Reduced-nicotine cigarettes increase platelet activation in smokers in vivo: A dilemma in harm reduction

Nicotine is a primary constituent of tobacco and smoke, and its roles in causing addiction and causing disease are commonly conflated. In the present work, we investigated whether nicotine protects smokers' platelets against smoke-induced activation in vivo, raising a possible dilemma in harm-reduction strategies. In vivo platelet activation state (PAS) was measured by fixing blood at drawing and measuring a standard marker, platelet P-selectin (CD62P). We conducted two studies: (1) 32 smokers smoked three medium-nicotine (0.6mg nicotine) cigarettes for 1h. Following this initial conditioning phase, 16 subjects continued with five of the same cigarettes from 1-2.5h, resulting in a 33% increase in PAS. The other 16 subjects smoked five low/zero-nicotine cigarettes (0.05mg nicotine), causing a 94% increase in PAS. The increase in PAS caused by nicotine withdrawal in the second group is very significant (p.02). Any compensation in smoke-intake due to nicotine withdrawal in the second group was not measured in this study. (2) To determine whether nicotine modulates platelet activation by secondhand smoke (SHS), 16 nonsmokers were exposed to medium-nicotine smoke and 16 to low/zero-nicotine smoke for 1.5h on two consecutive days. Exposure to SHS increased PAS by 60% (p.01), but no difference in the medium and zero nicotine groups was observed (p.09). We conclude that in smokers, nicotine modulates platelet activation, and it may significantly moderate the risk of cardiovascular disease caused by non-nicotine smoke components. Conversely, reduced-nicotine cigarettes may increase harm.