Changes in Cardiovascular Disease Risk, Lung Function, and Other Clinical
Health Outcomes When People Who Smoke Use E-cigarettes to Reduce Cigarette
Smoking: An Exploratory Analysis from a Randomized Placebo-Controlled
Trial
Authors: Dahal Sitasnu , Yingst Jessica , Wang Xi , Cobb Caroline O. , Carrillo Matthew , Hrabovsky Shari , Bascom Rebecca , Lopez Alexa A , Kang Le , Maloney Sarah , Halquist Matthew , Foulds Jonathan , Veldheer Susan 
Published: January 2025

ABSTRACT

Introduction
The health effects of dual use of electronic cigarettes (e-cigarettes)
and combustible cigarettes are unclear. We report on differences in
cardiovascular disease (CVD) risk factors, lung function, and clinical
laboratory markers among people who smoke used e-cigarettes to reduce their
cigarette smoking in a randomized placebo-controlled trial.

Methods
Participants (n=520) who regularly smoked cigarettes were randomized to
1 of 4 conditions (e-cigarette device paired with liquid containing 0, 8, or
36 mg/mL of nicotine or a cigarette-substitute [CS]) and encouraged to
reduce their smoking over 6 months. Group differences were assessed between
the e-cigarettes and CS conditions at baseline and 6-month using one-way
ANOVA and linear mixed-effects model. Multi-testing adjustment was not
applied as the analysis was exploratory in nature. Primary outcomes were:
CVD risk (i.e., blood lipids, C-reactive protein, blood pressure, heart
rate, waist-to-hip ratio, body mass index, and INTERHEART risk score), lung
function (i.e., spirometry indices and clinical COPD questionnaire), and
other clinical laboratory markers (i.e., complete blood count and complete
metabolic panel).

Results
At 6-month, use of nicotine e-cigarettes caused no significant
differences from control groups for most measures. However, participants
randomized to 36 mg/mL e-cigarettes had significantly higher levels of
high-density lipoprotein (HDL) (p=0.003 in
unadjusted analysis,p=0.002 in adjusted
analysis), and lower levels of low-density lipoprotein (LDL)
(p=0.044 in adjusted analysis) and
cholesterol/HDL ratio (p=0.034 in unadjusted
analysis,p=0.026 in adjusted analysis) as
compared to CS. Also, those in the 36 mg/mL e-cigarette condition had higher
levels of HDL as compared to those in 0 mg/mL condition
(p=0.016 in unadjusted
analysis,p=0.019 in adjusted
analysis).

Conclusions
Those randomized to the highest nicotine e-cigarettes had small
improvement in some measures of blood lipids (e.g., increased HDL, and
reduced LDL and cholesterol/HDL ratio) as compared to a non-aerosol CS among
individuals attempting to reduce their cigarette smoking. Future studies of
e-cigarettes for smoking cessation would benefit from including these
measures to further explore the results found in this study.

Trial Registration
ClinicalTrials.gov,NCT02342795.

Strengths and limitations of this study

The use of a randomized double-blind placebo-controlled trial
design with two nicotine concentrations and a relatively long
follow-up period (6 months).

Use of an additional randomized control group who did not use an
electronic cigarette device, but were given a “cigarette substitute”
product with no aerosol but similar behavioral
requirements.

Participants had to be daily cigarette smokers with no plans to
quit smoking, but an interest in reducing, and were recruited from
two U.S. sites. The results may only be generalizable to similar
populations.

These were exploratory analyses of a comprehensive group of
commonly used clinical markers, rather than hypothesis-driven
primary outcomes. These results therefore provide a preliminary
assessment of effects that may inform future studies.