Lifestyle and venous thrombosis

In the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study), a large population-based case-control study, we investigated lifestyle factors as risk factors for venous thrombosis. Overweight, smoking and alcohol consumption were addressed and pregnancy and the postpartum period were evaluated in women. Due to the large sample size of the study it was possible to investigate the joint effect of these risk factors with important genetic risk factors for venous thrombosis such as the factor V Leiden and the prothrombin 20210A mutation. In addition to these lifestyle related risk factors, two polymorphisms within the promoter region of the protein C gene were studied as risk factors for venous thrombosis and the influence of genotypic variation on plasma protein C levels was assessed. Finally, we described our experience with the inclusion of two different control groups in the MEGA study.The Netherlands Heart foundation J.E. Jurriaanse StichtingUBL - phd migration 201

Middelengebruik en criminaliteit: Een overzicht

Contains fulltext : 134393.pdf (publisher's version ) (Open Access)Achtergrond: Het gebruik van psychoactieve middelen gaat regelmatig samen met allerlei vormen van criminaliteit, waaronder gewelddadig gedrag. Doel: Een overzicht geven van de relaties tussen (problematisch) middelengebruik en criminaliteit, waaronder geweldscriminaliteit. Methode: Een literatuuronderzoek werd uitgevoerd naar meta-analyses, reviews en empirische artikelen over de relaties tussen (problematisch) gebruik en verslaving van psychoactieve middelen enerzijds en criminaliteit, antisociaal en agressief gedrag alsmede recidive anderzijds. Resultaten: Zowel voor mannen als voor vrouwen bestaan er significante relaties tussen problematisch gebruik van middelen en crimineel gedrag. Het merendeel van de gebruikers is echter niet crimineel en de misdrijven betreffen vooral vermogensdelicten. De relatie met geweld is voor alcohol sterker dan voor andere middelen. Verder bestaan alleen voor cocaïne aanwijzingen voor psychofarmacologische effecten die gewelddadig gedrag stimuleren. Of problematische middelengebruikers crimineel en met name gewelddadig zijn, wordt bepaald door interacties tussen een aantal factoren: de mate waarin het gebruik problematisch is, individuele psychologische, sociale en neurobiologische kenmerken, situationele factoren en verwachtingen omtrent het effect van middelen. Conclusie: Middelenmisbruik, vooral de combinatie van alcohol en drugs, is een voorspellende factor voor (recidive van) criminaliteit.8 p

Pregnancy, the postpartum period and prothrombotic defects: risk of venous thrombosis in the MEGA study

Background: Venous thrombosis is one of the leading causes of maternal morbidity and mortality. Objective: In the MEGA study, we evaluated pregnancy and the postpartum period as risk factors for venous thrombosis in 285 patients and 857 control subjects. Patients/methods: Between March 1999 and September 2004, consecutive patients with a first episode of venous thrombosis were included from six anticoagulation clinics. Partners of patients and a random digit dialing group were included as control subjects. Participants completed a questionnaire and DNA was collected. Results: The risk of venous thrombosis was 5-fold (OR, 4.6; 95% CI, 2.7–7.8) increased during pregnancy and 60-fold (OR, 60.1; 95% CI, 26.5–135.9) increased during the first 3 months after delivery compared with non-pregnant women. A 14-fold increased risk of deep venous thrombosis of the leg was found compared with a 6-fold increased risk of pulmonary embolism. The risk was highest in the third trimester of pregnancy (OR, 8.8; 95% CI, 4.5–17.3) and during the first 6 weeks after delivery (OR, 84.0; 95% CI, 31.7–222.6). The risk of pregnancy-associated venous thrombosis was 52-fold increased in factor V Leiden carriers (OR, 52.2; 95% CI, 12.4–219.5) and 31-fold increased in carriers of the prothrombin 20210A mutation (OR, 30.7; 95% CI, 4.6–203.6) compared with non-pregnant women without the mutation. Conclusion: We found an increased risk of venous thrombosis during pregnancy and the postpartum period, with an especially high risk during the first 6 weeks postpartum. The risk of pregnancy-associated venous thrombosis was highly increased in carriers of factor V Leiden or the prothrombin 20210A mutatio

Polymorphisms in the protein C gene as risk factor for venous thrombosis\ud

Protein C is an important inhibitor of blood coagulation. We investigated the effect of two polymorphisms within the promoter region of the protein C gene (C/T at position 2405 and A/G at position 2418) on risk of venous thrombosis and on plasma protein C levels. In addition the combined effect of the two polymorphisms with factor V Leiden and oral contraceptive use was investigated. Previous studies on these polymorphisms were small and were not able to investigate synergistic effects. In the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study), protein C levels were determined in 2,043 patients with venous thrombosis and 2,857 control subjects, and the two polymorphisms in 4,285 patients and 4,863 control subjects. The CC/GG genotype was associated with the lowest protein C levels. Compared to carriers of the TT/AA genotype – a genotype associated with higher protein C levels – the risk of venous thrombosis in CC/GG carriers was 1.3-fold increased (95% confidence interval 1.09–1.48). The combination of factor V Leiden with the CC/GG genotype led to a 4.7-fold increased risk, compared to non-carriers with the TT/AA genotype. Oral contraceptive use together with the CC/ GG genotype resulted in a 5.2-fold increased risk. In conclusion, the CC/GG genotype is associated with lower levels of protein C and an elevated risk of venous thrombosis compared to the TT/AA genotype. There is no clear synergistic effect of the CC/ GG genotype with factor V Leiden or oral contraceptive use on thrombotic ris

Mechanisms of the Factor V Leiden Paradox

Objective— Carriers of the factor V Leiden mutation (FVL-carriers) have a substantially increased risk of deep venous thrombosis (DVT), whereas the risk of pulmonary embolism (PE) is only mildly increased compared with noncarriers. So far few studies have investigated possible mechanisms for this so-called FVL paradox. Methods and Results— Consecutive patients with a first DVT or PE were included in a large population-based case-control study (MEGA study). Patients, aged 18 to 70 years, provided a questionnaire, DNA (n=3313), or plasma (n=1474). Surgery, injury, and travel were considered thrombosis-provocative. Of 2063 patients with isolated DVT, 20% were FVL-carrier, as were 8% of the 885 patients with isolated PE. Among DVT patients, FVL-carriers had their thrombi more often proximal and a higher number of affected veins than noncarriers. No differences were observed between FVL-carriers and noncarriers in time between provocation and diagnosis, in vitro coagulation time, and thrombus density. Compared with patients with both DVT and PE, isolated DVT patients more often had thrombi located distally and had a similar number of affected veins. Compared with isolated PE patients, isolated DVT patients had a similar time between provocation and diagnosis, and similar in vitro coagulation time and thrombus density. Conclusion— Although some effects were differential for FVL-carriers and noncarriers, and some were differential for PE and DVT patients, none of the potential mechanisms offered a clear explanation. Carriers of the factor V Leiden mutation have substantial risk of deep venous thrombosis but a mild pulmonary embolism risk. Five potential mechanisms were explored; thrombus location, number of affected veins, time between provocation and diagnosis, in vitro coagulation time, and thrombus density. None of the mechanisms offered a clear explanatio