Research Projects

Project 1: Cardiovascular Toxicity of Tobacco Products

Daniel J. Conklin, PhD University of Louisville

The goal of this project is to test the hypothesis that cardiovascular injury due to tobacco product use could be attributed primarily to volatile organic compounds (VOCs; e.g., formaldehyde, acetaldehyde, acrolein, benzene, xylene, etc...) generated in a variety of tobacco products.

This project aims to:

1. Quantify the cardiovascular (CV) toxicity of tobacco product-derived volatile organic compounds (VOCs) in vitro. To assess VOC-induced CV toxicity, we will evaluate the direct effects of VOC on human myocardial cell excitability, endothelial cells, and thrombosis.
2. Assess short-term and chronic toxicity of tobacco products in vivo. Using wild type (WT) and atherosclerosis prone (apoE-null) mice, we will determine whether short-term or chronic exposure to different tobacco products (combustible cigarettes, smokeless tobacco, ENDs, electronic and conventional hookah, with and without nicotine) affect atherosclerotic lesion formation, thrombosis, biomarkers of CV harm including circulating angiogenic and immune cells by flow cytometry, as well as changes in hemodynamics and cardiac electrophysiology, as measured by telemetry; and
3. Identify those individual VOCs that appear as likely mediators of the cardiovascular toxicity of tobacco products. To select VOCs to test for CV injury in vivo, we will distill results of both in vitro assays and in vivo animal models to arrive at VOCs that associate with acute or chronic outcomes in order to perform targeted assessment of VOC CV toxicity. In addition, we will dialog with Projects 2 & 3 regarding which VOC exposures are most associated with CV toxicity, e.g., MACE, in their cohort and population studies.

Project 2: Cardiovascular Injury Due to Tobacco Use

Naomi Hamburg, MD, MS    Boston University

Rachel Keith, MSN, PhD University of Louisville

The overall goal of this project is to evaluate how the use of tobacco products affects markers of cardiovascular health. The main objective of the CITU 2.0 project, which is an expansion of the CITU 1.0 project, is to continue to examine the cardiovascular effects of tobacco products with a focus on new and emerging products such as e-cigarettes and cigarillos.

The project specifically aims to:

1. Identify cardiovascular health effects associated with the use of e-cigarettes and cigarillos.
2. Examine acute cardiovascular health effects of e-cigarettes and cigarillos.
3. Identify cardiovascular health effects of chronic use of e-cigarettes and cigarillos.

Project 3: Cardiovascular Effects of Tobacco Products in Community-based Cohorts (CCC)

Michael J. Blaha, MD, MPH    Johns Hopkins University

Andrew DeFilippis, MD, ScM University of Louisville

Evaluation of products that are used less frequently in the US, such as cigars, pipes, and smokeless tobacco is challenging because epidemiological cohorts using these products are difficult to assemble and follow over time. As a result, there is limited data on the health effects of these products, and their short and long-term cardiovascular effects remain largely unknown. To overcome the limitation of insufficient power in individual NHLBI cohorts, Project 3 will leverage the Cross Cohort Collaboration (CCC) to harmonize data on tobacco use and its health effects across 18 cohort studies, creating the largest cardiovascular health assessment of cigar, pipe, and smokeless tobacco users till date.

This project aims to:

1. Create a harmonized “CCC-Tobacco” dataset leveraging individual participant tobacco use data (on cigar, pipe, smokeless tobacco (ST), and combustible cigarette use) from each cohort within the CCC.
2. Evaluate the impact of cigar, pipe, ST, and combustible cigarettes on biomarkers of subclinical cardiovascular injury, cardiovascular events, and VOC exposure profile within these cohorts.
3. Develop e-cigarette use data from existing NHLBI cohorts and study the pooled association with candidate markers of cardiovascular toxicity.