Risk of venous thrombosis in persons with increased body mass index and interactions with other genetic and acquired risk factors

Abstract

To cite this article: Ribeiro DD, Lijfering WM, Rosendaal FR, Cannegieter SC. Risk of venous thrombosis in persons with increased body mass index and interactions with other genetic and acquired risk factors. J Thromb Haemost 2016; 14:1572-8. Essentials • Obesity, factor V Leiden (FVL) and blood group non-O are common. • We studied the combined effect of these factors on the risk of venous thrombosis (VT). • The combination of obesity, non-O blood group and FVL increased VT risk up to tenfold. • Identifying high VT may be beneficial in thrombosis prevention. Summary. Background: Overweight/obesity has a substantial effect on the occurrence of venous thrombosis (VT). Blood group non-O has a high prevalence in Western populations, and the factor V Leiden mutation could be present in 5% of Caucasians. These frequent prothrom-botic risk factors will have a considerable impact on the incidence of VT, especially when combined. Objectives: We investigated whether FV Leiden with blood group non-O modifies VT risk in individuals with different body mass index (BMI) strata in a case-control study (n = 11253). Results: We observed a progressively increasing risk of VT with higher BMI, with an odds ratio of 1.9 (95% confidence interval [CI] 1.6-2.3) for those in the upper BMI tertile (BMI > 26.7 kg m À2), as compared with the first BMI tertile (BMI < 23.5 kg m À2 , blood group O, and no FV Leiden) (reference group). The addition of FV Leiden and blood group non-O to the model increased the risk in all BMI tertiles; the odds ratios were 3.8 (95% CI 3.2-4.6) in the third BMI tertile of individuals with blood group non-O, and 5.4 (95% CI 3.5-8.5) in the third BMI tertile of individuals with FV Leiden. When both FV Leiden and blood group non-O were present , the odds ratios were 9.1 (95% CI 5.9-14.0) in the first BMI tertile, 9.4 (95% CI 6.6-13.5) in the second BMI tertile, and 12.5 (95% CI 8.9-17.6) in the third BMI tertile. Conclusion: Individuals with a high BMI, blood group non-O and/or FV Leiden have a high VT risk. The high VT risks in some subgroups may justify targeted screening and thromboprophylaxis decisions in these patients.

Polymorphisms in PARK2 and MRPL37 are associated with higher risk of recurrent venous thromboembolism in a sex-specific manner

“…Furthermore, VTE risk factors such as smoking, obesity and hypercholesterolemia are associated with increased mtDNA damage [42][43][44][45]. However, the role of mitochondrial dysfunction is not well studied in VTE except for a few studies suggesting an indirect role of mtDNA in venous thrombosis.…”

Oestrogen and anti-androgen therapy for transgender women

“…Modifiers in transgender women include the oestrogen preparation used (ethinylestradiol or conjugated oestrogens vs 17–β oestradiol), dosing method (oral vs transdermal), age (older than 50 years is associated with increased risk), obesity (body-mass index >27), 54 and postoperative state (with prophylaxis for deep venous thrombosis vs without). 27 We believe that transgender women who continue to smoke should be switched to transdermal oestrogens, although there are few data to suggest that this reduces risk of thromboembolism.…”

Venous thromboembolism laboratory testing (factor V Leiden andfactor II c.*97G>A), 2018 update: a technical standard of the American College of Medical Genetics and Genomics (ACMG)

“…42,43 Lifetime risks of VTE are higher when environmental risk factors such as obesity and smoking are also present. [42][43][44][45] Heterozygosity for factor V Leiden has at most a modest effect on recurrence risk after a first VTE, with conflicting results between studies. 46 Some studies have demonstrated no increased recurrence for factor V Leiden heterozygotes.…”