Background: The Framingham risk models and pooled cohort equations (PCE) are widely used and advocated in guidelines for predicting 10-year risk of developing coronary heart disease (CHD) and cardiovascular disease (CVD) in the general population. Over the past few decades, these models have been extensively validated within different populations, which provided mounting evidence that local tailoring is often necessary to obtain accurate predictions. The objective is to systematically review and summarize the predictive performance of three widely advocated cardiovascular risk prediction models (Framingham Wilson 1998, Framingham ATP III 2002 and PCE 2013) in men and women separately, to assess the generalizability of performance across different subgroups and geographical regions, and to determine sources of heterogeneity in the findings across studies.

Methods: A search was performed in October 2017 to identify studies investigating the predictive performance of the aforementioned models. Studies were included if they externally validated one or more of the original models in the general population for the same outcome as the original model. We assessed risk of bias for each validation and extracted data on population characteristics and model performance. Performance estimates (observed versus expected (OE) ratio and c-statistic) were summarized using a random effects models and sources of heterogeneity were explored with meta-regression.

Results: The search identified 1585 studies, of which 38 were included, describing a total of 112 external validations. Results indicate that, on average, all models overestimate the 10-year risk of CHD and CVD (pooled OE ratio ranged from 0.58 (95% CI 0.43-0.73; Wilson men) to 0.79 (95% CI 0.60-0.97; ATP III women)). Overestimation was most pronounced for high-risk individuals and European populations. Further, discriminative performance was better in women for all models. There was considerable heterogeneity in the c-statistic between studies, likely due to differences in population characteristics.

Conclusions: The Framingham Wilson, ATP III and PCE discriminate comparably well but all overestimate the risk of developing CVD, especially in higher risk populations. Because the extent of miscalibration substantially varied across settings, we highly recommend that researchers further explore reasons for overprediction and that the models be updated for specific populations.