Smoking is Associated with Increased Risk of Major Bleeding: A Prospective Cohort Study

Anne Langsted; Børge G. Nordestgaard

doi:10.1055/s-0038-1675798

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2019; 119(01): 039-047
DOI: 10.1055/s-0038-1675798

Coagulation and Fibrinolysis

Georg Thieme Verlag KG Stuttgart · New York

Smoking is Associated with Increased Risk of Major Bleeding: A Prospective Cohort Study

Anne Langsted

¹Department of Clinical Biochemistry, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark

²The Copenhagen General Population Study Program, Copenhagen University Hospital, Herlev and Gentofte Hospital, Copenhagen University, Copenhagen, Denmark

,

Børge G. Nordestgaard

¹Department of Clinical Biochemistry, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark

²The Copenhagen General Population Study Program, Copenhagen University Hospital, Herlev and Gentofte Hospital, Copenhagen University, Copenhagen, Denmark

³Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

› Author Affiliations

Abstract

Background Tobacco smoking represents the most preventable cause of several fatal and disabling diseases worldwide. Several ingredients in tobacco have been suspected to cause changes in the arterial wall leading to instability of blood vessels. The association of smoking with major bleeding is largely unexplored. We tested the hypothesis that smoking and high tobacco consumption are associated with increased risk of bleeding.

Materials and Methods This is a prospective cohort study with a mean follow-up of 5.9 years including 99,359 individuals from the Copenhagen General Population Study, with a questionnaire including self-reported smoking status and information on smoking intensity in cigarettes per day and pack-years. In this study, 17,555 were current smokers, 40,182 former smokers and 41,622 were never smokers.

Results Multivariable adjusted hazard ratios for current smokers versus never smokers were 1.49 (95% confidence interval [CI]: 1.38–1.61) for any major bleeding, 1.71 (1.37–2.13) for intracranial bleeding, 1.35 (1.14–1.60) for airway bleeding, 2.20 (1.84–2.62) for gastrointestinal bleeding and 1.39 (1.26–1.55) for urinary bleeding. Increased smoking intensity was also associated with increased risk of any major bleeding, where > 40 pack-years in current and former smokers compared with never smokers had a multivariable adjusted hazard ratio of 1.59 (95% CI: 1.45–1.73) (p for trend across four groups: < 0.001). Also, current smokers smoking > 20 cigarettes per day compared with former and never smokers had a corresponding hazard ratio of 1.67 (1.51–1.85) (p for trend across four groups: < 0.001).

Conclusion Current smokers have an increased risk of any major bleeding as well as of intracranial, airway, gastrointestinal and urinary bleeding. Also, increased smoking intensity was associated with increased risk of major bleeding.

Keywords

tobacco - pack-years - haemorrhage - epidemiology

Full Text

References

References
1 Mokdad AH, Marks JS, Stroup DF, Gerberding JL. Actual causes of death in the United States, 2000. JAMA 2004; 291 (10) 1238-1245
2 Frieden TR, Bloomberg MR. How to prevent 100 million deaths from tobacco. Lancet 2007; 369 (9574): 1758-1761
3 Jha P, Ramasundarahettige C, Landsman V. , et al. 21st-century hazards of smoking and benefits of cessation in the United States. N Engl J Med 2013; 368 (04) 341-350
4 Holford TR, Meza R, Warner KE. , et al. Tobacco control and the reduction in smoking-related premature deaths in the United States, 1964-2012. JAMA 2014; 311 (02) 164-171
5 Powell JT. Vascular damage from smoking: disease mechanisms at the arterial wall. Vasc Med 1998; 3 (01) 21-28
6 Yalcin E, de la Monte S. Tobacco nitrosamines as culprits in disease: mechanisms reviewed. J Physiol Biochem 2016; 72 (01) 107-120
7 Khan F, Datta YH. Risk of bleeding during long-term anticoagulation with warfarin: a tertiary care center experience. Blood Coagul Fibrinolysis 2015; 26 (01) 110-112
8 Braekkan SK, van der Graaf Y, Visseren FL, Algra A. Obesity and risk of bleeding: the SMART study. J Thromb Haemost 2016; 14 (01) 65-72
9 Decousus H, Tapson VF, Bergmann JF. , et al; IMPROVE Investigators. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest 2011; 139 (01) 69-79
10 Hostler DC, Marx ES, Moores LK. , et al. Validation of the International Medical Prevention Registry on Venous Thromboembolism Bleeding Risk Score. Chest 2016; 149 (02) 372-379
11 Bluhm AL, Weinstein J, Sousa JA. Free radicals in tobacco smoke. Nature 1971; 229 (5285): 500
12 Ding YS, Zhang L, Jain RB. , et al. Levels of tobacco-specific nitrosamines and polycyclic aromatic hydrocarbons in mainstream smoke from different tobacco varieties. Cancer Epidemiol Biomarkers Prev 2008; 17 (12) 3366-3371
13 Feigin VL, Rinkel GJ, Lawes CM. , et al. Risk factors for subarachnoid hemorrhage: an updated systematic review of epidemiological studies. Stroke 2005; 36 (12) 2773-2780
14 Stack WA, Atherton JC, Hawkey GM, Logan RF, Hawkey CJ. Interactions between Helicobacter pylori and other risk factors for peptic ulcer bleeding. Aliment Pharmacol Ther 2002; 16 (03) 497-506
15 Weil J, Langman MJ, Wainwright P. , et al. Peptic ulcer bleeding: accessory risk factors and interactions with non-steroidal anti-inflammatory drugs. Gut 2000; 46 (01) 27-31
16 Peters SA, Huxley RR, Woodward M. Smoking as a risk factor for stroke in women compared with men: a systematic review and meta-analysis of 81 cohorts, including 3,980,359 individuals and 42,401 strokes. Stroke 2013; 44 (10) 2821-2828
17 Kurth T, Kase CS, Berger K, Schaeffner ES, Buring JE, Gaziano JM. Smoking and the risk of hemorrhagic stroke in men. Stroke 2003; 34 (05) 1151-1155
18 Kurth T, Kase CS, Berger K, Gaziano JM, Cook NR, Buring JE. Smoking and risk of hemorrhagic stroke in women. Stroke 2003; 34 (12) 2792-2795
19 Zhang Y, Tuomilehto J, Jousilahti P, Wang Y, Antikainen R, Hu G. Lifestyle factors on the risks of ischemic and hemorrhagic stroke. Arch Intern Med 2011; 171 (20) 1811-1818
20 Xu L, Schooling CM, Chan WM, Lee SY, Leung GM, Lam TH. Smoking and hemorrhagic stroke mortality in a prospective cohort study of older Chinese. Stroke 2013; 44 (08) 2144-2149
21 Song YM, Cho HJ. Risk of stroke and myocardial infarction after reduction or cessation of cigarette smoking: a cohort study in Korean men. Stroke 2008; 39 (09) 2432-2438
22 Feigin V, Parag V, Lawes CM. , et al; Asia Pacific Cohort Studies Collaboration. Smoking and elevated blood pressure are the most important risk factors for subarachnoid hemorrhage in the Asia-Pacific region: an overview of 26 cohorts involving 306,620 participants. Stroke 2005; 36 (07) 1360-1365
23 Savage RL, Moller PW, Ballantyne CL, Wells JE. Variation in the risk of peptic ulcer complications with nonsteroidal antiinflammatory drug therapy. Arthritis Rheum 1993; 36 (01) 84-90
24 Tzourmakliotis D, Economou M, Manolakopoulos S. , et al. Clinical significance of cytotoxin-associated gene A status of Helicobacter pylori among non-steroidal anti-inflammatory drug users with peptic ulcer bleeding: a multicenter case-control study. Scand J Gastroenterol 2004; 39 (12) 1180-1185
25 Ng TM, Fock KM, Khor JL. , et al. Non-steroidal anti-inflammatory drugs, Helicobacter pylori and bleeding gastric ulcer. Aliment Pharmacol Ther 2000; 14 (02) 203-209
26 Lewis SC, Langman MJ, Laporte JR, Matthews JN, Rawlins MD, Wiholm BE. Dose-response relationships between individual nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) and serious upper gastrointestinal bleeding: a meta-analysis based on individual patient data. Br J Clin Pharmacol 2002; 54 (03) 320-326
27 Strate LL, Singh P, Boylan MR, Piawah S, Cao Y, Chan AT. A prospective study of alcohol consumption and smoking and the risk of major gastrointestinal bleeding in men. PLoS One 2016; 11 (11) e0165278
28 Kaplan RC, Heckbert SR, Koepsell TD. , et al; Cardiovascular Health Study Investigators. Risk factors for hospitalized gastrointestinal bleeding among older persons. J Am Geriatr Soc 2001; 49 (02) 126-133
29 Hiyama J, Horita N, Shiota Y, Ono T, Yamakido M. Cryptogenic hemoptysis and smoking. Chest 2002; 121 (04) 1375-1376
30 Jeong CW, Lee S, Byun SS, Lee DH, Lee SE. No increase in risk of microscopic hematuria with aspirin use by asymptomatic healthy people. JAMA Intern Med 2013; 173 (12) 1145-1146

Supplementary Material

Supplementary Material