Key result
Heterozygous factor V Leiden increased VTE (HR 1.8) and DVT (HR 2.2) risk but not PE, confirming the FVL paradox, whereas homozygous FVL significantly increased PE risk (HR 8.7; 95% CI 2.1-36).
Why the study?
Does Factor V Leiden carriership increase the risk of VTE, DVT, and PE in middle-aged individuals without previous VTE or cancer?
Cohort (n=4,890)
Does Factor V Leiden carriership increase the risk of VTE, DVT, and PE in middle-aged individuals without previous VTE or cancer?
The Factor V Leiden paradox (higher risk for DVT than PE) is confirmed for heterozygous carriers, but homozygous carriers have a high risk for PE.
FVL status may refine individualized VTE risk discussions in middle-aged adults; leaves open whether genotype should guide prophylaxis or screening.
Few prospective studies have examined the factor V paradox: factor V Leiden (FVL) is a stronger risk factor for deep venous thrombosis (DVT) than for pulmonary embolism (PE). The present study, to the best of our knowledge, is the first population-based study aimed to examine the relationship between FVL and incidence of venous thromboembolism (VTE), DVT and PE in a prospective cohort study of middle-aged Swedish individuals. FVL was determined in 4890 subjects (aged 46-68 years, 57% women) from the general population without previous VTE or cancer, who participated in the Malmö Diet and Cancer study between 1991 and 1994. Incident cases of VTE were identified from the Swedish patient register during a mean follow-up of 15.6 years. Of 4890 subjects with determination of FVL (10.2% carriers), 220 had VTE during follow-up (113 DVT, 78 PE, 29 both). Incidence of VTE was significantly higher in subjects with heterozygous and homozygous FVL: adjusted hazard ratios (HR) were 1.8 (95% CI 1.3-2.6, p=0.001) and 6.5 (2.1-21, p=0.001), respectively. The population attributable fraction was 8.7% for FVL. Adjusted HRs for DVT were 2.2 (1.4-3.3, p<0.001) for heterozygotes and 3.3 (0.5-24, p=0.233) for homozygotes. Adjusted HRs for PE were 1.2 (0.65-2.2, p=0.582) for heterozygotes and 8.7 (2.1-36, p=0.003) for homozygotes. The FVL paradox was confirmed for heterozygotes for FVL. However, homozygotes for FVL had a high risk for PE, suggesting that the FVL paradox is related to the carriership of one wild type and one mutated factor V allele.
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Zöller et al. (2018) conducted a cohort in Venous thromboembolism (n=4,890). Factor V Leiden (FVL) mutation vs. Non-carriers (wild type) was evaluated on Incidence of VTE (HR 1.8 (heterozygous), HR 6.5 (homozygous), 95% CI 1.3-2.6 (heterozygous), 2.1-21 (homozygous), p=0.001 (heterozygous), 0.001 (homozygous)). Heterozygous factor V Leiden increased VTE (HR 1.8) and DVT (HR 2.2) risk but not PE, confirming the FVL paradox, whereas homozygous FVL significantly increased PE risk (HR 8.7; 95% CI 2.1-36).
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