Current Pharmaceutical Design - Volume 16, Issue 23, 2010

Smoking appears to be always the most harmful risk factor for heart and blood vessels being targeted by some of the organs tobacco components [1-3]. Of these, primarily nicotine and its metabolites and carbon monoxide, the latter is not a product of tobacco fresh leaf but develops from lit cigarette, are strongly associated with the damage of cardiovascular system. Generally, the reviews on tobacco smoke indicate the damage caused by cigarettes and lacking the systematic findings on the harm caused by pipe or cigar smoking that are common industrial products of tobacco [4]. In addition, a question that needs some clarifying concepts is: what is the definition of tobacco smoke and what is the socio-cultural dimension of the association of smoking with cardiovascular risk? The review of Leone et al. [5] discusses the subject. The common definition of smoking as the inhalation of the smoke of burned tobacco that may occur occasionally or habitually as a consequence of a physical addiction to some chemicals, primarily nicotine, cannot be fully accepted today since several clinical, biological, metabolic, epidemiologic, statistic and socio-economic factors that play a basic role in determining individual damage due to smoking are missing in this assessment. The analysis of findings shows undoubtedly that several constituents of cigarette smoking play a strong role in the development and progression of cardiovascular damage, primarily atherosclerotic lesions. Nicotine and its metabolites, carbon monoxide and also thiocyanate seem to be the most specific markers of damage that, in the time, becomes irreversible. Cigarette smoking is addictive because of nicotine and nicotine withdrawal causes many side effects of quitting smoking and usually increases cardiovascular risk. Therefore, what is smoking? Smoking must be defined as a chemical toxicosis which is able to cause detrimental effects either of acute or chronic type on different structures of the body like cardiovascular system, respiratory system and epithelial glands target organs. In addition, smoking causes physical addiction, primarily due to nicotine, that adversely influences smoking cessation. From these observations there is evidence that a large number of socio-economic and epidemiologic implications arise in smokers and that require the necessity of specific structures which may help to face up the problem. A large number of findings relate smoking to other major cardiovascular risk factors and, among this, hypertension plays a strong role that increases the harmful effects caused on cardiovascular system by smoking. However, there is no unanimous opinion on the interaction blood pressure and smoking [6-10]. Some reports identified that cigarette smoking in males was inversely related to systolic BP with, when compared to non-smokers, a reduction of 1.3 mmHg in 1.1% of light smokers, 3.8 mmHg in 3.1% of moderate smokers and 4.6 mmHg in 3.7% of heavy smokers. There was no clear relation with diastolic blood pressure. This finding was conducted in an oriental population enrolled in the study, but also in western countries blood pressure reduction was observed primarily in young smokers. In addition, some epidemiologic surveys [7, 9, 10] demonstrated that individuals who smoked a different number of cigarettes had lower blood pressure than that of non-smokers. Such a characteristic occurred in males, females, adolescents, adults and different races. However, this observation was attributed primarily to chronic smoking. There was opinion that associated loss in body weight of active smokers contributes to lowering BP. Such data contrast strongly with the results obtained in active smokers while they are smoking cigarettes as well as in dated chronic smokers [6, 11-14]. These individuals displayed an evident increase in blood pressure that seemed to be clearly related to the toxic effects of nicotine and carbon monoxide of acute type but, particularly for what concerns carbon monoxide, also of chronic type with structural arterial lesions associated. The review of Virdis et al. [15] analyzes the relationship between smoking and hypertension in an attempt to clarify this subject. Authors underline that cigarette smoking is a powerful cardiovascular risk factor and smoking cessation is the single most effective lifestyle measure for the prevention of a large number of cardiovascular diseases. Impairment of endothelial function, arterial stiffness, inflammation, lipid modification as well as an alteration of antithrombotic and prothrombotic factors are smoking-related major determinants of initiation, and acceleration of the atherothrombotic process, leading to cardiovascular events. Cigarette smoking acutely exerts an hypertensive effect, mainly through the stimulation of the sympathetic nervous system. Concerning the impact of chronic smoking on blood pressure, available data do not put clearly in evidence a direct causal relationship between these two cardiovascular risk factors, a concept supported by the evidence that no lower blood pressure values have been observed after chronic smoking cessation....

The definition of smoking as the inhalation of the smoke of burned tobacco that may occur occasionally or habitually as a consequence of a physical addiction to some chemicals, primarily nicotine, cannot be fully accepted today since several clinical, biological, metabolic, epidemiologic, statistic and socio-economic factors which play a basic role in determining individual damage due to smoking are missing in this assessment. The analysis of findings shows undoubtedly that several constituents of cigarette smoking play a strong role in the development and progression of cardiovascular damage, primarily atherosclerotic lesions. Nicotine and its metabolites, carbon monoxide and thiocyanate seem to be the most specific markers of damage that, in the time, become irreversible. Cigarette smoking is addictive because of nicotine and nicotine withdrawal causes many side effects of quitting smoking as well as nicotine itself usually increases cardiovascular risk. Therefore, what is smoking? Smoking must be defined as a chemical toxicosis which is able to cause detrimental effects either of acute or chronic type on different structures of the body being some of these like cardiovascular system, respiratory system and epithelial glands target organs. Smoking also causes physical addiction, primarily due to nicotine, that adversely influences smoking cessation. From these observations there is evidence that a large number of socio-economic and epidemiologic implications arise in smokers and that requires the necessity of specific structures which may help to face up the problem.

Cigarette smoking is a powerful cardiovascular risk factor and smoking cessation is the single most effective lifestyle measure for the prevention of a large number of cardiovascular diseases. Impairment of endothelial function, arterial stiffness, inflammation, lipid modification as well as an alteration of antithrombotic and prothrombotic factors are smoking-related major determinants of initiation, and acceleration of the atherothrombotic process, leading to cardiovascular events. Cigarette smoking acutely exerts an hypertensive effect, mainly through the stimulation of the sympathetic nervous system. As concern the impact of chronic smoking on blood pressure, available data do not put clearly in evidence a direct causal relationship between these two cardiovascular risk factors, a concept supported by the evidence that no lower blood pressure values have been observed after chronic smoking cessation. Nevertheless, smoking, affecting arterial stiffness and wave reflection might have greater detrimental effect on central blood pressure, which is more closely related to target organ damage than brachial blood pressure. Hypertensive smokers are more likely to develop severe forms of hypertension, including malignant and renovascular hypertension, an effect likely due to an accelerated atherosclerosis.

Tobacco smoking is the most important preventable cause of cardiovascular disease. In this paper we review current epidemiological and pathophysiological evidence linking smoking with cardiovascular and metabolic diseases. Among the effects of smoking there is the alteration of lipid metabolism through the increase in lipolysis, insulin resistance and tissue lipotoxicity. Smoking is both prothrombotic and atherogenic. As an effect, the risk of acute myocardial infarction, sudden cardiac death, stroke, aortic aneurysm and peripheral vascular disease is increased. Even very low doses of exposure increase the risk of cardiovascular disease (CVD) and metabolic alterations. On the other hand, smoking cessation restores, at least in part, lipid metabolism and the benefits can be observed already after a short period of abstinence from smoking, although it occurs several years before the risks approach those of the never-smoker.

Tobacco smoking remains the second largest preventable cause of mortality and morbidity worldwide. Exposure to tobacco smoke causes coronary disease, atherosclerosis and ischaemic vessel disease. The degree of this risk is proportional to the amount of smoking and it varies from individual to individual because of between-individual differences in genetic background. While the chemical properties of tobacco smoke are relatively well characterized, the mechanisms by which smoking leads to disease and the genetic factors that determine susceptibility to these diseases are not well understood. The purpose of the present review is to describe the interacti0on between DNA variants in some important genes and cardiovascular diseases; and how the exposure to cigarette smoke significantly modifies the association between genetic variants and cardiovascular risk. A great number of gene-enzymes that usually protect against cardiovascular events may be adversely influenced by tobacco smoke and, through this way, exert less effective action.

Smoking is a significant independent risk factor for cardiovascular disease and is a leading cause of structural and functional alterations of the cardiovascular system. Increasing evidence supports the hypothesis that oxidative stress and endothelial dysfunction are the fundamental pathophysiological mechanisms linking cigarette smoking to cardiovascular disease. The cardiovascular system is a rich source of NADPH oxidase - derived reactive oxygen species, which under pathological conditions play a fundamental role in vascular damage. Endothelium-derived nitric oxide (NO) plays a major role in the regulation of vascular tone, structure, and function, and endothelial dysfunction could be considered the first step in the pathogenesis of atherosclerosis and cardiovascular disease. Indeed, the bioavailability of NO is modulated by reactive oxygen species that degrade NO, uncouple NO synthase, and inhibit synthesis. Reduced bioavailability of NO and consequent endothelial dysfunction are involved in the initiation, progression and complications of atherosclerosis and also are predictive of future cardiovascular events. Thus, although data from clinical trials exploring the role of antioxidants on cardiovascular risk and disease are equivocal as yet, the role of oxidative stress in cardiovascular disease is an important area of research, which is likely to continue to be fruitful. This review focuses on possible interactions between oxidative stress, endothelial dysfunction and cigarette smoking - favouring the atherosclerotic process and cardiovascular disease - also focusing on the potential role for antioxidants in the prevention of adverse cardiovascular outcomes.

Active and passive exposure to cigarette smoke (CS) increases the risk of, and has deleterious effects in, ischemic heart disease. Exposure to CS increases infarct size in experimental models of coronary occlusion and reperfusion. Among many possible mechanisms for these deleterious effects in intact animals and humans three have more substantial evidence: 1) functional alterations of endothelial cells, neutrophils and platelets; 2) impaired mitochondrial function and energy metabolism caused by toxins in CS, including oxidative free radicals; 3) increased arterial stiffness and vulnerability of the atherosclerotic plaque. In addition to the various pro-mitogenic, carcinogenic and apoptotic pathways thought to be affected and upregulated by CS, a direct necrotic action on cardiomyocytes is also believed to exist. Many, if not all, of these alterations are caused by oxidative stress, either as a direct consequence of inhalation of free radicals, or by induction from the vast range of chemicals present in both the gas and solid phase of tobacco smoke. Here, some of the proposed mechanisms will be reviewed and their impact on the cardiomyocytes and peripheral vasculature discussed.

Accumulating evidence indicates that circulating endothelial progenitor cells (EPCs) derived from bone marrow contribute to reendothelialization of injured vessels as well as neo-vascularization of ischemic lesions in either a direct or an indirect way. Moreover, the number and/or the functional activity of EPCs are inversely correlated with risk factors for cardiovascular disease. Among the different risk factors, cigarette smoking is a major cause of reducing the numbers and function of circulating EPCs. This review is a revision of recent literature on EPC alteration associated with smoking. In particular, we show the recent observation on the effects of active and second hand smoke (SHS) exposure on EPC number and functional activity. This review also considers the effects of nicotine and other smoke compounds on EPC number and activity, in in vitro and in vivo models.

Chronic smoking is associated with functional and structural vascular changes underlying inflammatory processes responsible for plaque formation and rupture. Cyclooxygenase (COX) is the key enzyme linking smoking action to inflammatory damages: it is responsible for the conversion of arachidonic acid to prostanoids, and lipid mediators involved in most of pathological processes. Two COX isoenzymes have been characterized, COX-1 and COX-2, that differ in terms of regulatory mechanisms of expression, tissue distribution, substrate specificity, and preferential coupling to upstream and downstream enzymes. The aim of this review is to highlight the pathogenetic role of chronic smoking in vasomotor dysfunction, inflammation, and modification of lipids underlying the initiation and the progression of atherosclerosis and to remark the hypothesis that plaque composition rather than plaque size is the real determinant of the plaque evolution toward rupture and the major responsible for acute ischemic syndromes. The concomitantly higher expression of EP4, COX-2, mPGES-1, MMP-2 and MMP-9 in unstable plaques is focused and the role of PGE2 as pathophysiological link between smoking, COX-2 and MMP activity is stressed. Indeed, the intracellular pathways regulating COX-2 and the mechanisms suggested to clarify the role of COX-2 and downstream synthases in atherothrombosis are summarized.

Cigarette smoking is a powerful human germ cell mutagen and teratogen. Congenital heart defects (CHD) are the most prevalent of all birth defects and leading cause of death in the first year of life. The purpose of this article is to review the epidemiology of the impact of cigarette smoking on CHD risk as well as to discuss the potential biological mechanisms of smoking-mediated abnormal cardiac development. Although epidemiological studies of association between parental smoking and CHD are limited, biological evidence supports the concept that cigarette smoking may substantially contribute to the aetiology of CHD through induction of either male and female germ-cell mutation or interference with epigenetic pathways. Further research is needed to better define the relationship between parental smoking and the risk of heart defects as well as to assess parental-fetal gene-smoking interactions.

This article reviews the current techniques employed to assess endothelial dysfunction in different categories of smokers. Simple but effective methods to assess regional and local properties of large arteries for epidemiologic studies are firstly discussed. After, more complex but accurate image-based methods are described. In particular, the role of high resolution magnetic resonance to quantify, in a single examination, vascular function at different sites of peripheral and central arteries is summarized. Finally, the role of positron emission tomography and magnetic resonance flow mapping is described to assess myocardial microcirculation at rest and under external stressors.

Cigarette smoking is the leading preventable cause of death worldwide, and a considerable proportion of smoking-related fatalities are attributable to coronary artery disease (CAD). The detrimental effects of smoking span all stages in the development of CAD ranging from the early functional alterations in the endothelium and the microcirculation to the late clinicopathological manifestations of atherosclerotic plaques. Smoking results in the generation of free radicals and increased oxidative stress which plays a central role in the pathogenetic mechanisms leading to atherosclerotic disease. It causes reduced nitric oxide bioavailability and lipid peroxidation which are crucial initial steps of plaque formation. Furthermore, smoking enhances leukocyte and platelet activation and promotes local and systemic inflammation, which contribute to plaque progression and maturation. Finally, alterations in fibrinolytic and prothrombotic factors create a pro-thrombogenic environment which harbours the risk of plaque rupture and thrombosis. In smokers, the cessation of smoking is the most important intervention for cardiovascular risk reduction. Total mortality can be reduced by 36% which is comparable to established modern secondary preventive therapies. Nonetheless, non-aided cessation attempts are notoriously poor with a success rate of less than 10%. Patient counselling and pharmacological therapies are important aides for smoking cessation and can improve success rates by two to threefold. However, there is still need for improved strategies of smoking cessation to reduce the high socioeconomic impact of smoking.