While RCTs remain the gold standard for solving therapeutic issues, it is equally clear that it would be unreasonable to expect that all these questions can realistically be answered by RTCs in a foreseeable future. Approaching some of these questions, such as those of the reduction of CV morbid and fatal events by treating grade 1 hypertensive individuals at low risk for CVD or the CV event reduction of liofestyle measures, would require trials involving many thousands of individuals for a very extended period and may also raise ethnical problems.