Effects of E-cigarette Use on Health (VAPECHECK)

Longitudinal Effects of E-cigarette Use on Cardiovascular and Pulmonary Health

Electronic nicotine delivery systems (ENDS) are used by millions of Americans, however their long-term health effects are unknown. This research proposal will quantify the effects of long-term ENDS use on validated and novel biomarkers of cardiovascular and pulmonary disease and how they are influenced by use heaviness, age, body weight, and co-use of other products. This study will produce the most informative evidence to date on how long-term ENDS use affects cardiovascular and pulmonary health.

Study Overview

• Status: Recruiting
• Conditions: Electronic Cigarette Use
• Intervention / Treatment: Other: Health Assessments

Detailed Description

Electronic nicotine delivery systems (ENDS) are used by millions of Americans, however, their long-term health effects are unknown. Although ENDS use delivers far lower levels of carcinogens than tobacco smoking, very little is known about whether ENDS use affects the risks of developing cardiovascular (CV) or pulmonary diseases, two of the most highly prevalent causes of morbidity and mortality in the United States. This research proposal will quantify the effects of long-term ENDS use on validated and novel biomarkers of CV and pulmonary disease and how they are influenced by use heaviness, age, body weight, and co-use of other products. This research also will shed additional light on long-term ENDS use patterns and ENDS dependence. The importance of this study does not rest upon demonstrating adverse effects of ENDS use.

The study team will recruit up to 400 long-term, stable users of ENDS and up to 200 age- and gender-matched control participants who do not use ENDS or combustible cigarettes. They will undergo comprehensive biomarker assessments over 36 months. Biomarkers assess CV and pulmonary health status and risk and include vital signs, blood samples for systemic inflammation and oxidative stress, lipids, and markers of insulin resistance and cardiometabolic health. Arterial structure changes will be assessed using carotid ultrasound. Sympathetic nervous system activation will be assessed by heart rate variability and arterial diameters. For pulmonary measures, the study team will obtain non-contrast quantitative computed tomography (CT) images to assess air trapping and texture-based measures of inflammation. The researcher also will perform spirometry. Integrated cardiopulmonary health will be assessed via treadmill stress testing. Other measures will include exhaled carbon monoxide, real-time measures of nicotine product use, nicotine dependence, and use of cannabis and alcohol. Biomarker status over time will be compared across groups and related to ENDS use heaviness, use of other products, and person factors (i.e., age, gender, race/ethnicity, weight, and smoking history). About 130 participants who were phenotyped from 2019-2021 will be included.

The Primary Aim is to determine relationships between ENDS use heaviness and changes in our CV and pulmonary health biomarkers over 3 years. Biomarker status across ENDS users and non-users over time will be compared and associations between biomarker status and ENDS use heaviness within the ENDS user group will be examined.

The Secondary Aim is to characterize changes in ENDS use patterns and dependence over time and to determine how these are related to biomarker status changes and how they are influenced by the person factors described above. The primary and secondary CV measures are changes in common carotid artery intima-media thickness (CCA IMT) and grayscale median (GSM). The primary and secondary pulmonary measures are the changes in the quantitative CT measures of air trapping and parenchymal texture. This proposal will produce the most informative evidence to date on how long-term ENDS use affects CV and pulmonary health and disease risk.

• Study Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

• Study Contact: Name: James Stein, MD; Phone Number: 608-262-2075; Email: jhs@medicine.wisc.edu
• Study Contact Backup: Name: Timothy Baker, PhD; Phone Number: 503-387-5167; Email: tbb@ctri.wisc.edu

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53711
      • Recruiting
      • UW Center for Tobacco Research and Intervention

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The participants enrolled will comprise a large group of exclusive ENDS users who do not use combusted cigarettes and who have used ENDS regularly for at least 1 year. ENDS participants must have vaped at least 2 days/week for greater than or equal to 12 months, smoke very infrequently, and have no plans to try to stop vaping in the foreseeable future. The comparison non-user group also will be gender-matched and comprise those who report no vaping or smoking in the past 6 months and less than 5 times in 2 years.

Description

Inclusion Criteria:

• greater than or equal to 21 years of age
• has vaped a nicotine e-cigarette product at least 2 days/week for most weeks for greater than or equal to 12 months
• plans to remain in catchment area for greater than or equal to 3 years
• smoked 5 or fewer tobacco cigarettes in the past 6 months
• no serious CV, pulmonary, or other medical problems
• not currently pregnant
• no plans to stop vaping

Exclusion Criteria:

• serious CV, pulmonary, or other medical problems (e.g., moderate or severe aortic stenosis, class III or IV heart failure, blood pressure greater than or equal to 160/100 mmHg, interstitial lung disease, sarcoidosis, Stage 3 or 4 cancer)
• combusted or vaped cannabis use 3 days/week or more in the past 3 months
• currently pregnant
• not able to read an write English
• incarceration

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Non-users; Gender-matched control participants who do not use ENDS or combustible cigarettes	Other: Health Assessments; Participants will complete the blood tests, questionnaires, cardiovascular tests, and pulmonary test at visits 1, 2, and 4. Non-Contrast Chest CT and cardiopulmonary treadmill (VO2 max) stress tests will occur at visits 1 and 4. Visit 3 will not include cardiovascular and pulmonary tests.
ENDS users; Long-term stable users of electronic nicotine delivery systems, 21 years of age or older, who do not use combustible (conventional) cigarettes	Other: Health Assessments; Participants will complete the blood tests, questionnaires, cardiovascular tests, and pulmonary test at visits 1, 2, and 4. Non-Contrast Chest CT and cardiopulmonary treadmill (VO2 max) stress tests will occur at visits 1 and 4. Visit 3 will not include cardiovascular and pulmonary tests.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mean common carotid artery intima-media thickness (CCA-IMT)	Carotid ultrasound CCA-IMT measures the thickness of the carotid artery wall and is a measure of arterial injury. Rates of change vary by age, sex, and race, but less increase is associated with less cardiovascular disease risk.	Baseline to 3 years
Change in LAA-856	Quantitative computed tomography (CT) can measure LAA-856 [percent of lung voxels less than -856 HU], which describes air trapping. Less air trapping indicates less progression of obstructive ventilation in and risk of obstructive lung diseases.	Baseline to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in common carotid artery intima-media Grayscale Median (GSM)	Changes in Parenchymal Texture will be in part measured with carotid GSM. Captured via ultrasound, images analyzed using LifeQ Medical Plaque Analysis Software for GSM.	Baseline to 3 years

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Timothy Baker, PhD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2025
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2029

Study Registration Dates

• First Submitted: September 19, 2024
• First Submitted That Met QC Criteria: September 19, 2024
• First Posted (Actual): September 24, 2024

Study Record Updates

• Last Update Posted (Actual): December 24, 2025
• Last Update Submitted That Met QC Criteria: December 23, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavior; Smoking; Vaping
• Other Study ID Numbers: 2024-0684; A534253 (Other Identifier: UW- Madison); SMPH/MEDICINE/GEN INT MD (Other Identifier: UW Madison); 1R01HL175602-01 (U.S. NIH Grant/Contract); Protocol Version 10/23/25 (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All of the questionnaire and interview responses, the ecological momentary assessment (EMA) data, results of cardiovascular and pulmonary tests, and urine and blood test results will be preserved and shared to the Biologic Specimen and Data Repository (BioLINCC) in comma separated value (CSV) format.
• IPD Sharing Time Frame: The study team will submit processed and cleaned data to the Biologic Specimen and Data Repository (BioLINCC) approximately 3 months prior to any publication date or 3 months after the end of the performance period, whichever is sooner. Data will be available indefinitely (i.e., for as long as the BioLINCC repository is maintained or chooses to continue to archive our study data).
• IPD Sharing Access Criteria: Data will be shared with controlled access in BioLINCC for general research use, as allowed by the participant's informed consent agreement and the Institutional Certification.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No