NICOTINE has been consumed in the form of tobacco and other plants for many hundreds of years. The compulsive use of tobacco has been observed in nearly every culture into which tobacco has been introduced. Nearly 30 percent of adult Americans smoke despite, in most cases, a desire to quit and despite common knowledge of the health hazards.1 Their failure to quit smoking is attributable in large part to the addictive properties of nicotine. Recently, nicotine has become available as a pharmaceutical agent, marketed as a chewing gum to help people stop smoking. In addition to its direct effect on . . .

Drug therapy. Pharmacologic aspects of cigarette smoking and nicotine addiction.

Objectives: To estimate the risk of ischaemic heart disease caused by exposure to environmental tobacco smoke and to explain why the associated excess risk is almost half that of smoking 20 cigarettes per day when the exposure is only about 1% that of smoking. Design: Meta-analysis of all 19 acceptable published studies of risk of ischaemic heart disease in lifelong non-smokers who live with a smoker and in those who live with a non-smoker, five large prospective studies of smoking and ischaemic heart disease, and studies of platelet aggregation and studies of diet according to exposure to tobacco smoke. Results: The relative risk of ischaemic heart disease associated with exposure to environmental tobacco smoke was 1.30 (95% confidence interval 1.22 to 1.38) at age 65. At the same age the estimated relative risk associated with smoking one cigarette per day was similar (1.39 (1.18 to 1.64)), while for 20 per day it was 1.78 (1.31 to 2.44). Two separate analyses indicated that non-smokers who live with smokers eat a diet that places them at a 6% higher risk of ischaemic heart disease, so the direct effect of environmental tobacco smoke is to increase risk by 23% (14% to 33%), since 1.30/1.06=1.23. Platelet aggregation provides a plausible and quantitatively consistent mechanism for the low dose effect. The increase in platelet aggregation produced experimentally by exposure to environmental tobacco smoke would be expected to have acute effects increasing the risk of ischaemic heart disease by 34%. Conclusion: Breathing other people9s smoke is an important and avoidable cause of ischaemic heart disease, increasing a person9s risk by a quarter. Key messages Analysis of 19 epidemiological studies shows that people who have never smoked have an estimated 30% greater risk of ischaemic heart disease if they live with a smoker (P This is surprisingly large—almost half the risk of smoking 20 cigarettes per day even though the exposure is only 1% of that of a smoker The excess risk from smoking one cigarette per day is 39%—similar to the risk in a non-smoker living with a smoker The effect is mainly explained by a non-linear dose-response relation between expsoure to tobacco smoke and risk of heart disease Detailed analysis shows no significant bias; dietary confounding can account for an excess risk of only 6%, so revising the excess risk from 30% to 23%

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Environmental tobacco smoke exposure and ischaemic heart disease: an evaluation of the evidence

Conventional nonsteroidal anti-inflammatory drugs inhibit both cyclooxygenase (Cox) isoforms (Cox-1 and Cox-2) and may be associated with nephrotoxicity. The present study was undertaken to assess the renal effects of the specific Cox-2 inhibitor, MK-966. Healthy older adults ( n = 36) were admitted to a clinical research unit, placed on a fixed sodium intake, and randomized under double-blind conditions to receive the specific Cox-2 inhibitor, MK-966 (50 mg every day), a nonspecific Cox-1/Cox-2 inhibitor, indomethacin (50 mg t.i.d.), or placebo for 2 weeks. All treatments were well tolerated. Both active regimens were associated with a transient but significant decline in urinary sodium excretion during the first 72 h of treatment. Blood pressure and body weight did not change significantly in any group. The glomerular filtration rate (GFR) was decreased by indomethacin but was not changed significantly by MK-966 treatment. Thromboxane biosynthesis by platelets was inhibited by indomethacin only. The urinary excretion of the prostacyclin metabolite 2,3-dinor-6-keto prostaglandin F1α was decreased by both MK-966 and indomethacin and was unchanged by placebo. Cox-2 may play a role in the systemic biosynthesis of prostacyclin in healthy humans. Selective inhibition of Cox-2 by MK-966 caused a clinically insignificant and transient retention of sodium, but no depression of GFR. Inhibition of both Cox isoforms by indomethacin caused transient sodium retention and a decline in GFR. Our data suggest that acute sodium retention by nonsteroidal anti-inflammatory drugs in healthy elderly subjects is mediated by the inhibition of Cox-2, whereas depression of GFR is due to inhibition of Cox-1.

Effects of specific inhibition of cyclooxygenase-2 on sodium balance, hemodynamics, and vasoactive eicosanoids.

The isoprostanes: Unique bioactive products of lipid peroxidation

Cardiovascular Toxicity of Nicotine: Implications for Nicotine Replacement Therapy

Cigarette smoking and hemostatic function

Measurement of renal and non-renal eicosanoid synthesis

Sudden cardiac death is the most frequent cause of mortality in industrialized societies accounting for the majority of the over 325,000 smoking-related deaths each year in the United States1. The strong link between cigarette smoking and the platelet-modulated syndrome of sudden cardiac death2,3 implicates smoking as a cause of platelet activation. Consistent with this hypothesis of a direct activation of platelets is that platelet turnover appears to be accelerated in apparently healthy smokers4,5. However, an enhanced turnover of platelets may be the result of their increased clearance following membrane alterations after interaction with a damaged vasculature and conversely, thrombosis has been shown to occur in vivo without evidence of increased turnover6–8. Thus, an enhanced platelet turnover in smokers may not necessarily reflect a direct activation of platelets in vivo. In fact, ex vivo aggregation has been found to be either increased9,10, unchanged4,12–14 or significantly decreased15,16 in chronic smokers.

Jacek Nowak

Papers

Cigarette smoking and hemostatic function

Measurement of renal and non-renal eicosanoid synthesis

Platelet — Vessel Wall Interactions in Individuals who Smoke Cigarettes

In vivo formation of prostacyclin and thromboxane A2 at the site of platelet-vascular interaction in humans.

Eicosanoids and sudden cardiac death.