Nicotine-containing products and the cardiovascular system: mechanisms and global health implications

Tobacco use and emerging nicotine-delivery systems remain major, preventable drivers of cardiovascular disease worldwide. Although tobacco cigarette smoking has declined in some high-income regions, progress is uneven, with persistently high rates across parts of Europe, alongside rapidly expanding global markets for e-cigarettes, heated-tobacco products and oral nicotine formulations. Youth addiction to nicotine-containing products has emerged as an urgent public health challenge, as engineered e-cigarette devices delivering large nicotine doses facilitate early dependence and might establish lifelong exposure trajectories. Regulatory frameworks have not kept pace with this innovation, allowing new platforms to enter markets faster than safety evidence can mature. Leading cardiovascular societies and regulatory authorities agree that no nicotine-containing product can be safe for the cardiovascular system. Nicotine promotes sympathetic activation, haemodynamic stress, oxidative imbalance and inflammation, and endothelial nitric oxide synthase uncoupling and dysfunction, contributing to atherosclerotic plaque instability in animal models and humans. Studies in humans demonstrate adverse vascular responses across all nicotine-containing products, although interpreting studies requires caution and long-term outcome data are lacking. In this Review, we integrate mechanistic, biomarker, preclinical and clinical data to define a cardiovascular continuum of harm from nicotine-containing products, in which eliminating combustion reduces but does not eliminate vascular toxicity.