ACE Inhibition and Novel Cardiovascular Risk Factors

• ClinicalTrials.gov Identifier: NCT00051389
• Recruitment Status: Completed
• First Posted: January 13, 2003
• Last Update Posted: February 18, 2016
• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by: National Heart, Lung, and Blood Institute (NHLBI)

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cardiovascular Diseases; Heart Diseases; Hypertension	Drug: Fosinopril	Phase 2

Detailed Description:

BACKGROUND:

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.

DESIGN NARRATIVE:

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 factor.

Study Design

• Study Type: Interventional (Clinical Trial)
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double
• Primary Purpose: Prevention
• Study Start Date: February 2002
• Actual Primary Completion Date: January 2007
• Actual Study Completion Date: January 2007

Arms and Interventions

Outcome Measures

Eligibility Criteria

• Ages Eligible for Study: 55 Years to 100 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

No eligibility criteria

Contacts and Locations

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• OverallOfficial: Marco Pahor; Wake Forest University Health Sciences

More Information

Publications:

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.

• ClinicalTrials.gov Identifier: NCT00051389
• Other Study ID Numbers: 155; R01HL068901 ( U.S. NIH Grant/Contract )
• First Posted: January 13, 2003
• Last Update Posted: February 18, 2016
• Last Verified: January 2008

Additional relevant MeSH terms:

Cardiovascular Diseases; Heart Diseases; Fosinopril; Angiotensin-Converting Enzyme Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents