<qa>  What was the primary goal of the double-blind cross-over, randomized, placeboThis was a double-blind cross-over, randomized, placebo controlled trial in 286 persons with high cardiovascular risk to compare the effects of 6 months of treatment with fosinopril and 6 months with placebo on the following primary outcomes: plasma plasminogen activator inhibitor-1 PAI-1 antigen, C- reactive protein CRP, interleukin-6 IL-6 and soluble vascular cell adhesion molecule-1 sVCAM-1. The secondary objectives were a to assess the effects of fosinopril on IL-6IL-6 Soluble Receptor ratio, PAI-1 activity, tissue plasminogen activator TPA antigen, fibrinogen, endothelin-1, TNF-alpha, soluble intercellular cell adhesion molecule-1 sICAM-1, E-selectin, matrix metalloproteinase-1 MMP-1 and tissue inhibitor of metalloproteinase-1 TIMP-1; and b to explore the effects of ACE, angiotensinogen, PAI-1, and IL-6 gene polymorphisms on these biomarkers, and test the interaction of the gene polymorphisms with the effects of fosinopril. The study had sufficient power to detect small changes in several biomarkers compared to placebo. The assessment of these biological mechanisms had clinical relevance for identifying the patients who may benefit the most from ACE inhibition. While the focus of the study was on novel cardiovascular risk factors, the results may also have future implications for developing new indications for ACE inhibitors, such as, for example, the prevention of age-related muscle wasting and physical disabilities in older persons, for which inflammation may be a causal factor. 