Vitamin supplementation on the risk of venous thrombosis: results from the MEGA case-control study.
BACKGROUND
Whether vitamin supplements decrease venous thrombosis risk is controversial. Previous reports did not all take confounding fully into account, either by randomization or by extensive adjustment.


OBJECTIVE
The aim of our study was to determine whether vitamin supplementation decreases the risk of venous thrombosis.


METHODS
A large case-control study included 2506 patients with venous thrombosis, 2506 partner controls, and 2684 random-digit dialing (RDD) controls. When patients were compared with RDD controls, unconditional logistic regression was used to calculate ORs with 95% CIs. When patients were compared with partner controls, conditional logistic regression was used, providing further adjustment for unmeasured confounding.


RESULTS
Vitamin use yielded a 37% lower risk of venous thrombosis than no vitamin use (OR: 0.63; 95% CI: 0.57, 0.70) when comparing patients with RDD controls. Adjustment for several putative confounders did not change the estimate (OR: 0.68; 95% CI: 0.61, 0.77). The fully adjusted ORs for vitamin A, vitamin B-6, vitamin B-12, folic acid, vitamin C, vitamin D, vitamin E, and multivitamin use were in the same range. However, when patients were compared with partner controls, ORs attenuated to unity. Results were similar for provoked and unprovoked events, as well as for deep vein thrombosis and pulmonary embolism.


CONCLUSIONS
After extensive adjustments, vitamin supplementation was no longer associated with a decreased risk of venous thrombosis in this study. Previous positive results may have been spurious as a result of uncontrolled confounding.
From the Department of Pathophysiology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia (BAV), and Einthoven Laboratory for Experimental Vascular Medicine (NvR, SCC, FRR, and WML) and the Departments of Thrombosis and Hemostasis (NvR) and Clinical Epidemiology (SCC, FRR, and WML), Leiden University Medical Center, Leiden, The Netherlands.
Biljana A
BA
Vučković
From the Department of Pathophysiology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia (BAV), and Einthoven Laboratory for Experimental Vascular Medicine (NvR, SCC, FRR, and WML) and the Departments of Thrombosis and Hemostasis (NvR) and Clinical Epidemiology (SCC, FRR, and WML), Leiden University Medical Center, Leiden, The Netherlands.
Nienke
N
van Rein
From the Department of Pathophysiology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia (BAV), and Einthoven Laboratory for Experimental Vascular Medicine (NvR, SCC, FRR, and WML) and the Departments of Thrombosis and Hemostasis (NvR) and Clinical Epidemiology (SCC, FRR, and WML), Leiden University Medical Center, Leiden, The Netherlands.
Suzanne C
SC
Cannegieter
From the Department of Pathophysiology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia (BAV), and Einthoven Laboratory for Experimental Vascular Medicine (NvR, SCC, FRR, and WML) and the Departments of Thrombosis and Hemostasis (NvR) and Clinical Epidemiology (SCC, FRR, and WML), Leiden University Medical Center, Leiden, The Netherlands.
Frits R
FR
Rosendaal
From the Department of Pathophysiology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia (BAV), and Einthoven Laboratory for Experimental Vascular Medicine (NvR, SCC, FRR, and WML) and the Departments of Thrombosis and Hemostasis (NvR) and Clinical Epidemiology (SCC, FRR, and WML), Leiden University Medical Center, Leiden, The Netherlands.
Willem M
WM
Lijfering
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015986:Confounding Factors, Epidemiologic; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011655:Pulmonary Embolism / Q000453:epidemiology / Q000517:prevention & control*; D015203:Reproducibility of Results; D012307:Risk Factors; D020246:Venous Thrombosis / Q000453:epidemiology / Q000517:prevention & control*; D014815:Vitamins / Q000627:therapeutic use*; D055815:Young Adult
D014815:Vitamins
cardiovascular diseases; epidemiology; public health; risk; venous thrombosis