Cardiovascular risk factors, atherosclerosis and venous thromboembolism - The Tromsø study

Abstract

Venous thromboembolism (VTE) is a common and potentially fatal disease, often occuring in the absence of obvious predisposing factors. Recent observational studies in selected populations have suggested a closer association between arterial thrombosis (myocardial infarction (MI) and stroke) and VTE, two disease entities considered separate in terms of pathophysiology, epidemiology and treatments. The aim of this thesis was to investigate the relation between atherosclerosis, atherosclerotic risk factors and risk of incident VTE in a general population. We recruited study participants from the fourth survey of the Tromsø study, conducted in 1994-95. In this study, more than 27,000 men and women, aged 25-97 years, participated, and a subset of participants (n= 9056) were also invited to a more extensive second visit. Incident VTE events were registered from the date of inclusion until the end of follow up, and in papers 1 and 4, incident MI events were also registered. Furthermore, we performed a case-control study in which 20 participants with a previous history of unprovoked VTE and 20 healthy controls were subjected to a fat-tolerance test in order to examine the potential impact of postprandial lipemia on VTE risk. In a cause-specific hazards model, increasing age and obesity were shared risk factors for both MI and VTE. Traditional cardiovascular risk factors (diabetes, current smoking, higher levels of blood pressure, triglycerides and total cholesterol, and lower levels of HDL-cholesterol) were associated with increased risk of MI, but not with VTE. Carotid atherosclerosis, measured by intima-media thickness and total plaque area, did also increase MI risk, while showing no association with VTE. Increasing levels of high-sensitivity C-reactive protein (hs-CRP) did not increase VTE risk. Subjects with a history of unprovoked VTE had similar lipoprotein subclasses size, distribution, and postprandial lipemia as healthy controls. Based on our findings, atherosclerosis and atherosclerotic risk factors do not appear to be associated with VTE risk. The observed association between arterial and venous thrombosis may be explained by other common risk factors or restricted to the events themselves.