Professor Lin Yee Chen

Medical School
Twin Cities
Project Title: 
Multi-omics of Atrial Fibrillation and Atrial Myopathy

Atrial fibrillation (AF) is the most common heart rhythm abnormality. It affects more than 6 million people in the U.S., and that number is expected to rise to 12.1 million by 2030. AF increases with age and contributes to greater than 130,000 deaths and $6 billion in medical costs each year. Most importantly, it is associated with increased risks of stroke, heart failure, heart attacks, dementia, and death.

Unfortunately, there are still many aspects of AF that we do not know. We have yet to answer the following critical questions: Given how often AF is asymptomatic, are we finding everyone that has AF? Who is at greatest risk for AF? How can we best prevent AF? Once diagnosed, how do we determine the personalized risk for each AF patient for stroke, heart failure, heart attacks, or dementia? Are there other abnormalities of the heart that accompany AF that can indicate the severity of disease or risk of complications?

On the treatment side, current options for AF are limited. Invasive ablation procedures are only approximately 60% effective. Medications for AF can cause adverse side effects such as new abnormal heart rhythms. Blood thinners, which have bleeding risk, are often needed as well to help prevent AF-associated stroke. More research is needed to develop new procedures and novel medications to treat AF, and ddressing these questions will help advance the science and clinical practice of AF. 

Recent compelling evidence indicates that upstream to AF, atrial myopathy (characterized by structural or functional abnormalities in the atria) is a critical factor that drives the risk of cardiovascular disease (CVD) and neurocognitive outcomes. However, prior research has been limited by evaluating atrial myopathy as a static entity at a single time point; data on the trajectory of atrial myopathy progression and its determinants and biological underpinnings are critically lacking.

The development of high-throughput analysis tools, such as the SOMAScan proteomics platform, presents an opportunity to examine circulating plasma proteins in relation to atrial myopathy progression. Previous studies have directly profiled the proteins expressed in the left atrial (LA) via tissue samples, or LA protein expression changes in patients with AF. These studies have been limited by small sample sizes, lack of covariate adjustment, and cross-sectional design. Three longitudinal cohort studies have profiled plasma proteins with respect to risk of AF.  In regards to LA size and function, previous research from MESA has been reported that as compared to participants with persistently low NTpro-BNP (low and high based on the median value), participants with persistently high NTpro-BNP levels experienced a greater increase in LA maximum and minimum indexed volumes and a greater decrease in LA total, passive, active emptying fraction and longitudinal strain. However, large-scale examination of plasma proteins in relation to change in LA size and function has not been conducted.

To address this knowledge gap, these researchers will leverage the extensive data that are available from two cohort studies: Atherosclerosis Risk in Communities (ARIC) Study and MESA. These data include demographic/clinical, large-scale proteomics measured by SOMAscan (SomaLogic, Boulder, CO), and cardiac imaging. This project will be conducted in two stages. The first stage will evaluate the association of plasma proteins with change in LA size and function.


Project Investigators

Professor Lin Yee Chen
Yuekai Ji
Wendy Wang
Michael Zhang
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