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  1. The FDA Science Forum

2021 FDA Science Forum

Oxidative Stress and Ischemic Heart Disease (IHD) and Chronic Obstruction Pulmonary Disease (COPD) Mortality in the Golestan Cohort of Tobacco Users

Authors:
Poster Author(s)
Carol Christensen, FDA/CTP; Jia Wang, FDA/CTP; Sapna Thakur, FDA/CTP; Arash Etemadi, NIH/NCI; Neal Freedman, NIH/NCI; Christian Abnet; Sanford Dawsey; Mitchell Gail, NIH/NCI; Barry Graubard, NIH/NCI; Maki Inoue-Choi, NIH/NCI; Cory Holder, CDC; Lanqing Wang, CDC; Benjamin Blount, CDC; Jun Feng, CDC; Reza Malekzadeh; Mahdi Nalini; Hossein Poustchi; Masoud Khoshnia; Gholamreza Roshandel; Farin Kamangar; Paolo Boffetta, WHO; Cindy Chang, FDA/CTP;
Center:
Contributing Office
Center for Tobacco Products

Abstract

Poster Abstract

Background:

Biomarkers predictive of disease could improve our understanding of new tobacco product health risks. Oxidative stress from exposure to tobacco smoke has a role in the pathogenetic process leading to chronic obstructive pulmonary disease (COPD) and ischemic heart disease (IHD). The urinary metabolite 8-isoprostane is a biomarker of oxidative stress.

Methods:

We conducted a nested case-cohort analysis within the prospective Golestan Cohort Study (GCS) to estimate the relationship between 8-isoprostane concentration and mortality due to IHD and COPD. The GCS enrolled 50,045 Iranian adults ages 40-75 years between 2004-2008 and collected tobacco use data and urine specimens. Mortality was assessed by active follow-up through 2017. At baseline, we selected a stratified random sample of disease-free participants from age (+/- 55 years), sex (male/female), region (urban/rural) and smoking status (yes/no) groups. We measured 8-isoprostane concentration in baseline spot urine samples. We estimated the odds of IHD and COPD mortality by tertiles of creatinine-corrected 8-isoprostane among current cigarette smokers using conditional logistic regression adjusting for socioeconomic status, physical activity, body mass index, opiate use, smoking intensity and smoking duration. The IHD model additionally adjusted for diabetes and hypertension.

Results:

We included 347 participants (cases 179, noncases 168) in the IHD analysis and 235 participants (cases 60, and noncases 175) in the COPD analysis. The risk of IHD did not differ by 8-isoprostane tertile (T1: OR=1.0, T2: OR=0.7 (95% CI 0.4, 1.2), T3: OR= 0.9 (95% CI 0.5, 1.5). In contrast, the risk of COPD was greater in T2 (OR: 1.6, 95% CI 0.6, 4.4), and significantly greater in T3 (OR: 2.9, 95% CI 1.2, 7.4) compared to T1.

Conclusion:

We demonstrate that a baseline measure of an oxidative stress biomarker among smokers is associated with greater mortality risk of COPD, but not IHD, over an average of ten years of follow-up. This is one of the first investigations to link a biomarker measure and smoking-related disease outcomes and informs potential use of biomarkers to predict future disease risk.

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