European Heart Journal

European Heart Journal Advance Access originally published online on October 17, 2005
European Heart Journal 2006 27(4):386-392; doi:10.1093/eurheartj/ehi601

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Secondhand smoke as an acute threat for the cardiovascular system: a change in paradigm

Tobias Raupach, Katrin Schäfer, Stavros Konstantinides^* and Stefan Andreas

Department of Cardiology and Pulmonology, University Clinic, Georg August University of Goettingen, D-37099 Goettingen, Germany

Received 29 June 2005; revised 23 September 2005; accepted 29 September 2005; online publish-ahead-of-print 17 October 2005.

^* Corresponding author. Tel: +49 551 39 8927; fax: +49 551 39 14131. E-mail address: skonstan{at}med.uni-goettingen.de

See page 382 for the editorial comment on this article (doi:10.1093/eurheartj/ehi679)

	Abstract

Top Abstract Increasing awareness of the... Components of secondhand smoke Impairment of endothelial... Effects on platelet activation Oxidative stress, lipoprotein... Further evidence for acute... Maximal activation at low... Conclusion References

 
The evidence that active smoking is a risk factor for cardiovascular disease (CVD) and the leading cause of preventable death is overwhelming. However, numerous epidemiological findings indicate that even passive exposure to cigarette smoke may exert detrimental effects on vascular homoeostasis. Recent experimental data provide a deeper insight into the pathophysiological mechanisms linking secondhand smoke (SHS) to CVD. Importantly, most of these effects appear to be characterized by a rapid onset. For example, the relatively low doses of toxins inhaled by passive smoking are sufficient to elicit acute endothelial dysfunction, and these effects may be related, at least in part, to the inactivation of nitric oxide. Moreover, passive smoking may directly impair the viability of endothelial cells and reduce the number and functional activity of circulating endothelial progenitor cells. In addition, platelets of non-smokers appear to be susceptible to pro-aggregatory changes with every passive smoke exposure. Overall, SHS induces oxidative stress and promotes vascular inflammation. Apart from vascoconstriction and thrombus formation, however, the myocardial oxygen balance is further impaired by SHS-induced adrenergic stimulation and autonomic dysfunction. These data strongly suggest that passive smoking is capable of precipitating acute manifestations of CVD (atherothrombosis) and may also have a negative impact on the outcome of patients who suffer acute coronary syndromes.

Key Words: Passive smoking • Atherosclerosis • Cardiovascular disease • Acute manifestation

	Increasing awareness of the problem

Top Abstract Increasing awareness of the... Components of secondhand smoke Impairment of endothelial... Effects on platelet activation Oxidative stress, lipoprotein... Further evidence for acute... Maximal activation at low... Conclusion References

 
Epidemiological evidence has unequivocally confirmed that active smoking is a risk factor for cardiovascular disease (CVD) and the leading cause of preventable death.^1,2 For example, the risk of death from coronary heart disease is elevated at least two-fold among smokers when compared with non-smokers,^3,4 two-thirds of sudden cardiac deaths due to acute coronary thrombosis occur in cigarette smokers,⁵ and smoking is associated with an 50% increase in the risk of stroke.^6,7 Clinical and experimental researches carried out over the past years have revealed a number of potential pathomechanisms underlying the increased cardiovascular risk in active smokers. Importantly, however, the impact of passive smoking on the cardiovascular system was also recognized almost 20 years ago, when evidence of the harmful effects of secondhand smoke (SHS) began to emerge.^8,9 In the past decade, clinical data from the Atherosclerosis Risk in Communities (ARIC) studies demonstrated that both active and passive smoking were associated with accelerated atherosclerosis progression as assessed by the increase in carotid artery intimal–medial thickness.¹⁰ Moreover, Steenland¹¹ reported that the risk of death due to CVD increases by 30% in non-smokers who live together with smokers and another report from the United States suggested that more than 50 000 deaths annually from ischaemic heart disease are associated with SHS.¹² These findings, combined with experimental data which indicate that not only active smoking but also the passive exposure to secondhand smoke may exert detrimental effects on vascular homoeostasis,¹³ are particularly alarming in view of the huge economic burden imposed on public health systems by CVD.^14,15

Epidemiological data suggest a non-linear dose–response relationship between the intensity of exposure to SHS and the risk of ischaemic heart disease.^16,17 For example, the excess risk of developing CVD amounts to 80% in active smokers at the age of 65, but it may also be as high as 30% in passive smokers.¹⁸ Using measurements of the serum concentration of cotinine (a biomarker of smoke exposure) in a large prospective population study, Whincup et al.¹⁹ recently concluded that the risk of coronary heart disease related to passive smoke exposure has probably been underestimated in earlier reports and might, in fact, be very close to the risk reported for active smokers. According to the conceptual model advanced by Glantz and Parmley²⁰ and further developed by Law and Wald,²¹ this alarming observation may be related to the fact that some of the effects which cigarette smoke exerts on the cardiovascular system may already plateau upon exposure to very low doses and thus smoke exposure, even if passive, may be capable of maximally activating the pathological processes discussed subsequently. Besides, most of the well-described effects of passive smoking on vascular homoeostasis appear to be characterized by a rapid onset and can therefore be regarded as acute, even though SHS exposure at home or at the workplace almost always occurs on a regular, recurrent basis rather than being a single event. Importantly, this latter concept also implies that passive exposure to SHS has the potential to trigger acute cardiovascular events.^22–24

A recently published article reviewed the epidemiological evidence which strongly supports the detrimental effects of secondhand smoke on the cardiovascular system.²⁵ The present review extends these findings and concentrates on our current state of knowledge regarding the pathomechanisms which mediate the impact of SHS on cardiovascular pathophysiology. We performed an extensive Pubmed search using specific key terms related to secondhand smoke (secondhand smoke, environmental tobacco smoke, sidestream smoke, passive smoking, and involuntary smoking) in combination with CVD (cardiovascular disease, coronary artery/coronary heart disease, mechanism, pathophysiology, and acute manifestation). The search also included the articles cited in the identified studies. A particular focus of our review is on how SHS-related endothelial dysfunction, platelet activation, oxidative stress, and inflammation may contribute to the acute clinical manifestations of coronary artery disease (Figure 1).

View larger version (20K): [in this window] [in a new window]   Figure 1 Mechanisms linking passive smoke exposure to acute clinical manifestations.

 

	Components of secondhand smoke

Top Abstract Increasing awareness of the... Components of secondhand smoke Impairment of endothelial... Effects on platelet activation Oxidative stress, lipoprotein... Further evidence for acute... Maximal activation at low... Conclusion References

 
In general, secondhand smoke has two main components, sidestream and mainstream smoke. Sidestream smoke emerges from the tip of a burning cigarette, accounting for 85% of the total amount of SHS. The remaining 15% are made up of mainstream smoke, which has been inhaled and is exhaled by an active smoker.^26,27 Importantly, the concentration of numerous toxins has been shown to be dramatically (up to 100-fold) elevated in sidestream smoke when compared with mainstream smoke, underscoring the potential adverse impact of SHS on health.²⁸ With regard to the physicochemical composition of SHS, a vapour phase and a particular phase can be distinguished. With regard to the latter, particles <2.5 µm are of special interest because they can be inhaled deeply into the lungs. The finding that particles in sidestream smoke are smaller than those in mainstream smoke supports the assumption that sidestream smoke may, in fact, be more dangerous than mainstream smoke.²⁸ So far, only few clinical and experimental studies have investigated the effects of specific components of SHS^29–31 and the overall impact of passive smoking on an organism probably has to be attributed to the complex mixture of SHS rather than to a specific component of cigarette smoke.

	Impairment of endothelial function

Top Abstract Increasing awareness of the... Components of secondhand smoke Impairment of endothelial... Effects on platelet activation Oxidative stress, lipoprotein... Further evidence for acute... Maximal activation at low... Conclusion References

 
The endothelium plays a central role in vascular homoeostasis, because it expresses and secretes a number of regulatory factors including nitric oxide or prostaglandins and is involved in the regulation of the vascular tone. Moreover, platelet aggregation, fibrinolysis, monocyte adhesion, and the proliferation of vascular smooth muscle cells are regulated by signalling molecules derived from endothelial cells.³² In experimental in vivo studies, we and others described how injury to the endothelium triggers vascular remodeling and promotes neointimal growth,^33,34 and it is currently accepted that impairment of endothelial function predicts the initiation and progression of atherosclerosis.^35,36 Endothelial injury and activation result in the migration of monocytes into the vessel wall, their transformation into lipid-laden macrophages, and the subsequent growth and destabilization of lesions due to local inflammatory activity.³⁵

Smoking, alone or in combination with other cardiovascular risk factors such as adiposity, diabetes mellitus, or hypercholesterolaemia, has been demonstrated to result in endothelial dysfunction. For example, in vitro studies showed that cigarette smoke condensate induces the surface expression of cell adhesion molecules and promotes the transendothelial migration of monocyte-like cells^37–40 and a 5-min exposure to the smoke of one research cigarette elicited the adhesion of leucocytes to endothelial cells in hamsters.⁴¹ Clinical studies observed impaired endothelium-dependent vasorelaxation, the earliest sign of endothelial dysfunction, in smokers,^42–44 and active as well as passive smoking inhibited endothelium-dependent vasodilatation to a similar extent.⁴⁵ Moreover, Sumida et al.⁴⁶ found that passive smoking turns the acetylcholine-induced coronary artery relaxation into a vasoconstriction. In another study, coronary flow reserve, although higher in non-smokers than in active smokers under control conditions, was similar in the two groups after a 30-min exposure to SHS.⁴⁷ These findings indicate that the relatively low doses of toxins inhaled by passive smoking are sufficient to elicit a strong acute response. The agents and pathways responsible for these functional changes of endothelial function have not yet been completely elucidated, but they may be related, at least in part, to the inactivation of nitric oxide.⁴⁸ For example, animal studies suggested that passive smoking reduces the activity of endothelial NO synthase [possibly due to the action of carbon monoxide (CO)]⁴⁹ and the endothelial arginine content.⁵⁰ In accordance with these results, it was shown that L-arginine supplementation prevents endothelial dysfunction induced by secondhand smoke in rabbits⁵⁰ and reduces the infarct size in SHS-exposed rats.⁵¹

Apart from functional changes, passive smoking may directly impair the viability of endothelial cells. Earlier studies described ultrastructural features of increased permeability and cellular damage in nicotine-exposed endothelial cells.^52,53 Regeneration of vascular endothelial layers and restoration of endothelial function are of central importance for vascular homoeostasis and atherothrombosis prevention, but endothelial repair is often limited due to the high degree of differentiation of this particular cell type.⁵⁴ Recently, interest focused on circulating endothelial progenitor cells (EPCs) as a possible mechanism of vascular protection and repair following oxidative stress and endothelial damage. Adult bone marrow contains a subtype of haematopoietic stem cells with the potential to differentiate into mature endothelial cells.^54,55 Interestingly, clinical studies recently reported that the presence of established cardiovascular risk factors including smoking is inversely correlated with the number and functional activity of circulating EPCs.^56,57 In fact, cotinine, a metabolite of nicotine, was shown to suppress the growth of haematopoietic progenitor cells at concentrations equivalent to its serum levels in smokers.⁵⁸ Accordingly, a history of cigarette smoking was associated with a reduced number and differentiation of circulating VEGF-R2-positive/CD34-positive cells,⁵⁹ whereas smoking cessation resulted in a rapid increase in their number in healthy male individuals.⁶⁰ Moreover, smoking during pregnancy reduced the number of haematopoietic progenitor cells in the umbilical vein blood of the newborn.⁶¹ The possible impact of SHS on the mobilization and the circulating numbers of EPCs is an important issue that needs to be addressed by future trials.

	Effects on platelet activation

Top Abstract Increasing awareness of the... Components of secondhand smoke Impairment of endothelial... Effects on platelet activation Oxidative stress, lipoprotein... Further evidence for acute... Maximal activation at low... Conclusion References

 
Platelet activation and thrombosis at sites of vascular injury or atheromatous plaque disruption play a crucial role in the pathophysiology of acute coronary events.^5,62 Clinical and experimental studies found enhanced thrombosis and increased platelet aggregation in response to agonists in smokers.^63,64 Importantly, platelet -granule constituents, such as platelet factor-4, ß-thromboglobulin, and platelet-activating factor, are increased in the plasma of passive smokers, indicating ongoing platelet activation in these individuals.^13,65,66

Active smoking is thought to elicit an adrenal epinephrine release, which is capable of enhancing platelet activation. In a discussion of the non-linear dose–response hypothesis relating smoke exposure to the risk of CVD, Smith et al.⁶⁷ concluded that serum nicotine concentrations usually found in passive smokers are not sufficient to induce significant epinephrine release and that platelet activation related to passive smoking may thus be mediated by alternative (or additional) mechanisms.

In a number of in vitro and in vivo studies, nicotine alone resulted in attenuation (rather than enhancement) of platelet activation.^30,68–70 Importantly, however, although nicotine does not, by itself, appear to promote platelet aggregation, only 20 min of passive exposure to whole smoke may suffice to induce activation of platelets to an extent comparable to that of active smoking of one to two cigarettes.⁷¹ This fact points to a steep dose–response relationship for low SHS doses. Of note, although platelets of active smokers are already maximally activated, those of non-smokers appear to be susceptible to pro-aggregatory changes with every SHS exposure.⁷² Using a modified prothrombinase method, Rubenstein et al.³⁰ compared the effects of sidestream and mainstream smoke on platelet function. Surprisingly, the impact of sidestream smoke was as pronounced as that of mainstream smoke, and it was even stronger for the so-called ‘light’ cigarettes. Studies in humans identified decreased platelet sensitivity to the anti-aggregatory actions of prostaglandin I₂ as at least one potential pathomechanism.⁷³ Moreover, passive smoking increases thromboxane formation,⁷⁴ probably due to nicotine-induced catecholamine release.⁷⁵ Clearly, further research is needed to identify and analyse the mechanisms of platelet activation as a result of SHS.

Apart from the direct effects of cigarette smoke on platelet function and thrombosis, the interaction of activated platelets with a dysfunctional, ‘pro-coagulant’ endothelium may be one of the mechanisms mediating the pro-atherothrombotic effects of passive (and active) smoking.^76–78 Moreover, elevated circulating levels of coagulation factors such as thrombin, tissue factor, and fibrinogen, are present in plasma of smokers when compared with non-smokers.^40,79–82 High plasma levels of plasminogen activator inhibitor (PAI)-1 may also contribute to an impaired fibrinolysis in smokers and are correlated with the estimated pack-years of cigarettes smoked,^83,84 although this latter mechanism has not yet been examined in a population of passive smokers.

	Oxidative stress, lipoprotein modification, and inflammation

Top Abstract Increasing awareness of the... Components of secondhand smoke Impairment of endothelial... Effects on platelet activation Oxidative stress, lipoprotein... Further evidence for acute... Maximal activation at low... Conclusion References

 
Exposure to SHS produces oxidative stress.^85–89 In addition to oxidants contained in cigarette smoke itself,⁹⁰ free radicals are also released endogenously from activated neutrophils. Importantly, whereas active smokers seem to be adapted to chronic oxidative stress and often exhibit an elevated antioxidant enzyme activity,⁹¹ passive smoking impairs antioxidant mechanisms in non-smokers.⁴⁷ In the presence of free radicals and increased oxidative stress due to passive smoke,^92,93 low-density lipoprotein (LDL) is converted to oxidized LDL, which, in turn, elicits a multitude of effects in the vessel wall. Apart from causing endothelial activation and dysfunction,⁹⁴ intramural oxLDL is taken up by local macrophages which thereby undergo activation and transformation into foam cells.^35,95 In humans, elevated levels of thiocyanate, a typical finding in passive smokers,⁹⁶ have been linked to an increased number of macrophages in atherosclerotic plaques.⁹⁷ Moreover, according to experimental data, even short exposure to SHS significantly increases lipid accumulation in the wall of perfused rat arteries.⁹⁸ Of note, polycyclic aromatic hydrocarbons (e.g. benzpyrene), which can be integrated into the plaque after binding to lipoprotein subfractions, also promote the proliferation of vascular cells and plaque progression.^99,100 In vivo studies in animal models of atherosclerosis demonstrated that passive cigarette smoking increases the size and lipid content of lesions in apolipoprotein E-knockout (apoE–/–) mice¹⁰¹ and in cholesterol-fed rabbits.¹⁰² Exposure to SHS was also shown to change the ultrastructure and mechanical properties of rat pulmonary arteries.¹⁰³ Finally, it needs to be mentioned that recent evidence in apoE–/– mice suggests that exposure to SHS very early in life (e.g. in neonates) may predispose to adult atherogenesis.¹⁰⁴

Elevation of circulating inflammation markers (white blood cell count, C-reactive protein, homocysteine, and fibrinogen) was recently reported in passive smokers.¹⁰⁵ This adds to earlier findings of raised fibrinogen levels^106,107 and leukocyte counts accompanied by an activation of the immune cells¹⁰⁸ in response to SHS exposure. Thus, as passive smoking occurs on a regular basis in most individuals exposed to SHS, it is very likely to contribute to a persistent inflammatory response which promotes atherothrombosis.¹⁰⁹

	Further evidence for acute effects of secondhand smoke on the cardiovascular system

Top Abstract Increasing awareness of the... Components of secondhand smoke Impairment of endothelial... Effects on platelet activation Oxidative stress, lipoprotein... Further evidence for acute... Maximal activation at low... Conclusion References

 
Passive smoking stimulates sympathetic nervous activity (measured as muscle sympathetic nerve activity¹¹⁰) and inhibits vagal efferents to the heart.¹¹¹ Nicotine may partly be responsible for these effects.^{31,32,112–114} Moreover, it has been hypothesized that the odours prevailing in a smoke-filled room may initiate the release of catecholamines and stress hormones.¹¹⁵ Smoke-related alterations of autonomic nervous function are supported by a decreased heart rate variability in passive smokers as reported by Pope et al.¹¹⁶ In that study, the ECG of healthy non-smokers was continuously monitored for 8 h during which participants moved every 2 h between the smoking and the non-smoking areas of an airport. Secondhand smoke consistently and reversibly decreased heart rate variability. As autonomic dysfunction is linked to higher mortality rates in patients with chronic heart failure,¹¹⁷ the authors speculated that such deleterious effects might result from passive smoking as well¹¹⁶. In contrast, although active smoking has been unequivocally shown to raise heart rate and arterial blood pressure,¹¹⁸ the data on the effects of SHS on these parameters are still controversial.^27,28,110

CO is a component of secondhand smoke and a marker of smoke exposure in the exhaled air. CO binds to haemoglobin and impairs the capacity of red blood cells to transport oxygen. In this regard, CO has been blamed for the reduction in exercise tolerance observed after passive smoking.¹¹⁹ To date, CO is one of the few single substances which have been systematically studied in an attempt to explain the effects of SHS on the organism. However, the scarcity of data on the involvement of other possible mediators does not, by itself, justify the assumption that the impact of SHS on cardiovascular homoeostasis is solely (or mainly) attributable to carboxyhaemoglobin formation. Thus, oxygen utilization at the subcellular level may also be impaired by passive smoking, as suggested by a drop in the activity of the mitochondrial enzyme cytochrome oxidase following smoke exposure.¹²⁰ In addition to reduced oxygen transport capacity, coronary vasoconstriction due to adrenergic stimulation may further impair oxygen supply to the heart. At the same time, sympathetic activation increases cardiac afterload, thereby elevating the oxygen demand of cardiomyocytes. The resulting hypoxia lowers the threshold for cardiac arrhythmias in patients with coronary artery disease.²⁹ Moreover, exposure to SHS shortens the symptom-free interval in patients with stable angina.²² In summary, several factors apart from a reduction in the oxygen-carrying capacity of the blood seem to mediate the acute effects of SHS on the cardiovascular system. Most probably, the mechanisms discussed earlier may synergistically impair cardiovascular function and give rise to clinical manifestations.

	Maximal activation at low doses: linking experimental data to clinical evidence

Top Abstract Increasing awareness of the... Components of secondhand smoke Impairment of endothelial... Effects on platelet activation Oxidative stress, lipoprotein... Further evidence for acute... Maximal activation at low... Conclusion References

 
In the study by Whincup et al.,¹⁹ cotinine levels were related to the subsequent 20-year risk of suffering acute coronary events. In fact, it has been estimated that passive smoking elevates the overall risk of an acute cardiovascular event by 25–35%.²³ However, the CARDIO2000 trial¹²¹ suggested that the excess risk for acute coronary syndromes may be considerably higher, rising to 97% in people exposed to SHS in their homes. This finding is in accordance with earlier reports from Argentina, Australia, and New Zealand.^122,123 Not surprisingly, Sargent et al.²⁴ recently reported a drop of hospital admissions for acute myocardial infarction by 40% following the enactment of a local law banning smoking in public and workplaces. Despite some limitations of this study (relatively small study population and no measurement of actual smoke exposure), the results indicate that passive smoking and the incidence of acute coronary syndromes may indeed be more closely related than traditionally thought. Clearly, further systematic research is needed to correlate parameters of actual SHS exposure with the occurrence of subsequent acute coronary events and thus clinically confirm (or reject) the notion, thus far derived from experimental data, that even very low doses of smoke exposure may activate pathophysiological pathways, eventually leading to acute coronary syndromes.

Once an acute coronary syndrome occurs, the resulting damage to the heart might further be aggravated by ongoing passive smoking. Robinson et al.¹²⁴ already showed that the creatine kinase of active smokers suffering from myocardial infarction reached higher values than that of non-smokers, 15 years ago. Although an analogous study regarding passive smoking has not been conducted yet, data from studies in rats support the assumption that exposure to SHS increases infarct size.¹³ Greater reperfusion injury due to free radicals¹²⁵ or activation of platelets¹²⁶ caused by passive smoking may be the underlying patho-mechanism.

	Conclusion

Top Abstract Increasing awareness of the... Components of secondhand smoke Impairment of endothelial... Effects on platelet activation Oxidative stress, lipoprotein... Further evidence for acute... Maximal activation at low... Conclusion References

 
Epidemiological evidence clearly indicates that passive smoking is linked to an increase in the incidence of CVD. Extensive clinical and experimental researches have revealed that the acute effects elicited by smoke exposure, including endothelial dysfunction, platelet activation, oxidative stress, and inflammatory reactions are involved in the pathogenesis of atherosclerosis (Figure 1). Importantly, passive smoking appears to be capable of precipitating the acute manifestations of CVD (atherothrombosis) and may also have a negative impact on the outcome of patients who suffer acute coronary syndromes. In view of the available evidence and the fact that SHS-related changes in vascular function are at least partly reversible, clinicians need to inform their patients about the risks associated with passive smoking and strongly support the enforcement of smoking bans in all public places.

Conflict of interest: none declared.

	References

Top Abstract Increasing awareness of the... Components of secondhand smoke Impairment of endothelial... Effects on platelet activation Oxidative stress, lipoprotein... Further evidence for acute... Maximal activation at low... Conclusion References

 

1. Glantz SA, Parmley WW. Passive smoking and heart disease. Mechanisms and risk. JAMA 1995;273:1047–1053.[Abstract/Free Full Text]
2. European Network for Smoking Prevention. Smoke Free Workplaces: Improving the Health and Wellbeing of People at Work. Brussels: European Network for Smoking Prevention; 2001.
3. Haheim LL, Holme I, Hjermann I, Leren P. The predictability of risk factors with respect to incidence and mortality of myocardial infarction and total mortality. A 12-year follow-up of the Oslo Study, Norway. J Intern Med 1993;234:17–24.[Web of Science][Medline]
4. Ockene IS, Miller NH. Cigarette smoking, cardiovascular disease, and stroke: a statement for healthcare professionals from the American Heart Association. American Heart Association Task Force on Risk Reduction. Circulation 1997;96:3243–3247.[Free Full Text]
5. Burke AP, Farb A, Malcom GT, Liang YH, Smialek J, Virmani R. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N Engl J Med 1997;336:1276–1282.[Abstract/Free Full Text]
6. Wolf PA, D'Agostino RB, Kannel WB, Bonita R, Belanger AJ. Cigarette smoking as a risk factor for stroke. The Framingham Study. JAMA 1988;259:1025–1029.[Abstract/Free Full Text]
7. Shinton R, Beevers G. Meta-analysis of relation between cigarette smoking and stroke. BMJ 1989;298:789–794.[Abstract/Free Full Text]
8. US Department of Health and Human Services. The Health Consequences of Involuntary Smoking: A Report of the Surgeon General. Washington: Government Printing Office; 1986.
9. Taylor BV, Oudit GY, Kalman PG, Liu P. Clinical and pathophysiological effects of active and passive smoking on the cardiovascular system. Can J Cardiol 1998;14:1129–1139.[Web of Science][Medline]
10. Howard G, Wagenknecht LE, Burke GL, Diez-Roux A, Evans GW, McGovern P, Nieto FJ, Tell GS. Cigarette smoking and progression of atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) Study. JAMA 1998;279:119–124.[Abstract/Free Full Text]
11. Steenland K. Passive smoking and the risk of heart disease. JAMA 1992;267:94–99.[Abstract/Free Full Text]
12. Wells AJ. Passive smoking as a cause of heart disease. J Am Coll Cardiol 1994;24:546–554.[Abstract]
13. Zhu BQ, Sun YP, Sievers RE, Glantz SA, Parmley WW, Wolfe CL. Exposure to environmental tobacco smoke increases myocardial infarct size in rats. Circulation 1994;89:1282–1290.[Abstract/Free Full Text]
14. Nagle PC, Smith AW. Review of recent US cost estimates of revascularization. Am J Manag Care 2004;10(Suppl. 11):S370–S376.[Web of Science][Medline]
15. American Heart Association. Heart Disease and Stroke Statistics—2005 Update. Dallas, Texas: American Heart Association; 2005.
16. Howard G, Thun MJ. Why is environmental tobacco smoke more strongly associated with coronary heart disease than expected? A review of potential biases and experimental data. Environ Health Perspect 1999;107(Suppl. 6):853–858.
17. Barnoya J, Glantz SA. Secondhand smoke: the evidence of danger keeps growing. Am J Med 2004;116:201–202.[CrossRef][Web of Science][Medline]
18. Scientific Committee on Tobacco and Health Great Britain. Report of the Scientific Committee on Tobacco and Health. London: The Stationary Office; 1998.
19. Whincup PH, Gilg JA, Emberson JR, Jarvis MJ, Feyerabend C, Bryant A, Walker M, Cook DG. Passive smoking and risk of coronary heart disease and stroke: prospective study with cotinine measurement. BMJ 2004;329:200–205.[Abstract/Free Full Text]
20. Glantz SA, Parmley WW. Passive smoking and heart disease. Epidemiology, physiology, and biochemistry. Circulation 1991;83:1–12.[Abstract/Free Full Text]
21. Law MR, Wald NJ. Environmental tobacco smoke and ischemic heart disease. Prog Cardiovasc Dis 2003;46:31–38.[CrossRef][Web of Science][Medline]
22. Aronow WS. Effect of passive smoking on angina pectoris. N Engl J Med 1978;299:21–24.[Abstract]
23. WHO International Agency for Research on Cancer. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Tobacco Smoke and Involuntary Smoking. Lyon, France; 2004. Vol. 38.
24. Sargent RP, Shepard RM, Glantz SA. Reduced incidence of admissions for myocardial infarction associated with public smoking ban: before and after study. BMJ 2004;328:977–980.[Abstract/Free Full Text]
25. Barnoya J, Glantz SA. Cardiovascular effects of secondhand smoke: nearly as large as smoking. Circulation 2005;111:2684–2698.[Abstract/Free Full Text]
26. European Commission. Tobacco or health in the European union—past, present and future. The ASPECT Consortium 2004. Luxembourg: Office for Official Publications of the European Communities; 2004.
27. National Research Council Committee on Passive Smoking. Environmental Tobacco Smoke: Measuring Exposures and Assessing Health Effects. Washington, DC: National Academy Press; 1986.
28. Kritz H, Schmid P, Sinzinger H. Passive smoking and cardiovascular risk. Arch Intern Med 1995;155:1942–1948.[Abstract/Free Full Text]
29. Sheps DS, Herbst MC, Hinderliter AL, Adams KF, Ekelund LG, O'Neil JJ, Goldstein GM, Bromberg PA, Dalton JL, Ballenger MN, Davis SM, Koch GG. Production of arrhythmias by elevated carboxyhemoglobin in patients with coronary artery disease. Ann Intern Med 1990;113:343–351.[Abstract/Free Full Text]
30. Rubenstein D, Jesty J, Bluestein D. Differences between mainstream and sidestream cigarette smoke extracts and nicotine in the activation of platelets under static and flow conditions. Circulation 2004;109:78–83.[Abstract/Free Full Text]
31. Symons JD, Stebbins CL. Hemodynamic and regional blood flow responses to nicotine at rest and during exercise. Med Sci Sports Exerc 1996;28:457–467.[Web of Science][Medline]
32. Puranik R, Celermajer DS. Smoking and endothelial function. Prog Cardiovasc Dis 2003;45:443–458.[CrossRef][Web of Science][Medline]
33. Konstantinides S, Schafer K, Thinnes T, Loskutoff DJ. Plasminogen activator inhibitor-1 and its cofactor vitronectin stabilize arterial thrombi after vascular injury in mice. Circulation 2001;103:576–583.[Abstract/Free Full Text]
34. Schafer K, Konstantinides S, Riedel C, Thinnes T, Muller K, Dellas C, Hasenfuss G, Loskutoff DJ. Different mechanisms of increased luminal stenosis after arterial injury in mice deficient for urokinase- or tissue-type plasminogen activator. Circulation 2002;106:1847–1852.[Abstract/Free Full Text]
35. Glass CK, Witztum JL. Atherosclerosis: the road ahead. Cell 2001;104:503–516.[CrossRef][Web of Science][Medline]
36. Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med 1999;340:115–126.[Free Full Text]
37. Noronha-Dutra AA, Epperlein MM, Woolf N. Effect of cigarette smoking on cultured human endothelial cells. Cardiovasc Res 1993;27:774–778.[Abstract/Free Full Text]
38. Shen Y, Rattan V, Sultana C, Kalra VK. Cigarette smoke condensate-induced adhesion molecule expression and transendothelial migration of monocytes. Am J Physiol 1996;270(5 Pt 2): H1624–H1633.
39. Adams MR, Jessup W, Celermajer DS. Cigarette smoking is associated with increased human monocyte adhesion to endothelial cells: reversibility with oral L-arginine but not vitamin C. J Am Coll Cardiol 1997;29:491–497.[Abstract]
40. Matetzky S, Tani S, Kangavari S, Dimayuga P, Yano J, Xu H, Chyu KY, Fishbein MC, Shah PK, Cercek B. Smoking increases tissue factor expression in atherosclerotic plaques: implications for plaque thrombogenicity. Circulation 2000;102:602–604.[Abstract/Free Full Text]
41. Lehr HA, Hubner C, Finckh B, Angermuller S, Nolte D, Beisiegel U, Kohlschutter A, Messmer K. Role of leukotrienes in leukocyte adhesion following systemic administration of oxidatively modified human low density lipoprotein in hamsters. J Clin Invest 1991;88:9–14.[Web of Science][Medline]
42. Zeiher AM, Schachinger V, Minners J. Long-term cigarette smoking impairs endothelium-dependent coronary arterial vasodilator function. Circulation 1995;92:1094–1100.[Abstract/Free Full Text]
43. Celermajer DS, Sorensen KE, Georgakopoulos D, Bull C, Thomas O, Robinson J, Deanfield JE. Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium- dependent dilation in healthy young adults. Circulation 1993;88(5 Pt 1):2149–2155.[Abstract/Free Full Text]
44. Heitzer T, Yla-Herttuala S, Luoma J, Kurz S, Munzel T, Just H, Olschewski M, Drexler H. Cigarette smoking potentiates endothelial dysfunction of forearm resistance vessels in patients with hypercholesterolemia. Role of oxidized LDL. Circulation 1996;93:1346–1353.[Abstract/Free Full Text]
45. Celermajer DS, Adams MR, Clarkson P, Robinson J, McCredie R, Donald A, Deanfield JE. Passive smoking and impaired endothelium-dependent arterial dilatation in healthy young adults. N Engl J Med 1996;334:150–154.[Abstract/Free Full Text]
46. Sumida H, Watanabe H, Kugiyama K, Ohgushi M, Matsumura T, Yasue H. Does passive smoking impair endothelium-dependent coronary artery dilation in women? J Am Coll Cardiol 1998;31:811–815.[Abstract/Free Full Text]
47. Otsuka R, Watanabe H, Hirata K, Tokai K, Muro T, Yoshiyama M, Takeuchi K, Yoshikawa J. Acute effects of passive smoking on the coronary circulation in healthy young adults. JAMA 2001;286:436–441.[Abstract/Free Full Text]
48. Ohara Y, Peterson TE, Harrison DG. Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest 1993;91:2546–2551.[Web of Science][Medline]
49. Johnson FK, Johnson RA. Carbon monoxide promotes endothelium-dependent constriction of isolated gracilis muscle arterioles. Am J Physiol Regul Integr Comp Physiol 2003;285:R536–R541.[Abstract/Free Full Text]
50. Hutchison SJ, Sievers RE, Zhu BQ, Sun YP, Stewart DJ, Parmley WW, Chatterjee K. Secondhand tobacco smoke impairs rabbit pulmonary artery endothelium-dependent relaxation. Chest 2001;120:2004–2012.[Abstract/Free Full Text]
51. Zhu B, Sun Y, Sievers RE, Shuman JL, Glantz SA, Chatterjee K, Parmley WW, Wolfe CL. L-Arginine decreases infarct size in rats exposed to environmental tobacco smoke. Am Heart J 1996;132(1 Pt 1):91–100.[CrossRef][Web of Science][Medline]
52. Booyse FM, Osikowicz G, Quarfoot AJ. Effects of chronic oral consumption of nicotine on the rabbit aortic endothelium. Am J Pathol 1981;102:229–238.[Abstract]
53. Zimmerman M, McGeachie J. The effect of nicotine on aortic endothelium. A quantitative ultrastructural study. Atherosclerosis 1987;63:33–41.[CrossRef][Web of Science][Medline]
54. Hristov M, Erl W, Weber PC. Endothelial progenitor cells: mobilization, differentiation, and homing. Arterioscler Thromb Vasc Biol 2003;23:1185–1189.[Abstract/Free Full Text]
55. Quirici N, Soligo D, Caneva L, Servida F, Bossolasco P, Deliliers GL. Differentiation and expansion of endothelial cells from human bone marrow CD133(+) cells. Br J Haematol 2001;115:186–194.[CrossRef][Web of Science][Medline]
56. Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA, Finkel T. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 2003;348:593–600.[Abstract/Free Full Text]
57. Tepper OM, Galiano RD, Capla JM, Kalka C, Gagne PJ, Jacobowitz GR, Levine JP, Gurtner GC. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation 2002;106:2781–2786.[Abstract/Free Full Text]
58. Takahashi M, Shigeno N, Narita M, Takahashi H, Furukawa T, Koike T, Aizawa Y. Cotinine (a metabolite of nicotine) suppresses the growth of hematopoietic progenitor cells at the concentration range equivalent to its serum levels in smokers. Stem Cells 1999;17:125–126.[Free Full Text]
59. Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H, Zeiher AM, Dimmeler S. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 2001;89:E1–E7.[Web of Science][Medline]
60. Kondo T, Hayashi M, Takeshita K, Numaguchi Y, Kobayashi K, Iino S, Inden Y, Murohara T. Smoking cessation rapidly increases circulating progenitor cells in peripheral blood in chronic smokers. Arterioscler Thromb Vasc Biol 2004;24:1442–1447.[Abstract/Free Full Text]
61. Shlebak AA, Roberts IA, Stevens TA, Syzdlo RM, Goldman JM, Gordon MY. The impact of antenatal and perinatal variables on cord blood haemopoietic stem/progenitor cell yield available for transplantation. Br J Haematol 1998;103:1167–1171.[CrossRef][Web of Science][Medline]
62. Davies MJ. The composition of coronary-artery plaques. N Engl J Med 1997;336:1312–1314.[Free Full Text]
63. Fusegawa Y, Goto S, Handa S, Kawada T, Ando Y. Platelet spontaneous aggregation in platelet-rich plasma is increased in habitual smokers. Thromb Res 1999;93:271–278.[CrossRef][Web of Science][Medline]
64. Hung J, Lam JY, Lacoste L, Letchacovski G. Cigarette smoking acutely increases platelet thrombus formation in patients with coronary artery disease taking aspirin. Circulation 1995;92:2432–2436.[Abstract/Free Full Text]
65. Benowitz NL, Fitzgerald GA, Wilson M, Zhang Q. Nicotine effects on eicosanoid formation and hemostatic function: comparison of transdermal nicotine and cigarette smoking. J Am Coll Cardiol 1993;22:1159–1167.[Abstract]
66. Imaizumi T, Satoh K, Yoshida H, Kawamura Y, Hiramoto M, Takamatsu S. Effect of cigarette smoking on the levels of platelet-activating factor-like lipid(s) in plasma lipoproteins. Atherosclerosis 1991;87:47–55.[CrossRef][Web of Science][Medline]
67. Smith CJ, Fischer TH, Sears SB. Environmental tobacco smoke, cardiovascular disease, and the nonlinear dose–response hypothesis. Toxicol Sci 2000;54:462–472.[Abstract/Free Full Text]
68. Ramachandran J, Rubenstein D, Bluestein D, Jesty J. Activation of platelets exposed to shear stress in the presence of smoke extracts of low-nicotine and zero-nicotine cigarettes: the protective effect of nicotine. Nicotine Tob Res 2004;6:835–841.
69. Terres W, Becker BF, Schrodl W, Gerlach E. Inhibition of platelet aggregation following chronic in vivo treatment of rats with nicotine: prevention by simultaneous application of propranolol. J Cardiovasc Pharmacol 1989;13:233–237.[Web of Science][Medline]
70. Whiss PA, Lundahl TH, Bengtsson T, Lindahl TL, Lunell E, Larsson R. Acute effects of nicotine infusion on platelets in nicotine users with normal and impaired renal function. Toxicol Appl Pharmacol 2000;163:95–104.[CrossRef][Web of Science][Medline]
71. Davis JW, Shelton L, Watanabe IS, Arnold J. Passive smoking affects endothelium and platelets. Arch Intern Med 1989;149:386–389.[Abstract/Free Full Text]
72. Burghuber OC, Punzengruber C, Sinzinger H, Haber P, Silberbauer K. Platelet sensitivity to prostacyclin in smokers and non-smokers. Chest 1986;90:34–38.[Abstract/Free Full Text]
73. Sinzinger H, Kefalides A. Passive smoking severely decreases platelet sensitivity to antiaggregatory prostaglandins. Lancet 1982;2:392–393.[Web of Science][Medline]
74. Schmid P, Karanikas G, Kritz H, Pirich C, Stamatopoulos Y, Peskar BA, Sinzinger H. Passive smoking and platelet thromboxane. Thromb Res 1996;81:451–460.[CrossRef][Web of Science][Medline]
75. Alanko J, Riutta A, Mucha I, Kerttula T, Kaukinen S, Vapaatalo H, Metsa-Ketela T, Seppala E. Adrenaline stimulates thromboxane and inhibits leukotriene synthesis in man. Eicosanoids 1992;5:169–175.[Web of Science][Medline]
76. Zidovetzki R, Chen P, Fisher M, Hofman FM, Faraci FM. Nicotine increases plasminogen activator inhibitor-1 production by human brain endothelial cells via protein kinase C-associated pathway. Stroke 1999;30:651–655.[Abstract/Free Full Text]
77. Allen RA, Kluft C, Brommer EJ. Effect of chronic smoking on fibrinolysis. Arteriosclerosis 1985;5:443–450.[Abstract/Free Full Text]
78. Newby DE, Boon NA. Lower cardiac mortality in smokers following thrombolysis. Q J Med 1999;92:679–681.
79. Meade TW, Imeson J, Stirling Y. Effects of changes in smoking and other characteristics on clotting factors and the risk of ischaemic heart disease. Lancet 1987;2:986–988.[Web of Science][Medline]
80. Blann AD, Steele C, McCollum CN. The influence of smoking and of oral and transdermal nicotine on blood pressure, and haematology and coagulation indices. Thromb Haemost 1997;78:1093–1096.[Web of Science][Medline]
81. Toschi V, Gallo R, Lettino M, Fallon JT, Gertz SD, Fernandez-Ortiz A, Chesebro JH, Badimon L, Nemerson Y, Fuster V, Badimon JJ. Tissue factor modulates the thrombogenicity of human atherosclerotic plaques. Circulation 1997;95:594–599.[Abstract/Free Full Text]
82. Hioki H, Aoki N, Kawano K, Homori M, Hasumura Y, Yasumura T, Maki A, Yoshino H, Yanagisawa A, Ishikawa K. Acute effects of cigarette smoking on platelet-dependent thrombin generation. Eur Heart J 2001;22:56–61.[Abstract/Free Full Text]
83. Simpson AJ, Gray RS, Moore NR, Booth NA. The effects of chronic smoking on the fibrinolytic potential of plasma and platelets. Br J Haematol 1997;97:208–213.[CrossRef][Web of Science][Medline]
84. Margaglione M, Cappucci G, d'Addedda M, Colaizzo D, Giuliani N, Vecchione G, Mascolo G, Grandone E, Di Minno G. PAI-1 plasma levels in a general population without clinical evidence of atherosclerosis: relation to environmental and genetic determinants. Arterioscler Thromb Vasc Biol 1998;18:562–567.[Abstract/Free Full Text]
85. Howard DJ, Ota RB, Briggs LA, Hampton M, Pritsos CA. Environmental tobacco smoke in the workplace induces oxidative stress in employees, including increased production of 8-hydroxy-2'-deoxyguanosine. Cancer Epidemiol Biomarkers Prev 1998;7:141–146.[Abstract]
86. Kosecik M, Erel O, Sevinc E, Selek S. Increased oxidative stress in children exposed to passive smoking. Int J Cardiol 2005;100:61–64.[CrossRef][Web of Science][Medline]
87. Dietrich M, Block G, Benowitz NL, Morrow JD, Hudes M, Jacob P III, Norkus EP, Packer L. Vitamin C supplementation decreases oxidative stress biomarker f2-isoprostanes in plasma of nonsmokers exposed to environmental tobacco smoke. Nutr Cancer 2003;45:176–184.[CrossRef][Web of Science][Medline]
88. Yildiz L, Kayaoglu N, Aksoy H. The changes of superoxide dismutase, catalase and glutathione peroxidase activities in erythrocytes of active and passive smokers. Clin Chem Lab Med 2002;40:612–615.[CrossRef][Web of Science][Medline]
89. Visioli F, Galli C, Plasmati E, Viappiani S, Hernandez A, Colombo C, Sala A. Olive phenol hydroxytyrosol prevents passive smoking-induced oxidative stress. Circulation 2000;102:2169–2171.[Abstract/Free Full Text]
90. Tribble DL, Giuliano LJ, Fortmann SP. Reduced plasma ascorbic acid concentrations in nonsmokers regularly exposed to environmental tobacco smoke. Am J Clin Nutr 1993;58:886–890.[Abstract/Free Full Text]
91. McCusker K, Hoidal J. Selective increase of antioxidant enzyme activity in the alveolar macrophages from cigarette smokers and smoke-exposed hamsters. Am Rev Respir Dis 1990;141:678–682.[Web of Science][Medline]
92. Harats D, Ben-Naim M, Dabach Y, Hollander G, Stein O, Stein Y. Cigarette smoking renders LDL susceptible to peroxidative modification and enhanced metabolism by macrophages. Atherosclerosis 1989;79:245–252.[CrossRef][Web of Science][Medline]
93. Yokode M, Nagano Y, Arai H, Ueyama K, Ueda Y, Kita T. Cigarette smoke and lipoprotein modification. A possible interpretation for development of atherosclerosis. Ann NY Acad Sci 1995;748:294–300.[CrossRef][Web of Science][Medline]
94. Flavahan NA. Atherosclerosis or lipoprotein-induced endothelial dysfunction. Potential mechanisms underlying reduction in EDRF/nitric oxide activity. Circulation 1992;85:1927–1938.[Free Full Text]
95. Napoli C, de Nigris F, Palinski W. Multiple role of reactive oxygen species in the arterial wall. J Cell Biochem 2001;82:674–682.[CrossRef][Web of Science][Medline]
96. Gasparoni A, Autelli M, Ravagni-Probizer MF, Bartoli A, Regazzi-Bonora M, Chirico G, Rondini G. Effect of passive smoking on thyroid function in infants. Eur J Endocrinol 1998;138:379–382.[Abstract]
97. Botti TP, Amin H, Hiltscher L, Wissler RW. A comparison of the quantitation of macrophage foam cell populations and the extent of apolipoprotein E deposition in developing atherosclerotic lesions in young people: high and low serum thiocyanate groups as an indication of smoking. PDAY Research Group. Pathobiological determinants of atherosclerosis in youth. Atherosclerosis 1996;124:191–202.[CrossRef][Web of Science][Medline]
98. Roberts KA, Rezai AA, Pinkerton KE, Rutledge JC. Effect of environmental tobacco smoke on LDL accumulation in the artery wall. Circulation 1996;94:2248–2253.[Abstract/Free Full Text]
99. Albert RE, Vanderlaan M, Burns FJ, Nishizumi M. Effect of carcinogens on chicken atherosclerosis. Cancer Res 1977;37(7 Pt 1):2232–2235.[Abstract/Free Full Text]
100. Revis NW, Bull R, Laurie D, Schiller CA. The effectiveness of chemical carcinogens to induce atherosclerosis in the white Carneau pigeon. Toxicology 1984;32:215–227.[CrossRef][Web of Science][Medline]
101. Gairola CG, Drawdy ML, Block AE, Daugherty A. Sidestream cigarette smoke accelerates atherogenesis in apolipoprotein E–/– mice. Atherosclerosis 2001;156:49–55.[CrossRef][Web of Science][Medline]
102. Zhu BQ, Sun YP, Sievers RE, Isenberg WM, Glantz SA, Parmley WW. Passive smoking increases experimental atherosclerosis in cholesterol-fed rabbits. J Am Coll Cardiol 1993;21:225–232.[Abstract]
103. Liu SQ, Fung YC. Changes in the structure and mechanical properties of pulmonary arteries of rats exposed to cigarette smoke. Am Rev Respir Dis 1993;148:768–777.[Web of Science][Medline]
104. Yang Z, Knight CA, Mamerow MM, Vickers K, Penn A, Postlethwait EM, Ballinger SW. Prenatal environmental tobacco smoke exposure promotes adult atherogenesis and mitochondrial damage in apolipoprotein E–/– mice fed a chow diet. Circulation 2004;110:3715–3720.[Abstract/Free Full Text]
105. Panagiotakos DB, Pitsavos C, Chrysohoou C, Skoumas J, Masoura C, Toutouzas P, Stefanadis C. Effect of exposure to secondhand smoke on markers of inflammation: the ATTICA Study. Am J Med 2004;116:145–150.[CrossRef][Web of Science][Medline]
106. Dobson AJ, Alexander HM, Heller RF, Lloyd DM. Passive smoking and the risk of heart attack or coronary death. Med J Aust 1991;154:793–797.[Web of Science][Medline]
107. Iso H, Shimamoto T, Sato S, Koike K, Iida M, Komachi Y. Passive smoking and plasma fibrinogen concentrations. Am J Epidemiol 1996;144: 1151–1154.[Abstract/Free Full Text]
108. Anderson R, Theron AJ, Richards GA, Myer MS, van Rensburg AJ. Passive smoking by humans sensitizes circulating neutrophils. Am Rev Respir Dis 1991;144(3 Pt 1):570–574.[Web of Science][Medline]
109. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005;352:1685–1695.[Free Full Text]
110. Hausberg M, Mark AL, Winniford MD, Brown RE, Somers VK. Sympathetic and vascular effects of short-term passive smoke exposure in healthy nonsmokers. Circulation 1997;96:282–287.
111. Franco P, Chabanski S, Szliwowski H, Dramaix M, Kahn A. Influence of maternal smoking on autonomic nervous system in healthy infants. Pediatr Res 2000;47:215–220.[Web of Science][Medline]
112. Yoshida T, Sakane N, Umekawa T, Kondo M. Effect of nicotine on sympathetic nervous system activity of mice subjected to immobilization stress. Physiol Behav 1994;55:53–57.[CrossRef][Medline]
113. Tseng CJ, Appalsamy M, Robertson D, Mosqueda-Garcia R. Effects of nicotine on brain stem mechanisms of cardiovascular control. J Pharmacol Exp Ther 1993;265:1511–1518.[Abstract/Free Full Text]
114. Chow FA, Seidler FJ, McCook EC, Slotkin TA. Adolescent nicotine exposure alters cardiac autonomic responsiveness: beta-adrenergic and m2-muscarinic receptors and their linkage to adenylyl cyclase. Brain Res 2000;878:119–126.[CrossRef][Web of Science][Medline]
115. Smith CJ, Scott SM, Ryan BA. Cardiovascular effects of odors. Toxicol Ind Health 1999;15:595–601.[Abstract/Free Full Text]
116. Pope CA III, Eatough DJ, Gold DR, Pang Y, Nielsen KR, Nath P, Verrier RL, Kanner RE. Acute exposure to environmental tobacco smoke and heart rate variability. Environ Health Perspect 2001;109:711–716.
117. Nolan J, Batin PD, Andrews R, Lindsay SJ, Brooksby P, Mullen M, Baig W, Flapan AD, Cowley A, Prescott RJ, Neilson JM, Fox KA. Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart). Circulation 1998;98:1510–1516.[Abstract/Free Full Text]
118. Minami J, Ishimitsu T, Matsuoka H. Effects of smoking cessation on blood pressure and heart rate variability in habitual smokers. Hypertension 1999;33(1 Pt 2):586–590.[Abstract/Free Full Text]
119. McMurray RG, Hicks LL, Thompson DL. The effects of passive inhalation of cigarette smoke on exercise performance. Eur J Appl Physiol Occup Physiol 1985;54:196–200.[CrossRef][Web of Science][Medline]
120. Gvozdjakova A, Kucharska J, Gvozdjak J. Effect of smoking on the oxidative processes of cardiomyocytes. Cardiology 1992;81:81–84.[Web of Science][Medline]
121. Pitsavos C, Panagiotakos DB, Chrysohoou C, Skoumas J, Tzioumis K, Stefanadis C, Toutouzas P. Association between exposure to environmental tobacco smoke and the development of acute coronary syndromes: the CARDIO2000 case–control study. Tob Control 2002;11:220–225.[Abstract/Free Full Text]
122. McElduff P, Dobson AJ, Jackson R, Beaglehole R, Heller RF, Lay-Yee R. Coronary events and exposure to environmental tobacco smoke: a case–control study from Australia and New Zealand. Tob Control 1998;7:41–46.[Abstract/Free Full Text]
123. Ciruzzi M, Pramparo P, Esteban O, Rozlosnik J, Tartaglione J, Abecasis B, Cesar J, De Rosa J, Paterno C, Schargrodsky H. Case–control study of passive smoking at home and risk of acute myocardial infarction. Argentine FRICAS Investigators. Factores de Riesgo Coronario en America del Sur. J Am Coll Cardiol 1998;31:797–803.[Abstract/Free Full Text]
124. Robinson K, Conroy RM, Mulcahy R. Smoking and acute coronary heart disease: a comparative study. Br Heart J 1988;60:465–469.[Abstract/Free Full Text]
125. Bolli R, Jeroudi MO, Patel BS, Aruoma OI, Halliwell B, Lai EK, McCay PB. Marked reduction of free radical generation and contractile dysfunction by antioxidant therapy begun at the time of reperfusion. Evidence that myocardial ‘stunning’ is a manifestation of reperfusion injury. Circ Res 1989;65:607–622.[Abstract/Free Full Text]
126. Frossard M, Fuchs I, Leitner JM, Hsieh K, Vlcek M, Losert H, Domanovits H, Schreiber W, Laggner AN, Jilma B. Platelet function predicts myocardial damage in patients with acute myocardial infarction. Circulation 2004;110:1392–1397.[Abstract/Free Full Text]

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