ACE Inhibition and Novel Cardiovascular Risk Factors
Information source: National Heart, Lung, and Blood Institute (NHLBI)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cardiovascular Diseases; Heart Diseases; Hypertension
Intervention: Fosinopril (Drug)
Phase: Phase 2
Sponsored by: National Heart, Lung, and Blood Institute (NHLBI)
Official(s) and/or principal investigator(s):
Marco Pahor, Affiliation: Wake Forest University
To determine the effects of an angiotensin converting enzyme inhibitor (ACE inhibitor),
fosinopril, on multiple blood markers in 286 adults at high risk for cardiovascular disease.
Study design: Prevention, Randomized, Double-Blind, Placebo Control, Crossover Assignment
Angiotensin converting enzyme inhibitors (ACE inhibitors) may prevent cardiovascular events
in high risk persons and improve skeletal muscle function in heart failure patients by means
of mechanisms that are independent of blood pressure changes. However, there is limited
knowledge of all the mechanisms underlying the therapeutic benefits of ACE inhibition. ACE
inhibitors may favorably modify markers of fibrinolysis, inflammation, endothelial function,
and extracellular tissue remodeling, all of which are associated with atherosclerosis and
cardiovascular disease. But, clinical trial evidence on these effects is limited. In
addition, polymorphisms of the ACE, angiotensinogen, PAI-1 and IL-6 genes may modify the
therapeutic response to ACE inhibitors.
This 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-6/IL-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
Minimum age: 55 Years.
Maximum age: N/A.
No eligibility criteria
Locations and Contacts
Cesari M, Kritchevsky SB, Baumgartner RN, Atkinson HH, Penninx BW, Lenchik L, Palla SL, Ambrosius WT, Tracy RP, Pahor M. Sarcopenia, obesity, and inflammation--results from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors study. Am J Clin Nutr. 2005 Aug;82(2):428-34.
Starting date: February 2002
Ending date: January 2007
Last updated: January 18, 2008