E-Cigarettes and Endothelial Function: Impact, Mechanisms, and Clinical Implications
Vaping aerosol triggers vascular cell stress and inflammation beyond nicotine exposure.
E-cigarettes, often regarded as safer alternatives to traditional tobacco products, have raised substantial concern regarding their long-term implications for vascular health. A critical component of cardiovascular risk is endothelial dysfunction, an early marker and driver of atherosclerosis and cardiovascular disease (CVD). This comprehensive article explores the latest evidence on the relationship between e-cigarette use and endothelial function, including the underlying mechanisms, acute versus chronic effects, key biomarkers, clinical implications, and regulatory perspectives.
Table of Contents
- Introduction
- Endothelial Function: Basics and Clinical Relevance
- Measurement and Biomarkers of Endothelial Function
- E-Cigarettes: Constituents, Prevalence, and Perceived Risks
- Acute Effects of E-Cigarette Use on the Endothelium
- Chronic E-Cigarette Use and Endothelial Dysfunction
- Biological Mechanisms: How E-Cigarettes Affect Endothelial Cells
- Comparison to Traditional Cigarette Smoking
- Cardiovascular Implications and Disease Risk
- Public Health, Regulation, and Future Directions
- Frequently Asked Questions (FAQs)
Introduction
The global surge in e-cigarette (vaping) use, especially among young adults and ex-smokers, is reshaping tobacco consumption patterns. Marketing often highlights purported safety compared to combustible cigarettes. However, emerging scientific research raises questions about the vascular safety of e-cigarette aerosol exposure. The endothelium, a thin layer of cells lining blood vessels, is particularly sensitive to toxins and is a crucial determinant of cardiovascular health.
Endothelial Function: Basics and Clinical Relevance
The endothelium regulates vascular tone, blood fluidity, inflammatory responses, and permeability. Healthy endothelial cells produce nitric oxide (NO), a potent vasodilator with anti-inflammatory and anti-atherosclerotic properties. Endothelial dysfunction is characterized by reduced NO bioavailability, increased oxidative stress, and increased permeability, setting the stage for hypertension, atherosclerosis, and thrombosis.
- Key functions: Vasodilation, anti-coagulation, barrier against inflammatory cells, and regulation of vascular growth.
- Clinical importance: Endothelial dysfunction is an early, reversible step in cardiovascular disease progression and a target for prevention strategies.
Measurement and Biomarkers of Endothelial Function
The most common non-invasive method to assess endothelial function in humans is flow-mediated dilation (FMD) of the brachial artery. Additional biomarkers include:
- Nitric oxide (NO) levels: Indicative of vasodilatory capacity.
- Endothelial nitric oxide synthase (eNOS): Enzyme critical for NO production.
- Markers of endothelial permeability: Including vascular endothelial growth factor (VEGF)–induced cell permeability.
- Oxidative stress markers: Such as H2O2 release.
- Circulating biomarkers: Inflammation, thrombosis, advanced glycation end product (RAGE) ligands (e.g., S100A8, HMGB1).
A 7.1% FMD cutoff has been suggested to denote healthy endothelial function, with values below signaling endothelial dysfunction and higher cardiovascular risk.
E-Cigarettes: Constituents, Prevalence, and Perceived Risks
E-cigarettes use a battery-powered heating element to aerosolize a liquid containing propylene glycol, glycerol, nicotine (often), and flavorings. Compared to combustible cigarettes, they produce fewer combustion products but create new compounds, some of which may be toxic to vascular tissues. Their popularity among youth and former smokers has increased dramatically in the last decade.
- Main constituents: Nicotine, propylene glycol, vegetable glycerin, various flavorings, and contaminants.
- Perceptions: Often marketed as safer than cigarettes, but long-term health data remain incomplete.
Acute Effects of E-Cigarette Use on the Endothelium
Several studies have assessed the immediate (acute) impact of e-cigarette inhalation on endothelial function:
- FMD impairment: Both nicotine-containing and nicotine-free e-cigarettes acutely reduce FMD, indicting impaired endothelial function after just one session or even as few as 10 puffs.
- Pooled analyses: Acute exposure leads to increased arterial stiffness (pulse wave velocity and augmentation index), suggesting increased cardiovascular load.
- Comparison with non-users: Immediate negative effects have been seen even with nicotine-free e-cigarette use, implicating components of the aerosol rather than nicotine alone.
These acute changes may temporarily compromise vascular health, even in individuals with no pre-existing cardiovascular disease.
Chronic E-Cigarette Use and Endothelial Dysfunction
The long-term consequences of chronic e-cigarette exposure on the endothelium are a central concern:
- Meta-analyses: Chronic exclusive e-cigarette use correlates with numerically lower FMD levels, suggestive of impaired endothelial function, though some studies show statistically non-significant differences.
- Notable cohort findings: FMD values among chronic e-cigarette users were consistently found to be below the 7.1% diagnostic threshold of healthy endothelial function (e.g., 5.3% vs 10.7% in non-users in some studies).
- Inflammatory biomarkers: Increased markers of inflammation, cell adhesion, and thrombosis are seen in e-cigarette users relative to non-users.
- Altered vascular biomarkers: Higher risks of hypercholesterolemia and hypertension observed through increased augmentation index (Alx).
These results support growing evidence that e-cigarettes may not be benign for vascular health and may contribute to early vascular pathology.
Biological Mechanisms: How E-Cigarettes Affect Endothelial Cells
Key mechanisms by which e-cigarettes induce endothelial dysfunction include:
- Reduced NO secretion: Sera from chronic e-cigarette users reduce VEGF-induced NO production in endothelial cells, despite unchanged eNOS expression.
- Oxidative stress: Increased H2O2 and reactive oxygen species production, suggesting that e-cigarette aerosol promotes oxidative stress in vascular tissues.
- Increased permeability: Enhanced microvascular permeability, potentially via the RAGE pathway and its ligands (e.g., S100A8, HMGB1), which are elevated in e-cigarette users.
- Distinct biomarker profiles: Patterns of inflammation and thrombosis markers differ from those induced by traditional smoking, indicating both shared and unique toxicological effects.
Collectively, these processes undermine endothelial health, increase cardiovascular risk, and may facilitate the development of atherosclerosis, hypertension, and thrombosis.
Comparison to Traditional Cigarette Smoking
| Parameter | E-Cigarettes | Traditional Cigarettes |
|---|---|---|
| Acute FMD impairment | Significant | Significant |
| Chronic FMD impairment | Lower FMD than non-users, magnitude varies | Lower FMD than non-users, larger and more consistent effect |
| Main toxic constituents | Aerosol particles, nicotine, flavorings, aldehydes | Combustion products, tar, CO, nicotine |
| Biomarker changes | Elevated RAGE ligands, oxidative stress | Inflammation, oxidative stress, carbon monoxide exposure |
| Major risk | Potential unique long-term endothelial harm via permeability and oxidative stress | Established high cardiovascular risk |
Notably, while some studies showed that switching from cigarettes to e-cigarettes improved some vascular markers, chronic e-cigarette use alone still resulted in lower FMD than non-use, and the issue is not fully settled in the scientific community.
Cardiovascular Implications and Disease Risk
Impaired endothelial function is an accepted surrogate marker and predictor for future cardiovascular disease. The evidence surrounding e-cigarettes indicates:
- Early marker: Endothelial dysfunction may serve as the first sign of vascular injury from e-cigarette use, preceding overt CVD.
- Atherosclerosis risk: Chronic exposure to endothelial-disrupting agents (including e-cigarette aerosol components) may accelerate the atherosclerotic process.
- Other cardiac risks: Associations with hypertension, arterial stiffness, and changes in heart rate variability are reported with regular e-cigarette use.
Restoration of endothelial function is possible by removing or reducing exposure to risk factors, highlighting the importance of early identification and regulatory control.
Public Health, Regulation, and Future Directions
With e-cigarettes gaining regulatory approval in many countries as a harm reduction tool, the vascular effects require careful consideration:
- Regulatory standards: FDA and other regulatory agencies rely on endothelial function data to design safe product standards and labeling requirements.
- Need for long-term studies: While acute and some chronic data point toward vascular harm, long-term human outcome data are limited and needed to clarify actual cardiovascular event rates attributable to e-cigarettes.
- Consumer safety: Public health messaging must carefully balance harm reduction benefits for smokers who switch to e-cigarettes with risks of endothelial and cardiovascular damage, especially for never-smokers and youth.
- Research directions: Identification of particular vape constituents causing vascular harm, genetic susceptibility markers, and reversal strategies are ongoing areas of investigation.
Frequently Asked Questions (FAQs)
Q: Do e-cigarettes cause endothelial dysfunction even without nicotine?
A: Yes, studies demonstrate that both nicotine-containing and nicotine-free e-cigarettes acutely impair flow-mediated dilation (FMD), indicating endothelial dysfunction is not solely attributable to nicotine.
Q: How do the effects of e-cigarettes on endothelium compare to traditional cigarette smoking?
A: Both forms negatively affect endothelial function. Chronic e-cigarette use impairs FMD to a lesser degree than conventional cigarette smoking based on current data, but still represents a risk compared to non-use.
Q: What is flow-mediated dilation (FMD), and why is it important?
A: FMD is a non-invasive ultrasound measure of endothelial function; lower values correspond to higher risk for developing cardiovascular diseases.
Q: Can switching from cigarettes to e-cigarettes restore endothelial function?
A: Some improvements may occur, but studies show that chronic exclusive e-cigarette use still results in suboptimal or below-threshold FMD values compared to non-users, signaling persistent endothelial dysfunction.
Q: Are the vascular risks of e-cigarettes reversible?
A: Endothelial dysfunction is often reversible upon removing the harmful exposure; however, evidence on the time frame and extent of recovery after quitting e-cigarettes is still emerging and may vary among individuals.
Conclusion
Emerging research indicates that both acute and chronic exposure to e-cigarette aerosol impairs endothelial function, as evidenced by reductions in FMD, altered NO release, heightened oxidative stress, and increased microvascular permeability and inflammation. While less damaging than traditional cigarettes, e-cigarettes are not without vascular risk. Given the endothelium’s central role in cardiovascular homeostasis, ongoing research and evidence-based regulation will be key to safeguarding public health, particularly among vulnerable groups like youth.
References
- https://pubmed.ncbi.nlm.nih.gov/36288290/
- https://www.tobaccoinduceddiseases.org/The-impact-of-chronic-electronic-cigarette-use-on-endothelial-dysfunction-measured,186932,0,2.html
- https://www.nature.com/articles/s41598-023-42750-6
- https://pubmed.ncbi.nlm.nih.gov/36316290/
- https://www.tobaccoinduceddiseases.org/Examining-the-association-of-habitual-e-cigarette-use-with-ninflammation-and-endothelial,162327,0,2.html
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