Prediction of individual lifetime cardiovascular risk and potential treatment benefit: development and recalibration of the LIFE-CVD2 model to four European risk regions.

Abstract

Aim: 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%CI 0.767-0.822). Predicted and observed CVD event risks were well calibrated in population-wide electronic health records data in the UK (CPRD) and Netherlands (ELAN). 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 SBP of 140 mm Hg was estimated to gain 0.9 years in the low risk region versus 1.6 years in the very high risk region from lifelong 10 mm Hg 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.

Interpretation: 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.

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Identifiers

ORCID for Leo Westbury: orcid.org/0009-0008-5853-8096

ORCID for Elaine Dennison: orcid.org/0000-0002-3048-4961

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