Environmental tobacco smoke, cardiovascular disease, and the nonlinear dose-response hypothesis

Two recent government reports have focused attention on the hypothesis that environmental tobacco smoke (ETS) exposure increases the risk of cardiovas cular disease (CVD) in nonsmokers. The first report was published by the Ca lifornia Environmental Protection Agency (CAEPA) in 1997. The second report was issued in 1998 by the Scientific Committee on Tobacco and Health (SCOT H) in the United Kingdom. A meta-analysis of five large prospective epidemi ology studies reports that the relative risk for actively smoking 20 cigare ttes per day is 1.78. Active smoking exposes the smoker to approximately 16 times the ETS concentration, and 100- to 300-fold the total smoke dose exp erienced by a nonsmoker (Smith and Ogden, 1998, JAMA 280, 32-33.). Despite the much lower smoke exposure, these government reports estimate the relati ve risk for ischemic heart disease in ETS-exposed nonsmokers at 1.30 (CAEPA ) and 1.23 (SCOTH). As an explanation for this nonlinear dose-response anom aly, platelet aggregation is proposed to be a plausible and quantitatively consistent mechanism. Herein, evidence is presented suggesting that this lo w-dose hypothesis is inconsistent with the biochemistry and physiology of p latelets and with the literature on the cardiovascular pathology of active smoking. In addition, several important biases and confounders are ignored. These epidemiologic biases and confounders include the following: misclass ification of smokers as nonsmokers; improper use of death certificates as s urrogates for mortality statistics; underreporting of diabetes and hyperten sion in the relatives of smokers; and additional atherogenic risk factors i n smoking households. Future field studies on ETS and CVD should emphasize proximal markers of risk for thrombosis in exposed nonsmokers. Proximal thr ombogenic risk markers identified in field studies should be mechanisticall y examined under controlled exposure conditions.