PROJECTS LIST

1. Genetic bases of atherosclerotic vascular disease
   
   

   Identifying the genetic basis of complex disease such as atherosclerotic vascular disease is challenging. We have adopted several strategies to gain insights into the genetic basis of vascular disease, including:

   • Linkage analyses of ankle brachial index, a non-invasive measure of peripheral arterial disease (PAD) to identify genomic loci that influence PAD. The study population consists of African-American and non-Hispanic white hypertensive sibpairs participating in the GENOA study (PI: Dr. Stephen Turner). We are also performing linkage analyses of intermediate traits including lipid traits and novel risk factors such as C-reactive protein, homocysteine, fibrinogen, LDL particle size, and lipoprotein(a).
   • SNP association studies to identify variants in candidate genes in pathways of inflammation, coagulation, blood pressure regulation, vascular wall matrix, and lipid metabolism that are related to the ankle-brachial index and other vascular disease phenotypes.
   • Population and evolutionary genetics methods to identify genes in pathways of inflammation, coagulation, and blood pressure regulation, that may be under the influence of selection and therefore a higher priority in association studies of vascular disease.
2. Proteomic markers for vascular disease
   
   

   We are studying the relationship of novel protein markers in etiologic pathways of vascular disease to quantitative phenotypes of arteriosclerotic vascular disease (coronary artery calcium, cerebral cerebral leukoaraiosis, albuminuria, and ankle brachial index) in participants of the in participants of the Genetic Epidemiology Network of Arteriopathy (GENOA) study.

3. Physiological markers of arterial function
   
   

   We are evaluating the association of measures of arterial function with vascular disease phenotypes in 2 large community-based cohorts. The motivating hypothesis is that functional arterial measures (endothelial function and arterial compliance) provide integrated measures of the effects of diverse vascular risk factors and are associated with structural changes of arteriosclerosis. We want to know whether measures of arterial wall function improve the prediction of quantitative measures of arteriosclerosis beyond what is possible with current algorithms for risk-assessment (e.g., the Framingham Risk Score).

   The measures of arterial wall function are assessed non-invasively in the Echocardiography Research Center, (a GCRC satellite) in the Mayo Clinic's Gonda building. Endothelial function is evaluated by measuring brachial artery reactivity using vascular ultrasound. Arterial compliance or ‘stiffness’ is assessed by measuring pulse wave velocity using applanation tonometry. Arterial wave reflection is assessed by pulse analysis using applanation tonometry of the radial artery.

   The measures of arterial function are being obtained in two well-characterized, community-based cohorts with different burdens of conventional risk factors. The ‘high-risk’ cohort includes hypertensive sibships enrolled in the Genetic Epidemiology Network of Arteriopathy study (n = 1000 individuals) which is identifying genes influencing blood pressure and the cerebral, cardiac, and renal complications of hypertension. The ‘average risk’ cohort includes participants in the Epidemiology of Coronary Artery Calcification study (n = 938) who were ascertained without regard to hypertension or other cardiovascular risk factors.