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      Performance of the Framingham risk models and pooled cohort equations for predicting 10-year risk of cardiovascular disease: a systematic review and meta-analysis

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          Abstract

          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.

          Electronic supplementary material

          The online version of this article (10.1186/s12916-019-1340-7) contains supplementary material, which is available to authorized users.

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          Most cited references50

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          2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults

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            Validation of the Framingham coronary heart disease prediction scores: results of a multiple ethnic groups investigation.

            The Framingham Heart Study produced sex-specific coronary heart disease (CHD) prediction functions for assessing risk of developing incident CHD in a white middle-class population. Concern exists regarding whether these functions can be generalized to other populations. To test the validity and transportability of the Framingham CHD prediction functions per a National Heart, Lung, and Blood Institute workshop organized for this purpose. Sex-specific CHD functions were derived from Framingham data for prediction of coronary death and myocardial infarction. These functions were applied to 6 prospectively studied, ethnically diverse cohorts (n = 23 424), including whites, blacks, Native Americans, Japanese American men, and Hispanic men: the Atherosclerosis Risk in Communities Study (1987-1988), Physicians' Health Study (1982), Honolulu Heart Program (1980-1982), Puerto Rico Heart Health Program (1965-1968), Strong Heart Study (1989-1991), and Cardiovascular Health Study (1989-1990). The performance, or ability to accurately predict CHD risk, of the Framingham functions compared with the performance of risk functions developed specifically from the individual cohorts' data. Comparisons included evaluation of the equality of relative risks for standard CHD risk factors, discrimination, and calibration. For white men and women and for black men and women the Framingham functions performed reasonably well for prediction of CHD events within 5 years of follow-up. Among Japanese American and Hispanic men and Native American women, the Framingham functions systematically overestimated the risk of 5-year CHD events. After recalibration, taking into account different prevalences of risk factors and underlying rates of developing CHD, the Framingham functions worked well in these populations. The sex-specific Framingham CHD prediction functions perform well among whites and blacks in different settings and can be applied to other ethnic groups after recalibration for differing prevalences of risk factors and underlying rates of CHD events.
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              Predicting the 10-Year Risks of Atherosclerotic Cardiovascular Disease in Chinese Population: The China-PAR Project (Prediction for ASCVD Risk in China).

              The accurate assessment of individual risk can be of great value to guiding and facilitating the prevention of atherosclerotic cardiovascular disease (ASCVD). However, prediction models in common use were formulated primarily in white populations. The China-PAR project (Prediction for ASCVD Risk in China) is aimed at developing and validating 10-year risk prediction equations for ASCVD from 4 contemporary Chinese cohorts.
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                Author and article information

                Contributors
                +31 88 75 693 77 , J.A.A.Damen@umcutrecht.nl
                R.Pajouheshnia@umcutrecht.nl
                P.Heus@umcutrecht.nl
                K.G.M.Moons@umcutrecht.nl
                J.B.Reitsma-2@umcutrecht.nl
                R.J.P.Scholten@umcutrecht.nl
                L.Hooft@umcutrecht.nl
                T.Debray@umcutrecht.nl
                Journal
                BMC Med
                BMC Med
                BMC Medicine
                BioMed Central (London )
                1741-7015
                13 June 2019
                13 June 2019
                2019
                : 17
                : 109
                Affiliations
                [1 ]Cochrane Netherlands, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
                [2 ]Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, P.O. Box 85500, Str. 6.131, 3508 GA Utrecht, The Netherlands
                Author information
                http://orcid.org/0000-0001-7401-4593
                Article
                1340
                10.1186/s12916-019-1340-7
                6563379
                31189462
                81f0e8c8-f0f1-46a8-892e-61979c32f13d
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 5 February 2019
                : 7 May 2019
                Funding
                Funded by: Cochrane Methods Innovation Funds Round 2
                Award ID: MTH001F
                Funded by: Cochrane Trusted methods and Support for Cochrane Reviews of Prognostic studies
                Award ID: -
                Funded by: Netherlands Organization for Scientific Research
                Award ID: 918.10.615
                Award ID: 91208004
                Award ID: 91617050
                Funded by: CREW NHS project
                Award ID: 2013T083
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Medicine
                cardiovascular disease,prediction models,prognosis,systematic review,meta-analysis
                Medicine
                cardiovascular disease, prediction models, prognosis, systematic review, meta-analysis

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