Coronary heart disease (CHD) increases with smoking and this factor interacts with hypercholesterolemia and hypertension in raising the incidence of this condition in a greater than linear fashion. This can be explained by the adverse effect of smoking on plasma fibrogen, platelet turnover and lipid profile. It may also be accounted for, however, by the acute bradycardia, increase in blood pressure and generalized vasoconstriction accompanying smoking, due to a nicotine-dependent activation of the sympathetic nervous system. These effects (which in heavy smokers can raise blood pressure permanently) are only partly offset by beta-blockers and can only be abolished by opposing the cardiac and vascular sympathetic influences by alpha and beta-blockade combined.