Investigating the Pathogenesis and Clinical Applications of Arterial Health in Cardiovascular Diseases

Principal Investigator
de Azeredo Coutinho, Thais (Cardiology, University of Ottawa Heart Institute)

Mentor
Robert Beanlands

Network Affiliation
Canadian Vascular Network

 

1. The Health Problem/Issue

Many types of cardiovascular disease start in the arteries. More than simple blood pipes, the arteries have important additional functions. Due to their high elasticity, they serve as a pressure cushion to buffer the pulsatile energy that is created by the beating heart, and also maintain a steady flow of blood to all organs throughout the cardiac cycle. For these reasons, measuring arterial elasticity is a simple way to assess the health of the arteries. We have chosen to evaluate 2 diseases as part of this research program: thoracic aorta aneurysms (TAA) and heart failure with preserved ejection fraction (HFpEF). These are conditions that are increasingly common and are associated with a poor prognosis, but represent a clinical challenge for health care providers.
 
In TAA, the biggest artery in the body, the aorta, dilates and stretches. This may lead to tears or ruptures, which are often fatal. Our only tool to assess the risk of the aneurysm is its size. However, this is an imperfect strategy, and there is an urgent need to identify additional markers of aneurysm risk.
HFpEF is a syndrome where people have symptoms of heart failure despite having a normal pumping function of the heart. It is a poorly understood condition of growing incidence, but that has no effective treatments. Since arterial elasticity is important to optimize the performance of the heart, assessing how the heart and the arteries interact will provide new insights into this important condition.
 

2. The Objectives 

Our long-term goal is to identify markers of arterial health that are good biomarkers for cardiovascular diseases and that can be used throughout the disease spectrum: early on in pre-clinical stages, for early detection, risk assessment and prevention; and later on when disease is already established, for new therapies, therapeutic monitoring and assessment of prognosis. Since assessing measures of arterial health have significant potential to improve our knowledge and the care of people with TAA and HFpEF, this program will focus on these 2 conditions.
 
Thus, we have structured our research program in 3 stages: in the first stage, we will evaluate the role of arterial elasticity in the mechanisms underlying TAA and HFpEF. In the second stage, we will determine key measures of arterial elasticity that are predictors of growth of TAA, and that predict worsening of heart perfusion, metabolism and function in people at risk for HFpEF. In the third stage, we will consolidate the findings from the first 2 stages by testing the clinical utility of key measures of arterial elasticity as tools for risk stratification and therapeutic monitoring of TAA; and for early detection, prevention and prognostication of HFpEF. The present proposal represents THE FIRST STAGE of our program.
 

3. The Approach

As part of this program, over the next 3 years we will measure arterial elasticity in people with TAA, HFpEF as well as in volunteers without TAA or HFpEF (with and without high blood pressure). This will be done with special equipment that combines ultrasound of the heart with arterial tracings to non-invasively estimate the stiffness of the arteries. We will also measure the blood flow to the heart, and the metabolic efficiency of the heart using positron-emission tomography (PET) scans.
 
We will then determine whether patients with TAA have stiffer arteries than the volunteers without TAA. In addition, we will determine whether people with HFpEF have worse blood flow to the heart and impaired metabolic efficiency of the heart when compared to volunteers without HFpEF. We will also assess whether people with HFpEF who have stiffer arteries also have worse heart perfusion and impaired heart metabolic efficiency.
 

4. The Unique Factors 

So far, most research about TAA has focused on imaging techniques to visualize and measure the aneurysm, or on surgical techniques to correct it. Most HFpEF research has focused on abnormalities of the heart itself. Therefore, our proposition to approach these conditions from a functional arterial perspective (by studying the elasticity of the arteries) is innovative and not pursued by any other groups in Canada at present. In addition, the non-invasive technique we will use in this project is also unique and innovative, allowing us to estimate a number of arterial hemodynamic parameters that would otherwise only be available with invasive, intra-arterial catheters.
 

5. How the project is relevant to the objectives of the initiative 

TAA is considered a ‘killer at large’. When not fatal, TAA often leads to significant complications, such as need for emergency surgery, prolonged hospitalizations, and even heart attacks, strokes and loss of movement in the limbs. In addition, HFpEF is a condition that is growing more common each day, and that is associated with high rates of death and hospitalizations. Therefore, our research program links directly with two of the missions of the Heart and Stroke Foundation: to prevent disease and to save lives. By identifying new markers of disease activity that can help us identify TAA patients at higher risk of complications, our research will potentially improve our ability to prevent aortic tears and ruptures and save lives. In addition, by identifying new mechanisms that may predispose to HFpEF, our research program will highlight new targets for early detection and therapy development for people with this condition, also having significant potential to prevent disease and save lives.
 

6. The Impact

Firstly, by describing the abnormalities of arterial elasticity in patients with TAA, the proposed research will be valuable in the discovery of a new marker of disease activity in TAA. These findings will have immediate implications, as they will highlight new potential targets for therapies and for monitoring. In the long run, findings from this study will be used by us to conduct future evaluations that will determine the role of measuring arterial stiffness as a simple, cheap and non-invasive tool for identifying TAA patients at highest risk of complications. Given the very high rates of death and complications associated with this disease, our research has significant potential to positively impact the health and medical care of people with TAA.
 
Secondly, by studying the associations of measures of arterial elasticity with heart perfusion and metabolism in people with HFpEF, we will describe new mechanisms through which the stiffness of the arteries may adversely affect the heart. Identification of new mechanisms predisposing to HFpEF will be of great importance for development of new targeted treatments, and to allow us to identify people at risk early on and prevent this condition. Given the growing burden of HFpEF in our society, our research has excellent potential to lead to novel discoveries that will improve the health and medical care of people with HFpEF in the future.
 
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