No Risk-Free Nicotine Use: International Research Team Maps the Biological Hierarchy Risks to the Cardiovascular System
A recent review led by University Medical Center Mainz compares the effects of cigarettes, waterpipes, heated tobacco products, e-cigarettes, and nicotine pouches
Nicotine use is associated with measurable effects on the cardiovascular system, regardless of the delivery method used. This is the finding of a recent review led by University Medical Center Mainz. The researchers compiled molecular biology, preclinical, clinical, and biomarker data to compare the health consequences of cigarettes, waterpipes, e-cigarettes, heated tobacco products, and oral nicotine products such as nicotine pouches. The study revealed a graded cardiovascular risk: the greatest burden on the cardiovascular system was associated with combustion products such as cigarettes and waterpipes, while heated tobacco products and e-cigarettes fell into the moderate range. Oral nicotine products also posed a measurable cardiovascular risk. The findings were published in the renowned journal Nature Reviews Cardiology.
Tobacco use and nicotine addiction remain among the leading preventable causes of death. Worldwide, an estimated 1.20 to 1.25 billion people use tobacco. In 2023 alone, approximately 5.81 million people died as a result of direct tobacco use. In addition, another 1.66 million non-smokers died from the effects of secondhand smoke. Tobacco use is thus responsible for around 15 percent of all deaths among men and around 3 percent of deaths among women. Up to 40% of all tobacco- and nicotine-related deaths are attributable to cardiovascular disease.
The recent review by an international research team led by Univ.-Prof. Dr. Thomas Münzel, senior professor at the Department of Cardiology at University Medical Center Mainz, and Univ.-Prof. Dr. Andreas Daiber, head of the Molecular Cardiology research group at the Department of Cardiology at University Medical Center Mainz, shows that nicotine plays a significant role in damaging the cardiovascular system, irrespective of its form of administration. The analysis of molecular biology studies and clinical trials demonstrates that nicotine damages the blood vessels, increases oxidative stress, constricts blood vessels, and raises blood pressure and the risk of thrombosis.
The reasons for this are manifold. Among other effects, nicotine inhibits potassium channels in vascular smooth muscle, as well as the production of the enzyme eNOS (endothelial NO synthase) and the hormone prostacyclin. This impairs their vasoprotective and vasodilatory properties. At the same time, nicotine releases the messenger substance endothelin-1, which further constricts blood vessels. According to the study authors, the resulting vascular damage – so-called endothelial dysfunction – increases the risk of atherosclerosis, hypertension and heart failure.
In the review, these effects were measurable even after a single exposure to nicotine, and occurred across all delivery methods. "Nicotine is not an inert component that merely sustains addiction. Rather, it causes measurable, reproducible vascular damage. This has been demonstrated in animal models as well as in healthy volunteers and clinical cohorts," explains Professor Münzel.
To compare the different nicotine products – tobacco cigarettes, waterpipes, e-cigarettes, heated tobacco products, and oral nicotine products – the research team systematically combined three levels of evidence that have rarely been considered jointly until now: detailed data on toxic constituents and emissions, preclinical animal studies on vascular and endothelial mechanisms, and large-scale clinical and biomarker studies. Based on this data, the researchers were able to determine the extent to which every nicotine delivery method currently in use causes cardiovascular harm. "The result is unambiguous: combustion causes the greatest toxicity, but no nicotine-containing product – whether smoked, heated, vaped or taken orally – is risk-free for the cardiovascular system," emphasizes lead author Professor Münzel.
Original publication:
Münzel, T., Kuntic, M., Keaney, J. F. Jr, Lurz, J., Crea, F., Lüscher, T. F., Rajagopalan, S. & Daiber, A.
Nicotine-containing products and the cardiovascular system: mechanisms and global health implications. Nature Reviews Cardiology (2026).
DOI: https://doi.org/10.1038/s41569-026-01331-6
Contact:
Univ.-Prof. Dr. Thomas Münzel
Department of Cardiology
University Medical Center Mainz
phone +49 (0)174 218 9542
email
Press contact:
Nadine Berger M. Sc.
Corporate Communications
University Medical Center Mainz
phone +49 (0)6131 17-8434
email
The University Medical Center of the Johannes Gutenberg University Mainz is the only medical institution of supra-maximum supply in the German state of Rhineland-Palatinate and an internationally recognized science location. Medical and scientific specialists at more than 60 clinics, institutes organised in 11 departments work interdisciplinarily to treat around 395,000 patients per year. Highly specialized patient care, research and teaching are inseparably intertwined. Around 3,700 medicine and dentistry students as well as around 600 future medical, commercial and technical professionals are trained in Mainz. With a workforce of approximately 9,000 colleagues the University Medical Center Mainz is one of the largest employers in the region and an important driver of growth and innovation. Find more information online at www.unimedizin-mainz.de
[2025]