group and the 40.8 seen in the high-risk group. This share of events occurring among the supposedly low-risk was strongly tied to a country's wealth, ranging from 32% in high-income countries to 38% in middle-income countries and 54% in low-income countries, and it was substantially higher among women (51%) than men (32%). Nearly two-thirds of all events occurred in participants older than 55, and about a tenth of events occurred in those originally classified as high risk, underscoring how few events that category actually captures. Among low-risk participants specifically, lower country income, less education, lower physical activity, and lower handgrip strength were each independently linked to a higher chance of a future cardiovascular event. The authors note that calibration of the WHO risk score varied by country income level, overestimating risk in middle-income countries while underestimating it in low-income countries. They conclude that because roughly 40% of major cardiovascular events occur in adults not considered high risk, achieving a meaningful population-level reduction in cardiovascular disease will require extending prevention strategies beyond high- and intermediate-risk groups to include those currently considered low risk.