Position: Assistant Professor
Degrees: MS, MD
Office Phone: 434-243-9396, Fax: 2-1998
Office Address: MR5 1206A
Project 1: Early Noninvasive Detection of Myocardial Microvascualr Dysfunction in Diabetes
Type 2 Diabetes has become an epidemic in the United States. Cardiovascular disease is the most common cause of death in this population and is two to four fold higher than the general population. This increased risk is at least partially attributable to the high prevalence of the metabolic syndrome with its multiple coronary heart disease risk factors including central obesity, hypertension, glucose intolerance, chronic inflammation, and dyslipidemia. However, recent trials have demonstrated that traditional risk factors alone are not completely predictive of disease burden particularly early in the disease process prior to the development of flow-limiting coronary stenoses. Diagnosis and prevention of cardiovascular disease development has, thus, been elusive in this high risk population. It is not entirely clear which factors, known or novel, contribute the most in very early disease and which therapies may be most beneficial.
It has been suggested that microvascular dysfunction, a composite of endothelial dysfunction, abnormal blood cell rheology, and abnormal blood viscosity, precedes the development of overt coronary stenoses and contributes to increased cardiovascular risk very early in disease development. Microvascular reactivity is affected by many aspects of the metabolic syndrome. Microvascular reactivity can be measured invasively at the time of cardiac catheterization by measuring myocardial blood flow and calculating the coronary flow reserve (CFR). Commonly used noninvasive tools may not be adequate to evaluate microvascular function in the heart at baseline or in response to therapy. The American Diabetes Association has recently released a consensus statement stating that better approaches are needed to screen for and identify coronary artery disease in patients with diabetes. Myocardial contrast echocardiography (MCE) and cardiac magnetic resonance imaging (CMR) provide noninvasive technology capable of directly measuring microvascular function within the heart. Our preliminary data with these modalities shows significantly reduced microvascular function in diabetes in the absence of significant coronary stenoses.
Prior to development of stenoses in the coronary arteries, plaque accumulates via positive remodeling preserving the lumen. This can be detected invasively through the use of intravascular ultrasound (IVUS). Coronary CT is a potential noninvasive modality able to assess this early remodeling process, but it requires a substantial radiation dose and iodinated contrast dye. In addition, CT requires calcification to have occurred within the plaque, a finding believed to occur well into the life of the plaque. It is unclear how early plaque development is related to microvascular function and if stabilization or regression of plaque with available therapies improves microvascular function.
The overall hypothesis is that CMR will predict invasive findings on CFR and IVUS providing a noninvasive mechanism to diagnose microvascular dysfunciton and thus early coronary disease. Secondary objectives will include demonstrating that CMR can be used to follow microvascular function noninvasively over time and that risk factors for the metabolic syndrome will predict disease burden using invasive and noninvasive meaasurements contrary to recent literature using standard noninvasive diagnostic methods. Such techniques may allow earlier noninvasive detection of disease as well as tailor treatment early in the disease process making prevention more cost effective.
Taylor, AM. Cardiometabolic risk management in type 2 diabetes and obesity. Current Diabetes Reports. 2008;8(5):345-352 (invited review).
Taylor AM, Hanchett R, Natarajan R, Hedrick CC, Forrest S, Nadler JL, McNamara CA. The effects of leukocyte-type 12/15-lipoxygenase on Id3-mediated vascular smooth muscle cell growth. Atherosclerosis, Thrombosis and Vascular Biology. 2005;25:2069-2074.
Taylor AM, McNamara CA, Hedelt A, Chaney C, Perry ML, Miller III TM, Tyler KD, McCall AL. Outcomes of a multidisciplinary team approach to cardiovascular risk reduction. Therapy. 2005;2(4):587-595.
Taylor AM, McNamara CA. Regulation of Vascular Smooth Muscle Cell Growth: Targeting the Final Common Pathway. Arterioscler. Thromb. Vasc. Biol. 2003;23:1717-1720.