Tobacco Regulation and Addiction Center (A-TRAC)

The American Heart Association's Tobacco Regulation and Addiction Center (A-TRAC) researches the health effects of existing and emerging tobacco products to provide the FDA with the scientific evidence needed to responsibly regulate these products.

Despite how much we know about the harmful effects of tobacco, more than 1.2 billion people use tobacco and tobacco products worldwide. Nearly 6 million people die prematurely as a direct result of tobacco-related causes. 

45.3 million adults smoke in the United States and as a result, smoking kills nearly 443,000 people per year, or roughly 1 in every 5 deaths can be attributed to smoking. 

Although smoking is often associated with lung disease and cancer, heart disease is the leading cause of death for people who use tobacco products. To understand the relationship between heart disease and tobacco use, it’s critical to study tobacco products effects on the heart and lung systems. The American Heart Association's Tobacco Research and Addiction Center (A-TRAC) gathers cardiologists, scientists, and toxicologists to investigate the health impacts of existing and emerging tobacco products to inform responsible regulation. 

 

Mission

The American Heart Association has convened the University of Louisville and eight other academic institutions across the United States to form the Tobacco Regulation and Addiction Center (A-TRAC). A-TRAC supports development and evaluation of tobacco product regulation in order to protect public health and reduce tobacco-related disease, disability, and death. A-TRAC investigators conduct comprehensive multi-disciplinary research that addresses the FDA’s tobacco research priorities and trains future investigators.A-TRAC has helped to shape the production, marketing, and regulation of tobacco and tobacco-related products since 2013.


Videos


Research

Summary

ATRAC research  investigates the underlying mechanisms of tobacco-induced tissue damage that leads to heart disease, investigates the short and long term health impacts of tobacco use, identifies biomarkers for detecting cardiovascular injury, and identifies effective communication methods for changing perceptions about tobacco use. 

A-TRAC research generates scientific evidence of:

  • Toxicity of tobacco smoke, aerosol, and other inhaled substances,
  • Effects of tobacco products on addiction and abuse,
  • Short and long-term health effects of tobacco products,
  • Knowledge, attitudes, and behaviors related to tobacco product use,
  • Effective communication about the health effects of tobacco products,
  • Influence of tobacco marketing, and 
  • Impact of potential FDA regulatory actions.

 

Selected Publications

 See all A-TRAC Publications here


Team Members

 A-TRAC investigators at the 2017 annual meeting in Louisville, Kentucky.




Participating Institutions


Projects and Cores

Project 1: Cardiovascular Toxicity of Tobacco Products

Successful completion of this project will lead to the development of an animal model to establish standard toxicity changes and to the discovery of novel biomarkers of cardiovascular injury that can be associated with tobacco exposure. This project will provide new information regarding the contribution of reactive aldehydes to the cardiovascular toxicity of cigarette smoke and smokeless tobacco. These findings will be useful in developing policies for regulating HPHC in smokeless tobacco, cigarettes, and emerging tobacco products.

  1. Examine tobacco-induced endothelial injury. To examine tobacco-induced endothelial injury: In adult mice exposed to varying intensities of tobacco smoke and smokeless tobacco, we will identify urinary metabolites of tobacco-derived aldehydes and determine how these relate to the extent and duration of exposure. We will also determine how these markers are affected by gender, time, and duration of exposure.   We will identify specific indices of endothelial function and damage that robustly and sensitively reflect endothelial injury and thrombosis, as well as how these biomarkers of injury are related to the biomarkers of exposure.
  2. Delineate the contribution of harmful and potentially harmful (HPHC) constituents, such as aldehydes, to endothelial injury induced by tobacco exposure. To identify which constituents of tobacco and tobacco smoke contribute to endothelial damage, we will examine changes in the biomarkers of endothelial injury in mice exposed to individual constituents of exposure: nicotine, acrolein and crotonaldehyde. We will determine how removing them affects endothelial injury due to tobacco smoke and whether increases in the extent of exposure to these aldehydes and related reactive chemicals increases the extent of endothelial injury. 

 

Project 2: Cardiovascular Injury Due to Tobacco Use

Completion of this project will lead to the identification and validation of the novel biomarkers of endothelial injury that are associated with exposure to tobacco and tobacco constituents. From these studies, we will be able to assess which tobacco-associated biomarkers of injury reflect the extent and progression of cardiovascular disease and what magnitude of changes in these biomarkers translates into meaningful impacts on CVD outcomes.

  1. Elucidate the relationship between biomarkers of cardiovascular injury and exposure to tobacco smoke and smokeless tobacco. We will evaluate biomarkers of endothelial damage and predilection for thrombosis in a cohort of 480 smokers, smokeless tobacco users and non-smokers without overt CVD. We will determine how these biomarkers are associated with the extent and duration of exposure to tobacco constituents. To assess injury, we will measure endothelial vasodilator function, arterial stiffness, endothelium-derived microparticles, endothelial progenitor cells (EPCs), and changes in thrombosis. Exposure will be evaluated by measuring the urinary metabolites of nicotine and tobacco and tobacco-smoke derived aldehydes.
  2. Identify and compare the dose-dependent associations between tobacco exposure, measures of subclinical cardiovascular disease, and clinical cardiovascular events.  Using data from the Multi-Ethnic Study of Atherosclerosis (MESA) prospective cohort, we will examine associations between tobacco exposure and subclinical vascular disease as assessed by carotid intima-media thickness, coronary artery calcification, ankle brachial index, flow mediated dilation and arterial stiffening, and biomarkers of inflammation. We will also investigate the influence of tobacco exposure on progression of subclinical CVD surrogates in longitudinal assessments. These data will be analyzed after stratification by age, gender, race/ethnicity and medication use.  We will also elucidate the nature of the interaction between tobacco exposure, subclinical cardiovascular injury and subsequent 10-year cardiovascular events as well as total mortality.
  3. Validate candidate biomarkers associated with tobacco exposure in independent human cohorts. Candidate bio-measures reflective of tobacco-induced cardiovascular injury, identified in Aims 1 and 2 will be independently validated in The Jackson Heart Study (JHS) cohort and assessed for their association with urinary metabolites of nicotine and aldehydes. To determine the relationship between biomarkers of endothelial injury and tobacco exposure identified in Aim 1 that cannot be measured in banked samples, we will seek to conduct testing on baseline banked samples in the MESA cohort and/or the emerging ELSA-Brazil cohort and procure additional samples for the analysis of candidate biomarkers that cannot be evaluated in banked samples.

 

Project 3: Perception of Tobacco Use in Vulnerable Populations

To document communication methods for tobacco use, knowledge, risk perception and intention and determine the effect of socio-economic status, gender, age group and race on these outcomes. Investigators will examine channel use frequency (i.e., what are the most frequent channels for seeking tobacco-related communication and what are the most frequent channels for communicating with others about tobacco?) and the influence of several factors that modify these choices. 

 

Tobacco Product Evaluation and Exposure Core

The Tobacco Product Evaluation and Expose Core will provide members of AHA Tobacco Regulation and Addiction Center (A-TRAC) the research capabilities to 1) identify and evaluate tobacco product composition and constituents; 2) perform realistic tobacco product exposures in animal models such that delivery of tobacco products that replicates real world human exposures; 3) measure biomarkers of tobacco exposure and develop analytical techniques and approaches that improve our understanding of the complex relationship between markers of tobacco exposure and biomarkers of cardiovascular injury. The core will serve both the needs of center projects and be an active research core in its own right as it develops new and improved techniques that enhance the breadth and sensitivity of detection of tobacco product constituents and promotes better understanding of new and emerging tobacco products.

 

Cardiovascular Pathology Core

The Cardiovascular Pathology Core (Core C) will provide unified and validated measurements of several biomarkers of cardiovascular injury for Center Projects. Using state-of-the-art techniques, this core has already established Standard Operating Procedures (SOPs) for quantifying a range of biochemicals, metabolites, cytokines, and common and rare blood cells. The scope of the core services will not be limited to the requirements of these projects. It will refine ongoing areas of exploration and strive for developing novel assays to expand its repertoire.
 
The fertile and dynamic resources of the Core and the technical excellence of its investigators in cardiovascular pathology and toxicology will also enable other Tobacco Research Centers to interface with A-TRAC. The core will be housed in the Baxter II building in the Health Sciences Center of UofL. The core currently has state-of-the-art equipment for all its needs. Among the flowcytometers, the core has an LSR II an Accuri C6 and a MoFlo Legacy cell sorter. Other essential equipment includes a Cobas-Mira Plus chemistry analyzer, a CellDyn hematology analyzer, a Chrono-log aggregometer, a BioTek SynergyMX plate reader, and a Zeiss LSM 510 confocal microscope. Additional equipment for histology, immunohistochemistry and microscopic imaging are also available to core personnel. 


Research Training and Education Core

The overall goal of our Multidisciplinary Educational Training Core in the AHA-Tobacco Regulation and Addiction Center (A-TRAC) is to develop the next generation of basic, clinical, and translational academic investigators in tobacco-related cardiovascular medicine and policy and to cross-train investigators in tobacco regulatory science.