Smoking and CVD in the Multi-Ethnic Study of Atherosclerosis: Functional Form, Mediating Pathways, and Implications of Intensity Reduction

Abstract

Smoking as an epidemiological exposure can be quantified in terms of duration, intensity, pack-years, recency, and time of life. It is not clear which of these are important for cardiovascular disease, and how they should be modeled. Using the Multi-Ethnic Study of Atherosclerosis, generalized additive models for time to incident CVD were used to investigate the functional form of each aspect of smoking. Cox models were compared including various combinations of smoking intensity, duration, pack-years, and compound smoking indices. Duration was not associated with CVD, while current intensity was. Former smokers, regardless of duration, intensity or recency, were not at increased risk. We looked for mediating factors for current smoking and found modest mediation through coronary artery calcium, IL-6, tumor necrosis factor alpha, and fibrinogen. Unlike mortality outcomes, the association of smoking with incident CVD events was well captured by including merely a term for current smoking intensity.