Use of intermediate cardiovascular endpoints in intervention studies: not as easy as it seems?

In the current issue of the Journal, Van den Berkmortel and coworkers' report on the effect of smoking cessation on cardiovascular risk reduction, as estimated by assessment of progression of carotid intima-media thickness (CIMT) and arterial stiffness. Much to the authors' surprise, their nonrandomised study among 33 subjects who stopped smoking for at least two years, 55 persistent smokers and 50 never-smokers showed no difference in rate of change in CIMT or arterial stiffness across the groups after two years of intervention. The intriguing question of the paper is whether the finding is true or may be attributed to potential flaws of the study, focussing on design and analytical procedures, the choice of the endpoint and the power of the study.