What happens to inflammatory markers when smokers kick the habit? A UW study published in the American Heart Association journal Arteriosclerosis, Thrombosis, and Vascular Biology reported on 1,652 smokers, including 888 that made an aided quit attempt. The authors analyzed levels of six markers of inflammation at baseline and a year later.

“Although the link between smoking and atherosclerosis is well-established and we know that inflammation mediates atherosclerosis, few studies have investigated the longitudinal effects of smoking cessation or continued smoking on inflammatory markers associated with cardiovascular disease risk,” said first author Cecile King, MD, MS, clinical instructor, Cardiovascular Medicine.

“This study helps characterize the inflammatory processes that contribute to increased cardiovascular disease risk in smokers. Our cohort is large and highly representative of the age, sex distribution, adiposity, and insulin resistance of contemporary smokers compared to older observational studies in the literature. By measuring newer inflammatory markers using state-of-the-art techniques, we addressed a critical gap in our understanding of smoking-associated arterial disease and the benefits of quitting smoking,” said James H. Stein, MD, Robert Turell Professor in Cardiovascular Research, Cardiovascular Medicine.

Researchers measured baseline and one-year follow-up levels of six inflammatory markers (urinary F₂ isoprostane:creatinine ratio, white blood cell count, C-reactive protein, plasma myeloperoxidase, D-dimer, and fibrinogen) in fasting blood samples from study subjects. The investigators also measured levels of insulin resistance and weight gain, and compared results between subjects who were still smoking at the end of one year versus those who had successfully quit. Cessation success was evaluated by monitoring exhaled carbon monoxide (CO) levels.

At baseline, among all smokers, smoking heaviness (exhaled CO level, number of cigarettes smoked per day, and pack-years [cigarettes per day multiplied by number of years smoked]) correlated with levels of three biomarkers of inflammation: urinary F₂ isoprostane:creatinine ratio, white blood cell count, and plasma myeloperoxidase. Two of these biomarkers reflect oxidative stress.

As expected, successful abstainers (n=344) gained more weight (an average of 4.0 pounds) and had larger increases in insulin resistance scores after one year in comparison to those who did not quit. Yet, in spite of weight gain, urinary F₂ isoprostanes and white blood cell count still declined in successful abstainers. The researchers concluded that smoking increases the risk of cardiovascular disease by increasing oxidant stress, which improves on successful cessation, despite an associated weight gain.

“This suggests that reduced inflammation in smokers who successfully quit is related to less oxidant stress. In addition to providing a mechanistic insight for cardiovascular disease risk in smokers, it provides a possible set of targets for preventive interventions among smokers,” said Dr. Stein.

Additional authors include UW Center for Tobacco Research and Intervention members Megan Piper, PhD, associate professor, Michael Fiore, MD, MPH, MBA, professor and director, and Timothy Baker, PhD, emeritus professor, all of General Internal Medicine, and Adam Gepner, MD, clinical adjunct assistant professor, Cardiovascular Medicine.

Resources:

• King CC, Piper ME, Gepner AD, Fiore MC, Baker TB, Stein JH. 2017. Longitudinal Impact of Smoking and Smoking Cessation on Inflammatory Markers of Cardiovascular Disease Risk. Arterioscler Thromb Vasc Biol. 37(2):374-379.