Smoking and Atherosclerotic Cardiovascular Disease: Part II: Role of Cigarette Smoking in Cardiovascular Disease Development

Abstract

Potential mechanisms and biomarkers of atherosclerosis related to cigarette smoking – a modifiable risk factor for that disease – are discussed in this article. These include smoking-associated inflammatory markers, such as leukocytes, high-sensitivity C-reactive protein, serum amyloid A, ICAM-1 and IL-6. Other reviewed markers are indicative for smoking-related impairment of arterial endothelial function (transcapillary leakage of albumin, inhibition of endogenous nitric oxide synthase activity and reduced endothelium-dependent vasodilation) or point to oxidative stress caused by various chemicals (cholesterol oxidation, autoantibodies to oxidized low-density lipoprotein, plasma levels of malondialdehyde and F₂-isoprostanes and reduced antioxidant capacity). Smoking enhances platelet aggregability, increases blood viscosity and shifts the pro- and antithrombotic balance towards increased coagulability (e.g., fibrinogen, von Willebrand factor, ICAM-1 and P-selectin). Insulin resistance is higher in smokers compared with nonsmokers, and hemoglobin A1c is dose-dependently elevated, as is homocysteine. Smoke exposure may influence the kinetics of markers with different response to transient or chronic changes in cigarette smoking behavior.

KEYWORDS::

• atherosclerosis
• biomarker
• cardiovascular disease
• cigarette smoking

Acknowledgements

The authors gratefully acknowledge the support of Lynda Conroy in the editing process of this article and of the library staff of Philip Morris USA and of Philip Morris Research Laboratories GmbH, Germany, for managing all activities related to searching for and organizing the references.

Financial & competing interests disclosure

This work was supported in part by Philip Morris International, Inc. This work was also supported in part by Philip Morris USA, Inc., prior to the spin-off of Philip Morris International, Inc., by the Altria Group, Inc. on 28 March, 2008. The opinions and conclusions of the researchers are their own and do not necessarily reflect Philip Morris International, Inc.‘s position. Klaus von Holt is a former employee of Philip Morris International, Inc., now serving as a consultant. Martin Unverdorben is also a former employee of Philip Morris USA, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Notes

*Predisposing risk factors are presumed to work – at least in part – by impacting on causal risk factors.

^‡Nonmodifiable risk factors may act as surrogate measures for the amount of exposure to causal risk factors. With increasing age, the male sex tends to lose its predominant risk status compared with females as the females become postmenopausal.

HDL-C: High-density lipoprotein-cholesterol; LDL-C: Low-density lipoprotein-cholesterol.

Data taken from [43,44].

Data taken from [43].

Additional information

Funding

This work was supported in part by Philip Morris International, Inc. This work was also supported in part by Philip Morris USA, Inc., prior to the spin-off of Philip Morris International, Inc., by the Altria Group, Inc. on 28 March, 2008. The opinions and conclusions of the researchers are their own and do not necessarily reflect Philip Morris International, Inc.‘s position. Klaus von Holt is a former employee of Philip Morris International, Inc., now serving as a consultant. Martin Unverdorben is also a former employee of Philip Morris USA, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.