1. Inge M. van Schouwenburg
Population Based Cohort Study on the Risk of Arterial Thrombosis in Subjects with Venous Thrombosis
Inge M. van Schouwenburg
Division of Hemostasis and Thrombosis, Department of Hematology
University Medical Center Groningen
The Netherlands

2. Disclosures for I.M. van Schouwenburg
In compliance with ACCME policy, ISTH requires the following disclosures to the session audience:
Research Support/P.I.
No relevant conflicts of interest to declare
Employee
Consultant
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Presentation includes discussion of the following off-label use of a drug or medical device:
<N/A> 2

3. Background
Previous studies have shown an increased relative risk of arterial thrombosis after venous thrombosis1,2
Absolute risks are unknown
Previous studies have shown a mild relation between arterial thrombotic risk factors and venous thrombosis3
1. Sørensen et al. Lancet Klok et al. Blood Ageno et al. Circulation 2008

4. Aim of the study
To assess the absolute risk of arterial thrombosis after venous thrombosis
- Type of event
- Environmental risk factors
- Persistence of risk through time
If an association is present, could this be explained by the presence of arterial thrombotic risk factors?

5. Methods – Study Population
Prevention of REnal and Vascular ENd-stage Disease (PREVEND)
Groningen population aged years (n=85,421)
Questionnaire regarding arterial thrombotic risk factors and morbidity + a vial to collect a first morning urine sample
40,856 responders
Follow-up between
End follow-up: death, moving out of the city, arterial bleeding, arterial thrombosis, end of study,

6. Methods – Adjudication of events
Anticoagulation clinics and national registry of hospital discharge diagnoses, confirmed in patients medical records
ATE: Myocardial infarction, Coronary artery disease, Peripheral arterial occlusive disease, Ischemic stroke
VTE: Deep vein thrombosis, Pulmonary embolism
Provoked: surgery, trauma, immobilization for more than 7 days, pregnancy, puerperium, the use of oral contraceptives or hormonal replacement therapy, or malignancy

7. Results – Baseline Characteristics
Total
40,856
Male, n
18,625
Mean age at enrollment, y 50
Arterial thrombotic risk factors
Hypertension, % 29
Hyperlipidemia, % 14
Diabetes Mellitus, % 3
Current Smokers, % 42
Microalbuminuria (>20 mg/L) , % 8
Previous ATE, % 4
INTERHEART: HT: 21% (39% in cases), DM:8, rokers: 27 (45 in cases)

8. Results – Number of events
Characteristic
Value
Venous thrombosis, n
537
Mean age at onset, y 62
Arterial thrombosis, n
2314 66

9. Results – Risk of ATE AI, per 1,000 py (95% CI) Adjusted HRa
Venous thrombosis
24 (16-34)
1.8 ( )
Previous ATE
47 (43-51)
2.2 ( )
Hypertension
14 (13-14)
1.3 ( )
Hyperlipidemia
19 (17-20)
1.4 ( )
Diabetes Mellitus
27 (23-31)
1.5 ( )
Current Smokers
9 (9-10)
1.9 ( )
Albumin Excretion
<10 mg/L
7 (7-7)
Reference
10-20 mg/L
8 (8-9)
1.1 ( )
mg/L
17 (15-19)
1.4 ( )
>200 mg/L
31 (23-40)
1.6 ( ) a
Adjusted for age, sex and all other arterial thrombotic risk factors (Reference group are those
without the exposure)

10. Results – Risk of VTE Crude HR (95% CI) Adjusted HRa Hypertension
1.5 ( )
1.1 ( )
Hyperlipidemia
1.1 ( )
0.8 ( )
Diabetes Mellitus
1.2 ( )
0.7 ( )
Current Smokers
0.9 ( )
Albumin Excretion
<10 mg/L
Reference
10-20 mg/L
1.0 ( )
1.1 ( )
mg/L
1.8 ( )
1.5 ( )
>200 mg/L
2.9 ( )
2.0 ( )
Crude HR Ageno, HT 1.51 sig, HC 1.16 niet sig, DM: 1.42 sig, smok: 1.18, niet sig. a
Adjusted for age and sex (Reference group are those without the exposure)

11. Risk of arterial thrombosis after venous thrombosis
Results
Risk of arterial thrombosis after venous thrombosis
AI, per 1,000 py (95% CI)
Adjusted HRa
(95% CI)
Venous thrombosis
24 (16-34)
1.8 ( )
Unprovoked VTE
28 (16-45)
1.9 ( )
Provoked VTE
15 (6-30)
1.4 ( )
Deep vein thrombosis
26 (16-40)
2.3 ( )
Pulmonary embolism
20 (9-37)
1.2 ( ) a
Adjusted for age, sex and all other arterial thrombotic risk factors (Reference group are those
without the exposure)

12. Risk of arterial thrombosis after venous thrombosis
Results
Risk of arterial thrombosis after venous thrombosis
Adjusted HRa
(95% CI)
1 year
After 1 year
All venous thrombosis
2.6 ( )
1.5 ( )
Unprovoked VTE
2.5 ( )
1.7 ( )
Provoked VTE
2.4 ( )
0.9 ( )
Deep vein thrombosis
3.5 ( )
1.8 ( )
Pulmonary embolism
1.4 ( )
1.1 ( ) a
Adjusted for age, sex and all thrombotic arterial risk factors

13. Conclusions
Patients with venous thrombosis have a high absolute risk of subsequent arterial thrombosis
This risk could not be explained by the presence of arterial thrombotic risk factors
The risk of arterial thrombosis was highest within the first year after venous thrombosis, especially in patients with unprovoked venous thrombosis

14. Authors Inge M. van Schouwenburg Bakhtawar K. Mahmoodi
Ron T. Gansevoort
Nic J.G.M. Veeger
Margaretha M. Visser
Willem M. Lijfering
Jan van der Meer †