Classic risk factors as included in the Framingham Risk Score become blurred in old age, and therefore may no longer predict cardiovascular mortality in older persons without history of cardiovascular disease.Also, in the past decades new biomarkers have emerged as predictors of cardiovascular mortality.In younger age groups, however, the additional value of these biomarkers beyond (combinations of) classic risk factors has been disappointing.We investigated the performance of classic risk factors and of some new biomarkers, in predicting cardiovascular mortality in very old people from the general population without history of cardiovascular disease.This study was performed in 302 participants without history of cardiovascular disease from the Leiden 85-plus Study, a population-based prospective observational cohort study among 599 85-year olds in the city of Leiden, the Netherlands.Classic risk factors did not predict cardiovascular mortality when used in the Framingham Risk Score, nor when used in a refitted model.Of the new biomarkers studied, homocysteine had most predictive power.Therefore, in very old people from the general population without history of cardiovascular disease, a plasma homocysteine level alone more accurately identifies those at high risk of cardiovascular mortality than classic risk factors included in the Framingham Risk Score (BMJ 2009; 338: a3083).Age-specific guidelines for primary prevention of cardiovascular disease in old age are needed.