Prediction of individualized lifetime benefit from cholesterol lowering, blood pressure lowering, antithrombotic therapy, and smoking cessation in apparently healthy people
Jaspers, Nicole E.M.; Blaha, Michael J.; Matsushita, Kunihiro; Van Der Schouw, Yvonne T.; Wareham, Nicholas J.; Khaw, Kay Tee; Geisel, Marie H.; Lehmann, Nils; Erbel, Raimund; Jöckel, Karl Heinz; Van Der Graaf, Yolanda; Verschuren, W. M.Monique; Boer, Jolanda M.A.; Nambi, Vijay; Visseren, Frank L.J.; Dorresteijn, Jannick A.N.
(2020) European heart journal, volume 41, issue 11, pp. 1190 - 1199
(Article)
Abstract
Aims: The benefit an individual can expect from preventive therapy varies based on risk-factor burden, competing risks, and treatment duration. We developed and validated the LIFEtime-perspective CardioVascular Disease (LIFE-CVD) model for the estimation of individual-level 10 years and lifetime treatment-effects of cholesterol lowering, blood pressure lowering, antithrombotic therapy, and smoking
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cessation in apparently healthy people. Methods and results: Model development was conducted in the Multi-Ethnic Study of Atherosclerosis (n = 6715) using clinical predictors. The model consists of two complementary Fine and Gray competing-risk adjusted left-truncated subdistribution hazard functions: one for hard cardiovascular disease (CVD)-events, and one for non-CVD mortality. Therapy-effects were estimated by combining the functions with hazard ratios from preventive therapy trials. External validation was performed in the Atherosclerosis Risk in Communities (n = 9250), Heinz Nixdorf Recall (n = 4177), and the European Prospective Investigation into Cancer and Nutrition-Netherlands (n = 25 833), and Norfolk (n = 23 548) studies. Calibration of the LIFE-CVD model was good and c-statistics were 0.67-0.76. The output enables the comparison of short-term vs. long-term therapy-benefit. In two people aged 45 and 70 with otherwise identical risk-factors, the older patient has a greater 10-year absolute risk reduction (11.3% vs. 1.0%) but a smaller gain in life-years free of CVD (3.4 vs. 4.5 years) from the same therapy. The model was developed into an interactive online calculator available via www.U-Prevent.com. Conclusion: The model can accurately estimate individual-level prognosis and treatment-effects in terms of improved 10-year risk, lifetime risk, and life-expectancy free of CVD. The model is easily accessible and can be used to facilitate personalized-medicine and doctor-patient communication.
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Keywords: Apparently healthy people, Cardiovascular disease prevention, Lifetime prediction, Therapy-benefit, Cardiology and Cardiovascular Medicine, Journal Article
ISSN: 0195-668X
Publisher: Oxford University Press
Note: Funding Information: The MESA study is supported by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the National Heart, Lung, and Blood Institute, and by grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from NCATS. The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract nos. (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I). Funding Information: The EPIC-NL study is supported by the ‘Europe Against Cancer’ programme of the European commission; Dutch ministry of health, Welfare and Sports; Netherlands Organization for Research and Development; and World Cancer Research Fund. The EPIC-Norfolk study was supported by the Medical Research Council, UK http://www.mrc.ac.uk/ (Ref: G9502233 and MR/N003284/1) and Cancer Research UK http://www.can cerresearchuk.org/ (CRUK, Ref: SP2024/0201 and 14136). The HNR study was funded by the Heinz Nixdorf Foundation [Chairman: Martin Nixdorf; Past Chairman: Dr jur. Gerhard Schmidt (deceased)]. This study is also supported by the German Ministry of Education and Science (BMBF), and the German Aero-space Center [Deutsches Zentrum für Luft-und Raumfahrt (DLR)], Bonn, Germany. The German Research Council Assessment supported the study (DFG project: ER 155/6-2) and funded the study of psychosocial factors and neighbourhood level information (DFG project SI 236/8-1 and SI 236/9-1). The sponsor of the study transferred the monitoring of the study to the German Ministry of Education and Science, Bonn, using an international advisory board and quality control as well as event committee. Funding Information: This work was partially funded by a grant from the Netherlands Heart Foundation (2016T026). Funding Information: The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; the Department of Veterans Affairs; or the U.S. Department of Health and Human Services. The authors thank the staff and participants of the ARIC study for their important contributions. The authors acknowledge and thank study participants, general practitioners, and the EPIC Norfolk study team for their contribution to the work. This work was partially funded by a grant from the Netherlands Heart Foundation (2016T026). The MESA study is supported by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01- HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC- 95167, N01-HC-95168, and N01-HC-95169 from the National Heart, Lung, and Blood Institute, and by grants UL1-TR-000040, UL1-TR- 001079, and UL1-TR-001420 from NCATS. The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract nos. (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I). The EPIC-NL study is supported by the Europe Against Cancer programme of the European commission; Dutch ministry of health, Welfare and Sports; Netherlands Organization for Research and Development; and World Cancer Research Fund. The EPIC-Norfolk study was supported by the Medical Research Council, UK http://www.mrc.ac.uk/ (Ref: G9502233 and MR/N003284/1) and Cancer Research UK http://www.can cerresearchuk.org/ (CRUK, Ref: SP2024/0201 and 14136). The HNR study was funded by the Heinz Nixdorf Foundation [Chairman: Martin Nixdorf; Past Chairman: Dr jur. Gerhard Schmidt (deceased)]. This study is also supported by the German Ministry of Education and Science (BMBF), and the German Aero-space Center [Deutsches Zentrum fur Luft- und Raumfahrt (DLR)], Bonn, Germany. The German Research Council Assessment supported the study (DFG project: ER 155/6-2) and funded the study of psychosocial factors and neighbourhood level information (DFG project SI 236/8-1 and SI 236/9-1). The sponsor of the study transferred the monitoring of the study to the German Ministry of Education and Science, Bonn, using an international advisory board and quality control as well as event committee. Publisher Copyright: © 2019 Published on behalf of the European Society of Cardiology. All rights reserved.
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