Structural and functional manifestations of human atherosclerosis: do they run in parallel?

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Luscher and colleagues have presented the much-awaited results of the ENCORE II multicentre trial.1 Its intent was to determine whether long-acting nifedipine, given in addition to statins, reverses endothelial dysfunction and retards progression of coronary atherosclerosis over 18–24 months in patients with stable coronary artery disease (CAD). Considered broadly, this study investigated the relationship between functional and structural expression of atherosclerosis. Coronary endothelial function was assessed with acetylcholine, a measure of nitric oxide (NO) bioavailability (see Figure 1 ).2 In 214 patients, as compared with placebo, nifedipine significantly improved coronary endothelial function. ENCORE II reinforces the conclusions of ENCORE I which found improved coronary endothelial function after just 6 months of nifedipine treatment and in the absence of background statins.3 The consistency of these findings indicates that multicentre trials of coronary endothelial testing yield reproducible results when conducted by capable investigators. While confirming the ENCORE I results, ENCORE II also demonstrates that the nifedipine-induced improvement in endothelial function persists for 2 years. Furthermore, as study drugs were washed out in advance of the follow-up endothelial testing, nifedipine appears to have favourably altered the biology of human atherosclerosis. In ENCORE II, change in coronary plaque volume was assessed by intravascular ultrasound (IVUS). In 193 patients, nifedipine as compared with placebo failed to retard the increase in plaque volume (1.0 vs. 1.9% increase in plaque size, nifedipine vs. placebo, respectively, P = non-significant). Thus, while nifedipine improved coronary endothelial function, it did not alter the progression of atherosclerosis. As endothelial function and atherosclerosis progression are both viewed as ‘barometers of cardiovascular risk’,4,5 the apparent dissociation between endothelial function and structural atherosclerosis in ENCORE II may not seem at first glance very satisfying. However, this result suggests that endothelial function and measures of structural atherosclerotic progression provide … *Corresponding author. Tel: +1 415 206 3024, Fax: +1 415 206 5447, Email: ganzp{at}medsfgh.ucsf.edu