Novel CVD risk assessment model to assess individual treatment benefit in healthy people
A novel model (LIFEtime-perspective CardioVascular Disease: LIFE-CVD) has been developed that can accurately estimate individual-level prognosis and treatment-effects in terms of improved 10-year risk, lifetime risk and life-expectancy free of CVD. This can guide treatment decisions, as the benefit an individual can expect from preventive therapy varies based on risk factor burden, competing risks and treatment duration. To this end, the model considers both risk of hard CVD events and of non-CVD mortality. The LIFE-CVD can be used free of charge in the online calculator U-Prevent.
Recent guidelines now endorse lifetime risk-assessment, along with short-term risk estimation. Some of the lifetime risk estimators have limitations, however. For instance, they do not account for competing risk, like LIFE-CVD does by incorporating the risk of non-CVD mortality. Moreover, use of older data for development of the models lead to overestimation of risk. Generalizability across ages and nationalities is limited. Those considerations formed the rationale to develop an internationally validated competing-risk adjusted model that allows estimation of both 10-year and lifetime therapy benefit. The aim was to develop a model that estimates the effects of starting, stopping, altering or postponing specific pharmacotherapies and lifestyle strategies.
The LIFE-CVD model was developed based on data of the Multi-Ethnic Study of Atherosclerosis (MESA), using clinical predictors. The MESA cohort was chosen because of its wide range of baseline ages, relatively recent commencement (2000) and because participants show a high degree of ethnic diversity. CVD events were defined as fatal or non-fatal MI or stroke, resuscitated cardiac arrest and coronary heart disease-death. Baseline age-specific survival was combined with clinical predictors to estimate the risk of having a CVD-event or non-CVD mortality for each life year. Subsequently, the cumulative survival for each life-year was estimated, which is a combination of CVD risk and non-CVD risk. CVD-free life expectancy is defined as the median survival without a CVD event or death. By subtracting off-treatment from on-treatment CVD-free life-expectancy, the gain in life-years free of CVD was determined.
External validation was performed in the Atherosclerosis Risk in Communities, Heinz Nixdorf Recall, and the European Prospective Investigation into Cancer and Nutrition-Netherlands and Norfolk studies. The LIFE-CVD model showed good calibration and c-statistics were 0.67-0.76.
LIFE-CVD can assess the effect of cholesterol lowering, blood pressure lowering, aspirin-equivalent antithrombotic therapy and smoking cessation on 10-year and lifetime CVD absolute risk reduction, and life-years gained free of CVD, in apparently healthy people. Using the tool can enhance insight into therapy-benefit when using both the 10-year and lifetime estimates, and may facilitate personalized medicine and communication between doctor and patient.