Prediction of individual lifetime cardiovascular risk and potential treatment benefit: development and recalibration of the LIFE-CVD2 model to four European risk regions
Authors: Hageman Steven H J , Kaptoge Stephen , de Vries Tamar I , Lu Wentian , Kist Janet M , van Os Hendrikus J A , Numans Mattijs E , Läll Kristi , Bobak Martin , Pikhart Hynek , Kubinova Ruzena , Malyutina Sofia , Pająk Andrzej , Tamosiunas Abdonas , Erbel Raimund , Stang Andreas , Schmidt Börge , Schramm Sara , Bolton Thomas R , Spackman Sarah , Bakker Stephan J L , Blaha Michael , Boer Jolanda M A , Bonnefond Amélie , Brenner Hermann , Brunner Eric J , Cook Nancy R , Davidson Karina , Dennison Elaine , Donfrancesco Chiara , Dörr Marcus , Floyd James S , Ford Ian , Fu Michael , Gansevoort Ron T , Giampaoli Simona , Gillum Richard F , Gómez-de-la-Cámara Agustín , Håheim Lise Lund , Hansson Per-Olof , Harms Peter , Humphries Steve E , Ikram M Kamran , Jukema J Wouter , Kavousi Maryam , Kiechl Stefan , Kucharska-Newton Anna , Pablos David Lora , Matsushita Kunihiro , Meyer Haakon E , Moons Karel G M , Mortensen Martin Bødtker , Muilwijk Mirthe , Nordestgaard Børge G , Packard Chris , Pamieri Luigi , Panagiotakos Demosthenes , Peters Annette , Potier Louis , Providencia Rui , Psaty Bruce M , Ridker Paul M , Rodriguez Beatriz , Rosengren Annika , Sattar Naveed , Schöttker Ben , Schwartz Joseph E , Shea Steven , Shipley Martin J , Sofat Reecha , Thorand Barbara , Verschuren W M Monique , Völzke Henry , Wareham Nicholas J , Westbury Leo , Willeit Peter , Zhou Bin , Danesh John , Visseren Frank L J , Di Angelantonio Emanuele , Pennells Lisa , Dorresteijn Jannick A N 
Published: May 2024

Abstract

Aims
The 2021 European Society of Cardiology prevention guidelines recommend the use of (lifetime) risk prediction models to aid decisions regarding initiation of prevention. We aimed to update and systematically recalibrate the LIFEtime-perspective CardioVascular Disease (LIFE-CVD) model to four European risk regions for the estimation of lifetime CVD risk for apparently healthy individuals.

Methods and results
The updated LIFE-CVD (i.e. LIFE-CVD2) models were derived using individual participant data from 44 cohorts in 13 countries (687 135 individuals without established CVD, 30 939 CVD events in median 10.7 years of follow-up). LIFE-CVD2 uses sex-specific functions to estimate the lifetime risk of fatal and non-fatal CVD events with adjustment for the competing risk of non-CVD death and is systematically recalibrated to four distinct European risk regions. The updated models showed good discrimination in external validation among 1 657 707 individuals (61 311 CVD events) from eight additional European cohorts in seven countries, with a pooled C-index of 0.795 (95% confidence interval 0.767–0.822). Predicted and observed CVD event risks were well calibrated in population-wide electronic health records data in the UK (Clinical Practice Research Datalink) and the Netherlands (Extramural LUMC Academic Network). When using LIFE-CVD2 to estimate potential gain in CVD-free life expectancy from preventive therapy, projections varied by risk region reflecting important regional differences in absolute lifetime risk. For example, a 50-year-old smoking woman with a systolic blood pressure (SBP) of 140 mmHg was estimated to gain 0.9 years in the low-risk region vs. 1.6 years in the very high-risk region from lifelong 10 mmHg SBP reduction. The benefit of smoking cessation for this individual ranged from 3.6 years in the low-risk region to 4.8 years in the very high-risk region.

Conclusion
By taking into account geographical differences in CVD incidence using contemporary representative data sources, the recalibrated LIFE-CVD2 model provides a more accurate tool for the prediction of lifetime risk and CVD-free life expectancy for individuals without previous CVD, facilitating shared decision-making for cardiovascular prevention as recommended by 2021 European guidelines.