Venous Thromboembolism Portends Future Stroke and MI

AARHUS, Denmark, Nov.26 -- A deep venous thrombosis (DVT) or a pulmonary embolism predicts a substantially increased likelihood of a heart attack or stroke over the next 20 years, researchers here reported.
Action Points
Explain to interested patients that the evidence from this study indicates that patients with a venous thromboembolism have an increased risk of heart attack or stroke over the next two decades, although the causes are still not clear.
The excess risk was most pronounced during the first year of follow-up, but persisted for up to 20 years with a 20% to 40% higher combined risk versus controls, Henrik T. Sorensen, M.D., Ph.D., of Aarhus University Hospital here, and colleagues reported in the Nov. 24 issue of The Lancet.
These risks were similar for those with provoked (cancer, trauma, surgery, pregnancy) and unprovoked DVT and for pulmonary embolism, the researchers said.
The mechanisms underlying the associations between venous thromboembolism and atherosclerotic disease are not clear, the researchers wrote.
The study was designed to clarify recent epidemiological studies that have examined the association between venous thromboembolism and measures of atherosclerosis or arterial thromboembolic events, such as stroke or MI, and that have reported conflicting results.
The researchers undertook a 20-year population-based cohort study using data from nationwide Danish medical databases.
After excluding patients with known cardiovascular disease, they assessed the risk of MI and stroke in 2,199 patients with DVT, 16,925 patients with pulmonary embolism, and 163,566 population controls.
In the first year after a thrombotic event, for patients with deep venous thrombosis, the relative risk of MI was 60% higher versus controls (RR: 1.60, 95% CI: 1.35 to 1.91), and the risk for stroke was 119% higher (RR: 2.19, 95% CI: 1.85 to 2.60).
These risks were even higher for pulmonary embolism. For these patients, the relative risks for myocardial infarction in the first year were more than two-and-a-half times higher than the risks for controls (RR: 2.60, 95% CI: 2.14 to 3.14) and almost three times higher for stroke (RR: 2.93, 95% CI: 2.34 to 3.66).
Over the following 20 years, the combined increased risk for arterial cardiovascular events compared with controls was 20% to 40% higher for patients with venous thromboembolism (RR: 1.2 to 1.4).
It is not plausible, the investigators wrote, that venous thromboembolism in itself causes myocardial infarction and stroke. Rather, they said, the association must be due to shared risk factors or etiologic pathways, or both.
With the exception of obesity, they wrote, there is only weak evidence that venous and atherosclerotic diseases share common risk factors, such as diabetes, hypertension, hyperlipidemia, and smoking. Differences in the etiology of ischemic stroke and myocardial infarction might explain some of these differences, they said.
However, the value of preventive measures against MI and stroke in these patients is uncertain, and trials are ongoing to establish the effect of aspirin on long-term treatment of venous thromboembolism.
Regarding study limitations, the researchers mentioned that the lack of specificity for the outcome diagnosis in the Danish databank may have biased the risk estimates. Also, they noted that they did not have information on the use of oral anticoagulants, which would reduce the risk of MI and stroke.
"We find strong evidence that venous thromboembolism is associated with an increased long-term risk of arterial cardiovascular events irrespective of the presence or absence of classic risk factors for venous thromboembolism.
"Common risk factors or pathways are most likely responsible for the association. Future studies are needed to further clarify the association, and to evaluate its implications for clinical practice," the researchers concluded.
In an accompanying comment, Gordon D.O. Lowe, M.D., of the University of Glasgow in Scotland, wrote that finding an increased risk of MI and stroke in the first year after diagnosis of venous thromboembolism is surprising, perhaps because the standard treatment of oral anticoagulant drugs for three to six months should lower the risk.
Possible explanations, Dr. Lowe said, include an increased risk of hemorrhagic stroke during anticoagulant therapy, rebound hypercoagulability and/or failure to restart aspirin after cessation of anticoagulants, or hypercoagulability induced by a common exposure such as infection.
Further prospective epidemiological studies are needed, he said, but in the meantime an assessment of absolute risk of myocardial infarction or stroke should be done, as has been recommended for all people age 40 and older. This should be followed by lifestyle advice and consideration of drugs that lower cardiovascular risk, including low-dose aspirin where appropriate, Dr. Lowe wrote.
The study obtained support from the Western Danish Research Forum for Health Sciences and a grant from the Danish Research Agency.
The study investigators declared no conflicts of interest.
Dr. Lowe declared no conflicts of interest.
Primary source: The LancetSource reference: Sorensen HT, et al "Venous thromboembolism and subsequent hospitalization due to acute arterial cardiovascular events: a 20-year cohort study" The Lancet 2007; 370: 1773-1779.Additional source: The LancetSource reference: Lowe, G "Is venous thrombosis a risk factor for arterial thrombosis?" The Lancet 2007; 370: 1742-1744.