Targeting Inflammation to Treat Cardiovascular Aging
Status:
Completed
Trial end date:
2016-02-01
Target enrollment:
Participant gender:
Summary
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United
States with older age being a primary risk factor. The number of adults greater than age 65
years will almost double to 70 million by 2030, therefore identifying therapeutic strategies
for treating or preventing age-related disorders in humans is of major biomedical importance.
Cardiovascular aging, defined as a reduction in vascular and cardiac functions with normal
aging, occurs even in the absence of CVD risk factors and overt CVD. A key feature of
cardiovascular aging is stiffening of the large elastic central arteries such as the aorta.
This is important because aortic stiffness directly contributes to clinical problems such as
increased blood pressure, reduced blood flow to the heart muscle, and thickening of the heart
muscle. Therefore, these clinical consequences are hypothesized to mediate a substantial
proportion of the increase in CVD risk in older adults. However, effective drug treatments
for aortic stiffness are not currently available and the biological reasons (mechanisms)
involved in causing aortic stiffening remain undefined. In addition, the inability of smaller
blood vessels to relax, impairment of the heart to relax during the filling phase of the
heart cycle (i.e., diastole), and increased blood pressure variability, have all been linked
to aortic stiffness. Furthermore, chronic low-grade inflammation with advancing age has been
proposed to be a common mechanistic link (i.e., biological reason) between these reductions
in cardiovascular function in older adults. Therefore, the investigators propose that
inflammation could be a novel therapeutic target to treat cardiovascular aging in older
adults. Our central hypothesis is that inflammation mediates the age-related deterioration in
cardiovascular functions observed with advancing age through the development of oxidative
stress (i.e., imbalance between damaging oxygen free radicals vs. protective antioxidants).
Our hypothesis predicts that chronic inhibition of inflammation with Salsalate, an
FDA-approved anti-inflammatory drug similar to aspirin that is used to treat rheumatoid
arthritis pain and known to inhibit the 'master' regulator of inflammation in the cell (i.e.,
nuclear factor kappa B), will improve cardiovascular function in older adults. In addition,
the investigators hypothesize that the mechanism for the improvement in cardiovascular
function during inhibition of inflammation will be by suppressing oxidative stress. To test
our hypothesis, the investigators will randomize older healthy adults (age 50-79 years) to 3
g/day of salsalate or placebo (i.e., pill with inactive substance) pills for 4 weeks and have
cardiovascular function measured at baseline and again after 4 weeks.