Synergistic and non-synergistic associations for cigarette smoking and non-tobacco risk factors for Cardiovascular disease incidence in the atherosclerosis risk in communities (ARIC) study

Jay H. Lubin, David Couper, Pamela L. Lutsey, Hiroshi Yatsuya

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Introduction:: Cigarette smoking, various metabolic and lipid-related factors and hypertension are well-recognized cardiovascular disease (CVD) risk factors. Since smoking affects many of these factors, use of a single imprecise smoking metric, for example, ever or never smoked, may allow residual confounding and explain inconsistencies in current assessments of interactions. Methods:: Using a comprehensive model in pack-years and cigarettes/day for the complex smoking-related relative risk (RR) of CVD to reduce residual confounding, we evaluated interactions with non-tobacco risk factors, including additive (non-synergistic) and multiplicative (synergistic) forms. Data were from the prospective Atherosclerosis Risk in Communities (ARIC) Study from four areas of the United States recruited in 1987-1989 with follow-up through 2008. Analyses included 14 127 participants, 207 693 person-years and 2857 CVD events. Results:: Analyses revealed distinct interactions with smoking: including statistical consistency with additive (body mass index [BMI], waist to hip ratio [WHR], diabetes mellitus [DM], glucose, insulin, high density lipoproteins [HDL] and HDL(2)); and multiplicative (hypertension, total cholesterol [TC], low density lipoproteins [LDLs], apolipoprotein B [apoB], TC to HDL ratio and HDL(3)) associations, as well as indeterminate (apolipoprotein A-I [apoA-I] and triglycerides) associations. Conclusions:: The forms of the interactions were revealing but require confirmation. Improved understanding of joint associations may help clarify the public health burden of smoking for CVD, links between etiologic factors and biological mechanisms, and the consequences of joint exposures, whereby synergistic associations highlight joint effects and non-synergistic associations suggest distinct contributions. Implications:: Joint associations for cigarette smoking and non-tobacco risk factors were distinct, revealing synergistic/multiplicative (hypertension, TC, LDL, apoB, TC/HDL, HDL(3)), non-synergistic/additive (BMI, WHR, DM, glucose, insulin, HDL, HDL(2)) and indeterminate (apoA-I and TRIG) associations. If confirmed, these results may help better define the public health burden of smoking on CVD risk and identify links between etiologic factors and biologic mechanisms, where synergistic associations highlight joint impacts and non-synergistic associations suggest distinct contributions from each factor.

Original languageEnglish (US)
Pages (from-to)826-835
Number of pages10
JournalNicotine and Tobacco Research
Volume19
Issue number7
DOIs
StatePublished - Jul 1 2017

Bibliographical note

Funding Information:
The authors thank the staffand participants of the Atherosclerosis Risk In Communities (ARIC) study for their important contributions. DC, as a study PI, designed and directed the ARIC study. JHL developed the current proposal, designed and executed analyses. All authors contributed equally to development of analytic strategies, interpretation of results and preparation of the manuscript. The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). JHL was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics. The authors maintained full control over the management, analysis and interpretation of the data; the preparation, review, and approval of the manuscript; and were independent of funders. The authors do not have permission to share the data used in this project, which were sourced from the ARIC Coordinating Center (www2.cscc.unc.edu/aric/).

Publisher Copyright:
© The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.

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