Tabac et Maladie Veineuse Thrombo-Embolique. Antoine ELIAS Hôpital Sainte Musse Toulon Novembre 2018

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1 Tabac et Maladie Veineuse Thrombo-Embolique Antoine ELIAS Hôpital Sainte Musse Toulon Novembre 2018

2 Tabac: Facteur de risque de MTEV? Tabac - Thrombose Veineuse Association? Force de l association? Association ou causalité? Situations cliniques 1. EP/ TVP symptomatique Provoquée Non provoquée 2. Récidive Impact potentiel Santé publique (nombre de sujets tabagiques en population générale)? Pratique clinique?

3 Yun-Jiu Cheng et al. Current and Former Smoking and Risk for Venous Thromboembolism: A Systematic Review and Meta-Analysis. PLOS Medicine September 2013 Volume 10 Issue 9 e observational studies 3,966,184 participants and 35,151 VTE events VTE ever smokers vs never smokers : RR 1.17 (95% CI ) current smokers vs never smokers: RR 1.23 (95% CI ) former smokers vs never smokers: RR 1.10 (95% CI ) VTE/ BMI-adjusted analysis (13 studies) current smokers vs never somkers: RR (1.30; 95% CI ) Population attributable fractions of VTE ever smoking: 8.7% (95% CI 4.8% 12.3%) current smoking: 5.8% (95% CI 3.6% 8.2%) former smoking: 2.7% (95% CI 0.8% 4.5%). Smoking: absolute risk increase of 24.3 (95% CI ) cases per 100,000 person-years

4 Yun-Jiu Cheng et al. Current and Former Smoking and Risk for Venous Thromboembolism: A Systematic Review and Meta-Analysis. PLOS Medicine September 2013 Volume 10 Issue 9 e The risk increased by 10.2% (95% CI 8.6% 11.8%) for every additional ten cigarettes per day smoked The risk increased by 6.1% (95% CI 3.8% 8.5%) for every additional ten pack-years.

5 Tan L, Qi B, Yu T, Wang C. Incidence and risk factors for venous thromboembolism following surgical treatment of fractures below the hip: a meta-analysis. Int Wound J 2016; doi: /iwj Incidence of VTE: 21% (95% CI: 17%, 24%; P=0.000) Risk factors associated with an increased risk of developing VTE Age ( 60 years) (RR = 1.85, 95% CI: 1.34, 2.55; P=0.000) Previous VTE (RR=5.25, 95% CI: 2.77, 9.96; P=0.000) Heart failure (RR=1.74, 95% CI: 1.34, 2.27; P=0.000) Current smoking status (RR=1.23, 95% CI: 1.07, 1.41; P=0.004) Hypertension (RR=1.62, 95% CI: 1.27, 2.06; P=0.000) Hyperlipidaemia (RR=2.16, 95% CI: 1.79, 2.62; P=0.000) Diabetes mellitus (RR=1.46, 95% CI: 1.27, 1.68; P=0.000) Obesity (RR=1.58, 95% CI: 1.35, 1.85; P=0.000) Multiple fractures (RR=2.14, 95% CI: 1.00, 4.60; P=0.050) Varicose veins (RR=3.07, 95% CI: 1.12, 8.47; P=0.030) Prolonged operation time (WMD=1.22, 95% CI: 0.63, 1.81; P=0.000) Prolonged bed rest time (WMD=3.12, 95% CI: 2.96, 3.29; P=0.000)

6 Tan L, Qi B, Yu T, Wang C. Incidence and risk factors for venous thromboembolism following surgical treatment of fractures below the hip: a meta-analysis. Int Wound J 2016; doi: /iwj.12533

7 Bakhtawar K. Mahmoodi et al. Association of Traditional Cardiovascular Risk Factors With Venous Thromboembolism. An Individual Participant Data Meta-Analysis of Prospective Studies Circulation. 2017;135:7 16. DOI: /CIRCULATIONAHA Association CVD risk factors and VTE Individual-level data meta-analyses of 9 prospective studies Exposure self-reported smoking current smoking versus former or never smoking combined former smoking versus never smoking. Outcome: Symptomatic validated VTE events (DVT/ PE) Provoked Major trauma, surgery, significant immobilization, or active cancer in the preceding 3 months (±) oral contraceptives or hormone therapy, pregnancy, long-distance travel, active infectious disease, acute myocardial infarction, paresis/paralysis of the leg, and heart failure Unprovoked participants and 4910 VTE events Ajustement: prise en compte des facteurs de confusion

8 Bakhtawar K. Mahmoodi et al. Association of Traditional Cardiovascular Risk Factors With Venous Thromboembolism. An Individual Participant Data Meta-Analysis of Prospective Studies Circulation. 2017;135:7 16. DOI: /CIRCULATIONAHA Model 1: univariate analysis Model 2: age-, sex-, and BMI-adjusted models Model 3: fully adjusted models (age, sex, race, BMI (continuous), history of cardiovascular disease (CVD), history of VTE, hypertension, hypercholesterolemia, diabetes mellitus, and former and current smoking.

9 Bakhtawar K. Mahmoodi et al. Association of Traditional Cardiovascular Risk Factors With Venous Thromboembolism. An Individual Participant Data Meta-Analysis of Prospective Studies Circulation. 2017;135:7 16. DOI: /CIRCULATIONAHA

10 Bakhtawar K. Mahmoodi et al. Association of Traditional Cardiovascular Risk Factors With Venous Thromboembolism. An Individual Participant Data Meta-Analysis of Prospective Studies Circulation. 2017;135:7 16. DOI: /CIRCULATIONAHA Tabagisme actuel MTEV provoquée (HR=1,36; IC95% 1,22-1,52) MTEV non provoquée (HR=1,08; 0,90-1,29) Tabagisme passé MTEV provoquée (HR=1,11 ; 1,00-1,23) MTEV non provoquée (HR=1,01 ; 0,89-1,16).

11 Sonia S. Anand Smoking A Dual Pathogen for Arterial and Venous Thrombosis Circulation. 2017;135: DOI: /CIRCULATIONAHA

12 Victor F. Tapson The Role of Smoking in Coagulation and Thromboembolism in Chronic Obstructive Pulmonary Disease Proc Am Thorac Soc Vol 2. pp 71 77, 2005 DOI: /pats MS Increased fibrinogen levels from: Increased interleukin-6 Increased catecholamine release Free fatty acids Increased clotting factor levels including factors II (thrombin), V, VIII, X, and XIII Increased tissue factor level Reduced tissue factor pathway inhibitor level Increased homocysteine level Lower antithrombin III activity Impaired fibrinolysis Reduced tissue plasminogen activator production Impaired tissue plasminogen activator release Increased plasminogen activator inhibitor production Increased platelet activation

13 Bradford-Hill criteria Hill AB. The environment and disease: association or causation? Proc R Soc Med1965; 58: strength of association(effect size) consistency in different studies, settings specificity of association of risk factor with disease temporality - exposure precedes disease dose-response relationship biological plausibility for causality coherence - association consistent with current knowledge experimental evidence for causality analogous evidence between a similar exposure and disease

14 Philippe Carruzzo et al. Association between smoking and recurrence of venous thromboembolism and bleeding in elderly patients with past acute venous thromboembolism Thrombosis Research 138 (2016) Prospective Swiss multicenter cohort 988 patients, (52%) had never smoked, (41%) were former smokers - 76 (8%) current smokers. Median follow-up of 29.6 months, Associations between smoking status and VTE were analysed using proportional hazard models for the subdistribution of a competing risk of death Adjustments: age and gender and for variables associated with VTE recurrence, including prior VTE, active cancer, overt PE, and provoked VTE (defined as the presence of immobilization, major surgery, or current estrogen therapy during the last 3 months)

15 CONCLUSIONS Tabac: Facteur de risque indépendant de MTEV Association faible (RR) Relation dose-réponse Impact en population Proportion de MTEV attribuable au tabac en population Situations cliniques MTEV provoquée Pas la MTEV non provoquée Pas la récidive Mécanismes probables Inflammation Activation de la coagulation

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