Key takeaways
- A review published in Nature Reviews Cardiology maps, for the first time, the full biological pathway by which nicotine damages blood vessels — from receptor activation to plaque rupture — and ranks cardiovascular harm across every major nicotine-containing product.
- The evidence shows a hierarchy of cardiovascular harm across all nicotine-containing products: highest with combustion products (cigarettes and waterpipes), then heated products, e-cigarettes and oral nicotine products – with complete abstinence the only risk-free option.
- Nicotine acts directly on two separate cell types in the vessel wall — the endothelial lining and the surrounding smooth muscle — compounding the damage through independent mechanisms.
- Tighter, unified regulation of all nicotine products is an urgent priority.
Sophia Antipolis, France – 20 August 2026: A review published today in Nature Reviews Cardiology provides the most detailed picture yet of how nicotine damages the cardiovascular system – tracing the biological chain of events from the moment nicotine binds to receptors in blood vessel walls through to the atherosclerotic plaque rupture that triggers heart attacks and strokes.1
Tobacco use and nicotine addiction remain among the leading preventable causes of premature death worldwide.2 In 2023 alone, more than 1 billion people globally smoked tobacco, causing an estimated 5.81 million deaths from direct tobacco use and a further 1.66 million deaths among non-smokers exposed to second-hand smoke.2,3 Close to 40% of these deaths are attributable to cardiovascular disease.2,3
Rather than focusing on a single product category, the review integrates mechanistic, biomarker, preclinical and clinical data across all major nicotine-containing products for the first time. "We wanted to settle a question that has been argued for years: is the harm caused by nicotine related to smoking or is nicotine toxic by itself?" explained lead author of the review, Professor Thomas Münzel from the University Medical Center Mainz, Germany. "We now show that nicotine activates receptors on blood vessel cells that switch off the enzyme that keeps vessels relaxed and open. This floods the vessel wall with damaging molecules and sets off a self-amplifying cycle of inflammation and clot formation. The pathway is active regardless of how the nicotine is delivered."
The review describes how nicotine attacks the vessel wall through two independent routes. In the endothelial lining, it suppresses prostacyclin — a natural vasodilator — and triggers release of endothelin-1, one of the body's most powerful vessel-constricting hormones. Separately, nicotine acts directly on the vascular smooth muscle cells that control vessel tone, blocking ATP-sensitive potassium channels and disrupting calcium handling, which favours constriction even when the endothelium itself is undamaged. "Nicotine doesn't only disable the vessel's protective lining — it directly tightens the muscle around it," said Professor Münzel. "These are two separate attack routes converging on the same outcome: a vessel that constricts more, relaxes less and clots more easily."
Building on this mechanistic map, the review establishes a consistent, evidence-graded hierarchy of vascular harm across product categories: highest with combustion products (cigarettes and waterpipes), then heated products, followed by aerosol devices (e-cigarettes), then oral nicotine products (chewing tobacco and pouches), with abstinence the only risk-free option. "E-cigarettes and heat-not-burn devices were initially marketed as reduced-risk alternatives to combustible cigarettes, but our data show these products sit on a continuum of cardiovascular risk, not off it," said Professor Münzel. "Removing combustion clearly reduces harm – but it does not remove it."
Author, Professor Filippo Crea, said, "This review closes an important evidence gap by evaluating, for the first time, existing mechanistic, biomarker and clinical data side by side across products, rather than product by product in isolation. It is apparent that nicotine is an active driver of endothelial dysfunction, the earliest step on the path to atherosclerosis, hypertension and heart failure — and only abstinence is risk free," he noted.
The authors highlight that nicotine is marketed as little more than a mild stimulant, comparable to caffeine. However, nicotine's dependence-forming potential is ranked alongside that of cocaine and heroin. "Nicotine's cardiovascular toxicity at the molecular level, combined with its well-documented, high dependence-forming potential make the case for a coherent, nicotine-based regulatory framework rather than the current patchwork of product-specific rules," said Professor Münzel.
President of the European Society of Cardiology and author, Professor Thomas F. Lüscher, said: "This research underscores why the ESC and the EU are calling for updated tobacco and nicotine regulation as an integral part of the Safe Hearts Plan. The evidence is clear that nicotine cannot be considered harmless. We must take this seriously in how these products are regulated, marketed and communicated to the public, especially to young people."
The review calls for greater efforts to prevent the initiation of nicotine-product consumption, particularly among young people, given the risk of addiction and lifelong exposure trajectories. In addition, integrating taxation, flavour bans and evidence-based cessation support are highlighted as being essential to end the evolving epidemic of nicotine-containing product consumption.
