Functional Arterial Changes in Atherogenesis

Project: Research project

Project Details

Description

Proposal. The broad long-term goal of the candidate is to develop new strategies to improve
cardiovascular risk assessment. The goal of this proposal is to evaluate the association of two measures
of arterial function - endothelial function and arterial compliance - with conventional and novel risk factors
on one hand and with sub-clinical atherosclerosis on the other hand. The hypothesis is that these
measures of arterial function mediate the deleterious effects of conventional and novel risk factors and
are associated with coronary atherosclerosis in asymptomatic individuals. The novel risk factors to be
studied include the 'conditional' risk factors (homocysteine, fibrinogen, lipoprotein (a), triglycerides, small
lense LDL, and C-reactive protein) and polymorphisms in selected candidate genes (endothelial nitric
:oxide synthase and angiotensin converting enzyme). Endothelial function will be assessed by brachial
artery reactivity using vascular ultrasound and arterial compliance assessed by pulse wave velocity using
applanation tonometry. Because the effects of novel risk factors on arterial function may depend on the
background of conventional risk factors, the measures of arterial function will be obtained in two
well-characterized, community-based cohorts with different burdens of conventional risk factors. In both
cohorts, coronary artery calcification measured by electron beam computed tomography, a quantitative
measure of subclinical atherosclerosis, is available at no cost for the present proposal.
Candidate. To obtain additional skills necessary for a career as an independently funded clinical
investigator, the candidate will complete courses in research design, biostatistics and genetic
epidemiology. Based on the training and experience obtained, the candidate plans to submit an RO1
application in Year 4 of the award building on the studies proposed in this application.
Environment. The candidate is supported by an accomplished team of mentors and consultants and has
access to unparalleled resources at Mayo Clinic Rochester for patient-oriented research including one of
the finest General Clinical Research Centers in the country.
StatusNot started

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