An Evaluation of the Clinical Evidence on the Role of Inflammation and Oxidative Stress in Smoking-Mediated Cardiovascular Disease

The number of fatalities due to cardiovascular disease (CVD) continues to be far ahead of loss of human life caused by any other type of disease worldwide. According to the WHO, the annual global tobacco death toll is already 8.4 million and will reach 10 million by the year 2025. However, in contrast to other modifiable primary risk factors for CVD such as obesity, primary prevention strategies for smokers unable to quit are not available to date. This Review, by adopting the principles of evidence-based medicine, summarizes the most recent clinical studies on CVD in smokers, and concludes by suggesting a novel primary prevention strategy for CVD in smokers unable to quit. Evidence gathered from mechanistic studies involving basic research as well as large population-based approaches point to oxidative stress as the major insult imposed by cigarette smoke (CS), and a state of systemic inflammation, as signified by increased hs (high sensitivity) CRP levels in smokers, as the decisive pro-atherogenic response of the body to the initial insult. Since we identified oxidative stress induced by heavy metals as a significant pro-atherogenic activity of CS, strategies aimed at detoxifying heavy metals and combating inflammation appear as plausible approaches to counteract the accelerated onset of CVD in smokers. For this purpose, we discuss metal chelating agents and statins as promising novel primary prevention strategies in smokers unable to quit.