Smoking is a well-documented risk factor for CVD that is amenable to intervention. A potential mechanism for the atherogenic effect of cigarette smoke is via plasma HDL. Most research to date has looked at smoking effects on HDL-C concentration rather than HDL structure or function. One issue that is particularly difﬁcult to address in observational smoking research is the presence of confounding lifestyle behaviours that may cluster with smoking behaviour (such as low physical activity, poor diet and increased alcohol consumption). Thus, comparison of the properties of HDL isolated from smokers and non-smokers does not allow direct causal relationships to be determined, and there is a need for more direct experimental approaches to dissect the biological effects of smoking and to identify speciﬁc mediating factors (i.e. the combustible products of tobacco such as nicotine, carbon monoxide and other gaseous products and free radicals). To further complicate the issue, smoking has effects on TAG metabolism, via increased sympathetic drive, insulin resistance or both, leading to increased plasma TAG concentrations and consequent remodelling effects of plasma HDL resulting in higher plasma turnover [reviewed in Freeman and Packard (1995)].
Smoking and HDL-C Concentration
A meta-analysis carried out almost 25 years ago indicated that smoking has a strong independent effect on plasma HDL-C levels with smokers having on average 6 % lower HDL-C concentrations compared to non-smokers (Craig et al. 1989). A more recent meta-analysis, which compared within individual differences before and after stopping smoking, indicated that the absolute HDL-C concentration difference was between 0.06 and 0.11 mmol/L (Forey et al. 2013). There also appears to be a larger smoking effect in women than men (Freeman and Packard 1995). HDL-C concentrations rise after stopping smoking and fall on restarting, and the magnitude of the effect on HDL-C is related to the number of cigarettes smoked (Fortmann et al. 1986; Moffatt et al. 1995; Stubbe et al. 1982; Tuomilehto et al. 1986). There are no long-lasting effects of smoking on HDL-C concentration after cessation (Forey et al. 2013), and there is no association between number of years stopped and plasma HDL-C (Wilson et al. 1983). Passive smoking is also associated with lower plasma HDL (Moffatt et al. 1995; Neufeld et al. 1997), and a reduction in HDL-C has been observed acutely only 6 h after exposure to environmental tobacco smoke (Moffatt et al. 2004). The reduction in plasma HDL-C levels appears to be limited to a 0.15 mmol/L reduction in the larger HDL2 particles, independent of confounders, as determined by analytical ultracentrifugation (Freeman et al. 1993). This has been conﬁrmed by others (Moriguchi et al. 1991; Shennan et al. 1985; Moffatt et al. 2004), although one study attributed the acute effects of smoking to the smaller HDL3 fraction (Gnasso et al. 1984). Plasma apoA-I levels are also 6 % lower in smokers (Craig et al. 1989), and in some studies apoA-II has also been shown to be reduced in smokers (Berg et al. 1979; Haffner et al. 1985) and ex-smokers (Richard et al. 1997).