An international study validates two of the leading cardiovascular risk prediction tools in more than 6.4 million people

The PREVENT and SCORE2 algorithms are two of the leading tools used in the United States and Europe to estimate cardiovascular risk. An international study published on Wednesday in the journal Nature Medicine has validated both tools in populations from different regions of the world, demonstrating that they have strong predictive capacity. The research analysed data from more than 6.4 million people drawn from 44 observational cohorts and 18 randomised clinical trials, with the aim of validating both models across diverse geographical and clinical settings. The study involved the participation of the head of Vascular and Renal Translational Research Group at the Lleida Institute for Biomedical Research (IRBLleida), José Manuel Valdivielso, last author of the article and one of the supervisors of this multicentre work, conducted within the framework of the Chronic Kidney Disease Prognosis Consortium (CKD-PC), the international consortium bringing together more than one hundred cohorts and trials from different regions of the world.

Cardiovascular diseases remain the leading cause of death worldwide and the greatest cause of years of life lost. Tools such as PREVENT, recently developed by the American Heart Association, and SCORE2, used in European cardiovascular prevention guidelines, make it possible to estimate an individual's risk of experiencing cardiovascular events and help guide preventive strategies, such as initiating cholesterol-lowering treatments or blood pressure control.

Until now, both tools had been developed and validated primarily in their regions of origin. However, there was a lack of large-scale studies assessing their performance in global populations - outside their original geographical scope and across multinational clinical trials - that would allow results to be generalised and confirm their applicability to other populations.

"The great value of this work is that it demonstrates that these tools maintain robust and consistent performance across very different populations", explains José Manuel Valdivielso, head of the Vascular and Renal Translational Research Group at IRBLleida. "This reinforces their usefulness for the early identification of individuals at high cardiovascular risk and for moving towards more personalised and precise prevention". He adds: "We are confident that these results will lead to changes in current clinical guidelines".

The study assessed the ability of both models to correctly discriminate which individuals would experience cardiovascular events and to adequately calibrate that risk. Over a mean follow-up of 5.1 years, the researchers recorded 293,737 total cardiovascular disease events under the PREVENT definition (myocardial infarction, stroke or heart failure) and 258,086 cardiovascular events under SCORE2 (myocardial infarction, stroke or cardiovascular death). The results demonstrate good performance of both tools in North America, Europe, Australia and other regions, as well as in international clinical trials, which - according to the study's expert authors - supports recommending their widespread use.

José Manuel Valdivielso notes: "Cardiovascular prevention depends to a large extent on correctly identifying who is most likely to develop cardiovascular disease in the coming years. Validating these tools across different countries and clinical settings builds confidence for both healthcare professionals and health systems, and above all allows us to get ahead of the disease". "And not only that", José Manuel Valdivielso continues, "but these two predictive scales have a high discriminative power in patients at intermediate risk. This group accounts for nearly half of all cardiovascular events and, as they fall into a 'grey zone', they often do not receive preventive treatments or adequate follow-up.  PREVENT and SCORE2 make it possible to identify which individuals in this group are truly at higher risk and, consequently, give us the opportunity to apply preventive measures and appropriate treatments, significantly reducing cardiovascular events and their consequences in people who were not even aware they were at risk".

Drawing on the extensive data from chronic kidney disease patients compiled by the Chronic Kidney Disease Prognosis Consortium (CKD-PC), the researchers also demonstrated an improvement in the predictive formulas when a renal health parameter - the presence of the protein albumin in the urine - was incorporated. "Chronic kidney disease is one of the conditions whose prevalence is rising worldwide, and the World Health Organization (WHO) estimates that by 2040 it will have become the fifth leading cause of global mortality. We also know that chronic kidney disease significantly increases cardiovascular risk. The study shows that incorporating an easy and inexpensive parameter to measure, such as albuminuria, further improves the predictive power of these tools," José Manuel Valdivielso emphasises.

In addition to validating both algorithms, the team developed scaling factors that allow PREVENT to be adapted for short-term risk predictions - between one and nine years - which could facilitate its use in clinical research and in the design of therapeutic trials, according to the experts.

In summary: The results support the use of PREVENT and SCORE2 across diverse clinical settings and may contribute to more precise cardiovascular risk stratification on a global scale. This could translate into better preventive decision-making and a more efficient allocation of healthcare resources aimed at reducing the burden of cardiovascular disease.

Article: Neuen, B.L., Major, R.W., Grams, M.E. et al. Multinational validation of the PREVENT and SCORE2 cardiovascular risk equations across 6.4 million individuals. Nat Med (2026). DOI: https://doi.org/10.1038/s41591-026-04437-z