Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults.

Celermajer, David S.; Sørensen, Keld E.; Georgakopoulos, Dimitri; Bull, Catherine; Thomas, Odette; Robinson, JH; Deanfield, John

doi:10.1161/01.cir.88.5.2149

Cited by 1,390 publications

(931 citation statements)

References 39 publications

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“…This study was among the first in humans to demonstrate the important role of endothelial dysfunction early in the course of atherosclerosis. Similarly, abnormal vasomotion occurs in subjects with uncomplicated hypertension (71), diabetes (72)(73)(74)(75), cigarette smoking (76,77) and low levels of high density lipoprotein (78,79). Oxidized low density lipoprotein plays an important role in abnormal endothelial vasorelaxation, leukocyte adhesion and endothelin production (80)(81)(82)(83).…”

Section: Relationship Of Endothelial Function To Risk Factors and Thementioning

confidence: 99%

Arterial stiffness or endothelial dysfunction as a surrogate marker of vascular risk

Anderson

2006

Canadian Journal of Cardiology

154

113

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T he understanding of the pathophysiology of atherosclerosis and its vascular complications has increased dramatically over the past decade. Numerous measurable biomarkers play a role in the atherosclerosis process, and are associated with clinically important vascular events. Not only has their evaluation advanced our knowledge of the atherosclerotic process but it has also accelerated a search for new diagnostic tools to aid in risk stratification. Putative factors include soluble biomarkers and imaging assessments of vascular structure and function. The endothelium plays a key role in vascular homeostasis through the release of a variety of paracrine factors that interact with platelets, inflammatory cells and the vessel wall. The endothelium's central location allows it to sense and respond to a variety of perturbations. Endothelial dysfunction is an early marker of disease. Risk factors can also affect mechanical properties such as arterial stiffness, which is now recognized as a major contributor to systolic hypertension in elderly people. Methods of assessing endothelial function and arterial stiffness are available for clinical research and recent evidence suggests that these measures may provide important prognostic information. ATTRIBUTES OF A SURROGATE BIOMARKEREpidemiological studies, such as Framingham, have allowed longitudinal assessment of cardiovascular events and the development of simple scoring tables for risk calculation (1,2). These factors involved include blood pressure, lipid profile, smoking status and age. More recently, many factors thought to be associated with the atherosclerotic process have been studied. Some of these have been shown to correlate with clinical outcomes and have been deemed biomarkers (3,4). However, association does not necessarily imply causation and, due to a variety of limitations, most of these markers will not be useful for the clinical evaluation of risk or drug therapy (5). To become clinically important, a biomarker must fulfill the criteria for a surrogate marker. A surrogate substitutes for clinically important end points with respect to how an individual feels, functions or survives. Classic examples include blood pressure and low density lipoprotein cholesterol. These are targets of treatment. A surrogate should meet the following criteria:• Adds independent information above currently used criteria;• Is reliably and reproducibly measured;• Accounts for a significant proportion of disease risk;• Provides good predictive value;• Is reasonably associated with the underlying pathophysiology;• If it is to be used in risk prevention, is present before the clinical appearance of the outcome; and• Is available and practical for widespread application (5-8). ADVANCES IN VASCULAR BIOLOGY

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Section: Relationship Of Endothelial Function To Risk Factors and Thementioning

confidence: 99%

Arterial stiffness or endothelial dysfunction as a surrogate marker of vascular risk

Anderson

2006

Canadian Journal of Cardiology

154

113

View full text Add to dashboard Cite

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“…The endothelium plays a central role in the control of vascular tone. 11 Impaired endothelium-dependent arterial dilatation has been demonstrated in both active smoking 12,13 and in prolonged exposure to environmental tobacco smoke. 14 Endothelial dysfunction has been implicated in the pathogenesis of coronary arterial spasm in atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Increased severity of multifocal renal arterial fibromuscular dysplasia in smokers

et al. 1999

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Renal arterial fibromuscular dysplasia (FMD) is a significant cause of renovascular hypertension, especially in younger females. Tobacco constituents have been shown to stimulate proliferation and synthetic activity of cultured human vascular smooth muscle cells. We examined the relationship between smoking and severity of FMD in a group of 50 subjects with the multifocal form of renal arterial FMD. A detailed smoking history was obtained by interview, clinical data at diagnosis of FMD were obtained from medical records, and angiograms were reviewed. Clinical and angiographic features were compared between smokers and non-smokers. Twenty-four sub-

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“…Oxidized LDL (OxLDL) in turn may induce endothelial expression of adhesion molecules, like intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) (Penn & Chisolm, 1994;Holvoet, 1999). Previous reports (Celermajer et al, 1993;Zeiher et al, 1995;Heitzer et al, 1996) have suggested that smoking induces endothelial dysfunction, which is regarded as an early event in atherogenesis.…”

Section: Introductionmentioning

confidence: 99%

Does vitamin C supplementation influence the levels of circulating oxidized LDL, sICAM-1, sVCAM-1 and vWF-antigen in healthy male smokers?

et al. 2004

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Objective: To examine the effects of vitamin C supplementation on the concentration of oxidation markers, in particular, circulating oxidized LDL (OxLDL) and on endothelial activation markers. Design: Randomized double-blind, placebo-controlled crossover trial. Setting: Belgian population of the city of Leuven. Subjects: A total of 34 healthy male smokers aged 26-73 y. Intervention: Smokers were randomly assigned to receive either vitamin C (250 mg twice daily) or placebo capsules, each to be taken for 4 weeks. After a 1-week washout period, participants then crossed over to the alternative capsules for further 4 weeks. Mean outcome measures: Markers of oxidation (bilirubin, uric acid, a-tocopherol, retinol, malondialdehyde, circulating Oxidized LDL (OxLDL)) and markers of endothelial activation (sICAM-1, sVCAM-1, vWF-antigen) were analysed. Results: Plasma ascorbate concentrations significantly increased from 46.6717.6 to 70.1721.2 mmol/l after a 4-week treatment with 500 mg vitamin C per day. The other plasma antioxidants concentrations, including bilirubin, uric acid, a-tocopherol and retinol, were similar in both treatment periods. Vitamin C did not change plasma malondialdehyde and circulating OxLDL compared with placebo (vitamin C 0.7370.25 mg/dl OxLDL; placebo 0.7270.21 mg/dl OxLDL). After vitamin C supplementation, neither sICAM-1 and sVCAM-1 levels nor the concentration of vWF-antigen significantly differed from placebo condition. Conclusions: Oral supplementation of vitamin C is not associated with changes in markers of oxidation or endothelial activation in healthy male smokers.

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Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults.

Abstract: Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent arterial dilation in asymptomatic young adults, consistent with endothelial dysfunction.

Cited by 1,390 publications

References 39 publications

Arterial stiffness or endothelial dysfunction as a surrogate marker of vascular risk

Arterial stiffness or endothelial dysfunction as a surrogate marker of vascular risk

Increased severity of multifocal renal arterial fibromuscular dysplasia in smokers

Does vitamin C supplementation influence the levels of circulating oxidized LDL, sICAM-1, sVCAM-1 and vWF-antigen in healthy male smokers?

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