Smoking
Authors: Sonia S. Anand
Journal: Circulation (2016)

raditional book learning and clinical training of common risk factors for venous thromboembolism (VTE) did not include cigarette smoking.I recall as a medical student, after giving the history of a patient presenting with deep venous thrombosis, being told that smoking was not a risk factor for venous disease, only arterial disease.This perplexed me.If smoking was known to "thicken the blood," as evidenced by the increased fibrinogen, and venous thromboses typically represent a larger clot burden compared with arterial thromboses, why wouldn't cigarette smoking be a dual pathogen for venous and arterial disease?Prior evaluations have compared the risk of smoking and other traditional arterial risk factors (ie, diabetes mellitus, hypertension, and elevated cholesterol) for arterial vascular disease with the risk of these factors for VTE. 1 Our understanding of the pathophysiology of arterial vascular diseases is based on atherosclerosis, which becomes atherothrombosis when plaque rupture occurs, platelets are recruited, and the coagulation cascade is activated.Clinically apparent venous thrombosis is usually the result of venous stasis (immobility or obstruction), stimulation of the coagulation cascade from circulating or exogenous inciters leading to a hypercoagulable state, or mechanical injury to the vessel wall.One may expect that there are unique risk factors for arterial and venous thrombosis and some shared risk factors for which stasis conditions, hypercoagulable states, and vessel injury are the inciters (Figure).Some evidence supports a shared pathogenesis of arterial and venous thrombosis.The Tromsø study of 21 624 subjects recruited from Norway showed that a family history of myocardial infarction is associated with a 52% increased risk of myocardial infarction and a 26% increased risk of VTE after adjustment for traditional risk factors for VTE. 2 Furthermore, both hormone replacement therapy and oral contraceptive pills are associated with an increased risk of myocardial infarction, stroke, and VTE, and their effects are magnified in the presence of other thrombosis promoters such as genetic polymorphisms (ie, factor V Leiden) and cigarette smoke.Comparison studies of arterial and venous risk factors have produced mixed results, in large part because cardiovascular disease outcomes are 2.5 to 3.5 times more common in similar cohorts of middle-aged adults who are apparently healthy. 3,4 Prior analyses from the US Physicians Health Study reported no association between hypertension, elevated cholesterol, diabetes mellitus, and smoking with VTE, whereas increasing body mass index (BMI) and height were associated with incident VTE more than with cardiovascular disease. 3Notably, only 358 VTE events were observed in this study compared with 2300 cardiovascular disease events, which makes the null finding of smoking as a risk factor for VTE potentially a type 2 error.Furthermore, although meta-analysis may overcome the relatively low number of VTE events observed in individual cohorts, the correlation between putative risk factors and heterogeneity in study design, including definitions of risk factors, may be more difficult Smoking a dual Pathogen for arterial and Venous thrombosis