Incidence, mortality and riskfactors of first venous thrombosisin a general population: Results from the second Nord-Trøndelag Health Study (HUNT 2)

Abstract

Venous thrombosis (VT) is the third most common cardiovascular disease after myocardial infarction and stroke. The most frequent clinical manifestation is thrombosis of the leg (deep venous thrombosis), which may embolize to the lungs (pulmonary embolism). The thrombus may disappear spontaneously or give raise to chronic leg or lung problems, which may have major impact on quality of life, and may even cause death. Numerous risk factors are known to increase the risk of venous thrombosis. Among these are hereditary defects in the coagulation system, hormonal changes (e.g., pregnancy, use of oestrogens), other diseases (e.g., malignancy), and physical factors (e.g., inactivity).

The primary aim of this thesis was to study incidence, mortality, and risk factors for venous thrombosis. The studies are based on an endpoint register on venous thrombosis in Nord-Trøndelag County from 1995 to 2001 linked to the second Nord-Trøndelag Health Study (HUNT 2) performed in 1995-1997. We identified 740 cases with a first venous thrombosis after six years of follow-up among all the residents in the county, and 515 of the cases were among those who participated in the HUNT 2 study.

We found an overall incidence of venous thrombosis of 1.43 per 1000 person-years in Nord-Trøndelag County. The incidence rate increased exponentially with increasing age, and was similar in men and women. The 30-days case-fatality rate was two times higher after pulmonary embolism than after deep venous thrombosis. The risk of dying was highest in the first months after the thrombotic event, after which it gradually approached the mortality rate in the general population.

Elevated anticardiolipin antibodies have been associated with a two-fold increased risk for venous thrombosis in presence of autoimmune disease, whereas in patients without autoimmune disease the results have been inconsistent. We found no association between venous thrombosis and elevated anticardiolipin antibody levels measured in blood samples drawn before the thrombotic event. Our results indicate that elevated anticardiolipin antibody levels are a result rather than a cause of venous thrombosis.

Previous case-control studies in which blood samples were drawn after the thrombotic event have found that elevated levels of interleukin 6 and 8 may be associated with venous thrombosis. We studied the association between elevated levels of six inflammatory markers prior to the thrombotic event and found no association. The results indicated that elevated levels of cytokines are secondary to venous thrombosis and not a primary cause.

Homocysteine has been considered as one of the risk factors for venous thrombosis. Most of the studies which have been performed, have measured homocysteine in blood sampled after the event, and thus could not rule out whether homocysteine was a cause or a result of the thrombosis. In this prospective study where blood was sampled before the thrombotic event, we found no clear association between elevated levels of homocysteine and VT, but high levels of homocysteine was associated with a two-fold increased risk of a first venous thrombosis in men. The MTHFR C677T genotype, which increases homocysteine levels, was not associated with VT.