Prevention of cardiovascular disease in the elderly: moving towards an accurate risk predictor

Cardiovascular risk prevention programmes base on accurate risk prediction of cardiovascular morbidity and mortality. Within the Leiden 85-plus Study we recently showed (De Ruijter et al, BMJ 2009; 338:a3083) that the Framingham risk score, based on traditional risk factors, does not predict this risk correctly in older persons from age 85 years onwards. However, the 5-years cardiovascular mortality was predicted accurately by plasma homocysteine levels (HCYS). Before HCYS can replace traditional prediction scores for older persons in clinical practice and cardiovascular prevention programs, several questions need to be answered. First, the findings need to be replicated in a large cohort study of older individuals. Moreover, risk prediction based on HCYS in older persons younger than 85 years needs to be studied. Finally, the beneficial effect of preventive cardiovascular treatment in older persons with increased cardiovascular risk based on plasma HCYS has to be explored. And if cardiovascular treatment based on plasma HCYS proves to be effective, do plasma HCYS levels change with treatment? This project will give an answer to these questions by secondary analyses within the PROSPER study (Shepherd J et al. Pravastatin in elderly individuals at risk of vascular disease: a randomised controlled trial. Lancet 2002; 360:1623-1630) which has studied the effect of statins for primary and secondary cardiovascular prevention in older persons aged between 70 and 82 years. HCYS will be measured for all participants. The predictive value of HCYS for the incidence of cardiovascular events will be evaluated in the group without intervention (n=2913), depending on age. Effects of pravastatin treatment on cardiovascular morbidity and mortality will be evaluated comparing outcomes in treatment (n=2891) and placebo group, stratified for strata of HCYS. In this way, evidence for HCYS as risk predictor will thus be established in a simple and economical way, avoiding the cost of a new, large randomized controlled trial. If HCYS is confirmed to predict high risk of cardiovascular disease, and treatment based on HCYS will reduce this risk, results can be directly introduced in (inter)national guidelines.