Nicotine use is often framed as a problem of cigarettes, but a new review in Nature Reviews Cardiology argues that the cardiovascular threat extends across the rapidly expanding universe of nicotine-delivery products. E-cigarettes, heated-tobacco devices, nicotine pouches and other oral formulations may eliminate or reduce exposure to many toxic chemicals produced by combustion, yet they do not make nicotine harmless to the heart and blood vessels. Instead, the evidence points to a continuum of cardiovascular harm in which the absence of smoke lowers risk without removing the biological effects of nicotine or the vascular injury caused by other inhaled and absorbed substances.
The review comes at a moment when tobacco use is changing rather than disappearing. Cigarette smoking has declined in several high-income countries, but rates remain persistently high in parts of Europe and many other regions. At the same time, commercial markets for alternative nicotine products are expanding worldwide. Modern e-cigarettes can deliver substantial doses of nicotine through highly engineered heating systems, while heated-tobacco products aerosolize processed tobacco without fully burning it. Oral nicotine products, including pouches and other formulations, provide still another route into the bloodstream. Their different designs create different exposure profiles, but all are capable of sustaining nicotine dependence.
The most urgent concern may be the speed with which these products are reaching young people. Compact, discreet devices, sweet flavours, sophisticated branding and high nicotine concentrations can make initiation easier and dependence faster. Some newer systems use nicotine salts, which reduce the harshness of inhaled nicotine and allow users to consume larger quantities without the immediate irritation associated with older products. Early exposure may establish a long-term pattern of nicotine use, even among people who would otherwise never have smoked cigarettes. The review describes youth addiction as an escalating public-health challenge made more serious by regulatory systems that often move more slowly than product innovation.
Nicotine itself acts directly on the cardiovascular system through the sympathetic nervous system, the network responsible for the body’s rapid stress response. By stimulating the release of catecholamines such as adrenaline and noradrenaline, nicotine can increase heart rate, blood pressure and the force with which the heart contracts. This raises haemodynamic stress, requiring the cardiovascular system to work harder. Repeated exposure may impose recurrent episodes of vascular constriction and elevated pressure, particularly in people with underlying hypertension, diabetes, atherosclerosis or other cardiovascular vulnerabilities.
The biological effects extend beyond short-term changes in pulse and blood pressure. The review describes evidence that nicotine promotes oxidative imbalance and inflammation, two processes closely linked to vascular ageing and atherosclerosis. Oxidative stress occurs when reactive oxygen species overwhelm the body’s antioxidant defenses, damaging proteins, lipids and cellular signaling pathways. Inflammation can activate endothelial cells, alter immune-cell behavior and encourage the development of unstable arterial plaques. These effects matter because atherosclerotic disease is not simply the accumulation of cholesterol; it is an active process in which injured vessel walls, immune responses and disrupted blood flow can eventually produce a heart attack or stroke.
One mechanism highlighted by the authors involves endothelial nitric oxide synthase, or eNOS, an enzyme that helps blood vessels produce nitric oxide. Nitric oxide signals the smooth muscle surrounding arteries to relax, supports healthy blood flow and helps prevent platelets and inflammatory cells from adhering excessively to the vessel wall. Under conditions of oxidative stress, eNOS can become “uncoupled,” producing reactive molecules instead of beneficial nitric oxide. The result is endothelial dysfunction, a measurable failure of the inner lining of blood vessels to regulate tone and protect against inflammation and clot formation. This dysfunction is considered an early warning sign of cardiovascular disease and has been observed in studies of people using different nicotine-containing products.
Laboratory and animal research adds to the concern. Experimental studies have associated nicotine exposure with vascular constriction, oxidative injury, inflammatory signaling and changes that may promote plaque instability. Human investigations have reported adverse vascular responses after exposure to cigarettes, e-cigarettes and other nicotine products, although the review emphasizes that these studies must be interpreted carefully. Many are small, use short follow-up periods or examine surrogate markers rather than heart attacks, strokes and cardiovascular deaths. Product formulations also vary widely, making direct comparisons difficult. A device’s effects may depend on nicotine concentration, heating temperature, aerosol composition, frequency of use and whether the user also smokes conventional cigarettes.
That uncertainty does not mean the products are risk-free; it means that the full scale of their long-term danger is still being established. Cigarette smoking has been studied for decades, producing overwhelming evidence of cardiovascular harm. By contrast, many newer devices have existed for too little time to reveal their consequences across an entire lifetime. The absence of definitive long-term outcome data can therefore be misleading, especially when products are marketed as modern, clean or safer alternatives. Reduced exposure to combustion products is biologically meaningful, but it should not be confused with the elimination of vascular toxicity.
The distinction is particularly important for people who use more than one product. Dual use of cigarettes and e-cigarettes or other nicotine systems may preserve much of the exposure associated with smoking while adding a new source of nicotine and aerosol constituents. Even when combustion is eliminated, inhaled particles, flavoring chemicals, thermal degradation products and other components may interact with nicotine to affect the cardiovascular system. Oral products avoid inhalation but still deliver pharmacologically active nicotine, which can produce sympathetic stimulation and haemodynamic stress. No route should be assumed to be cardiovascularly neutral simply because it does not generate tobacco smoke.
The review’s broader message is that public-health policy must keep pace with a market capable of evolving faster than safety research. Leading cardiovascular organizations and regulatory authorities agree that no nicotine-containing product can be considered safe for the cardiovascular system. Effective prevention will require stronger protection for young people, careful oversight of nicotine concentrations and product design, restrictions on marketing that normalizes dependence, and research capable of tracking long-term outcomes. For adults who smoke, switching completely away from combustible tobacco may reduce exposure to some of the most dangerous toxicants, but the safest cardiovascular strategy remains stopping nicotine use altogether. As the nicotine market fragments into increasingly sophisticated forms, the central scientific warning remains consistent: less harmful than cigarettes is not the same as harmless.
Subject of Research: The cardiovascular effects and global health implications of nicotine-containing products, including cigarettes, e-cigarettes, heated-tobacco products and oral nicotine formulations.
Article Title: Nicotine-containing products and the cardiovascular system: mechanisms and global health implications
Article References: Münzel, T., Kuntic, M., Keaney, J.F. et al. Nicotine-containing products and the cardiovascular system: mechanisms and global health implications. Nature Reviews Cardiology (2026). https://doi.org/10.1038/s41569-026-01331-6
Image Credits: AI Generated
DOI: 10.1038/s41569-026-01331-6
Keywords: nicotine, cardiovascular disease, tobacco, e-cigarettes, heated-tobacco products, oral nicotine, endothelial dysfunction, oxidative stress, inflammation, youth addiction, atherosclerosis, public health
