Smoking as a Risk Factor in Atherosclerotic Cardiovascular Disease



Smoking as a Risk Factor in Atherosclerotic Cardiovascular Disease



Thomas R. Wyss and Florian Dick


Tobacco smoke is a major cause of death; it leads to an estimated 443,000 deaths per year in the United States. Cardiovascular disease accounts for a third of these smoking-associated deaths. Many decades ago, the epidemiologic association of smoking and cardiovascular disease was first recognized. Since then, a plethora of studies have supported these early findings and shown evidence for the dire consequences of exposure to tobacco smoke.


Active and passive (i.e., secondhand, environmental) smoking is a prominent independent risk factor for cardiovascular disease causing ischemic heart disease, cerebrovascular disease, peripheral arterial disease, and aortic aneurysm. Furthermore, smoking aggravates the effect of other major cardiovascular risk factors including dyslipidemia, hypertension, and diabetes. Smoking results in hemodynamic modifications, damages the endothelium, and produces thrombogenic and inflammatory effects leading to atherosclerosis and thrombosis. Small and large vessels are affected by these changes.


Last but not least, tobacco use is a major public health issue. Socioeconomically it causes an enormous financial burden through illnesses and related workforce loss. Prevention and elimination of tobacco consumption in turn is lifesaving. Even though smoking cessation programs have lowered the prevalence of nicotine addiction, today approximately 20% of the Unites States population are still active smokers. This chapter aims to discuss the general pathophysiologic mechanisms and the specific consequences on cardiovascular disease.



Pathophysiology


A large array of different substances (more than 4000 toxic chemicals) is inhaled to the alveoli when smoking tobacco, and a variety of biochemical processes are affected. Nicotine smoke has three key components:



Nicotine has a sympathomimetic effect by binding to cholinergic receptors and causes increased heart rate, blood pressure, and myocardial contractility, all of which in turn increase cardiac workload. Dopamine is also released, stimulating central nervous system receptors, causing alterations in stimulation and pleasure, which sets the ground for addiction.


Carbon monoxide binds to hemoglobin, creating carboxyhemoglobin, thus rendering hemoglobin incompetent to carry oxygen. This results in a subsequent reduction in oxygen availability. In turn, red blood cell mass increases and erythrocytosis develops to compensate for this loss of oxygen carriers, causing higher levels of hematocrit and thickening of blood.


Free radicals result in oxidant stress, causing inflammation, lipoprotein oxidation, platelet activation, and endothelial dysfunction.


Distinctive pathophysiologic actions are thought to be important aspects of evolution of cardiovascular disease driven by cigarette smoke. Vasomotor dysregulation, inflammation, predisposition to thrombosis, and abnormal lipid and sugar metabolism initiate a multilevel cascade in atherosclerotic transformation inducing vessel wall degeneration, which eventually forms the basis of cardiovascular disease.



Vasomotor Dysregulation


Nitric oxide plays an important role in the vasodilator function of the endothelium. The physiologic reaction to increased blood flow is an increase in cellular calcium, stimulating production of nitric oxide. Diffusion of nitric oxide from the endothelium into the smooth muscle cells mediates vessel wall relaxation, reducing vascular tone. In contrast, smoking inhibits endothelial production of nitric oxide and triggers sympathomimetic stimulation and therefore release of catecholamines, prompting smooth muscle cell activation and vasoconstriction reducing peripheral blood flow. Association of smoking with the level of coronary blood flow is variable. On the one hand it seems to be increased when smoking cigarettes, though less than expected for the amount of cardiac work increase; on the other hand a decrease in coronary blood flow has been documented in patients with existing coronary heart disease.



Inflammation


Smoking instigates an inflammatory process that leads to atherosclerosis. Generally, cigarette smoke causes leukocytosis and an increase in several inflammatory serum markers (e.g., interleukins, tumor necrosis factor α, and C-reactive protein), reflecting a chronic inflammatory process and functional abnormality, a thorough disorder of homeostasis—a systemic disease. Locally, at the vessel wall, this promotes specific changes. In brief, smoking prompts leukocyte adhesion, activation, and migration.


First, expression of leukocyte adhesion molecules (e.g., vascular cell adhesion molecule 1 [VCAM-1] and intercellular adhesion molecule 1 [ICAM-1]) on the endothelium is up-regulated. This is mediated by the decreased endothelial nitric oxide content and altered shear stress and hemodynamics at the vessel’s surface caused by smoking. Chemokines (e.g., monocyte chemotactic protein 1 [MCP-1]) directly attract monocytes, and their adhesion to endothelium further compromises its nitric oxide synthesis.


In addition, free radicals oxidize low-density lipoprotein (LDL) cholesterol, which activates monocytes as well. Activated monocytes then migrate through the chronically injured endothelium into the intima and release messenger substances that mediate vascular smooth muscle cell proliferation and attract even more macrophages. Complement activation and stimulated T lymphocytes also perpetuate the ongoing process by releasing proinflammatory cytokines, stimulating the whole course of inflammation. Endocytosis of cholesterol by the attracted cells creates foam cells, which found atherosclerotic plaques. Angiogenesis and neovascularization further distort the overlying endothelium, unsettling the vessel wall.


Eventually, inflammatory cells lead to destruction of the fibrous cap. Characterization of the stability and vulnerability of a plaque is difficult and appropriate imaging techniques for identification of plaques at risk and possible prediction of progression are still lacking.

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Aug 25, 2016 | Posted by in CARDIOLOGY | Comments Off on Smoking as a Risk Factor in Atherosclerotic Cardiovascular Disease

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